Role of Genetic Thrombophilia Markers in Thrombosis Events in Elderly Patients with COVID-19

Abstract

Thrombosis is an extremely dangerous complication in elderly patients with COVID-19. Since the first months of the pandemic, anticoagulants have been mandatory in treatment protocols for patients with COVID-19, unless there are serious contraindications. We set out to discover if genetic thrombophilia factors continue to play a triggering role in the occurrence of thrombosis in patients with COVID-19 with prophylactic or therapeutic anticoagulants. We considered the following genetic markers as risk factors for thrombophilia: G1691A in the FV gene, C677T and A1298C in the MTHFR gene, G20210A and C494T in the FII gene, and (−675) 4G/5G in the PAI-I gene. In a cohort of 176 patients, we did not obtain a reliable result indicating a higher risk of thrombotic complications when taking therapeutic doses of anticoagulants in carriers of genetic markers for thrombophilia except the C494T mutation in the FII gene. However, there was still a pronounced tendency to a higher incidence of thrombosis in patients with markers of hereditary thrombophilia, such as FV G1691A and FII G20210A mutations. The presence of the C494T (Thr165Met) allele in the FII gene in this group of patients showed a statistically significant effect of the mutation on the risk of thrombotic complications despite anticoagulant therapy.

Association between COVID-19 Infection or Vaccination Outcomes and Methylenetetrahydrofolate Reductase Gene Polymorphism: A Systematic Review of the Literature

“…The remaining two studies were conducted in Asia (one in Russia, one in Uzbekistan). The thromboembolic events reported in the studies included pulmonary embolism, disseminated intravascular coagulation, acute cardiovascular events, myocardial infarction, acute cerebrovascular injury, venous thromboembolism, and thrombosis [15][16][17][18][19][20][21][22]. All studies included both male and female study participants and the most commonly occurring MTHFR polymorphisms (C677T and A1298C).…”

“…Of the eight studies, four established an association between the presence of hereditary MTHFR variants and COVID-19 severity or specified thromboembolic events (n = 2200). The remaining four studies failed to identify a link between MTHFR and SARS-CoV-2 outcomes (n = 538) [15][16][17][18][19][20][21][22].…”

“…Out of a total of eight cross-sectional or observational studies, four studies indicated a connection between MTHFR variants and the outcome of COVID-19 infection, while the remaining four studies did not find a link between MTHFR variants (MTHFR C667T and MTHFR A1298C) and thromboembolic events and more severe outcomes of COVID-19 infection [15][16][17][18][19][20][21][22]. When we compared study population groups, the total number of subjects where the connection between the MTHFR gene variant and thromboembolic events was not proven was 538.…”

“…Therefore, a preventive therapeutic integration of folic acid and B vitamins could result in a reduction in the prevalence and mortality of COVID-19 viral infection [29]. On the other hand, in a cohort of 176 patients, Fevraleva et al [21] could not demonstrate a higher risk of thrombotic complications during COVID-19 disease in carriers of the genetic markers for thrombophilia, including G1691A in the FV gene, C677T and A1298C in the MTHFR gene, G20210A in the FII gene, and (-675) 4G/5G in the PAI-I gene, relative to patients without these markers. Both groups were taking therapeutic doses of anticoagulants.…”

A Rare Case of Pulmonary Embolism, Deep Vein Thrombosis, Bilateral Avascular Necrosis of the Femoral Head, and Miscarriage following COVID-19 in a Patient with Multiple Genetic Coagulation Factor Deficiency—A Case Report

“…Furthermore, a higher risk of thrombotic complications has been reported in adult SARS-CoV-2 carriers of the G1691A mutations in the FVL gene, despite administration of anticoagulants in therapeutic doses. This is the reason strict control should be applied over coagulation indicators and enhanced therapeutic regimens [26].…”