Procoagulant properties of microparticles released from red blood cells in paroxysmal nocturnal haemoglobinuria

• Published in: British journal of haematology Vol. 152; no. 5; pp. 631 - 639
• Main Authors: Kozuma, Yukinori, Sawahata, Yuka, Takei, Yumi, Chiba, Shigeru, Ninomiya, Haruhiko
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2011; Blackwell
• Subjects: Anemias. Hemoglobinopathies; Biological and medical sciences; Blood Coagulation - physiology; Calcium - physiology; Calpain - physiology; Caspases - physiology; Cell-Derived Microparticles - drug effects; Cell-Derived Microparticles - physiology; Cells, Cultured; Complement Activation - physiology; Diseases of red blood cells; Enzyme Inhibitors - pharmacology; Erythrocytes - drug effects; Erythrocytes - physiology; Erythrocytes - ultrastructure; Hematologic and hematopoietic diseases; Hemoglobinuria, Paroxysmal - blood; Humans; Medical sciences; microparticle; Naphthalenes - pharmacology; PKC; PNH; Protein Kinase C - antagonists & inhibitors; RBC; Tetradecanoylphorbol Acetate - pharmacology; thrombosis; Erythrocytic membrane disease; Protein kinase C; Hematology; Enzyme; Transferases; Red blood cell; Procoagulant activity; Cardiovascular disease; PKC; Hemopathy; PNH; Thrombosis; Vascular disease; Blood cell; RBC; Hemolytic anemia; Nocturnal paroxystic anemia; Microparticle
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2010.08505.x

Summary Thrombosis in paroxysmal nocturnal haemoglobinuria (PNH) has been suggested to be due to several pathophysiological states: a suppressed fibrinolytic system, increased leucocyte‐derived tissue factor, complement (C′)‐mediated damage to platelets and endothelia, or increased platelet‐ and endothelium‐derived microparticles (MPs). Because haemolytic attack is often accompanied by thrombosis in PNH, we studied the role of C′‐induced release of MPs in the thrombogenesis of PNH. C′ activation induced procoagulant alteration in PNH red blood cells (RBC), when assessed by thrombin generation in the presence of C′‐activated PNH RBC, which was abolished by their subsequent treatment with annexin V. Significant amounts of procoagulant MPs, measured by phosphatidylserine‐binding prothrombinase activity, were released from PNH RBC in association with the formation of C5b‐9, but not significantly before C5b‐8. Generation of procoagulant, annexin V‐binding, MPs from C′‐activated RBC was studied also by flow cytometry. While phorbol 12‐myristate 13‐acetate, an activator of protein kinase C (PKC), induced the release of MPs from normal RBC as well as PNH RBC, C′‐induced release of MPs from PNH RBC was Ca2+‐independent and not associated with the activation of PKC, calpain or caspase. Procoagulant properties of MPs released from PNH RBC could contribute to the thrombogenesis of PNH.