Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (389 page)

   CBC: Severe thrombocytopenia with normal red and white cell counts.

   Laboratory tests to demonstrate the presence of specific antibodies are used in research laboratories but have not been validated for general use.

   The gold standard for diagnosis is recovery from thrombocytopenia following discontinuation of the drug, which is usually prompt.

HEPARIN-INDUCED THROMBOCYTOPENIA (HIT)

   Definition

HIT is a complication of heparin therapy resulting in a reduction in platelet count. HIT is an immune-mediated thrombocytopenia, with antibodies developing against the complex of heparin and platelet factor 4 (PF4). HIT develops in about 3% of patients treated with unfractionated heparin but rarely (0.2%) in those receiving low molecular weight heparin (but there is cross-reactivity of the antibodies between the two). It is extremely rare with the use of fondaparinux. It develops more frequently in surgical rather than medical patients, particularly after cardiac surgery. Its seriousness is underlined by the frequent complication of venous (approximately 60% of HIT patients) and arterial (14% of HIT patients in one study) thrombosis resulting in up to 20% mortality and limb loss rates of 2–3%. The term HITT is used for HIT associated with thrombosis. Skin necrosis at the site of heparin injection is a known complication related to HIT.

   Diagnosis

   The clinical diagnosis of HIT is based on the “4Ts” criteria:

  1.  >50% fall in platelet count, or platelet nadir 20–100,000/μL;

  2.  Onset between days 5 and 10 following initiation of heparin, or <1 day in patients with exposure to heparin within the previous 100 days;

  3.  New thrombosis, skin necrosis, or acute systemic reaction post–heparin bolus;

  4.  No other obvious cause for fall in platelet count.

There are exceptions to these rules. One such situation is seen in patients who develop HIT after discontinuation of heparin (delayed onset HIT). In patients with typical HIT, the platelet count generally recovers within 1 week after discontinuing heparin administration.

   Laboratory Findings

   There are two types of assays: immunologic and functional. Some patients may develop specific antibodies without clinical manifestations of HIT. In these cases, the immunoassays are positive, but the functional ones are not. The immunoassays are sensitive in detecting HIT antibodies, but none is completely specific. To increase the specificity of immunoassays, manufacturers have developed IgG-specific assays. The resulting assays have a very high negative predictive value.

   Immunoassays presently available to coagulation laboratories:

    PF4 IgG
^M
is an ELISA assay designed to detect IgG antibodies reactive with PF4. This assay has both excellent negative predictive value (with a cutoff <0.4 optical density [OD]) and high positive predictive value. A good relationship with the serotonin release assay (see below) has been found at OD readings of >1.4. Successful performance of the assay requires high technical skills.

   Flow cytometry for detecting PF4 antibodies is available in research laboratories.