The Impact of Laboratory Sample Request Evaluation and the Use of Probability Testing for HIT By Trained Physician on the Decrease of Unnecessary Tests and Increase the Likelihood of Positivity

Abstract

Introduction: Heparin-induced thrombocytopenia (HIT) is an extremely serious and potentially fatal condition that can develop in patients taking heparin-based medications, such as unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). The laboratory tests for diagnosis of HIT is expensive and time consuming. Clinical assessment (4Ts) followed by testing for Heparin/platelet factor 4 antibody in intermediate and high risk patients is the standard algorithm of pretest for (HIT) which can be later confirmed by serotonin releasing assay if available. Materials and methods: We conducted a retrospective analysis of laboratory practice of pretest evaluation of samples submitted for HIT testing in a cohort of patients treated in a tertiary hospital in Saudi Arabia who had a clinical suspicion of HIT. The 4 T score was a pretest requisite to proceed for electronic request for HIT. It had to be performed by the requesting physicians of different medical specialties. The request then been evaluated by hematopathologist before proceeding. The test will be cancelled if: the 4T score calculated by attending physician is < 4 or if platelet count is normal with no evidence of significant drop in the last 4 days from request or the test was performed at least 2 days before the new request. Additional exercise was performed by two physicians in training after train them to standardize the calculation of the 4T scores without re evaluation by the hematopatologist. The sample proceeded for testing if it met the testing criteria of 4T score > 3 and passed the evaluation by the hematopathologist. All tested sample were performed by immunoglobulin G (IgG) antibodies via an ELISA (Asserachrom HPIA-IgG, Stago Diagnostica STA®) and Optic density ( OD) and was evaluated and considered positive if OD >0.39 with sub classification to low positive 0.4-1, moderate 1-2 and strong if >2. Over a period of 2 years, we received 449 samples for patients who were admitted to our hospital, received prophylactic or therapeutic doses of LMWH or UFH, and underwent an HIT test due to clinical suspicion ( > 50% drop in platelet count from baseline, or ≥ 2 consecutive platelet counts < 150,000 per mm 3 and was defined as possible HIT). The 4 T score was calculated in the hospital system by attending physicians referred to as (system 4T score) and recalculated by trained two physicians and referred to (re calculated 4T score). Descriptive statistics, paired samples statistics, correlations, and analysis of variance (ANOVA) were performed. Results: The test was labeled by the laboratory physician ( hematopathologist ) as not indicated and test was not performed in 156 (35%) for various reasons including low 4 T score <3 in 90 (57%), Normal platelet count > 150 at time of test ( and wrong calculated 4T score) in 28 (18%), duplication of test order in 10 (6.4%%), There was clear other cause of thrombocytopenia in 15 (10%), Bad sample quality 5 (3.2%%) and 8 (5%) for other reasons. The samples for HIT test were for 231(51%) males and 220 (49%) females with mean age 56.3 (1-102) years. The mean platelet count at time of request was 82.9 (2-384) per mm 3. Out of the total cohort 422 (95.1%) patients had received UFH and only 22 (4.9%) received LMWH. There is only 69/449 (15.4%) agreement between the two calculations (system and re calculated score) . Out of the tested samples 293, total positive tests 19 (6.5%), were 11 (3.8%) had low positive for HIT test, moderate positive in 6 (2%) and only 2 strongly positive for HIT. The calculated (system 4T score) of < 4 were 142 (32%) samples while the (re calculated 4T score) were 136 (30%) of which 60 ( 38%) of the cancelled tests by hematopathologist, of which 68 (23%) of tested samples were negative and 7 (37%) of positive tests could have been missed based on this calculation. There were 12 out of 19 had moderate and high score by calculation and positive HIT while there were 17 out of 19 had moderate and high score by system calculation. Conclusion: We are reporting improved detection of HIT and confirmed the value of applying the 4 T score for HIT testing with added value of pre test screening to exclude low probability and cancel samples with no clear indication of HIT due to presence of other causes of thrombocytopenia.The retrospective re calculation even with more trained physicians did not add a value compared to pretest evaluation and screening by hematopathologist which had resulted in cancelation or more than third of the requested tests.