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.

thrombocytopenia in post-cardiac surgery patients is rarely due to heparin-induced thrombocytopenia, even when antibody tests are positive. See also Gruel Y, Pouplard C. Post-operative platelet count profile: the most reliable tool for identifying patients with true heparin-induced thrombocypenia after cardiac surgery. This issue, pp 27-9.Summary. Background: The high frequency of thrombocytopenia in post-cardiac surgery patients makes it challenging to diagnose heparin-induced thrombocytopenia (HIT). Two platelet count profiles are reported as indicating possible HIT in these patients: profile 1 describes a platelet count fall that begins between postoperative days 5 and 10, whereas profile 2 denotes early-onset thrombocytopenia that persists beyond day 5. Objectives: Toexaminehowthese platelet count profiles correlate withantibodystatusandHITpost-cardiacsurgery.Methods:We prospectively screened 581 cardiac surgery patients for heparindependent antibodies by platelet factor 4 (PF4)-heparin immunoassay and platelet-activation test, and performed daily platelet counts (until day 10) with 30-day follow-up. Results: All three patients with platelet count profile 1 tested positive for platelet-activating anti-PF4-heparin IgG antibodies [odds ratio (OR) 521.7, 95% confidence interval (CI) 3.9-34 000, P = 0.002], and were judged to have HIT. In contrast, none of 25 patients with early-onset and persisting thrombocytopenia (profile 2) was judged to have HIT, including five patients testing positivefor platelet-activating anti-PF4-heparin IgG antibodies. In these patients, the frequency of heparin-dependent antibodies didnot differfromthat in non-thrombocytopeniccontrols, either for anti-PF4-heparin IgG (OR 1.7, 95% CI 0.7-4.1, P = 0.31) or for platelet-activating antibodies (OR 1.9, 95% CI 0.6-5.7, P = 0.20). Multivariate analysis revealed that type of cardiac surgery, but not HIT antibody status, predicted early-onset and persisting thrombocytopenia. Together, these findings show that HIT was uncommon in this study population [overall frequency, 3/581 (0.5%), 95% CI 0.1-1.5%]. Conclusions: Thrombocytopenia that begins between 5 and 10 days post-cardiac surgery is highly predictive for HIT. In contrast, early-onset and persisting thrombocytopenia is usually caused by non-HIT factors with coinciding heparin-dependent antibody seroconversion.

Key Points• Immunization against protamine/heparin complexes was frequently observed in patients undergoing cardiac surgery.• Platelet-activating antiprotamine-heparin antibodies are a potential risk factor for early postoperative thrombosis and thrombocytopenia.Protamine, which is routinely used after cardiac surgery to reverse the anticoagulant effects of heparin, is known to be immunogenic. Observing patients with an otherwise unexplained rapid decrease in platelet count directly after protamine administration, we determined the incidence and clinical relevance of protamine-reactive antibodies in patients undergoing cardiac-surgery. In vitro, these antibodies activated washed platelets in a FcgRIIa-dependent fashion. Using a nonobese diabetic/severe combined immunodeficiency mouse model, those antibodies induced thrombocytopenia only when protamine and heparin were present but not with protamine alone. Of 591 patients undergoing cardiopulmonary bypass surgery, 57 (9.6%) tested positive for anti-protamine-heparin antibodies at baseline and 154 (26.6%) tested positive at day 10. Diabetes was identified as a risk factor for the development of anti-protamine-heparin antibodies. In the majority of the patients, these antibodies were transient and titers decreased substantially after 4 months (P < .001). Seven patients had platelet-activating, anti-protamine-heparin antibodies at baseline and showed a greater and more prolonged decline in platelet counts compared with antibody-negative patients (P 5 .003). In addition, 2 of those patients experienced early arterial thromboembolic complications vs 9 of 584 control patients (multivariate analysis: odds ratio, 21.58; 95% confidence interval, 2.90-160.89; P 5 .003). Platelet-activating antiprotamine-heparin antibodies show several similarities with anti-platelet factor 4-heparin antibodies and are a potential risk factor for early postoperative thrombosis. (Blood. 2013;121(15):2821-2827

Heparin-induced thrombocytopenia (HIT) is a serious, prothrombotic, immune-mediated complication of heparin therapy that can cause limb- and life-threatening thromboembolic events. Prompt diagnosis and therapeutic dose anticoagulation by an alternative anticoagulant are crucial to improve clinical outcome. In critically ill patients, the diagnosis of HIT is difficult due to the high incidence of thrombocytopenia, often caused by reasons other than HIT, and the high incidence of clinically irrelevant, non-platelet-activating anti-PF4-heparin antibodies. Also, treatment of HIT is problematic in these patients. No antidote is available for any of the alternative anticoagulants, and their half-lives are often prolonged in the presence of renal or hepatic insufficiency. This increases the risk of bleeding complications and mandates careful balancing of both risks, thrombosis and bleeding. Therefore, accurate diagnosis of HIT and individual choice of alternative anticoagulant are important for the adequate management of critically ill HIT patients.

No abstract