Heparin-induced thrombocytopenia: interest and difficulties to identify the immunologic mechanism

lHeparin-induced thrombocytopenia (HIT) is a drug induced immunohematologic adverse reaction which is a rare but potentially very severe accident. Its diagnosis is important for epidemiologic and pharmacovigilance studies and in order to decide the most appropriate treatment. Its importance is enhan ced since there is no gold standard diagnostic criteria In clinical practic e the diagnosis is based on a group of criteria related to clinical events and laboratory tests. We have established a score based on anamnestic crite ria which allowed us to evaluate and compare two different laboratory tests : a platelet aggregation test (PAT) and a test for the detection of heparin dependent antibodies (Heparin Platelet Induced Antibodies or HPIA). The fu nctional test PAT which is commonly used in expert laboratories detects ant ibodies inducing platelet aggregation in the presence of heparin. The HPIA rest more recently developed is an ELISA test which detects antibodies dire cted at heparin-platelet factor 4 complexes. The relative value of theses t wo methods for the diagnosis of NIT is not well documented We have analysed the results of these two tests in 273 consecutive patients with a suspicio n of HIT. The results were concordant in 70 % of patients. In selecting the patients with the lowest and the highest probability of HIT according to t he score, PAT was found a more sensitive and HPIA a more specific test than the other: At low probability PAT is more often positive than HPIA 18% and 9% respectively No test is 100 % reliable, the specificity being limited f or both tests since in about 20 % of cases one or both tests are negative c ontrasting with a highly probable HIT. In this last group of patients, PA w as more frequently positive (86 %) than HPIA (72 %). Both tests are negativ e in 6 % of patients suggesting the existence of presently unknown antigeni c targets. Considering a group of 19 patients with a high probability of HI I: Mie have found antibodies against IL-8 or NAP-2 in only 7 patients. The discrepancy between a HPIA positive and a PAT negative encountered in 8 % o f patients may be explained by the existence of IgA or IgM immunoglobulins since in contrast to IgG they are unable to promote platelet aggregation vi a the CD32 platelet membrane receptor This work suggests than neither test is 100 % reliable and that they play a complementary role in the diagnosis of HIT. The potential advantage of using both tests should be confirmed in complementary studies.