A Simple Two Step Approach for Diagnosis of Heparin Induced Thrmbocytopenia Using 4T Score and PaGIA Testing

Heparin-induced thrombocytopenia (HIT) is an important adverse event of treatment with Heparins. It is associated with significant morbidity and mortality if unrecognized. Following diagnosis of HIT proper treatment should be started as soon as possible to avoid thrombosis and occasionally death. Thrombocytopenia is a relatively frequent finding in hospitalized patients and can be caused by many different factors so that establishing diagnosis of HIT is not straight forward and depends on complex laboratory tests and is often time consuming.

In our retrospective cohort study we aimed to test whether a simple 2 step approach for diagnosis of HIT will simplify and shorten the diagnostic process. We screened all suspected patients with careful history of risk factors, platelet counts and timing relative to heparin exposure and scored the 4T score for each patient. Then we tested all patients with the Platelet Aggregation Gel ImmunoAssay (PaGIA) test and followed carefully each patient clinical course and platelet counts for 30 days. True HIT was diagnosed when no significant alternative diagnoses for thrombocytopenia were present and the platelet counts returned to normal after appropriate treatment for HIT was started. During the 3 years of the study we screened and analyzed HIT sera of hospitalized patients from different wards at the Sheba Medical Center. All together 107 thrombocytopenic patients (median age-71, 60 women) had PaGIA tests sent of whom 95 were eventually studied. About half of patients (52%) were surgical patients from various wards and the rest were medical patients. Most patients were treated with LMWh (60%) or UFH (28%) for a median of 6 days prior to HIT testing and most (84%) patients had other causes for the low platelet counts mainly infection (37%) and concomitant medications (16%). Based on our pre-defined criteria HIT was diagnosed in 15/95 (16%) of patients. We found that a 4T score of 0-2 resulted in none of the patients (0/24) being diagnosed as HIT and the PaGIA was negative in all these patients whereas a high score of 6-8 was associated with a 100% (6/6) likelihood for having HIT (and all tested PaGIA positive). In patients with an intermediate 4T score of 3-5 (65 patients) PaGIA was positive in 25 patients of whom 9 (36%) had HIT while in the 40 patients who tested negative for PaGIA no patient was diagnosed with HIT. Fifteen patients had thrombotic events of whom 5 were diagnosed with HIT (p=0.057 compared to patients without HIT diagnosis). Overall PaGIA sensitivity was 100% with an excellent negative predictive value (100%) but with 74% specificity and poor positive predictive value (42%).

In conclusion we found that in our cohort of patients low 4T score (0-2) was by itself sufficient to rule out HIT whereas a high score (6-8) confirmed HIT in all patients. In patients with an intermediate score testing with PaGIA proved beneficial when test results were negative but in patients with positive PaGIA additional test may be needed. Our conclusions will naturally have to be tested in a large prospective management study.