title: Coagulation abnormalities in type 1 Gaucher disease are due to low-grade activation and can be partly restored by enzyme supplementation therapy.
abstract: In type 1 Gaucher disease a bleeding tendency occurs which is partly caused by thrombocytopenia due to massive splenomegaly. In addition, low levels of factors IX and XI have been described. The mechanism responsible for these clotting factor abnormalities is unknown. We performed a detailed study of parameters of coagulation and fibrinolysis in 30 type 1 Gaucher disease patients (14 splenectomized) before and after treatment with enzyme supplementation therapy. Pre-treatment aPTT and PT were prolonged in 42% and 38% of patients, respectively. In 30-60% serious deficiencies (< 50%) of coagulation factors XI, XII, VII, X, V and II were observed. The low levels of factor V correlated with platelet count and were inversely associated with splenic volume. Levels of inhibitors were mildly decreased. Markers for activation of coagulation (thrombin-antithrombin (TAT) complex) and fibrinolysis (PAP complex, fibrin cleavage product D-dimer) were significantly elevated, especially in the splenectomized patients, indicating ongoing activation of these processes. After 12 months of enzyme supplementation therapy partial correction occurred. Thus, severe disorders of the coagulation system occur in Gaucher disease, contributing to the bleeding tendency. The deficiencies may be the result of consumption of coagulation factors caused by ongoing low-level coagulation activation. possibly due to mononuclear cell activation.
authors.affiliation: Department of Internal Medicine and Haematology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: C E
authors.initials: CE
authors.lastname: Hollak
authors.forename: M
authors.initials: M
authors.lastname: Levi
authors.forename: F
authors.initials: F
authors.lastname: Berends
authors.forename: J M
authors.initials: JM
authors.lastname: Aerts
authors.forename: M H
authors.initials: MH
authors.lastname: van Oers
mesh_terms: D000328:Adult; D000368:Aged; D001778:Blood Coagulation Disorders / Q000188:drug therapy*; D001779:Blood Coagulation Factors / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005342:Fibrinolysis; D005776:Gaucher Disease / Q000097:blood* / Q000150:complications; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010976:Platelet Count; D011517:Prothrombin Time; D013156:Splenectomy
chemical_list: D001779:Blood Coagulation Factors; D001798:Blood Proteins; C070292:alglucerase; D005962:Glucosylceramidase