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These findings suggest that platelet transfusions are an important risk factor for mortality after OLT. The current study extends previous observations by identifying acute lung injury as the main determinant of increased mortality. The higher rate of graft loss in patients receiving platelets is related to the higher overall mortality rate and does not result from specific adverse effects of transfused platelets on the grafted liver.

Apart from the well-known role of blood platelets in hemostasis, there is emerging evidence that platelets have various nonhemostatic properties that play a critical role in inflammation, angiogenesis, tissue repair and regeneration, and ischemia/reperfusion (I/R) injury. All these processes may be involved in the (patho)physiological alterations occurring in patients undergoing liver transplantation. Experimental and clinical research points toward a dualistic role of platelets in patients undergoing liver transplantation, resulting in both beneficial and detrimental effects. Although a low platelet count is generally considered a risk factor for perioperative bleeding, recent studies have indicated that platelet function in patients with cirrhosis may not be as abnormal as previously assumed. Platelet transfusions are frequently considered in liver transplant recipients to correct low platelet counts and to prevent bleeding; however, evidence-based transfusion thresholds are lacking, and the other detrimental and nonhemostatic properties of platelets are generally not weighed in this respect. First, platelets have been shown to contribute to I/R injury of the liver graft via induction of sinusoidal endothelial cell apoptosis. Second, platelet transfusion has been identified as an independent risk factor for reduced survival via mechanisms that are not completely understood yet. On the other hand, recent studies indicate that platelets are critically involved in restoration after liver injury and in liver regeneration via serotonin-mediated mechanisms. These findings make platelets both friend and foe in liver transplantation. The scientific challenge will be to further dissect the mechanisms and clinical relevance of these contrasting roles of platelets in liver transplantation. Liver Transpl 14: 923-931, 2008.

Patients with liver disease show profound changes in their hemostatic system, which may further change during liver transplantation. We previously demonstrated that highly elevated levels of the platelet adhesive protein von Willebrand factor (VWF) in patients with cirrhosis lead to an increased VWF-dependent platelet deposition under flow as compared to healthy controls. In this study we examined VWF parameters during the course of liver transplantation. We collected serial plasma samples from 20 patients undergoing liver transplantation in which we determined plasma levels of VWF and the VWF-cleaving protease ADAMTS13. Furthermore, we performed functional tests of VWF-dependent platelet adhesion. We found persistently elevated levels of VWF during and after liver transplantation. The capacity of VWF to interact with platelets normalized during the course of transplantation, and flow-mediated VWF-dependent platelet adhesion remained at levels far exceeding those observed in healthy individuals during and after transplantation. Plasma levels of ADAMTS13 dropped during transplantation, and in four patients levels below 10% of normal were observed after reperfusion. We observed the development of a hyperreactive primary hemostatic system, as evidenced by high levels of fully functional VWF and a temporary ADAMTS13 deficiency, during liver transplantation, and speculate that these changes contribute to postoperative thrombotic complications.

In all 15 samples, a substantial and clinically relevant variation in the calculated MELD score was observed between laboratories. The mean difference in the MELD score between the highest- and the lowest-scoring laboratory was 4.8. The variation in creatinine measurements resulted in differences of up to three MELD points in a single patient when comparing the highest and the lowest scoring lab. The variation in bilirubin measurements only accounted for a difference of one point between the highest- and the lowest-scoring laboratory, but the variation in INRs resulted in differences of 2 to 12 MELD points. MELD scores or INR values were not substantially different in laboratories that used the Owren instead of the more widely used Quick methodology for INR measurements. The variability in the INR in patients on oral anticoagulants was substantially less as compared with the variability in patients with liver disease. In conclusion, we observed a large interlaboratory variation in the MELD score. This variation in the MELD score is primarily caused by the INR.

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Platelet function is thought to deteriorate during liver transplantation as a result of platelet activation and proteolysis of platelet receptors by plasmin following reperfusion. However, this hypothesis has never been formally tested. Twenty patients undergoing a first or second liver transplant were included in the study. Blood samples were taken at standardized time points during transplantation and up to 10 days after transplantation. Platelet activation was assessed by detection of the activation markers P-selectin and activated integrin ␣IIb␤3 with flow cytometry. Proteolytic cleavage of platelet receptors was assessed by flow cytometry measurement of the constitutively expressed platelet receptors glycoprotein Ib␣ and integrin ␣IIb␤3. In addition, using enzyme-linked immunosorbent assay techniques, we measured plasma levels of platelet activation products ␤-thromboglobulin and platelet factor 4 and plasma levels of cleaved fragments of glycoproteins Ib␣ and V. Flow cytometry analyses provided no evidence of substantial platelet activation during transplantation. In fact, the expression of activated integrin ␣IIb␤3 decreased postoperatively; this indicated that platelets were in a slightly activated state prior to surgery. Plasma levels of ␤-thromboglobulin and platelet factor 4 also substantially decreased after transplantation. In addition, no changes were observed in the constitutively expressed platelet receptors or in the plasma levels of platelet receptor fragments, and this indicated a lack of substantial receptor proteolysis. In conclusion, no evidence was found for significant activation of circulating blood platelets or the proteolysis of key platelet receptors during liver transplantation. These findings suggest that the platelet functional capacity does not decrease during liver transplantation. Liver Transpl 15:956-962, 2009.