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Published July 10, 2019

Heparin-induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a condition in which an antibody — immunoglobulin G (IgG) — recognizes a complex of heparin and platelet factor 4 (PF4) on the platelet surface. The antibody binds the heparin–PF4 complex and leads to platelet activation and significant risk of thrombosis (about 50% of patients with HIT develop thrombosis). When accompanied by thrombosis, HIT is called heparin-induced thrombocytopenia with thrombosis (HITT).

When is it appropriate to suspect HIT? The "4T" scoring system for evaluating the pretest probability of HIT is as follows:



The PF4 antibody test is the most sensitive test available, but false positives are common because the threshold set for a positive test is low in order to maximize sensitivity.

Optical density (OD): Always ask the lab for the OD in order to assess the likelihood of true HIT.

  • Most labs use an OD cutoff of 0.4 for a positive test, but most patients with an OD of 0.4 do not have HIT.

  • An OD >1.5 is almost always a true positive.

  • If the OD is equivocal but there is a high clinical suspicion for HIT, the serotonin release assay (SRA) can be ordered (only after consultation with a hematologist); although SRA is usually the most specific test, it is less sensitive than the PF4 test for HIT and takes about a week to get results.

The recommended approach to diagnosis and management of HIT is as follows:

Diagnosis of HIT



If HIT is suspected based on the 4T score and high clinical suspicion, all heparin should be stopped (including flushes for intravascular lines, such as IVs or central venous catheters, which often contain heparin to prevent line clots) and a workup should be performed (see above).

If a patient is on warfarin at the time of diagnosis, hold warfarin and administer vitamin K to reverse (warfarin may increase risk of thrombosis in HIT via depletion of protein C).

The most commonly used agents for anticoaulgation therapy in patients diagnosed with HIT include the direct thrombin inhibitors argatroban and bivalirudin; subcutaneous fondaparinux (which has no heparin cross-reactivity) can also be used.

  • argatroban or fondaparinux is preferred for urgent surgery and nonurgent cardiac surgery

  • avoid argatroban with liver dysfunction

  • avoid bivalirudin and fondaparinux in patients with renal dysfunction


Patients with HIT are at very high risk of thrombosis. Therefore, it is reasonable to perform upper- and lower-extremity ultrasounds to rule out occult thrombosis since this affects duration of treatment.

Clots can occur in odd locations in HIT, including distal veins (a common presentation is a cold blue toe after cardiac surgery) or the adrenal veins (leading to adrenal hemorrhage). Consider HIT in a patient with adrenal hemorrhage and thrombocytopenia and recent heparin exposure.

Risk of clotting can persist for >30 days with HIT, so anticoagulation therapy, usually with warfarin, should be started once the patient is stabilized and platelets have risen to ≥150,000 cells/mm3.

  • It is key to continue nonwarfarin anticoagulation therapy until platelets are >150,000 cells/mm3 and bridge to warfarin.

  • Duration of treatment is approximately one month if no thrombosis is present and 3 months if thrombosis is present.

See Clinical Pearls & Morning Reports for more on heparin-induced thrombocytopenia.

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