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heme.ttp.core.v1PRODUCTION
heme.ttp.core.v1

Thrombotic Thrombocytopenic Purpura (immune-mediated)

hematologyacuteadult
Hard-required inputs
0 / 9
Care setting:

Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Triage MAHA + thrombocytopenia presentations: TTP vs aHUS vs STEC-HUS vs CAPS vs DIC vs HELLP — ASH 2020; ISTH 2017

Inputs
4
Actions
0
Advance rule
Set
Advance when

TMA syndrome confirmed

Patient inputs (9)

Activity ≤10% confirms iTTP; distinguishes from cTTP — ASH 2020; ISTH 2017

TTP peaks 30s–40s women; pediatric variants different — ASH 2020

Renal involvement; differentiates aHUS (more renal) and DIC — ASH 2020; ISTH 2017

PLASMIC score component; severity — Bendapudi 2017; ASH 2020

Schistocytes confirm MAHA — distinguishes from ITP — ASH 2020; ISTH 2017

MAHA marker + PLASMIC component — Bendapudi 2017; ISTH 2017

Indirect hyperbilirubinemia (hemolysis) — ISTH 2017

Suppressed in intravascular hemolysis — ISTH 2017

Normal in TTP — abnormal coag should redirect to DIC — ASH 2020; BSH 2012

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (7)

7 need judgement
  • informationallife_threateningplasmic_high
    PLASMIC score ≥5 (intermediate-high probability iTTP) (Bendapudi Blood 2017)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningcardiac_involvement
    Troponin elevation OR ST changes OR new HF in TTP (ASH 2020 TTP)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningcns_involvement
    Seizure / stroke / encephalopathy in TTP (ASH 2020 TTP)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevererefractory_after_5_pex
    No platelet response after 5 PLEX sessions (ASH 2020 TTP refractory definition)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverecaplacizumab_bleeding
    Major bleeding on caplacizumab (Scully NEJM 2019 HERCULES)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateplatelet_transfusion_request
    Request for platelet transfusion in active TTP (ASH 2020 TTP; BSH 2012)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateadamts13_low_post_remission
    ADAMTS13 <20% during follow-up post-remission (ISTH 2017; ASH 2020 TTP)
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

This dossier does not reference any calculators.

Recommended regimen

Acute iTTP induction (PLEX + caplacizumab + steroid + rituximab — HERCULES NEJM 2019)
axis: ttp_acute_inductionstep plex - Therapeutic plasma exchange (PLEX) — STAT
Selected step "Therapeutic plasma exchange (PLEX) — STAT" — PLASMIC ≥5 OR confirmed iTTP (ADAMTS13 ≤10%) OR pending result + intermediate-high suspicion — Bendapudi 2017; ASH 2020
  • plasma_exchange_TPE
    first line
    apheresis
    1.5 plasma volumes per session, exchanged with FFP or solvent-detergent plasma • apheresis • daily until plt >150 × 2 days
    triggers: ttp_suspected
    Rock NEJM 1991 — mortality 90%→10%; mainstay even before ADAMTS13 result

ed playbook — drug actions (5)

  1. 1. methylprednisolone pulse
    1 g IV • IV • daily × 3
    trigger: PLASMIC ≥5 OR strong suspicion — Bendapudi 2017; ASH 2020
    ASH 2020 TTP — empirical immunosuppression
  2. 2. caplacizumab IV bolus
    11 mg IV pre-PLEX • IV • single bolus
    trigger: iTTP highly likely + apheresis available — Scully NEJM 2019 HERCULES
    Scully NEJM 2019 HERCULES — start before PLEX
  3. 3. plasma exchange
    1.5 plasma volumes • apheresis • daily
    trigger: PLASMIC ≥5 — Bendapudi 2017; ASH 2020
    Rock NEJM 1991 — mortality 90% to 10%; DO NOT WAIT for ADAMTS13
  4. 4. caplacizumab SC
    11 mg SC after each PLEX • SC • daily
    trigger: After bolus — Scully NEJM 2019 HERCULES
    Scully NEJM 2019 HERCULES — continue 30 d post last PLEX
  5. 5. AVOID platelet transfusion
    Hold unless ICH or life-threatening bleed • IV • avoid
    trigger: Active TTP — ASH 2020; BSH 2012
    ASH 2020 TTP; BSH 2012 — worsens microthrombi

Auto-drafted A&P note

ed

Subjective

- Possible entry pathways: Thrombocytopenia + MAHA (schistocytes + LDH up + indirect bili up) — ASH 2020; ISTH 2017; Pentad: thrombocytopenia + MAHA + neuro + renal + fever (rare complete) — ASH 2020; High PLASMIC score → ADAMTS13 send-out + STAT PEX — Bendapudi 2017; ASH 2020.

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Thrombotic Thrombocytopenic Purpura (immune-mediated)** (heme.ttp.core.v1).
Phenotype framing: iTTP / cTTP (Upshaw-Schulman) / aHUS (complement) / STEC-HUS / CAPS / DIC / HELLP / drug-induced / malignancy-associated TMA / scleroderma renal crisis — ASH 2020; ISTH 2017
Scope: Triage MAHA + thrombocytopenia presentations: TTP vs aHUS vs STEC-HUS vs CAPS vs DIC vs HELLP — ASH 2020; ISTH 2017

No severity triggers fired against current inputs.

Plan

Regimen axis: **Acute iTTP induction (PLEX + caplacizumab + steroid + rituximab — HERCULES NEJM 2019)** — step "Therapeutic plasma exchange (PLEX) — STAT".
1. plasma_exchange_TPE 1.5 plasma volumes per session, exchanged with FFP or solvent-detergent plasma apheresis daily until plt >150 × 2 days (apheresis, first line) — Rock NEJM 1991 — mortality 90%→10%; mainstay even before ADAMTS13 result

Setting playbook (ed) — Recognize MAHA + thrombocytopenia, calculate PLASMIC, place PLEX line, initiate empirical PLEX + steroid + caplacizumab — ASH 2020; Scully NEJM 2019
2. methylprednisolone pulse 1 g IV IV daily × 3 — PLASMIC ≥5 OR strong suspicion — Bendapudi 2017; ASH 2020 (ASH 2020 TTP — empirical immunosuppression)
3. caplacizumab IV bolus 11 mg IV pre-PLEX IV single bolus — iTTP highly likely + apheresis available — Scully NEJM 2019 HERCULES (Scully NEJM 2019 HERCULES — start before PLEX)
4. plasma exchange 1.5 plasma volumes apheresis daily — PLASMIC ≥5 — Bendapudi 2017; ASH 2020 (Rock NEJM 1991 — mortality 90% to 10%; DO NOT WAIT for ADAMTS13)
5. caplacizumab SC 11 mg SC after each PLEX SC daily — After bolus — Scully NEJM 2019 HERCULES (Scully NEJM 2019 HERCULES — continue 30 d post last PLEX)
6. AVOID platelet transfusion Hold unless ICH or life-threatening bleed IV avoid — Active TTP — ASH 2020; BSH 2012 (ASH 2020 TTP; BSH 2012 — worsens microthrombi)

Non-pharmacologic actions:
- STAT apheresis line placement (ASH 2020 TTP — PLEX within hours of diagnosis)
- STAT hematology consult (ASH 2020 TTP)
- ICU admission (ASH 2020 TTP — all suspected iTTP)
- Replace electrolytes (Ca, Mg) post-PLEX (BSH 2012 — citrate-related depletion)

AVOID / contraindication checks:
- Avoid platelet transfusion unless life threatening (ASH 2020 TTP; BSH 2012 — platelet transfusion worsens microthrombi)
- Caplacizumab bleeding risk monitor (Scully NEJM 2019 HERCULES — VWF depletion bleeding)
- Steroid glucose bp monitor (ASH 2020 TTP — standard steroid monitoring)
- Rituximab vaccinate prior (ASH 2020 TTP — live vaccine contraindication post anti CD20)
- Plex replace fibrinogen Ca mg (BSH 2012 — electrolyte and fibrinogen depletion post PLEX)

Monitoring

Regimen monitoring:
- Plt + LDH + Hb + retic daily during induction (ASH 2020 TTP; ISTH 2017)
- Schistocyte count daily (BSH 2012 — MAHA resolution marker)
- ADAMTS13 weekly during induction then q3m (ISTH 2017 — relapse surveillance)
- Coag pre-PLEX (BSH 2012 — fibrinogen depletion risk)
- Troponin if cardiac involvement (ASH 2020 TTP — cardiac TTP mortality marker)
- Caplacizumab bleeding surveillance (Scully NEJM 2019 HERCULES)

Setting (ed) monitoring:
- Continuous ECG + telemetry (ASH 2020 TTP — cardiac TTP surveillance)
- CBC q6h (ASH 2020 TTP)
- Hemodynamic monitoring (BSH 2012)

Follow-up plan: Hem clinic for ADAMTS13 surveillance; vaccination; preventive rituximab if low ADAMTS13 trend; pregnancy risk counseling — ASH 2020; ISTH 2017
- Close-out criterion: Long-term plan documented

Monitoring phase: 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

Disposition

Current setting: ed — Recognize MAHA + thrombocytopenia, calculate PLASMIC, place PLEX line, initiate empirical PLEX + steroid + caplacizumab — ASH 2020; Scully NEJM 2019

Disposition criteria:
- Admit ICU/HDU pending PLEX (ASH 2020 TTP — all suspected iTTP require monitored bed)
- Transfer to apheresis-equipped center if local unavailable (BSH 2012)

Escalation triggers (move to higher acuity):
- Cardiac symptoms (chest pain, troponin) → ICU + cardiology (ASH 2020 TTP — cardiac involvement high mortality)
- CNS symptoms (seizure, stroke) → ICU + neurology (ASH 2020 TTP)
- Hemodynamic instability → ICU (BSH 2012)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] PLASMIC score ≥5 (intermediate-high probability iTTP) (Bendapudi Blood 2017)
- [LIFE_THREATENING] Troponin elevation OR ST changes OR new HF in TTP (ASH 2020 TTP)
- [LIFE_THREATENING] Seizure / stroke / encephalopathy in TTP (ASH 2020 TTP)

Citations

- ISTH 2020 TTP Guidelines — diagnosis (Zheng et al, J Thromb Haemost 2020) + treatment; 2025 ISTH focused update; Rock et al NEJM 1991 plasma exchange (Canadian Apheresis Study Group); HERCULES caplacizumab (Scully NEJM 2019); PLASMIC score (Bendapudi Lancet Haematol 2017) [PMID:32914582](https://pubmed.ncbi.nlm.nih.gov/32914582/)
- Cited evidence (PMID 32914526) [PMID:32914526](https://pubmed.ncbi.nlm.nih.gov/32914526/)
- Cited evidence (PMID 40533296) [PMID:40533296](https://pubmed.ncbi.nlm.nih.gov/40533296/)
- Cited evidence (PMID 30625070) [PMID:30625070](https://pubmed.ncbi.nlm.nih.gov/30625070/)
- Cited evidence (PMID 2062330) [PMID:2062330](https://pubmed.ncbi.nlm.nih.gov/2062330/)

Last reconciled with current guidelines: 2026-05-16.
References
  • ISTH 2020 TTP Guidelines — diagnosis (Zheng et al, J Thromb Haemost 2020) + treatment; 2025 ISTH focused update; Rock et al NEJM 1991 plasma exchange (Canadian Apheresis Study Group); HERCULES caplacizumab (Scully NEJM 2019); PLASMIC score (Bendapudi Lancet Haematol 2017) — PMID:32914582
  • Cited evidence (PMID 32914526) — PMID:32914526
  • Cited evidence (PMID 40533296) — PMID:40533296
  • Cited evidence (PMID 30625070) — PMID:30625070
  • Cited evidence (PMID 2062330) — PMID:2062330