Enzymes that hydrolyze adenine nucleotides in platelets and polymorphisms in the alpha2 gene of integrin alpha2beta1 in patients with von Willebrand disease.

Abstract

Von Willebrand disease (VWD) is one of the most common inherited bleeding diseases caused by a qualitative or quantitative deficiency of the von Willebrand factor (FvW). FvW is a multimeric glycoprotein synthesized by megakaryocytes and endothelial cells and it is present in the subendothelial matrix, blood plasma, platelets, and endothelium. This glycoprotein plays an important role in thrombus formation by initiating platelet adhesion to sites of injury as well as platelet aggregation. The aim of this study was to evaluate the activities of enzymes that hydrolyze adenine nucleotides in platelets, ristocetin-induced platelet aggregation (RIPA), and polymorphisms of the alpha2 gene of alpha2beta1 integrin from VWD patients. Platelet nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase, and ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP) activities were verified in 14 VWD patients. For RIPA determination, a final concentration of 1.25 mg/ml of ristocetin was used. Polymorphisms of the alpha2 gene were analyzed through PCR. Platelet NTPDase and E-NPP were decreased in VWD patients. 5'-Nucleotidase activity was not statistically significant between controls and VWD patients. RIPA was significantly reduced, with an allelic frequency of 78.57% for 807C in VWD patients. Our results indicated reduced platelet NTPDase and E-NPP activities which might be related to the low platelet adhesiveness. The prevalence of the 807C allele might account for the variability in bleeding in VWD.

• Authors: Karen Freitas Santos, Vanessa Battisti, Maísa de Carvalho Corrêa, Thaís Rapachi Mann, Renata da Silva Pereira, Maria do Carmo Araújo, Alice Odete Brülê, Maria Rosa Chitolina Schetinger, Vera Maria Morsch
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 340 Issue 1-2 Pg. 249-56 (Jul 2010) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 20336352 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenine Nucleotides
• Integrin alpha2
• Integrin alpha2beta1
• Hydrolases
• 5'-Nucleotidase
• Phosphoric Diester Hydrolases
• Pyrophosphatases
• Nucleoside-Triphosphatase

Topics

• 5'-Nucleotidase (blood)
• Adenine Nucleotides (blood)
• Adolescent
• Adult
• Blood Platelets (enzymology)
• Brazil
• Case-Control Studies
• Child
• Female
• Gene Frequency
• Genotype
• Hemostasis (genetics)
• Humans
• Hydrolases (blood)
• Hydrolysis
• Integrin alpha2 (genetics)
• Integrin alpha2beta1 (genetics)
• Male
• Nucleoside-Triphosphatase (blood)
• Partial Thromboplastin Time
• Phenotype
• Phosphoric Diester Hydrolases (blood)
• Platelet Aggregation (genetics)
• Platelet Count
• Polymorphism, Genetic
• Prothrombin Time
• Pyrophosphatases (blood)
• Young Adult
• von Willebrand Diseases (blood, enzymology, genetics)