Inhibited Adenosine Diphosphate Research Articles

Factors associated with clopidogrel resistance and clinical outcomes in ischemic cerebrovascular disease: A retrospective study

ObjectiveClopidogrel resistance may lead to the recurrence of cerebrovascular diseases. We aimed to identify potential factors associated with clopidogrel resistance and evaluate the clinical outcomes of the patients. Materials and methodsIn this retrospective study, patients with ischemic cerebrovascular disease treated with clopidogrel were included and classified into 2 groups according to the adenosine diphosphate (ADP)-induced platelet aggregation. Patients with the ADP inhibition rate of <30 % were included in clopidogrel resistance group, otherwise were included in clopidogrel sensitive group. CYP2C19 genotype and other clinical data were analyzed to identify factors and clinical features in the multivariate analysis. The outcomes were vascular events in 6 months. ResultsIn total, 139 patients were enrolled with 81 (58.27 %) in clopidogrel sensitive group and 58 (41.73 %) in clopidogrel resistance group. Female and CYP2C19 *2*3 carrying were risk factors for clopidogrel resistance, and female was an independent risk factor (OR 2.481, 95 % CI 1.066-5.771, P=0.035). The clopidogrel resistance group showed a higher use rate of argatroban (P=0.030) and a lower arachidonic acid-induced inhibition of platelet aggregation (P=0.036). Clopidogrel resistance was related to the progressing stroke (HR 3.521, 95 % CI 1.352-9.170, P=0.010), but had no influence on the bleeding events (P>0.05). ConclusionsThe risk of clopidogrel resistance increased significantly in female patients. Patients with clopidogrel resistance may have an increased incidence of stroke progression in the acute phase.

Daboialipase, a phospholipase A2 from Vipera russelli russelli venom posesses anti-platelet, anti-thrombin and anti-cancer properties

Snake venoms are known to contain toxins capable of interfering with normal physiological processes of victims. Specificity of toxins from snake venoms give scope to identify new molecules with therapeutic action and/or help to understand different cellular mechanisms. Russell's viper venom (RVV) is a mixture of many bioactive molecules with enzymatic and non-enzymatic proteins. The present article describes Daboialipase (DLP), an enzymatic phospholipase A2 with molecular mass of 14.3 kDa isolated from RVV. DLP was obtained after cation exchange chromatography followed by size-exclusion high performance liquid chromatography (SE-HPLC). The isolated DLP presented strong inhibition of adenosine di-phosphate (ADP) and collagen induced platelet aggregation. It also showed anti-thrombin properties by significantly extending thrombin time in human blood samples. Trypan blue and resazurin cell viability assays confirmed time-dependent cytotoxic and cytostatic activities of DLP on MCF7 breast cancer cells, in vitro. DLP caused morphological changes and nuclear damage in MCF7 cells. However, DLP did not cause cytotoxic effects on non-cancer HaCaT cells. Peptide sequences of DLP obtained by O-HRLCMS analysis showed similarity with a previously reported PLA2 (Uniprot ID: PA2B_DABRR/PDB ID: 1VIP_A). An active Asp at 49th position, calcium ion binding site and anticoagulant activity sites were identified in 1 VIP_A. These findings are expected to contribute to designing new anti-platelet, anticoagulant and anti-cancer molecules.

Risk factors for intraoperative in-stent thrombosis during stent-assisted coiling of paraclinoid aneurysms.

To identify independent risk factors for intraoperative in-stent thrombosis (IST) in paraclinoid aneurysms (PAs). 172 PA patents undergoing stent-assisted coiling (SAC) were divided into an IST group (n = 12) and a non-IST group (n = 160). Clinical characteristics, aneurysm morphologies, and laboratory parameters were measured. We performed independent t tests (for normally distributed data) or non-parametric tests (for non-normally distributed data) to compare continuous parameters. Multivariate logistic regression analysis with a stepwise forward method was conducted to determine independent risk factors. Receiver operating characteristic curves were generated, and the Delong test was employed for comparisons. Independent risk factors for IST included size ratio (SR) (p < 0.001, odds ratio [OR] = 3.909, confidence interval [CI] = 1.925-7.939), adenosine diphosphate (ADP) inhibition (p = 0.028, OR = 0.967, CI = 0.938-0.996), and reaction time (R) (p = 0.006, OR = 0.326, CI = 0.147-0.725). The combined factors (SR, ADP inhibition, and R) exhibited area under the curves of 0.870, 0.720, 0.716, and 0.697, with cutoff values of 2.46, 69.90%, and 4.65, respectively. The SR, ADP inhibition, and R values were independent risk factors for the IST in the PAs undergoing SAC. For PAs with a large SR, surgeons could prepare for long-term dual antiplatelet therapy before SAC.

Daboxin P, a phospholipase A2 of Indian Daboia russelii venom, modulates thrombin-mediated platelet aggregation.

Daboxin P, reported earlier from the venom of Daboia russellii, disturbs the blood coagulation cascade by targeting factor X and factor Xa. The present study exhibits that Daboxin P also inhibits platelet aggregation induced by various agonists. The thrombin-induced platelet aggregation was inhibited maximum whereas inhibition of collagen-induced platelet aggregation was found to be 50% and no inhibition of adenosine diphosphate (ADP)and arachidonic acid-induced aggregation was observed. Daboxin P dose-dependently inhibited the thrombin-induced platelet aggregation with Anti-Aggregation 50 (AD50 ) dose of 55.166 nM and also reduced the thrombin-mediated calcium influx. In-silico interaction studies suggested that Daboxin P binds to thrombin and blocks its interaction with its receptor on the platelet surface. Quenching of thrombin's emission spectrum by Daboxin P and electrophoretic profiles of pull-down assay further reveals the binding between Daboxin P and thrombin. Thus, the present study demonstrates that Daboxin P inhibits thrombin-induced platelet aggregation by binding to thrombin.

Evidence based Scientific Narrative Review on the Anticoagulant Mechanisms of Allium sativum (Garlic)

Introduction: Garlic (Allium sativum, Family: Amaryllidaceae) is a seasoning plant cultivated all over the world. Garlic contains a lot of bioactive compounds including organosulfur compounds, saponins, phenolic compounds, and polysaccharides. Anticoagulant activity is one of the pharmacological properties of Garlic. The aim of this study was to review the mechanism of the anticoagulant activity of garlic and summarise the potential evidence about the anticoagulant activity of garlic from past studies. Method: Literature searches were conducted on PubMed and Google Scholar databases. 44 full articles were reviewed in detail in this study. The findings were reviewed and potential evidence for the anticoagulant mechanisms of garlic was summarised. Results: Organosulfur compounds in garlic play a major role in the anticoagulant property of garlic. Garlic exhibits anticoagulant activity mainly through three mechanisms. Those are inhibiting platelet aggregation, retarding thrombin formation, and promoting fibrinolysis. The anticoagulant activity of garlic is proven by several human, animal and in-vitro studies. Garlic significantly inhibits adenosine diphosphate and epinephrine induced platelet aggregation in healthy subjects. Garlic administration inhibit the thrombus formation in rats. Aqueous and methanolic extracts of garlic prolong prothrombin time. Extension in clotting time is reported with increasing concentrations of garlic extract. Conclusions: Garlic has been reported as a medicinal plant showing anticoagulant activity by resisting platelet aggregation, inhibiting thrombin formation and enhancing fibrinolysis and this study suggests that garlic reduces the risk of thrombosis therefore cardiovascular complications.&#x0D; &#x0D; Keywords: Anticoagulant Activity, Garlic, Thrombosis

Thromboelastography 6s for assessment of platelet function during coil embolization of unruptured intracranial aneurysms

ObjectivesMethods for assessing platelet function in patients with neurovascular disease remain controversial and poorly studied. This study aimed to assess associations between thromboelastography 6s (TEG6s) measurements and postoperative ischemic complications in patients with unruptured intracranial aneurysms (UIAs) treated by coil embolization. MethodsEighty-four patients with UIAs taking a combined aspirin and clopidogrel protocol were retrospectively reviewed from January 2021 to May 2022. Blood samples were obtained for TEG6s to assess platelet function on the day of coil embolization. To identify acute ischemic complications, diffusion-weighted imaging (DWI) was performed within 24 h after coil embolization. Multivariate logistic regression analysis was conducted to identify potential risk factors for postoperative positive DWI (DWI (+)) lesions. ResultsForty-three of the 84 patients (51%) with DWI (+) lesions were identified. Compared with patients without DWI (+) lesions, Adenosine diphosphate (ADP)-induced platelet-fibrin clot strength (MAADP) was significantly higher (53.6 mm [Interquartile range (IQR): 48.3–58.3 mm] vs 46.7 mm [IQR: 36.8–52.2 mm]; p=0.001) and ADP inhibition rate (ADP%) was significantly lower (19% [IQR: 11–31%] vs 31% [IQR: 21–44%]; p=0.001) in DWI (+) patients. Multivariate analysis identified MAADP, ADP%, and procedure time as significant independent predictors of subsequent DWI (+) lesions (odds ratios: 1.07, 0.96, and 1.02, respectively). Based on receiver operating characteristic curve analysis, MAADP >50.9 mm and ADP% <28.8% were associated with postoperative DWI (+) lesions in patients undergoing coil embolization for UIAs. ConclusionsMAADP and ADP% as assessed by TEG6s can offer reliable parameters to predict postoperative ischemic complications after coil embolization of UIAs. Lower MAADP values and higher ADP% may decrease the risk of postoperative ischemic complications.

Ticagrelor versus Clopidogrel in the Dual Antiplatelet Regimen for Unruptured Intracranial Aneurysm Treated with Stent-Assisted Coil Embolization: A Single-Center Cohort Study

Dual antiplatelet therapy (DAPT) of aspirin plus clopidogrel is commonly utilized in patients with unruptured intracranial aneurysms treated with stent-assisted coil (SAC) embolization. However, the unpredictable clopidogrel efficacy of the 5% to 55% non-responders limits its use. Ticagrelor, as a potential alternative of clopidogrel, is an antiplatelet agent with low resistance rates but uncertain efficacy and safety in these patients. A single-center, cohort study was performed to compare the efficacy and safety of ticagrelor with clopidogrel in the DAPT regimen in patients with unruptured intracranial aneurysms and treated with SAC. The patients with clopidogrel resistance identified as inadequate adenosine diphosphate (ADP) inhibition rate determined by thromboelastography were treated with ticagrelor instead, and both drugs achieved adequate suppression of platelet aggregation when stents were implanted. The occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and bleeding events was recorded through 6-month follow-up. Data from 86 patients with 99 unruptured intracranial aneurysms and treated by SAC with clopidogrel were compared with those from 108 patients with 111 aneurysms and treated with ticagrelor. Neither the baseline characteristics nor the incidence of the MACCE or bleeding events differ between the groups. Ticagrelor exerted significantly higher ADP inhibition rate than that of the clopidogrel. Multivariable logistic regression analysis demonstrated that the incidence of MACCE was relate to hematocrit and fibrinogen levels. Ticagrelor appeared to be as effective and safe as clopidogrel for SAC in unruptured intracranial aneurysms. Hematocrit and fibrinogen levels were independent risk factors for the incidence of MACCE.

Effects of Guideline-Based Correction of Platelet Inhibition on Outcomes in Moderate to Severe Isolated Blunt Traumatic Brain Injury.

Platelet dysfunction has been demonstrated after traumatic brain injury (TBI) regardless of the use of platelet inhibitors. The purpose of this study was to determine the efficacy of a platelet-mapping thromboelastography (PM-TEG) in predicting TBI patients who would benefit from platelet transfusion. We hypothesized that adenosine diphosphate (ADP) and arachadonic acid (AA) inhibition in patients with TBI is associated with increased mortality and can be corrected with platelet transfusion. This is a retrospective review of patients admitted to a level 1 trauma center from January 2016 through September 2017 with moderate to severe blunt TBI (msTBI), defined by an initial Glasgow Coma Scale (GCS) ≤12 with intracranial hemorrhage. Patients received PM-TEG. Those with platelet dysfunction (ADP or AA inhibition ≥60%) received one unit of platelets followed by repeat PM-TEG, until inhibition <60% or three units of platelets. Cohorts were defined as patients initially without (NPI) and with (PI) inhibition and subdivided into those whose inhibition corrected (PI-C) versus those whose did not correct (PI-NC). From 69 patients with isolated blunt TBI, 40 (58%) presented with NPI, 29 (42%) with PI. Of those with PI, 16 (55%) were with PI-C and 13 (45%) with PI-NC. Platelet inhibition in msTBI patients undergoing guideline-based transfusion is associated with age and GCS and an increase in mortality. Platelet inhibition seems to have a more adverse effect on patients >55 years of age or with GCS <8. Correction of platelet inhibition normalized mortality to that of NPI.

Effect of Biofunctional Green Synthesized MgO-Nanoparticles on Oxidative-Stress-Induced Tissue Damage and Thrombosis.

The present study describes the green biofunctional synthesis of magnesium oxide (MgO) nanoparticles using the aqueous Tarenna asiatica fruit extract. The characterization of Tarenna asiatica fruit extract MgO nanoparticles (TAFEMgO NPs) was achieved by X-ray powder diffraction, UV-Vis spectroscopy, FTIR, TEM, SEM, and energy-dispersive X-ray diffraction. TAFEMgO NPs scavenged the DPPH free radicals with an IC50 value of 55.95 μg/μL, and it was highly significant compared to the standard. To authenticate the observed antioxidant potential of TAFEMgO NPs, oxidative stress was induced in red blood cells (RBC) using sodium nitrite (NaNO2). Interestingly, TAFEMgO NPs ameliorated the RBC damage from oxidative stress by significantly restoring the stress parameters, such as the protein carbonyl content (PCC), lipid peroxidation (LPO), total thiol (TT), super-oxide dismutase (SOD), and catalase (CAT). Furthermore, oxidative stress was induced in-vivo in Sprague Dawley female rats using diclofenac (DFC). TAFEMgO NPs normalized the stress parameters in-vivo and minimized the oxidative damage in tissues. Most importantly, TAFEMgO NPs restored the function and architecture of the damaged livers, kidneys, and small intestines by regulating biochemical parameters. TAFEMgO NPs exhibited an anticoagulant effect by increasing the clotting time from 193 s in the control to 885 s in the platelet rich plasma. TAFEMgO NPs prolonged the formation of the clot process in the activated partial thromboplastin time and the prothrombin time, suggest the effective involvement in both intrinsic and extrinsic clotting pathways of the blood coagulation cascade. TAFEMgO NPs inhibited adenosine di-phosphate (ADP)-induced platelet aggregation. TAFEMgO NPs did not show hemolytic, hemorrhagic, and edema-inducing properties at the tested concentration of 100 mg/kgbody weight, suggesting its non-toxic property. In conclusion, TAFEMgO NPs mitigates the sodium nitrite (NaNO2)- and diclofenac (DFC)-induced stress due to oxidative damage in both in vitro and in vivo experimental models.

Impact of Oral Anticoagulation and Adenosine Diphosphate Inhibitor Therapies on Short-term Outcome of Traumatic Brain Injury.

Usage of oral anticoagulants (OACs) or adenosine diphosphate inhibitors (ADPi) is known to increase the risk of bleeding. We aimed to investigate the impact of OAC and ADPi therapies on short-term outcomes after traumatic brain injury (TBI). All adult patients hospitalized for TBI in Finland during 2005-2018 were retrospectively studied using a combination of national registries. Usage of pharmacy-purchased OACs and ADPi at the time of TBI was analyzed with the pill-counting method (Social Insurance Institution of Finland). The primary outcome was 30-day case-fatality (Finnish Cause of Death Registry). The secondary outcomes were acute neurosurgical operation (ANO) and admission duration (Finnish Care Register for Health Care). Baseline characteristics were adjusted with multivariable regression, including age, sex, comorbidities, skull or facial fracture, OAC/ADPi treatment, initial admission location, and the year of TBI admission. The study population included 57,056 persons (mean age 66 years) of whom 0.9% used direct OACs (DOACs), 7.1% vitamin K antagonists (VKA), and 2.3% ADPi. Patients with VKAs had higher case-fatality than patients without OAC (15.4% vs 7.1%; adjusted hazard ratio [aHR] 1.35, CI 1.23-1.48; p < 0.0001). Case-fatality was lower with DOACs (8.4%) than with VKAs (aHR 0.62, CI 0.44-0.87; p = 0.005) and was not different from patients without OACs (aHR 0.93, CI 0.69-1.26; p = 0.634). VKA usage was associated with a higher neurosurgical operation rate compared with non-OAC patients (9.1% vs 8.3%; adjusted odds ratio 1.33, CI 1.17-1.52; p < 0.0001). There was no difference in operation rate between DOAC and VKA. ADPi was not associated with case-fatality or operation rate in the adjusted analyses. VKAs and DOACs were not associated with longer admission length compared with the non-OAC group, whereas the admissions were longer in the ADPi group compared with the non-ADPi group. Preinjury use of VKA is associated with increases in short-term mortality and in need for ANOs after TBI. DOACs are associated with lower fatality than VKAs after TBI. ADPi were not independently associated with the outcomes studied. These results point to relative safety of DOACs or ADPi in patients at risk of head trauma and encourage to choose DOACs when oral anticoagulation is required. This study provides Class II evidence that among adults with TBI, mortality was significantly increased in those using VKAs but not in those using DOACs or ADPi.

Traumatic brain injury patients with platelet inhibition receiving platelet transfusion demonstrate decreased need for neurosurgical intervention and decreased mortality.

Platelet dysfunction is known to occur in patients with traumatic brain injury (TBI), and the correction of platelet dysfunction may prevent hemorrhagic progression in TBI. Thromboelastography with platelet mapping (TEG-PM; Haemonetics) evaluates the degree of platelet function inhibition through the adenosine diphosphate (ADP) and arachidonic acid (AA) pathways. We hypothesized that ADP and AA inhibition would improve with the transfusion of platelets in patients with TBI. A retrospective review was conducted at a Level I trauma center of all patients presenting with TBI from December 2019 to December 2020. Per a practice management guideline, a platelet mapping assay was obtained on all patients with TBI upon admission. If ADP or AA was found to be inhibited (>60%), the patient was transfused 1 unit of platelets and a repeat platelet mapping assay was ordered. Demographic data, laboratory values, and outcomes were analyzed. Over the 13-month study period, 453 patients with TBI underwent TEG-PM with a protocol adherence rate of 66.5% resulting in a total of 147 patients who received platelets for ADP and/or AA inhibition; of those, 107 underwent repeat TEG-PM after platelets were administered. With the administration of platelets, ADP (p < 0.0001), AA (p < 0.0001), and MA (p = 0.0002) all significantly improved. Of 330 patients with TBI not taking antiplatelet medications, 50.9% showed inhibition in ADP and/or AA. If AA or ADP inhibition was noted on admission, mortality was increased (p = 0.0108). If ADP improved with platelet administration, the need for neurosurgical intervention was noted to decrease (p = 0.0182). Patients with TBI and platelet inhibition may benefit from the administration of platelets to correct platelet dysfunction. Thromboelastography with platelet mapping may be implemented in the initial workup of patients presenting with TBI to assess platelet dysfunction and provide prognostic information, which may guide treatment. Therapeutic / Care Management, level III.

Protein extract of kenaf seed exhibits anticoagulant, antiplatelet and antioxidant activities

Objective: To explore the anticoagulant, antiplatelet and antioxidant activities of protein extract of kenaf seed (PEKS).Methods: Sodium dodecyl sulphate polyacrylamide gel electrophoresis and reverse-phase high-performance liquid chromatography techniques were employed for protein characterization. Antioxidant activity of PEKS was assessed using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The protective effect of PEKS on sodium nitrite (NaNO2) induced oxidative stress was evaluated using the in vitro red blood cell model, while the effect of PEKS on diclofenac-induced oxidative stress was examined in vivo in rats. Platelet-rich plasma and platelet-poor plasma were used for anticoagulant and antiplatelet activities of PEKS.Results: PEKS revealed similar protein bands on SDS-PAGE under reduced and non-reduced conditions. Several acidic proteins were present in native PAGE. PEKS showed antioxidant properties by scavenging DPPH with an IC50 of 24.58 μg. PEKS exhibited a protective effect on NaNO2 induced oxidative stress in red blood cells by restoring the activity of stress markers. In addition, PEKS alleviated diclofenac-induced tissue damage of the liver, kidney, and small intestine. PEKS showed an anticoagulant effect in both in vivo and in vitro experiments by enhancing normal clotting time. PEKS did not affect prothrombin time but increase activated partial thromboplastin time. Furthermore, PEKS inhibited adenosine diphosphate and epinephrine-induced platelet aggregation.Conclusions: PEKS protects tissues from oxidative stress and exhibits antithrombotic activity.

Sex Differences in Cardiovascular Outcomes of Older Adults After Myocardial Infarction.

BackgroundEvidence on the impact of sex on prognoses after myocardial infarction (MI) among older adults is limited. We evaluated sex differences in long‐term cardiovascular outcomes after MI in older adults.Methods and ResultsAll patients with MI ≥70 years admitted to 20 Finnish hospitals during a 10‐year period and discharged alive were studied retrospectively using a combination of national registries (n=31 578, 51% men, mean age 79). The primary outcome was combined major adverse cardiovascular event within 10‐year follow‐up. Sex differences in baseline features were equalized using inverse probability weighting adjustment. Women were older, with different comorbidity profiles and rarer ST‐segment–elevation MI and revascularization, compared with men. Adenosine diphosphate inhibitors, anticoagulation, statins, and high‐dose statins were more frequently used by men, and renin‐angiotensin‐aldosterone inhibitors and beta blockers by women. After balancing these differences by inverse probability weighting, the cumulative 10‐year incidence of major adverse cardiovascular events was 67.7% in men, 62.0% in women (hazard ratio [HR], 1.17; CI, 1.13–1.21; P<0.0001). New MI (37.0% in men, 33.1% in women; HR, 1.16; P<0.0001), ischemic stroke (21.1% versus 19.5%; HR, 1.10; P=0.004), and cardiovascular death (56.0% versus 51.1%; HR, 1.18; P<0.0001) were more frequent in men during long‐term follow‐up after MI. Sex differences in major adverse cardiovascular events were similar in subgroups of revascularized and non‐revascularized patients, and in patients 70 to 79 and ≥80 years.ConclusionsOlder men had higher long‐term risk of major adverse cardiovascular events after MI, compared with older women with similar baseline features and evidence‐based medications. Our results highlight the importance of accounting for confounding factors when studying sex differences in cardiovascular outcomes.

Prediction of Hematoma Expansion in Patients With Intracerebral Hemorrhage Using Thromboelastography With Platelet Mapping: A Prospective Observational Study

Background and Purpose: The purpose of the study was to evaluate the usefulness of thromboelastography with platelet mapping (TEG-PM) for predicting hematoma expansion (HE) and poor functional outcome in patients with intracerebral hemorrhage (ICH).Methods: Patients with primary ICH who underwent baseline computed tomography (CT) and TEG-PM within 6 h after symptom onset were enrolled in the observational cohort study. We performed univariate and multivariate logistic regression models to assess the association of admission platelet function with HE and functional outcome. In addition, a receiver operating characteristic (ROC) curve analysis investigated the accuracy of platelet function in predicting HE. A mediation analysis was undertaken to determine causal associations among platelet function, HE, and outcome.Results: Of 142 patients, 37 (26.1%) suffered HE. Multivariate logistic regression identified arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition as significant independent predictors of HE. The area under the ROC curves was 0.727 for AA inhibition and 0.721 for ADP inhibition. Optimal threshold for AA inhibition was 41.75% (75.7% sensitivity; 67.6% specificity) and ADP inhibition was 65.8% (73.0% sensitivity; 66.7% specificity). AA and ADP inhibition were also associated with worse 3-month outcomes after adjusting for age, admission Glasgow Coma Scale score, intraventricular hemorrhage, baseline hematoma volume, and hemoglobin. The mediation analysis showed that the effect of higher platelet inhibition with poor outcomes was mediated through HE.Conclusions: These findings suggest that the reduced platelet response to ADP and AA independently predict HE and poor outcome in patients with ICH. Platelet function may represent a modifiable target of ICH treatment.

Thromboelastography-Platelet Mapping Allows Safe and Earlier Urgent Coronary Artery Bypass Grafting

BackgroundThe Society of Thoracic Surgeons current (STS) guidelines recommend delaying coronary artery bypass graft surgery (CABG) for several days or performing platelet function testing in stable patients who received P2Y12 inhibitors. Our program routinely uses thromboelastography-platelet mapping (TEG-PM) to expedite CABG in P2Y12 nonresponders. We hypothesize that P2Y12 nonresponders had no difference in length of stay to surgery and blood product transfusion compared with patients undergoing urgent inpatient CABG not treated with a P2Y12 inhibitor. MethodsA total of 221 patients from 2015 to 2019 were P2Y12 nonresponders based on TEG-PM result of less than 50% adenosine diphosphate inhibition. The control group was 232 consecutive patients who also had urgent inpatient CABG but were not treated preoperatively with a P2Y12 inhibitor. Exclusion criteria were identical between groups. ResultsSixty-seven percent of inpatient CABG patients who were treated preoperatively with a P2Y12 inhibitor were nonresponders. The mean number of days from cardiac surgical consultation to CABG in the TEG-PM nonresponders group was 1.6 ± 0.1 vs 2.1 ± 0.1 in the control group (P < .01). The mean total number of blood product units transfused was 1.6 ± 0.2 in the TEG-PM nonresponders group vs 1.6 ± 0.4 in the control group (P = .91). ConclusionsOur results demonstrate a very high incidence of P2Y12 nonresponders among patients undergoing urgent CABG at our program. These patients underwent surgery at least 3 days earlier than STS recommendations and common practice with no difference in transfusion requirement. Routine use of TEG-PM to identify P2Y12 nonresponders can safely decrease preoperative hospital length of stay and associated cost and improve resource utilization and patient satisfaction.

Thromboelastography predicts dual antiplatelet therapy-related hemorrhage in patients with acute ischemic stroke

BackgroundStratification of the risk of hemorrhage in patients with acute ischemic stroke following dual antiplatelet therapy (DAPT) is challenging. It remains unclear whether thromboelastography (TEG) can be used to predict...

Thromboelastography with platelet mapping: Limited predictive ability in detecting preinjury antiplatelet agent use.

Preinjury antiplatelet agent (APA) use in trauma patients can increase traumatic hemorrhage and worsen outcomes. Thromboelastography with platelet mapping (TEGPM) has characterized platelet function via arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition in nontrauma settings, but limited data exist in the acute trauma population. A prospective observational study of adult trauma patients with suspected preinjury APA use who received TEGPM testing from 2017 to 2020 was performed. Patients on anticoagulants were excluded. Patients were grouped according to preinjury APA regimen: 81 mg or 325 mg of aspirin daily, 81 mg of aspirin and 75 mg of clopidrogrel daily, 75 mg of clopidrogrel daily, or no antiplatelet. Ability of TEGPM to detect APA use was assessed using predictive statistics and area under receiver operating characteristic curves (AUROCs). A total of 824 patients were included with most patients taking 81 mg of aspirin (n = 558). Patients on no antiplatelet were younger and had higher baseline platelet counts, while patients on 75 mg of clopidrogrel were more likely to be admitted after ground level fall. All other baseline characteristics were balanced. Admission TEG values were similar between groups. Median AA inhibition was higher in patients on aspirin containing regimens (p < 0.0001). Median ADP inhibition was higher in patients on clopidogrel containing regimens and those taking 325 mg of aspirin (p < 0.0001). Arachidonic acid inhibition accurately detected preinjury APA use and aspirin use (AUROC, 0.89 and 0.84, respectively); however, ADP inhibition performed poorly (AUROC, 0.58). Neither AA nor ADP inhibition was able to discern specific APA regimens or rule out APA use entirely. High AA inhibition accurately detects preinjury APA use in trauma patients. High ADP inhibition after trauma is common, limiting its utility to accurately identify preinjury APA use. Further study is needed to identify assays that can reliably detect and further characterize preinjury APA use in trauma populations. Diagnostic test, level II.

Clinical Profile of Patients Presenting with Acute Myocardial Infarction in United Arab Emirates: A Tertiary Care Center Government Hospital Experience

Background: Acute myocardial infarction (AMI) is one of the major causes of hospitalization and mortality worldwide. There has been limited data available to characterize AMI presentation, contemporary patterns of medical care, and outcomes in Dubai, United Arab Emirates. Methods: A single-center observational registry for patients with AMI was used. All patients admitted to Dubai Hospital with AMI (ST elevation and non-ST elevation) with positive troponin from the mid of August 2017 till the end of April 2018 were included in this registry. Clinical data, prior history, demographics, treatments, and outcomes were recorded from the patient’s electronic medical file of the hospital. Result: A total of 329 patients (male 92%, mean age 53.6 years) were included in our registry. The use of ambulance service was only 25%. Electrocardiogram findings of ST-segment elevation myocardial infarction (STEMI) were found in 57% and non-STEMI in 43%. History of prior ischemic heart disease was present in 21% of all cohort, diabetes in 36%, hypertension in 38%, and the current smoking rate was 35%. Reperfusion therapy was provided to 94% of the patients with STEMI; only 32% of them had primary angioplasty, and medical reperfusion was performed in 68%. One-third of them received thrombolysis within 30 min, and primary percutaneous coronary intervention (PCI) was provided to 38% within 90 min. All the patients received aspirin and adenosine diphosphate inhibitors within the first 24 h. The majority of the patients received other key medicines like beta-blocker, statin, and anticoagulant agents within 24 h. The in-hospital mortality rate was about 3%. Conclusions: Using data from the registry may provide an overview of the current status of AMI in Dubai. Medical reperfusion therapy is the most common reperfusion modality in our center, and this will raise the question of whether we need to launch a 24-h primary PCI program in our center.

Sex-Based Outcomes After Coronary Artery Bypass Grafting

BackgroundSex is suggested to influence outcomes after coronary artery bypass grafting (CABG), although evidence on long-term mortality is controversial and cardiovascular outcome data are lacking. We studied sex differences in outcomes after isolated CABG. MethodsConsecutive patients with first-time isolated CABG for stable coronary artery disease between 2004 and 2014 in Finland were retrospectively recognized from national registry (n = 14,681; 21% women). Propensity scoring and inverse probability weighting were used to adjust for baseline features. Median follow-up was 10.0 (maximum 14.6) years. ResultsCumulative major adverse cardiovascular event (myocardial infarction, stroke, or cardiovascular death) rate was 44.5% in men and 49.9% in women during follow-up (hazard ratio [HR], 0.98; P = .633). All-cause mortality was 48.5% in men vs 46.0% in women (HR, 1.20; 95% confidence interval, 1.11-1.30; P < .0001), and cardiovascular mortality was 29.5% vs 31.3% (P = .625). Stroke rate was comparable between men and women (19.4% vs 23.6%; P = .625). Myocardial infarction occurred more frequently in women (20.0% vs 23.6%; HR, 0.84; 95% confidence interval, 0.75-0.95; P = .005). Redo revascularization was performed to 12.8% of women and to 12.6% of men (P = .100). Anticoagulation was more frequently used by men and adenosine diphosphate inhibitors and diuretics were more frequently used by women after CABG. Usage of statins, angiotensin-converting-enzyme inhibitors or angiotensin-blockers, beta-blockers, calcium-channel blockers, or nitrates did not differ between sexes after CABG. ConclusionsSex was not an independent predictor of long-term major adverse cardiovascular events after CABG in this population-based cohort study. However, men had higher long-term all-cause mortality and women higher risk of myocardial infarction. Long-term outcomes should be accounted for when considering sex as a risk factor for CABG.

Does the Degree of Platelet Adenosine Diphosphate and Arachidonic Acid Receptor Inhibition Correlate With the Severity of Injury in Non-Brain-Injured Trauma Patients?

Direct correlations between platelet adenosine diphosphate (ADP) and arachidonic acid (AA) receptor inhibition have been described in the traumatic brain injury (TBI) population. Our goal was to evaluate the percent inhibition of ADP receptor inhibition (ADPri) and AA receptor inhibition (AAri) receptors in non-TBI patients and correlate injury severity and outcomes. We performed a retrospective review of non-TBI patients admitted to our trauma center, who received thromboelastography with platelet mapping prior to blood transfusion. Exclusion criteria included patients younger than 18years, current antiplatelet therapy, or history of renal failure. Univariate descriptive statistics and bivariate comparisons were performed on patient demographic and outcomes. Multivariable linear regression models were constructed to quantify any association between ADPri and AAri with injury outcomes. High ADP inhibition was defined >20% and high AA inhibition >7%. 117 patients met inclusion criteria. Mean age was 53years with 61% male. Mean ADPri was 64% and AAri 42%. On bivariate analysis, no statistically significant differences with respect to injury severity measures or outcomes were identified. On multivariable linear regression, AAri was associated with longer hospital length of stay. There was a high degree of platelet dysfunction in this cohort of severely injured patients without TBI. Despite this, the only correlation identified between injury severity and outcomes was AAri correlating with hospital length of stay. Irrespective of injury severity or outcomes, these patients' results were far from reported "normal" values. Further, research is needed to determine the significance and clinical implications of thromboelastography with platelet mapping use in trauma care.