Characteristics of type I Gaucher disease associated with persistent thrombocytopenia after treatment with imiglucerase for 4-5 years

• Published in: British journal of haematology Vol. 158; no. 4; pp. 528 - 538
• Main Authors: Hollak, Carla E. M., Belmatoug, Nadia, Cole, J. Alexander, vom Dahl, Stephan, Deegan, Patrick B., Goldblatt, Jack, Rosenbloom, Barry, van Dussen, Laura, Tylki-Szymańska, Anna, Weinreb, Neal J., Zimran, Ari, Cappellini, Maria Domenica
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01.08.2012; Blackwell
• Subjects: Adult; Aged; Anemia - etiology; Biological and medical sciences; enzyme replacement therapy; Enzyme Replacement Therapy - methods; Errors of metabolism; Female; Gaucher disease; Gaucher Disease - blood; Gaucher Disease - complications; Gaucher Disease - drug therapy; Glucosylceramidase - therapeutic use; Hematologic and hematopoietic diseases; Humans; imiglucerase; Lipids (lysosomal enzyme disorders, storage diseases); Male; Medical sciences; Metabolic diseases; Middle Aged; Platelet Count; Platelet diseases and coagulopathies; Recombinant Proteins - therapeutic use; Registries; Retrospective Studies; Splenomegaly - blood; Splenomegaly - etiology; thrombocytopenia; Thrombocytopenia - blood; Thrombocytopenia - etiology; Young Adult; Thrombocytopenia; Nervous system diseases; Replacement therapy; enzyme replacement therapy; Hematology; Enzyme; Metabolic diseases; Lipids; Hemopathy; Enzymopathy; Genetic disease; Cerebral disorder; Glycosylases; Imiglucerase; Platelet; Gaucher disease; Glycosidases; Central nervous system disease; Hydrolases; Glucosylceramidase; Lipoidosis
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2012.09175.x

Summary The characteristics of Gaucher disease (GD) associated with persistent thrombocytopenia despite imiglucerase enzyme therapy in type 1 GD (GD1) were investigated by retrospective analysis of International Collaborative Gaucher Group (ICGG) Registry data. The study involved 1016 GD1 patients with an intact spleen for whom date of diagnosis, therapy initiation, and platelet counts were known, and who received continuous imiglucerase therapy for 4 to 5 years. These patients were stratified by last platelet count: ≥120 × 109/l (n = 772); ≥100 to <120 × 109/l (n = 94); ≥80 to <100 × 109/l (n = 80); and <80 × 109/l (n = 70; 20 with <60 × 109/l) and characterized by initial and cumulative average imiglucerase dose, body mass index, platelet count, anaemia, hepatomegaly, splenomegaly, and skeletal assessments at baseline and after 4–5 years of therapy. Statistically significant associations were found between persistent thrombocytopenia and baseline platelet count (<80 × 109/l), splenomegaly, and anaemia (all P < 0·0001). After 4–5 years, statistically significant associations were found with splenomegaly (P < 0·0001), anaemia (P < 0·0001), white blood cell count (P = 0·049), hepatomegaly (P = 0·004) and bone pain (P = 0·035). Exponential platelet decay in relation to splenomegaly suggests that platelets increase only when spleen volume decreases substantially.