Heparin-Induced Thrombocytopenia

Heparin-induced thrombocytopenia

The College of American Pathologists recently published consensus recommendations for the laboratory diagnosis and monitoring of heparin-induced thrombocytopenia (HIT).1 HIT is an adverse drug reaction to the administration of the anticoagulant heparin resulting in a decrease in the platelet count (thrombocytopenia) while paradoxically dramatically increasing the risk for thrombosis. The risk for HIT depends on the type of heparin used; unfractionated heparin (UFH) has a higher association with HIT than the low-molecular-weight heparins (LMWH). The surgical patient treated with heparin is at greater risk of developing HIT than the medical patient. Approximately 5% of orthopedic surgery patients and 3% of cardiac surgery patients who receive UFH will develop clinical HIT (defined as a 50% or greater fall in the platelet count). The overall risk of thrombosis in the HIT patient is 75%, the risk being proportional to the severity of the fall in the platelet count.

HIT is an acquired antibody-mediated drug reaction. For unknown reasons, some patients develop antibodies that recognize a complex of platelet factor 4 (PF4) and heparin. At the same time, various products released from the activated platelets lead to the generation of thrombin, resulting in a hypercoagulable state and subsequent risk for venous and arterial thrombosis. The hypercoagulable state can persist for days after the discontinuation of heparin.

In patients who have never received heparin but who develop HIT, the fall in the platelet count begins 5 to 10 days after heparin therapy is instituted (day 0 is the day heparin is started) and the median platelet count nadir is 55 to 60 x 109/L. To aid in the early detection of HIT, the frequency of platelet-count monitoring should be appropriate for the risk of developing HIT. Patients at highest risk include postoperative patients receiving prophylactic or therapeutic-dose UFH; these patients should receive platelet counts at least every other day between day 4 and day 10 of therapy. Patients in the intermediate-risk category (medical/obstetrical patients receiving UFH, postoperative patients receiving prophylactic LMWH, patients receiving intravenous [IV] catheter flushes with UFH) should have their platelet counts monitored at least 2 or 3 times between days 4 and 10. The low-risk patients (medical/obstetrical patients receiving LMWH, or medical patients receiving IV flushes with UFH) do not need routine monitoring. Those patients who have been exposed to heparin within the past 100 days need a platelet count within 24 hours of reinitiation of heparin to identify those with rapid-onset HIT due to pre-existing circulating HIT antibodies. A platelet fall of 50% or greater from baseline can indicate HIT, even if the platelet count nadir remains >150 x 109/L.

Patients with suspected HIT are then tested for HIT antibodies. HIT is a clinicopathologic diagnosis and requires that both clinical abnormalities and HIT antibodies be present. Acute serum or plasma should be used as HIT antibodies are transient and are usually not detectable after a median of 50 to 85 days. HIT antibody assays fall into 2 categories: washed platelet activation assays and antigen assays. Both show similar high sensitivity. The platelet assays show greater specificity (in that the antigen assays are more likely to detect antibodies in the absence of clinical HIT), especially in cardiac surgery patients. If no HIT antibodies are detected, another etiology to the thrombocytopenia must be sought. 1Arch Pathol Lab Med. 2002:126;1415-1423.

See also 0310_HIT_Algorithm.jpg