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  • Type 1: Isolated HIT develops early in heparin therapy and is benign. No resultant bleeding or thrombotic complications. Not mediated by the immune system: passive heparin binding to platelets resulting in a modest shortening of the platelet life span. The platelet count rarely falls below 100 × 109/L
  • Type 2: Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is associated with severe thrombocytopenia and paradoxically thrombotic episodes instead of hemorrhagic complications. Occurs in patients receiving heparin for more than 5 days; may occur within 1 day if prior heparin therapy exposure <100 days


Frequency varies widely depending on type of heparin used and the patient group:


  • Unfractionated heparin is associated with a higher frequency of HIT than fractionated heparin
  • Surgical patients have a higher frequency of HIT than either medical or obstetric patients with the same heparin exposure
  • Postoperative orthopedic patients receiving unfractionated heparin have the highest HIT frequency (<5%), and require more intense platelet count monitoring
  • Pregnant women receiving LMWH have an almost negligible risk

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  • Heparin exposure can induce the formation of pathogenic IgG antibodies that can cause platelet activation by recognizing complexes of platelet factor 4 (PF4) and heparin on platelet surfaces
  • Platelet activation results in further release of PF4 and the appearance of platelet microparticles in circulation, both of which magnify the procoagulant state of HIT. PF4 complex binding to endothelial cells stimulates thrombin release. There is an increased clearance of platelets with resultant thrombocytopenia and venous and/or arterial thrombus formation with the potential for severe organ damage (loss of limbs, stroke, MI) and unusual sites of thrombosis (adrenal, portal vein, skin)
  • Potential for severe organ damage (loss of limbs, stroke, MI) and unusual sites of thrombosis (adrenal, portal vein, skin)
  • In rare cases, targets other than PF4 are involved (NAP-2, IL8)
  • The risk of heparin-induced thrombosis is far lower than the incidence of antibody formation. Fewer than 10% of those who develop an antibody to the heparin–PF4 complex will exhibit a thrombotic event
  • PF4 antibodies usually decline to undetectable levels within a few weeks or months of an episode of HIT, and there is no anamnestic response

Figure 68-1. Pathophysiology of HIT
Graphic Jump Location

PF4: platelet factor 4.


  • Testing should be performed when HIT is clinically suspected. HIT antibodies are detected using either PF4-dependent antigen immunoassays (PF4–heparin antibody ELISA) or functional assays (serotonin release assay) of platelet activation and aggregation. Both tests are very sensitive but specificity is poor
  • Clinically insignificant HIT antibodies are common in patients who have received heparin 5–100 days earlier. In the ICU setting, HIT is uncommon (0.3–0.5%), whereas thrombocytopenia from other causes is very common (30–50%)


  • The diagnosis of HIT should be based on clinical abnormalities (thrombocytopenia with or without thrombosis) and a positive test for HIT antibodies
  • HITTS has an incidence of <1% of patients receiving heparin. Platelet counts as low as 20 × 109/L can result in arterial ...

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