Hematology, Oncology & Immunology · Topic 7 of 26

Heparin-Induced Thrombocytopenia (HIT)

Hematology · drug-induced thrombocytopenia

Heparin-Induced Thrombocytopenia (HIT)

A clotting disorder disguised as low platelets: score the 4Ts, stop all heparin and start a non-heparin anticoagulant — never warfarin first.

Key numbers

Platelets fall >50% on days 5–10> 50% fall, days 5–10

Score the 4Ts first4Ts ≤ 3 = low

No warfarin until platelets reach 150,000Plt ≥ 150,000 before VKA

01 · Defined byPlatelets fall >50% on days 5–10

HIT is an immune reaction to platelet factor 4–heparin complexes: platelets fall by more than 50%, typically 5–10 days after heparin starts; bleeding is rare, but one-third to one-half develop venous or arterial thrombosis.

02 · Defined byScore the 4Ts first

Estimate pretest probability with the 4Ts score, not gestalt: 0–3 low, 4–5 intermediate, 6–8 high. A low score effectively excludes HIT — do not send HIT tests or treat empirically.

03 · DoStop all heparin, including flushes

With an intermediate or high 4Ts score, stop every heparin source immediately — infusions, prophylactic doses, line flushes and LMWH, which cross-reacts with HIT antibodies — before test results return.

Causes & risk factors

Why it happens

Unfractionated heparin carries 10-fold higher riskHIT is about 10 times more common with unfractionated heparin than with LMWH and most common after surgery, especially cardiac surgery; even small heparin flushes can trigger it.

Presentation

What you'll see

Rapid-onset HIT after recent heparinA fall within 1 day of re-exposure still scores full timing points if heparin was given in the past 30 days; a fall before day 4 without recent heparin argues against HIT.

Diagnosis & monitoring

Work-up

4Ts: thrombocytopenia, timing, thrombosis, other causes4Ts, 0–2 points each; 2 points for a fall > 50% with nadir ≥ 20,000/mcL, onset on days 5–10, new thrombosis or skin necrosis, and no other cause (a definite one scores 0).

Do right now

In this order

First moves

Score the 4Ts first4Ts ≤ 3 = low

→

Stop all heparin, including flushes

→

Start a non-heparin anticoagulant

→

Immunoassay, then functional assay if positive

Why each step

Score the 4Ts firstEstimate pretest probability with the 4Ts score, not gestalt: 0–3 low, 4–5 intermediate, 6–8 high. A low score effectively excludes HIT — do not send HIT tests or treat empirically.

Stop all heparin, including flushesWith an intermediate or high 4Ts score, stop every heparin source immediately — infusions, prophylactic doses, line flushes and LMWH, which cross-reacts with HIT antibodies — before test results return.

Start a non-heparin anticoagulantStart a non-heparin anticoagulant — argatroban, bivalirudin, fondaparinux or a DOAC — at therapeutic intensity for a high 4Ts score; with an intermediate score use prophylactic intensity only if bleeding risk is high.

Immunoassay, then functional assay if positiveFor an intermediate or high 4Ts score, send a PF4–heparin immunoassay (ELISA); if it is positive, confirm with a functional assay such as the serotonin release assay.

Management

Orders

Argatroban 2 mcg/kg/min; reduce in liver diseaseArgatroban (IV direct thrombin inhibitor): no bolus, 2 mcg/kg/min titrated to aPTT 1.5–3 times baseline; hepatically cleared, so start lower (0.5–1.2 mcg/kg/min) in liver dysfunction, heart failure or after cardiac surgery.

Critically ill or bleeding: argatroban or bivalirudinIn critical illness, high bleeding risk or a likely urgent procedure, prefer a short-acting IV agent: argatroban or bivalirudin (0.15 mg/kg/h, aPTT 1.5–2.5 times baseline, dose-reduced in renal or hepatic dysfunction).

Stable patient: fondaparinux or a DOACClinically stable patients at average bleeding risk can take fondaparinux (5, 7.5 or 10 mg SC daily by weight) or a DOAC such as rivaroxaban; life- or limb-threatening thrombosis calls for a parenteral agent.

Screen legs with compression ultrasoundIn isolated HIT, order bilateral lower-extremity compression ultrasound to look for silent DVT (found in 12–44%), plus upper-extremity ultrasound on the side of any central venous catheter.

Red flags & don'ts

Avoid harm

No warfarin until platelets reach 150,000 avoidDo not start warfarin until platelets recover to at least 150,000/mcL; early warfarin causes venous limb gangrene and skin necrosis. If the patient is already on warfarin, stop it and give IV vitamin K.

Argatroban falsely raises the INR interactionArgatroban prolongs the INR: when overlapping with warfarin, give no warfarin loading dose, stop argatroban once the combined INR exceeds 4, and recheck the INR 4–6 hours later.

No routine platelet transfusion in HIT avoidAvoid routine platelet transfusion in HIT at average bleeding risk — it has been linked to more arterial thrombosis; consider it only for active bleeding or a high-bleeding-risk procedure.

The rules

Know these

HIT with thrombosis: anticoagulate 3–6 monthsHIT with thrombosis needs 3–6 months of anticoagulation; isolated HIT is treated at least until platelets recover, commonly for 4–6 weeks and up to 3 months.

HIT likely or unlikely? (4Ts)

Commonly confused

Size of fall	More than 50%, nadir 20,000/mcL or higher
Timing	Clear onset on days 5–10, or within 1 day if heparin in the past 30 days
Thrombosis	New thrombosis, skin necrosis, or systemic reaction after an IV bolus
Other cause	None apparent

More detail

Reference

Show 6 reference facts

A low-probability 4Ts score has a negative predictive value of about 99.8%; positive predictive values are only about 14% for intermediate and 64% for high scores, so those patients need laboratory testing.

HIT is usually mediated by IgG antibodies that bind platelet factor 4–heparin complexes and activate platelets, releasing procoagulant microparticles — a profoundly hypercoagulable state.

Each day of delayed treatment carries roughly a 6% risk of new thrombosis, amputation or death; HIT is also frequently overdiagnosed.

A functional assay may be unnecessary when the 4Ts score is high and the immunoassay is very strongly positive (optical density above 2.0).

A patient with past HIT whose antibodies are now negative (remote HIT) may receive heparin during cardiac surgery, limited to the operation; monitor platelets afterward for delayed-onset HIT.

HIT occurs in up to 2.4% of patients receiving unfractionated heparin; the nadir is usually 20,000/mcL or higher, and a fall under 30% or a nadir below 10,000/mcL scores zero on the 4Ts.

Pearl

In HIT the platelets fall but the blood clots — treat it with an anticoagulant, not with platelets.

Sources · Cuker A et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv 2018;2(22):3360–3392 · ASH teaching slide set — Diagnosis & Management of Heparin-Induced Thrombocytopenia (ASH 2018 VTE guidelines: HIT; reviewed 2022) · Merck Manual Professional — Thrombocytopenia: Other Causes (heparin-induced thrombocytopenia section, Jun 2026) · MDCalc — 4Ts Score for Heparin-Induced Thrombocytopenia · Gauer RL, Whitaker DJ. Thrombocytopenia: Evaluation and Management. Am Fam Physician 2022;106(3):288–298 · Cuker A et al. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood 2012;120(20):4160–4167 · Argatroban injection prescribing information — DailyMed · ASH — 2018 Clinical Practice Guidelines on VTE: HIT snapshot (What You Should Know) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).