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Coagulation abnormalities in patients with Gaucher's disease: effect of therapy
H H Billett1, S Rizvi, A Sawitsky
1Division of Hematology, Department of Pathology, Long Island Jewish Medical Center Campus, Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA.
Insights
Coagulation tests in Gaucher
Area of Science:
- Hematology
- Genetic Metabolic Disorders
Background:
- Gaucher's disease is linked to coagulation abnormalities.
- Previous studies suggest factor IX deficiency and acquired von Willebrand's disease (VWD).
Purpose of the Study:
- To investigate coagulation profiles in Gaucher's disease patients.
- To assess the impact of cerebroside accumulation on clotting factor assays.
Main Methods:
- Repeated coagulation assays over 2 years in 9 Gaucher's disease patients.
- Assessed prothrombin time (PT), partial thromboplastin time (PTT), factor IX, factor XI, anticardiolipin (ACL) IgM and IgG, factor VIII, and von Willebrand factor (VWF) antigen and activity.
- Evaluated assay results before and after alglucerase administration.
Main Results:
- PT and fibrinogen were mostly normal; PTT was often abnormal but corrected with mixing tests.
- Factor IX was normal; factor XI decreased in some patients.
- Factor VIII and VWF activity showed variability; ACL IgG was also variable.
- No significant improvement in coagulation assays post-alglucerase or over time.
- Some abnormalities were corrected by specimen dilution.
Conclusions:
- Previously reported factor IX and VWF decreases may be artifacts due to elevated cerebrosides.
- Caution is advised when interpreting clotting assays in Gaucher's disease patients.
- Cerebroside interference may explain observed coagulation anomalies.
Abstract:
Various coagulation defects have been associated with Gaucher's disease, including factor IX deficiency and acquired von Willebrand's disease (VWD). We performed repeated coagulation assays in 9 patients with Gaucher's disease over a period of 2 years. The prothrombin time (PT) and fibrinogen levels were normal in 8 of 9 patients, while the partial thromboplastin time (PTT) was abnormal in 5 of 9; all mixing PTT tests showed correction. Factor IX was normal repeatedly in the 7 of 7 patients tested. In contrast, factor XI was decreased in 3 of 9 patients assayed. Anticardiolipin (ACL) IgM was normal in all patients. ACL IgG was highly variable; levels were abnormal at least once in 6 of 8 patients, but were also normal at least once in 7 of 8 patients. Factor VIII was also quite variable: levels were decreased at least once in 4 of 9 patients, and normal at least once in 8 of 9 patients. Von Willebrand factor antigen (VWF Ag) studies were normal in 7 of 8 patients, but VWF activity was decreased at least once in 4 of 8 patients. In some patients, these problems could be overcome by specimen dilution. In ony 1 patient was VWF Ag decreased; this patient had a factor VIIIC level of 13% , and VWF activity of 18.7%. Coagulation assays performed before and after alglucerase administration failed to demonstrate any significant improvement in these assays, and neither was there a consistent improvement over the duration of therapy. We suggest that previously reported decreases in factor IX and VWF may be secondary to the interfering presence of increased cerebroside levels. Caution must be used in the interpretation of clotting assays in the patient with Gaucher's disease.