Post-transplant HAT and/or PVT increase the potential for graft loss. The frequency of post-transplant HAT has been previously recorded as 4.5% to 6%[14, 15]. In our study, the most frequent post-transplant thrombotic event was HAT, with a frequency of 9% (41/441 cases, 63.5% of all post-transplant thrombotic event). However, there is no extensive thrombophilia study in a large cohort of liver recipients. We evaluated the thrombophilia-associated risk factors and their clinical impact was assessed. The partial retrospective design and heterogeneity of the study population are limitations of our study.
Liver transplantation itself also changes the dynamics of coagulation, with a pro-coagulant pattern in the first weeks post-transplant. Due to the thrombophilia study was carried out between 1.2 months to 4.1 months post-transplant, thrombophilic abnormalities in immediate post-surgery, with influence in the development of early HAT, could be underestimated. Nevertheless, we detected thrombophilic abnormalities that were still evident during the first 3 months post-surgery or during the late post-transplant period, and which were associated with HAT.
The importance of genetic thrombophilia risk factors in PVT has been investigated in several studies [16–19] but all of them have excluded cases with local risk factors. The incidence of Factor V Leiden, prothrombin mutation, decreased PC, decreased PS, and decreased AT has been recorded between 3-30%, 3-22%, 0-26%, 2-43%, and 1-26%, respectively. In our study the incidence of decreased PC, decreased PS, and decreased AT was 2.4%, 4.5%, 10.2%, 18%, and 7.2%, respectively. The incidences of decreased PC, PS and AT were higher than that observed in the general population. Nevertheless, these deficiencies coincided with deteriorating liver function in most cases.
Most of the coagulation changes due to genetic mutations in the recipient are corrected by liver transplantation. Of the 293 patients screened for genetic analysis of Factor V Leiden and who underwent functional studies of APCR after OLT, 7 heterozygous carriers of Factor V Leiden displayed a loss of APCR after transplantation, as previously described [20–22]. In our study, recipients of graft Factor V Leiden did not acquire APCR, probably because the platelet derived Factor V originates from the plasma pool [23–25]. However, these results do not correlate with previous work which states that APCR associated with a Factor V Leiden donor is fully transferable to the graft recipient .
Some of the variables associated with post-transplant thrombotic event could relate to difficulties in surgical technique, such as in a child recipient, and also their primary cause of liver transplantation, biliary atresia. In a recent study , post-transplant complication rates, including the re-operation rate, were higher in the younger group. In our study, fibrinogen level was the one variable independently associated with post-transplant thrombotic event in the global cohort of liver recipients. Previously this factor has been associated both with thrombosis and inflammation. A meta-analysis showed that risk of coronary heart disease may increase 1.8 fold for 1 g/L of increased fibrinogen, independent of traditional risk factors . But, in the retrospective cohort of recipients, the toxicity was the only variable independently associated. This factor could be involved in graft thrombosis due to its role in endothelial injury and inflammation. Plasma levels of fibrinogen (high) and protein C recipient (low) were associated post-transplant thrombotic event in the prospective group. Low plasma levels of protein C recipient was associated, in this work, with liver disease relapse (Additional File 2, Table S2), and this fact could be a consequence of disbalance of coagulation factors in terminal cirrhosis . A previous paper had shown that PC was decreased at day 7 (p = 0.04) and day 30 (p = 0.009) in DDLT and DDRT/LRT groups with complications, respectively . Nevertheless, high plasma fibrinogen levels are not a consequence of liver function alteration, and could be an important pro-thrombotic factor in development graft thrombosis that has not been previously described.
Our results were in agreement with previous studies  showing that the presence of post-transplant thrombotic event, HAT in the majority of cases, in this liver recipient cohort influenced recipient overall survival. High factor VIII was associated with a poor outcome, as previously reported. Levels of factor VIII, a potent pro-coagulant involved in thrombin generation, increased progressively with Child-Pugh Score (from Child-Pugh class A to C). A correlation between the severity of liver disease and von Willebrand factor (VWF) plasma antigen levels has been previously documented [31, 32]. In agreement with other authors , we emphasize the need for studies to evaluate the clinical relevance of including thrombotic risk factors (such as factor VIII associated to poor outcome) in the Prognostic scores ej. Model for End-stage Liver Disease (MELD).