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The classic presentation of HIT is a hospitalized patient receiving heparin whose platelet count falls by more than 50% from baseline, though generally to a level still above 50,000/mcL. There may be associated thrombosis, either venous (deep venous thrombosis, pulmonary embolism, venous limb gangrene) or arterial (cold digits or extremity). Skin necrosis at the site of heparin injections may also be seen.


  1. Caused by the development of an antibody directed against a heparin-platelet factor 4 complex; the antibody occurs more commonly with unfractionated heparin than with low-molecular-­weight heparin. The antibody causes aggregation and activation of platelets, which paradoxically increases the risk of thrombosis.

  2. Develops in about 5% of patients who receive heparin.

  3. Surgical patients are at higher risk.

  4. HIT manifests between 5 and 10 days after starting any kind of heparin—full-dose intravenous heparin, low-dose prophylactic heparin, or even just heparin flushes to maintain patency of indwelling intravascular catheters. Thrombocytopenia may develop earlier in patients with recent heparin exposure.

    image Any exposure to heparin, including small heparin flushes, can lead to HIT.

  5. Thrombosis develops in about 50% of patients who have HIT, and the thrombosis may be evident at the same time as the platelet count drop, though it may also be delayed by several days or weeks. Thrombosis may be arterial (previously called the white clot syndrome), although it is more often venous.

  6. The platelet count does not usually drop below 50,000/mcL in HIT; a lower platelet count suggests another etiology.


  1. The most sensitive, readily available screening test is an enzyme-­linked immunosorbent assay (ELISA) for anti-PF4 antibody.

    1. It is nearly 100% sensitive, although specificity is between 75% and 85%. Thus, a negative test is very reassuring that HIT is not present, but false-positive tests are not uncommon.

    2. The serotonin-release assay (SRA) is more specific but not readily available; it can be run if a false-positive ELISA is suspected.

  2. Because the poor specificity of the anti-PF4 assay leads to overdiagnosis of HIT, a pretest probability scoring system (the 4“T’s”) has been validated.

    1. Thrombocytopenia

      1. Fall of platelets by > 50% and nadir > 20,000/mcL = 2 points

      2. Fall of platelets by 30–50% or nadir 10–19,000/mcL = 1 point

      3. Fall by < 30% or nadir < 10,000/mcL = 0 points

    2. Timing of platelet fall

      1. Clear onset between days 5 and 10 after exposure, or < 1 day if prior heparin exposure within 30 days = 2 points

      2. Consistent with fall between 5 and 10 days, but some data missing, or fall > 10 days, or < 1 day if prior heparin exposure within 30–100 days = 1 point

      3. Fall at < 4 days and without recent exposure = 0 points.

    3. Thrombosis or other sequelae

      1. Confirmed new thrombosis, skin necrosis, or acute systemic reaction after IV unfractionated heparin bolus = 2 points

      2. Progressive or recurrent thrombosis, non-necrotizing skin lesions or suspected thrombosis that has not ...

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