ORIGINAL ARTICLESPlasmatic coagulation and fibrinolytic system alterations in PNH: relation to clone sizeGrünewald, Martina; Siegemund, Annelieb; Grünewald, Anjaa; Schmid, Ankea; Koksch, Marioc; Schöpflin, Christinea; Schauer, Stefaniea; Griesshammer, MartinaAuthor Information aDepartment of Haematology, Haemostaseology Division, University of Ulm, Germany and bIntensive Care Unit and cDepartment of Cardiology and Angiology, University of Leipzig, Germany. Sponsorsip: This study was supported by research funding from Baxter Germany GmbH, Heidelberg, Germany to M.G. Correspondence and requests for reprints to Dr med. Martin Grünewald, Department of Haematology, Haemostaseology Division, University of Ulm, Robert-Koch-Strasse 8, D 89081 Ulm, Germany. Tel: +49 731 5002 4528; fax: +49 731 5003 3883; e-mail: firstname.lastname@example.org Received 13 February 2003 Revised 3 May 2003 Accepted 8 May 2003 Blood Coagulation & Fibrinolysis: October 2003 - Volume 14 - Issue 7 - p 685-695 Buy Abstract Paroxysmal nocturnal haemoglobinuria (PNH) is characterized pathophysiologically by intravascular lysis of blood cells and clinically by thromboembolic events, often atypical in localization. In this study, we examined the plasmatic coagulation system of PNH patients to investigate a potential relation between coagulation alterations and disease intensity (PNH clone size). We found evidence for both an increase in procoagulant and in fibrinolytic activity, resulting in increased fibrin generation and turnover. Whereas a positive association of the procoagulant potential with PNH clone size was notable, fibrinolytic activity showed an inverse association with clone size. As a possible cause, a growing impairment of fibrinolytic activation and/or an increasing displacement of fibrinolytic activity is assumed. These mechanisms are most likely caused by the detachment of the glycosyl-phosphatidyl-inositol-anchored urokinase plasminogen activator receptor from cell surfaces, causing a progressive resistance to fibrinolytic stimuli, together with a probable shift of the fibrinolytic potential from cell surfaces to soluble, circulating complexes, resulting in a cellular fibrinolysis-steal phenomenon. Together, these processes are accused of mediating an increased thrombophilic risk in PNH. As hereditary prothrombogenic defects were found more frequently in patients suffering ischaemic complications, genetic thrombophilia seems to confer an additional thromboembolic risk in PNH, and should therefore be screened for. © 2003 Lippincott Williams & Wilkins, Inc.