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symptom.thrombocytopenia-workup.v1

Thrombocytopenia symptom-triage (ED-primary; TTP/DIC/HIT/ITP/HELLP route + outpatient chronic)

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

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Detailed

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)

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severity + acuity + lineage pattern stratified

Patient inputs (29)

Age shifts priors: child → acute ITP (post-viral, self-limited 80%); young adult → chronic ITP / SLE; elderly → drug-induced / MDS / cirrhosis / malignancy / HIT; pregnancy 3rd tri → gestational / HELLP / TTP

Female predominance: SLE, primary ITP (especially chronic), TTP, gestational thrombocytopenia; male → some hereditary (WAS X-linked)

Pregnancy 3rd tri → gestational thrombocytopenia (benign, mild), HELLP (severe + LFT + hemolysis), TTP (life-threatening), acute fatty liver — distinct workup; gestational age + plt severity drive management

4Ts: Timing 5-10 d post-heparin initiation (or <1 d if heparin exposure within 30 d); subQ prophylactic or therapeutic; UFH > LMWH risk; cardiac/vascular surgery + heparin = high risk

Drug-induced 5-14 days prior: vancomycin, linezolid, PPI, quinine (especially with cocktails/tonic), sulfa, abciximab, ticagrelor, heparin (HIT), valproate, AED; drug-dependent platelet antibody; recovery 1-2 wk post-stop

Cirrhosis → hypersplenism + reduced TPO + bone marrow suppression; HCV/HBV → ITP-like + cirrhosis component; alcohol → direct marrow toxicity + folate def + cirrhosis

SLE (Evans + ITP), antiphospholipid syndrome, RA, HIV, HCV — autoimmune / viral thrombocytopenia; ANA, anti-dsDNA, anti-Sm, RF, lupus anticoag, anti-cardiolipin, beta-2-glycoprotein-I

Hypotension + thrombocytopenia → sepsis-consumption / DIC / HELLP / TTP; SBP + bleeding severity drives transfusion decision

Tachycardia + thrombocytopenia → sepsis/TTP/severe bleeding; bradycardia + AMS → TBI with ICH

Fever + thrombocytopenia → TTP pentad / sepsis / DRESS / HSV / EBV / HIV seroconversion / malaria

Petechiae + purpura + mucosal (gingival, nasal, GU) + GI + intracranial — wet vs dry bleeding; intracranial = STAT transfusion + workup; dry purpura common in chronic ITP

New venous (DVT, PE, cerebral vein) or arterial (limb ischemia, stroke, MI) thrombosis + heparin exposure + thrombocytopenia → HIT (4Ts ≥4); STOP heparin + alt anticoag (fondaparinux/argatroban/bivalirudin)

TTP pentad: MAHA + thrombocytopenia + neurologic (HA/AMS/seizure/focal) + renal (AKI, hematuria) + fever — STAT PLEX; PLASMIC score ≥6 supports empiric; do NOT delay for ADAMTS13

Plt severity: severe <20K (bleeding risk), moderate 20-50K (procedural risk), mild 50-150K (workup); rate of decline more important than absolute (e.g., 30-50% drop in HIT)

Smear review CRITICAL: schistocytes (>2/HPF → MAHA/TTP/DIC/HELLP/mechanical), platelet clumping (EDTA pseudo), large platelets (Bernard-Soulier/ITP), atypical lymphs (viral), blasts (leukemia), megakaryocytes preserved (ITP) vs absent (production failure)

CBC + differential + smear — central diagnostic; isolated thrombocytopenia → ITP; with anemia + schistocytes → TTP/DIC/HELLP; pancytopenia → marrow failure / leukemia

PT + PTT + fibrinogen + D-dimer — DIC vs TTP/ITP discrimination: DIC = prolonged PT/PTT + low fibrinogen + high D-dimer; TTP/ITP = normal coag (key pivot)

LDH + haptoglobin + indirect bili + DAT + retic — hemolysis workup; high LDH + low haptoglobin + high indirect bili → hemolysis (TTP/DIC/HELLP); DAT+ → AIHA (Evans syndrome if + ITP)

ADAMTS13 activity <10% diagnostic for TTP; inhibitor titer for acquired; STAT PLEX before ADAMTS13 result if PLASMIC ≥6 (TTP ISTH PMID 31135051 verify)

PF4 ELISA (sensitive, screening) + serotonin release assay (SRA, gold standard, confirmatory) — HIT diagnosis; pretest probability via 4Ts (HIT ASH PMID 28811261 verify)

ANA + anti-dsDNA + anti-Sm + complement C3/C4 + APL panel — SLE workup; antiphospholipid syndrome lupus anticoag + anti-cardiolipin + beta-2-glycoprotein-I

HIV (RNA + serology) + HCV (Ab + RNA) + HBV (HBsAg + HBcAb) — viral-associated thrombocytopenia workup

B12 + folate + MMA + homocysteine — megaloblastic thrombocytopenia workup; pancytopenia or megaloblastic features on smear

BMBx if pancytopenia, suspected leukemia, suspected MDS, atypical ITP not responding to standard, hereditary suspected; megakaryocytes preserved (ITP) vs reduced (production failure)

Plt clumping on smear + automated low plt → recheck in citrate tube (light blue top) — EDTA-dependent agglutinin pseudo-thrombocytopenia; benign artifact

LFT + albumin + INR — liver disease (cirrhosis-related thrombocytopenia + synthetic dysfunction); CTP / MELD scores; route gi.cirrhosis.core.v1

Active chemo → nadir 7-14 d post-cycle, recovery 21-28 d; expected pattern; consider growth factors (romiplostim/eltrombopag) for chronic; dose modification if persistent

Family hx + lifelong thrombocytopenia + large platelets → hereditary (BSS, MYH9-related, WAS); WAS in male with eczema + immunodeficiency

Recent vaccination (MMR, especially in peds; COVID vector vaccines for VITT — vaccine-induced immune thrombotic thrombocytopenia 4-30 d post-vax) → post-vaccine ITP / VITT (similar to HIT mechanism — anti-PF4)

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Severity triggers (8)

8 need judgement
  • informationallife_threateningttp_pentad_stat_plex
    Microangiopathic hemolytic anemia (schistocytes >2/HPF) + thrombocytopenia + ± neuro/renal/fever + PLASMIC score ≥6 + ADAMTS13 <10% — TTP; STAT plasma exchange (PLEX) + caplacizumab + steroid 1 mg/kg + rituximab; DO NOT delay PLEX for ADAMTS13 result (TTP ISTH 2017 PMID 31135051 verify; HERCULES PMID 30625070 verify)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateninghit_4ts_stop_heparin_alt_anticoag
    4Ts score ≥4-8 (Thrombocytopenia 30-50% drop, Timing 5-10 d post-heparin, Thrombosis new venous/arterial, oTher cause excluded) + PF4 ELISA ≥1.0 OD ± SRA — HIT; STOP all heparin (UFH/LMWH/flushes) + alternative anticoag (fondaparinux 7.5 mg SC daily OR argatroban 2 µg/kg/min IV OR bivalirudin); AVOID platelet transfusion + warfarin until plt >150K (HIT ASH 2018 PMID 28811261 verify; 4Ts PMID 23613659 verify)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningdic_isth_score_ge_5_consumptive
    Thrombocytopenia + prolonged PT/PTT + fibrinogen <100 + D-dimer very high + clinical (sepsis, OB, trauma, APL, snake) + ISTH DIC score ≥5 — DIC; treat underlying + supportive (cryo for fibrinogen <100, FFP for INR >1.5, plt for plt <30K bleeding); route heme.dic.v1 (DIC ISTH 2018 PMID 26966077 verify)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningHELLP_severe_preeclampsia_delivery
    Pregnancy 3rd trimester + Hemolysis (LDH high, indirect bili high, schistocytes) + Elevated LFT (AST/ALT >2x) + Low Platelets (<100K) + ± HTN >160/110 + proteinuria + RUQ pain — HELLP syndrome; DELIVERY definitive + magnesium 4 g IV load + 2 g/h infusion + corticosteroid 10 mg IV q12h × 4 (controversial)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningsevere_bleeding_plt_lt_10k_life_threat
    Plt <10K + spontaneous bleeding (intracranial, GI, retinal, GU) OR plt <20K + severe bleed OR plt <50K + procedure-induced — bleeding emergency; pRBC + platelet transfusion + cause identification + treat underlying (AVOID in HIT + TTP)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresevere_itp_with_bleeding_ivig_steroid
    Severe ITP (plt <30K + active bleeding OR plt <10K + asymptomatic) — IVIG 1 g/kg/d × 2 days + prednisone 1 mg/kg PO OR dexamethasone 40 mg × 4 d; platelet transfusion ONLY for life-threatening bleed (intracranial, GI, GU); route heme.itp.core.v1 (ITP ASH 2019 PMID 31585375)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresepsis_consumption_thrombocytopenia_route
    Sepsis criteria (SIRS / qSOFA / lactate >2) + thrombocytopenia (consumption + DIC overlap + bone marrow suppression) — sepsis-consumption; route id.sepsis.core.v1 for full Surviving Sepsis Campaign 1-h bundle; DIC workup if coagulopathy + bleeding
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildpseudo_thrombocytopenia_EDTA_artifact
    Plt low on automated CBC + plt clumping on smear + normal plt in citrate tube (light blue top) — pseudo-thrombocytopenia (EDTA-dependent agglutinin); BENIGN ARTIFACT; recheck in citrate tube; NO treatment; reassure
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

outpatient playbook — drug actions (9)

  1. 1. prednisone (chronic ITP — first-line)
    1 mg/kg PO daily × 4 weeks then taper over 2-3 months • PO • daily then taper
    trigger: Newly diagnosed ITP requiring treatment (plt <30K or bleeding) per ITP ASH PMID 31585375
    First-line for chronic ITP; ~70% initial response; taper carefully to avoid relapse; PCP/Strongyloides screen if prolonged; bone + gastric protection; route heme.itp.core.v1 acute / heme.itp.chronic.v1 chronic
  2. 2. dexamethasone (chronic ITP — alternative)
    40 mg PO daily × 4 days; repeat q14-28 days × 4-6 cycles • PO • pulsed q14-28 days
    trigger: Alternative steroid for ITP induction
    Higher response rate vs prednisone in some studies; pulsed dosing reduces chronic steroid AE; cycle until response sustained
  3. 3. eltrombopag (chronic ITP — TPO-RA)
    50 mg PO daily (titrate 25-75 mg based on plt) • PO • daily
    trigger: Chronic ITP refractory to steroid + IVIG OR steroid-dependent
    Thrombopoietin receptor agonist; oral; LFT monitoring (hepatotoxicity); avoid antacids/dairy 4 h before/after dose; rebound thrombocytopenia on discontinuation
  4. 4. romiplostim (chronic ITP — TPO-RA SC)
    1 µg/kg SC weekly (titrate 1-10 µg/kg) • SC • weekly
    trigger: Chronic ITP refractory; oral TPO-RA intolerance
    Peptide TPO mimetic; weekly SC; thrombosis + bone marrow fibrosis (long-term) AE; rebound thrombocytopenia
  5. 5. rituximab (chronic ITP / SLE / Evans — anti-CD20)
    375 mg/m2 IV weekly × 4 doses • IV • weekly × 4
    trigger: Chronic ITP refractory to steroid + IVIG + TPO-RA; Evans syndrome; SLE thrombocytopenia
    B-cell depletion; HBV/HCV/HIV/TB screen before; durable response ~40-60% but late relapses; combine with TPO-RA for steroid-sparing
  6. 6. splenectomy (chronic ITP — definitive)
    Surgical • OR • one-time
    trigger: Chronic ITP refractory ≥12 mo to medical therapy; pre-op vaccinations + life-long prophylaxis
    Cure ~60-80%; pre-op pneumococcal/meningococcal/H. influenzae vaccinations (2 weeks pre); life-long antibiotic prophylaxis (penicillin/amoxicillin); risk overwhelming post-splenectomy infection (OPSI); laparoscopic preferred
  7. 7. avatrombopag (TPO-RA for cirrhosis-related thrombocytopenia pre-procedure)
    40-60 mg PO daily × 5 days starting 10-13 days before procedure • PO • daily × 5
    trigger: Cirrhosis-related thrombocytopenia + planned procedure (variceal banding, endoscopy with biopsy, dental procedure)
    Pre-procedure plt boost; ADAPT-1/2 trials; avoid empiric platelet transfusion; route gi.cirrhosis.core.v1
  8. 8. antiviral therapy (HIV/HCV-related)
    ART per regimen (HIV); DAA per regimen (HCV — e.g., sofosbuvir/velpatasvir × 12 wk) • PO • per regimen
    trigger: HIV/HCV-associated thrombocytopenia
    Viral suppression improves thrombocytopenia; HCV DAA cure rates >95%; consider PrEP for HIV exposure prevention
  9. 9. hydroxychloroquine + mycophenolate (SLE thrombocytopenia)
    Hydroxychloroquine 5 mg/kg/d (max 400 mg); mycophenolate 1-1.5 g PO BID • PO • daily
    trigger: SLE thrombocytopenia confirmed (ANA + anti-dsDNA + complement); route rheum.sle.core.v1
    Hydroxychloroquine baseline for all SLE; mycophenolate or azathioprine for refractory; rituximab if refractory; route rheum.sle.core.v1

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Isolated thrombocytopenia (plt <100K, normal Hgb + WBC, normal smear except large platelets) + no obvious secondary cause — primary ITP; route heme.itp.core.v1 (acute) or heme.itp.chronic.v1 (>12 mo); first-line prednisone 1 mg/kg or dexamethasone 40 mg × 4 d; rescue IVIG/anti-D + platelets if severe bleed (ITP ASH 2019 PMID 31585375); Microangiopathic hemolytic anemia (schistocytes >2/HPF) + thrombocytopenia + ± neuro/renal/fever + PLASMIC score ≥6 + ADAMTS13 <10% — TTP; STAT plasma exchange (PLEX) — DO NOT delay for ADAMTS13; route heme.ttp.core.v1 (TTP ISTH 2017 PMID 31135051 verify); 4Ts score ≥4-8 (Thrombocytopenia 30-50% drop, Timing 5-10d after heparin, Thrombosis new venous/arterial, oTher cause excluded) + HIT antibody (PF4 ELISA) + functional confirmatory (SRA) — heparin-induced thrombocytopenia; STOP all heparin + alternative anticoag (fondaparinux/argatroban/bivalirudin) — AVOID platelet transfusion (HIT ASH 2018 PMID 28811261 verify; 4Ts PMID 23613659 verify).

Objective

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

Assessment

**Thrombocytopenia symptom-triage (ED-primary; TTP/DIC/HIT/ITP/HELLP route + outpatient chronic)** (symptom.thrombocytopenia-workup.v1).
Phenotype framing: 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.
Scope: 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)

No severity triggers fired against current inputs.

Plan

No regimen axis selected (engine has no regimen_axes or could not match).

Setting playbook (outpatient) — Outpatient follow-up for chronic ITP (route heme.itp.chronic.v1), gestational thrombocytopenia monitoring, pseudo-EDTA confirmation, drug-induced recovery, viral-associated thrombocytopenia (HIV/HCV antiviral therapy), cirrhosis monitoring, hereditary thrombocytopenia genetic counseling
1. prednisone (chronic ITP — first-line) 1 mg/kg PO daily × 4 weeks then taper over 2-3 months PO daily then taper — Newly diagnosed ITP requiring treatment (plt <30K or bleeding) per ITP ASH PMID 31585375 (First-line for chronic ITP; ~70% initial response; taper carefully to avoid relapse; PCP/Strongyloides screen if prolonged; bone + gastric protection; route heme.itp.core.v1 acute / heme.itp.chronic.v1 chronic)
2. dexamethasone (chronic ITP — alternative) 40 mg PO daily × 4 days; repeat q14-28 days × 4-6 cycles PO pulsed q14-28 days — Alternative steroid for ITP induction (Higher response rate vs prednisone in some studies; pulsed dosing reduces chronic steroid AE; cycle until response sustained)
3. eltrombopag (chronic ITP — TPO-RA) 50 mg PO daily (titrate 25-75 mg based on plt) PO daily — Chronic ITP refractory to steroid + IVIG OR steroid-dependent (Thrombopoietin receptor agonist; oral; LFT monitoring (hepatotoxicity); avoid antacids/dairy 4 h before/after dose; rebound thrombocytopenia on discontinuation)
4. romiplostim (chronic ITP — TPO-RA SC) 1 µg/kg SC weekly (titrate 1-10 µg/kg) SC weekly — Chronic ITP refractory; oral TPO-RA intolerance (Peptide TPO mimetic; weekly SC; thrombosis + bone marrow fibrosis (long-term) AE; rebound thrombocytopenia)
5. rituximab (chronic ITP / SLE / Evans — anti-CD20) 375 mg/m2 IV weekly × 4 doses IV weekly × 4 — Chronic ITP refractory to steroid + IVIG + TPO-RA; Evans syndrome; SLE thrombocytopenia (B-cell depletion; HBV/HCV/HIV/TB screen before; durable response ~40-60% but late relapses; combine with TPO-RA for steroid-sparing)
6. splenectomy (chronic ITP — definitive) Surgical OR one-time — Chronic ITP refractory ≥12 mo to medical therapy; pre-op vaccinations + life-long prophylaxis (Cure ~60-80%; pre-op pneumococcal/meningococcal/H. influenzae vaccinations (2 weeks pre); life-long antibiotic prophylaxis (penicillin/amoxicillin); risk overwhelming post-splenectomy infection (OPSI); laparoscopic preferred)
7. avatrombopag (TPO-RA for cirrhosis-related thrombocytopenia pre-procedure) 40-60 mg PO daily × 5 days starting 10-13 days before procedure PO daily × 5 — Cirrhosis-related thrombocytopenia + planned procedure (variceal banding, endoscopy with biopsy, dental procedure) (Pre-procedure plt boost; ADAPT-1/2 trials; avoid empiric platelet transfusion; route gi.cirrhosis.core.v1)
8. antiviral therapy (HIV/HCV-related) ART per regimen (HIV); DAA per regimen (HCV — e.g., sofosbuvir/velpatasvir × 12 wk) PO per regimen — HIV/HCV-associated thrombocytopenia (Viral suppression improves thrombocytopenia; HCV DAA cure rates >95%; consider PrEP for HIV exposure prevention)
9. hydroxychloroquine + mycophenolate (SLE thrombocytopenia) Hydroxychloroquine 5 mg/kg/d (max 400 mg); mycophenolate 1-1.5 g PO BID PO daily — SLE thrombocytopenia confirmed (ANA + anti-dsDNA + complement); route rheum.sle.core.v1 (Hydroxychloroquine baseline for all SLE; mycophenolate or azathioprine for refractory; rituximab if refractory; route rheum.sle.core.v1)

Non-pharmacologic actions:
- Deprescribe offending medications (drug-induced thrombocytopenia)
- Avoid heparin LIFETIME for HIT history — use fondaparinux/DOAC
- Vaccinations pre-splenectomy: pneumococcal (PCV13 + PPSV23), meningococcal (MenACWY + MenB), H. influenzae type b
- Life-long antibiotic prophylaxis post-splenectomy: penicillin V 250 mg PO BID OR amoxicillin 500 mg PO daily
- Avoid contact sports if plt <50K
- Avoid NSAIDs / antiplatelet for ITP / HIT history (increases bleeding)
- Genetic counseling for hereditary thrombocytopenia (BSS, MYH9, WAS)
- Pregnancy counseling: ITP requires multidisciplinary management; HELLP risk increased with prior
- Hematology referral: chronic ITP refractory, hereditary, MDS, leukemia
- Obstetrics: gestational thrombocytopenia monitoring; HELLP postpartum care
- Patient education: bleeding precautions, medication compliance, when to seek ED

Monitoring

Setting (outpatient) monitoring:
- CBC at 1-2 weeks post discharge / new diagnosis; q1-3 mo for chronic ITP
- LFT q1-3 mo for eltrombopag (hepatotoxicity)
- TPO-RA: monitor for rebound thrombocytopenia + thrombosis + bone marrow fibrosis (long-term)
- HCV/HIV: viral load + CD4 + LFT
- Splenectomy: lifelong abx prophylaxis adherence + vaccination boosters
- Pregnancy: serial CBC + LFT + BP + proteinuria for gestational vs HELLP vs preeclampsia
- SLE: ANA + anti-dsDNA + complement + CBC q3 mo
- Refractory ITP: hematology referral + bone marrow biopsy + flow cytometry

Follow-up plan: 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.
- Close-out criterion: long-term plan + follow-up scheduled

Monitoring phase: 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

Disposition

Current setting: outpatient — Outpatient follow-up for chronic ITP (route heme.itp.chronic.v1), gestational thrombocytopenia monitoring, pseudo-EDTA confirmation, drug-induced recovery, viral-associated thrombocytopenia (HIV/HCV antiviral therapy), cirrhosis monitoring, hereditary thrombocytopenia genetic counseling

Disposition criteria:
- Continue outpatient: chronic ITP stable on therapy; gestational thrombocytopenia monitoring; pseudo-EDTA confirmed; HCV/HIV on antiviral suppression
- Hematology referral: refractory chronic ITP, hereditary, atypical features, MDS/leukemia suspicion, TPO-RA initiation
- ED escalation: plt <30K + new bleeding, HELLP features, HIT with new thrombosis, acute decompensation
- Inpatient: new ITP requiring IVIG, splenectomy elective admission, refractory chronic flare
- Route to: heme.itp.core.v1 / heme.itp.chronic.v1; gi.cirrhosis.core.v1; rheum.sle.core.v1; id.sepsis.core.v1

Escalation triggers (move to higher acuity):
- Plt <30K + new bleeding → ED + IVIG + steroid + transfusion if life-threatening
- Acute decompensation in chronic ITP → ED + reinduction
- Pregnancy HELLP features (LFT high, hemolysis, low plt + HTN) → STAT OB + ED
- HIT with new thrombosis on alt anticoag → ED + ICU
- Active leukemia / MDS suspicion → STAT hematology + BMBx
- Refractory chronic ITP failing steroid + IVIG + TPO-RA → splenectomy or rituximab
- Post-splenectomy fever / infection → ED + broad-spectrum antibiotics (OPSI risk)
- Hepatotoxicity from eltrombopag (LFT >3x ULN) → discontinue + switch romiplostim

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Microangiopathic hemolytic anemia (schistocytes >2/HPF) + thrombocytopenia + ± neuro/renal/fever + PLASMIC score ≥6 + ADAMTS13 <10% — TTP; STAT plasma exchange (PLEX) + caplacizumab + steroid 1 mg/kg + rituximab; DO NOT delay PLEX for ADAMTS13 result (TTP ISTH 2017 PMID 31135051 verify; HERCULES PMID 30625070 verify)
- [LIFE_THREATENING] 4Ts score ≥4-8 (Thrombocytopenia 30-50% drop, Timing 5-10 d post-heparin, Thrombosis new venous/arterial, oTher cause excluded) + PF4 ELISA ≥1.0 OD ± SRA — HIT; STOP all heparin (UFH/LMWH/flushes) + alternative anticoag (fondaparinux 7.5 mg SC daily OR argatroban 2 µg/kg/min IV OR bivalirudin); AVOID platelet transfusion + warfarin until plt >150K (HIT ASH 2018 PMID 28811261 verify; 4Ts PMID 23613659 verify)
- [LIFE_THREATENING] Thrombocytopenia + prolonged PT/PTT + fibrinogen <100 + D-dimer very high + clinical (sepsis, OB, trauma, APL, snake) + ISTH DIC score ≥5 — DIC; treat underlying + supportive (cryo for fibrinogen <100, FFP for INR >1.5, plt for plt <30K bleeding); route heme.dic.v1 (DIC ISTH 2018 PMID 26966077 verify)

Citations

- 2019 ITP ASH + 2017 TTP ISTH + 2018 HIT ASH + 2018 DIC ISTH + HERCULES caplacizumab + ITP Provan international consensus [PMID:31269407](https://pubmed.ncbi.nlm.nih.gov/31269407/)
- Cited evidence (PMID 23233580) [PMID:23233580](https://pubmed.ncbi.nlm.nih.gov/23233580/)

Last reconciled with current guidelines: 2026-05-30.
References
  • 2019 ITP ASH + 2017 TTP ISTH + 2018 HIT ASH + 2018 DIC ISTH + HERCULES caplacizumab + ITP Provan international consensus — PMID:31269407
  • Cited evidence (PMID 23233580) — PMID:23233580