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      Temporal presentations of heparin‐induced thrombocytopenia following cardiac surgery: A single‐center, retrospective cohort study

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          Abstract

          Background

          Heparin‐induced thrombocytopenia (HIT) is an important adverse drug reaction that can occur postcardiac surgery. Preoperative exposure to unfractionated heparin (UFH) is common, raising the issue of how frequently cardiac surgery‐associated HIT occurs after immunizing preoperative exposure to heparin.

          Objective

          To determine the frequency and clinical picture of HIT occurring within 4 days of cardiac surgery (early presentation) versus later presentations (typical, delayed).

          Methods

          We identified patients with laboratory‐confirmed HIT following cardiac surgery over 30 years in a single cardiac surgery center. Three different clinical presentations of HIT were identified: typical (HIT‐related platelet count fall beginning between postoperative days [PODs] 5–10), delayed (patients with falls after POD10 or who presented following hospital discharge), and early (established before POD5, including during cardiac surgery [acute intraoperative HIT]).

          Results

          Of 129 patients identified with HIT complicating cardiac surgery, 100 had typical and 16 had delayed presentation of HIT; only 13 patients (10.1%) presented with early HIT, all of whom had received exposure to UFH during the 10 days before cardiac surgery. No patient was identified in whom remote preoperative UFH exposure was implicated in explaining early HIT. Notably, five patients appeared to have had acute intraoperative HIT, without immediate adverse consequences.

          Conclusions

          Approximately 90% of patients with HIT after cardiac surgery appear to develop this complication due to immunization triggered by cardiac surgery; however, in approximately 10% of patients, early presentation during the first four PODs (or intraoperatively) can be explained by recent immunizing exposure to heparin.

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          Most cited references62

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          Autoimmune heparin-induced thrombocytopenia.

          Autoimmune heparin-induced thrombocytopenia (aHIT) indicates the presence in patients of anti-platelet factor 4 (PF4)-polyanion antibodies that are able to activate platelets strongly even in the absence of heparin (heparin-independent platelet activation). Nevertheless, as seen with serum obtained from patients with otherwise typical heparin-induced thrombocytopenia (HIT), serum-induced platelet activation is inhibited at high heparin concentrations (10-100 IU mL-1heparin). Furthermore, upon serial dilution, aHIT serum will usually show heparin-dependent platelet activation. Clinical syndromes associated with aHIT include: delayed-onset HIT, persisting HIT, spontaneous HIT syndrome, fondaparinux-associated HIT, heparin 'flush'-induced HIT, and severe HIT (platelet count of < 20 × 109 L-1) with associated disseminated intravascular coagulation (DIC). Recent studies have implicated anti-PF4 antibodies that are able to bridge two PF4 tetramers even in the absence of heparin, probably facilitated by non-heparin platelet-associated polyanions (chondroitin sulfate and polyphosphates); nascent PF4-aHIT-IgG complexes recruit additional heparin-dependent HIT antibodies, leading to the formation of large multimolecular immune complexes and marked platelet activation. aHIT can persist for several weeks, and serial fibrin, D-dimer, and fibrinogen levels, rather than the platelet count, may be helpful for monitoring treatment response. Although standard anticoagulant therapy for HIT ought to be effective, published experience indicates frequent failure of activated partial thromboplastin time (APTT)-adjusted anticoagulants (argatroban, bivalirudin), probably because of underdosing in the setting of HIT-associated DIC, known as 'APTT confounding'. Thus, non-APTT-adjusted therapies with drugs such as danaparoid and fondaparinux, or even direct oral anticoagulants, such as rivaroxaban or apixaban, are suggested therapies, especially for long-term management of persisting HIT. In addition, emerging data indicate that high-dose intravenous immunoglobulin can interrupt HIT antibody-induced platelet activation, leading to rapid platelet count recovery.
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            American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia

            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.
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              CLINICAL PRACTICE. Heparin-Induced Thrombocytopenia.

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                Author and article information

                Contributors
                twarken@mcmaster.ca
                Journal
                J Thromb Haemost
                J Thromb Haemost
                10.1111/(ISSN)1538-7836
                JTH
                Journal of Thrombosis and Haemostasis
                John Wiley and Sons Inc. (Hoboken )
                1538-7933
                1538-7836
                11 August 2022
                November 2022
                : 20
                : 11 ( doiID: 10.1111/jth.v20.11 )
                : 2601-2616
                Affiliations
                [ 1 ] Department of Pathology and Molecular Medicine McMaster University Hamilton Ontario Canada
                [ 2 ] Department of Medicine McMaster University Hamilton Ontario Canada
                [ 3 ] Transfusion Medicine Hamilton Regional Laboratory Medicine Program Hamilton Ontario Canada
                [ 4 ] Service of Benign Hematology Hamilton Health Sciences Hamilton Ontario Canada
                [ 5 ] Department of Surgery, Division of Cardiac Surgery McMaster University Hamilton Ontario Canada
                Author notes
                [*] [* ] Correspondence

                Theodore E. Warkentin, Hamilton Regional Laboratory Medicine Program, Room 1‐270B, Hamilton General Hospital (Hamilton Health Sciences), 237 Barton St. East, Hamilton, ON L8L 2X2, Canada.

                Email: twarken@ 123456mcmaster.ca

                Author information
                https://orcid.org/0000-0002-8046-7588
                https://orcid.org/0000-0002-4402-7809
                https://orcid.org/0000-0002-6863-5884
                Article
                JTH15826 JTH-2022-00521.R1
                10.1111/jth.15826
                9805231
                35869817
                a6a1b90e-b5b2-4052-a8a2-35590bd26d8d
                © 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 05 July 2022
                : 09 May 2022
                : 18 July 2022
                Page count
                Figures: 5, Tables: 3, Pages: 16, Words: 9333
                Categories
                Original Article
                PLATELETS
                Original Articles
                Custom metadata
                2.0
                November 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.3 mode:remove_FC converted:31.12.2022

                Hematology
                cardiopulmonary bypass,heparin,platelet count,thrombocytopenia,thrombosis
                Hematology
                cardiopulmonary bypass, heparin, platelet count, thrombocytopenia, thrombosis

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