Heparin therapy may result in two different syndromes of thrombocytopenia. One form is mild and benign, while the second can be severe and life threatening.


Heparin-induced thrombocytopenia type I:

(1) the platelet count drops for the first few days of heparin therapy (early onset)

(2) occurs in about 10% of patients receiving heparin

(3) results from direct interaction between heparin and the platelet membrane proteins, resulting in enhanced platelet aggregation

(4) the platelet count usually stays above 100,000 per µL

(5) the platelet count tends to rise again despite continued heparin therapy, with counts often returning to initial levels

(6) not associated with increased risk of thrombosis


Heparin-induced thrombocytopenia type II:

(1) an uncommon complication of heparin therapy (from 1-3% of those receiving unfractionated heparin)

(2) associated with IgG antibodies forming heparin-platelet factor 4 (PF4) complexes which bind to platelets and which cause platelet activation with release of dense granule contents, including platelet factor 4

(3) most common with heparin derived from bovine lung, less common with heparin from porcine gut, and much less common with low molecular weight heparins

(4) more common with high dose therapeutic regimens than low dose prophylactic regimens

(5) results in a progressive decrease in platelet count, either to < 50% of initial levels and/or to < 100,000 per µL

(6) associated with an increased risk of thrombosis, which can be life-threatening

(7) DIC can occur

(8) less often it may be associated with hemorrhage, which usually is not severe

(9) in patients who have never been exposed to heparin before, the thrombocytopenia may occur on day 4-20 of heparin therapy (typically day 10)

(10) in patients with a past history of heparin therapy, the thrombocytopenia can occur at any time up to day 20 of therapy; it has been reported to occur within hours of initiation of heparin infusion in previously exposed patients

(11) platelet levels return to normal levels in about 4-10 days if the heparin infusion is discontinued; the thrombocytopenia continues and progresses if heparin therapy is continued


Thrombosis in heparin-induced thrombocytopenia type II:

(1) may be arterial or venous

(2) there may be extension of existing venous thrombi, with pulmonary embolization

(3) arterial thrombi may occur in the aorta, its major branches, cerebral, coronary, mesenteric, renal or upper extremity arteries

(4) can result in limb gangrene

(5) skin necrosis can occur at injection sites


Diagnosis of heparin-induced thrombocytopenia type II:

(1) exclusion of other causes of thrombocytopenia

(2) return in platelet count to normal after discontinuation of heparin

(3) demonstration of heparin-dependent antibodies (heparin-induced platelet aggregation, platelet factor 4 ELISA, serotonin release assay)


Therapy of heparin-induced thrombocytopenia type II:

(1) immediate discontinuation of heparin infusion

(2) low molecular weight heparins may be of use, but cross-reactivity with heparin antibodies can occur

(3) Orgaran 10172 is a heparinoid compound which shows minimal cross-reactivity with heparin-dependent antibodies

(4) hirudine, hirulog, argatroban and other compounds with direct antithrombin effect can be used

(5) ancrod (defibrinogenating agent) may be an alternative

(6) coumarins should not be used alone, since (1) delay in onset, (2) drop in protein S and C early in therapy can result in thrombosis, aggravating the heparin-related problems

(7) antiplatelet agents such as aspirin or dipyridamole should not be used alone

(8) deep venous thrombi may require insertion of an inferior vena caval filter

(9) platelet transfusions should be avoided


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