12-phase flow (12)

1. 1FRAME
   Confirm clinical scenario: thrombocytopenia (platelet drop >50% from baseline OR drop to <150K) in patient on heparin exposure (any form, any duration); calculate 4Ts pretest probability (Thrombocytopenia / Timing / Thrombosis / oTher causes) — ASH 2018 PMID 30482768; Lo JTH 2006 PMID 16634744
   inputs: current_or_recent_heparin_exposure, platelet_count_trajectory, days_of_heparin_exposure
   actions: calc.4ts
   advance: 4Ts score calculated; low (≤3) effectively rules out HIT (high NPV); intermediate (4-5) or high (6-8) requires testing + empiric non-heparin AC — ASH 2018
2. 2ENTRY
   Document the trigger event (thrombocytopenia on heparin, new thrombosis on heparin, skin necrosis at injection site, anaphylactoid reaction after IV heparin bolus, or unexplained thrombosis with recent heparin within 100 d) — ASH 2018
   inputs: current_or_recent_heparin_exposure, platelet_count_trajectory
   advance: Clinical trigger event documented; heparin exposure timeline mapped — ASH 2018
3. 3CONTEXT
   Map heparin exposure (UFH IV bolus or infusion, LMWH SC, heparin flushes for lines / hemodialysis / ECMO, heparin-coated catheters, cardiac surgery exposure, prior exposure within 100 days), current platelet count and trajectory, current renal + hepatic function (drives non-heparin AC selection), planned procedures, and competing diagnoses (sepsis, drug-induced thrombocytopenia, DIC, post-transfusion purpura) — ASH 2018
   inputs: current_or_recent_heparin_exposure, days_of_heparin_exposure, thrombosis_event_on_heparin, alternative_thrombocytopenia_causes, planned_cardiac_surgery_or_dialysis
   advance: 4Ts score finalized; alternative thrombocytopenia causes screened; renal + hepatic function documented for non-heparin AC choice — ASH 2018
4. 4RED_FLAGS
   Screen for HITT with major thrombosis (new arterial or venous thrombosis on heparin — DVT, PE, MI, stroke, limb ischemia, mesenteric ischemia, adrenal hemorrhage) — emergency non-heparin AC and consider catheter-directed thrombolysis or thrombectomy if limb-threatening; screen for limb ischemia driving emergent thrombectomy; screen for skin necrosis at heparin injection site (pathognomonic regardless of platelet count); screen for acute anaphylactoid reaction within minutes of IV heparin bolus (rigors, hypotension, dyspnea, cardiac arrest) — STOP heparin immediately and start non-heparin AC — ASH 2018
   inputs: thrombosis_event_on_heparin, platelet_count_trajectory
   actions: workup.hit_full
   advance: Major thrombosis identified or excluded; pathognomonic findings documented; emergent interventions ordered if applicable — ASH 2018
5. 5INITIAL_WORKUP
   CBC + smear (rule out pseudothrombocytopenia, MAHA features); coagulation panel (PT/aPTT/fibrinogen — DIC DDx); send PF4/heparin ELISA (sensitive screening test); CrCl + LFT for non-heparin AC selection; CT/Doppler imaging if any thrombosis suspected on examination — ASH 2018 PMID 30482768
   inputs: cbc_baseline_pre_heparin, pf4_heparin_elisa, creatinine_crcl, lft_alt_bili, coagulation_pt_ptt_fibrinogen
   actions: panel.cbc, panel.coag, panel.renal, panel.lft, calc.4ts, workup.hit_full, workup.thrombocytopenia
   advance: PF4 ELISA sent; baseline labs obtained for non-heparin AC selection; thrombosis imaging completed if clinically indicated — ASH 2018
6. 6BRANCHING_WORKUP
   If PF4 ELISA positive (optical density ≥0.4 typical cutoff; higher OD ≥1.0 has higher PPV), send confirmatory serotonin release assay (SRA) — high specificity functional test. While awaiting SRA (typically 3-7 days turnaround), START non-heparin anticoagulation empirically. If new thrombosis suspected: lower-extremity Doppler, CTPA for dyspnea, ECG + troponin for chest pain, head CT for neuro signs. Consider autoimmune HIT spectrum (Greinacher JTH 2017 PMID 28846826): spontaneous HIT without heparin exposure, persisting HIT after heparin stopped, severe HIT with DIC — may need IVIG (high-dose IVIG 1 g/kg/day x 2 days) as adjunct to non-heparin AC for refractory cases
   inputs: serotonin_release_assay, pf4_heparin_elisa
   advance: SRA sent if ELISA positive; thrombosis imaging completed; consideration of autoimmune HIT spectrum documented — ASH 2018; Greinacher JTH 2017
7. 7DIFFERENTIAL
   Distinguish HIT from competing thrombocytopenia causes: sepsis-induced thrombocytopenia (often DIC features; explains 4Ts oTher), drug-induced thrombocytopenia (vancomycin / linezolid / fluoroquinolones / GP2b3a inhibitors — abrupt drop on drug initiation), post-transfusion purpura (recent transfusion within 7-14 d, severe thrombocytopenia <20K, anti-HPA-1a antibodies), ITP exacerbation, pseudothrombocytopenia (EDTA platelet clumping — repeat in citrate tube), marrow suppression, DIC (low fibrinogen, schistocytes, high D-dimer — but may coexist with autoimmune HIT) — ASH 2018; Greinacher JTH 2017
   inputs: alternative_thrombocytopenia_causes, coagulation_pt_ptt_fibrinogen
   advance: HIT confirmed (high 4Ts + PF4 positive + SRA positive when available) OR excluded (low 4Ts OR PF4 negative) OR autoimmune HIT spectrum recognized — ASH 2018
8. 8RISK_STRATIFICATION
   Classify HIT phenotype: isolated HIT (thrombocytopenia without new thrombosis) vs HITT (HIT with thrombosis — DVT/PE/arterial); within HITT classify by thrombosis severity (limb-threatening / hemodynamically significant / minor). 4Ts score interpretation: low ≤3 (NPV ~99%; HIT effectively excluded), intermediate 4-5 (treat empirically and test), high 6-8 (treat empirically and test; PPV ~50-80%). Combine with PF4 optical density: high OD ≥1.4 has PPV approaching SRA-positive — ASH 2018; Lo JTH 2006
   inputs: thrombosis_event_on_heparin, pf4_heparin_elisa
   actions: calc.4ts
   advance: HIT phenotype assigned (isolated HIT vs HITT); risk class documented; non-heparin AC strategy selected — ASH 2018
9. 9TREATMENT
   IMMEDIATELY upon intermediate / high 4Ts: (1) STOP ALL HEPARIN — IV infusion, SC LMWH, all heparin flushes, hemodialysis circuit (use citrate or argatroban), heparin-coated catheters; (2) Document heparin allergy in chart and medical-alert ID; (3) Start non-heparin anticoagulation EMPIRICALLY — do NOT wait for SRA: argatroban 2 mcg/kg/min IV titrated by aPTT 1.5-3x baseline (reduce to 0.5 mcg/kg/min if significant hepatic dysfunction Child-Pugh B/C — ARG-911 Lewis Circulation 2001 PMID 11294800), OR bivalirudin 0.15 mg/kg/h titrated by aPTT 1.5-2.5x (preferred in significant hepatic dysfunction — argatroban hepatically cleared; or in cardiac surgery), OR fondaparinux 5-10 mg SC daily by weight (off-label for HIT but ASH 2018 conditional support — avoid if CrCl <30); (4) Once platelets recover to >150K and stable, may transition to DOAC (apixaban 5 mg BID or rivaroxaban 15 mg BID x 21 d then 20 mg daily — Ezekwudo Exp Hematol Oncol 2017 PMID 28725494; Greinacher JTH 2017 PMID 28846826) OR warfarin (overlap with non-heparin AC ≥5 d and INR ≥2 x 24 h, NEVER warfarin alone during acute thrombocytopenia — risk of protein-C-deficiency-mediated venous limb gangrene + skin necrosis); (5) AVOID prophylactic platelet transfusion (may worsen thrombosis — ASH 2018 strong recommendation against); transfuse only for active bleeding or invasive procedure — ASH 2018 PMID 30482768
   inputs: creatinine_crcl, lft_alt_bili, platelet_count_trajectory
   advance: All heparin stopped; non-heparin AC initiated; warfarin avoided; platelet transfusion avoided unless bleeding — ASH 2018
10. 10DISPOSITION
    ICU for HITT with hemodynamic compromise, major thrombosis (PE with shock, limb ischemia), or anaphylactoid reaction; INPATIENT for all other intermediate/high-4Ts HIT until platelet recovery >150K AND stable on non-heparin AC for ≥48 h AND any thrombosis addressed; OUTPATIENT transition to DOAC or warfarin once platelets recover and HIT antibodies declining; HEMATOLOGY consultation for all confirmed HIT — ASH 2018
    advance: Disposition selected; hematology consulted; transition AC plan documented — ASH 2018
11. 11MONITORING
    Daily platelet count until recovery >150K; aPTT or anti-IIa for argatroban / bivalirudin titration; anti-Xa for fondaparinux titration; daily clinical surveillance for new thrombosis (limb pain/swelling, chest pain/dyspnea, neuro changes, abdominal pain); LFT q1-3 d on argatroban; renal function on bivalirudin; coagulation profile q1-2 d initially — ASH 2018
    inputs: platelet_count_trajectory
    advance: Platelet count recovering; non-heparin AC titrated to therapeutic range; no new thrombosis — ASH 2018
12. 12FOLLOWUP
    Duration: isolated HIT (no thrombosis) → minimum 4 weeks of anticoagulation (until platelet recovery + several days stable platelets); HITT (HIT with thrombosis) → at least 3 months — ASH 2018. Long-term: lifelong heparin avoidance documented in chart and medical-alert ID; HIT antibodies decline over ~100 days; if heparin re-exposure required emergently (cardiac surgery) AND antibodies still positive → use bivalirudin intraop; if antibodies negative ≥100 d post-event → heparin may be used short-course (cardiac surgery, hemodialysis) with close monitoring. Hematology follow-up at 1 mo, 3 mo, and 1 year; consider switch from warfarin to DOAC once HIT resolved and patient stable — ASH 2018
    advance: Duration plan documented (≥4 wk isolated HIT, ≥3 mo HITT); lifelong heparin avoidance counseled; re-exposure planning if relevant — ASH 2018