American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia

Abstract

Background: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction mediated by platelet-activating antibodies that target complexes of platelet factor 4 and heparin. Patients are at markedly increased risk of thromboembolism.

Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about diagnosis and management of HIT.

Methods: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment.

Results: The panel agreed on 33 recommendations. The recommendations address screening of asymptomatic patients for HIT, diagnosis and initial management of patients with suspected HIT, treatment of acute HIT, and special situations in patients with acute HIT or a history of HIT, including cardiovascular surgery, percutaneous cardiovascular intervention, renal replacement therapy, and venous thromboembolism prophylaxis.

Conclusions: Strong recommendations include use of the 4Ts score rather than a gestalt approach for estimating the pretest probability of HIT and avoidance of HIT laboratory testing and empiric treatment of HIT in patients with a low-probability 4Ts score. Conditional recommendations include the choice among non-heparin anticoagulants (argatroban, bivalirudin, danaparoid, fondaparinux, direct oral anticoagulants) for treatment of acute HIT.

Figure 1.

Algorithm for the diagnosis and initial management of patients with suspected HIT. Numbered recommendations are listed in the corresponding portion of the algorithm. Actions are in dark gray boxes; test results are in light gray boxes. ^aMissing or inaccurate information may lead to a faulty 4Ts score and inappropriate management decisions. Every effort should be made to obtain accurate and complete information necessary to calculate the 4Ts score. If key information is missing, it may be prudent to err on the side of a higher 4Ts score. HIT laboratory testing may be appropriate for patients with a low-probability 4Ts score if there is uncertainty about the 4Ts score (eg, because of missing data). Patients should be reassessed frequently. If there is a change in the clinical picture, the 4Ts score should be recalculated. ^bIf the patient has an intermediate-probability 4Ts score, has no other indication for therapeutic-intensity anticoagulation, and is judged to be at high risk for bleeding, the panel suggests treatment with a non-heparin anticoagulant at prophylactic intensity rather than therapeutic intensity. If the patient has an intermediate-probability 4Ts score and is not judged to be at high risk for bleeding or has another indication for therapeutic-intensity anticoagulation, the panel suggests treatment with a non-heparin anticoagulant at therapeutic intensity rather than prophylactic intensity. In a patient with a high-probability 4Ts score, the panel recommends treatment with a non-heparin anticoagulant at therapeutic intensity. ^cDifferent immunoassays are available. The choice of assay may be influenced by accuracy, availability, cost, feasibility, and turnaround time. If an enzyme-linked immunoassay is used, a lower threshold is preferred over a high threshold. ^dFor all patients with a positive immunoassay, including those who were receiving prophylactic-intensity treatment with a non-heparin anticoagulant before the availability of the immunoassay result, the panel recommends treatment with a non-heparin anticoagulant at therapeutic intensity. ^eDifferent functional assays are available. The choice of assay may be influenced by accuracy, availability, cost, feasibility, and turnaround time. In some settings, a functional assay may not be available, and decisions may need to be made on the basis of the results of the 4Ts score and immunoassay. A functional assay may not be necessary in patients with a high 4Ts score and a strongly positive immunoassay. ^fMost patients with a negative functional assay do not have HIT and may be managed accordingly. However, depending on the type of functional assay and the technical expertise of the laboratory, false-negative results are possible. Therefore, a presumptive diagnosis of HIT may be considered for some patients with a negative functional assay, especially if there is a high-probability 4Ts score and a strongly positive immunoassay (represented in the figure by a dashed line).