Preemptive anticoagulation for post-acute and long-term care residents infected with SARS-CoV-2 is worth consideration, given that venous thromboembolism (VTE) is not uncommon in COVID-19 and most PALTC residents have a higher risk for VTE to begin with, said Nadia Mujahid, MD, CMD, at the Annual Conference of AMDA – The Society for Post-Acute and Long-Term Care Medicine during a session on antithrombotic treatments for residents with SARS CoV-2/COVID-19. “Let’s not wait for residents to develop a VTE. Let’s anticipate a VTE event,” she said. Hospitalized patients with COVID-19 are started on VTE prophylaxis immediately upon admission, but there are no studies to guide prophylactic anticoagulation in the PALTC setting where residents are not as severely ill or have chosen to be treated in place. Dr. Mujahid, an associate professor in the Division of Geriatric and Palliative Care Medicine at the Warren Alpert Medical School of Brown University, recommends assessing the individual’s underlying risk for VTE and risk for bleeding, and considering prophylaxis in the context of COVID-19. For deciding whether to preemptively treat and what medications to choose, Dr. Mujahid advised consideration of both individual factors (e.g., thrombotic and bleeding risks, renal issues) and institutional/contextual factors (e.g., staffing, access to medications, prior vaccination, personal protective equipment availability). If staffing is not adequate, then once- or twice-daily direct oral anticoagulants may be preferred. Preemptive anticoagulation can still be considered when Paxlovid is employed, through the choice of medication and dosage may need to be carefully thought out, Dr. Mujahid said in an interview after the session. Regarding the duration of thromboprophylaxis therapy, cardiology guidelines recommend extended posthospital VTE prophylaxis for all COVID-19 patients with elevated VTE risks (e.g., reduced mobility, active cancer, and D-dimer greater than two times the upper normal limit) for up to 45 days. Thromboprophylaxis initiated in the nursing home, however, should be informed by the resident’s clinical status and progression, she said during the presentation. Dr. Mujahid shared her approach of initiating treatment for at least 14 days after diagnosis of a confirmed SARS-CoV-2 infection and then reassessing. “If they continue to worsen, or continue to have reduced functional status and immobility, we might consider a [longer duration]” of a week or two, she said. D-dimer increases with SARS-CoV-2 hypercoagulopathy and will be broadly elevated across residents with COVID-19, negating its usefulness as a screening test for likely VTE, Dr. Mujahid noted in her presentation. In the later interview she said that other tools for assessing VTE risk, such as the Caprini score or the Padua score, have been validated in hospital or outpatient settings but not in nursing homes; they may be more helpful, however, especially “if you want ... to be more confident in starting someone on medication to prevent a DVT [deep vein thrombosis] or PE [pulmonary embolism].” The risk of hypercoagulability and thrombosis from SARS-CoV-2 infection has been well documented. Arterial thrombosis emerged early in the pandemic as a complication of COVID-19, as did VTE — the latter with an early incidence of almost 20% for both DVT and PE. Studies published in 2022 showed that the incidence of VTE became reduced with vaccinations and evolving strains, said Yasin Abul, MD, also of Brown’s Division of Geriatric and Palliative Care Medicine. For instance, one 2022 review reported PE at 15% in an original strain cohort, 10.6% in a Delta cohort, and 9.2% in an Omicron cohort (Emerg Radiol 2022;29:625–629). The reviewers also reported that unvaccinated patients had a 2.75-fold increased risk of COVID-associated PE during the Delta and Omicron periods. Also interesting, Dr. Abul said, are data from another 2022 review showing a much lower incidence of VTE in the outpatient and postdischarge settings as compared with the inpatient setting, likely due to the severity of disease and immobility in the latter patients. The reviewers documented VTE in 1.0% to 1.5% of COVID-19 outpatients (including postdischarge patients) compared with 13% in the ward and 30% in the intensive care unit (Infect Public Health 2022;15:689–702). (Neither review was focused on PALTC communities.) Platelets are the “predominant cell type responsible for COVID-19–induced coagulopathy,” as compared with leukocytes in bacterial sepsis-associated coagulopathy, noted Dr. Abul, who is also affiliated with Brown’s Center for Gerontology and Health Care Research. In COVID-19–induced coagulopathy, prothrombin time is normal most of the time, platelet counts are unchanged or only slightly elevated, and disseminated intravascular coagulation is rare. Aspirin has a theoretical advantage due to its antiplatelet effects, and several retrospective studies in the United States and Germany have shown an association between baseline aspirin use (before infection) and reduced mortality. In a retrospective cohort analysis of nursing home residents led by Dr. Abul and published as a preprint, low-dose aspirin use for primary or secondary prevention of chronic cardiovascular events was independently associated with reduced 30-day and 56-day mortality compared with no aspirin use (adjusted hazard ratio [HR] 0.60; 95% CI, 0.40–0.90, and adjusted HR 0.67; 95% CI, 0.47–0.95, respectively). Adjustments were made for a history of major adverse cardiac events, stroke, diabetes, and other morbidities [medRxiv, Aug. 4, 2022; https://doi.org/10.1101/2022.08.03.22278392]. However, no mortality benefit was found in two prospective, randomized controlled trials — the RECOVERY study and ACTIVE-4B trial — in which aspirin was initiated after SARS-CoV-2 infection (Lancet 2022;399:143–151; JAMA 2021;326:1703–1712). Given the data from these prospective studies and the known bleeding risk that accompanies aspirin, especially in frail geriatric patients, “I don’t think we should start aspirin in COVID-19 patients,” Dr. Abul said. She noted that the patients in the retrospective studies on aspirin therapy were likely already at higher risk and thus may have benefitted more. In a published article on preemptive anticoagulation with SARS-CoV-2 infection in long-term care facilities, Dr. Mujahid, Dr. Abul, and their coauthors wrote that early in the pandemic they prescribed the direct oral anticoagulant rivaroxaban because of its once-a-day administration, its desirable effect on platelets, and its minimal monitoring requirements. Pharmacologically, low-molecular-weight heparin or unfractionated heparin would be better options, they said (Aging Clin Exp Res 2022;34:3171–3177). In a presentation on thromboembolic risks after COVID-19 vaccination, Elie A. Saade, MD, MPH, assistant professor of medicine at Case Western Reserve University, said that vaccine-induced thrombotic thrombocytopenia is “extremely rare” and should not preclude vaccination. Per million doses of the Johnson & Johnson/Janssen vaccine (Ad26.COV2.S), 3.83 cases were reported, and the emergency use authorization carries a warning for thrombosis with thrombocytopenia syndrome. However, it’s still unclear whether these cases were actually caused by the vaccine, Dr. Saade said. For the Oxford/AstraZeneca vaccine (ChAdOx1 nCov-19), which is the other adenoviral vector–based vaccine, 7.9 to 37.7 cases per million vaccine doses have been reported. Thrombosis with thrombocytopenia syndrome is not a concern with mRNA-based vaccines. Rare cases have been described (<1 per 100 million doses), but there is “no confirmed association,” Dr. Saade said. He pointed out that an investigation into a potential increased risk of stroke for adults aged 65+ years who received the bivalent BNT116b2 vaccine (Pfizer’s updated booster) failed to validate a safety signal picked up by the Vaccine Safety Datalink, the Centers for Disease Control and Prevention’s vaccine safety monitoring system. The signal was based on “self-comparison,” Dr. Saade explained, and he suggested there could be an increased risk of stroke in the 21 days after vaccination compared with days 22 to 42. Further investigations of Vaccine Safety Datalink data showed the 1–21-day risk to be similar to that of nonboosted eligible comparators, and the 22–42-day risk to be lower in boosted compared with nonboosted individuals (see “CDC & FDA identify preliminary COVID-19 vaccine safety signal for persons aged 65 years and older,” https://bit.ly/3VXyJQz). Research in other systems (e.g., Medicare and Department of Veterans Affairs populations) has also failed to confirm the initial signal, Dr. Saade said.