Does dutasteride reduce the bleeding in transurethral resection of the prostate in patients on antiplatelet drugs?

Background The aim of this study was to assess the effect of a 4-week dutasteride treatment on reducing the intraoperative and postoperative bleeding,as well as the amount and duration of irrigation required to clear the urine after transurethral resection of the prostate(TURP)≥50 g in men receiving the antiplatelet drug(APD).Materials and methods This double-blind randomized clinical trial included patients with a prostate size≥50 g who were indicated for TURP and were already receiving APD.The study was conducted in the Urology Department of Cairo University over a 12-month period.Routine preoperative laboratory investigations were performed in all patients.Moreover,baseline prostate size,serum prostate-specific antigen level,and International Prostate Symptom Score were estimated.The patients were randomly divided into 2 equal groups(groups A and B).Group A,the dutasteride group,received dutasteride(0.5 mg)once daily for 4 weeks.Group B,the placebo group,received a placebo capsule once daily for 4 weeks.Both groups underwent bipolar TURP.Fifteen patients were excluded from the study;9 patients from group A and 6 patients from group B,either due to drug intolerability or loss follow-up.Results The mean blood loss was insignificant between the 2 groups immediately after and 24 hours after surgery(Δhemoglobin:1.41±0.63 g/dL vs.1.48±0.54 g/dL,2.12±0.70 g/dL vs.2.31±0.78 g/dL,respectively,p=0.631,p=0.333;Δhematocrit:2.97%±1.51%vs.3.16%±1.36%,4.96%±1.87%vs.5.73%±4.39%,respectively,p=0.610,p=0.380).However,there were significant differences in duration of indwelling urethral catheter(5.10±0.55 days vs.5.80±1.79 days,p=0.048),duration of bladder irrigation(13.60±2.85 hours vs.16.33±6.62 hours,p=0.044),and the amount of saline used for bladder irrigation(11.03±2.30 L vs.13.87±6.13 L,p=0.046)between group A and group B.respectively.Conclusions Treatment with dutasteride for 4 weeks before TURP in men receiving APD did not significantly reduce intraoperative or postoperative bleeding after TURP but could significantly reduce the duration of indwelling catheter placement,as well as the duration and amount of saline irrigation.

Incidence of pocket hematoma after electrophysiological device placement：dual antiplatelet therapy versus low-molecular-weight heparin regimen

Background Given the increasing number of patients who require dual antiplatelet （DAP） therapy and electrophysiological device （EPD） placement, perioperative antiplatelet management is a current challenge. In this study, we investigated the incidence of pocket hema-toma formation after EPD placement in patients undergoing DAP therapy or an alternative low-molecular-weight heparin （LMWH） regimen. Methods This clinical observational study was performed from July 2010 to July 2012. In total, 171 patients were enrolled in the analysis after meeting the inclusion criteria. These patients were divided into two groups： 86 patients were treated with DAP therapy at the time of device implantation, and the DAP therapy was discontinued for 5 to 7 days and replaced with enoxaparin before device implantation in the other 85 patients. Adenosine phosphate （ADP）-mediated platelet aggregation and arachidonic acid-induced platelet aggregation were tested preoperatively. We compared the incidence of pocket hematoma between the two groups and the association of pocket hematoma develop-ment with ADP-mediated platelet aggregation and arachidonic acid-induced platelet aggregation.Results The incidence of pocket hema-toma in the patients who continued DAP was lower than that in the patients who replaced the dual antiplatelet regimen with LMWH （3.49%vs. 16.47%, respectively;X2 = 6.66,P 〈 0.01）. Among the patients who continued DAP therapies, the rate of ADP-mediated platelet aggre-gation inhibition in patients with pocket hematomas was higher than that in patients without pocket hematomas. None of the patients under-going DAP or enoxaparin therapy developed pocket infection, thromboembolic events, or other serious complications. Multiple logistic re-gression analysis revealed that LMWH therapy was an independent risk factor for the development of pocket hematoma （RR = 0.054, 95%CI = 0.012-0.251）. Furthermore, patients undergoing LMWH therapy were 5.1-fold more likely to develop pocket hematomas than were DAP-treated individuals.Conclusion Continuance of DAP therapy does not increase the risk of pocket hematoma formation after EPD placement.

EFFECT OF 764－3 ON AGGREGATION AND CALCIUM MOVEMENTS IN AEQUORIN－LOADED HUMAN PLATELETS

Washed human platelets were loaded with the Ca2+-sensitive photoprotein, aequorin. using hypoosmotic shock treatment-technique. Then aggregation and cytoplasmic ionized calcium concentration ( [Ca2+] i) changes in response to collagen or thrombin were measured simultaneously in the aequorin-loaded human platelets with a Platelet Ionized Calcium Aggregometer. 764-3. an active component isolated from the Chinese medicinal herb Salvia Miltiorrhiza Bge, inhibited platelet [Ca2+]i rise as well as aggregation evoked by collagen or thrombin in the presence of extracellular Ca2+. After the extracellular Ca2+. was removed by addition of EGTA, collagen or thrombin. causing no aggregation. still elicited platelet [Ca2+] i rise which reflected Ca2+ mobilization from intraplatelet stores. Under this condition, 764-3 could also suppress platelet [Ca2+] i rise. Analysis shows that 764-3 inhibrts platelet Ca2+ influx and Ca2+ mobilization with similar potency. which accounts for its suppression of platelet [Ca2+] i rise, and must contribute to its inhibition of platelet aggregation.

A 20-Year Follow-up after the Fontan Operation in a Population with Hypoplastic Left Heart Syndrome

Background:Thromboembolic events are a cause of significant morbidity and mortality in the Fontan population.We previously reported on coagulation profile changes in a cohort of patients with hypoplastic left heart syndrome(HLHS)from Stage I through Fontan completion.In this report,we examine their clinical status,anticoagulation and incidence of thromboembolic events up to 20 years post Fontan.Methods:A retrospective chart review was conducted for twenty(20)surviving patients,from 1998 through December 2020.Patients who underwent orthotopic heart transplantation(OTx)were followed until their transplant.Patients who were found in the original study to have a factor VIII activity level>160%,were examined separately.Results:Most patients had follow-up within the last two years(2018–2020).Two patients underwent OTx and two patients died.Anticoagulation strategy was variable.Most patients were on aspirin monotherapy.There was a total of twelve thrombotic events(63.2%).These included six cerebrovascular accidents(two of which were fatal).Three out of the seven patients with elevated factor VIII activity from the original study had thromboembolic events(42.9%).Fontan complications were variable.Some degree of Fontan Associated Liver Disease was universal.Conclusions:This retrospective review of a group of single-ventricle patients post Fontan,illustrates the variability in anticoagulation therapy that exists in this population.A large proportion of patients suffered a significant thromboembolic event,including the patients with elevated factor VIII.Further investigation into the patients with elevated factor VIII may help determine whether a different antithrombotic strategy post Fontan would be beneficial.

Limited Efficacy of Aspirin in Patients with Peripheral Arterial Occlusive Disease

Antiplatelet drugs represent one of the basic options for management of patients with different atherosclerotic diseases. Aspirin is the oldest and most often prescribed antiplatelet drug. It seems that it is most effective in coronary patients with clinically unstable disease, less effective in prevention of cerebrovascular incidents, and its efficacy is uncertain in peripheral artery disease （PAD） patients. One of the first meta-analysis indicated that antiplatelet drugs also significantly reduce cardiovascular events in patients with PAD. However, latest meta-analysis of randomized control trials of aspirin therapy involving patients with diabetes and PAD demonstrated no benefit of aspirin in reducing cardiovascular events. Also in patients with preclinical PAD aspirin did not result in a significant reduction of vascular events. The new anti-platelet drugs prasugrel, ticagrelol, picotamide seem to be more effective than aspirin in PAD patients, particularly in diabetic patients with PAD. However, evidence based data are scanty. New studies on PAD patients are necessary to better define the role of anti-platelet agents in these patient and one of the promising ways of access to anti-platelet treatment would be personalized anti-platelet therapy.

Clopidogrel and proton pump inhibitors-where do we stand in 2012?

Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events.Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines.Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19(CYP2C19) and proton pump inhibitors(PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well.Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole,but not for pantoprazole.Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events,when under clopidogrel and PPI treatment at the same time.These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI(especially omeprazole) in the same year.In contrast,more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel.Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality,with high and moderate quality studies not reporting any association,rising concern about unmeasured confounders biasing the low quality studies.Thus,no definite evidence exists for an effect on mortality.Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding,combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.

Effect of Dialysis on Antiplatelet Drug Efficacy in Uremic Patients with Coronary Heart Disease

Background： Coronary intervention therapy is the main treatment for uremic patients with coronary heart disease. The studies on whether dialysis reduces the efficacy of dual antiplatelet drugs are limited. The aim of this study was to examine the effect of dialysis on antiplatelet drugs in uremic patients with coronary heart disease. Methods： This study included 26 uremic patients who had undergone percutaneous coronary intervention in China-Japan Friendship Hospital from November 2015 to May 2017. We examined their thromboelastography results before and after hemodialysis. Self-paired t-tests were employed to analyze changes in the inhibition rate of platelet aggregation. Results： The mean inhibition rates of arachidonic acid-induced platelet aggregation before and after hemodialysis were 82.56 ± 2.79% and 86.42±3.32%, respectively （t =-1.278, P = 0.213）. The mean inhibition rates of adenosine diphosphate-induced platelet aggregation before and after hemodialysis were 67.87± 5.10% and 61.9± 5.90%, respectively （t = 1.425, P = 0.167）. There was no significant difference in the inhibition rates ofplatelet aggregation before or after hemodialysis. These results also applied to patients with different sensitivity to aspirin and clopidogrel. Conclusion： Dialysis did not affect the antiplatelet effects of aspirin and clopidogrel in uremic patients with coronary heart disease.

Obstructive Sleep Apnea Affecting Platelet Reactivity in Patients Undergoing Percutaneous Coronary Intervention

Background：The relationship between obstructive sleep apnea （OSA） and platelet reactivity in patients undergoing percutaneous coronary intervention （PCI） has not been defined.The present prospective,single-center study explored the relationship between platelet reactivity and OSA in patients with PCI.Methods：A total of 242 patients were finally included in the study.OSA was screened overnight by polysomnography.Platelet reactivity was assessed with a sequential platelet counting method,and the platelet maximum aggregation ratio （MAR） and average aggregation ratio were calculated.All patients were assigned per apnea-hypopnea index （AHI） to non-OSA （n =128） and OSA （n =l 14） groups.The receiver operating characteristic curve analysis was used to evaluate the accuracy of AHI for high platelet reactivity （HPR） on aspirin and clopidogrel,and multivariable logistic regression was used to determine the independent predictors of HPR on aspirin and clopidogrel.Results：Median AHI was significantly higher in the OSA group than in the non-OSA group （34.5 events/h vs.8.1 events/h,Z =-13.422,P 〈 0.001）.Likewise,median arachidonic acid-and adenosine diphosphate-induced maximum aggregation rate （MAR） in the OSA group was significantly higher than those in the non-OSA group （21.1% vs.17.7%,Z=-3.525,P 〈 0.001 and 45.8% vs.32.2%,Z =-5.708,P 〈 0.001,respectively）.Multivariable logistic regression showed that OSA was the only independent predictor for HPR on aspirin （odds ratio [OR]：1.055,95% confidence interval [CI]：1.033-1.077,P 〈 0.001） and clopidogrel （OR：1.036,95% CI：1.017-1.056,P 〈 0.001）.The cutoffvalue of AHI for HPR on aspirin was 45.2 events/h （sensitivity 47.1% and specificity 91.3%）,whereas cutoffvalue of AHI for HPR on clopidogrel was 21.3 events/h （sensitivity 68.3% and specificity 67.7%）.

Latest Advancement of Non ST-segment Elevation Acute Coronary Syndrome

Further understanding of the pathphophisyology, advance of the diagnosis instrument and renovation of the risk delamination standard can offer better therapy evidence for the non-ST-segment elevation acute coronary syndrome(NSTE-ACS). Drugs, such as trigeminy antiplatelet drug, prasugrel, fondaparinux and bivalirudin, have brought great clinical effect to the high risk patients. Since the result of the ICTUS test announced and the drug eluting balloon developed, we have reached the newest recognition of how to select a chance for intervention and how to prevent and cure the restenosis of in-stent.