Clinical impact of glycans in platelet and megakaryocyte biology

Blood ◽  
2022 ◽  
Author(s):  
Leonardo Rivadeneyra ◽  
Hervé Falet ◽  
Karin Hoffmeister

Humans produce and remove 1011 platelets daily to maintain a steady-state platelet count. The production of platelets by bone marrow megakaryocytes and their removal from the blood circulation are tightly regulated mechanisms, and abnormalities in both processes can result in thrombocytopenia (low platelet count) or thrombocytosis (high platelet count), often associated with the risk of bleeding or overt thrombus formation, respectively. This review focuses on the role of glycans, also known as carbohydrates or oligosaccharides, including N- and O-glycans, proteoglycans, and glycosaminoglycans, in human and mouse platelet and megakaryocyte physiology. Based on recent clinical observations and mouse models, we focused on the pathological aspects of glycan biosynthesis and degradation and its effects on platelet numbers and megakaryocyte function.

Blood ◽  
2009 ◽  
Vol 113 (3) ◽  
pp. 526-534 ◽  
Author(s):  
Augusto B. Federici ◽  
Pier M. Mannucci ◽  
Giancarlo Castaman ◽  
Luciano Baronciani ◽  
Paolo Bucciarelli ◽  
...  

Abstract Type 2B von Willebrand disease (VWD2B) is caused by an abnormal von Willebrand factor (VWF) with increased affinity for the platelet receptor glycoprotein Ib-α (GPIb-α) that may result in moderate to severe thrombocytopenia. We evaluated the prevalence and clinical and molecular predictors of thrombocytopenia in a cohort of 67 VWD2B patients from 38 unrelated families characterized by VWF mutations. Platelet count, mean platelet volume, and morphologic evaluations of blood smear were obtained at baseline and during physiologic (pregnancy) or pathologic (infections, surgeries) stress conditions. Thrombocytopenia was found in 20 patients (30%) at baseline and in 38 (57%) after stress conditions, whereas platelet counts were always normal in 16 patients (24%) from 5 families carrying the P1266L/Q or R1308L mutations. VWF in its GPIb-α–binding conformation (VWF–GPIb-α/BC) was higher than normal in all except the 16 cases without thrombocytopenia (values up to 6-fold higher than controls). The risk of bleeding was higher in patients with thrombocytopenia (adjusted hazard ratio = 4.57; 95% confidence interval, 1.17-17.90) and in those with the highest tertile of bleeding severity score (5.66; 95% confidence interval, 1.03-31.07). Prediction of possible thrombocytopenia in VWD2B by measuring VWF–GPIb-α/BC is important because a low platelet count is an independent risk factor for bleeding.


2020 ◽  
Vol 18 (2) ◽  
pp. 522-523
Author(s):  
Marie Warny ◽  
Jens Helby ◽  
Henrik S. Birgens ◽  
Stig E. Bojesen ◽  
Børge G. Nordestgaard

2020 ◽  
Author(s):  
Qingshan Li ◽  
Yue Wang ◽  
Tao Ma ◽  
Fenggang Ren ◽  
Fan Mu ◽  
...  

Abstract Background The role of platelets on the prognosis of patients with liver transplantation remains unclear. Thus, we aimed to evaluate the influence of preoperative platelet count on postoperative morbidity after liver transplantation. Methods Clinical data of the patients who received liver transplantation from January 2015 to September 2018 were evaluated. Results Of the 329 patients included, the average age was 46.71 ± 0.55 years, and 243 were men (75.2%). The incidence of posttransplant portal vein complication was significantly higher in the high platelet count group (> 49.5 × 109/L; n = 167) than in the low platelet count group (≤ 49.5 × 109/L, n = 162, 12.6% vs. 1.9%). After multivariable regression analysis, high platelet count was independently associated with postoperative portal vein complication (odds ratio [OR]: 8.821, 95% confidence interval [CI]: 2.260 to 34.437). After the inverse probability of treatment weighting analysis, patients in the high platelet count group had significantly higher risk of portal vein complication (OR: 9.210, 95%CI: 1.907 to 44.498, p = 0.006) and early allograft dysfunction (OR: 2.087, 95%CI: 1.131 to 3.853, p = 0.019). Conclusions Preoperative platelet count > 49.5 × 109/L was an independent risk factor for posttransplant portal vein complication and early allograft dysfunction. High preoperative platelet count could be an adverse prognostic predictor for liver transplantation recipients.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xiao-Qing Quan ◽  
Hong-Yan Ji ◽  
Jie Jiang ◽  
Jia-Bao Huang ◽  
Cun-Tai Zhang

Background and Aim. Acute myocardial infarction represents the vital cause of cardiac death, and many measurable biomarkers have been reported to be related to the prognosis of acute myocardial infarction. Our study was to investigate the role of a novel biomarker, the combination of platelet count, and neutrophil-to-lymphocyte ratio, for predicting in-hospital and long-term mortality of aged patients with acute myocardial infarction. Method. This was a study recording 637 patients who were diagnosed with acute myocardial infarction. Our patients were grouped according to the combination of platelet count and neutrophil-to-lymphocyte ratio. The prognostic role of the combination of platelet count and neutrophil-to-lymphocyte ratio on mortality was assessed by the univariate and multivariate Cox regression analysis. Result. Our study population was divided into three parts according to the median values of platelet count and neutrophil-to-lymphocyte ratio. It was indicated that platelet count and neutrophil-to-lymphocyte ratio were correlative mutually to a certain degree ( p = 0.010 ). The Kaplan–Meier analysis showed that the combination of high platelet count and high neutrophil-to-lymphocyte ratio had a greater risk of death in short- and long-term endpoints (log-rank p = 0.046 , p < 0.001 , respectively). Moreover, by multivariate analysis, both high platelet count and high neutrophil-to-lymphocyte ratio groups were an independent predictor (hazard ratio: 2.132, 95% confidence interval: 1.020–4.454, p = 0.044 ) and long-term mortality (hazard ratio: 2.791, 95% confidence interval: 1.406–5.538, p = 0.003 ). Conclusion. The combination of platelet count and neutrophil-to-lymphocyte ratio could be a useful predictor for the prediction of in-hospital and long-term mortality in aged patients with acute myocardial infarction.


2020 ◽  
Author(s):  
Qingshan Li ◽  
Yue Wang ◽  
Tao Ma ◽  
Fenggang Ren ◽  
Fan Mu ◽  
...  

Abstract Background: The role of platelets on the prognosis of patients with liver transplantation remains unclear. Thus, we aimed to evaluate the influence of preoperative platelet count on postoperative morbidity after liver transplantation. Methods: Clinical data of the patients who received liver transplantation from January 2015 to September 2018 were evaluated. Results: Of the 329 patients included, the average age was 46.71±0.55 years, and 243 were men (75.2%). The incidence of posttransplant portal vein complication was significantly higher in the high platelet count group (> 49.5×109/L; n=167) than in the low platelet count group (≤ 49.5×109/L, n=162, 12.6% vs. 1.9%). After multivariable regression analysis, high platelet count was independently associated with postoperative portal vein complication (odds ratio [OR]: 8.821, 95% confidence interval [CI]: 2.260 to 34.437). After the inverse probability of treatment weighting analysis, patients in the high platelet count group had significantly higher risk of portal vein complication (OR: 9.210, 95%CI: 1.907 to 44.498, p=0.006) and early allograft dysfunction (OR: 2.087, 95%CI: 1.131 to 3.853, p=0.019). Conclusions: Preoperative platelet count > 49.5×109/L was an independent risk factor for posttransplant portal vein complication and early allograft dysfunction. High preoperative platelet count could be an adverse prognostic predictor for liver transplantation recipients.


2020 ◽  
Author(s):  
Qingshan Li ◽  
Yue Wang ◽  
Tao Ma ◽  
Fenggang Ren ◽  
Fan Mu ◽  
...  

Abstract Background: The role of platelets on the prognosis of patients with liver transplantation remains unclear. Thus, we aimed to evaluate the influence of preoperative platelet count on postoperative morbidity after liver transplantation.Methods: Clinical data of the patients who received liver transplantation from January 2015 to September 2018 were evaluated.Results: Of the 329 patients included, the average age was 46.71±0.55 years, and 243 were men (75.2%). The incidence of posttransplant portal vein complication was significantly higher in the high platelet count group (> 49.5×109/L; n=167) than in the low platelet count group (≤ 49.5×109/L, n=162, 12.6% vs. 1.9%). After multivariable regression analysis, high platelet count was independently associated with postoperative portal vein complication (odds ratio [OR]: 8.821, 95% confidence interval [CI]: 2.260 to 34.437). After the inverse probability of treatment weighting analysis, patients in the high platelet count group had significantly higher risk of portal vein complication (OR: 9.210, 95%CI: 1.907 to 44.498, p=0.006) and early allograft dysfunction (OR: 2.087, 95%CI: 1.131 to 3.853, p=0.019).Conclusions: Preoperative platelet count > 49.5×109/L was an independent risk factor for posttransplant portal vein complication and early allograft dysfunction. High preoperative platelet count could be an adverse prognostic predictor for liver transplantation recipients.


1987 ◽  
Author(s):  
A Bernat ◽  
E Vallée ◽  
J P Maffrand ◽  
J Gordon

Venous stasis in the rat, induced by ligature of the vena cava, provokes thrombosis. This venous thrombosis was initially believed to be platelet-independent because severe thrombocytopenia (95 % reduction in platelet count), aspirin and dipyridamole had little effect. However, the model responded to other platelet anti-aggregators, such as Ticlopidine and its analogue PCR 4099, although these compounds had no effect on coagulation, fibrinolysis or leucocyte functions (Thromb. Res. 37, 279-285, 1985). Both these drugs are known to exert their main antiplatelet effect against aggregation induced by ADP.The aim of the present study was to re-evaluate the role of platelets in this model of venous thrombosis. We have been able to show that :1) complete thrombocytopenia (99 %), achieved with an antiplatelet anti-serum, dramatically inhibited thrombus formation (by 84 % ; p < 0.01).2) partial transfusion of platelets (23 %) from control animals to these thrombocytopenic rats re-established the thrombosis.3) transfusion (under identical conditions) of platelets from rats treated with PCR 4099 had no effect.4) vena cava ligature in Fawn Hooded rats (deficient in platelet dense granules) induced less thrombosis (64 % of control ; p < 0.05).We conclude that this venous stasis model is platelet-dependent. Furthermore, because thrombus formation was reduced in normal rats treated with anti-aggregants acting selectively against ADP, and in rats lacking ADP in their platelet dense granules, it appears that ADP plays a major role in this model of thrombosis.


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