Rapid Versus Typical Onset of Thrombocytopenia

We will discuss the diagnostic approach to HIT based on the timing of onset of thrombocytopenia, either rapid (<5 days) or typical (>5 days) (see Chapter 2).

In general, there are two broad pretest probabilities for patients with rapid thrombocytopenia: low and high. Patients with low pretest probability for HIT are those who have not recently been exposed to heparin (thus, they would not be expected to have circulating HIT antibodies, or to have generated them so quickly), or who have another good explanation for thrombocytopenia. (An important caveat is that sometimes a recent heparin exposure is not known to the patient or has not been documented in the medical records.) With a low pretest probability for HIT, either of the sensitive assays for HIT (washed platelet activation assay or antigen assay) can reliably rule out HIT. However, an unexpected negative result in a patient with a high pretest probability, or an unexpected positive result in a patient with a low pretest probability, should lead to repeating the test or performance of the complementary activation or antigen assay. Additionally, further clinical information should be sought. (For example, has another explanation for the thrombocytopenia become apparent? Could the patient have had an unrecognized recent heparin exposure?)

In contrast, for patients with the typical temporal onset of thrombocytopenia (i.e., a platelet count fall that begins 5-10 days after beginning heparin treatment), we believe that, in general, there are two different pretest probabilities for HIT: moderate and high. Because HIT is a relatively common explanation for thrombo-cytopenia that begins during this characteristic time period, it should be considered a plausible diagnosis even if another possible explanation for thrombocytopenia is identified (hence, a moderate pretest probability). In a patient without another apparent explanation for thrombocytopenia, or one in whom an unexplained new

FIGURE 6 (Figure on facing page) Comparison of activation and antigen assays for HIT-IgG: analysis of prospective studies. Quantitative results of an activation assay, the SRA, are shown on the x-axis (although samples that gave <20% serotonin release are shown without reference to the actual quantitative result obtained [see box designated <20%]); quantitative results of the antigen assay (which detected only IgG anti-PF4-H antibodies) are shown on the y-axis. (A) Orthopedic surgery patients who received UFH; (B) orthopedic surgery patients who received LMWH; and (C) cardiac surgery patients who also received postoperative UFH. The arrows indicate the data points corresponding to the 15 patients who developed clinical HIT (>50% platelet count fall from the postoperative peak). The data show similarly high sensitivity of the activation and antigen assays for clinical HIT; however, the activation assay had higher specificity for clinical HIT. Most sera (13/15, 87%) from patients with clinical HIT strongly activated platelets (>80% serotonin release). Abbreviations: HIT, heparin-induced thrombocytopenia; LMWH, low molecular weight heparin; PF4, platelet factor 4; SRA, serotonin release assay; UFH, unfractionated heparin. Source: From Warkentin et al., 2000.

thrombotic event has occurred, the pretest probability for HIT would be considered to be high.

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