How Should Clinical HIT Be Defined

HIT is a clinicopathologic syndrome, and thus can be defined as a patient with a clinical profile consistent with HIT, and in whom heparin-dependent, platelet-activating antibodies can be detected. From an operational point-of-view, this corresponds to at least an "intermediate" pretest probability score (e.g., >4 points in the 4 T's scoring system) and having a positive washed platelet activation assay for "strong" heparin-dependent platelet-activating antibodies (generally >50% serotonin release or <25 min lag time in the HIPA). If a positive EIA is used to support the presence of antibodies, the clinician should be aware that non-platelet-activating antibodies could give a "false-positive" test result, and so if the clinical picture

FIGURE 6 (Caption on facing page)

suggests alternative diagnoses, requesting the more specific washed platelet assay may be helpful. Another relevant issue is that a higher "strength" of a positive washed platelet activation assay or solid-phase EIA increases the likelihood of the patient having HIT, given a certain pretest probability (Warkentin, 2005). This is discussed in the section "Diagnostic Interpretation of Laboratory Results."

Laboratory testing for HIT antibodies is often performed in clinical situations suggesting a low probability for HIT, presumably because physicians wish to "rule out" this diagnosis (Lo et al., 2006). We have found that only about 7% to 10% of patients who undergo testing for HIT antibodies have a serological profile consistent with the diagnosis (Juhl et al., 2006; Warkentin and Sheppard, 2006a).

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