Higher risk for DVT, PE, bleeding seen after COVID-19; long-term risk for VTE recurrence may be low

Patients who have had COVID-19 appear to be at higher risk for deep venous thrombosis (DVT), pulmonary embolism (PE), and bleeding, a recent study found.

Researchers in Sweden used data from national registries to perform a self-controlled case series and matched cohort study of patients who tested positive for SARS-CoV-2 between Feb. 1, 2020, and May 25, 2021. Incidence rate ratios and risk ratios were determined for first DVT, PE, or bleeding event, and incidence rate ratios for first-time outcomes after COVID-19 in the self-controlled case series were determined using set time intervals and the spline model. The matched cohort study was used to determine risk ratios for first-time and all events during days 1 to 30 after COVID-19 or the index date, with adjustment for potential confounders (comorbid condition, cancer, surgery, long-term anticoagulation, previous venous thromboembolism [VTE], or previous bleeding event). The study results were published April 6 by BMJ

A total of 1,057,174 people who tested positive for SARS-CoV-2 were matched on age, sex, and county of residence to 4,076,342 controls. Compared with the control period, incidence rate ratios were significantly increased 70 days after COVID-19 for DVT, 110 days afterward for PE, and 60 days afterward for bleeding. Incidence rate ratios for a first PE were particularly high in the acute period after COVID-19 (36.17 [95% CI, 31.55 to 41.47] during the first week and 46.40 [95% CI, 40.61 to 53.02] during the second week). During days 1 to 30 after COVID-19, incidence rate ratios were 5.90 (95% CI, 5.12 to 6.80) for DVT, 31.59 (95% CI, 27.99 to 35.63) for PE, and 2.48 (95% CI, 2.30 to 2.68) for bleeding. Corresponding risk ratios in the same time period, meanwhile, were 4.98 (95% CI, 4.96 to 5.01) for DVT, 33.05 (95% CI, 32.8 to 33.3) for PE, and 1.88 (95% CI, 1.71 to 2.07) for bleeding after adjustment for potential confounders. Rate ratios were highest for those with critical COVID-19 and during the first versus the second and third waves of the pandemic in Sweden. Absolute risk among patients with COVID-19 during days 1 to 30 was 0.039% (401 events) for DVT, 0.17% (1,761 events) for PE, and 0.101% (1,002 events) for bleeding.

The researchers noted that COVID-19 might have been underdiagnosed in their study sample and that vaccine data were not available, among other limitations. They concluded that COVID-19 appears to be a risk factor for DVT, PE, and bleeding for up to three months, up to six months, and up to two months, respectively, with risk for PE being particularly elevated soon after COVID-19 diagnosis.

“Our findings arguably support thromboprophylaxis to avoid thrombotic events, especially for high risk patients, and strengthens the importance of vaccination against covid-19,” they wrote. “It remains to be established whether SARS-CoV-2 infection increases the risk of venous thromboembolism or bleeding more than it does for respiratory infections, such as influenza, but also whether the period of thromboprophylaxis after covid-19 should be extended. Future clinical research would be beneficial in this context.”

An accompanying editorial said that vaccination could reduce overall risk for thromboembolism and bleeding since risks in this study were highest in patients with more severe disease. The editorialists also noted, however, that increased risk was seen even in those with mild infection who did not require hospitalization. “Despite the potential for new variants of concern, most governments are removing restrictions and shifting their focus to determining how best to ‘live with covid,’” the editorialists wrote. “[The current study] reminds us of the need to remain vigilant to the complications associated with even mild SARS-CoV-2 infection, including thromboembolism.”

Another study, published as a research letter April 6 by CHEST, found that risk for VTE recurrence did not appear to persist long-term in patients who had been hospitalized for COVID-19. Researchers in France conducted a prospective observational cohort study that included all consecutive COVID-19 patients with VTE diagnosed during hospitalization from March 2020 to April 2021 and referred for follow-up after discharge to the outpatient thrombosis unit.

Patients diagnosed with DVT or PE were recommended to receive initial anticoagulant therapy with low-molecular-weight heparin or unfractionated heparin if contraindicated and were switched to a direct oral anticoagulant at discharge. Anticoagulant treatment was planned to last for three to six months. Symptomatic VTE recurrence and onset of a bleeding event were the primary and secondary outcomes, respectively, and patient visits were planned at 1, 3, 6, and 12 months after VTE diagnosis, with additional visits beyond 12 months if needed.

The study included 40 patients who developed PE during hospitalization and 8 who developed isolated DVT. Anticoagulants were discontinued after three months in one patient and after six months in 38 additional patients. Eight patients continued to receive them due to antiphospholipid syndrome, history of VTE, or an underlying cancer diagnosis. During anticoagulant therapy and after discontinuation, no patient had a symptomatic VTE recurrence. Five patients developed bleeding during therapy, including three major hemorrhages affecting the gastrointestinal tract and two minor episodes. One patient, a 66-year-old man with past polycythemia vera who had received six months of apixaban for PE and then switched to aspirin, died nine months later of a major duodenal hemorrhage. The authors concluded that patients with COVID-19 are at low risk for VTE recurrence while taking anticoagulant therapy and six months after therapy is discontinued, similar to what is observed in patients with VTE provoked by a transient nonsurgical factor. “Our data support limited anticoagulant therapy duration of 3-6 months in COVID-19 patients, in agreement with current guidelines, although selected individuals (e.g., with a past VTE history) may require long-term anticoagulation,” they wrote.