Antithrombotic agents reduce risk of thromboembolism in severely ill patients. Patients with coronavirus disease 2019 (COVID‐19) may realize additional benefits from heparins. Optimal dosing and ...timing of these treatments and benefits of other antithrombotic agents remain unclear. In October 2021, ISTH assembled an international panel of content experts, patient representatives, and a methodologist to develop recommendations on anticoagulants and antiplatelet agents for patients with COVID‐19 in different clinical settings. We used the American College of Cardiology Foundation/American Heart Association methodology to assess level of evidence (LOE) and class of recommendation (COR). Only recommendations with LOE A or B were included. Panelists agreed on 12 recommendations: three for non‐hospitalized, five for non–critically ill hospitalized, three for critically ill hospitalized, and one for post‐discharge patients. Two recommendations were based on high‐quality evidence, the remainder on moderate‐quality evidence. Among non–critically ill patients hospitalized for COVID‐19, the panel gave a strong recommendation (a) for use of prophylactic dose of low molecular weight heparin or unfractionated heparin (LMWH/UFH) (COR 1); (b) for select patients in this group, use of therapeutic dose LMWH/UFH in preference to prophylactic dose (COR 1); but (c) against the addition of an antiplatelet agent (COR 3). Weak recommendations favored (a) sulodexide in non‐hospitalized patients, (b) adding an antiplatelet agent to prophylactic LMWH/UFH in select critically ill, and (c) prophylactic rivaroxaban for select patients after discharge (all COR 2b). Recommendations in this guideline are based on high‐/moderate‐quality evidence available through March 2022. Focused updates will incorporate future evidence supporting changes to these recommendations.
Vaccine administration is under way worldwide to combat the current COVID‐19 pandemic. The newly developed vaccines are highly effective with minimal adverse effects. Recently, the AstraZeneca ...ChadOx1 nCov‐19 vaccine has raised public alarm with concerns regarding the rare, but serious, development of thrombotic events, now known as vaccine‐induced immune thrombotic thrombocytopenia (VITT). These thrombotic events appear similar to heparin‐induced thrombocytopenia, both clinically and pathologically. In this manuscript, the ISTH SSC Subcommittee on Platelet Immunology outlines guidelines on how to recognize, diagnose and manage patients with VITT.
Hemophilia A and B predominantly attracts clinical attention in males due to X‐linked inheritance, introducing a bias toward female carriers to be asymptomatic. This common misconception is ...contradicted by an increasing body of evidence with consistent reporting on an increased bleeding tendency in hemophilia carriers (HCs), including those with normal factor VIII/IX (FVIII/IX) levels. The term HC can hamper diagnosis, clinical care, and research. Therefore, a new nomenclature has been defined based on an open iterative process involving hemophilia experts, patients, and the International Society on Thrombosis and Haemostasis (ISTH) community. The resulting nomenclature accounts for personal bleeding history and baseline plasma FVIII/IX level. It distinguishes five clinically relevant HC categories: women/girls with mild, moderate, or severe hemophilia (FVIII/IX >0.05 and <0.40 IU/ml, 0.01–0.05 IU/ml, and <0.01 IU/ml, respectively), symptomatic and asymptomatic HC (FVIII/IX ≥0.40 IU/ml with and without a bleeding phenotype, respectively). This new nomenclature is aimed at improving diagnosis and management and applying uniform terminologies for clinical research.
Background
Observational studies indicate that children hospitalized with COVID‐19‐related illness, like adults, are at increased risk for venous thromboembolism (VTE). A multicenter phase 2 clinical ...trial of anticoagulant thromboprophylaxis in children hospitalized with COVID‐19‐related illness has recently been initiated in the United States. To date, there remains a paucity of high‐quality evidence to inform clinical practice world‐wide. Therefore, the objective of this scientific statement is to provide consensus‐based recommendations on the use of anticoagulant thromboprophylaxis in children hospitalized for COVID‐19‐related illnesses, and to identify priorities for future research.
Methods
We surveyed 20 pediatric hematologists and pediatric critical care physicians from several continents who were identified by Pediatric/Neonatal Hemostasis and Thrombosis Subcommittee leadership as having experience and expertise in the use of anticoagulant thromboprophylaxis and/or the management of COVID‐19‐related illness in children. A comprehensive review of the literature on COVID‐19 in children was also performed.
Results
Response rate was 90%. Based on consensus of expert opinions, we suggest the administration of low‐dose low molecular weight heparin subcutaneously twice‐daily as anticoagulant thromboprophylaxis (in the absence of contraindications, and in combination with mechanical thromboprophylaxis with sequential compression devices, where feasible) in children hospitalized for COVID‐19‐related illness (including the multisystem inflammatory syndrome in children MIS‐C) who have markedly elevated D‐dimer levels or superimposed clinical risk factors for hospitalassociated VTE. For children who are clinically unstable or have severe renal impairment, we suggest the use of unfractionated heparin by continuous intravenous infusion as anticoagulant thromboprophylaxis. In addition, continued efforts to characterize VTE risk and risk factors in children with COVID‐19, as well as to evaluate the safety and efficacy of anticoagulant thromboprophylaxis strategies in children hospitalized with COVID‐19‐related illness (including MIS‐C) via cooperative multicenter trials, were identified among several key priorities for future research.
Conclusion
These consensus‐based recommendations on the use of anticoagulant thromboprophylaxis in children hospitalized for COVID‐19‐related illnesses and priorities for future research will be updated as high‐quality evidence emerges.
Patients with liver diseases acquire complex alterations in their hemostatic system that may lead to abnormalities in routine diagnostic test of hemostasis. Thrombocytopenia, prolongations in the ...prothrombin time and activated partial thromboplastin time, and decreased plasma fibrinogen are common in patients with advanced liver disease. Historically, liver diseases therefore have been classified as an acquired bleeding disorder. Laboratory and clinical observations have demonstrated that although routine diagnostic tests of hemostasis suggest a hypocoagulable state, patients with liver disease also tend to develop thrombotic events. Overall, patients have commensurate changes in both pro‐ and antihemostatic pathways. This new hemostatic balance, however, appears much more fragile than the hemostatic balance in individuals with normal liver function, and patients with liver disease can readily experience both hemostasis‐related bleeding and thrombotic events. These insights into the hemostatic balance in patients with liver disease have led to revised recommendations for clinical management of hemostasis. In 2020, an SSC working group within the ISTH has been founded with the aim to disseminate new concepts on prevention and treatment of bleeding and thrombosis in patients with liver disease. The current document will outline the hemostatic changes in patients with liver disease, the limitations of routine diagnostic tests of hemostasis, and the concept of rebalanced hemostasis.
Hypercoagulability is an increasingly recognized complication of SARS‐CoV‐2 infection. As such, anticoagulation has become part and parcel of comprehensive COVID‐19 management. However, several ...uncertainties exist in this area, including the appropriate type and dose of heparin. In addition, special patient populations, including those with high body mass index and renal impairment, require special consideration. Although the current evidence is still insufficient, we provide a pragmatic approach to anticoagulation in COVID‐19, but stress the need for further trials in this area.
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