12-phase flow (12)

1. 1FRAME
   AFLP = rare (~ 5/100,000 maternities; Knight UKOSS 2008 PMID 18332072) 3rd-trimester microvesicular hepatic steatosis caused by impaired fetal/maternal long-chain fatty acid beta-oxidation (LCHAD deficiency in the fetus → maternal hepatic mitochondrial overload). Clinical Swansea-criterion-defined diagnosis (≥ 6/14 criteria; Ch'ng 2002 PMID 12427793). Cornerstone treatment = PROMPT DELIVERY; maternal recovery is rapid once delivered. Maternal mortality with modern care 1.8-12 %; perinatal mortality 10 %. Always consider HELLP/severe pre-eclampsia overlap (LFTs alone do not differentiate); BP + proteinuria + platelets are the pivots.
   inputs: gestational_age_weeks
   advance: GA + multifetal status documented; AFLP clinical suspicion vs HELLP overlap tier set
2. 2ENTRY
   Recognise AFLP via 3rd-trimester onset of nausea/vomiting + abdominal pain + jaundice + encephalopathy ± hypoglycemia ± coagulopathy. Common prodrome: malaise, anorexia, polydipsia/polyuria. Differential at entry: HELLP/severe pre-eclampsia (HTN + proteinuria + low platelets), viral hepatitis (esp. HEV in endemic regions), ICP (much milder, no encephalopathy), drug-induced liver injury (acetaminophen, antiepileptics), septic shock with shock liver, Wilson disease, autoimmune hepatitis, gallstone disease with cholangitis.
   inputs: gestational_age_weeks
   advance: AFLP suspected based on clinical pattern; STAT lab workup initiated
3. 3CONTEXT
   Capture GA (typically > 30 wk; peak 35-36 wk), multifetal status (3-fold AFLP risk per Knight 2008), prior AFLP / known LCHAD carrier status (recurrence risk 20-70% if LCHAD-confirmed), maternal BMI (low BMI < 20 a Knight 2008 risk factor), fetal sex if known (~ 1.7:1 M:F), recent medication exposure (acetaminophen, antiepileptics, antibiotics for DILI ddx).
   inputs: multifetal_gestation_status, prior_aflp_or_lchad_carrier_status, maternal_bmi_or_weight, fetal_sex_if_known, recent_medications_acetaminophen_antiepileptics
   advance: Risk-factor context captured; subsequent-pregnancy + LCHAD counseling primed
4. 4RED_FLAGS
   Hypoglycemia (< 4 mmol/L) → immediate D10W + ICU; coagulopathy + active bleeding → MTP + FFP + cryoprecipitate; encephalopathy (GCS deterioration, asterixis, confusion) → ICU + emergent delivery; HTN + proteinuria → HELLP/severe PE overlap (ob.hellp-syndrome.v1 / ob.pre-eclampsia.core.v1); fulminant liver failure features (rising INR > 2, persistent hypoglycemia despite D10W, refractory encephalopathy) → transplant center transfer.
   inputs: maternal_glucose_fingerstick_and_serum, maternal_mental_status_gcs, maternal_bp, maternal_coagulation_pt_aptt_inr_fibrinogen
   advance: Red-flag pathway activated: emergent delivery decision + ICU level of care + transplant center consideration if fulminant
5. 5INITIAL_WORKUP
   STAT CBC + CMP + glucose + ammonia + lactate + PT/INR + aPTT + fibrinogen + uric acid + type & crossmatch ≥ 4 units PRBC + viral hepatitis serology + LFTs + hepatic ultrasound (bright liver / ascites; rule out biliary obstruction). Apply Swansea criteria scoring (≥ 6/14 supports AFLP per Knight 2008 PMID 18332072). Continuous EFM. Establish baseline glucose target ≥ 4 mmol/L with D10W if needed.
   inputs: maternal_glucose_fingerstick_and_serum, liver_function_tests_alt_ast_bilirubin_alp_ggt, maternal_cbc_with_diff_and_platelets, maternal_comprehensive_metabolic_panel, maternal_coagulation_pt_aptt_inr_fibrinogen, maternal_ammonia_level, maternal_lactate, maternal_type_and_crossmatch, viral_hepatitis_serology_hav_hbv_hcv_hev, fetal_heart_rate_baseline
   actions: panel.cbc, panel.lft, panel.renal, panel.coag
   advance: Labs drawn; Swansea criteria score documented; type & crossmatch active; ICU + L&D coordinated
6. 6BRANCHING_WORKUP
   Swansea criteria ≥ 6/14 + no alternative explanation → AFLP clinical diagnosis. If HELLP-overlap (HTN + proteinuria + platelets < 100 + schistocytes) → workup.preeclampsia + ob.hellp-syndrome.v1. If AST > 1000 + viral risk → expand viral hepatitis ddx (HEV PCR especially); acetaminophen level if exposure. Liver biopsy is the gold standard (microvesicular steatosis) but RARELY performed acutely due to coagulopathy + the urgency to deliver; not required for diagnosis when Swansea criteria met.
   actions: workup.preeclampsia, workup.abnormal_lft, workup.thrombocytopenia
   advance: Swansea score documented; overlap with HELLP routed; viral hepatitis ruled out
7. 7DIFFERENTIAL
   HELLP/severe pre-eclampsia (HTN + proteinuria + platelets < 100; sibling engine); viral hepatitis especially HEV (markedly elevated AST/ALT > 1000; serology); ICP (mild transaminitis, no encephalopathy, no hypoglycemia, no coagulopathy beyond vitamin-K-dependent factors; ob.intrahepatic-cholestasis-of-pregnancy.v1); drug-induced liver injury (medication history; acetaminophen level); septic shock with shock liver (fever + hypotension + leukocytosis + procalcitonin); Wilson disease (young, low ceruloplasmin, Kayser-Fleischer rings, hemolytic anemia); autoimmune hepatitis (ANA, SMA, anti-LKM); Reye-like syndrome with salicylates; gallstone disease with cholangitis (US biliary dilation, charcot triad).
   advance: AFLP confirmed by Swansea ≥ 6 + alternative dx excluded OR alternative dx confirmed and routed
8. 8RISK_STRATIFICATION
   Swansea criteria score (≥ 6 = AFLP; ≥ 7 correlates with worse outcomes per Wang 2017 PMID 27923319); MELD score for ALF severity; West Haven encephalopathy grade; hypoglycemia depth (< 2.2 mmol/L = profound); INR trajectory (> 2 = severe); AKI (creatinine > 150 µmol/L = Swansea criterion); ammonia > 100 µmol/L = high-grade hepatic failure. Fulminant features → transplant center transfer; otherwise ICU + L&D at delivering hospital.
   inputs: maternal_glucose_fingerstick_and_serum, maternal_coagulation_pt_aptt_inr_fibrinogen, maternal_ammonia_level, maternal_mental_status_gcs
   advance: Severity tier assigned; transplant center transfer decision made if fulminant
9. 9TREATMENT
   PROMPT DELIVERY IS THE CORNERSTONE — vaginal delivery preferred if cervix ripe, hemodynamics stable, and coagulopathy manageable; otherwise cesarean (after FFP + cryoprecipitate correction if possible). ICU SUPPORTIVE CARE: D10W IV to maintain glucose ≥ 4 mmol/L (RxCUI 4850 glucose), serial glucose q2-4h; FFP + cryoprecipitate + platelets for coagulopathy (target fibrinogen ≥ 200; INR < 2 pre-delivery if possible); MTP (1:1:1 PRBC:FFP:platelets) if active bleeding (Pacheco SMFM 47 framework); vitamin K1 phytonadione 10 mg IV/PO daily (RxCUI 8308); ammonia management (lactulose 30-45 mL PO q6h adjust to 3 BMs/day, rifaximin per hepatology); empiric broad-spectrum antibiotics if SBP/sepsis ddx; AVOID hepatotoxic drugs (acetaminophen, statins). HEPATOLOGY + TRANSPLANT REFERRAL if fulminant (rising INR > 2 despite FFP, persistent encephalopathy, persistent hypoglycemia despite D10W). PLASMAPHERESIS / MARS / molecular adsorbent recirculating system — selective use per hepatology in fulminant cases (limited evidence base). NEWBORN: cord blood + acylcarnitine profile for LCHAD/MCAD screening (mandatory; positive screen → metabolic specialist consult + dietary management).
   inputs: gestational_age_weeks, maternal_glucose_fingerstick_and_serum, maternal_coagulation_pt_aptt_inr_fibrinogen
   advance: Delivery executed; ICU supportive care active; transplant center transfer if fulminant; newborn LCHAD screening initiated
10. 10DISPOSITION
    ICU + L&D + hepatology + neonatology; transplant center transfer if fulminant; multidisciplinary team activation; family meeting given high acuity. Post-delivery: ICU until extubated + hemodynamically stable + coagulopathy resolving + LFTs trending down + mental status normal; typically 5-10 days in ICU for survivors. Newborn admitted to NICU for LCHAD screening + monitoring.
    inputs: maternal_mental_status_gcs
    advance: Multidisciplinary team coordinated; transplant center transfer if fulminant; newborn NICU coordination
11. 11MONITORING
    Glucose q2-4h (target ≥ 4 mmol/L; D10W if needed); coag panel q4-6h while active bleeding then q12h; daily LFTs (expect peak within 24-48 h post-delivery then steady decline); daily ammonia; renal function daily; serial neuro checks (West Haven grade); intrapartum continuous EFM; post-delivery uterine tone + bleeding (PPH risk from coagulopathy). Continue vitamin K daily.
    inputs: maternal_glucose_fingerstick_and_serum, maternal_coagulation_pt_aptt_inr_fibrinogen, liver_function_tests_alt_ast_bilirubin_alp_ggt, maternal_ammonia_level
    actions: panel.lft, panel.coag
    advance: Glucose stable off D10W; LFTs trending down; coagulopathy resolving; mental status normalizing; extubated
12. 12FOLLOWUP
    Maternal liver typically recovers within 1-2 weeks post-delivery; full biochemical recovery within 4-6 weeks. NEWBORN: mandatory LCHAD/MCAD/long-chain FAO screening (newborn screen acylcarnitine profile + targeted genetic testing); positive screen → pediatric metabolism specialist + dietary management. MATERNAL genetic counseling — heterozygous LCHAD carrier status confers ~ 20-70 % recurrence in subsequent pregnancy + lifelong implications. Mental-health screen (peripartum PTSD + EPDS — survival from a near-fatal pregnancy event carries significant burden). Subsequent-pregnancy counseling — tertiary-center delivery + early-3rd-trimester surveillance + family planning input.
    advance: Maternal recovery confirmed; newborn LCHAD screen result acted upon; genetic counseling delivered; mental-health support arranged; subsequent-pregnancy plan documented