heparin-induced thrombocytopaenia

pathophysiology

• Heparin binds platelet factor 4 (PF4) on platelet surfaces → neoantigen
• IgG antibodies against PF4/heparin complexes → activate platelets via FcγIIA receptors → massive platelet aggregation and thrombin generation
• UFH >> LMWH risk (larger heparin molecules form more immunogenic complexes)
• Surgical patients > medical patients (tissue injury → more PF4 release)

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when to suspect

• Platelet drop >50% from baseline (not necessarily below 150 × 10⁹/L — the drop matters more than the absolute count)
• Timing: days 5–14 after heparin initiation (classic window)
• Rapid-onset: <24 hours — if heparin exposure within the preceding 100 days (pre-formed antibodies)
• New thrombosis while on heparin — venous (DVT/PE) more common than arterial (stroke, limb ischaemia)
• Skin necrosis at heparin injection sites
• Anaphylactoid reaction after IV heparin bolus (rapid-onset HIT)

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diagnosis

4T score — pretest probability

Thrombosis Canada provides an online 4T calculator at thrombosiscanada.ca.

laboratory testing

graph TD
    A[4T score] -->|0-3: low| B[HIT excluded]
    A -->|4-5: intermediate| C[Anti-PF4/heparin ELISA]
    A -->|6-8: high| D[Stop heparin + start alternative AC]
    D --> C
    C -->|negative OD <0.4| E[HIT excluded]
    C -->|positive OD ≥0.4| F{OD strength}
    F -->|OD ≥2.0| G[HIT confirmed — treat]
    F -->|OD 0.4-2.0| H[Functional assay: SRA or HIPA]
    H -->|positive| G
    H -->|negative| E

• Anti-PF4/heparin ELISA: high sensitivity (~97%), lower specificity — many false positives (especially post-cardiac surgery). OD ≥2.0 has >90% positive predictive value.
• Serotonin release assay (SRA): gold standard functional assay — high specificity. Send when ELISA is weakly positive (OD 0.4–2.0).

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management

immediate actions

1. Stop ALL heparin — including line flushes, heparin-coated catheters, heparin locks
2. Start non-heparin anticoagulant at therapeutic dose (not prophylactic — HIT is a prothrombotic state)
3. Image for thrombosis — bilateral lower extremity US even if asymptomatic (50% have occult DVT at diagnosis)
4. Do not transfuse platelets unless life-threatening bleeding (may fuel thrombosis)

non-heparin anticoagulant options

• Argatroban — preferred in renal failure; prolongs INR (complicates warfarin transition monitoring)
• Bivalirudin — short half-life (25 min); preferred if PCI or cardiac surgery needed
• Fondaparinux — not formally approved for HIT in Canada, but strong evidence base and recommended by ASH 2018 guidelines; simplest option for stable patients; avoid if CrCl <30

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transition to warfarin

This is where most errors occur.

1. Do not start warfarin until platelets ≥150 × 10⁹/L — warfarin in acute HIT depletes protein C before reducing procoagulant factors → risk of venous limb gangrene and skin necrosis
2. Overlap non-heparin anticoagulant with warfarin for ≥5 days AND until INR therapeutic on two consecutive measurements
3. Start low — warfarin 5 mg/day (not loading doses)
4. If warfarin was given during acute HIT: give vitamin K to reverse it, continue non-heparin anticoagulant, and restart warfarin only after platelet recovery

duration of anticoagulation

• HIT with thrombosis: minimum 3 months (some experts recommend longer based on clot burden)
• Isolated HIT (no thrombosis): minimum 4 weeks — high risk of delayed thrombosis in the first 30 days
• Transition to warfarin or DOAC for long-term therapy (DOACs are acceptable for long-term management after the acute phase; the heparin-related pathology is time-limited)

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special forms

delayed-onset HIT

• Thrombocytopaenia and/or thrombosis 5–40 days after stopping heparin
• PF4/heparin antibodies persist and activate platelets autonomously (no ongoing heparin needed)
• Presents as unexplained DVT/PE in a recently hospitalised patient — always ask about heparin exposure in the preceding 6 weeks
• 4T score may underestimate risk (timing criterion scores poorly when heparin has been stopped)

autoimmune HIT

• Severe thrombocytopaenia (often <20 × 10⁹/L) with strong platelet activation despite heparin cessation
• PF4-dependent antibodies activate platelets without heparin → resembles DIC clinically
• May require high-dose IVIG (1 g/kg × 2 days) + therapeutic anticoagulation + plasma exchange in refractory cases

rapid-onset HIT

• Platelet drop within hours of re-exposure to heparin (pre-formed antibodies from exposure within 100 days)
• Can present with anaphylactoid features: rigors, hypotension, dyspnoea after IV heparin bolus
• High thrombotic risk — treat as confirmed HIT immediately

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traps

• Waiting for lab results before acting — HIT is a clinical diagnosis. A high 4T score mandates action. ELISA takes days; SRA may take longer.
• Starting warfarin before platelet recovery — the single most dangerous error. Protein C depletion → venous limb gangrene, skin necrosis. Wait until platelets ≥150.
• Only stopping heparin without starting an alternative — HIT is a hypercoagulable state; simply removing heparin leaves the patient at >50% thrombosis risk in the next 30 days.
• Missing the 100-day rapid-onset window — “day 1 of heparin, platelets dropped” seems too early for HIT. But if the patient had surgery 3 weeks ago with heparin prophylaxis → pre-formed antibodies → rapid onset.
• Heparin flushes — a common source of ongoing heparin exposure after “stopping heparin”. Audit every line flush order.
• Argatroban and INR confusion — argatroban prolongs INR independently. During warfarin overlap, target a combined INR >4 before stopping argatroban, then recheck INR 4–6 hours later to confirm warfarin-only INR is therapeutic.
• Post-cardiac surgery overtesting — anti-PF4 antibodies are common after CPB (50–70% seroconversion) without clinical HIT. Do not reflexively test; use the 4T score.

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related: thrombocytopaenia · deep vein thrombosis · heparins · warfarin · periprocedural anticoagulation