@precisa-saude/fhir 0.15.2 → 0.15.3

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  1. package/dist/{chunk-ZKN5UI7R.cjs → chunk-ARB4UYVQ.cjs} +9 -5
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  3. package/dist/{chunk-V5X3RU6M.js → chunk-EX6EOFWH.js} +9 -5
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  8. package/dist/reference-ranges.cjs +2 -2
  9. package/dist/reference-ranges.d.cts +6 -0
  10. package/dist/reference-ranges.d.ts +6 -0
  11. package/dist/reference-ranges.js +1 -1
  12. package/package.json +1 -1
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- {"version":3,"sources":["../src/reference-ranges.ts"],"sourcesContent":["/**\n * 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 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