Plasma Fibrinogen Independently Predicts Hypofibrinolysis in Severe COVID-19

High rates of thrombosis are present in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Deeper insight into the prothrombotic state is essential to provide the best thromboprophylaxis care. Here, we aimed to explore associations among platelet indices, conventional hemostasis parameters, and viscoelastometry data. This pilot study included patients with severe COVID-19 (n = 21) and age-matched controls (n = 21). Each patient received 100 mg aspirin therapy at the time of blood sampling. Total platelet count, high immature platelet fraction (H-IPF), fibrinogen, D-dimer, Activated Partial Thromboplastin Time, von Willebrand factor antigen and von Willebrand factor ristocetin cofactor activity, plasminogen, and alpha2-antiplasmin were measured. To monitor the aspirin therapy, a platelet function test from hirudin anticoagulated whole blood was performed using the ASPI test by Multiplate analyser. High on-aspirin platelet reactivity (n = 8) was defined with an AUC > 40 cut-off value by ASPI tests. In addition, in vitro viscoelastometric tests were carried out using a ClotPro analyser in COVID-associated thromboembolic events (n = 8) (p = 0.071) nor the survival rate (p = 0.854) showed associations with high on-aspirin platelet reactivity status. The platelet count (p = 0.03), all subjects. COVID-19 patients presented with higher levels of inflammatory markers, compared with the controls, along with evidence of hypercoagulability by ClotPro. H-IPF (%) was significantly higher among non-survivors (n = 18) compared to survivors (p = 0.011), and a negative correlation (p = 0.002) was found between H-IPF and plasminogen level in the total population. The platelet count was significantly higher among patients with high on-aspirin platelet reactivity (p = 0.03). Neither the ECA-A10 (p = 0.008), and ECA-MCF (p = 0.016) were significantly higher, while the tPA-CFT (p < 0.001) was significantly lower among patients with high on-aspirin platelet reactivity. However, only fibrinogen proved to be an independent predictor of hypofibrinolysis in severe COVID-19 patients. In conclusion, a faster developing, more solid clot formation was observed in aspirin ‘non-responder’ COVID-19 patients. Therefore, an individually tailored thromboprophylaxis is needed to prevent thrombotic complications, particularly in the hypofibrinolytic cluster.

Early Surgery with Neuraxial Anaesthesia in Patients on Chronic Antiplatelet Therapy with a Proximal Femur Fracture: Multicentric Randomised Clinical Trial

Background: Patients with proximal femur fracture on antiplatelet treatment benefit from early surgery. Our goal was to perform early surgery under neuraxial anaesthesia when indicated by the platelet function test. Methods: We conducted a multicentre randomised open-label parallel clinical trial. Patients were randomised to either early platelet function-guided surgery (experimental group) or delayed surgery (control group). Early surgery was programmed when the functional platelet count (as measured by Plateletworks) was >80 × 109/L. The primary outcome was the emergency admission-to-surgery interval. Secondary outcomes were platelet function, postoperative bleeding, medical and surgical complications, and mortality. Results: A total of 156 patients were randomised, with 78 in each group, with a mean (SD) age of 85.96 (7.9) years, and 67.8% being female. The median (IQR) time to surgery was 2.3 (1.5–3.7) days for the experimental group and 4.9 (4.4–5.6) days for the control group. One-third of patients did not achieve the threshold functional platelet count on the first day of admission, requiring more than one test. There was no difference in clinical outcomes between groups. Conclusions: A strategy individualised according to the platelet function test shortens the time to proximal femur fracture surgery under neuraxial anaesthesia in patients on chronic antiplatelet treatment. Better powered randomised clinical trials are needed to further evaluate the clinical impact and safety of this strategy.

Plateletworks® as a Point-of-Care Test for ASA Non-Sensitivity

Aspirin (ASA) therapy is proven to be effective in preventing adverse cardiovascular events; however, up to 30% of patients are non-sensitive to their prescribed ASA dosage. In this pilot study, we demonstrated, for the first time, how ASA non-sensitivity can be diagnosed using Plateletworks®, a point-of-care platelet function test. Patients prescribed 81 mg of ASA were recruited in a series of two successive phases—a discovery phase and a validation phase. In the discovery phase, a total of 60 patients were recruited to establish a cut-off point (COP) for ASA non-sensitivity using Plateletworks®. Each sample was simultaneously cross-referenced with a light transmission aggregometer (LTA). Our findings demonstrated that >52% maximal platelet aggregation using Plateletworks® had a sensitivity, specificity, and likelihood ratio of 80%, 70%, and 2.67, respectively, in predicting ASA non-sensitivity. This COP was validated in a secondary cohort of 40 patients prescribed 81 mg of ASA using Plateletworks® and LTA. Our data demonstrated that our established COP had a 91% sensitivity and 69% specificity in identifying ASA non-sensitivity using Plateletworks®. In summary, Plateletworks® is a point-of-care platelet function test that can appropriately diagnose ASA non-sensitive patients with a sensitivity exceeding 80%.

Role of Platelet Function Test in Predicting Postoperative Bleeding Risk after Coronary Artery Bypass Grafting: A Prospective Observational Study

Patients undergoing cardiac surgery are at risk of excessive bleeding and its associated complications. Excessive bleeding during and after cardiac surgery has an incidence of ~20%. Massive bleeding and subsequent requirement for blood product administration and mediastinal reexploration are associated with significant morbidity and mortality. Postoperative, nonsurgical bleeding in cardiac surgical patients is often multifactorial. Platelet dysfunction, excessive fibrinolysis, hypothermia, preoperative anemia, and deficiency of coagulation factors or their dilution are all suggested etiologies of postoperative bleeding. In the Arachidonic Acid Thromboelastometry (ARATEM) test, platelets are activated with arachidonic acid; in Adenosine diphosphate Thromboelastometry (ADPTEM) test, platelets are activated with adenosine diphosphate; and in TRAPTEM test, platelets are activated with thrombin receptor-activating peptide 6. Measurement time is 6 minutes, and results are expressed in three different parameters: A6 (amplitude at 6 minutes, in Ohm); MS (maximum slope of the aggregation curve in Ohm/min), and AUC (area under the curve in Ohm.min). Algorithm-based point-of-care platelet function testing helped us to preemptively give the right blood component therapy, avoiding fibrinolytic bleeding in the postoperative period.

Correlation between PlateletWorks® and PFA-100® for Measuring Platelet Function before Urgent Surgery in Patients with Chronic Antiplatelet Therapy

Hemostasis is crucial for reducing bleeding during surgical procedures. The points-of-care based on the platelet function test could be useful to minimize the complications related to chronic antiplatelet therapy during surgery. The present study is aimed at comparing two point-of-care platelet function devices—Platelet Function Analyzer PFA-100® (Siemens Canada, Mississauga, ON, Canada) and Plateletworks®(Helena Laboratories, Beaumont, TX, USA). Our objective is to evaluate if they provide comparable and useful information to manage anti-aggregate patients before surgery. We included patients with a femoral fracture receiving chronic antiplatelet therapy and a median age of 89 years (range from 70 to 98). A platelet function evaluation was performed on all patients before surgery using both devices—Plateletworks® and PFA-100®. The correlation between Plateletworks® and PFA-100® was performed using Cohen’s Kappa coefficient. Twenty consecutive patients participated in the trial; 16 patients were under treatment with 75 mg/day of clopidogrel, three with >300 mg/day of acetylsalicylic acid (ASA), and only one was in treatment with both antiplatelet agents. Cohen’s Kappa coefficient was 0.327 comparing PFA-100®-ADP (adenosine diphosphate) and Plateletworks® and, 0.200 comparing PFA-100®-EPI (epinephrine) and Plateletworks®. In conclusion, we found a weak concordance comparing PFA-100® and Plateletworks®. This could partially be due to the advanced age of the included patients. However, given the limited sample size, more studies are necessary to confirm these results.

Effect of bodyweight on VerifyNow Aspirin platelet function test: a retrospective review

BackgroundAntiplatelet therapy is used to prevent stent thrombosis in intracranial stents, but the optimal dose of aspirin is unknown. This study sought to determine whether the degree of platelet inhibition with aspirin is affected by bodyweight as observed through a platelet reactivity assay.MethodsThis is a retrospective review of patients who underwent neurovascular stent placement and had a VerifyNow Aspirin assay result. The primary outcome was the correlation between the VerifyNow Aspirin result, bodyweight, and the initial dose of aspirin. Secondary outcomes included the impact of the VerifyNow P2Y12 result and of weight on the incidence of bleeding or a thrombotic event.ResultsOf the 142 included patients, 62.7% weighed ≥70 kg and 88.7% were initiated on aspirin 300–325 mg daily. 83.8% achieved a therapeutic VerifyNow Aspirin result. There was minimal correlation between the VerifyNow Aspirin result, bodyweight, and aspirin dose (R2=0.02). Between patients who weighed <70 kg versus ≥70 kg, there was no difference in the mean aspirin reaction units (ARU) (449 vs 435, p=0.32) or in the incidence of bleeding (28% vs 17.1%, p=0.14) or a thrombotic event (4% vs 5.3%, p=0.59). No patient experienced stent thrombosis and eight patients experienced in-stent stenosis. In a multivariate analysis, only the VerifyNow P2Y12 result predicted the development of either bleeding or a thrombotic event (p<0.01).ConclusionsBodyweight did not influence the likelihood of obtaining a therapeutic VerifyNow Aspirin result. The clinical utility of obtaining VerifyNow Aspirin assays for this patient population is unknown.

Analysis of Platelet Function from Thromboelastography Examination in Patients with Single and Multiple Antiplatelet Therapy after Percutaneous Coronary Intervention in Dr. Saiful Anwar Malang

Each year, approximately 3 million people with coronary heart disease worldwide undergo percutaneous coronary intervention (PCI). Dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitors became the primary therapy for 6-12 months after PCI. DAPT can be continued > 12 months at a high risk of thrombosis. About 9-10% of patients with dual antiplatelet therapy still experience ischemia. The platelet function examination by thromboelastography (TEG). This research is an analytic observational study using a cross-sectional method. This study was conducted in Saiful Anwar General Hospital. Patients were divided into two groups: (1) on-single antiplatelet therapy; (2) on-dual antiplatelet therapy. The outcome measured result of the platelet function test was divided into standard, low platelet function, and platelet hypercoagulability. An analysis of the differences between single or multiple antiplatelet administration and the platelet function results was performed. There were 52 research subjects, each group of single and multiple antiplatelet therapies as many as 26 people, most of the subjects were male (82.6%) with a mean age of 57. The results of this study showed that there was no significant difference in the results of platelet function examinations between single and multiple antiplatelet therapies after 12 months of dual antiplatelet therapy.

Platelet Inhibition in Acute Coronary Syndrome and Percutaneous Coronary Intervention: Insights from the Past and Present

Platelet activation and aggregation have a pivotal role in arterial thrombosis and in the pathogenesis of both acute coronary syndromes (ACS) and in the thrombotic complications that occur in patients undergoing percutaneous coronary intervention (PCI). The past 30 years has seen the progress from early trials of clopidogrel and glycoprotein IIb/IIIa inhibitors to the application of more potent P2Y12 inhibitors prasugrel and ticagrelor. Early enthusiasm for newer and more potent antiplatelet agents, which could reduce ischemic events, has led to the understanding of the importance of bleeding and a desire to individualize and optimize treatment. It has increasingly become apparent that the potency and duration of dual antiplatelet therapy (DAPT) has to reflect the balance between ischemic and bleeding risk. Recently, multiple strategies have been proposed to individualize DAPT intensity and duration to reduce the bleeding and ischemic risks. Strategies of de-escalation of DAPT intensity, as well as shorter (less than a year) or more prolonged (beyond a year) treatment have been proposed, as well as platelet function test and genotype guidance of P2Y12 inhibitor therapy. Herein, we provide an overview of the progress in the field of antiplatelet therapy for ACS and PCI over the years, showing the current directions of travel. Ongoing studies focusing on personalized antiplatelet treatment will hopefully yield further insight into ways of optimizing outcomes for the individual.