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 × 10⁹/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 (ADP₅ 0.46) and collagen 5 µmol/L (Col₅ 0.47). Splenic volume inversely correlated with the platelet count and a reduced response to arachidonic acid (AA), Col₅ and ADP₅ (p < 0.05). The splenectomized GDPs had a significantly lower platelet aggregation to Col₁₀ (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 ERT₆ (1/10; p < 0.01). The platelet count had significantly increased by ERT₆ (ERT₆ 180 × 10⁹/L, p < 0.01). The PT increased significantly from ERT₀ to ERT₂₄ (PT₀ 65%, PT₂₄ 81%; p < 0.05). The von Willebrand factor had increased significantly by ERT₆ and ERT₂₄ (ERT₀ 56%, ERT₆ 70%, ERT₁₂ 70%, ERT₂₄ 86%; p < 0.01). The number of GDPs with abnormal platelet aggregation had decreased significantly by ERT₆ (10/19; p < 0.05). Platelet aggregation on ADP₁₀ and AA significantly increased by ERT₆ (ADP₁₀: ERT₀ 0.75, ERT₆ 0.8 p < 0.01; AA: ERT₀ 0.7, ERT₆ 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.

• Gaucher's disease, bleeding, coagulation, platelet aggregation