The vexed question of whether or not to measure levels of direct oral anticoagulants before surgery or invasive procedures.

Direct oral anticoagulants (DOAC) possess high bioavailability, and their anticoagulant effect is more predictable than that of vitamin K antagonists, hence they do not require routine dose adjustment based on laboratory testing. However, there are circumstances when laboratory testing may be useful, including patients who need to undergo surgery or invasive procedures. Most guidelines state that patients on DOAC may safely undergo surgery/invasive procedures by stopping anticoagulation for a few days before intervention without testing if renal function is within normal limits. This review article discusses the pros and cons of measuring (or not measuring) DOAC levels before surgery/invasive procedures by a multidisciplinary team of experts with different background, including the thrombosis laboratory, clinical thrombosis, internal medicine, cardiology and nephrology. The conclusion is that measuring DOAC with dedicated tests before surgical or invasive procedures is important for patient safety. It provides the best and most direct evidence to rule in (or to rule out) clinically relevant concentrations of residual drugs. Regulatory agencies should urgently approve their use in clinical practice. Hospital administrators should make them available, and clinical laboratories should set up the relative methods and make them available to clinicians.

Platelet function and long-term antiplatelet therapy in women: is there a gender-specificity? A 'state-of-the-art' paper.

Although the female gender is generally less represented in cardiovascular studies, observational and randomized investigations suggest that-compared with men-women may obtain different benefits from antiplatelet therapy. Multiple factors, including hormonal mechanisms and differences in platelet biology, might contribute to such apparent gender peculiarities. The thrombotic and bleeding risks, as well as outcomes after a cardiovascular event, appear to differ between genders, partly in relation to differences in age, comorbidities and body size. Equally, the benefits of antiplatelet therapy may differ in women compared with men in different vascular beds, during primary or secondary prevention and according to the type of an antiplatelet agent used. This document is an attempt to bring together current evidence, clinical practices and gaps of knowledge on gender-specific platelet function and antiplatelet therapy. On the basis of the available data, we provide suggestions on current indications of antiplatelet therapy for cardiovascular prevention in women with different clinical features; no strong recommendation may be given because the available data derive from observational studies or post hoc/subgroup analyses of randomized studies without systematic adjustments for baseline risk profiles.

Perioperative assessment of platelet function by Thromboelastograph Platelet Mapping in cardiovascular patients undergoing non-cardiac surgery.

UNLABELLED: Five percent of patients on dual antiplatelet therapy after coronary artery stent implantation will need non-cardiac surgery within the first year of therapy, and many more will need surgery later on. A function assay that evaluates platelet reactivity and inhibition by drug therapy is beneficial for such patients. Platelet Mapping assay (PM) using the TEG analyzer was tested in surgical patients. After IRB approval, 60 patients on combined aspirin and clopidogrel therapy were consented and enrolled. The TEG maximal amplitude (MA) and the percentage (%) platelet inhibition were recorded and analyzed. Fifty-seven patients (mean age 65.7 ± 10.9 years) had preoperative data only. Distribution of preoperative ADP (43.6 ± 24.4%) and AA inhibition (52.8 ± 30.2%) was determined, as well as for the preoperative MA ADP (43.1 ± 15.9 mm) and MA AA (37.2 ± 19.6 mm), showing an offset of the effect of both medications starting from day 3. Patients with complete pre- and postoperative data were stratified depending on duration off antiplatelet therapy (≤3 days, 3-7 days and >7 days): n = 27, ADP % preop inhibition (43.2 ± 21.6%), ADP % postop inhibition (32.3 ± 18.3%), p = 0.048. Distribution of immediate pre- and post- ADP and AA % inhibitions, showing a possible reduction in Δ of inhibition for clopidogrel at 3 days, were also assessed. CONCLUSION: According to the findings, the TEG PM assay might be a feasible approach to objectively evaluate the effects of aspirin and clopidogrel during the perioperative period and potentially guide drug management.

Cardiovascular risk assessment beyond Systemic Coronary Risk Estimation: a role for organ damage markers.

BACKGROUND: Cardiovascular risk assessment in the clinical practice is mostly based on risk charts, such as Framingham risk score and Systemic Coronary Risk Estimation (SCORE). These enable clinicians to estimate the impact of cardiovascular risk factors and assess individual cardiovascular risk profile. Risk charts, however, do not take into account subclinical organ damage, which exerts independent influence on risk and may amplify the estimated risk profile. Inclusion of organ damage markers in the assessment may thus contribute to improve this process. OBJECTIVE: Our aim was to evaluate the influence of implementation of SCORE charts with widely available indexes of organ damage, with the purpose to ameliorate individual risk assessment. METHODOLOGY: We searched www.Pubmed.gov for evidence about the predictive value of left ventricular hypertrophy (LVH), estimated glomerular filtration rate (eGFR), microalbuminuria (MAU) and metabolic syndrome on different risk profiles estimated by SCORE. Interventional and observational trials including at least 200 patients and published after 2000 were selected. RESULTS: The presence of organ damage as well as the number of abnormal parameters indicating organ damage is associated with increased cardiovascular risk, independently of SCORE. In the area of high risk, the impact of different markers of organ damage is heterogeneous. Combined risk models of SCORE and subclinical organ damage have major impact on risk stratification and may impact on recommendation in primary prevention in all SCORE categories. CONCLUSION: Available evidence suggests a tangible clinical advantage of adding the evaluation of simple organ damage markers to risk charts in cardiovascular risk prediction.

Assessment of fibrinolytic activity by measuring the lysis time of a tissue-factor-induced clot: a feasibility evaluation.

A clot lysis time assay in which a tissue factor-induced fibrin clot is lysed by exogenously added tissue plasminogen activator has been recently reported. We evaluated the feasibility of clot lysis time in a routine hemostasis laboratory, and its correlation with thrombin activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 levels and changes with aging in 185 healthy participants. Clot lysis time was assessed by monitoring changes in turbidity during clot formation and subsequent lysis using a computerized kinetic spectrophotometric microtiter plate. After preliminary experiments, 100 and 160 ng/mL tissue plasminogen activator concentrations were chosen for the study. Clot lysis time was calculated by a new mathematical analysis of the lysis curve based on discrete derivative. Clot lysis time, thrombin activatable fibrinolysis inhibitor, and plasminogen activator inhibitor-1 plasma levels showed a normal distribution. For both concentrations of tissue plasminogen activator, clot lysis time progressively increased with increase in age (P < .0001) and was significantly correlated with thrombin activatable fibrinolysis inhibitor antigen, thrombin activatable fibrinolysis inhibitor activity, and plasminogen activator inhibitor-1 antigen (at least P < .01). During linear regression analysis, thrombin activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 antigen were found to significantly influence clot lysis time (at least P < .01). Clot lysis time determination has a good laboratory performance. Our new method of calculation is independent of the time of reading and allows a more accurate and consistent detection of both short and prolonged lysis times. Our data suggest the feasibility of the use of this test in the work of routine hemostasis laboratory.

Different models for oral anticoagulation management may be applied provided that minimal assistance criteria are fulfilled: an Italian experience.

The efficacy of adjusted-dose oral anticoagulant therapy (OAT) in the prevention of thrombotic complications in various clinical conditions is well documented. Management of OAT requires a trained physician, an organized system of follow-up, reliable international normalized ratio monitoring, and good patient communication and education. Drug interactions with coumarins are a major cause of excessive anticoagulation and hence could be an important determinant of bleeding in patients on OAT. An analysis conducted in Toscana in 2005 found 31,221 patients persistently on OAT. During the same period, potential drug-drug interactions were detected in 11,778 of these patients (37.7%). Thus, the regional government enacted a specific law for the organization of OAT management to give all patients a minimal standard of quality of OAT. A specific educational campaign was promoted with the slogan "Written is better." Three possible models to follow individual patients were identified in relation to available resources and geographic characteristics of the living area: Anticoagulation Clinic (AC), General Practitioner (GP), or combined AC and GP management. This experience, although obtained in a limited geographic area, could help improve the efficacy and safety of OAT management.

Assessment of platelet function on whole blood by multiple electrode aggregometry in high-risk patients with coronary artery disease receiving antiplatelet therapy.

This study sought to compare Multiplate impedance platelet aggregometry (IPA) with light transmission aggregometry (LTA) and the PFA-100 for determining the prevalence of residual platelet reactivity (RPR) by the Multiplate IPA in 297 patients with acute coronary syndrome receiving dual antiplatelet therapy. Aggregations were induced by adenosine-5 diphosphate (ADP), arachidonic acid, and collagen. PFA-100 closure times were measured by collagen and ADP and epinephrine (CEPI) cartridges. Significant correlations were observed between Multiplate IPA and LTA after all stimulations (P < .0001) and between Multiplate IPA (arachidonate and collagen) and PFA-100 CEPI closure time (P < .0001 for both). Cutoff values of Multiplate IPA (for all stimulations) were calculated for the identification of RPR. Between the Multiplate IPA and LTA good agreement was found with all 3 agonists (P < .0001 for all). Multiplate IPA might represent a reliable, handy, rapid tool to monitor antiplatelet therapy in clinical practice and for clinical investigations.

Stroke risk in atrial fibrillation patients on warfarin. Predictive ability of risk stratification schemes for primary and secondary prevention.

Atrial fibrillation (AF) patients are widely heterogeneous in terms of ischaemic stroke risk, and several risk stratification schemes have been developed. We performed a prospective study on 662 AF patients on long-term oral anticoagulant therapy (OAT), evaluating the agreement among the different schemes and their correlation with adverse events recorded during follow-up. Patients at low risk were similarly distributed among the different models. Instead, patients classed at moderate risk were 49.2% by CHADS(2) score, 27.6% by NICE and 2.3% by ACCP. As a consequence patients classed at high risk were 46.1% by CHADS(2), 69.8% by NICE and 95.3% by ACCP. CHADS(2 )and NICE scores were associated to the best predictive accuracy. A separate analysis was performed for patients on treatment for secondary prevention, and we observed that they were included in high risk groups by all models, except for 14 patients (6.3%) classed at moderate risk by CHADS(2) even though these patients are at very high risk and the use of aspirin could be unsafe for them. During follow-up 32 major bleeding (1.35 per 100 patient/years) and 39 thrombotic events (1.64 per 100 patient/years) were observed. Among patients on OAT for secondary prevention, both bleeding and thrombotic events mostly occurred in high-risk patients. Even if the absolute rate of adverse events is low, this finding seems to confirm the high stroke risk of this group of patients. For patients on secondary prevention there is no need for further stratification and warfarin should be the treatment of choice.