title: A chronic hypercoagulable state in patients with beta-thalassaemia major is already present in childhood.
abstract: A higher than normal incidence of thromboembolic events has been observed in adult patients with beta-thalassaemia major (TM) and certain haemostatic anomalies found in these patients suggest the existence of a chronic hypercoagulable state. Thalassaemic red blood cells (RBC) were demonstrated to facilitate thrombin formation due to altered asymmetry of the membrane phospholipids with enhanced exposure of phosphatidylserine. Since RBC anomalies exist in thalassaemia from the first months of life, we studied markers of hypercoagulability and thrombophilia in 36 adult patients (range 19-38 years) and 26 children (range 2-18 years) with beta-TM. All the patients were in steady state and none had experienced clinical signs or symptoms of thrombosis. Highly elevated urinary levels of 11-dehydro-thromboxane B2 and significantly elevated plasma levels of thrombin-antithrombin III (TAT) complexes were observed to the same extent in TM children and adults. The levels of factor II were decreased while factors V, VII + X and plasminogen were within the normal range. The natural coagulation inhibitors, protein C (PC) and protein S (PS) were significantly decreased in all TM patients investigated, regardless of age, but the PS binding protein (C4bBP) and antithrombin III levels were normal. The frequency of other thrombophilic mutations was not increased. Thus, a chronic hypercoagulable state already exists in thalassaemia in childhood and may contribute to the cardiac and pulmonary anomalies and the thrombotic events which occur later.
authors.affiliation: Institute of Haematology, Tel-Aviv Sourasky Medical Centre, The Sackler Faculty of Medicine, Tel-Aviv University, Israel. aeldor@post.tau.ac.il
authors.forename: A
authors.initials: A
authors.lastname: Eldor
authors.forename: R
authors.initials: R
authors.lastname: Durst
authors.forename: E
authors.initials: E
authors.lastname: Hy-Am
authors.forename: A
authors.initials: A
authors.lastname: Goldfarb
authors.forename: S
authors.initials: S
authors.lastname: Gillis
authors.forename: E A
authors.initials: EA
authors.lastname: Rachmilewitz
authors.forename: A
authors.initials: A
authors.lastname: Abramov
authors.forename: J
authors.initials: J
authors.lastname: MacLouf
authors.forename: Y C
authors.initials: YC
authors.lastname: Godefray
authors.forename: E
authors.initials: E
authors.lastname: De Raucourt
authors.forename: M C
authors.initials: MC
authors.lastname: Guillin
mesh_terms: D000293:Adolescent; D000328:Adult; D001779:Blood Coagulation Factors / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D006801:Humans; D009154:Mutation / Q000235:genetics; D010958:Plasminogen / Q000378:metabolism; D011461:Prostaglandins F, Synthetic / Q000652:urine; D011486:Protein C / Q000378:metabolism; D017293:Protein S / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism; D019851:Thrombophilia / Q000150:complications* / Q000235:genetics / Q000652:urine; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D017086:beta-Thalassemia / Q000150:complications* / Q000652:urine
chemical_list: D001779:Blood Coagulation Factors; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D011461:Prostaglandins F, Synthetic; D011486:Protein C; D017293:Protein S; D011951:Receptors, Complement; C081960:11-dehydro-2,3-dinor-thromboxane B2; D013929:Thromboxane B2; C028291:2,3-dinor-6,15-diketo-13,14-dihydroprostaglandin F1alpha; D010958:Plasminogen