Platelet aggregation studies: autologous platelet-poor plasma inhibits platelet aggregation when added to platelet-rich plasma to normalize platelet count

Adjusting platelet count (PC) in platelet-rich plasma (PRP) using platelet-poor plasma (PPP) is recommended for platelet aggregation (PA) studies, but it could also affect PA independently of the decrease in PC. Analysis of aggregation tracings from healthy controls showed that PC correlated with PA in 47 diluted-PRPs, but not in 104 undiluted-PRPs. Dilution of 9 PRPs with PPP progressively decreased PA, while dilution of washed platelets with buffer hardly affected PA. Apyrase partially prevented the inhibitory effect of PPP. Therefore, the practice of diluting PRP with PPP to adjust platelet count should be avoided because it artefactually inhibits PA

Post-operative arterial thrombosis with non-vitamin K antagonist oral anticoagulants after total hip or knee arthroplasty

The incidence of post-operative arterial thrombosis (AT) (acute myocardial infarction [AMI] and ischaemic stroke) is increased in patients undergoing total hip replacement (THR) or total knee replacement (TKR). We compared the incidence of post-operative AT in non-vitamin K antagonist oral anticoagulants (NOACs)-treated and enoxaparintreated patients, performing a systematic review of phase III randomised controlled trials (RCTs) of venous thromboembolism (VTE) prophylaxis in THR and TKR. Studies were identified by electronic search of MEDLINE and EMBASE database until July 2014. Differences between NOACs and enoxaparin groups in the efficacy and safety outcomes were expressed as odds ratios (ORs) with pertinent 95 % confidence intervals (95 % CI). Statistical heterogeneity was assessed with the I2 statistic. Eleven phase III RCTs for a total of 31,319 patients were included. Patients underwent TKR in six studies and THR in fivestudies. The NOACs under study were dabigatran (four studies), apixaban (three studies) and rivaroxaban (four studies). AT occurred in 0.23 % of patients on NOACs and in 0.27 % of patients on enoxaparin: the OR at fixed-effect model was 0.86 (95 % CI 0.53\u20131.40; I2 11 %). No differences in AT incidence among the three NOACs were observed. The incidence of major and clinically relevant bleeding was similar in NOACs and enoxaparin groups (OR 1.03, 95 % CI 0.92\u20131.15; I2 38 %). In conclusion, in RCTs of pharmacological VTE prophylaxis in patients undergoing THR or TKR, there was no difference in the incidence of post-operative AT among patients treated with NOACs, compared to those treated with enoxaparin

Effect of thromboprophylaxis with anticoagulant drugs on the incidence of arterial thrombotic events in medical inpatients: a systematic review

Pharmacological prophylaxis of venous thromboembolism (VTE) is recommended for medical inpatients. Since arterial thrombosis (AT) shares some risk factors with VTE, it would be reasonable to assess the efficacy of thromboprophylaxis by considering both VTE and AT as outcome events. We performed a systematic review and meta-analysis of phase III RCTs on thromboprophylaxis in medical inpatients, to evaluate the quality of reporting and the incidence of AT, and the effect of thromboprophylaxis with anticoagulants on AT incidence. Studies were identified by a combined search strategy until May 2015. Differences in outcomes among groups were expressed as pooled odds ratios (OR) and 95\ua0% confidence intervals (CI). Statistical heterogeneity was assessed by I2 statistic. Twenty phase III RCTs, encompassing 54,742 patients, were included; of these, 3 (15\ua0%) reported on AT as a pre-defined secondary outcome and 8 (40\ua0%) on at least one AT outcome. Raw-unweighed incidence of fatal MI in the three RCTs is 0.37\ua0% in patients receiving unfractionated heparin or enoxaparin, and 0.38\ua0% in controls (OR 0.97, 95\ua0% CI 0.62\u20131.52; I2\ua0=\ua00\ua0%). A non-statistically significant increase in AT is reported in patients on enoxaparin compared to control (OR 1.95, 95\ua0% CI 0.89\u20134.27; I2\ua0=\ua013\ua0%). AT is underreported in RCTs on VTE prophylaxis in medical inpatients. Published data suggest that incidence of fatal MI in these patients may be clinically relevant. Insufficient data are available to draw firm conclusions on the effects of thromboprophylaxis with anticoagulants on AT incidence in this setting

A systematic review on the effect of aspirin in the prevention of post-operative arterial thrombosis in patients undergoing total hip and total knee arthroplasty

Introduction: Major surgery is associated with increased risk of venous thromboembolism (VTE), which is decreased by anticoagulant drugs. Evidence is growing that major surgery is associated with increased risk of arterial thrombosis (AT). With the aim of testing aspirin ability in reducing the risk of post-operative AT, we performed a systematic review of studies in which acetylsalicylic acid (ASA) was compared to anticoagulant drugs in VTE prophylaxis of patients undergoing total hip replacement (THR) or total knee replacement (TKR). Materials and Methods: Studies were identified by reviewing the reference of the ACCP guidelines and by electronic search of MEDLINE database from January 2012 to December 2013 and of the web database www.trialresultscenter.org. Results: We analyzed 5 of the 78 studies that were identified by our search strategy; they included 5179 patients; the median follow-up was 90. days. The incidence of post-operative AT tended to be lower in ASA-treated patients, compared to anticoagulant-treated patients, although the difference did not reach statistical significance (OR 0.56, 95%CI 0.23-1.35). In contrast, the incidence of post-operative VTE tended to be higher in ASA-treated patients, compared to anticoagulant-treated patients (1.48, 95% CI 0.93-2.36). Conclusions: Due to the heterogeneity and low quality of the studies, which do not allow firm conclusions, it is uncertain whether aspirin is effective in reducing the incidence of postoperative AT. Our results do emphasize the need for developing specifically designed studies to test the safety and efficacy of ASA in the prevention of post-operative AT. \ua9 2014 Elsevier Ltd

Venous thrombosis at unusual sites and the role of thrombophilia

Thrombophilia includes multiple inherited and acquired risk factors that determine a shift in the balance of procoagulant and anticoagulant factors promoting hypercoagulability, which is associated with an increased risk of venous thromboembolism (VTE). VTE is characterized by more common clinical manifestations, such as deep vein thrombosis of the lower limbs or pulmonary embolism, and less common clinical manifestations affecting cerebral, splanchnic, upper limbs, and retinal veins. The role of inherited thrombophilia in the pathogenesis of VTE at unusual sites is better established in cerebral vein thrombosis, but its role is less clear in splanchnic, upper limbs, and retinal vein thrombosis, in which acquired risk factors such as malignancy, central venous catheters, or systemic diseases also are frequently involved. The complex interactions between different inherited and acquired thrombophilic risk factors and their relationship with endothelium may be considered the pathophysiologic key of underlying phenotypic manifestations of thrombosis. The understanding of these mechanisms might facilitate diagnosis with appropriate investigations and improve therapeutic decision makin

Optimal Use of Novel Immunotherapeutics in B-Cell Precursor ALL

Novel immune therapies are currently being used for patients with R/R ALL based on their ability to induce not only hematologic but also molecular remission. Despite promising results, specific clinical conditions, such as high tumor burden or extra medullary relapse, are still associated with a remarkably poor clinical outcome. Therefore, how to optimize the choice and the timing of such new treatments within different clinical settings remains a matter of debate. In addition, with the aim of increasing the rate and depth of molecular remission, clinical studies are currently evaluating the combination of these immunotherapies with chemotherapy in the contest of frontline treatment. The preliminary data suggest that this approach may increase the cure rate and perhaps reduce the use of allogeneic stem cell transplantation (alloHSCT) in first remission. In Ph-positive ALL, reproducible results are showing that frontline treatment programs, based on the combination of tyrosine kinase inhibitors and immunotherapy, can achieve unprecedented rates of hematologic and molecular remission as well as a long-term cure, even in the absence of chemotherapy and alloHSCT. The results from these studies have led to the development of potentially curative treatment modalities, even for older ALL patients who cannot be treated with conventional intensive chemotherapy. The present review examined the evidence for an appropriate use of the new immunotherapies in ALL patients and provided some appraisal of the current and future possible uses of these drugs for achieving further therapeutic improvement in the treatment of this disease