Complications of Factor V Leiden in Adults Undergoing Noncardiac Surgical Procedures: A Systematic Review

Factor V Leiden is the commonest hereditary prothrombotic allele, affecting 1% to 5% of the world's population. The objective of this study was to characterize the perioperative and postoperative outcomes of patients with Factor V Leiden compared to patients without a diagnosis of hereditary thrombophilia. This was a focused systematic review of studies including adult (>18 years) patients with Factor V Leiden (heterozygous or homozygous) undergoing noncardiac surgery. Included studies were either randomized controlled trials or observational. The primary clinical outcomes of interest were thromboembolic events occurring from the perioperative period up to 1 year postoperatively, defined as deep venous thrombosis, pulmonary embolism, or other clinically significant thrombosis occurring during or after a surgical procedure. Secondary outcomes included cerebrovascular events, cardiac events, death, transplant-related outcomes, and surgery-specific morbidity. Pediatric and obstetrical patients were excluded, as were case reports and case series. Databases searched included MEDLINE and EMBASE from inception until August 2021. Study bias was assessed through the CLARITY (Collaboration of McMaster University researchers) Risk of Bias tools, and heterogeneity through analysis of study design and end points, as well as the I-2 statistic with its confidence interval and the Q statistic. A total of 5275 potentially relevant studies were identified, with 115 having full text assessed for eligibility and 32 included in the systematic review. On the whole, the literature suggests that patients with Factor V Leiden have an increased risk of perioperative and postoperative thromboembolic events compared to patients without the diagnosis. Increased risk was also seen in relation to surgery-specific morbidity and transplant-related outcomes, particularly arterial thrombotic events. The literature did not support an increased risk for mortality, cerebrovascular, or cardiac complications. Limitations of the data include predisposition toward bias due in many study designs and small sample sizes across the majority of published studies. Variable outcome definitions and durations of patient follow-up across different surgical procedures resulted in high study heterogeneity precluding the effective use of meta-analysis. Factor V Leiden status may confer additional risk for surgery-related adverse outcomes. Large, adequately powered studies are required to accurately estimate the degree of this risk by zygosity.