High Incidence of True Heparin-Induced Thrombocytopenia and Heparin-Induced Thrombocytopenia Antibody Development in Critically Ill Medical Patients

Background: Thrombocytopenia is very prevalent in critically ill medical patients. Heparin-induced thrombocytopenia (HIT), which is a serious immunologic complication of heparin administration, is one of the major concerns. Diagnosis of HIT in critically ill patients is challenging due to concomitant illnesses. We previously reported the HIT cohort with the high proportion of critically ill medical patients (61.7%) in Thailand (Uaprasert N, etal. Blood Coagul Fibrinolysis 2013;24:261-8). However, data of the true incidence and risk factors for HIT in this particular population in Thailand are still lacking. In addition, the confirmatory assay is not readily available and unlikely to be useful for timely clinical management. Therefore, clinical predictors and screening assays are important for immediate clinical judgment. This study aimed to determine the incidence and define risk factors for HIT and HIT antibody (HIT-Ab) development as well as an appropriate clinical predicting model for HIT in critically ill medical patients.

Methods: Consecutive critically ill medical patients who received heparins and were admitted in the intensive care unit (ICU), coronary care unit (CCU) and intensive coronary care unit (ICCU) at King Chulalongkorn Memorial Hospital between October 2013 and May 2017 were included in this study. Patients admitted in general wards who met one of the following criteria: 1) on mechanical ventilator 2) receiving inotropic agents 3) recent undergoing renal replacement therapy due to acute kidney injury and/or 4) APACHE II score > 25, were also included for analysis. Blood samples were collected between 6 and 8 days after heparin exposure. Patients died or discharged before day 6^th after heparin exposure were excluded from the study. The rapid particle gel immunoassay (PaGIA) was used as the screening test for detecting antibodies against the heparin/platelet factor 4 complex. Subjects yielding positive PaGIA were sent for the confirmatory test using the in-house platelet aggregometry measuring heparin-induced platelet aggregation (HPA). Details of the medical history and hospital course of individual patient were reviewed to obtain risk factors for HIT as well as to compute two well-defined clinical probability scores (4Ts and HIT expert probability, HEP).

Results: There were 217 patients included for analysis. The average age was 64.9 ± 18.7 (mean ± standard deviation) years. The baseline platelet counts were 217 ± 116 x 10⁹/L. A platelet fall ≥ 50% from baseline was found in 135 (62.2%) patients. The most common type of heparin administered was unfractionated heparin (165; 76%). HIT-Ab using PaGIA was detected in 52 (24%) patients, while true HIT was confirmed using HPA in 3 patients (1.38%). Most common underlying illnesses found in patients developing HIT-Ab were hypertension, coronary arterial disease and active infection. Acute stroke, a platelet fall ≥ 50% from baseline, 4Ts score of > 3 and HEP score of ≥ 2 were significantly associated with development of HIT-Ab in univariate analysis, while heparin types and hemodialysis were not statistically associated with HIT-Ab development. Notably, only acute stroke was significantly associated with HIT-Ab development in multivariate analysis (Odds ratio 6.56; 95% confidence interval 1.42-30.31, p=0.016).

Conclusion: The incidence of HIT-Ab detected in critically ill medical patients in our cohort was comparable to most studies, while the incidence of true HIT in this cohort was apparently higher than previous reports, which their incidences were ≤ 0.5%. The reasons underlying the high incidence of true HIT in critically ill medical patients in Thailand remains elusive. Acute stroke is a significant risk for HIT-Ab development in critically ill medical patients receiving heparin.