Hematology, Oncology & Immunology · Topic 7 of 28

Heparin-Induced Thrombocytopenia (HIT)

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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.

01 · Suspect whenPlatelets fall over 50% on heparin day 5–10

02 · First move4Ts score: 0–3 low effectively excludes HIT

03 · Stop nowAll heparin, including flushes and LMWH

Why it happens

Antibodies to PF4–heparin complexes activate platelets

Immune reaction to platelet factor 4–heparin complexes

Activated cells generate thrombin; platelets are consumed: low count, yet clotting

Bleeding is rare

One-third to one-half develop venous or arterial thrombosis

Who gets it

Unfractionated heparin: about 10× the risk of LMWH

Most common after surgery, especially cardiac surgery

Even small heparin flushes can trigger it

HIT occurs in up to 2.4% of patients receiving unfractionated heparin.

What you'll see

Platelet fall over 50%, typically days 5–10 of heparin hallmark

Nadir usually 20,000/mcL or higher

Heparin in the past 30 days: fall can start within 1 day

New venous or arterial thrombosis thrombosis

Skin necrosis, or a systemic reaction after an IV bolus

Diagnosis: 4Ts, then the lab

Score first — not gestalt. 0–2 points for each of 4 items

Thrombocytopenia: fall over 50%, nadir ≥ 20,000 = 2 points

Timing: onset day 5–10, or ≤ 1 day if recent heparin = 2

Thrombosis: new clot or skin necrosis = 2

Other cause: none = 2 · a definite one = 0

4Ts 0–3 low: HIT excluded — no tests, no empiric treatment

4Ts 4–5 intermediate · 6–8 high: stop heparin, send tests

Send a PF4–heparin immunoassay (ELISA) first

ELISA positive: confirm with a functional assay (SRA)

Low 4Ts score: negative predictive value about 99.8%. Positive predictive value is only about 14% (intermediate) and 64% (high), so those patients need lab testing. A functional assay may be unnecessary when the 4Ts score is high and the immunoassay is very strongly positive (optical density above 2.0).

Red flags

Intermediate or high 4Ts: every heparin source stop heparin

LMWH — it cross-reacts with HIT antibodies stop LMWH

Warfarin before platelets reach ≥ 150,000/mcL no warfarin

Already on warfarin: stop it and give IV vitamin K reverse warfarin

Routine platelet transfusion at average bleeding risk no platelets

Life- or limb-threatening thrombosis parenteral agent

Early warfarin causes venous limb gangrene and skin necrosis. Platelet transfusion has been linked to more arterial thrombosis — consider it only for active bleeding or a high-bleeding-risk procedure.

Treatment

Stop heparin and anticoagulate — stopping alone is not enough

First moves, in order

Score the 4Ts0–3: HIT excluded, stop here

→

Stop every heparin sourceinfusions, prophylaxis, flushes, LMWH

→

Start a non-heparin anticoagulanttherapeutic intensity for a high 4Ts score

→

Send the PF4–heparin immunoassaypositive → functional assay

Critically illshort-acting IV

Argatroban Bivalirudin

Critical illness, high bleeding risk or likely procedure: IV agent

Life- or limb-threatening thrombosis: a parenteral agent

Argatrobanliver-cleared

Argatroban 2 mcg/kg/min IV, no bolus

Titrate to aPTT 1.5–3× baseline

Liver dysfunction, HF, after cardiac surgery: start 0.5–1.2

Bivalirudinshort-acting

Bivalirudin 0.15 mg/kg/h IV

Titrate to aPTT 1.5–2.5× baseline

Reduce the dose in renal or hepatic dysfunction

Stableaverage bleeding risk

Fondaparinux 5, 7.5 or 10 mg SC daily Rivaroxaban (DOAC)

Fondaparinux (dosed by weight) or a DOAC

Fondaparinux: renal, 17-h half-life — poor if a procedure is near

Intensityby 4Ts score

High 4Ts score: therapeutic intensity

Intermediate score + high bleeding risk: prophylactic intensity

Screensilent DVT

Isolated HIT: bilateral leg compression ultrasound

Silent DVT in 12–44%; scan the arm with a central line too

Durationby thrombosis

HIT with thrombosis: anticoagulate 3–6 months

Isolated HIT: until platelets recover, often 4–6 weeks, up to 3 months

Delay risk and remote HIT

Each day of delayed treatmentroughly a 6% risk of new thrombosis, amputation or death — yet HIT is also frequently overdiagnosed

Remote HIT (antibodies now negative)heparin may be used during cardiac surgery, limited to the operation; monitor platelets afterward for delayed-onset HIT

The optimal duration for isolated HIT is not settled (AFP; ASH 2018 lists it as a research gap).

Switching to warfarin

Start warfarin only once platelets are ≥ 150,000/mcL

No warfarin loading dose

Argatroban falsely raises the INR

Stop argatroban once the combined INR is over 4

Recheck the INR 4–6 hours after stopping argatroban

HIT likely or unlikely? (4Ts)

	Points toward HIT	Points away from HIT
Size of fall	Over 50%, nadir 20,000/mcL or higher	Under 30%, or nadir under 10,000/mcL
Timing	Onset days 5–10, or within 1 day if heparin in past 30 days	Fall within 4 days, no recent heparin
Thrombosis	New thrombosis, skin necrosis, or reaction after IV bolus	None
Other cause	None apparent	Definite other cause (eg, sepsis, another drug)

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) · Merck Manual Professional — Overview of Thrombotic Disorders (Jul 2025) · Marchetti M et al. Heparin-Induced Thrombocytopenia: A Review of New Concepts in Pathogenesis, Diagnosis, and Management. J Clin Med 2021;10(4):683 · Follow your institution's protocols.