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

Abstract

SummaryThe 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 9 10 9 /l (n = 772); 100 to <120 9 10 9 /l (n = 94); 80 to <100 9 10 9 /l (n = 80); and <80 9 10 9 /l (n = 70; 20 with <60 9 10 9 /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 9 10 9 /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.

A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

“…Cases of GD without thrombocytopenia are observed. These cytopenias are attributed to splenic sequestration and bone marrow infiltration, but a direct impact of the enzyme deficiency on immature hematopoietic cells has also been described [26,129]. The blood count may be normal in patients with a history of splenectomy.…”

Splenomegaly, hypersplenism, and hereditary disorders with splenomegaly

“…Therefore, changes in splenomegaly in response to proposed treatments including ASM ERT that are currently in clinical trial may be a reasonable surrogate marker for evaluating response with the possible exception of pulmonary function where the correlation with spleen volume seems less certain [69,70]. A poor correlation between splenomegaly and platelet count that was observed in patients with NPD-B was also documented in patients with GD1, particularly for spleen volumes greater than 12 multiples of normal [8].…”

“…Although there was a statistically significant inverse correlation between spleen volume and red blood cell and platelet counts presumably attributable to more pronounced hypersplenism, the actual changes in cell counts per "fold-increase" in spleen size were clinically unimportant. Similarly, a recent report from the International Collaborative Gaucher Registry and Amsterdam Medical Center demonstrated that although splenomegalic patients with Gaucher disease with volumes in excess of 2000 mL almost always have persistent moderate to severe decreases in platelet count, the magnitude of thrombocytopenia differs relatively little over a spleen volume range of 2000 -5000 mL [8].…”

“…Solitary or multiple focal splenic nodules were reported present in 18.4% of patients with GD1 [95] although the prevalence may actually be greater because such nodules may not always be detected if MR imaging is restricted to T1-weighting. Patients with focal splenic lesions are more likely to have larger splenic volumes, more severe thrombocytopenia, and a greater prevalence of osteonecrosis than patients lacking these lesions and the response to treatment in terms of reduction in spleen size and improvement in platelet count may be less satisfactory [96] although not invariably so [8].…”

Plasma chitotriosidase activity versus CCL18 level for assessing type I Gaucher disease severity: protocol for a systematic review with meta-analysis of individual participant data

“…The secondary outcomes include symptomatic bone manifestations with imaging confirmation, a composite of massive hepatomegaly or splenomegaly, severe anemia or thrombocytopenia, and individual components of the primary and secondary composite outcomes. Cut-off values for continuous parameter are set according to published guidelines or previous studies [28, 29]. …”