Degradation of von Willebrand factor in patients with acquired clinical conditions in which there is heightened proteolysis

Abstract

The behavior of plasma von Willebrand factor (vWF) in patients with acute leukemia (n = 5), decompensated cirrhosis (n = 10), and acute pancreatitis (n = 5) was investigated to evaluate whether the systemic proteolytic states associated with these diseases had affected the structure and function of the molecule. vWF antigen and, to a lesser degree, ristocetin cofactor activity in patient plasma were high. Multimeric analysis of plasma vWF revealed loss of high molecular weight multimers. The subunit composition and proteolytic pattern of vWF immunopurified from patient plasmas and reduced were studied by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis followed by transblotting and probing with monoclonal antibodies that distinguish cleavages caused by plasmin from those caused by other proteases. There was marked reduction of the relative concentration of the native vWF subunit of 225 Kd in all patient groups, indicating heightened cleavage of the protein. The concentrations of 189- and 140- Kd vWF fragments, normally present in plasma, were increased in cirrhosis and pancreatitis but not in leukemia. Novel fragments, ranging in size from less than 225 to approximately 120 Kd were present in leukemia and cirrhosis, including plasmin-generated fragments of 176 and 145 Kd. These data indicate that in clinical conditions in which there is heightened proteolysis vWF is degraded in vivo by plasmin and other proteases. Degraded vWF may be less effective than native vWF in supporting primary hemostasis, thereby being a cofactor in the multifactorial bleeding diathesis accompanying systemic proteolytic states.

Management of epistaxis in patients with ventricular assist device: a retrospective review

“…Serious bleeding, defined as episodes that result in death, reoperation, hospitalization, or transfusion, occurs in 19–40% of patients with the HMII, making it the most frequent complication [ 27 ], with the gastrointestinal tract and the nasal cavity being the most common sites [ 28 ]. The proteolytic mechanism that reduces VWF multimers also occurs in those with aortic valve stenosis, pancreatitis, liver cirrhosis, and leukemia [ 29 ]. According to the International Society on Thrombosis and Haemostasis, AvWS is most frequently associated with lymphoproliferative (48%), cardiovascular (21%), myeloproliferative (15%), other neoplastic (5%), and autoimmune disorders (2%) [ 30 ].…”

Disseminated Intravascular Coagulation in Hematologic Malignancies

“…This action is reverted by administration of ATRA. [74][75][76] Microparticles Microparticles (MP), cell-derived membrane fragments 0.1 to 1.0 mm in size, originate from normal cells, such as platelets, white blood cells and endothelial cells, or malignant cells. Soluble or free TF found in plasma may actually be MP bound directly to FVIIa.…”

No evidence for systemic platelet activation during or after orthotopic liver transplantation

“…In addition, 2 observations have pointed toward a deterioration of platelet function during liver transplantation, providing an argument to support the use of blood products such as platelet transfusions. First, after graft reperfusion, a hyperfibrinolytic state may develop because of the release of tissue‐type plasminogen activator (tPA) from the graft 14, 15. The resulting formation of plasmin is potentially capable of proteolysis of key platelet receptors, which could compromise platelet function and number 16.…”