Prolonged thrombocytopenia after living donor liver transplantation is a strong prognostic predictor irrespective of history of splenectomy: the significance of ADAMTS13 and graft function

Abstract

The precise mechanism of prolonged thrombocytopenia following living donor liver transplantation (LDLT) remains unclear. To determine risk factors associated with prolonged thrombocytopenia following LDLT, with a focus on the activity of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs member 13) and the influence of splenectomy. Adult LDLT patients were divided into two groups on the basis of platelet counts (100 × 10(3)/μL) on POD 14: high and low platelet (HP and LP) groups. Survival analysis was performed in the 100 patients, and ADAMTS13 activity and von Willebrand factor (VWF) levels in the plasma were measured in 65 adult recipients. The 6-month survival rate was significantly lower in the LP group (n = 36) than in the HP group (n = 62) (61.1 vs. 93.5 %). ADAMTS13 activity had been significantly lower in the LP group (n = 23) than in the HP group (n = 42). The VWF/ADAMTS13 ratio was significantly higher in the LP group than in the HP group. The independent risk factors for thrombocytopenia on POD14 were preoperative AT levels and ADAMTS13 activity on POD14. TPO levels on POD14 were significantly higher in the LP group than in the HP group, while those on POD28 in the LP group were significantly decreased, despite the low platelet levels. Irrespective of splenectomy, platelet counts and ADAMTS13 activity in the LP group remained low until POD28, while VWF/ADAMTS13 ratio significantly increased until POD28. These results suggest that prolonged thrombocytopenia after LDLT was associated with not only a decrease in ADAMTS13 due to sinusoidal endothelial cell injury, but also low TPO production due to hepatocyte dysfunction, irrespective of splenectomy [corrected].

De novo thrombotic microangiopathy after non-renal solid organ transplantation

“…Two authors have described an elevated ratio of vWF/ADAMTS13 as a potential diagnostic tool [32,43]. However, this ratio changes depending on the interval after transplantation and presence of other factors like splenectomy, and their real significance and reference values still need to be determined in prospective studies [43][44][45][46].…”

“…Acute rejection was no risk factor in Shindoh's series. A decrease in ADAMTS13 has been reported to accompany graft dysfunction so the risk may be elevated in the setting of graft dysfunction [44].…”

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“…Platelet consumption because of splenomegaly and hypersplenism was caused by elevated portal venous pressure in a small sized graft, 6 and prolonged thrombocytopenia after LDLT was associated with a decrease in ADAMTS13 (a disintegrinlike and metalloproteinase with thrombospondin type-1 motifs 13), which cleaves multimers of von Willebrand factor into smaller sizes and prevents platelet aggregation and/or thrombus formation. 2 Pathophysiological examination has shown a relation between platelet aggregation in allograft tissue obtained soon after reperfusion and clinical features. 7,8 However, the regional specificity of platelet aggregation in allografts has not been fully assessed.…”

“…Similarly, 1-year survival rates were found to be significantly lower in LDLT recipients with platelet counts less than 100 × 10 3 /μL on POD 14, similar to our EPA-positive group, than in patients with higher platelet counts not (58.3% vs 90.3%). 2 Increased platelet aggregation in allograft tissue obtained before and 2 hours after reperfusion of deceased-donor liver transplants was associated with significantly higher serum levels of aspartate aminotransferase and lactate, and longer time in the intensive care unit after transplant. 8 These results indicate that platelet aggregation or platelet consumption in the allograft may partially contribute to the deterioration in graft function.…”

“…1,2 Few pathophysiological studies have assessed post-LT thrombocytopenia, because of difficulties in obtaining tissue samples. 3 Evaluation of allograft tissue from a living-donor LT (LDLT) recipient with thrombocytopenia plus sinusoidal obstruction syndrome (SOS) shows platelet aggregation in the space of Disse along the sinusoidal vessels and platelet phagocytosis by hepatocytes, a morphology called extravasated platelet aggregation (EPA).…”