Brain-Derived Neurotrophic Factor (BDNF) Is Associated with Platelet Activity and Bleeding Tendency in Patients with Gaucher Disease.

Bleeding tendency, a prominent feature of patients with Gaucher disease (GD), is associated with abnormal platelet function. Brain-derived neurotrophic factor (BDNF) is a protein with neuroprotective potential stored in alpha granules of circulating platelets. Here we studied BDNF levels in 50 patients with type I GD (GD1) and their correlation with platelet activity and bleeding tendency. Flow cytometry was used to test unstimulated and stimulated measurement of platelet surface-activated expression of αIIbß3 integrin, P-selectin and lysosomal-associated membrane protein (LAMP3/CD63). Serum and plasma BDNF levels were quantified using ELISA. The bleeding history was recorded by a bleeding questionnaire. Serum BDNF levels were positively correlated with platelet count and moderately correlated with unstimulated and stimulated platelet P-selectin expression. Patients with more than one bleeding manifestation were shown to have lower serum BDNF levels, albeit similar platelet count. Plasma BDNF levels were significantly elevated in splenectomized patients and showed a moderate positive correlation with stimulated platelet CD63 expression. These observations demonstrate the first association between BDNF levels in the peripheral blood with platelet dysfunction and increased bleeding manifestation. The role of measuring serum BDNF for assessing platelet alpha degranulation defects and bleeding risk in patients with GD and the general population needs further study.

Platelet Activation and Reactivity in a Large Cohort of Patients with Gaucher Disease.

OBJECTIVES: Patients with Gaucher disease (GD) are at increased risk of bleeding and have varying degrees of thrombocytopenia, making the analysis of platelet function difficult. This study aimed to provide a clinically relevant quantitative assessment of platelet function and determine its relationship with bleeding and GD-related data. METHODS: Unstimulated and stimulated platelet function was measured by whole blood flow cytometry of platelet surface-activated αIIbß3 integrin (detected with monoclonal antibody PAC1), P-selectin (CD62P), and lysosomal-associated membrane protein (LAMP3/CD63) in 149 GD patients. RESULTS: GD patients had a higher level of unstimulated CD63 expression than healthy subjects, which was mildly correlated with glucosylsphingosine (lyso-Gb1) levels (r = 0.17, p-value = 0.042). Splenectomized GD patients had a higher level of unstimulated αIIbß3 integrin and P-selectin expression. Reduced platelet reactivity (-2 standard deviation of reference range) was found in 79 (53%, 95% confidence interval [CI]: 44-61%) patients, of whom 10 (6.7%, 95% CI: 3.3-12%) had more severe platelet dysfunction. In a multivariate model, only lyso-Gb1 levels were associated with the more severe platelet dysfunction. Fifty-four (49%) of 128 adult patients who completed the bleeding tendency questionnaire reported positive bleeding history. In a multivariate logistic model, older age (odds ratio [OR]: 1.05, 95% CI: 1.01-1.1) and low P-selectin reactivity (OR: 2.03, 95% CI: 1.25-3.35) were associated with more than one bleeding manifestation. CONCLUSION: Flow cytometry enables the study of platelet function in thrombocytopenic GD patients. A platelet degranulation defect, but not αIIbß3 integrin activation defect, is associated with clinical bleeding. In vivo increased CD63 expression may be related to GD-related inflammation.

The Predictive Value of Thromboelastogram in the Evaluation of Patients with Suspected Acute Venous Thromboembolism.

INTRODUCTION: The objective of this prospective study was to examine whether thromboelastogram (TEG) can predict the presence of venous thromboembolism (VTE) in patients who arrive at the emergency room with signs/symptoms that raise the suspicion of acute VTE. METHODS: Every patient was tested for D-dimer and all TEG parameters, including: reaction time, clot time formation, alpha-angle, maximal amplitude, clot viscoelasticity, coagulation index, and clot lysis at 30 min. For categorical variables, χ2 or the Fisher exact test were used, and for continuous variables the t test or other non-parametric tests were used. RESULTS: During 2016, a total of 109 patients were enrolled with a median age of 55.7 (21-89) years. Eighteen patients were diagnosed with VTE. Analyzing the different TEG parameters, both as continuous and categorical variables, did not reveal a statistically significant difference between VTE-positive and VTE-negative patients. Combining different TEG parameters or dividing the cohort according to gender, clinical suspicion of VTE (Well's criteria), or different levels of D-dimer did not change the results of the analysis. CONCLUSION: The current study could not demonstrate a significant value of any TEG parameter as a predictor of VTE among patients who came to the emergency room with signs/symptoms that raise the suspicion of VTE.

Patient blood management programs: how to spread the word?

Red blood cell (RBC) transfusions save lives and improve health; however, unnecessary transfusion practice exposes patients to immediate and long-term negative consequences. Indirect consequences of unnecessary transfusions are the reduced availability of RBC units for patients who are in need. Accumulating evidence shows that restricting RBC transfusions improves outcomes and current guidelines suggest limiting RBC transfusion to the minimum number of units required to relieve symptoms of anemia or to return the patient to a safe hemoglobin range (7-8 g/dl in stable, non-cardiac inpatients). Still, studies show that there is over-utilization of RBC transfusion, partly due to low level of knowledge of physicians regarding restrictive RBC transfusion policy across a broad range of professions and specialties. Patient blood management (PBM) programs have been developed to promote clear hospital transfusion guidelines, strive for optimization of patient hemoglobin and iron stores and, most importantly, improve education regarding restrictive RBC policy. Understanding what and where the gaps of knowledge are, as was done in the study by Dr. Koren and his colleagues, is an important step for developing effective PBM programs.

Thromboelastography as a Surrogate Marker of Perisurgical Hemostasis in Gaucher Disease.

Thromboelastography (TEG) has long been available for routine monitoring of perisurgical and postpartum hemostasis, especially at point of care. The purpose of this study is to retrospectively compare TEG parameters to concomitant standard clotting test results in an unselected cohort of patients with Gaucher disease to ascertain whether TEG values are specific and sensitive enough to substitute for classic coagulation tests for decision making. This remains a cogent concern because of high incidence of thrombocytopenia in patients with Gaucher disease. Thromboelastography values were compared to concomitant platelet counts, partial thromboplastin time, international normalization ratio, and plasma fibrinogen. Demographic characteristics were collected from patients' files. There were 22 patients with Gaucher disease (2 children; 12.5%) for whom there were 24 TEG results at the same time as classic coagulation test results and 30% performed platelet function tests. The current study shows linear and/or monotonic relationships between platelet counts and several TEG values that were significant over a range of platelet counts including severe thrombocytopenia. The fibrinogen component, correlating only with the rate of clot lysis, played a lesser role. Based on these preliminary results albeit in a small cohort with only 1 case of hemorrhage, there is putative support for the intention to treat patients with Gaucher disease based on TEG results using the same TEG protocol as for other patients undergoing comparable procedures in our institution.