Prospective Evaluation of 4T's Score and Rapid Particle Gel Immuno-Assay Specific to H/PF4 Complexes To Exclude Heparin-Induced Thrombocytopenia.

Abstract

Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin treatment because of the risk of venous and arterial thromboses. HIT is often difficult to diagnose in practice since most patients have several potential causes of thrombocytopenia. A scoring system named 4T's and based on four criteria (i.e. Thrombocytopenia, Timing of platelet count fall, Thrombosis or other sequelae, oTher cause of thrombocytopenia) has recently been proposed to estimate the probability of HIT before laboratory testing (T Warkentin, BJH 2003), and a particle gel immunoassay (H/PF4-PaGIA, Diamed, Switzerland) has also been developed to provide a rapid detection of HIT antibodies in less than one hour after blood sampling. The aim of this study was to compare the performance of both methods to exclude HIT in emergency conditions. One hundred twenty consecutive patients suspected of having HIT were included in 4 different centers over 9 months. Medical records were independently analyzed by two physicians, and the probability of HIT was evaluated using the 4T's score blind to the results of the PaGIA. In addition to PaGIA performed on the day of suspicion, serotonin release assay (previously identified as higly specific for HIT) and PVS/PF4 ELISA (GTI, Brookfiled, WI) were also performed, and HIT was confirmed when both assays were positive. The risk of HIT was evaluated by the 4T's score as low (LR), intermediate (IR) and high (HR) in 35% (n = 42), 63% (n = 73) and 4% (n = 5) of patients, respectively (Table). Since SRA (that detects pathogenic HIT IgG antibodies) was negative in all LR patients, the negative predictive value (NPV) of the 4T's score, which allowed the diagnosis of HIT to be eliminated in 35% of cases, was 100%. PaGIA was negative in 99 cases, including 16 patients for whom PVS/PF4 ELISA was positive (median 0.519, range 0.410 – 2.4). The diagnosis of HIT was excluded in all of these patients by the clinical evolution and since SRA was consistently negative. The NPV of PaGIA was thus 100% and this test was able to eliminate HIT in 82% of patients. The diagnosis of HIT was confirmed in 12 patients (SRA positive), including 5 evaluated as HR and 7 as IR by the 4T's score, and PaGIA was positive in all these cases (sensitivity 100%). However, the positive predictive value (PPV) of PaGIA was lower (51%) since positive results were also obtained in 9 cases for whom the diagnosis of HIT was eliminated. In conclusion, the 4T's scoring system appears to be a reliable first step to evaluate the likelihood of HIT, and to avoid unecessary biological assays in patients evaluated as LR. In addition, PaGIA can be applied to eliminate HIT with a high NPV, and could be particularly useful in patients classified as IR by the 4T's score. Finally, platelet activation tests such as SRA are always mandatory to confirm HIT in every patient having developed antibodies specific to polyanion-modified PF4.PaGIAPVS/PF4 ELISASRA4T's scoren−/+−/+−/+Low Risk (LR)4237/533/942/0Intermediate Risk (IR)7362/1152/2166/7High Risk (HR)50/50/50/5Total12099/2185/35108/12