Major thrombosis is a significant danger for patients with MPN who become infected with COVID-19, and antithrombotic prophylaxis does not appear to eliminate the risk.
A new multicenter study of patients with myeloproliferative neoplasms (MPNs) found that those with essential thrombocythemia (ET) have the greatest risk of venous thromboembolism (VTE) when infected with COVID-19.
The new data are notable in part because arterial thrombosis—rather than venous thrombosis—is widely considered the more common danger for patients with MPNs. The new study was published in the Blood Cancer Journal.
Although COVID-19 is primarily a respiratory ailment, corresponding author Tiziano Barbui, MD, of the Papa Giovanni XXIII Hospital, in Italy, and colleagues, noted in the published report that the disease can affect a number of organs, including the heart, kidney, and vascular system. These complications can include VTE and/or arterial thrombosis. It can be difficult to know the true rate of thromboembolic events in patients with COVID-19, they said, since not every patient is screened for them. However, existing evidence suggests thrombosis is a relatively common occurrence, particularly among patients transferred to intensive care units (ICUs), where the estimated prevalence was 22.7%.
Barbui and colleagues wrote that patients with certain pre-existing conditions might be at higher risk for VTE and arterial thrombosis, including patients with MPNs, which they said might be the most vulnerable of all patients. However, there was a lack of data to characterize the risk, in part because of the relatively low prevalence of MPNs and in part due to the novelty of the SARS-CoV-2 virus itself.
In hopes of evaluating the incidence of thrombosis and bleeding and identifying risk factors, Barbui and colleagues embarked on a major, multicenter, retrospective cohort study involving 38 European hematology centers. A total of 162 patients with MPNs and COVID-19 infection were identified and included in the study and followed for a median of 50.5 days (interquartile range [IQR], 16.0-69.0). Among those patients, 48 had ET, 42 had polycythemia vera, 56 had myelofibrosis, and the remaining 16 were categorized as prefibrotic myelofibrosis. Of those patients, 15 major thromboses were reported, spread across 14 patients. Of the 15 thromboses, just 3 were arterial and the remaining 12 were venous. All but 1 of those patients was receiving low molecular weight heparin (LMWH) as antithrombotic prophylaxis. After adjusting for competing risk of death, the investigators found that the incidence of arterial and venous thromboembolic events was 8.5% after 60 days of follow-up. In the study data, 8 of the 12 patients with VTE were in the ET group, suggesting those patients face the highest risk.
Barbui told Targeted Oncology that typically 60% to 70% of thromboembolic events in patients with MPNs are arterial, rather than venous.
“The opposite occurs in SARS-CoV-2 infection, where thromboses of the veins substantially prevail over those of the arteries,” he said. “This is due to several factors including bed rest, endothelial damage produced by the virus, activation of coagulation mediated by a series of factors, and the viral attack.”
Barbui said on the surface, the data suggest that patients with MPNs have the same risk of thrombosis as non-MPN patients, but he said such a comparison is not reliable, since these data are based on easier-to-diagnose manifest thromboses. He added that thrombosis of the lung is also a concern, though this is frequently diagnosed via autopsy.
The investigators noted that patients with MPNs had markedly lower platelet counts upon COVID-19 diagnosis compared to their most recent pre-COVID follow-up, particularly among patients with ET, where the decline was 23.3% (P < .0001). The decline was associated with a higher mortality rate for pneumonia.
Risk factors for thrombosis were transfer to ICU (sub-distribution hazard ratio [SHR], 3.73; 95% CI, 1.14-12.23; P = .029), neutrophil/lymphocyte ratio (SHR, 1.16; 95% CI, 1.06-1.27; P = .001), and ET phenotype (SHR, 4.37; 95% CI, 1.51-12.64; P = .006). They said the higher susceptibility to VTE and pneumonia among patients with ET may warrant new tailored antithrombotic regimens for those patients, including antiplatelet drugs.
Barbui and colleagues noted that most of the cases of thrombosis reported in the study took place in patients who were on LMWH prophylaxis. However, they said that antithrombotic prophylaxis was not treated as standard therapy for patients with COVID-19, and thus was only prescribed in 57% of MPN cases. Although LMWH was the chosen prophylactic in almost all cases, dosing varied significantly. The Scientific and Standardization Committee of the International Society of Thrombosis and Hemostasis has suggested universal thromboprophylaxis after assessment of bleeding risk, the authors wrote, but with the current dearth of evidence regarding dosing, most such decisions are made empirically.
“The problem of anti-thrombotic prophylaxis is still not well resolved,” Barbui said. “It must be done in patients hospitalized in intensive care units, but the doses are not yet codified by convincing studies. In particular, in patients with myeloproliferative diseases, attention should be paid to the onset of bleeding that occurred in our patients, mainly in myelofibrosis. Guidelines should therefore be followed, which are not evidence-based, but represent a consensus among experts.”
Barbui T, De Stefano V, Alvarez-Larran A, et al. Among classic myeloproliferative neoplasms, essential thrombocythemia is associated with the greatest risk of venous thromboembolism during COVID-19. Blood Cancer J. 2021;11(2):21. doi:10.1038/s41408-021-00417-3