12-phase flow (12)

1. 1FRAME
   Plt severity (severe <20K bleeding risk / moderate 20-50K procedural / mild 50-150K workup); acuity (acute vs chronic >12 mo); single-line vs multi-line cytopenia; pivot questions: schistocytes? coag abnormal? heparin exposure? pregnancy? medication? (ITP ASH 2019 PMID 31585375)
   inputs: platelet_count_value
   advance: severity + acuity + lineage pattern stratified
2. 2ENTRY
   Bleeding severity (petechiae/purpura/mucosal/intracranial); thrombosis (HIT marker); neuro/renal/fever (TTP pentad); ± obstetric (HELLP); fever + sepsis criteria (consumption)
   inputs: bleeding_severity_petechiae_purpura_mucosal_intracranial, thrombosis_venous_or_arterial_for_HIT, neuro_renal_fever_for_TTP_pentad
   advance: phenotype-defining feature captured
3. 3CONTEXT
   Age + sex + pregnancy status + vitals + heparin exposure (5-10 d for HIT) + new medication (5-14 d for drug-induced) + recent chemo + liver disease + autoimmune (SLE/APS/RA) + HIV/HCV + family hx (hereditary) + recent vaccination (VITT/post-vaccine ITP)
   inputs: age, sex, pregnancy_status, sbp, hr, temp, heparin_exposure_5_to_10_days_for_HIT, new_medication_PPI_vanco_linezolid_quinine_sulfa, recent_chemotherapy_or_radiation, liver_disease_cirrhosis_alcohol_HCV_HBV, autoimmune_SLE_APS_RA_HIV_HCV, family_history_for_hereditary_BSS_WAS_MYH9, recent_vaccination_for_post_vaccine_ITP_VITT
   advance: context complete
4. 4RED_FLAGS
   TTP pentad → STAT PLEX (route heme.ttp.core.v1; do NOT delay for ADAMTS13). HIT 4Ts ≥4 → STOP heparin + alt anticoag (fondaparinux/argatroban/bivalirudin; AVOID platelet transfusion). DIC + bleeding → cryo/FFP/plt + treat underlying. Severe bleeding plt <20K → transfusion + emergent workup. HELLP → delivery + magnesium + steroid. Sepsis → route id.sepsis.core.v1.
   inputs: bleeding_severity_petechiae_purpura_mucosal_intracranial, thrombosis_venous_or_arterial_for_HIT, neuro_renal_fever_for_TTP_pentad
   advance: no immediate emergency OR emergency intervention initiated
5. 5INITIAL_WORKUP
   CBC + differential + smear (CRITICAL — schistocytes, clumping, megakaryocyte preservation, blasts); coag panel (PT, PTT, fibrinogen, D-dimer — DIC vs TTP/ITP pivot); hemolysis panel (LDH, haptoglobin, indirect bili, DAT); BMP + LFT + INR; pseudo-thrombocytopenia recheck in citrate
   inputs: cbc_with_diff_smear, coagulation_panel_PT_PTT_fibrinogen_D_dimer, hemolysis_panel_LDH_haptoglobin_indirect_bili_DAT
   actions: panel.cbc, panel.coag, panel.lft, panel.renal
   advance: smear + coag + hemolysis reviewed
6. 6BRANCHING_WORKUP
   Isolated thrombocytopenia + no schistocytes + normal coag → ITP (route heme.itp.core.v1 acute / heme.itp.chronic.v1 chronic >12 mo). Schistocytes + thrombocytopenia + ± neuro/renal/fever → TTP (PLASMIC ≥6 + ADAMTS13 <10%) → STAT PLEX route heme.ttp.core.v1. Heparin exposure + 4Ts ≥4 → PF4 ELISA + SRA → HIT (STOP heparin + alt anticoag). Prolonged coag + low fibrinogen + high D-dimer → DIC (route heme.dic.v1). Cirrhosis features → route gi.cirrhosis.core.v1. Sepsis criteria → route id.sepsis.core.v1. SLE features → ANA + anti-dsDNA → route rheum.sle.core.v1. HIV/HCV → viral suppression. Pregnancy 3rd tri + LFT high + hemolysis → HELLP. Drug exposure → stop offending drug. Pseudo-EDTA → recheck citrate.
   inputs: ADAMTS13_for_TTP, PF4_ELISA_and_SRA_for_HIT, ANA_anti_dsDNA_anti_Sm_complement_for_SLE, HIV_HCV_HBV_serologies, B12_folate_for_megaloblastic, bone_marrow_biopsy_if_pancytopenia_or_unclear, EDTA_pseudo_thrombocytopenia_citrate_tube, lft_albumin_INR_for_liver
   advance: definitive cause identified or routed
7. 7DIFFERENTIAL
   Decreased production: marrow failure (aplastic, MDS, leukemia, infiltration), megaloblastic (B12/folate), congenital (BSS, MYH9, WAS), drug-induced marrow suppression, HIV, HCV, alcohol. Increased destruction: immune (ITP primary, secondary SLE/HIV/HCV/CLL/drugs, HIT, post-transfusion, neonatal alloimmune), non-immune (TTP/HUS/HELLP, DIC, mechanical valve, march hemoglobinuria). Sequestration: hypersplenism (cirrhosis). Dilutional: massive transfusion.
   advance: phenotype ranked
8. 8RISK_STRATIFICATION
   Severity by plt + bleeding + thrombosis; TTP pentad + PLASMIC ≥6 → STAT PLEX; HIT 4Ts → STOP heparin + alt anticoag; DIC ISTH score ≥5 → treat underlying; severe ITP (plt <30K + bleed) → emergent + IVIG + steroid; HELLP → delivery; sepsis criteria → route id.sepsis.core.v1
   advance: urgency + risk documented
9. 9TREATMENT
   ITP: prednisone 1 mg/kg PO × 4 wk taper OR dexamethasone 40 mg PO × 4 d; IVIG 1 g/kg/d × 2 d for severe bleed; anti-D 50-75 µg/kg IV for Rh+ non-splenectomized; eltrombopag/romiplostim for chronic; rituximab/splenectomy for refractory (route heme.itp.core.v1 acute / heme.itp.chronic.v1 chronic). TTP: STAT PLEX 1.5 vol exchange daily + caplacizumab 11 mg SC × 30 d + steroid 1 mg/kg + rituximab (route heme.ttp.core.v1) (HERCULES PMID 30625070 verify). HIT: STOP heparin + alternative anticoag (fondaparinux 7.5 mg SC daily OR argatroban 2 µg/kg/min IV titrate OR bivalirudin); transition to warfarin only after plt >150K; AVOID platelet transfusion (HIT ASH PMID 28811261 verify). DIC: treat underlying (route heme.dic.v1) + cryo for fibrinogen <100 + FFP for INR >1.5 + plt for plt <30K bleeding. HELLP: delivery + magnesium 4 g IV load + 1-2 g/h infusion + corticosteroid (controversial). Sepsis: route id.sepsis.core.v1. SLE: prednisone + hydroxychloroquine + mycophenolate/rituximab (route rheum.sle.core.v1). Drug-induced: STOP drug + supportive. Pseudo-EDTA: no treatment.
   inputs: platelet_count_value, bleeding_severity_petechiae_purpura_mucosal_intracranial
   advance: definitive treatment initiated or routed
10. 10DISPOSITION
    ED: TTP, HIT, severe DIC, severe ITP with bleeding, HELLP, severe sepsis. Inpatient: new ITP requiring IVIG, HIT on alt anticoag, DIC, chemo-induced with severe nadir, HELLP postpartum, SLE flare. Outpatient: chronic ITP stable (route heme.itp.chronic.v1), gestational thrombocytopenia mild, resolved pseudo-EDTA. ICU: TTP on PLEX, severe DIC with hemodynamic compromise, HELLP with severe organ injury, septic shock.
    advance: disposition assigned
11. 11MONITORING
    Plt count q6-12 h initial → q24 h once stabilizing; TTP — plt + LDH + retic + neuro daily during PLEX (target plt >150K × 2-3 d off PLEX); HIT — plt q12 h until >150K then daily on alt anticoag (caution warfarin transition timing); DIC — fibrinogen + plt + D-dimer + coag q6-12 h; ITP — plt + bleeding + steroid taper response weekly; pregnancy HELLP — plt + LFT + Cr + delivery planning
    advance: response trajectory documented
12. 12FOLLOWUP
    Hematology for ITP chronic + HIT + TTP relapse + hereditary. ID for HIV/HCV/HBV viral suppression. Rheumatology for SLE flares. Obstetrics for HELLP postpartum + future pregnancy planning. Avoid future heparin exposure for HIT (lifelong); use fondaparinux/DOAC instead. ITP — vaccinations for splenectomy candidates; eltrombopag/romiplostim long-term monitoring (bone marrow fibrosis). Recurrence prevention.
    advance: long-term plan + follow-up scheduled