Coagulation Abnormalities in Type 1 Gaucher Disease in Children

Abstract

Gaucher disease is the most prevalent inherited lysosomal storage disorder caused by deficiency of beta-glucocerebrosidase enzyme. Clinically, 3 forms of Gaucher disease are recognized, of which type 1 is the mild to moderately severe, slowly progressive, nonneuropathic form. Bleeding disorders in Gaucher disease are believed to be due to thrombocytopenia but there may be additional factors that influence coagulation and fibrinolysis in Gaucher disease patients. The aim of the present work was to study some coagulation parameters in the Egyptian children with type 1 Gaucher disease. Five newly diagnosed patients and another 5 patients on enzyme replacement therapy (ERT) were enrolled in the study. Their coagulation profile, including coagulation factors, was evaluated. The results showed that in newly diagnosed cases factors II and VII were deficient in 40%, factor V was deficient in 20%, and all the cases had low levels of serum fibrinogen. In patients on ERT, factors VII and VIII were deficient in 60%, factor XI was deficient in 40% and factors V, X, and XII were deficient in 20% of cases. In conclusion, Egyptian patients with type 1 Gaucher disease, whether newly diagnosed or receiving enzyme replacement therapy, experience coagulation factor abnormalities regardless the clinical expression of bleeding diathesis. This should be taken into consideration before these patients are subjected to surgery for, e.g., splenectomy, which is common in these patients.

A cytometric study of the red blood cells in Gaucher disease reveals their abnormal shape that may be involved in increased erythrophagocytosis

“…Our finding suggests that schistocytes are more frequent in childhood-onset GD than has previously been reported (17). This is consistent with the finding of low-grade coagulation activation in GD patients (31,32) accounting for fibrin strand formation. The presence of schistocytes suggests intravascular hemolysis but biological makers of hemolysis are normal in most anemic patients (17), though a slight decrease of the seric haptoglobin level may be found in some of them (J. Strinemann, personal communication).…”

Haematological manifestations and complications of Gaucher disease

“…For example, there may be coinheritance of genetic factor XI deficiency among Ashkenazi Jewish patients. In a study of newly diagnosed and previously treated Egyptian patients, factors II, V and VII and fibrinogen were deficient in all newly diagnosed patients and factors V, VII, VIII, X, XI and XII were noted to be reduced to various extents in patients receiving ERT [22]. Markers for activation of coagulation (thrombin-antithrombin complex) and fibrinolysis (PAP complex, fibrin cleavage product D-dimer) were significantly elevated, especially in the splenectomized patients.…”

Gaucher Disease

“…Liver enzymes may be elevated 40 and coagulation factor deficiencies 53 causing abnormal clotting have been described in addition to platelet function problems. Platelet adhesion defect and not aggregation defects contribute to the thrombocytopathy in GD patients and therefore predispose to an increased tendency to bleeding.…”