Pitfalls of Clinical Diagnosis Strategies for Heparin-Induced Thrombocytopenia (HIT) After Cardiac Surgery (CS).

HIT is an infrequent but potentially serious complication of heparin therapy. Its diagnosis is complex and depends on a combination of clinical suspicion and laboratory confirmation through ELISA and functional tests such as the serotonin release assay (SRA). The 4Ts score comprises 4 clinical parameters (severity and timing of onset of thrombocytopenia, development of thrombosis, and clinician's appraisal of the likelihood of alternate causes for thrombocytopenia) and has been proposed to predict the probability of HIT in patients deemed to be at risk. However, the validity of the 4Ts score in patients undergoing cardiac surgery (CS) is questionable considering the numerous other factors that predispose such patients to thrombocytopenia and thrombosis. In addition, in CS patients the HIT ELISA assay has been reported to have 25 - 50% false positive results making it less useful.

To determine the usefulness of the 4T score in the post cardiac surgical population and the value of the HIT ELISA optical density for predicting HIT.

Retrospective case-control study of patients admitted for cardiac surgery to the London Health Sciences Centre between January 2006 and December 2008 and for whom a HIT ELISA assay was requested. Patients with an equivocal or positive ELISA test were tested by SRA which considered the gold standard. Information collected included clinical variables related to the surgery and post-operative period, calculated 4T scores, ELISA optical density (OD) and SRA results. Categorical variables were compared using chi² or Fisher's exact tests as appropriate. Continuous variables were compared using a Mann-Whitney U test. Covariates achieving a p value ≤0.1 in univariate analysis and the components of the 4Ts score were incorporated in logistic regression models using stepwise forward selection. Finally, we constructed a Receiver Operating Characteristic (ROC) curve for the ELISA OD.

73 patients were included in the analysis. Results of the univariate analysis are shown in the table. On regression analysis only the ELISA optical density (per each OD arbitrary unit increase) was correlated with a diagnosis of HIT (OR 37.266; 95% CI 2.342-593.013; p=0.010). For the ELISA OD the area under the ROC curve was 0.990 (SE 0.013) (Figure). A cutoff value for the OD of 0.475 had a Sensitivity of 1, a specificity of 0.9, a positive likelihood ratio (LR) of 10 and a negative LR of 0.00. Assuming a prevalence proportion of 0.082 the posterior probability of HIT if the ELISA has an OD <0.475 is 0 (95% CI 0 – 9). On the other hand, an OD >0.92 resulted in a LR+ of 20 with a posterior probability of 64% (95% CI 35 – 80).

In this study, we found that the 4T score does not accurately predict HIT in post CS patients. Limitations of this study include a reduced sample size and its retrospective nature. Our findings suggest that in post CS patients developing thrombocytopenia between 10 and 100 × 10⁹ or a platelet drop of 50% or more (100% of our population) a HIT ELISA with an OD < 0.475 could be used to rule out HIT. Our findings need to be confirmed in prospective studies.

No relevant conflicts of interest to declare.