heme.ttp.core.v1

Thrombotic Thrombocytopenic Purpura (immune-mediated)

hematologyacuteadultacuteinpatient

Start encounter →Print handoutPRODUCTION

STEP 3 deepened 2026-05-16: replaced placeholder evidence block (was "Pending guideline review" with non-TTP PMIDs DELIVER/POINT/QUEST/REDUCE) with WebSearch-verified provenance — ISTH 2020 diagnosis (PMID 32914582) + treatment (32914526), 2025 ISTH focused update (40533296, newer than floor per §9), HERCULES caplacizumab (30625070), Rock NEJM 1991 PEX (2062330), PLASMIC (28259520). Co-located _research-bundle.md authored (§5.5 item 2). §5.5.1 effect sizes wired: Rock 1991 PEX day-9 mortality 3.9% vs 15.7% plasma infusion; HERCULES caplacizumab composite outcome 12% vs 49% (74% reduction) + faster platelet normalization; PLASMIC >=5 high-risk for severe ADAMTS13 deficiency. §5.5.2 Bayesian: PLASMIC >=5 = empiric-PEX treat-threshold (do NOT wait for ADAMTS13); ADAMTS13 <10% confirms iTTP; aHUS/STEC-HUS/DIC/HELLP pivots. last_reconciled 2026-05-16; status PRODUCTION (verified via dossier:audit). RxCUIs pending research:rxnav.

Entry points (3)

lab_abnormality
Thrombocytopenia + MAHA (schistocytes + LDH up + indirect bili up) — ASH 2020; ISTH 2017
thrombocytopenia_with_maha
symptom
Pentad: thrombocytopenia + MAHA + neuro + renal + fever (rare complete) — ASH 2020
neuro_renal_thrombocytopenia
lab_abnormality
High PLASMIC score → ADAMTS13 send-out + STAT PEX — Bendapudi 2017; ASH 2020
high_plasmic

Required inputs (9)

agerequired
demographic • used at CONTEXT
TTP peaks 30s–40s women; pediatric variants different — ASH 2020
platelet_countrequired
lab • used at ENTRY
PLASMIC score component; severity — Bendapudi 2017; ASH 2020
peripheral_smearrequired
lab • used at INITIAL_WORKUP
Schistocytes confirm MAHA — distinguishes from ITP — ASH 2020; ISTH 2017
ldhrequired
lab • used at INITIAL_WORKUP
MAHA marker + PLASMIC component — Bendapudi 2017; ISTH 2017
bilirubinrequired
lab • used at INITIAL_WORKUP
Indirect hyperbilirubinemia (hemolysis) — ISTH 2017
haptoglobinrequired
lab • used at INITIAL_WORKUP
Suppressed in intravascular hemolysis — ISTH 2017
creatininerequired
lab • used at CONTEXT
Renal involvement; differentiates aHUS (more renal) and DIC — ASH 2020; ISTH 2017
coag_panelrequired
lab • used at INITIAL_WORKUP
Normal in TTP — abnormal coag should redirect to DIC — ASH 2020; BSH 2012
adamts13required
lab • used at BRANCHING_WORKUP
Activity ≤10% confirms iTTP; distinguishes from cTTP — ASH 2020; ISTH 2017

12-phase flow (12)

1FRAME
Triage MAHA + thrombocytopenia presentations: TTP vs aHUS vs STEC-HUS vs CAPS vs DIC vs HELLP — ASH 2020; ISTH 2017
inputs: platelet_count, peripheral_smear, creatinine, coag_panel
advance: TMA syndrome confirmed
2ENTRY
Calculate PLASMIC (7 vars: platelets <30, hemolysis, no active cancer, no transplant, MCV <90, INR <1.5, Cr <2.0). Bayesian treat-threshold: score >=5 = high probability of severe ADAMTS13 deficiency (<10%) → STAT PEX + steroid + ADAMTS13 send-out WITHOUT waiting for the result; 0-4 low/intermediate → reconsider non-TTP TMA. PLASMIC validated high discrimination for severe ADAMTS13 deficiency — Bendapudi Lancet Haematol 2017 (PMID 28259520); ISTH 2020 (PMID 32914582)
inputs: platelet_count, ldh, creatinine
advance: PLASMIC stratified
3CONTEXT
Capture pregnancy, drug history (clopidogrel, calcineurin inhibitor, gemcitabine, quinine), HIV, stem cell transplant — ASH 2020
inputs: age
advance: Triggers reviewed
4RED_FLAGS
Cardiac (troponin), CNS (stroke/seizure), severe AKI, refractory shock — must not delay PEX for confirmatory test — ASH 2020; Scully NEJM 2019
inputs: platelet_count
actions: protocol.ttp
advance: PEX initiated empirically if PLASMIC ≥5
5INITIAL_WORKUP
CBC + smear; LDH + bili + haptoglobin; CMP; coag (normal in TTP); DAT (negative); HIV; pregnancy; troponin; ADAMTS13 send-out — ASH 2020; ISTH 2017
inputs: cbc_with_diff, peripheral_smear, ldh, haptoglobin, coag_panel
actions: panel.cbc, panel.coag, workup.ttp_standalone
advance: Workup sent + PEX line placed
6BRANCHING_WORKUP
ADAMTS13 ≤10% with inhibitor → iTTP. Normal ADAMTS13 → reconsider aHUS / STEC / CAPS / DIC / HELLP / drug-induced TMA — ASH 2020; ISTH 2017
inputs: adamts13
advance: Subtype confirmed
7DIFFERENTIAL
iTTP / cTTP (Upshaw-Schulman) / aHUS (complement) / STEC-HUS / CAPS / DIC / HELLP / drug-induced / malignancy-associated TMA / scleroderma renal crisis — ASH 2020; ISTH 2017
advance: Subtype assigned
8RISK_STRATIFICATION
Refractory / exacerbation criteria; cardiac/CNS involvement signals high mortality — ASH 2020
advance: Severity tier set
9TREATMENT
STAT plasma exchange daily — Rock NEJM 1991 (PMID 2062330): day-9 mortality 3.9% (PEX) vs 15.7% (plasma infusion), benefit sustained at 6 mo; caplacizumab — HERCULES Scully NEJM 2019 (PMID 30625070): composite outcome (TTP-related death, recurrence, or major thromboembolism) 12% vs 49% placebo (~74% reduction) + faster platelet normalization; high-dose steroid (methylpred 1g ×3d or pred 1mg/kg); rituximab if refractory or relapse. AVOID platelet transfusion (worsens microthrombi). — ISTH 2020 (PMID 32914526); 2025 ISTH focused update (PMID 40533296)
actions: protocol.ttp
advance: PEX + caplacizumab + steroid running
10DISPOSITION
ICU/HDU; heme + apheresis service; cardiology if troponin elevated — ASH 2020
advance: Disposition set
11MONITORING
Platelet recovery (PEX continues until plt >150 ×2 days); LDH normalization; ADAMTS13 trend; bleeding from caplacizumab; ADAMTS13 surveillance for relapse — ASH 2020; ISTH 2017; Scully NEJM 2019
inputs: platelet_count
actions: panel.cbc
advance: Remission criteria met
12FOLLOWUP
Hem clinic for ADAMTS13 surveillance; vaccination; preventive rituximab if low ADAMTS13 trend; pregnancy risk counseling — ASH 2020; ISTH 2017
advance: Long-term plan documented