Studies of haemostasis in acute coronary syndromes and diabetes mellitus

The pathophysiology of acute coronary syndromes (ACS) includes atherosclerotic plaque rupture and coronary thrombus formation. Antithrombotic treatment is effective but recurrent atherothrombotic or bleeding complications are not uncommon. Aim: To study new markers and methods concerning haemostasis in ACS and conditions associated with high risk of this disease, in the search for laboratory tools that could help increase understanding of disease mechanisms and help to identify patients at risk. Methods and Results: Eighty-seven patients suffering from ACS were investigated at admission (S1), after 24 h on standard antithrombotic treatment (S2), and six months after the acute event (S3). Sex- and age-matched healthy controls were also investigated. Thrombin generation in vivo was assessed by measurement of prothrombin fragment F1+2 in plasma and in vitro by using the calibrated automated thrombogram (CAT). Fibrinolysis was measured by assessment of PAI-1 and TAFI activity concentrations. The latter method was used as a result of a methods evaluation study. We also employed a global method developed by our group (Ohindex), to evaluate haemostasis. Oh-index gives a measure of fibrin formation and degradation capacity in plasma. Furthermore, a flow cytometric assay set up by our group was employed to measure platelet microparticles (PMP) in plasma formed upon platelet activation. In addition, we investigated ADAMTS13, an enzyme previously called von Willebrand factor (VWF)-degrading protease, and we also measured its substrate (i.e. VWF). The ACS patients, of whom more than half were high-risk patients (TIMI score ≥ 4), showed signs of inflammation and endothelial activation, as expected. Only the CAT method could detect hypercoagulability in the patients (increased peak thrombin concentration) and this finding was evident acutely and 6 months after the event. Thrombin generation in vivo (F1+2) or fibrin generation capacity in plasma did not indicate hypercoagulability at any time point. CAT, F1+2 and fibrin generation capacity were strongly reduced following initiation of antithrombotic treatment (S2), as expected. PAI-1 and TAFI levels were elevated, reflecting impaired fibrinolysis, but this was not observed with our method that assesses fibrin degradation capacity; rather, this method indicated increased fibrinolytic capacity at admission and this capacity was grossly increased after initiation of standard antithrombotic treatment (S2). ADAMTS13 activity and antigen concentrations were unchanged during and after ACS, but the VWF:ADAMTS13 ratio was significantly elevated in ACS patients and two different populations of patients with diabetes mellitus. The ACS patients had significantly elevated concentrations of PMP at admission, particularly PMP subpopulations with exposed P-selectin and tissue factor (TF). Concentrations of PMP decreased following initiation of antithrombotic treatment (S2), but in the subpopulations with exposed P-selectin and TF they remained significantly higher than in controls at 6 months (S3). Conclusions: Our PMP data are in agreement with the concept of a dominating role of platelets in the pathophysiology of ACS, and PMP deserve to be studied in more detail in coronary artery disease, including their roles in the effects of treatment and relationships to coagulation, risk and prognosis. However, the data on coagulation and fibrinolysis obtained in this study indicate that there is not yet sufficient information to support the clinical use of markers to assess coagulation or fibrinolysis in individual patients

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701