@precisa-saude/fhir 0.14.1 → 0.15.1

package/dist/{chunk-BSR2RHMT.cjs → chunk-ZKN5UI7R.cjs}

@@ -60,8 +60,14 @@ var biomarkerRangeDefinitions = {
       }
     ]
   },
+  // AMH — fortemente dependente de idade e sexo. As variantes femininas por
+  // faixa etária são a referência clínica; o `default` foi ajustado para
+  // refletir uma faixa adulta conservadora (~18-40 anos, mulheres em idade
+  // reprodutiva geral). optimalMax anterior (6.9 ng/mL) sobrepunha-se a
+  // valores sugestivos de SOP ou risco de OHSS; clinicamente, valores acima
+  // de ~4 ng/mL já merecem investigação.
   AMH: {
-    default: { max: 10, min: 1, optimalMax: 6.9, optimalMin: 2, unit: "ng/mL" },
+    default: { max: 6, min: 1, optimalMax: 4, optimalMin: 1.5, unit: "ng/mL" },
     source: "tietz-7ed-2015",
     variants: [
       {
@@ -173,6 +179,15 @@ var biomarkerRangeDefinitions = {
     default: { max: 29, min: 23, optimalMax: 28, optimalMin: 24, unit: "mEq/L" },
     source: "tietz-7ed-2015"
   },
+  // β-Hidroxibutirato (BHB) sérico — corpos cetônicos. Faixa derivada de
+  // amostra populacional não-jejum (German National Cohort, n=304, 20–69 a)
+  // como percentis 2,5–97,5: 0,02–0,28 mmol/L. Em jejum prolongado ou
+  // cetose nutricional, valores acima de 0,5 mmol/L são esperados; o limite
+  // superior aqui reflete estado pós-prandial habitual, não jejum.
+  BetaHydroxybutyrate: {
+    default: { max: 0.28, min: 0.02, optimalMax: 0.28, optimalMin: 0.02, unit: "mmol/L" },
+    source: "klee-bhb-2020"
+  },
   BilirubinDirect: {
     default: { max: 0.3, min: 0, optimalMax: 0.2, optimalMin: 0, unit: "mg/dL" },
     source: "tietz-7ed-2015"
@@ -190,6 +205,12 @@ var biomarkerRangeDefinitions = {
     default: { max: 35, min: 0, optimalMax: 20, optimalMin: 0, unit: "pg/mL" },
     source: "sbc-ic-2018"
   },
+  // Razão BUN/Creatinina — faixa 10-20 aplica-se ao Nitrogênio Ureico (BUN).
+  // Laboratórios brasileiros que reportam Ureia (e não BUN) usam razão
+  // Ureia/Creatinina, cuja faixa normal é aproximadamente 21-43
+  // (Ureia ≈ BUN × 2,14). O biomarcador atualmente assume a convenção BUN;
+  // consumidores que dosem Ureia devem converter ou reportar como razão
+  // distinta. Ver issue #41 para alinhamento de nomenclatura/LOINC.
   BUN_Creatinine_Ratio: {
     default: { max: 20, min: 10, optimalMax: 18, optimalMin: 12, unit: "" },
     source: "tietz-7ed-2015"
@@ -259,8 +280,11 @@ var biomarkerRangeDefinitions = {
     default: { max: 106, min: 98, optimalMax: 105, optimalMin: 100, unit: "mEq/L" },
     source: "tietz-7ed-2015"
   },
+  // Colesterol total — SBC 2017/2025: valor desejável < 190 mg/dL para adultos,
+  // com ou sem jejum. Limite anterior (200 mg/dL) refletia a diretriz ATP III
+  // (NCEP, 2002), superada pelas atualizações brasileiras.
   Cholesterol: {
-    default: { max: 200, min: 0, optimalMax: 180, optimalMin: 0, unit: "mg/dL" },
+    default: { max: 190, min: 0, optimalMax: 170, optimalMin: 0, unit: "mg/dL" },
     source: "sbc-lipids-2025"
   },
   // Índice de Castelli I (CT/HDL-c)
@@ -616,19 +640,25 @@ var biomarkerRangeDefinitions = {
       }
     ]
   },
+  // HDL — SBC 2017/2025: desejável > 40 mg/dL (♂) e > 50 mg/dL (♀).
+  // A diretriz NÃO define teto de normalidade — HDL alto é cardioprotetor.
+  // Limites superiores anteriormente fixados em 60 mg/dL geravam falsos
+  // alertas. Mantém-se `max` apenas como limite técnico do gauge (100 mg/dL),
+  // não como ponto de corte clínico; consumidores devem tratar `direction:
+  // higher-better` como sinal autoritativo.
   HDL: {
-    default: { max: 60, min: 40, optimalMax: 60, optimalMin: 50, unit: "mg/dL" },
+    default: { max: 100, min: 40, optimalMax: 100, optimalMin: 50, unit: "mg/dL" },
     direction: "higher-better",
     source: "sbc-lipids-2025",
     variants: [
       {
         ageMin: 18,
-        range: { max: 60, min: 40, optimalMax: 60, optimalMin: 45, unit: "mg/dL" },
+        range: { max: 100, min: 40, optimalMax: 100, optimalMin: 45, unit: "mg/dL" },
         sex: "M"
       },
       {
         ageMin: 18,
-        range: { max: 60, min: 50, optimalMax: 60, optimalMin: 55, unit: "mg/dL" },
+        range: { max: 100, min: 50, optimalMax: 100, optimalMin: 55, unit: "mg/dL" },
         sex: "F"
       }
     ]
@@ -742,6 +772,29 @@ var biomarkerRangeDefinitions = {
     default: { max: 2.2, min: 0.5, optimalMax: 1.8, optimalMin: 0.7, unit: "mmol/L" },
     source: "tietz-7ed-2015"
   },
+  // DHL/LDH — método IFCC a 37 °C (padrão atual na maioria dos laboratórios
+  // brasileiros). Limites superiores de referência (97,5° percentil) obtidos
+  // por Schumann & Klauke (2002) em indivíduos ≥17 anos: 247 U/L (mulheres)
+  // e 248 U/L (homens). O IFCC publica apenas o limite superior; o limite
+  // inferior é fixado em 0 pois DHL baixa não tem significado clínico.
+  // Não comparar com método Wróblewski-LaDue (faixas mais antigas, ~240–480).
+  LDH: {
+    default: { max: 248, min: 0, optimalMax: 248, optimalMin: 0, unit: "U/L" },
+    direction: "lower-better",
+    source: "schumann-ifcc-ldh-2002",
+    variants: [
+      {
+        ageMin: 17,
+        range: { max: 248, min: 0, optimalMax: 248, optimalMin: 0, unit: "U/L" },
+        sex: "M"
+      },
+      {
+        ageMin: 17,
+        range: { max: 247, min: 0, optimalMax: 247, optimalMin: 0, unit: "U/L" },
+        sex: "F"
+      }
+    ]
+  },
   LDL: {
     default: { max: 100, min: 0, optimalMax: 70, optimalMin: 0, unit: "mg/dL" },
     direction: "lower-better",
@@ -822,8 +875,14 @@ var biomarkerRangeDefinitions = {
     default: { max: 35, min: 15, optimalMax: 28, optimalMin: 18, unit: "%" },
     source: "simopoulos-omega-ratio-2002"
   },
+  // Lp(a) — SBC 2025 (seção 3.1.1.2.7): níveis ≥ 50 mg/dL ou ≥ 125 nmol/L são
+  // considerados aumentados, com indicação de rastreamento em cascata familiar.
+  // A diretriz recomenda ensaio independente de isoforma medido em nmol/L; a
+  // unidade nmol/L é mantida aqui por refletir o padrão laboratorial atual.
+  // Limites anteriores (max=75) refletiam pontos de corte expressos em mg/dL,
+  // gerando incompatibilidade com a unidade nmol/L declarada.
   Lipoprotein_a: {
-    default: { max: 75, min: 0, optimalMax: 30, optimalMin: 0, unit: "nmol/L" },
+    default: { max: 125, min: 0, optimalMax: 75, optimalMin: 0, unit: "nmol/L" },
     direction: "lower-better",
     source: "sbc-lipids-2025"
   },
@@ -915,8 +974,13 @@ var biomarkerRangeDefinitions = {
     default: { max: 8, min: 4, optimalMax: 8, optimalMin: 5.5, unit: "%" },
     source: "harris-omega3-2004"
   },
+  // Ômega-3 Total (% de ácidos graxos eritrocitários) — Harris & von Schacky
+  // (2004) propõem ≥ 8% como zona ótima de proteção cardiovascular; valores
+  // entre 4% e 8% representam risco intermediário, < 4% risco alto.
+  // optimalMin anterior (5.5%) ficava em zona intermediária, contradizendo
+  // a literatura e o próprio texto educacional do `platform`.
   Omega3_Total: {
-    default: { max: 12, min: 3, optimalMax: 10, optimalMin: 5.5, unit: "%" },
+    default: { max: 12, min: 3, optimalMax: 10, optimalMin: 8, unit: "%" },
     source: "harris-omega3-2004"
   },
   Omega6_Total: {
@@ -952,9 +1016,37 @@ var biomarkerRangeDefinitions = {
     default: { max: 38, min: 18, optimalMax: 35, optimalMin: 20, unit: "mg/dL" },
     source: "tietz-7ed-2015"
   },
+  // Progesterona — varia drasticamente com a fase do ciclo menstrual.
+  // O schema atual não modela fase do ciclo, então adotamos faixas amplas
+  // por sexo: o `default` cobre homens/fase folicular/pós-menopausa; a
+  // variante feminina expande até a faixa esperada de fase lútea
+  // (~3-20 ng/mL). Interpretação correta exige correlação com a fase do
+  // ciclo, indisponível neste contexto.
   Progesterone: {
     default: { max: 0.9, min: 0.1, optimalMax: 0.7, optimalMin: 0.2, unit: "ng/mL" },
-    source: "tietz-7ed-2015"
+    source: "tietz-7ed-2015",
+    variants: [
+      {
+        ageMin: 18,
+        range: { max: 0.9, min: 0.1, optimalMax: 0.6, optimalMin: 0.2, unit: "ng/mL" },
+        sex: "M"
+      },
+      // Mulheres em idade reprodutiva: faixa que abarca fases folicular
+      // (0.1-0.9 ng/mL) e lútea (3-20 ng/mL). Sem contexto de fase do ciclo,
+      // valores intermediários (1-3 ng/mL) ficam em zona ambígua.
+      {
+        ageMax: 50,
+        ageMin: 18,
+        range: { max: 20, min: 0.1, optimalMax: 15, optimalMin: 0.2, unit: "ng/mL" },
+        sex: "F"
+      },
+      // Pós-menopausa: valores tipicamente < 0.5 ng/mL (sem ovulação).
+      {
+        ageMin: 51,
+        range: { max: 0.5, min: 0, optimalMax: 0.3, optimalMin: 0, unit: "ng/mL" },
+        sex: "F"
+      }
+    ]
   },
   Prolactin: {
     default: { max: 18, min: 2, optimalMax: 15, optimalMin: 4, unit: "ng/mL" },
@@ -1232,8 +1324,13 @@ var biomarkerRangeDefinitions = {
       }
     ]
   },
+  // Ureia — convenção brasileira (laboratórios reportam Ureia, não BUN).
+  // Faixa adulta de 15-50 mg/dL (Ureia ≈ BUN × 2,14). Limites anteriores
+  // (7-20 mg/dL) refletiam BUN/Nitrogênio Ureico, gerando falsos diagnósticos
+  // de azotemia em pacientes com Ureia normal. LOINC 3094-0 (BUN) também
+  // deve ser revisto em biomarkers.ts — ver issue #41.
   Urea: {
-    default: { max: 20, min: 7, optimalMax: 16, optimalMin: 10, unit: "mg/dL" },
+    default: { max: 50, min: 15, optimalMax: 40, optimalMin: 20, unit: "mg/dL" },
     source: "tietz-7ed-2015"
   },
   UricAcid: {
@@ -1777,4 +1874,4 @@ function applyFallbackReferenceRanges(biomarkers) {
 
 
 exports.biomarkerRangeDefinitions = biomarkerRangeDefinitions; exports.defaultReferenceRanges = defaultReferenceRanges; exports.getReferenceRange = getReferenceRange; exports.getRangeDirection = getRangeDirection; exports.getFallbackReferenceRange = getFallbackReferenceRange; exports.applyFallbackReferenceRanges = applyFallbackReferenceRanges;
-//# sourceMappingURL=chunk-BSR2RHMT.cjs.map
+//# sourceMappingURL=chunk-ZKN5UI7R.cjs.map

package/dist/chunk-ZKN5UI7R.cjs.map

@@ -0,0 +1 @@
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* Biomarker Reference Ranges\n *\n * Single source of truth for biomarker reference ranges used by both\n * web app (for display) and API (for fallback when LLM doesn't extract ranges).\n *\n * Data sources (priority order):\n * 1. Brazilian Government - SBPC/ML (Sociedade Brasileira de Patologia Clínica) guidelines\n * 2. International Standards - WHO, clinical laboratory guidelines\n * 3. Specific Labs - Fleury, Weinmann, Quest, LabCorp (when above unavailable)\n */\n\nimport { getCanonicalUnit as getCanonicalUnitForCode } from './units';\n\n// =============================================================================\n// TYPES\n// =============================================================================\n\n/**\n * Sex-specific key for reference ranges\n */\nexport type SexKey = 'M' | 'F' | 'all';\n\n/**\n * Pré-condição de jejum para a faixa de referência.\n *\n * - `strict`: coleta exige jejum mínimo (ex.: glicemia de jejum, insulina).\n * - `preferred`: jejum recomendado, mas faixa aplicável em não-jejum\n *   (ex.: perfil lipídico pós-SBC 2017, com corte de triglicérides distinto).\n * - `not-required`: valor independe do estado prandial (ex.: HbA1c, TSH).\n */\nexport type FastingRequirement = 'strict' | 'preferred' | 'not-required';\n\n/**\n * Reference range configuration for a biomarker\n */\nexport interface BiomarkerReferenceRange {\n  /**\n   * Pré-condição de jejum para a interpretação da faixa. Opcional;\n   * consumidores devem aplicar sinalização adequada quando `strict`.\n   */\n  fastingRequired?: FastingRequirement;\n  max?: number;\n  min?: number;\n  optimalMax?: number;\n  optimalMin?: number;\n  unit: string;\n  warningMax?: number;\n}\n\n/**\n * Trimestre gestacional. Usado em variantes e no contexto de consulta\n * para matching de faixas específicas da gestação.\n */\nexport type PregnancyTrimester = 1 | 2 | 3;\n\n/**\n * A variant of a reference range that applies to a specific sex, age group,\n * and/or pregnancy state.\n *\n * Ordem de avaliação: variantes são processadas na ordem em que aparecem.\n * Para que usuárias gestantes recebam a variante gestacional correta,\n * essas variantes devem ser listadas **antes** das variantes por idade/sexo.\n */\nexport interface RangeVariant {\n  ageMax?: number;\n  ageMin?: number;\n  pregnancyTrimester?: PregnancyTrimester;\n  /**\n   * Quando `true`, a variante só se aplica a contextos de gestação.\n   * Se `pregnancyTrimester` estiver definido, o trimestre deve coincidir.\n   */\n  pregnant?: boolean;\n  range: BiomarkerReferenceRange;\n  sex: SexKey;\n}\n\n/**\n * Extended biomarker range definition with sex/age-specific variants\n */\n/**\n * Direction indicates whether exceeding the reference range on one side is benign.\n * - 'range': both above-max and below-min are abnormal (default)\n * - 'higher-better': above-max is normal (e.g., BMC, HDL)\n * - 'lower-better': below-min is normal (e.g., LDL, CRP)\n */\nexport type RangeDirection = 'range' | 'higher-better' | 'lower-better';\n\nexport interface BiomarkerRangeDefinition {\n  default: BiomarkerReferenceRange;\n  direction?: RangeDirection;\n  /**\n   * Chave de fonte bibliográfica, opcionalmente com localizador.\n   *\n   * Formato: `'chave'` ou `'chave:localizador'`\n   *\n   * Exemplos:\n   * - `'sbc-lipids-2017'` — fonte sem localização específica\n   * - `'sbc-lipids-2017:p15'` — página 15\n   * - `'sbpc-ml-2021:t4.1'` — tabela 4.1\n   *\n   * As chaves devem corresponder a entradas em `SOURCE_REGISTRY` (sources.ts).\n   * Consulte `docs/fontes-referencia.md` para a bibliografia completa em formato ABNT.\n   */\n  source?: string;\n  variants?: RangeVariant[];\n}\n\n/**\n * User context for personalized reference range lookup.\n *\n * Para gestação, defina `pregnant: true` e, quando disponível,\n * `pregnancyTrimester` para obter a variante trimestre-específica.\n */\nexport interface ReferenceRangeContext {\n  age?: number;\n  biologicalSex?: 'M' | 'F';\n  pregnancyTrimester?: PregnancyTrimester;\n  pregnant?: boolean;\n}\n\n// =============================================================================\n// BIOMARKER RANGE DEFINITIONS\n// =============================================================================\n\n/**\n * Comprehensive biomarker reference range definitions with sex/age-specific variants\n *\n * Each marker has a default range (used as fallback) and optional variants\n * for sex/age-specific ranges.\n */\nexport const biomarkerRangeDefinitions: Record<string, BiomarkerRangeDefinition> = {\n  Albumin_Creatinine_Ratio: {\n    default: { max: 30, min: 0, optimalMax: 20, optimalMin: 0, unit: 'mg/g' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Adiponectin: {\n    default: { max: 26, min: 4, optimalMax: 20, optimalMin: 8, unit: 'mcg/mL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  ADMA: {\n    default: { max: 0.7, min: 0.3, optimalMax: 0.55, optimalMin: 0.3, unit: 'umol/L' },\n    source: 'nemeth-adma-2017',\n  },\n\n  AFP: {\n    default: { max: 10, min: 0, optimalMax: 8, optimalMin: 0, unit: 'ng/mL' },\n    source: 'sturgeon-nacb-2008',\n  },\n\n  Albumin_Globulin_Ratio: {\n    default: { max: 2.5, min: 1.0, optimalMax: 2.2, optimalMin: 1.2, unit: '' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Albumin: {\n    default: { max: 5.0, min: 3.5, optimalMax: 4.8, optimalMin: 4.0, unit: 'g/dL' },\n    source: 'pns-bioquimica-2019',\n  },\n\n  AlkalinePhosphatase: {\n    default: { max: 147, min: 44, optimalMax: 120, optimalMin: 50, unit: 'U/L' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 147, min: 44, optimalMax: 120, optimalMin: 50, unit: 'U/L' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 104, min: 35, optimalMax: 90, optimalMin: 40, unit: 'U/L' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  ALT: {\n    default: { max: 35, min: 0, optimalMax: 25, optimalMin: 0, unit: 'U/L' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 56, min: 7, optimalMax: 35, optimalMin: 10, unit: 'U/L' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 45, min: 7, optimalMax: 30, optimalMin: 10, unit: 'U/L' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // AMH — fortemente dependente de idade e sexo. As variantes femininas por\n  // faixa etária são a referência clínica; o `default` foi ajustado para\n  // refletir uma faixa adulta conservadora (~18-40 anos, mulheres em idade\n  // reprodutiva geral). optimalMax anterior (6.9 ng/mL) sobrepunha-se a\n  // valores sugestivos de SOP ou risco de OHSS; clinicamente, valores acima\n  // de ~4 ng/mL já merecem investigação.\n  AMH: {\n    default: { max: 6.0, min: 1.0, optimalMax: 4.0, optimalMin: 1.5, unit: 'ng/mL' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMax: 24,\n        ageMin: 18,\n        range: { max: 13.0, min: 1.5, optimalMax: 10.0, optimalMin: 3.0, unit: 'ng/mL' },\n        sex: 'F',\n      },\n      {\n        ageMax: 30,\n        ageMin: 25,\n        range: { max: 10.0, min: 1.5, optimalMax: 8.0, optimalMin: 2.5, unit: 'ng/mL' },\n        sex: 'F',\n      },\n      {\n        ageMax: 35,\n        ageMin: 31,\n        range: { max: 8.0, min: 1.0, optimalMax: 6.0, optimalMin: 2.0, unit: 'ng/mL' },\n        sex: 'F',\n      },\n      {\n        ageMax: 40,\n        ageMin: 36,\n        range: { max: 6.0, min: 0.5, optimalMax: 4.0, optimalMin: 1.0, unit: 'ng/mL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 41,\n        range: { max: 3.0, min: 0.1, optimalMax: 2.0, optimalMin: 0.5, unit: 'ng/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Ammonia: {\n    default: { max: 45, min: 15, optimalMax: 40, optimalMin: 20, unit: 'umol/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  AntiThyroglobulin: {\n    default: { max: 115, min: 0, optimalMax: 40, optimalMin: 0, unit: 'IU/mL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  AntiTPO: {\n    default: { max: 34, min: 0, optimalMax: 9, optimalMin: 0, unit: 'IU/mL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // Aortic valve calcium — no standardized clinical threshold; use mild cutoff\n  // Cálcio de válvula aórtica — usa mesma classificação Agatston\n  AorticValveCalcium: {\n    default: { max: 99, min: 0, optimalMax: 0, optimalMin: 0, unit: 'AU' },\n    direction: 'lower-better',\n    source: 'rumberger-cac-1999',\n  },\n\n  ApoA1: {\n    default: { max: 200, min: 100, optimalMax: 180, optimalMin: 120, unit: 'mg/dL' },\n    source: 'contois-apoa1-1996',\n  },\n\n  ApoB: {\n    default: { max: 90, min: 0, optimalMax: 70, optimalMin: 0, unit: 'mg/dL' },\n    direction: 'lower-better',\n    source: 'sbc-lipids-2025',\n  },\n\n  ApoCIII: {\n    default: { max: 10, min: 0, optimalMax: 7, optimalMin: 0, unit: 'mg/dL' },\n    source: 'khetarpal-apociii-2016',\n  },\n\n  // ApoCIII/ApoA1 Ratio: derivado de ApoCIII (~10 mg/dL) e ApoA1 (~100-150 mg/dL)\n  // NOTA: corte de 0.15 sem fonte publicada — valor calculado, não validado clinicamente\n  ApoCIII_ApoA1_Ratio: {\n    default: { max: 0.15, min: 0, optimalMax: 0.1, optimalMin: 0, unit: '' },\n  },\n\n  Omega6_AA: {\n    default: { max: 15.0, min: 5.0, optimalMax: 12.0, optimalMin: 7.0, unit: '%' },\n    source: 'simopoulos-omega-ratio-2002',\n  },\n\n  AA_EPA_Ratio: {\n    default: { max: 15.0, min: 1.0, optimalMax: 5.0, optimalMin: 1.5, unit: '' },\n    direction: 'lower-better',\n    source: 'simopoulos-omega-ratio-2002',\n  },\n\n  Arsenic: {\n    default: { max: 35, min: 0, optimalMax: 20, optimalMin: 0, unit: 'mcg/L' },\n    source: 'nr7-pcmso-2020',\n  },\n\n  AST: {\n    default: { max: 35, min: 0, optimalMax: 25, optimalMin: 0, unit: 'U/L' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 40, min: 10, optimalMax: 30, optimalMin: 10, unit: 'U/L' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 32, min: 9, optimalMax: 25, optimalMin: 10, unit: 'U/L' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Basophils: {\n    default: { max: 1, min: 0, optimalMax: 0.5, optimalMin: 0, unit: '%' },\n    source: 'pns-hemograma-2019',\n  },\n\n  Basophils_Abs: {\n    default: { max: 0.1, min: 0, optimalMax: 0.05, optimalMin: 0, unit: 'K/uL' },\n    source: 'pns-hemograma-2019',\n  },\n\n  Bicarbonate: {\n    default: { max: 29, min: 23, optimalMax: 28, optimalMin: 24, unit: 'mEq/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // β-Hidroxibutirato (BHB) sérico — corpos cetônicos. Faixa derivada de\n  // amostra populacional não-jejum (German National Cohort, n=304, 20–69 a)\n  // como percentis 2,5–97,5: 0,02–0,28 mmol/L. Em jejum prolongado ou\n  // cetose nutricional, valores acima de 0,5 mmol/L são esperados; o limite\n  // superior aqui reflete estado pós-prandial habitual, não jejum.\n  BetaHydroxybutyrate: {\n    default: { max: 0.28, min: 0.02, optimalMax: 0.28, optimalMin: 0.02, unit: 'mmol/L' },\n    source: 'klee-bhb-2020',\n  },\n\n  BilirubinDirect: {\n    default: { max: 0.3, min: 0, optimalMax: 0.2, optimalMin: 0, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  BilirubinIndirect: {\n    default: { max: 0.8, min: 0, optimalMax: 0.6, optimalMin: 0, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  BilirubinTotal: {\n    default: { max: 1.2, min: 0.1, optimalMax: 0.9, optimalMin: 0.2, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // BNP: 35 pg/mL = corte não-agudo para triagem de IC (SBC IC 2018)\n  BNP: {\n    default: { max: 35, min: 0, optimalMax: 20, optimalMin: 0, unit: 'pg/mL' },\n    source: 'sbc-ic-2018',\n  },\n\n  // Razão BUN/Creatinina — faixa 10-20 aplica-se ao Nitrogênio Ureico (BUN).\n  // Laboratórios brasileiros que reportam Ureia (e não BUN) usam razão\n  // Ureia/Creatinina, cuja faixa normal é aproximadamente 21-43\n  // (Ureia ≈ BUN × 2,14). O biomarcador atualmente assume a convenção BUN;\n  // consumidores que dosem Ureia devem converter ou reportar como razão\n  // distinta. Ver issue #41 para alinhamento de nomenclatura/LOINC.\n  BUN_Creatinine_Ratio: {\n    default: { max: 20, min: 10, optimalMax: 18, optimalMin: 12, unit: '' },\n    source: 'tietz-7ed-2015',\n  },\n\n  CA125: {\n    default: { max: 35, min: 0, optimalMax: 25, optimalMin: 0, unit: 'U/mL' },\n    source: 'sturgeon-nacb-2008',\n  },\n\n  CA199: {\n    default: { max: 37, min: 0, optimalMax: 30, optimalMin: 0, unit: 'U/mL' },\n    source: 'sturgeon-nacb-2008',\n  },\n\n  // CAC: Agatston classification — 0=none, 1-99=mild, 100-399=moderate, 400+=severe\n  // max=99 so only moderate+ scores (≥100) flag as ANORMAL; optimalMax=0 (zero is ideal)\n  CAC: {\n    default: { max: 99, min: 0, optimalMax: 0, optimalMin: 0, unit: 'AU' },\n    direction: 'lower-better',\n    source: 'rumberger-cac-1999',\n  },\n\n  // Per-vessel scores — same Agatston classification applied per vessel\n  CAC_LAD: {\n    default: { max: 99, min: 0, optimalMax: 0, optimalMin: 0, unit: 'AU' },\n    direction: 'lower-better',\n    source: 'rumberger-cac-1999',\n  },\n\n  CAC_LCX: {\n    default: { max: 99, min: 0, optimalMax: 0, optimalMin: 0, unit: 'AU' },\n    direction: 'lower-better',\n    source: 'rumberger-cac-1999',\n  },\n\n  CAC_LMA: {\n    default: { max: 99, min: 0, optimalMax: 0, optimalMin: 0, unit: 'AU' },\n    direction: 'lower-better',\n    source: 'rumberger-cac-1999',\n  },\n\n  CAC_Percentile: {\n    default: { max: 50, min: 0, optimalMax: 25, optimalMin: 0, unit: '%', warningMax: 75 },\n    direction: 'lower-better',\n    source: 'rumberger-cac-1999',\n  },\n\n  CAC_RCA: {\n    default: { max: 99, min: 0, optimalMax: 0, optimalMin: 0, unit: 'AU' },\n    direction: 'lower-better',\n    source: 'rumberger-cac-1999',\n  },\n\n  Cadmium: {\n    default: { max: 1.2, min: 0, optimalMax: 0.5, optimalMin: 0, unit: 'mcg/L' },\n    source: 'nr7-pcmso-2020',\n  },\n\n  Calcium: {\n    default: { max: 10.5, min: 8.5, optimalMax: 10.0, optimalMin: 9.0, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  CEA: {\n    default: { max: 3.0, min: 0, optimalMax: 2.5, optimalMin: 0, unit: 'ng/mL' },\n    source: 'sturgeon-nacb-2008',\n  },\n\n  // CK: valores conservadores baseados em faixas laboratoriais típicas\n  CK: {\n    default: { max: 190, min: 30, optimalMax: 170, optimalMin: 40, unit: 'U/L' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      { sex: 'F', range: { max: 170, min: 30, optimalMax: 150, optimalMin: 40, unit: 'U/L' } },\n    ],\n  },\n\n  Chloride: {\n    default: { max: 106, min: 98, optimalMax: 105, optimalMin: 100, unit: 'mEq/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // Colesterol total — SBC 2017/2025: valor desejável < 190 mg/dL para adultos,\n  // com ou sem jejum. Limite anterior (200 mg/dL) refletia a diretriz ATP III\n  // (NCEP, 2002), superada pelas atualizações brasileiras.\n  Cholesterol: {\n    default: { max: 190, min: 0, optimalMax: 170, optimalMin: 0, unit: 'mg/dL' },\n    source: 'sbc-lipids-2025',\n  },\n\n  // Índice de Castelli I (CT/HDL-c)\n  Cholesterol_HDL_Ratio: {\n    // Índice de Castelli I — SBC 2017: M <4.9, F <4.3\n    default: { max: 4.9, min: 0, optimalMax: 3.5, optimalMin: 0, unit: '' },\n    direction: 'lower-better',\n    source: 'castelli-ratio-1992',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 4.9, min: 0, optimalMax: 4.0, optimalMin: 0, unit: '' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 4.3, min: 0, optimalMax: 3.5, optimalMin: 0, unit: '' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  CO2: {\n    default: { max: 29, min: 23, optimalMax: 28, optimalMin: 24, unit: 'mEq/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Copper: {\n    default: { max: 175, min: 70, optimalMax: 150, optimalMin: 85, unit: 'mcg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  CoQ10: {\n    default: { max: 1.5, min: 0.5, optimalMax: 1.3, optimalMin: 0.7, unit: 'mg/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Cortisol: {\n    default: { max: 25, min: 5, optimalMax: 20, optimalMin: 10, unit: 'mcg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  CortisolFree: {\n    default: { max: 2.5, min: 0.5, optimalMax: 2.0, optimalMin: 0.8, unit: 'mcg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  CPeptide: {\n    default: {\n      fastingRequired: 'strict',\n      max: 3.9,\n      min: 0.8,\n      optimalMax: 3.0,\n      optimalMin: 1.0,\n      unit: 'ng/mL',\n    },\n    source: 'tietz-7ed-2015',\n  },\n\n  Creatinine: {\n    default: { max: 1.2, min: 0.6, optimalMax: 1.0, optimalMin: 0.7, unit: 'mg/dL' },\n    source: 'pns-bioquimica-2019',\n    variants: [\n      // Gestação: hiperfiltração glomerular (↑ 40–50% GFR) reduz a creatinina\n      // sérica. Valores \"normais\" de não-gestante podem sinalizar disfunção\n      // renal em gestante. Limites tipicamente citados: 0.4–0.8 mg/dL.\n      {\n        pregnant: true,\n        range: { max: 0.8, min: 0.4, optimalMax: 0.7, optimalMin: 0.5, unit: 'mg/dL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 18,\n        range: { max: 1.3, min: 0.7, optimalMax: 1.1, optimalMin: 0.8, unit: 'mg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 1.1, min: 0.5, optimalMax: 0.9, optimalMin: 0.6, unit: 'mg/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  CRP: {\n    default: { max: 3.0, min: 0, optimalMax: 1.0, optimalMin: 0, unit: 'mg/L' },\n    direction: 'lower-better',\n    source: 'tietz-7ed-2015',\n  },\n\n  CystatinC: {\n    default: { max: 1.0, min: 0.5, optimalMax: 0.9, optimalMin: 0.6, unit: 'mg/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // D-Dímero: 500 ng/mL é o corte clínico padrão para exclusão de TEV\n  DDimer: {\n    default: { max: 500, min: 0, optimalMax: 250, optimalMin: 0, unit: 'ng/mL' },\n    source: 'wells-ddimer-2003',\n  },\n\n  Omega3_DHA: {\n    default: { max: 8.0, min: 2.0, optimalMax: 6.5, optimalMin: 3.5, unit: '%' },\n    source: 'harris-omega3-2004',\n  },\n\n  DHEAS: {\n    default: { max: 500, min: 100, optimalMax: 400, optimalMin: 150, unit: 'mcg/dL' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMax: 39,\n        ageMin: 18,\n        range: { max: 640, min: 280, optimalMax: 500, optimalMin: 300, unit: 'mcg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 59,\n        ageMin: 40,\n        range: { max: 520, min: 120, optimalMax: 400, optimalMin: 150, unit: 'mcg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 60,\n        range: { max: 290, min: 42, optimalMax: 220, optimalMin: 80, unit: 'mcg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 39,\n        ageMin: 18,\n        range: { max: 380, min: 65, optimalMax: 300, optimalMin: 100, unit: 'mcg/dL' },\n        sex: 'F',\n      },\n      {\n        ageMax: 59,\n        ageMin: 40,\n        range: { max: 240, min: 32, optimalMax: 180, optimalMin: 60, unit: 'mcg/dL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 60,\n        range: { max: 140, min: 18, optimalMax: 100, optimalMin: 30, unit: 'mcg/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Omega3_DPA: {\n    default: { max: 2.0, min: 0.3, optimalMax: 1.5, optimalMin: 0.5, unit: '%' },\n    source: 'harris-omega3-2004',\n  },\n\n  eGFR: {\n    default: { max: 120, min: 90, optimalMax: 120, optimalMin: 90, unit: 'mL/min/1.73m²' },\n    source: 'kdigo-ckd-2024',\n    variants: [\n      {\n        ageMin: 60,\n        range: { max: 90, min: 60, optimalMax: 90, optimalMin: 60, unit: 'mL/min/1.73m²' },\n        sex: 'all',\n      },\n    ],\n  },\n\n  Eosinophils: {\n    default: { max: 5, min: 0, optimalMax: 4, optimalMin: 1, unit: '%' },\n    direction: 'lower-better',\n    source: 'pns-hemograma-2019',\n  },\n\n  Eosinophils_Abs: {\n    default: { max: 0.5, min: 0, optimalMax: 0.3, optimalMin: 0, unit: 'K/uL' },\n    source: 'pns-hemograma-2019',\n  },\n\n  Omega3_EPA: {\n    default: { max: 3.5, min: 0.5, optimalMax: 2.5, optimalMin: 1.0, unit: '%' },\n    source: 'harris-omega3-2004',\n  },\n\n  EPADPADHA: {\n    default: { max: 10.0, min: 3.0, optimalMax: 9.0, optimalMin: 5.0, unit: '%' },\n    source: 'harris-omega3-2004',\n  },\n\n  ESR: {\n    default: { max: 20, min: 0, optimalMax: 10, optimalMin: 0, unit: 'mm/hr' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Estradiol: {\n    default: { max: 40, min: 10, optimalMax: 35, optimalMin: 15, unit: 'pg/mL' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 40, min: 10, optimalMax: 30, optimalMin: 15, unit: 'pg/mL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 50,\n        ageMin: 18,\n        range: { max: 400, min: 30, optimalMax: 300, optimalMin: 50, unit: 'pg/mL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 51,\n        range: { max: 30, min: 0, optimalMax: 20, optimalMin: 0, unit: 'pg/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  F2Isoprostanes: {\n    default: { max: 86, min: 0, optimalMax: 60, optimalMin: 0, unit: 'pg/mL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // Ferritina — WHO 2020 é o documento de referência específico para avaliação\n  // do status de ferro via ferritina. Importante: inflamação aguda eleva\n  // ferritina (proteína de fase aguda); WHO 2020 recomenda dosagem concomitante\n  // de PCR para interpretação em contexto inflamatório (fora do escopo deste\n  // tipo de faixa, mas documentado aqui para consumidores).\n  Ferritin: {\n    default: { max: 150, min: 12, optimalMax: 120, optimalMin: 30, unit: 'ng/mL' },\n    source: 'who-iron-2020',\n    variants: [\n      // Gestação: ferritina cai fisiologicamente no 2º/3º trimestre pela expansão\n      // do volume plasmático e maior demanda fetal. WHO 2020: <15 ng/mL sugere\n      // depleção; muitas diretrizes nacionais usam <30 como gatilho mais sensível\n      // na gestação dada a alta prevalência de deficiência subclínica.\n      {\n        pregnant: true,\n        range: { max: 120, min: 15, optimalMax: 80, optimalMin: 30, unit: 'ng/mL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 18,\n        range: { max: 250, min: 20, optimalMax: 200, optimalMin: 40, unit: 'ng/mL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 50,\n        ageMin: 18,\n        range: { max: 120, min: 10, optimalMax: 80, optimalMin: 20, unit: 'ng/mL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 51,\n        range: { max: 200, min: 20, optimalMax: 150, optimalMin: 30, unit: 'ng/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // Fibrinogênio: 200-400 mg/dL — faixa de referência padrão (método de Clauss)\n  Fibrinogen: {\n    default: { max: 400, min: 200, optimalMax: 350, optimalMin: 250, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  FolicAcid: {\n    default: { max: 20, min: 3, optimalMax: 15, optimalMin: 5, unit: 'ng/mL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  FSH: {\n    default: { max: 12.4, min: 1.5, optimalMax: 10.0, optimalMin: 3.0, unit: 'mIU/mL' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 12.4, min: 1.5, optimalMax: 8.0, optimalMin: 1.5, unit: 'mIU/mL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 50,\n        ageMin: 18,\n        range: { max: 12.5, min: 3.5, optimalMax: 10.0, optimalMin: 3.5, unit: 'mIU/mL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 51,\n        range: { max: 134.8, min: 25.8, optimalMax: 80.0, optimalMin: 25.8, unit: 'mIU/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  GGT: {\n    default: { max: 55, min: 0, optimalMax: 30, optimalMin: 0, unit: 'U/L' },\n    direction: 'lower-better',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 61, min: 8, optimalMax: 40, optimalMin: 10, unit: 'U/L' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 36, min: 5, optimalMax: 25, optimalMin: 8, unit: 'U/L' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Ghrelin: {\n    default: { max: 1000, min: 300, optimalMax: 800, optimalMin: 400, unit: 'pg/mL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Globulin: {\n    default: { max: 3.5, min: 2.0, optimalMax: 3.2, optimalMin: 2.3, unit: 'g/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // Glicemia de jejum — 70–99 mg/dL é a faixa de normalidade (SBD 2024, ADA);\n  // hipoglicemia clinicamente acionável em não-diabético é <54 mg/dL (Level 2\n  // ADA/SBD), não 70. O corte 70 era Level 1 (alerta em diabético em tratamento)\n  // e gerava falsos \"abaixo do normal\" em indivíduos saudáveis cuja glicemia\n  // em jejum está fisiologicamente entre 54–70. optimalMin preserva o alvo.\n  Glucose: {\n    default: {\n      fastingRequired: 'strict',\n      max: 100,\n      min: 54,\n      optimalMax: 90,\n      optimalMin: 70,\n      unit: 'mg/dL',\n    },\n    source: 'sbd-diabetes-2024',\n    variants: [\n      // Gestação: DMG (IADPSG/SBD 2024) usa cortes mais restritivos na glicemia\n      // de jejum — ≥92 mg/dL já indica diabetes mellitus gestacional. Portanto\n      // a faixa \"normal\" em gestante vai até 91 mg/dL no jejum.\n      {\n        pregnant: true,\n        range: {\n          fastingRequired: 'strict',\n          max: 91,\n          min: 54,\n          optimalMax: 85,\n          optimalMin: 70,\n          unit: 'mg/dL',\n        },\n        sex: 'F',\n      },\n    ],\n  },\n\n  GlycoMark: {\n    default: { max: 40, min: 10, optimalMax: 35, optimalMin: 15, unit: 'mcg/mL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  GrowthHormone: {\n    default: { max: 5, min: 0, optimalMax: 3, optimalMin: 0, unit: 'ng/mL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // HbA1c — SBD 2024 não estabelece piso de referência clinicamente acionável.\n  // Valores <4.0% podem refletir anemia hemolítica, perda sanguínea recente ou\n  // hemoglobinopatia, não patologia do metabolismo glicêmico. Usamos min=2 como\n  // piso de sanidade (HbA1c <2% é quase sempre erro instrumental/entrada) sem\n  // criar flag clínico em valores fisiologicamente baixos. optimalMin preserva\n  // o alvo fisiológico da fração glicada.\n  HbA1c: {\n    default: { max: 5.7, min: 2, optimalMax: 5.3, optimalMin: 4.5, unit: '%' },\n    source: 'sbd-diabetes-2024',\n  },\n\n  Hct: {\n    default: { max: 50, min: 36, optimalMax: 48, optimalMin: 40, unit: '%' },\n    source: 'pns-hemograma-2019',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 54, min: 40, optimalMax: 50, optimalMin: 42, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 48, min: 36, optimalMax: 45, optimalMin: 38, unit: '%' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // HDL — SBC 2017/2025: desejável > 40 mg/dL (♂) e > 50 mg/dL (♀).\n  // A diretriz NÃO define teto de normalidade — HDL alto é cardioprotetor.\n  // Limites superiores anteriormente fixados em 60 mg/dL geravam falsos\n  // alertas. Mantém-se `max` apenas como limite técnico do gauge (100 mg/dL),\n  // não como ponto de corte clínico; consumidores devem tratar `direction:\n  // higher-better` como sinal autoritativo.\n  HDL: {\n    default: { max: 100, min: 40, optimalMax: 100, optimalMin: 50, unit: 'mg/dL' },\n    direction: 'higher-better',\n    source: 'sbc-lipids-2025',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 100, min: 40, optimalMax: 100, optimalMin: 45, unit: 'mg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 100, min: 50, optimalMax: 100, optimalMin: 55, unit: 'mg/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  HDL_Large: {\n    // HDL Large: higher is better\n    // Quest Ion Mobility reference: Male 4334-10815, Female 5038-17886 nmol/L, optimal >6729\n    default: { max: 17886, min: 4334, optimalMax: 17886, optimalMin: 6729, unit: 'nmol/L' },\n    direction: 'higher-better',\n    source: 'caulfield-ionmobility-2008',\n  },\n\n  Hgb: {\n    default: { max: 17.5, min: 12.0, optimalMax: 16.0, optimalMin: 13.5, unit: 'g/dL' },\n    source: 'pns-hemograma-2019',\n    variants: [\n      // Gestação: hemodiluição fisiológica reduz o piso aceitável.\n      // OMS e CDC: anemia gestacional quando Hgb <11 g/dL (1º e 3º tri) ou\n      // <10.5 g/dL (2º tri, dilucional mais acentuada). Catch-all adota a\n      // faixa mais conservadora (2º tri) quando trimestre é desconhecido.\n      {\n        pregnant: true,\n        pregnancyTrimester: 1,\n        range: { max: 14.0, min: 11.0, optimalMax: 13.0, optimalMin: 11.5, unit: 'g/dL' },\n        sex: 'F',\n      },\n      {\n        pregnant: true,\n        pregnancyTrimester: 2,\n        range: { max: 14.0, min: 10.5, optimalMax: 13.0, optimalMin: 11.0, unit: 'g/dL' },\n        sex: 'F',\n      },\n      {\n        pregnant: true,\n        pregnancyTrimester: 3,\n        range: { max: 14.0, min: 11.0, optimalMax: 13.0, optimalMin: 11.5, unit: 'g/dL' },\n        sex: 'F',\n      },\n      {\n        pregnant: true,\n        range: { max: 14.0, min: 10.5, optimalMax: 13.0, optimalMin: 11.0, unit: 'g/dL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 18,\n        range: { max: 17.5, min: 13.5, optimalMax: 16.5, optimalMin: 14.0, unit: 'g/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 15.5, min: 12.0, optimalMax: 14.5, optimalMin: 12.5, unit: 'g/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // HOMA-IR — corte 2.71 do estudo BRAMS (Geloneze et al., 2009) validado em\n  // população urbana brasileira; Tietz 7ª ed. não publica corte próprio de\n  // HOMA-IR, então a fonte anterior era citação inadequada.\n  HOMA_IR: {\n    default: {\n      fastingRequired: 'strict',\n      max: 2.71,\n      min: 0,\n      optimalMax: 1.5,\n      optimalMin: 0,\n      unit: '',\n    },\n    direction: 'lower-better',\n    source: 'geloneze-brams-2009',\n  },\n\n  Homocysteine: {\n    default: { max: 15, min: 4, optimalMax: 10, optimalMin: 5, unit: 'umol/L' },\n    direction: 'lower-better',\n    source: 'selhub-homocysteine-1999',\n  },\n\n  IGF1: {\n    default: { max: 350, min: 100, optimalMax: 300, optimalMin: 150, unit: 'ng/mL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  ImmatureGranulocytes: {\n    default: { max: 1.0, min: 0, optimalMax: 0.5, optimalMin: 0, unit: '%' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Insulin: {\n    default: {\n      fastingRequired: 'strict',\n      max: 25,\n      min: 2,\n      optimalMax: 8,\n      optimalMin: 3,\n      unit: 'µIU/mL',\n    },\n    source: 'tietz-7ed-2015',\n  },\n\n  Iron: {\n    default: { max: 170, min: 60, optimalMax: 140, optimalMin: 80, unit: 'mcg/dL' },\n    source: 'sbpc-ml-2021',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 175, min: 65, optimalMax: 150, optimalMin: 80, unit: 'mcg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 170, min: 50, optimalMax: 130, optimalMin: 60, unit: 'mcg/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Lactate: {\n    default: { max: 2.2, min: 0.5, optimalMax: 1.8, optimalMin: 0.7, unit: 'mmol/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // DHL/LDH — método IFCC a 37 °C (padrão atual na maioria dos laboratórios\n  // brasileiros). Limites superiores de referência (97,5° percentil) obtidos\n  // por Schumann & Klauke (2002) em indivíduos ≥17 anos: 247 U/L (mulheres)\n  // e 248 U/L (homens). O IFCC publica apenas o limite superior; o limite\n  // inferior é fixado em 0 pois DHL baixa não tem significado clínico.\n  // Não comparar com método Wróblewski-LaDue (faixas mais antigas, ~240–480).\n  LDH: {\n    default: { max: 248, min: 0, optimalMax: 248, optimalMin: 0, unit: 'U/L' },\n    direction: 'lower-better',\n    source: 'schumann-ifcc-ldh-2002',\n    variants: [\n      {\n        ageMin: 17,\n        range: { max: 248, min: 0, optimalMax: 248, optimalMin: 0, unit: 'U/L' },\n        sex: 'M',\n      },\n      {\n        ageMin: 17,\n        range: { max: 247, min: 0, optimalMax: 247, optimalMin: 0, unit: 'U/L' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  LDL: {\n    default: { max: 100, min: 0, optimalMax: 70, optimalMin: 0, unit: 'mg/dL' },\n    direction: 'lower-better',\n    source: 'sbc-lipids-2025',\n  },\n\n  LDL_Medium: {\n    // LDL Medium (LDL Média): lower is better\n    // Quest Ion Mobility reference: Male 167-485, Female 121-397 nmol/L, optimal <215\n    default: { max: 485, min: 121, optimalMax: 215, optimalMin: 121, unit: 'nmol/L' },\n    direction: 'lower-better',\n    source: 'caulfield-ionmobility-2008',\n  },\n\n  LDL_ParticleNumber: {\n    // LDL Particle Number: lower is better\n    // Quest Ion Mobility reference: 1016-2185 nmol/L, optimal <1138\n    default: { max: 2185, min: 1016, optimalMax: 1138, optimalMin: 1016, unit: 'nmol/L' },\n    direction: 'lower-better',\n    source: 'caulfield-ionmobility-2008',\n  },\n\n  LDL_Peak_Size: {\n    // LDL Peak Size: higher is better (larger particles less atherogenic)\n    // Quest Ion Mobility reference: optimal >222.9 Å (22.29 nm)\n    default: { max: 250.0, min: 217.4, optimalMax: 250.0, optimalMin: 222.9, unit: 'Å' },\n    direction: 'higher-better',\n    source: 'caulfield-ionmobility-2008',\n  },\n\n  LDL_Small: {\n    // LDL Small (LDL Pequena): lower is better (small dense LDL is most atherogenic)\n    // Quest Ion Mobility reference: Male 123-441, Female 126-382 nmol/L, optimal <142\n    default: { max: 441, min: 123, optimalMax: 142, optimalMin: 123, unit: 'nmol/L' },\n    direction: 'lower-better',\n    source: 'caulfield-ionmobility-2008',\n  },\n\n  Lead: {\n    default: { max: 5, min: 0, optimalMax: 2, optimalMin: 0, unit: 'mcg/dL' },\n    source: 'nr7-pcmso-2020',\n  },\n\n  Leptin: {\n    default: { max: 15, min: 2, optimalMax: 12, optimalMin: 3, unit: 'ng/mL' },\n    direction: 'lower-better',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 10, min: 1, optimalMax: 8, optimalMin: 2, unit: 'ng/mL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 25, min: 4, optimalMax: 18, optimalMin: 5, unit: 'ng/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  LH: {\n    default: { max: 8.6, min: 1.7, optimalMax: 8.0, optimalMin: 2.0, unit: 'mIU/mL' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 8.6, min: 1.7, optimalMax: 6.0, optimalMin: 1.7, unit: 'mIU/mL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 50,\n        ageMin: 18,\n        range: { max: 12.6, min: 2.4, optimalMax: 10.0, optimalMin: 2.4, unit: 'mIU/mL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 51,\n        range: { max: 58.5, min: 7.7, optimalMax: 40.0, optimalMin: 10.0, unit: 'mIU/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Omega6_LA: {\n    default: { max: 35.0, min: 15.0, optimalMax: 28.0, optimalMin: 18.0, unit: '%' },\n    source: 'simopoulos-omega-ratio-2002',\n  },\n\n  // Lp(a) — SBC 2025 (seção 3.1.1.2.7): níveis ≥ 50 mg/dL ou ≥ 125 nmol/L são\n  // considerados aumentados, com indicação de rastreamento em cascata familiar.\n  // A diretriz recomenda ensaio independente de isoforma medido em nmol/L; a\n  // unidade nmol/L é mantida aqui por refletir o padrão laboratorial atual.\n  // Limites anteriores (max=75) refletiam pontos de corte expressos em mg/dL,\n  // gerando incompatibilidade com a unidade nmol/L declarada.\n  Lipoprotein_a: {\n    default: { max: 125, min: 0, optimalMax: 75, optimalMin: 0, unit: 'nmol/L' },\n    direction: 'lower-better',\n    source: 'sbc-lipids-2025',\n  },\n\n  Lymphocytes: {\n    default: { max: 40, min: 20, optimalMax: 35, optimalMin: 25, unit: '%' },\n    source: 'pns-hemograma-2019',\n  },\n\n  Lymphocytes_Abs: {\n    default: { max: 4.0, min: 1.0, optimalMax: 3.0, optimalMin: 1.5, unit: 'K/uL' },\n    source: 'pns-hemograma-2019',\n  },\n\n  Magnesium: {\n    default: { max: 2.2, min: 1.7, optimalMax: 2.1, optimalMin: 1.9, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Magnesium_RBC: {\n    default: { max: 6.8, min: 4.0, optimalMax: 6.0, optimalMin: 4.5, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  MCH: {\n    default: { max: 33, min: 27, optimalMax: 32, optimalMin: 28, unit: 'pg' },\n    source: 'pns-hemograma-2019',\n  },\n\n  MCHC: {\n    default: { max: 36, min: 32, optimalMax: 35, optimalMin: 33, unit: 'g/dL' },\n    source: 'pns-hemograma-2019',\n  },\n\n  MCV: {\n    default: { max: 100, min: 80, optimalMax: 98, optimalMin: 82, unit: 'fL' },\n    source: 'pns-hemograma-2019',\n  },\n\n  Mercury: {\n    default: { max: 10, min: 0, optimalMax: 5, optimalMin: 0, unit: 'mcg/L' },\n    source: 'nr7-pcmso-2020',\n  },\n\n  Microalbumin: {\n    default: { max: 30, min: 0, optimalMax: 20, optimalMin: 0, unit: 'mg/L' },\n    source: 'kdigo-ckd-2024',\n  },\n\n  MMA: {\n    default: { max: 378, min: 0, optimalMax: 270, optimalMin: 0, unit: 'nmol/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Monocytes: {\n    default: { max: 8, min: 2, optimalMax: 7, optimalMin: 3, unit: '%' },\n    source: 'pns-hemograma-2019',\n  },\n\n  Monocytes_Abs: {\n    default: { max: 0.8, min: 0.2, optimalMax: 0.7, optimalMin: 0.3, unit: 'K/uL' },\n    source: 'pns-hemograma-2019',\n  },\n\n  MPV: {\n    default: { max: 11.5, min: 7.5, optimalMax: 10.5, optimalMin: 8.0, unit: 'fL' },\n    source: 'pns-hemograma-2019',\n  },\n\n  // MPO: Meuwese 2007 (EPIC-Norfolk) — risco CV elevado >322 pmol/L\n  Myeloperoxidase: {\n    default: { max: 470, min: 0, optimalMax: 322, optimalMin: 0, unit: 'pmol/L' },\n    source: 'meuwese-mpo-2007',\n  },\n\n  // WBC Differential (%)\n  Neutrophils: {\n    default: { max: 70, min: 40, optimalMax: 65, optimalMin: 50, unit: '%' },\n    source: 'pns-hemograma-2019',\n  },\n\n  // WBC Differential (Absolute)\n  Neutrophils_Abs: {\n    default: { max: 8.0, min: 1.5, optimalMax: 6.0, optimalMin: 2.0, unit: 'K/uL' },\n    source: 'pns-hemograma-2019',\n  },\n\n  NonHDL_Cholesterol: {\n    default: { max: 130, min: 0, optimalMax: 100, optimalMin: 0, unit: 'mg/dL' },\n    direction: 'lower-better',\n    source: 'sbc-lipids-2025',\n  },\n\n  NRBC: {\n    default: { max: 0, min: 0, optimalMax: 0, optimalMin: 0, unit: '/100WBC' },\n    source: 'tietz-7ed-2015',\n  },\n\n  NTproBNP: {\n    default: { max: 125, min: 0, optimalMax: 75, optimalMin: 0, unit: 'pg/mL' },\n    source: 'sbc-ic-2018',\n  },\n\n  Oleic_Acid: {\n    default: { max: 25.0, min: 15.0, optimalMax: 22.0, optimalMin: 18.0, unit: '%' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Omega3_Index: {\n    default: { max: 8.0, min: 4.0, optimalMax: 8.0, optimalMin: 5.5, unit: '%' },\n    source: 'harris-omega3-2004',\n  },\n\n  // Ômega-3 Total (% de ácidos graxos eritrocitários) — Harris & von Schacky\n  // (2004) propõem ≥ 8% como zona ótima de proteção cardiovascular; valores\n  // entre 4% e 8% representam risco intermediário, < 4% risco alto.\n  // optimalMin anterior (5.5%) ficava em zona intermediária, contradizendo\n  // a literatura e o próprio texto educacional do `platform`.\n  Omega3_Total: {\n    default: { max: 12.0, min: 3.0, optimalMax: 10.0, optimalMin: 8.0, unit: '%' },\n    source: 'harris-omega3-2004',\n  },\n\n  Omega6_Total: {\n    default: { max: 40.0, min: 20.0, optimalMax: 35.0, optimalMin: 25.0, unit: '%' },\n    source: 'simopoulos-omega-ratio-2002',\n  },\n\n  Omega6_Omega3_Ratio: {\n    default: { max: 10.0, min: 1.0, optimalMax: 4.0, optimalMin: 1.0, unit: '' },\n    direction: 'lower-better',\n    source: 'simopoulos-omega-ratio-2002',\n  },\n\n  OmegaCheck: {\n    default: { max: 8.0, min: 4.0, optimalMax: 8.0, optimalMin: 5.5, unit: '%' },\n    source: 'harris-omega3-2004',\n  },\n\n  Palmitic_Acid: {\n    default: { max: 30.0, min: 20.0, optimalMax: 27.0, optimalMin: 22.0, unit: '%' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Phosphorus: {\n    default: { max: 4.5, min: 2.5, optimalMax: 4.0, optimalMin: 3.0, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Platelets: {\n    default: { max: 400, min: 150, optimalMax: 350, optimalMin: 180, unit: 'K/uL' },\n    source: 'pns-hemograma-2019',\n  },\n\n  Potassium: {\n    default: { max: 5.0, min: 3.5, optimalMax: 4.6, optimalMin: 3.8, unit: 'mEq/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Prealbumin: {\n    default: { max: 38, min: 18, optimalMax: 35, optimalMin: 20, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // Progesterona — varia drasticamente com a fase do ciclo menstrual.\n  // O schema atual não modela fase do ciclo, então adotamos faixas amplas\n  // por sexo: o `default` cobre homens/fase folicular/pós-menopausa; a\n  // variante feminina expande até a faixa esperada de fase lútea\n  // (~3-20 ng/mL). Interpretação correta exige correlação com a fase do\n  // ciclo, indisponível neste contexto.\n  Progesterone: {\n    default: { max: 0.9, min: 0.1, optimalMax: 0.7, optimalMin: 0.2, unit: 'ng/mL' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 0.9, min: 0.1, optimalMax: 0.6, optimalMin: 0.2, unit: 'ng/mL' },\n        sex: 'M',\n      },\n      // Mulheres em idade reprodutiva: faixa que abarca fases folicular\n      // (0.1-0.9 ng/mL) e lútea (3-20 ng/mL). Sem contexto de fase do ciclo,\n      // valores intermediários (1-3 ng/mL) ficam em zona ambígua.\n      {\n        ageMax: 50,\n        ageMin: 18,\n        range: { max: 20.0, min: 0.1, optimalMax: 15.0, optimalMin: 0.2, unit: 'ng/mL' },\n        sex: 'F',\n      },\n      // Pós-menopausa: valores tipicamente < 0.5 ng/mL (sem ovulação).\n      {\n        ageMin: 51,\n        range: { max: 0.5, min: 0, optimalMax: 0.3, optimalMin: 0, unit: 'ng/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Prolactin: {\n    default: { max: 18, min: 2, optimalMax: 15, optimalMin: 4, unit: 'ng/mL' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 18, min: 2, optimalMax: 15, optimalMin: 4, unit: 'ng/mL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 29, min: 2, optimalMax: 23, optimalMin: 4, unit: 'ng/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  PSA: {\n    default: { max: 4.0, min: 0, optimalMax: 2.5, optimalMin: 0, unit: 'ng/mL' },\n    source: 'sturgeon-nacb-2008',\n    variants: [\n      {\n        ageMax: 49,\n        ageMin: 18,\n        range: { max: 2.5, min: 0, optimalMax: 1.5, optimalMin: 0, unit: 'ng/mL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 59,\n        ageMin: 50,\n        range: { max: 3.5, min: 0, optimalMax: 2.5, optimalMin: 0, unit: 'ng/mL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 69,\n        ageMin: 60,\n        range: { max: 4.5, min: 0, optimalMax: 3.0, optimalMin: 0, unit: 'ng/mL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 70,\n        range: { max: 6.5, min: 0, optimalMax: 4.0, optimalMin: 0, unit: 'ng/mL' },\n        sex: 'M',\n      },\n    ],\n  },\n\n  RBC: {\n    default: { max: 5.5, min: 4.0, optimalMax: 5.2, optimalMin: 4.3, unit: 'M/uL' },\n    source: 'pns-hemograma-2019',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 5.9, min: 4.5, optimalMax: 5.5, optimalMin: 4.7, unit: 'M/uL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 5.2, min: 4.0, optimalMax: 5.0, optimalMin: 4.2, unit: 'M/uL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  RDW: {\n    default: { max: 14.5, min: 11.5, optimalMax: 14.0, optimalMin: 12.0, unit: '%' },\n    source: 'pns-hemograma-2019',\n  },\n\n  Reticulocytes: {\n    default: { max: 2.5, min: 0.5, optimalMax: 2.0, optimalMin: 0.8, unit: '%' },\n    source: 'pns-hemograma-2019',\n  },\n\n  SDMA: {\n    default: { max: 0.6, min: 0.3, optimalMax: 0.5, optimalMin: 0.3, unit: 'umol/L' },\n    source: 'schwedhelm-sdma-2011',\n  },\n\n  Selenium: {\n    default: { max: 150, min: 70, optimalMax: 125, optimalMin: 85, unit: 'mcg/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  SHBG: {\n    default: { max: 54, min: 18, optimalMax: 50, optimalMin: 20, unit: 'nmol/L' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 54, min: 18, optimalMax: 45, optimalMin: 20, unit: 'nmol/L' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 122, min: 24, optimalMax: 90, optimalMin: 30, unit: 'nmol/L' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Sodium: {\n    default: { max: 145, min: 136, optimalMax: 143, optimalMin: 138, unit: 'mEq/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  SpecificGravity_Urine: {\n    default: { max: 1.03, min: 1.005, optimalMax: 1.025, optimalMin: 1.01, unit: 'SG' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Stearic_Acid: {\n    default: { max: 14.0, min: 8.0, optimalMax: 12.0, optimalMin: 10.0, unit: '%' },\n    source: 'tietz-7ed-2015',\n  },\n\n  T3Free: {\n    default: { max: 4.2, min: 2.3, optimalMax: 3.8, optimalMin: 2.8, unit: 'pg/mL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  T3Reverse: {\n    default: { max: 24, min: 10, optimalMax: 20, optimalMin: 12, unit: 'ng/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  T4Free: {\n    default: { max: 1.8, min: 0.8, optimalMax: 1.5, optimalMin: 1.0, unit: 'ng/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  T4Total: {\n    default: { max: 12.0, min: 4.5, optimalMax: 10.0, optimalMin: 6.0, unit: 'ug/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Testosterone: {\n    default: { max: 1000, min: 300, optimalMax: 800, optimalMin: 500, unit: 'ng/dL' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMax: 49,\n        ageMin: 18,\n        range: { max: 1000, min: 300, optimalMax: 800, optimalMin: 500, unit: 'ng/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 50,\n        range: { max: 800, min: 200, optimalMax: 650, optimalMin: 400, unit: 'ng/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 70, min: 15, optimalMax: 50, optimalMin: 20, unit: 'ng/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  TestosteroneBioavailable: {\n    default: { max: 200, min: 50, optimalMax: 150, optimalMin: 80, unit: 'ng/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // TestosteroneFree - using direct immunoassay ranges (Quest/LabCorp standard)\n  // Previous values (9.3-26.5 pg/mL) were based on equilibrium dialysis method\n  TestosteroneFree: {\n    default: { max: 155, min: 35, optimalMax: 120, optimalMin: 50, unit: 'pg/mL' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMax: 49,\n        ageMin: 18,\n        range: { max: 155, min: 35, optimalMax: 120, optimalMin: 50, unit: 'pg/mL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 50,\n        range: { max: 130, min: 30, optimalMax: 100, optimalMin: 40, unit: 'pg/mL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 5.0, min: 0.2, optimalMax: 3.0, optimalMin: 0.5, unit: 'pg/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  TIBC: {\n    default: { max: 370, min: 250, optimalMax: 350, optimalMin: 280, unit: 'mcg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  TotalProtein: {\n    default: { max: 8.3, min: 6.0, optimalMax: 7.8, optimalMin: 6.5, unit: 'g/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Trans_Fat_Index: {\n    default: { max: 1.0, min: 0, optimalMax: 0.5, optimalMin: 0, unit: '%' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Transferrin: {\n    default: { max: 360, min: 200, optimalMax: 340, optimalMin: 220, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  TransferrinSaturation: {\n    default: { max: 50, min: 20, optimalMax: 45, optimalMin: 25, unit: '%' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 55, min: 20, optimalMax: 45, optimalMin: 25, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 50, min: 15, optimalMax: 40, optimalMin: 20, unit: '%' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // Triglicérides — SBC 2017/2025 permite dosagem não-jejum com corte distinto\n  // (<175 mg/dL pós-prandial). Marcamos `preferred` para indicar que a faixa\n  // padrão é de jejum, mas não bloqueamos interpretação em não-jejum.\n  Triglycerides: {\n    default: {\n      fastingRequired: 'preferred',\n      max: 150,\n      min: 0,\n      optimalMax: 100,\n      optimalMin: 0,\n      unit: 'mg/dL',\n    },\n    direction: 'lower-better',\n    source: 'sbc-lipids-2025',\n  },\n\n  // TroponinI: 0.04 ng/mL = percentil 99 (ensaio Siemens TnI-Ultra)\n  TroponinI: {\n    default: { max: 0.04, min: 0, optimalMax: 0.02, optimalMin: 0, unit: 'ng/mL' },\n    source: 'keller-tni-2013',\n  },\n\n  // TroponinT: 14 ng/L = percentil 99 hs-cTnT (ensaio Roche Elecsys 5ª geração)\n  TroponinT: {\n    default: { max: 14, min: 0, optimalMax: 10, optimalMin: 0, unit: 'ng/L' },\n    source: 'giannitsis-hstnt-2010',\n  },\n\n  // TSH — 0.4–4.0 é a faixa de referência adulta geral. O alvo 2.5 µIU/mL é\n  // específico do 1º trimestre gestacional (ATA 2017) e não se aplica a\n  // não-gestantes; optimalMax=3.0 reflete o limite superior do tercil \"ótimo\"\n  // sem invadir a faixa subclínica. Variante ageMin=65 mantém limite superior\n  // expandido (tolerância fisiológica do eixo em idosos, SBEM 2013).\n  TSH: {\n    default: { max: 4.0, min: 0.4, optimalMax: 3.0, optimalMin: 1.0, unit: 'µIU/mL' },\n    source: 'sbem-thyroid-2013',\n    variants: [\n      // Variantes gestacionais (ATA 2017 / SBEM): supressão fisiológica por hCG\n      // no 1º trimestre, recuperação progressiva no 2º/3º. Trimestre-específicas\n      // precedem a catch-all; catch-all cobre contexto gestante sem trimestre\n      // conhecido.\n      // optimalMin/optimalMax definem subfaixa \"alvo\" mais estreita que o\n      // intervalo de referência — ex.: 1º tri aceita 0.1–2.5, mas o alvo\n      // terapêutico é 0.5–2.5.\n      {\n        pregnant: true,\n        pregnancyTrimester: 1,\n        range: { max: 2.5, min: 0.1, optimalMax: 2.0, optimalMin: 0.5, unit: 'µIU/mL' },\n        sex: 'F',\n      },\n      {\n        pregnant: true,\n        pregnancyTrimester: 2,\n        range: { max: 3.0, min: 0.2, optimalMax: 2.5, optimalMin: 0.5, unit: 'µIU/mL' },\n        sex: 'F',\n      },\n      {\n        pregnant: true,\n        pregnancyTrimester: 3,\n        range: { max: 3.0, min: 0.3, optimalMax: 2.5, optimalMin: 0.5, unit: 'µIU/mL' },\n        sex: 'F',\n      },\n      // Catch-all gestacional — usada quando o trimestre não é informado.\n      // Adota a faixa mais conservadora (2º/3º trimestre: 0.2–3.0).\n      {\n        pregnant: true,\n        range: { max: 3.0, min: 0.2, optimalMax: 2.5, optimalMin: 0.5, unit: 'µIU/mL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 65,\n        range: { max: 6.0, min: 0.4, optimalMax: 4.0, optimalMin: 1.0, unit: 'µIU/mL' },\n        sex: 'all',\n      },\n    ],\n  },\n\n  // Ureia — convenção brasileira (laboratórios reportam Ureia, não BUN).\n  // Faixa adulta de 15-50 mg/dL (Ureia ≈ BUN × 2,14). Limites anteriores\n  // (7-20 mg/dL) refletiam BUN/Nitrogênio Ureico, gerando falsos diagnósticos\n  // de azotemia em pacientes com Ureia normal. LOINC 3094-0 (BUN) também\n  // deve ser revisto em biomarkers.ts — ver issue #41.\n  Urea: {\n    default: { max: 50, min: 15, optimalMax: 40, optimalMin: 20, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  UricAcid: {\n    default: { max: 7.0, min: 2.5, optimalMax: 5.5, optimalMin: 3.0, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 7.0, min: 3.4, optimalMax: 6.0, optimalMin: 4.0, unit: 'mg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 6.0, min: 2.4, optimalMax: 5.0, optimalMin: 3.0, unit: 'mg/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Urobilinogen_Urine: {\n    default: { max: 1.0, min: 0.1, optimalMax: 1.0, optimalMin: 0.1, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  pH_Urine: {\n    default: { max: 8.0, min: 4.5, optimalMax: 7.0, optimalMin: 5.5, unit: 'pH' },\n    source: 'tietz-7ed-2015',\n  },\n\n  HyalineCasts_Urine: {\n    default: { max: 2, min: 0, optimalMax: 1, optimalMin: 0, unit: '/LPF' },\n    source: 'tietz-7ed-2015',\n  },\n\n  RBC_Urine: {\n    default: { max: 3, min: 0, optimalMax: 1, optimalMin: 0, unit: '/HPF' },\n    source: 'tietz-7ed-2015',\n  },\n\n  SquamousEpithelial_Urine: {\n    default: { max: 15, min: 0, optimalMax: 5, optimalMin: 0, unit: '/HPF' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Leukocytes_Urine: {\n    default: { max: 5, min: 0, optimalMax: 2, optimalMin: 0, unit: '/HPF' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Folate: {\n    default: { max: 20, min: 3.9, optimalMax: 17, optimalMin: 5, unit: 'ng/mL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  VitaminA: {\n    default: { max: 100, min: 20, optimalMax: 80, optimalMin: 30, unit: 'mcg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  VitaminB1: {\n    default: { max: 180, min: 70, optimalMax: 150, optimalMin: 80, unit: 'nmol/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  VitaminB12: {\n    default: { max: 900, min: 200, optimalMax: 800, optimalMin: 400, unit: 'pg/mL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  VitaminB6: {\n    default: { max: 50, min: 5, optimalMax: 40, optimalMin: 10, unit: 'ng/mL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  VitaminC: {\n    default: { max: 2.0, min: 0.4, optimalMax: 1.5, optimalMin: 0.6, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // Vitamina D — posicionamento conjunto SBEM/SBPC-ML 2017:\n  // ≥20 ng/mL é desejável para população saudável <60 anos\n  // ≥30 ng/mL é recomendado para grupos de risco (idosos, gestantes, DRC,\n  // osteoporose, hiperparatireoidismo secundário).\n  // A variante ageMin=60 cobre idosos. Gestação, doença renal crônica,\n  // osteoporose e hiperparatireoidismo secundário também exigem min=30;\n  // o tipo `BiomarkerReferenceRange` atual não expressa esses contextos\n  // clínicos além de gestação e idade, portanto consumidores devem aplicar\n  // o limiar ≥30 nessas populações quando souberem a comorbidade. Gestação\n  // será modelada quando `pregnant: true` — aceita-se TODO até lá.\n  // TODO(PR-vitd-pregnancy): adicionar variante `pregnant: true` com min=30\n  // quando a modelagem de comorbidades chegar ao schema.\n  VitaminD: {\n    default: { max: 100, min: 20, optimalMax: 70, optimalMin: 40, unit: 'ng/mL' },\n    source: 'ferreira-vitd-2017',\n    variants: [\n      {\n        ageMin: 60,\n        range: { max: 100, min: 30, optimalMax: 70, optimalMin: 40, unit: 'ng/mL' },\n        sex: 'all',\n      },\n    ],\n  },\n\n  VitaminD_1_25: {\n    default: { max: 72, min: 18, optimalMax: 60, optimalMin: 25, unit: 'pg/mL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  VitaminE: {\n    default: { max: 17, min: 5.5, optimalMax: 14, optimalMin: 7, unit: 'mg/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // VLDL — estimado clinicamente via TG/5 (método Friedewald). O corte de\n  // referência deriva de triglicérides <150 mg/dL (SBC 2025, dislipidemias),\n  // portanto VLDL <30. Friedewald-1972 permanece registrada como fonte do\n  // método de cálculo, mas a faixa de referência tem respaldo na diretriz\n  // SBC 2025.\n  VLDL: {\n    default: { max: 30, min: 2, optimalMax: 20, optimalMin: 5, unit: 'mg/dL' },\n    source: 'sbc-lipids-2025',\n  },\n\n  WBC: {\n    default: { max: 11.0, min: 4.0, optimalMax: 8.0, optimalMin: 5.0, unit: 'K/uL' },\n    source: 'pns-hemograma-2019',\n  },\n\n  Zinc: {\n    default: { max: 120, min: 60, optimalMax: 100, optimalMin: 70, unit: 'mcg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  AndroidFatPct: {\n    default: { max: 35, min: 10, optimalMax: 25, optimalMin: 15, unit: '%' },\n    direction: 'lower-better',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 30, min: 10, optimalMax: 22, optimalMin: 12, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 42, min: 15, optimalMax: 32, optimalMin: 20, unit: '%' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  AndroidGynoidRatio: {\n    default: { max: 1.2, min: 0.5, optimalMax: 1.0, optimalMin: 0.6, unit: '' },\n    direction: 'lower-better',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 1.2, min: 0.6, optimalMax: 1.0, optimalMin: 0.7, unit: '' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 1.0, min: 0.4, optimalMax: 0.8, optimalMin: 0.5, unit: '' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  BMC: {\n    default: { max: 3.5, min: 2.0, optimalMax: 3.2, optimalMin: 2.3, unit: 'kg' },\n    direction: 'higher-better',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 4.0, min: 2.5, optimalMax: 3.5, optimalMin: 2.8, unit: 'kg' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 3.0, min: 1.8, optimalMax: 2.7, optimalMin: 2.0, unit: 'kg' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // BodyFatPct — Age-bracketed ranges from Gallagher et al. Am J Clin Nutr 2000;72:694-701\n  // (PMID: 10966886) and ACSM Guidelines for Exercise Testing, 11th Ed (2021)\n  BodyFatPct: {\n    default: { max: 30, min: 10, optimalMax: 25, optimalMin: 15, unit: '%' },\n    direction: 'lower-better',\n    source: 'gallagher-bodyfat-2000',\n    variants: [\n      // Men — age brackets\n      {\n        ageMax: 25,\n        ageMin: 18,\n        range: { max: 25, min: 5, optimalMax: 20, optimalMin: 10, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMax: 35,\n        ageMin: 26,\n        range: { max: 26, min: 5, optimalMax: 21, optimalMin: 11, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMax: 45,\n        ageMin: 36,\n        range: { max: 27, min: 5, optimalMax: 22, optimalMin: 12, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMax: 55,\n        ageMin: 46,\n        range: { max: 28, min: 5, optimalMax: 23, optimalMin: 13, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMin: 56,\n        range: { max: 29, min: 5, optimalMax: 24, optimalMin: 14, unit: '%' },\n        sex: 'M',\n      },\n      // Women — age brackets\n      {\n        ageMax: 25,\n        ageMin: 18,\n        range: { max: 32, min: 13, optimalMax: 28, optimalMin: 18, unit: '%' },\n        sex: 'F',\n      },\n      {\n        ageMax: 35,\n        ageMin: 26,\n        range: { max: 33, min: 13, optimalMax: 29, optimalMin: 18, unit: '%' },\n        sex: 'F',\n      },\n      {\n        ageMax: 45,\n        ageMin: 36,\n        range: { max: 34, min: 13, optimalMax: 30, optimalMin: 19, unit: '%' },\n        sex: 'F',\n      },\n      {\n        ageMax: 55,\n        ageMin: 46,\n        range: { max: 35, min: 13, optimalMax: 31, optimalMin: 20, unit: '%' },\n        sex: 'F',\n      },\n      {\n        ageMin: 56,\n        range: { max: 36, min: 13, optimalMax: 32, optimalMin: 20, unit: '%' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  FatFreeMass: {\n    default: { max: 80, min: 40, optimalMax: 70, optimalMin: 45, unit: 'kg' },\n    direction: 'higher-better',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 90, min: 50, optimalMax: 80, optimalMin: 55, unit: 'kg' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 60, min: 35, optimalMax: 52, optimalMin: 38, unit: 'kg' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  FatMass: {\n    default: { max: 30, min: 5, optimalMax: 20, optimalMin: 8, unit: 'kg' },\n    direction: 'lower-better',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 25, min: 5, optimalMax: 18, optimalMin: 7, unit: 'kg' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 30, min: 8, optimalMax: 22, optimalMin: 10, unit: 'kg' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  GynoidFatPct: {\n    default: { max: 45, min: 15, optimalMax: 35, optimalMin: 20, unit: '%' },\n    direction: 'lower-better',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 35, min: 12, optimalMax: 28, optimalMin: 15, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 50, min: 20, optimalMax: 40, optimalMin: 25, unit: '%' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  LeanMass: {\n    default: { max: 75, min: 35, optimalMax: 65, optimalMin: 40, unit: 'kg' },\n    direction: 'higher-better',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 85, min: 45, optimalMax: 75, optimalMin: 50, unit: 'kg' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 55, min: 30, optimalMax: 48, optimalMin: 35, unit: 'kg' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  TotalMass: {\n    default: { max: 100, min: 50, optimalMax: 85, optimalMin: 55, unit: 'kg' },\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 100, min: 55, optimalMax: 90, optimalMin: 60, unit: 'kg' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 85, min: 45, optimalMax: 75, optimalMin: 50, unit: 'kg' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  VATMass: {\n    default: { max: 1.5, min: 0, optimalMax: 0.8, optimalMin: 0, unit: 'kg' },\n    direction: 'lower-better',\n    source: 'ofenheimer-vat-2020',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 1.5, min: 0, optimalMax: 1.0, optimalMin: 0, unit: 'kg' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 1.0, min: 0, optimalMax: 0.5, optimalMin: 0, unit: 'kg' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  VATVolume: {\n    default: {\n      max: 852,\n      min: 0,\n      optimalMax: 600,\n      optimalMin: 0,\n      unit: 'cm³',\n      warningMax: 1837,\n    },\n    direction: 'lower-better',\n    source: 'ge-corescan',\n  },\n\n  BMD_Total: {\n    default: { max: 1.4, min: 0.9, optimalMax: 1.3, optimalMin: 1.0, unit: 'g/cm²' },\n    direction: 'higher-better',\n    source: 'who-osteoporosis-1994',\n  },\n\n  TScore_Total: {\n    default: { max: 4.0, min: -1.0, optimalMax: 2.0, optimalMin: -0.5, unit: '' },\n    direction: 'higher-better',\n    source: 'who-osteoporosis-1994',\n  },\n\n  ZScore_Total: {\n    default: { max: 2.0, min: -2.0, optimalMax: 1.0, optimalMin: -1.0, unit: '' },\n    direction: 'higher-better',\n    source: 'who-osteoporosis-1994',\n  },\n\n  Amylase: {\n    default: { max: 100, min: 28, optimalMax: 90, optimalMin: 35, unit: 'U/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Creatinine_Urine: {\n    default: { max: 300, min: 20, optimalMax: 250, optimalMin: 40, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 300, min: 40, optimalMax: 260, optimalMin: 60, unit: 'mg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 220, min: 20, optimalMax: 180, optimalMin: 40, unit: 'mg/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  IgA: {\n    default: { max: 400, min: 70, optimalMax: 350, optimalMin: 100, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Lipase: {\n    default: { max: 60, min: 0, optimalMax: 50, optimalMin: 10, unit: 'U/L' },\n    source: 'tietz-7ed-2015',\n  },\n\n  Microalbumin_Urine: {\n    default: { max: 30, min: 0, optimalMax: 20, optimalMin: 0, unit: 'mg/L' },\n    source: 'kdigo-ckd-2024',\n  },\n\n  PSA_Free: {\n    default: { max: 1.5, min: 0, optimalMax: 1.0, optimalMin: 0, unit: 'ng/mL' },\n    source: 'sturgeon-nacb-2008',\n  },\n\n  PSA_FreeRatio: {\n    default: { max: 100, min: 25, optimalMax: 100, optimalMin: 30, unit: '%' },\n    source: 'sturgeon-nacb-2008',\n  },\n\n  // BMI - WHO classification: 18.5–24.9 normal, 25–29.9 overweight, ≥30 obese\n  BMI: {\n    default: { max: 30, min: 18.5, optimalMax: 24.9, optimalMin: 18.5, unit: 'kg/m2' },\n    source: 'who-obesity-2000',\n  },\n\n  // eAG - Estimated Average Glucose, derived from HbA1c (ADAG study)\n  eAG: {\n    default: { max: 154, min: 70, optimalMax: 126, optimalMin: 70, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // INR - International Normalized Ratio (non-anticoagulated patients)\n  INR: {\n    default: { max: 1.2, min: 0.8, optimalMax: 1.1, optimalMin: 0.9, unit: 'ratio' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // Prothrombin Time\n  ProthrombinTime: {\n    default: { max: 13.5, min: 11, optimalMax: 13, optimalMin: 11, unit: 'seconds' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // DHT - Dihydrotestosterone (adult male reference; female values are much lower)\n  DHT: {\n    default: { max: 85, min: 30, optimalMax: 85, optimalMin: 30, unit: 'ng/dL' },\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 85, min: 30, optimalMax: 85, optimalMin: 30, unit: 'ng/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 22, min: 4, optimalMax: 22, optimalMin: 4, unit: 'ng/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // Total IgE - higher values suggest atopy/allergic sensitization\n  IgE_Total: {\n    default: { max: 100, min: 0, optimalMax: 100, optimalMin: 0, unit: 'IU/mL' },\n    direction: 'lower-better',\n    source: 'tietz-7ed-2015',\n  },\n\n  // IgG - Immunoglobulin G\n  IgG: {\n    default: { max: 1600, min: 700, optimalMax: 1600, optimalMin: 700, unit: 'mg/dL' },\n    source: 'tietz-7ed-2015',\n  },\n\n  // IgE E1 Cat Dander - Class 0 (≤0.35 kU/L) = negative\n  IgE_E1_CatDander: {\n    default: { max: 0.35, min: 0, optimalMax: 0.35, optimalMin: 0, unit: 'kU/L' },\n    direction: 'lower-better',\n    source: 'tietz-7ed-2015',\n  },\n\n  // IgE GX1 Grasses - Class 0 (≤0.35 kU/L) = negative\n  IgE_GX1_Grasses: {\n    default: { max: 0.35, min: 0, optimalMax: 0.35, optimalMin: 0, unit: 'kU/L' },\n    direction: 'lower-better',\n    source: 'tietz-7ed-2015',\n  },\n};\n\n// =============================================================================\n// HELPER FUNCTIONS\n// =============================================================================\n\n/**\n * Legacy flat reference ranges for backward compatibility\n * This is derived from biomarkerRangeDefinitions defaults\n */\nexport const defaultReferenceRanges: Record<string, BiomarkerReferenceRange> = Object.fromEntries(\n  Object.entries(biomarkerRangeDefinitions).map(([code, def]) => [code, def.default]),\n);\n\n/**\n * Get the reference range for a biomarker code, optionally personalized for user context\n * @param testCode - The biomarker code (e.g., \"HDL\", \"Testosterone\")\n * @param context - Optional user context for personalized ranges\n * @returns Reference range or undefined if not found\n */\nexport function getReferenceRange(\n  testCode: string,\n  context?: ReferenceRangeContext,\n): BiomarkerReferenceRange | undefined {\n  const definition = biomarkerRangeDefinitions[testCode];\n  if (!definition) return undefined;\n\n  // If no context or no variants, return default\n  if (!context || !definition.variants || definition.variants.length === 0) {\n    return definition.default;\n  }\n\n  const { age, biologicalSex, pregnancyTrimester, pregnant } = context;\n\n  // Detect whether the biomarker has pregnancy-specific variants at all.\n  // Se o biomarcador não modela gestação, uma usuária gestante deve continuar\n  // recebendo a variante por sexo/idade (mais informativa que o default). Apenas\n  // quando existe ao menos uma variante gestacional é que bloqueamos as variantes\n  // não-gestacionais para contextos gestantes — evitando mistura de faixas.\n  //\n  // Precedência quando pregnant=true: variantes gestacionais têm precedência\n  // absoluta sobre variantes etárias. Uma gestante de 65+ anos consultando\n  // TSH recebe a faixa gestacional, não a variante ageMin=65. Isto é\n  // intencional — em gestação, o eixo HPG domina sobre o envelhecimento\n  // fisiológico. Casos raros de gestação pós-menopausa (FIV) seguem essa\n  // regra; o consumidor que precise distinguir deve aplicar lógica de\n  // contexto adicional.\n  //\n  // Tratamento de `pregnant: undefined` vs `false`: ambos são tratados como\n  // \"não-gestante\" (fallback seguro). O consumidor deve setar pregnant: true\n  // explicitamente para ativar variantes gestacionais; contexto sem a flag\n  // recebe a faixa padrão da população geral.\n  const hasPregnancyVariant = definition.variants.some((v) => v.pregnant === true);\n\n  // Find matching variant (first match wins — more specific variants must be\n  // listed first). Ordem obrigatória quando há variantes gestacionais:\n  //   1. variantes trimestre-específicas (pregnant=true + pregnancyTrimester=N)\n  //   2. catch-all gestacional (pregnant=true, sem trimester)\n  //   3. variantes por sexo/idade não-gestacionais\n  // Reordenar quebraria o matching; a verificação `variant.pregnancyTrimester\n  // !== pregnancyTrimester` depende da catch-all vir por último.\n  for (const variant of definition.variants) {\n    if (variant.pregnant === true) {\n      if (!pregnant) continue;\n      // Variante com trimestre específico só casa quando o contexto também\n      // especifica o mesmo trimestre. Variantes gestacionais sem trimestre\n      // (catch-all) casam com qualquer contexto gestante, servindo de fallback.\n      if (\n        variant.pregnancyTrimester !== undefined &&\n        variant.pregnancyTrimester !== pregnancyTrimester\n      ) {\n        continue;\n      }\n    } else if (pregnant && hasPregnancyVariant) {\n      // Só pulamos variantes não-gestacionais se o biomarcador tem variantes\n      // gestacionais; caso contrário, a variante por sexo/idade é aplicável.\n      continue;\n    }\n\n    // Check sex match ('all' matches everyone)\n    if (variant.sex !== 'all' && variant.sex !== biologicalSex) {\n      continue;\n    }\n\n    // Check age range\n    if (variant.ageMin !== undefined && (age === undefined || age < variant.ageMin)) {\n      continue;\n    }\n    if (variant.ageMax !== undefined && (age === undefined || age > variant.ageMax)) {\n      continue;\n    }\n\n    return variant.range;\n  }\n\n  // No matching variant found - return default\n  return definition.default;\n}\n\n/**\n * Get the range direction for a biomarker code.\n * Returns 'range' (default) if not specified.\n */\nexport function getRangeDirection(testCode: string): RangeDirection {\n  return biomarkerRangeDefinitions[testCode]?.direction ?? 'range';\n}\n\n/**\n * Get fallback reference range for a biomarker code (default only, no personalization)\n * Used by API when LLM doesn't extract reference values\n * @param biomarkerCode - The biomarker code\n * @returns Reference range with min/max/unit or undefined\n */\nexport function getFallbackReferenceRange(\n  biomarkerCode: string,\n): { min: number; max: number; unit: string } | undefined {\n  const definition = biomarkerRangeDefinitions[biomarkerCode];\n  if (!definition || definition.default.min === undefined || definition.default.max === undefined) {\n    return undefined;\n  }\n  return {\n    max: definition.default.max,\n    min: definition.default.min,\n    unit: definition.default.unit,\n  };\n}\n\n/**\n * Apply fallback reference ranges to biomarkers that are missing them\n * @param biomarkers - Array of parsed biomarkers\n * @returns Count of biomarkers that received fallback references\n */\nexport function applyFallbackReferenceRanges<\n  T extends {\n    code: string;\n    referenceMin?: number | null;\n    referenceMax?: number | null;\n    unit?: string;\n  },\n>(biomarkers: T[]): number {\n  let fallbackCount = 0;\n\n  for (const biomarker of biomarkers) {\n    // Skip if already has reference values\n    if (biomarker.referenceMin != null && biomarker.referenceMax != null) {\n      continue;\n    }\n\n    const fallback = getFallbackReferenceRange(biomarker.code);\n    if (fallback) {\n      // Only apply if units are compatible or biomarker has no unit\n      const canonicalUnit = getCanonicalUnitForCode(biomarker.code);\n      const unitsMatch =\n        !biomarker.unit ||\n        biomarker.unit.toLowerCase() === fallback.unit.toLowerCase() ||\n        (canonicalUnit && biomarker.unit.toLowerCase() === canonicalUnit.toLowerCase()) ||\n        // Handle common unit variations\n        (biomarker.unit === '%' && fallback.unit === '%');\n\n      if (unitsMatch) {\n        if (biomarker.referenceMin == null) {\n          biomarker.referenceMin = fallback.min;\n        }\n        if (biomarker.referenceMax == null) {\n          biomarker.referenceMax = fallback.max;\n        }\n        fallbackCount++;\n      }\n    }\n  }\n\n  return fallbackCount;\n}\n"]}

package/dist/{chunk-ICSMWCVT.js → chunk-ZQXKRINW.js}

@@ -104,9 +104,13 @@ var BIOMARKER_DEFINITIONS = [
     unit: "nmol/L"
   },
   {
+    // LOINC 43583-4 = "Lipoprotein a [Moles/volume] in Serum or Plasma" (nmol/L).
+    // Anteriormente 10835-7 ("Lipoprotein a [Mass/volume]", mg/dL),
+    // incompatível com a unidade nmol/L declarada. SBC 2025 recomenda
+    // ensaio independente de isoforma reportado em nmol/L.
     category: "coracao",
     code: "Lipoprotein_a",
-    loinc: "10835-7",
+    loinc: "43583-4",
     names: {
       en: ["Lipoprotein (a)", "Lp(a)"],
       pt: ["Lipoprote\xEDna (a)", "Lp(a)"]
@@ -1426,11 +1430,16 @@ var BIOMARKER_DEFINITIONS = [
     unit: "mg/L"
   },
   {
+    // LOINC 3091-6 = "Urea [Mass/volume] in Serum or Plasma" (mg/dL).
+    // Anteriormente 3094-0 ("Urea nitrogen", BUN), inconsistente com a faixa
+    // de referência brasileira (15-50 mg/dL) e com os nomes pt-BR (Ureia).
+    // Aliases 'BUN' e 'Blood Urea Nitrogen' removidos para evitar matching
+    // de relatórios de BUN contra faixas de Ureia (BUN ≈ Ureia / 2,14).
     category: "rins",
     code: "Urea",
-    loinc: "3094-0",
+    loinc: "3091-6",
     names: {
-      en: ["Blood Urea Nitrogen", "BUN", "Urea"],
+      en: ["Urea"],
       pt: ["Ureia", "Ur\xE9ia"]
     },
     unit: "mg/dL"
@@ -2893,4 +2902,4 @@ export {
   getBiomarkersByCategory,
   getBiomarkersForCategories
 };
-//# sourceMappingURL=chunk-ICSMWCVT.js.map
+//# sourceMappingURL=chunk-ZQXKRINW.js.map