Clinical impact of glycans in platelet and megakaryocyte biology

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.

Essential thrombocythemia with portal vein thrombosis and splenic infarction successfully treated with platelet apheresis

A 63-year-old diabetic woman presented to the outpatient clinic with a 1-week history of abdominal pain. On complete evaluation, she was diagnosed to have essential thrombocythemia. Abdominal imaging revealed portal vein thrombosis with a large splenic infarct. The patient was started on anticoagulant, antiplatelet and cytoreductive therapy. In view of persistent high platelet count, plasma apheresis was done, following which the patient’s platelet counts were reduced. Essential thrombocythemia has a high rate of complications, resulting in significant morbidity and mortality. Few cases of this disease and its treatment have been described in the literature, especially pertaining to the Indian scenario. Further studies are needed to establish a multidisciplinary algorithm for its diagnosis and to elucidate the guidelines for the successful treatment of the condition.

Risk factors associated with progression of diabetic retinopathy in eyes treated with panretinal photocoagulation

Uncontrolled diabetes has been associated with progression of diabetic retinopathy (DR) in several studies. Therefore, we aimed to investigate systemic and ophthalmic factors related to worsening of DR even after completion of panretinal photocoagulation (PRP). We retrospectively reviewed DR patients who had completed PRP in at least one eye with a 3-year follow-up. A total of 243 eyes of 243 subjects (mean age 52.6 ± 11.6 years) were enrolled. Among them, 52 patients (21.4%) showed progression of DR after PRP (progression group), and the other 191 (78.6%) patients had stable DR (non-progression group). The progression group had higher proportion of proliferative DR (P = 0.019); lower baseline visual acuity (P < 0.001); and higher platelet count (P = 0.048), hemoglobin (P = 0.044), and hematocrit, (P = 0.042) than the non-progression group. In the multivariate logistic regression analysis for progression of DR, baseline visual acuity (HR: 0.053, P < 0.001) and platelet count (HR: 1.215, P = 0.031) were identified as risk factors for progression. Consequently, we propose that patients with low visual acuity or high platelet count are more likely to have progressive DR despite PRP and require careful observation. Also, the evaluation of hemorheological factors including platelet counts before PRP can be considered useful in predicting the prognosis of DR.

Prognostic Utility of the Combination of Platelet Count with Neutrophil-to-Lymphocyte Ratio in Aged Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

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.

Risk Factors Associated With Progression of Diabetic Retinopathy in Eyes Treated With Panretinal Photocoagulation

Uncontrolled diabetes has been associated with progression of diabetic retinopathy (DR) in several studies. Therefore, we aimed to investigate systemic and ophthalmic factors related to worsening of DR even after completion of panretinal photocoagulation (PRP). DR patients who had completed PRP in at least one eye with a 3-year follow-up after PRP were included. A total of 243 eyes of 243 subjects (mean age 52.6±11.6 years) were enrolled. Among them, 52 patients (21.4%) showed progression of DR after PRP (progression group), and the other 191 (78.6%) patients had stable DR (non-progression group). The progression group had higher proportion of proliferative DR (P=0.019); lower baseline visual acuity (P<0.001); and higher platelet count (P=0.048), hemoglobin (P=0.044), and hematocrit, (P=0.042) than the non-progression group. In the multivariate logistic regression analysis for progression of DR, baseline visual acuity (HR: 0.053, P<0.001) and platelet count (HR: 1.215, P=0.031) were identified as risk factors for progression. Consequently, we propose that patients with low visual acuity or high platelet count are more likely to have progressive DR despite PRP and require careful observation. Also, the evaluation of hemorheological factors including platelet counts before PRP can be considered useful in predicting the prognosis of DR.

Continuous Renal Replacement Therapy in COVID-19-associated AKI: Adding Heparin to Citrate to Extend Filter Life – a Retrospective Cohort

Background: Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk.Methods: This was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV+ AKI and COV− AKI, respectively), submitted to CRRT. Filter clotting risks in the first 72 hours were compared between groups.Results: Between January 2019 and July 2020, 248 patients were evaluated: 189 in the COV+ AKI group and 59 in the COV− AKI group. Filter clotting occurred during the first 72 hours of CRRT in 96 patients (38.7%). Heparin use conferred protection against filter clotting, resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV+ AKI patients than among the COV− AKI patients, although it was similar between the COV+ AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (6086 ng/ml). In the multivariate analysis, the protective effect of heparin against filter clotting persisted, whereas an elevated D-dimer level, high platelet count, and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was not a risk factor for filter clotting.Conclusions: In COV+ AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with low risk of complications.

Preoperative platelet count predicts posttransplant portal vein complications in orthotopic liver transplantation: a propensity score analysis

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.

Isolated ten-eleven translocation 2 positive in triple negative essential thrombocythemia: Case report and literature review

Essential thrombocythemia is one of the famous diseases under the category of myeloproliferative disorder. It is an end result of a genetic mutation of one or more of the most frequent oncogenes such as Janos kinase 2 (JAK2), MPL proto-oncogene, thrombopoietin receptor (MPL), and calreticulin (CALR). However, negative genetic markers, so-called (triple negative disease), can happen in the presence of other uncommon types of mutation. TET2 (ten-eleven translocation 2) positive as isolated genetic marker in triple negative essential thrombocythemia is uncommon genetic presentation. For that, we are reporting a 22-year-old lady who presented with a feature of dyspepsia and accidentally found to have persistently high platelet count, even after treating her mild iron deficiency anemia with no other secondary causes. Further investigations and bone marrow biopsy supported the diagnosis of isolated TET2 positive in triple negative essential thrombocythemia. We treated her conservatively with good hydration and low dose of aspirin. In conclusion, isolated TET2 positive in triple negative essential thrombocythemia at presentation is uncommon with no clear management or risk stratification guideline. However, it is hypothesized that TET2 mutation precedes JAK2; therefore, the detection of isolated TET2 in a triple negative essential thrombocythemia case should be closely followed for clonal evolution in long term. Further study and guidelines required in this area.

Preoperative platelet count predicts posttransplant portal vein complications in orthotopic liver transplantation: a propensity score analysis

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.