Association of Acquired Coagulation Changes and Genetic Polymorphisms on Microvascular Free Flap Thrombosis in Reconstructive Surgery. Summary of the Doctoral Thesis

Abstract

Microvascular free flap surgery possesses an ability to cover a broad range of tissue defects for reconstructive purpose fostering functional and aesthetic recovery. The restoration of blood flow is essential to ensure the viability of the transplanted tissue, as adequate vascular anastomosis facilitates the delivery of oxygen and nutrients, thereby preventing tissue ischaemia and necrosis. Despite remarkable advances in microsurgical techniques, instrumentation, and perioperative management protocols, thrombosis remains a significant complication that can hinder surgical success, resulting in dissatisfaction among patients and surgeons, as well as increased hospital stays and costs. The incidence of thrombosis ranges from 2 % to 9 %. The pathogenesis of thrombotic events in microvascular surgery appears multifactorial. Variants in genes regulating coagulation pathways, platelet function, and fibrinolysis might contribute to a predisposition for thrombotic events. Understanding these genetic influences might improve risk stratification and would personalise treatment strategies in microvascular surgery. The aim of the study was to evaluate the association between specific single nucleotide variant (SNV) and acquired coagulation changes with thrombotic complications in microvascular free flap surgery with the goal of developing genetic risk stratification parameters for individualised perioperative care. A prospective cross-sectional study was conducted, enrolling 155 adult patients scheduled for microvascular free flap surgery at the Centre of Plastic and Reconstructive Microsurgery of Latvia between December 2016 and July 2019. The study protocol was approved by the Latvian Central Medical Ethics Committee (No 1/28-11-16). Patient assessment included standardised interviews to collect data on thrombotic history, medication use, family history, and inherited thrombophilia. SNV genotyping was performed for five variants: rs6025 (in the Factor V gene, known as Factor V Leiden), rs1799963 (in the prothrombin gene, known as G20210A), rs2066865 (in the fibrinogen gamma chain gene), rs2227589 (in the SERPINC1 gene), and rs1801133 (in the MTHFR gene, known as the C677T variant). Preoperative coagulation parameters were assessed using standardised laboratory protocols, including fibrinogen concentration, activated protein C resistance, prothrombin time, antithrombin activity, and homocysteine levels. The study population consisted of 118 males (76.1 %) and 37 females (23.9 %), with a mean age of 45.07 ± 14.94 years. Flap thrombosis was observed in 14 patients (9.0 %), resulting in complete flap loss in 8 cases (5.16 %) and partial necrosis in 5 cases (3.22 %), yielding an overall flap success rate of 94.84 %. A statistically significant association was identified between the rs2066865 variant in the FGG gene and plasma fibrinogen concentrations. Homozygous A/A genotype carriers exhibited significantly elevated fibrinogen levels (5.57 ± 1.81 g/L, p=0.004) compared to G/G genotype carriers (4.08 ± 1.32 g/L) and G/A genotype carriers (4.64 ± 1.74 g/L, p=0.04). One patient with a heterozygous Factor V Leiden variant experienced recurrent thrombotic complications in multiple surgical procedures. However, no statistically significant association was found between any of the analysed single nucleotide variants and the incidence of microvascular free flap thrombosis. Acquired thrombophilia factors and standard coagulation parameters were insufficient as standalone predictors of flap thrombosis. A combined analysis of genetic and acquired factors showed only modest, non-significant trends toward an increased rate of thrombosis, and the resulting predictive models demonstrated poor discriminatory power (AUC: 0.61-0.69). While yielding negative results regarding the association of specific SNVs with thrombosis risk, this study provides valuable scientific information that redirects future research toward more comprehensive, multifactorial approaches to risk assessment. Fibrinogen polymorphisms were found to modulate plasma fibrinogen levels but lacked predictive utility for thrombosis. The current combination of genetic and acquired factors is inadequate for reliable preoperative risk stratification in microvascular free flap surgery. Future research should focus on large-scale, multicentre validation studies and the development of predictive models that integrate polygenic risk scores for personalised thromboprophylaxis in microvascular reconstruction.