Intracellular activation of the fibrinolytic cascade in the Quebec Platelet Disorder

Prameet M. Sheth; Walter H. A. Kahr; Anwar M. Haq; Dragoslava Kika Veljkovic; Georges E. Rivard; Catherine P. M. Hayward

doi:10.1160/TH02-12-0323

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2003; 90(02): 293-298
DOI: 10.1160/TH02-12-0323

Platelets and Blood Cells

Schattauer GmbH

Intracellular activation of the fibrinolytic cascade in the Quebec Platelet Disorder

Prameet M. Sheth

,

Walter H. A. Kahr

¹Departments of Pathology and Molecular Medicine and Medicine, McMaster University, Hamilton, Ontario, Canada and the Departments of Hematology/Oncology, Hôpital Sainte Justine, Montreal, Quebec, Canada

,

Anwar M. Haq

¹Departments of Pathology and Molecular Medicine and Medicine, McMaster University, Hamilton, Ontario, Canada and the Departments of Hematology/Oncology, Hôpital Sainte Justine, Montreal, Quebec, Canada

,

Dragoslava Kika Veljkovic

¹Departments of Pathology and Molecular Medicine and Medicine, McMaster University, Hamilton, Ontario, Canada and the Departments of Hematology/Oncology, Hôpital Sainte Justine, Montreal, Quebec, Canada

,

Georges E. Rivard

¹Departments of Pathology and Molecular Medicine and Medicine, McMaster University, Hamilton, Ontario, Canada and the Departments of Hematology/Oncology, Hôpital Sainte Justine, Montreal, Quebec, Canada

,

Catherine P. M. Hayward

¹Departments of Pathology and Molecular Medicine and Medicine, McMaster University, Hamilton, Ontario, Canada and the Departments of Hematology/Oncology, Hôpital Sainte Justine, Montreal, Quebec, Canada

› Institutsangaben

Abstract

Summary

The Quebec Platelet Disorder (QPD) is an unusual bleeding disorder associated with increased platelet stores of urokinase-type plasminogen activator (u-PA) and proteolysis of platelet α–granule proteins. The increased u-PA and proteolyzed plasmino-gen in QPD platelets led us to investigate possible contributions of intracellular plasmin generation to QPD α-granule proteolysis. ELISA indicated there were normal amounts of plasminogen and plasmin-α₂-antiplasmin (PAP) complexes in QPD plasmas. Like normal platelets, QPD platelets contained only a small proportion of the blood plasminogen, however, they contained an increased amount of PAP complexes compared to normal platelets (P < 0.005). The quantities of plasminogen stored in platelets were important to induce QPD-like proteolysis of normal α-granule proteins by two chain u-PA (tcu-PA) in vitro. Moreover, adding supplemental plasminogen to QPD, but not to control, platelet lysates, triggered further α-granule protein proteolysis to forms that comigrated with plasmin degraded proteins. These data suggest the generation of increased but limiting amounts of plasmin within platelets is involved in producing the unique phenotypic changes to α-granule proteins in QPD platelets. The QPD is the only known bleeding disorder associated with chronic, intracellular activation of the fibrinolytic cascade.

Keywords

Inherited platelet disorders - fibrinolysis - α-granule proteins - urokinase-type plasminogen activator - plasmin

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Referenzen

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