Impaired platelet function and peripartum bleeding in women with Gaucher disease

Abstract

The risk of bleeding during delivery may be increased in women with Gaucher disease. We aimed to evaluate potential predictors for peripartum haemorrhage (PPH) during childbirth in these patients, while focusing upon coagulation tests and platelet function assays. Women with type 1 Gaucher disease who gave birth at Sheba Medical Center between 1999-2009 comprised the study cohort. Data collected included disease history, enzyme treatment, platelet counts, delivery and pregnancy outcome. PPH was defined as excessive bleeding during or immediately following delivery. Coagulation studies and platelet function tests, including aggregometry and cone and platelet (CPA) analyses, were performed on all women. We compared women with PPH (bleeders) and non-bleeders. Furthermore, women with abnormal CPA platelet function tests were compared with those with normal CPA platelet function with regards to the risk for PPH in at least one pregnancy. Forty-five pregnancies of 20 women were studied. Six women received enzyme replacement therapy during pregnancy. Mean platelet count prior to delivery was 83,000/μl ± 35,000/μl. Fourteen out of 45 (31%) deliveries were complicated by PPH. Neither thrombocytopenia nor enzyme therapy predicted PPH. Twelve out of 13 women with PPH (92.3%) versus 2/7 non-bleeders (28.6%) had impaired platelet aggregation (less than the 3rd percentile of normal average aggregate size values), when tested by CPA, (odds ratio [OR] 17.8, 95% confidence interval [CI] 2.5; 126.2; p=0.007). Notably, 78.6% of women with impaired CPA aggregation developed PPH during at least one delivery, as opposed to 16.7% of those with normal CPA platelet function tests (OR 11.6, 95% CI 1.7-77.7, p=0.018). In conclusion, women with type 1 Gaucher disease who have abnormal platelet function tests may have an increased risk of PPH.

Outcome of pregnancies in women receiving velaglucerase alfa for Gaucher disease

“…Thus, although experience seems to point to a rather benign course during pregnancy and the post‐partum period for most patients with type 1 Gaucher disease, some patients with more severe manifestations, and patients with other causes for bleeding including inherited coagulation factor deficiencies (e.g. Factor XI among Ashkenazi Jews), may not all have an uneventful outcome even while being treated with ERT.…”

Haematological manifestations and complications of Gaucher disease

“…Enzyme replacement therapy before and during pregnancy has demonstrated benefits in reducing the risk of spontaneous abortion and Gaucher disease-related complications, especially bleeding during delivery and postpartum[26,27].Enlargement of the liver and spleen are common in untreated Gaucher disease type 1, and splenic nodules which can be mistaken for malignancy may be seen, particularly in individuals with massive splenomegaly(Fig. Pregnancy also has the potential to exacerbate Gaucher disease manifestations, and the risk of bleeding during delivery may be increased in women with Gaucher disease.…”

Thromboelastography as a Surrogate Marker of Perisurgical Hemostasis in Gaucher Disease

“…Platelet function testing was performed at the National Hemophilia Center as previously described. 13,17 In brief, aggregations were performed on a 4-channel optical aggregometer (aggram, Helena laboratories, Beaumont, Texas). Epinephrine (5 mg/mL), ADP (1.0 mmol/L), collagen (1.0 mg/mL, final concentration), and ristocetin (0.5 and 1.5 mg/mL) were used as agonists.…”

“…8 Heretofore, it had been recommended that, in addition to routine coagulation profiles, platelet function tests 9 are required [10][11][12] in Gaucher disease presurgery and/or delivery. 13 Second, there are coagulopathies that impact tendency to bleed even in nonthrombocytopenic patients who are partly responsive to ERT. 14 Finally, there are coagulation factor deficiencies that are relatively more prevalent among Ashkenazi Jews who have a predilection for the nonneuronopathic form of Gaucher disease.…”