title: Haemostatic abnormalities in treatment-naïve patients with Type 1 Gaucher's disease.
abstract: There is a paucity of data on the effects of enzyme replacement therapy (ERT) on the coagulation abnormalities and platelet function of patients with Gaucher's disease (GDPs) and much of this data are controversial. This study investigates the haemostatic parameters in treatment-naïve GDPs and the effects of ERT. 31 Serbian treatment-naïve type 1 GDPs (M/F 17/14; median age 49 years, splenectomized 9/31) were studied. The complete blood count, prothrombin time (PT), activated partial tromboplastin time (aPTT) and coagulation factors were measured using the standard methods. Platelet aggregation was assessed with a whole-blood aggregometer. Splenic volumes were assessed using computer tomography. Twenty-one patients were treated with ERT (Imiglucerase). The haemostatic parameters were assessed after 6, 12 and 24 months (ERT(6, 12, 24)). Initially bleeding episodes were registered in 10/31 GDPs. Median platelet count was 108 × 10(9)/L; 22/31 GDPs were thrombocytopenic. The PT and aPTT values were abnormal in 16/31 and 13/31 GDPs, respectively. Platelet aggregation abnormalities were recorded in 19/31GDPs. Median platelet aggregation was reduced in response to adenosine-diphosphate 5 µmol/L (ADP(5) 0.46) and collagen 5 µmol/L (Col(5) 0.47). Splenic volume inversely correlated with the platelet count and a reduced response to arachidonic acid (AA), Col(5) and ADP(5) (p < 0.05). The splenectomized GDPs had a significantly lower platelet aggregation to Col(10) (p < 0.05). Bleeding GDPs had a significantly lower platelet count, higher chitotriosidase levels and a greater splenic volume compared to non-bleeding patients (p < 0.01). ERT: The number of bleeding GDPs had significantly decreased by ERT(6) (1/10; p < 0.01). The platelet count had significantly increased by ERT(6) (ERT(6) 180 × 10(9)/L, p < 0.01). The PT increased significantly from ERT(0) to ERT(24) (PT(0) 65%, PT(24) 81%; p < 0.05). The von Willebrand factor had increased significantly by ERT(6) and ERT(24) (ERT(0) 56%, ERT(6) 70%, ERT(12) 70%, ERT(24) 86%; p < 0.01). The number of GDPs with abnormal platelet aggregation had decreased significantly by ERT(6) (10/19; p < 0.05). Platelet aggregation on ADP(10) and AA significantly increased by ERT(6) (ADP(10): ERT(0) 0.75, ERT(6) 0.8 p < 0.01; AA: ERT(0) 0.7, ERT(6) 0.8 p < 0.05). In conclusion, platelet dysfunction and coagulation abnormalities were found in a considerable number of our GDPs. The absence of severe bleeding episodes suggests that the haemostatic system is sufficiently balanced and therefore the exact mechanism of the etiology of these abnormalities need to be fully clarified. ERT resulted in the cessation of bleeding and marked increase in platelet count, PT, vWF and platelet aggregation.
authors.affiliation: Clinics of Hematology CCS, 2, Koste Todorovica, Beograd 11000, Serbia. mmg@beotel.net
authors.forename: Mirjana
authors.initials: M
authors.lastname: Mitrovic
authors.forename: Darko
authors.initials: D
authors.lastname: Antic
authors.forename: Ivo
authors.initials: I
authors.lastname: Elezovic
authors.forename: Dragana
authors.initials: D
authors.lastname: Janic
authors.forename: Predrag
authors.initials: P
authors.lastname: Miljic
authors.forename: Zorica
authors.initials: Z
authors.lastname: Sumarac
authors.forename: Tanja
authors.initials: T
authors.lastname: Nikolic
authors.forename: Nada
authors.initials: N
authors.lastname: Suvajdzic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy / Q000379:methods*; D005260:Female; D005776:Gaucher Disease / Q000097:blood* / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006470:Hemorrhage / Q000097:blood / Q000209:etiology; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D013154:Spleen / Q000503:physiopathology; D055815:Young Adult
chemical_list: D005962:Glucosylceramidase; C090568:imiglucerase