Clinical Presentation of HIT. Part 3
HIT should be suspected in any patient who develops thrombocytopenia (,150,000/ml) or a 50% or greater fall in the platelet count after 5 days of heparin therapy. The platelet count should be repeated and the blood film examined to exclude platelet clumping causing pseudothrombocytopenia. After confirmation of the low platelet count, the diagnosis of HIT may be made according to the following criteria:
1) occurrence of thrombocytopenia during heparin administration;
2) exclusion of other causes of thrombocytopenia such as infection, drugs and autoimmune thrombocytopenia;
3) resolution of thrombocytopenia after cessation of heparin therapy;
4) demonstration of a heparin-dependent platelet antibody by an in vitro test.
Criteria 1 and 2 only are required for the diagnosis of HIT type I. As in most hospitals, in vitro confirmation requires analysis of samples in a reference laboratory (see later discussion); the initial diagnosis of HIT is often made on clinical grounds (criteria 1, 2 and 3). In the absence of thrombocytopenia, HIT should also be considered if a patient receiving heparin experiences a new thrombosis or develops heparin resistance or (rarely) skin necrosis at sites of heparin administration.
Laboratory Studies for the Heparin-Dependent Platelet Antibody
A variety of laboratory tests for the detection of heparindependent platelet antibodies have been described. The most widely used is the platelet aggregation test, which measures the aggregation of normal donor platelets by patient serum or plasma in the presence of heparin. This test is popular because it is simple, inexpensive and based on a technique that is already in use in most hemostatic laboratories and can provide a result within 2 to 3 h. Although it has a specificity of ;90%, the sensitivity is reported to be between 30% and 50%, which, in the view of some investigators, limits its clinical usefulness. However, when performed under optimal conditions, with appropriate positive and negative controls, using donor platelets from individuals known to be highly reactive to the antibody, the sensitivity of the test is reported to exceed 80%. Using washed platelets (prepared as for the two-point 14C-serotonin release assay [see later discussion]) in place of platelet-rich plasma for the aggregation assay may increase its sensitivity and specificity (heparin-induced platelet aggregation [HIPA] test) The currently accepted reference standard for the laboratory diagnosis of HIT is the two point 14C-serotonin release assay. In this assay, radiolabeled, washed platelets from reactive donors are incubated with heat-treated patient serum in the presence of heparin. The test is positive if 14C-serotonin release occurs at therapeutic (0.1 U/ml) but not high (100 U/ml) heparin concentrations. It is technically demanding, uses radioactivity and is timing consuming, and therefore usually performed in a reference laboratory and used to confirm rather than to make the diagnosis of HIT.