Quantitative and Qualitative Analysis of Platelet GPIb and von Willebrand Factor in Liver Cirrhosis

Abstract

SummaryNumerous abnormalities of plasmatic coagulation and platelet function may contribute to the bleeding in liver cirrhosis with a defective platelet-von Willebrand factor interaction being a potential mechanism. To analyze GPIb and von Willebrand factor in cirrhosis, we quantified the number of GPIb molecules on the platelet surface by flow cytometry, assessed the total (and indirectly the internal) pool of GPIb by ELISA and measured the circulating amount of glycocalicin in plasma as a measure of proteolytic activity and platelet turnover. Von Willebrand factor was characterized by ELISA, by its ristocetin-cofactor activity and by multimer analysis. Botrocetin-induced agglutination was used for functional analysis.The data from 8 well-characterized cirrhosis patients indicate that total GPIb is insignificantly increased to 46,000 ± 5,000 molecules/P (normal: 39,500 ± 2,000 [SEM]), surface-GPIb is normal with some variability and that the glycocalicin levels are 2-3 times higher than would be expected from the platelet count (= 100 ±5 × 109/1). Von Willebrand factor antigen levels and -activity were 400-500 % of normal with a 22% reduction of the high molecular weight multimers. A significant hyperagglutination response to botrocetin was observed with platelets from both patients and controls using patient plasma as a source of von Willebrand factor. In conclusion, a hyperresponsiveness rather than a defective platelet-von Willebrand factor interaction can be observed in cirrhosis which may compensate for other hemostatic problems and appears to be mediated primarily by increased levels of von Willebrand factor.

Short‐ and long‐term effects of therapy with interferon‐α and pegylated interferon‐α/ribavirin on platelet plug formation and von Willebrand factor release in patients with chronic hepatitis C

“…In cirrhotic patients, vWF levels were already higher at baseline compared with noncirrhotic patients. This increase may reflect a compensatory release of vWF for thrombocytopenia and other haemostatic problems associated with cirrhosis 32–34 . It may be triggered by the chronic inflammation itself, by endotoxaemia, or reduced cleavage of vWF by metalloprotease 35 .…”

“…This increase may reflect a compensatory release of vWF for thrombocytopenia and other haemostatic problems associated with cirrhosis. [32][33][34] It may be triggered by the chronic inflammation itself, by endotoxaemia, or reduced cleavage of vWF by metalloprotease. 35 Apparently, PEG-IFN-a/ribavirin was not able to increase vWF levels beyond the already elevated baseline levels in cirrhotic patients.…”

Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity

“…In accordance, mean MELD scores paralleled the Child classification. The MELD score was 10 [6][7][8][9][10][11][12][13][14][15][16][17][18] (median [range]) in the Child A group, 13 [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] in the Child B group, 18 in the Child C group, and 28 [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] cirrhosis compared with control, P Ͼ .05 for mild cirrhosis compared with control). In the five patients with acute liver failure, the VWF collagen-binding activity was slightly decreased (90% [86-99]), but this difference did not reach statistical significance.…”

“…Conflicting reports on the capacity of VWF to bind platelets (as measured by ristocetin-or botrocetin-induced platelet aggregation) have appeared in literature, and patient numbers in these studies were small. 5,9,10 An important qualitative aspect of VWF is its multimeric composition. The high-molecular-weight multimers are more potent in supporting hemostasis, as they have a higher affinity for both glycoprotein Ib and collagen.…”

Predictors of Bleeding from Esophageal Varices: The Role of Factor VII and von Willebrand Factor (vWF)

“…Another possible mechanism of elevated vWF in cirrhosis is induction of synthesis of vWF in the liver with cirrhosis itself [8] or reduced liver-mediated clearance. Although it is established that vWF antigen levels are increased in patients with cirrhosis, relatively little is known on the relation between it and the bleeding from esophageal varices [9] [10] so we aimed in this study to determine the clinical predictors of bleeding esophageal varices and study the role of FVII and vWF in predicting bleeding in patients with eosphogeal varices.…”