Free-Flap Outcomes and Screening Options in Factor V Leiden: A Systematic Literature Review

INTRODUCTION: Factor V Leiden is the most common form of inherited thrombophilic syndrome, affecting five per cent of Caucasian people. Patients who are homozygous have an 80-fold relative risk of developing abnormal blood clots. Patients who are heterozygous, which is much more common, have a relative risk of three to eight. ^1,2 While increased rates of venous thromboembolic complications have been regularly reported in factor V Leiden patients, little is known regarding their relative risk of microvascular complications or flap failure in free-flap surgery. The primary aim of this study was to evaluate the statistical and clinical significance of data in the extant literature on this subject.

METHODS: Our study has three parts. First, we conducted a systematic (PRISMA) review on outcomes in factor V Leiden patients who had undergone free-flap surgery. Second, we assessed the current state of the literature on the pathophysiology of microvascular or intra-anastomotic thrombosis in patients with factor V Leiden. Third, we evaluated potential screening strategies for this patient population.

RESULTS: Only nine studies, with a total of 22 patients and 24 free-flaps, fit the inclusion criteria for our systematic literature review. The extant literature suggests a trend towards increased flap failure rates in factor V Leiden patients, even in those who are heterozygous. However, the majority of studies were case series and therefore at high risk of publication bias. Moreover, the total number of patients was too small to be of statistical or clinical significance.

Literature on the pathophysiology of microvascular, as opposed to macrovascular, thrombosis in this patient population was found to be similarly scant. Various opinions exist regarding the role and the extent of pre-operative screening strategies for thrombophilias prior to free-flap surgery. However, specific screening protocols are yet to be evaluated for their impact on surgical outcomes, cost and quality of life.

CONCLUSION: The current state of the literature on outcomes for free-flap reconstruction in factor V Leiden patients is inconclusive. Larger scale case-control studies are recommended. Knowledge on the pathophysiology of microvascular thrombosis in thrombophilic patients is also lacking. Given the significant economic and psychological costs associated with failed free-flap reconstructions, we advocate the use of a non-invasive screening protocol that involves preoperative collaboration with hematologists for theoretically at-risk patient populations.

1. Lee A. Factor V Leiden. Nursing. 2014; 44(6): 10-2.
2. Van Cott E, Khor B, Zehnder J. Factor V Leiden. Am J of Hematol. 2016; 91(1): 46-9.