Clinical Characteristics and Pharmacological Management of COVID-19 Vaccine-Induced Immune Thrombotic Thrombocytopenia With Cerebral Venous Sinus Thrombosis: A Review.

Importance: The COVID-19 pandemic saw one of the fastest developments of vaccines in an effort to combat an out-of-control pandemic. The 2 most common COVID-19 vaccine platforms currently in use, messenger RNA (mRNA) and adenovirus vector, were developed on the basis of previous research in use of this technology. Postauthorization surveillance of COVID-19 vaccines has identified safety signals, including unusual cases of thrombocytopenia with thrombosis reported in recipients of adenoviral vector vaccines. One of the devastating manifestations of this syndrome, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), is cerebral venous sinus thrombosis (CVST). This review summarizes the current evidence and indications regarding biology, clinical characteristics, and pharmacological management of VITT with CVST. Observations: VITT appears to be similar to heparin-induced thrombocytopenia (HIT), with both disorders associated with thrombocytopenia, thrombosis, and presence of autoantibodies to platelet factor 4 (PF4). Unlike VITT, HIT is triggered by recent exposure to heparin. Owing to similarities between these 2 conditions and lack of high-quality evidence, interim recommendations suggest avoiding heparin and heparin analogues in patients with VITT. Based on initial reports, female sex and age younger than 60 years were identified as possible risk factors for VITT. Treatment consists of therapeutic anticoagulation with nonheparin anticoagulants and prevention of formation of autoantibody-PF4 complexes, the latter being achieved by administration of high-dose intravenous immunoglobin (IVIG). Steroids, which can theoretically inhibit the production of new antibodies, have been used in combination with IVIG. In severe cases, plasma exchange should be used for clearing autoantibodies. Monoclonal antibodies, such as rituximab and eculizumab, can be considered when other therapies fail. Routine platelet transfusions, aspirin, and warfarin should be avoided because of the possibility of worsening thrombosis and magnifying bleeding risk. Conclusions and Relevance: Adverse events like VITT, while uncommon, have been described despite vaccination remaining the most essential component in the fight against the COVID-19 pandemic. While it seems logical to consider the use of types of vaccines (eg, mRNA-based administration) in individuals at high risk, treatment should consist of therapeutic anticoagulation mostly with nonheparin products and IVIG.

Improving Medication Adherence in Cardiometabolic Disease: Practical and Regulatory Implications.

Medication nonadherence, a major problem in cardiovascular disease (CVD), contributes yearly to approximately 125,000 preventable deaths, which is partly attributable to only about one-half of CVD patients consistently taking prescribed life-saving medications. Current interest has focused on how labeling and education influence adherence. This paper summarizes the scope of CVD nonadherence, describes key U.S. Food and Drug Administration initiatives, and identifies potential targets for improvement. We describe key adherence factors, methods, and technological applications for simplifying regimens and enhancing adherence, and 4 areas where additional collaborative research and implementation involving the regulatory system and clinical community could substantially reduce nonadherence: 1) identifying monitoring methods; 2) improving the evidence base to better understand adherence; 3) developing patient/health provider team-based engagement strategies; and 4) alleviating health disparities. Alignment of U.S. Food and Drug Administration approaches to dissemination of information about appropriate use with clinical practice could improve adherence, and thereby reduce CVD death and disability.