Thrombocytopenia: ITP, TTP/HUS & HIT
A high-yield walkthrough of the destruction/consumption thrombocytopenias — ITP, TTP, HUS, HIT, and DIC — contrasting mechanism, smear and coagulation labs, and first-line management, anchored by TTP and HIT clinical vignettes.
Approach to thrombocytopenia
Thrombocytopenia is a platelet count <150,000/µL; spontaneous bleeding risk climbs below ~30,000 and becomes severe below ~10,000. The pattern is platelet-type (mucocutaneous) bleeding — petechiae, purpura, epistaxis, gum bleeding, menorrhagia — unlike the deep tissue/joint bleeds and delayed rebleeding of coagulation-factor disorders.
Three mechanisms: decreased production (marrow failure, chemo, B12/folate), increased destruction/consumption (immune or thrombotic), and sequestration (splenomegaly, e.g., cirrhosis). This lesson targets the destruction/consumption group. The key fork: is the platelet drop isolated with a normal smear (think ITP), or accompanied by schistocytes plus hemolysis — a microangiopathic hemolytic anemia (MAHA) — pointing to TTP, HUS, or DIC? A separate lane is HIT, which uniquely causes thrombosis, not bleeding.
- ITP: isolated thrombocytopenia, normal smear, no schistocytes; a diagnosis of exclusion. Anti-GPIIb/IIIa IgG → splenic clearance. Kids: acute, post-viral, self-limited. Adults: chronic (F>M).
- TTP: ADAMTS13 deficiency (usually autoantibody) → uncleaved ultralarge vWF multimers → platelet microthrombi. MAHA + thrombocytopenia + neuro signs; normal PT/PTT/fibrinogen.
- HUS: Shiga toxin (EHEC O157:H7) after bloody diarrhea → endothelial injury, renal-predominant AKI; mostly children.
- HIT: heparin–PF4 IgG activates platelets → thrombosis (venous/arterial). Platelets fall >50% at days 5–10.
- DIC: systemic coagulation activation consumes platelets and factors → low fibrinogen, high PT/PTT/D-dimer, schistocytes; from sepsis, obstetric catastrophe, malignancy, trauma.
Stem: A 38-year-old woman has fatigue, confusion, and scattered petechiae. Labs: platelets 18,000, Hb 8.1, LDH markedly elevated, haptoglobin undetectable, indirect bilirubin high, creatinine 1.6; PT/PTT normal; smear shows numerous schistocytes. Direct Coombs negative.
Diagnosis: TTP — MAHA + thrombocytopenia with normal coagulation and neuro/renal findings (ADAMTS13 typically <10%). Coombs-negative hemolysis rules out warm autoimmune hemolysis; normal PT/PTT/fibrinogen rules out DIC.
Next step: Urgent plasma exchange (plasmapheresis) plus corticosteroids; add caplacizumab and rituximab for acquired disease. Do NOT transfuse platelets unless there is life-threatening hemorrhage — it fuels microthrombosis. Send ADAMTS13 level/inhibitor before starting therapy, but never delay PLEX awaiting results.
FAT RN captures the classic TTP pentad:
- F — Fever
- A — Anemia (microangiopathic hemolytic)
- T — Thrombocytopenia
- R — Renal dysfunction
- N — Neurologic changes (fluctuating: headache, confusion, seizure, focal deficits)
The full pentad appears in a minority of patients. The treatment-triggering core is simply MAHA + thrombocytopenia with no other explanation. Prominent neuro signs favor TTP; predominant renal failure in a child after bloody diarrhea favors HUS — but overlap is real, so treat empirically.
Side-by-side comparison
| Disorder | Core mechanism | Platelets / smear | Coags (PT/PTT · fibrinogen) | Key clue |
|---|---|---|---|---|
| ITP | Anti-platelet IgG → splenic clearance | Low; normal smear | Normal | Isolated ↓plt, otherwise well; child post-viral |
| TTP | ↓ADAMTS13 → vWF microthrombi | Low; schistocytes | Normal | Neuro signs, ↑↑LDH, adult female |
| HUS | Shiga toxin (EHEC) endothelial injury | Low; schistocytes | Normal | Bloody diarrhea, AKI, child |
| HIT | Heparin–PF4 IgG activates platelets | Fall >50%, day 5–10 | Normal | New thrombosis on heparin |
| DIC | Systemic coagulation activation | Low; schistocytes | ↑PT/PTT · ↓fibrinogen · ↑D-dimer | Sepsis/OB/trauma; diffuse oozing |
Stem: A 64-year-old man on prophylactic heparin since aortic valve surgery develops, on postoperative day 7, a swollen painful right calf. Platelets have fallen from 250,000 to 90,000 (>50% drop); there is no bleeding. Duplex confirms a DVT.
Diagnosis: HIT (heparin-induced thrombocytopenia, type II) — immune and prothrombotic, not a bleeding state. Estimate pretest probability with the 4Ts score, then confirm with PF4–heparin ELISA plus a functional serotonin-release assay.
Next step: Stop ALL heparin (including LMWH and line flushes) and start a non-heparin anticoagulant — argatroban or bivalirudin (direct thrombin inhibitors), or fondaparinux. Do NOT start warfarin alone while thrombocytopenic (risk of venous limb gangrene/skin necrosis), and do NOT transfuse platelets.
Transfusion cautions in bold:
- ITP: treat only if bleeding or platelets <30,000. First line: corticosteroids or IVIG/anti-D (IVIG raises the count fastest). Refractory: rituximab, TPO-receptor agonists (romiplostim, eltrombopag), splenectomy. Platelets only for life-threatening bleeding.
- TTP: plasma exchange + steroids ± caplacizumab/rituximab. Avoid platelet transfusion.
- HUS (typical/EHEC): supportive care + dialysis as needed; avoid antibiotics and antimotility agents (may ↑ toxin release). Atypical HUS (complement dysregulation): eculizumab.
- HIT: stop heparin → direct thrombin inhibitor; delay warfarin until platelets recover >150,000.
- DIC: treat the underlying cause; support active bleeding with FFP, cryoprecipitate (fibrinogen), and platelets.
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