Safety Of Antithrombotic Drugs Research Articles

Abstract 153: Multi-parametric Thrombus Profiling Microfluidics Uncovers Mechanobiology Of Hypertension And Aging-related Thrombosis

Arterial thrombosis, which represents a critical complication of cardiovascular diseases, is a leading cause of death and disability worldwide. A symbolic feature of arterial thrombosis is large-scale platelet aggregation due to high shear stress generated by stenosis. However, current hematological tests cannot evaluate arterial thrombosis in such physiological settings. To bridge this gap, we developed a microfluidics-based thrombus profiling assay (Fig. 1A) that combines multi-fluorescence imaging with a stenotic channel design to comprehensively characterize thrombi formed in high shear blood flow (Fig. 1B, C). Thrombi are characterized by a 7-dimensional profile indicating the thrombus size (Plt) and levels of fibrinogen (Fg), VWF, P-selectin, phosphatidylserine (PS) and extended (E + ) and activated α IIb β 3 in the thrombus (Fig. 1D). Using this assay, we discovered intensified thrombus formation in subjects with hypertension and/or aging (Fig. 1D). We also found extended integrin α IIb β 3 as a superior biomarker for platelet hyperreactivity than P-selectin and activated integrin α IIb β 3 and a potential predictor for arterial thrombosis (Fig. 1E). By studying the effects of anti-thrombotic agents NMC4 and 7E3 on hypertension patients’ blood, our work reveals a ‘treatment mismatch’ phenomenon that can seriously affect the efficacy and safety of anti-thrombotic drugs (Fig. 1F). Our findings provide mechanistic insights into the high risk of arterial thrombosis and antiplatelet resistance in populations with hypertension and aging. The discovered ‘treatment mismatch’ heralds a new era in thrombosis management where patients’ thrombus profiles dictate personalized therapeutic decisions to optimize treatment efficacy and reduce adverse outcomes. The outstanding performance of our assay underscores its translational potential for anti-thrombotic drug screening, thrombosis diagnosis, and personalized anti-thrombotic regimen selection.

Antithrombotic treatment after stroke due to intracerebral haemorrhage.

Antithrombotic treatment after stroke due to intracerebral haemorrhage.

EHA Guidelines on Management of Antithrombotic Treatments in Thrombocytopenic Patients With Cancer.

In cancer patients, thrombocytopenia can result from bone marrow infiltration or from anticancer medications and represents an important limitation for the use of antithrombotic treatments, including anticoagulant, antiplatelet, and fibrinolytic agents. These drugs are often required for prevention or treatment of cancer-associated thrombosis or for cardioembolic prevention in atrial fibrillation in an increasingly older cancer population. Data indicate that cancer remains an independent risk factor for thrombosis even in case of thrombocytopenia, since mild-to-moderate thrombocytopenia does not protect against arterial or venous thrombosis. In addition, cancer patients are at increased risk of antithrombotic drug-associated bleeding, further complicated by thrombocytopenia and acquired hemostatic defects. Furthermore, some anticancer treatments are associated with increased thrombotic risk and may generate interactions affecting the effectiveness or safety of antithrombotic drugs. In this complex scenario, the European Hematology Association in collaboration with the European Society of Cardiology has produced this scientific document to provide a clinical practice guideline to help clinicians in the management of patients with cancer and thrombocytopenia. The Guidelines focus on adult patients with active cancer and a clear indication for anticoagulation, single or dual antiplatelet therapy, their combination, or reperfusion therapy, who have concurrent thrombocytopenia because of either malignancy or anticancer medications. The level of evidence and the strength of the recommendations were discussed according to a Delphi procedure and graded according to the Oxford Centre for Evidence-Based Medicine.

Antithrombotic therapy in patients with acute coronary syndrome complicated by cardiogenic shock or out-of-hospital cardiac arrest: a joint position paper from the European Society of Cardiology (ESC) Working Group on Thrombosis, in association with the Acute Cardiovascular Care Association (ACCA) and European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Timely and effective antithrombotic therapy is critical to improving outcome, including survival, in patients with acute coronary syndrome (ACS). Achieving effective platelet inhibition and anticoagulation, with minimal risk, is particularly important in high-risk ACS patients, especially those with cardiogenic shock (CS) or those successfully resuscitated following out-of-hospital cardiac arrest (OHCA), who have a 30-50% risk of death or a recurrent ischaemic event over the subsequent 30 days. There are unique challenges to achieving effective and safe antithrombotic treatment in this cohort of patients that are not encountered in most other ACS patients. This position paper focuses on patients presenting with CS or immediately post-OHCA, of presumed ischaemic aetiology, and examines issues related to thrombosis and bleeding risk. Both the physical and pharmacological impacts of CS, namely impaired drug absorption, metabolism, altered distribution and/or excretion, associated multiorgan failure, co-morbidities and co-administered treatments such as opiates, targeted temperature management, renal replacement therapy and circulatory or left ventricular assist devices, can have major impact on the effectiveness and safety of antithrombotic drugs. Careful attention to the choice of antithrombotic agent(s), route of administration, drug-drug interactions, therapeutic drug monitoring and factors that affect drug efficacy and safety, may reduce the risk of sub- or supra-therapeutic dosing and associated adverse events. This paper provides expert opinion, based on best available evidence, and consensus statements on optimising antithrombotic therapy in these very high-risk patients, in whom minimising the risk of thrombosis and bleeding is critical to improving outcome.

Effectiveness and safety of antithrombotic drugs used for stroke prevention in nonvalvular atrial fibrillation (Esc-Fa Study)

Effectiveness and safety of antithrombotic drugs used for stroke prevention in nonvalvular atrial fibrillation (Esc-Fa Study)

Antithrombotic treatment in chronic heart failure and sinus rhythm: Systematic review

AIM: To assess the efficacy and safety of antithrombotic drugs(antiplatelet or anticoagulant drugs) compared to no antithrombotic treatment or placebo in patients with heart failure(HF) and sinus rhythm. METHODS: We searched Medline and Cochrane Library for randomized controlled trials evaluating antithrombotic treatment and no antithrombotic treatment in patients with HF and sinus rhythm. Risk ratio(RR) and 95%CIs were estimated performing meta-analysis with random effects method. RESULTS: Two studies met the inclusion criteria: Heart failure Long-term Antithrombotic Study and Warfarin/Aspirin Study in Heart failure, with 336 patients and mean follow-up 1.8-2.25 years. Stroke risk was not reduced by acetylsalicylic acid(RR = 1.18, 95%CI: 0.17-8.15), oral anticoagulation(RR = 0.30, 95%CI: 0.03-2.65) or overall antithrombotic drugs(RR = 0.52, 95%CI: 0.10-2.74). Acetylsalicylic acid showed a significant increased risk of worsening HF(RR = 1.78, 95%CI: 1.08-2.92), while oral anticoagulation had no impact in this outcome(RR = 1.03, 95%CI: 0.61-1.75). Overall antithrombotic drugs showed a significant risk increase of major bleeding(RR = 6.99, 95%CI: 0.89-54.64). CONCLUSION: Best available evidence does not support the routine use of antithrombotic drugs in patients with HF and sinus rhythm. These drugs, particularly oral anti-coagulation has the hazard of increase significantly major bleeding risk.