Acquired factor V inhibitor: a nation‐wide study of 38 patients

Abstract

Summary Acquired factor V inhibitor (AFVI) is an extremely rare disorder that may cause severe bleeding. To identify factors associated with bleeding risk in AFVI patients, a national, multicentre, retrospective study was made including all AFVI patients followed in 21 centres in France between 1988 and 2015. All patients had an isolated factor V (FV) deficiency <50% associated with inhibitor activity. Patients with constitutional FV deficiency and other causes of acquired coagulation FV deficiencies were excluded. The primary outcome was incident bleeding and factors associated with the primary outcome were identified. Thirty‐eight (74 [36–100] years, 42·1% females) patients with AFVI were analysed. Bleeding was reported in 18 (47·4%) patients at diagnosis and in three (7·9%) during follow‐up (7 [0·2–48.7] months). At diagnosis, FV was <10% in 31 (81·6%) patients. Bleeding at diagnosis was associated with a prolonged prothrombin time that strongly correlated with the AFVI level measured in plasma {r = 0·63, 95% confidence interval (CI) [0·36–0·80], P < 0·05}. Bleeding onset during follow‐up was associated with a slow AFVI clearance (P < 0·001). The corresponding receiver operating characteristics curve showed that AFVI clearance was predictive of bleeding onset with an AFVI clearance of seven months with a sensitivity of 100% (95% CI: 29–100) and a specificity of 86% (95% CI: 57–98, P = 0·02). Kaplan–Meier analysis showed that AFVI clearance >7 months increased the risk of bleeding by 8 (95% CI: [0·67–97], P = 0·075). Prothrombin time at diagnosis and time for clearance of FV inhibitor during follow‐up are both associated with bleeding in patients with AFVI.

Acquired Factor V Inhibitor after Coronavirus Disease 2019 (COVID-19)

“…3 4 According to the specific targeted epitope (i.e., domains of light chain or heavy chain of FV), anti-FV antibodies affect the balance between pro- and anticoagulant functions of FV. 2 5 No definitive treatment strategy has been established. In approximately 50% of cases, the inhibitor is eliminated spontaneously.…”

“…Inhibitors directed against factor V (FV) occur seldom, primarily in the elderly, and the clinical presentation varies from asymptomatic laboratory abnormalities to life-threatening bleedings. 1,2 Acquired FV inhibitors usually are immunoglobulin of the G class (IgG) directed to the binding site for phosphatidylserine (present in the second C-type domain of the light chain of FV). Infections, drugs, surgical procedures, blood transfusions, solid and hematological cancers, and autoimmune disorders are associated with the risk of developing acquired FV inhibitors.…”

“…In approximately 50% of cases, the inhibitor is eliminated spontaneously. [1][2][3] A 62-year-old Caucasian woman presented to the Hematology Department because of recurrent episodes of hematuria from 1 week, and bleeding from the sites of venous sampling. Coagulation tests showed that the platelet count was normal (►Table 1): prolonged prothrombin time (PT): 45.5 seconds, international normalized ratio: 4.09, and activated partial thromboplastin time (aPTT): 165 seconds, aPTT ratio: 5.5.…”

“…1,2 Some reports have shown that the administration of rituximab, cyclophosphamide, and plasma-exchange can be used. 1,2 However, no definitive treatment strategy has been established, and, in approximately 50% of cases, the inhibitor is eliminated spontaneously. 3 Coagulation abnormalities, thrombosis, and endothelial dysfunction are commonplace in patients with COVID-19, with higher incidence in severe cases, and the severity of alterations of coagulation parameters has been clearly associated with unfavorable prognosis.…”

High Mutational Heterogeneity, and New Mutations in the Human Coagulation Factor V Gene. Future Perspectives for Factor V Deficiency Using Recombinant and Advanced Therapies

“…Generally speaking, this treatment has not been associated with serious complications such as allergic reactions to plasma components, anaphylaxis or problems derived from perfusion of high levels of FFP. Inhibitors (anti- FVa antibodies) have also been reported, although their occurrence has been rare [ 48 ].…”