Abstract

Introduction: Heparin-induced thrombocytopenia (HIT) is an immune mediated, adverse effect related to both unfractionated heparin (UFH) and low-molecular weight heparin (LMWH). HIT may result in significant morbidity and mortality. The serotonin release assay (SRA) is utilized in conjunction with clinical information to diagnosis HIT. Employment of the pretest clinical scoring system, known as the “4Ts”, classifies patients as having a low, intermediate or high probability for developing HIT. Previous investigators have reported clinically diagnosed HIT in patients with a negative SRA. However, there is no systematic study evaluating such a group of patients. We determined the frequency of thromboses in SRA negative patients and determined the correlation between the 4T score in patients with and without thromboses.

Methods: We report a descriptive, single institution, retrospective study of 181 consecutive samples over the course of one year sent to the Coagulation Laboratory of St. Louis University for the work up of suspected HIT. A total of 142 patients were eligible. Patients with SRA negative samples were evaluated for evidence of thrombosis. Diagnosis of a thrombotic event was made by computed tomography (CT), venous Doppler ultrasonography (US), and ventilation-perfusion scanning (V/Q). Defined patient study groups were: all evalulable patients (PALL), patients with thromboses (TPOS) and patients without thromboses (TNEG). Analyses, between each patient group, the 4T score, mean platelet count prior to heparin therapy, and mean platelet nadirs were performed.

Results: The overall incidence of proven thromboses in evaluable SRA negative patients was 14.8% (n=21). Of the 21 thromboses, 17(81.0%) were deep venous thromboses (DVT), 3(14.3%) were DVT and pulmonary embolus (PE), and 1(0.7%) was an isolated PE. A significant difference in 4T score was observed between TPOS vs PALL (p<0.0001) and TPOS vs TNEG (p<0.0001) groups. There was no difference between the patient groups PALL vs TNEG (p=0.985). No statistically significant difference between the study groups was seen for either initial platelet averages (TPOS vs PALL [p=0.8923], TPOS vs TNEG [p=0.2091], PALL vs TNEG [p=0.2550]) or nadirs (TPOS vs PALL [p=0.4664], TPOS vs TNEG [p=0.3763], PALL vs TNEG [p=0.7860]).

Total Evaluable Patients (PALL)Patients without Thrombosis (TNEG)Patients with Thrombosis (TPOS)
* Missing data was included in calculations for patients without thrombosis 
n 142 (100%) 110 (77.46)/121(85.2%)* 21(14.8%) 
Avg. 4T Score 3.23 (±1.81) 2.79 (±1.61)* 5.50 (±0.83) 
Avg. Initial Platelet Count (1X109/L) 198.98 (±97.19) 194.16 (±99.39)* 223.90 (±79.31) 
Avg. Platelet Nadir (1X109/L) 75.02 (±48.57) 73.41 (±46.47)* 82.86 (±59.42) 
Avg. Platelet Drop (1X109/L) 123.96 (62.30%) 94.77 (48.81%)* 141.04 (62.99%) 
NO Data* 11 11(7.75%)* NA 
Total Evaluable Patients (PALL)Patients without Thrombosis (TNEG)Patients with Thrombosis (TPOS)
* Missing data was included in calculations for patients without thrombosis 
n 142 (100%) 110 (77.46)/121(85.2%)* 21(14.8%) 
Avg. 4T Score 3.23 (±1.81) 2.79 (±1.61)* 5.50 (±0.83) 
Avg. Initial Platelet Count (1X109/L) 198.98 (±97.19) 194.16 (±99.39)* 223.90 (±79.31) 
Avg. Platelet Nadir (1X109/L) 75.02 (±48.57) 73.41 (±46.47)* 82.86 (±59.42) 
Avg. Platelet Drop (1X109/L) 123.96 (62.30%) 94.77 (48.81%)* 141.04 (62.99%) 
NO Data* 11 11(7.75%)* NA 

Conclusions: A higher incidence of thrombotic events in SRA negative patients was seen compared to historical data. A strong positive and negative correlation exists between high and low 4T scores, respectively, and the probability of thromboses from HIT. Prospective data are needed to address the incidence of thrombosis for patients in whom the pretest probability of HIT is high and in whom the SRA is negative. Studies evaluating the utility of serial SRA testing in such patients may lead to earlier identification of those at high risk for thromboses. Limitations of this study were the retrospective design, single institution, and the lack of serial SRA testing.

Disclosures: No relevant conflicts of interest to declare.

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