Israel contains within it a unique variety of groups predisposed to autosomal recessive diseases secondary to the history of segregated religious communities. Indicated groups include Ashkenazi Jews and Israeli Arabs. Factor VII deficiency and Factor V deficiency are among the conditions that can be included in this group of diseases. Due to the risk for bleeding and delayed coagulation as a result of a deficiency in one of these factors, it has been postulated that an underlying cardiovascular benefit may protect the factor VII or factor V deficient individuals from developing an adverse cardiovascular event or venous thromboembolism. The objective of this study is to assess the association between Factor V and Factor VII deficiency with adverse cardiovascular event and venous thromboembolism
This historical cohort study was performed using the electronic database of Clalit Health Services, the largest health care provider in Israel. The study was approved by a centralized IRB committee. We identified all individuals who were tested for either Factor V activity or Factor VII activity between January 1, 2004 and June 30, 2017. We excluded individuals with liver cirrhosis who were tested for Factor V and Factor VII activity and patients treated with vitamin K antagonists who were tested for factor VII activity. Follow up started in January 2004 and ended in June 30, 2017. Subjects were included if they were 18 years or older at the start of follow up. Factor activity was classified into three categories; normal (activity >50%), mild deficiency (activity = 30-50%), and moderate-severe deficiency (activity ≤30%). The study outcomes included incidence of cardiovascular events (composite of myocardial infarction, stroke, and TIA) and venous thromboembolism (VTE). We used Cox proportional hazard regression analysis to assess the association between time to event and coagulations factors activity using normal activity (>50%) as reference category, and adjusting for potential confounders.
Of the 2,021 included individuals tested for Factor V activity 1,681 (83.2%) had normal factor V activity, 195 (9.6%) had mild deficiency, and 145 (7.2%) had moderate-severe deficiency. Compared to individuals with normal activity the adjusted hazard ratio (HR) for cardiovascular events was 1.10 (95% CI, 0.63-1.90) in those with mild deficiency, and 0.95 (95% CI, 0.49-1.8) in those with moderate-severe factor XI deficiency. None of the 195 patients with mild Factor V deficiency had VTE during follow up, therefore those with Factor V deficiency (activity <50%) were classified into one group. The incidence of VTE was lower in those with factor V deficiency (activity <50%) compared to those with normal activity; adjusted HR = 0.28 (95% CI, 0.09-0.91).
Of the 2,558 included individuals tested for Factor VII activity 1,440 (56.3%) had normal factor VII activity, 545 (21.3%) had mild deficiency, and 573 (22.4%) had moderate-severe deficiency. Compared to individuals with normal activity the adjusted hazard ratio (HR) for cardiovascular events was 1.38 (95% CI, 0.89-2.10) in those with mild deficiency, and 1.28 (95% CI, 0.84-1.9) in those with moderate-severe factor VII deficiency. Compared to individuals with normal activity the adjusted hazard ratio (HR) for VTE was 1.40 (95% CI, 0.65-3.20) in those with mild deficiency, and 0.75 (95% CI, 0.29-1.9) in those with moderate-severe factor VII deficiency.
Factor V deficiency but not Factor VII deficiency is associated with significant decreased incidence of VTE. No significant association was detected between Factor V deficiency or Factor VII deficiency and cardiovascular events.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.