Summary Patients with type I Gaucher Disease (GD) may have a clinically significant bleeding tendency that is disproportionate to their platelet count. We hypothesized that impaired platelet adhesion might contribute to bleeding tendency. Adult patients with type I GD with platelet counts ≥130 × 109/l and haematocrit ≥30% (n = 48), obligatory carriers (n = 52), and healthy controls (n = 19) were studied. Platelet adhesion, using the IMPACT‐R (Cone and Plate(let) Analyser), and platelet aggregation were determined. Type I GD patients had significantly lower platelet adhesion [surface coverage %, median (interquartile range)] 4·6 (3·2–7·5), compared to controls, 8·7 (7·6–10·3), or carriers, 8·1 (6·5–9·4; P = 0·001). Platelet adhesion was not affected by the use of disease‐specific enzyme replacement therapy but was improved in patients after splenectomy, 7·2 (5·8–9·3). Mixing tests showed that the reduced adhesion was an intrinsic platelet defect. Mucosal bleeding was reported in 17 (35·4%) patients and was associated with abnormal adhesion [P = 0·037, with an Odds Ratio (95% confidence interval) of 5·73 (1·1–29·6)]. Five patients (22%) had reduced platelet aggregation, all of whom had reduced platelet adhesion. Platelet aggregation defect was not associated with mucosal bleeding. In conclusion, platelet adhesion defect is a major thrombocytopathy in type I GD patients and can explain part of the increased tendency to bleeding.

Transverse myelitis is an inflammatory lesion of the spinal cord, occurring in different autoimmune, infectious, and traumatic diseases but is the hallmark of neuromyelitis optica (NMO), a rare neurologic autoimmune disease. Patients with systemic lupus erythematosus (SLE) may develop transverse myelitis as a neuropsychiatric complication of active disease; however, at times, NMO co-exists as an additional primary autoimmune condition in a SLE patient. Correct diagnosis of a SLE–NMO overlap is important not only for the different disease course and prognosis compared with SLE-related LETM, but especially for the emerging and highly specific NMO treatment options, not established for SLE-related LETM—such as anti-aquaporin 4 antibodies, anti-VEGF antibodies, complement modulation, or IVIg.

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Background: Bleeding diathesis is a common manifestation of Gaucher disease, usually attributed to thrombocytopenia due to hypersplenism and bone marrow infiltration by Gaucher cells. Hemorrhagic manifestations are not restricted to thrombocytopenic patients, and other mechanisms, e.g. platelet function defect, manifested in abnormal aggregation, have also been implicated. Aim: to evaluate platelet adhesion properties in Gaucher patients. Methods: Platelet function was studied in 44 Gaucher patients with a platelet count of ≥130×109/L, using a novel method for quantitative analysis of whole blood platelet interaction with immobilized plasma ligands under flow conditions, the Impact-R [Cone and Plate(let) analyzer] test. The results were compared to platelet function of 51 obligatory Gaucher carriers, 20 healthy volunteers and 5 transgenic Gaucher mice. Platelet’s glucocerebrosidase function was tested in platelet’s extract by incubation with C6-NBD-glucosylceramide, and by testing the fluorescence intensity of the end product, C6-NBD-ceramide. Results: Adhesion defect, manifested by surface coverage (SC) < 7.0%, was found in 70.4% of the patients (SC 5.1%±3.1), in 41.2% of the Gaucher carriers (SC 7.7%±2.8) and only in 20% of the control group (SC 8.7%±3.2, P=0.0007 and 0.09, respectively). This defect was independent of platelet count, or hematocrit. Further support for this observation was found in transgenic Gaucher mice, who also had low platelet adhesion compared to wild type mice (SC of 2.7%±0.6 vs. 12.5%±2.9, respectively). Average size of platelet aggregates was lower in Gaucher patients with bleeding tendency, compared to those with no bleeding history (23.5 μm2±12 and 29.2±10, p=0.026). A trend for lower SC in bleeders vs. non bleeders was also found (4.3±3.7 vs. 6.4±3.9, p=0.069). No difference was found in platelet counts between bleeder and non-bleeders (p=0.13). Surface coverage was higher in splenectomized patients and in patients receiving enzyme replacement therapy. Highest SC was observed in patients under both treatment modalities, SC= 8±4.6, compared to those treated with one modality, 4.9±3.7, and untreated ones, 3.3±2.3 (p=0.01). These differences were independent of platelet count. In order to elucidate the potential role of glucoceramide in the adhesion defect, we tested platelet’s glucocerebrozidase function in patients and controls. The specific activity thus calculated in 5 mildly thrombocytopenic Gaucher patients was 0.02–0.08 pmol/min/μgr protein compared to specific activity of 0.14-0.15 pmol/min/μg protein in platelet homogenate of 3 healthy volunteers. Conclusions: platelet adhesion defect is common in Gaucher disease, which may account for bleeding events in some patients with normal platelet count. Accumulation of glucoceramide in Gaucher platelets may be responsible for this defect. Further studies into the potential role of the stored material in the adhesion defect and bleeding phenomena in Gaucher is warranted.