Diagnosing heparin‐induced thrombocytopenia: The need for accuracy and speed

Abstract

Heparin‐induced thrombocytopenia (HIT) is a prothrombotic condition resulting from pathogenic antibodies to complexes of heparin and platelet factor 4 (PF4). The diagnosis of HIT can be challenging due to the widespread use of heparin and the frequency of thrombocytopenia in hospitalized patients. Laboratory testing for HIT typically includes an immunoassay to detect antibodies to PF4‐heparin and a functional assay. Current HIT diagnostic algorithms recommend using the 4Ts score to determine the need for HIT laboratory testing. Automated calculation of HIT clinical prediction scores in the electronic health record may improve the identification of patients who should undergo HIT testing. Another challenge in the management of patients with suspected HIT is the turnaround time of the laboratory testing needed to confirm the diagnosis. Due to the high daily thrombotic risk of HIT, clinicians must treat patients with intermediate to high pretest likelihood of HIT empirically while awaiting the test results. Treatment for HIT often involves alternative anticoagulants that lack reversal agents, which may increase bleeding risk, prolong hospital stays, and increase costs for patients suspected of having HIT. Rapid immunoassays hold promise to improve the speed of HIT diagnosis. These assays must retain a very high sensitivity for this “can't miss” diagnosis, yet have sufficient specificity to be of diagnostic value. A Bayesian approach has been proposed using two rapid immunoassays in succession, which decreased analytic turnaround time to 60 minutes. Such an approach has the potential to be a much‐needed clinical advance in improving accuracy and speed in the diagnosis of HIT.

Thrombocytopenia in the Time of COVID-19

“…Extrapolating from HIT in which ELISA is not recommended for patients with low clinical probability because of risk of false positives, after careful discussion we decided against recommending HIT ELISA. 20 Regarding management, although the two entities share some similarities, namely use of immunomodulatory therapies, including IVIG, 17,21 the most important divergent feature in management is initiation of anticoagulation. Based on the current comprehension, the pathophysiological basis of VITT is production of autoantibodies to PF4 provoked by adenoviral vector vaccines.…”

A machine-learning model for reducing misdiagnosis in heparin-induced thrombocytopenia: a prospective, multicenter, observational study

“…Washed platelet assays (i.e., HIPA and serotonin release assay [SRA]) demonstrated high diagnostic sensitivity and specificity and agreement with clinical HIT. 12 , 34 , 35 , 41 , 48 , 49 , 50 , 51 , 52 , 53 , 54 HIPA and SRA are both regarded as reference standards for the diagnosis of HIT by the American Society of Hematology (ASH) guidelines, 41 the British Committee for Standards in Haematology, 53 and many authors. 12 , 34 , 35 , 48 , 49 , 50 , 51 , 55 We decided against the adjudication of HIT cases by an expert panel to avoid incorporation/verification bias (clinical and laboratory variables of the prediction model are used for reference standard testing).…”

“… 19 , 20 , 22 , 25 , 27 , 28 , 29 , 30 , 31 , 32 Thus, a number of authors and guidelines call for new diagnostic instruments, which must not only be more accurate than conventional ones, but also easy to use. 8 , 28 , 31 , 33 , 34 , 35 …”

Treatment of drug-induced immune thrombocytopenias

“…Therefore, it is extremely important that physicians are able to discriminate between patients who actually have HIT and those who, although they may have PF4/heparin-specific antibodies and some degree of thrombocytopenia, actually do not. Diagnostic algorithms are available for diagnosis of HIT 40 , 41 (see Figure 3 for an example).…”