Thrombosis and Thrombolysis

Correction to: Use of oral anticoagulant drugs is associated with carotid intraplaque hemorrhage in atherosclerosis patients: a meta-analysis The article Use of oral anticoagulant drugs is associated with carotid intraplaque hemorrhage in atherosclerosis patients: a meta‑analysis, written by Xin Cao, Jun Zhang and Daoying Geng, was originally published electronically on the publisher's internet portal (currently SpringerLink) on April 2019 with open access. With the author(s)' decision to step back from Open Choice, the copyright of the article changed on May 2019 to © Springer Science+Business Media, LLC, part of Springer Nature 2019 and the article is forthwith distributed under the terms of copyright

Highlights from the 2019 American College of Cardiology Scientific Sessions in New Orleans, LA

Drug-eluting stents versus bare-metal stents with a single month of dual antiplatelet therapy: a trial sequential analysis

Exosome mediated differentiation of megakaryocytes: a study on TLR mediated effects Abstract Megakaryocytes are large polyploid bone marrow cells whose function is to produce circulatory platelets. Megakaryocytes are also known to release extracellular vesicles (EVs) of varying sizes. Toll like receptors (TLRs), present on the sentinel cells are essential components of the innate immune response, these receptors are also expressed by platelets and megakaryocytes. Our data provide the evidence that TLR-2 induced MKEVs are able to recapitulate TLR-2 signalling in megakaryocytic cell line (Dami cells) and that likely induces megakaryocytic maturation by increasing the production of cytokines involved in MK maturation. TLR-2 induced MKEVs may be involved in replenishment of the immune effector platelets in circulation and its progenitor megakaryocyte in bone marrow for the physiological need of the platelets by inducing the maturation of megakaryocyte.

Acquired Von Willebrand Syndrome (AVWS) in cardiovascular disease: a state of the art review for clinicians Abstract Von Willebrand Factor (vWF) is a large glycoprotein with a broad range of physiological and pathological functions in health and disease. While vWF is critical for normal hemostasis, vascular integrity and repair, quantitative and qualitative abnormalities in the molecule can predispose to serious bleeding and thrombosis. The heritable form of von Willebrand Disease was first described nearly a century ago, but more recently, recognition of an acquired condition known as acquired von Willebrand Syndrome (AVWF) has emerged in persons with hematological, endocrine and cardiovascular diseases, disorders and conditions. An in-depth understanding of the causes, diagnostic approach and management of AVWS is important for practicing clinicians.

De-escalation from ticagrelor to clopidogrel in acute coronary syndrome patients: a systematic review and meta-analysis Abstract De-escalation from ticagrelor to clopidogrel in acute coronary syndrome (ACS) may occur for a variety of reasons, including side effects (bleeding and non-bleeding) and costs. This study sought to assess the prevalence of de-escalation from ticagrelor to clopidogrel and the occurrence of adverse clinical outcomes following de-escalation. We conducted a systematic review of clinical trials and real-world studies in ACS patients treated with ticagrelor. Real-world data on the prevalence of de-escalation during hospitalization or at discharge, after hospital discharge, and during the whole study period were included for meta-analysis. Major adverse cardiovascular events (MACE) and bleeding events occurring after de-escalation were also assessed. A total of 12 studies were eligible for meta-analysis of the prevalence of de-escalation. De-escalation from ticagrelor to clopidogrel therapy occurred with a mean prevalence of 19.8% [95% confidence interval (CI) 11.2–28.4%]. De-escalation occurred more frequently in-hospital or at discharge than after hospital discharge (23.7% vs. 15.8%). For assessment of clinical outcomes, a total of six studies were eligible for meta-analysis. Mean rate of MACE for patients with de-escalation was 2.1% (95% CI 1.1–4.1%) and the rate of major bleeding events was 1.3% (95% CI 0.4–4.5%). In conclusion, de-escalation commonly occurs in real-world practice. Although rates of major cardiovascular and bleeding events in this analysis were generally low, the profile of patients suitable for de-escalation, the impact of de-escalation on adverse clinical outcomes and how this is affected by the timing after index ACS warrants further large-scale investigation.

Body mass index reduction improves the baseline procoagulant imbalance of obese subjects Abstract Obesity is a risk factor for cardiovascular diseases. The latter being dependent (at least in part) on plasma procoagulant imbalance (i.e., hypercoagulability). Information on hypercoagulability associated with obesity is scanty and mainly based on global traditional coagulation tests or on the measurement of individual components of coagulation (i.e., pro- and anticoagulants). Plasma from 33 obese subjects was investigated soon before endoscopic balloon placement and after removal (6 months later) by thrombin-generation procedures that are thought to represent much better than any other in vitro test the coagulation process occurring in vivo. We found that obese subjects possess a state of hypercoagulability as demonstrated by the modification of the main parameters of thrombin-generation. In particular, the median value (min–max) of the endogenous thrombin potential (ETP) of obese subjects at baseline was higher than that of controls [1968 (1335–2533) vs. 1710 (1010–2119), p < 0.001]. Endoscopic balloon placement achieved a BMI reduction from 38.9 (31.7–62.3) to 31.6 (21.9–53.3), p < 0.001 and a parallel reduction of thrombin-generation as demonstrated by the following findings. The ETP measured soon after balloon removal was significantly smaller than that measured at baseline [1783 (1224–2642) vs. 1968 (1335–2533), p < 0.01]. The other parameters of thrombin-generation, including lag-time, peak-thrombin, time-to-reach the peak and velocity index showed a pattern consistent with the ETP, both at baseline and soon after balloon removal. Endoscopic balloon placement achieves concomitant reduction of BMI and thrombin-generation in subjects with obesity.

Low incidence of thromboembolism in multiple myeloma patients receiving immunomodulatory drugs; a retrospective single-institution analysis Abstract Anti-platelet agents or anticoagulants are administered for patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) to prevent thrombotic events (TEs). However, there is a discrepancy between current guidelines and clinical practice in thromboprophylaxis and the varied incidence of TEs depending on patient cohort. Therefore, a consensus on the optimal thromboprophylactic strategy is needed. To determine an appropriate strategy for the prevention of TEs in MM patients receiving IMiDs, we performed a retrospective single-institution analysis. In total, 95 MM patients (62% male, median age 65 years, range 30–85 years) from November 2008 to January 2018 were recruited, and 140 cases were analyzed in the medical-record-based study. Thromboprophylactic drugs were given to 69% of patients, anti-platelet agents to 66%, and anticoagulants to 3.0%. Seven TEs (5.0%) and six bleeding events (4.3%) were observed, but no patients died from thrombohemorrhage. The median follow-up period was 184 days (range 21–2224), and the cumulative TE incidence was 1.7% at 3 months, 7.0% at 1 year, and 12.5% at 3 years. Multivariate analysis determined that age > 70 years (p = 0.012) and BMI < 18.5 kg/m2 (p = 0.042) were the significant risk factors of TE. A low incidence of TEs was observed despite the low adherence to guideline recommendations for anticoagulant administration. These results suggest that anti-platelet agents are sufficient for thromboprophylaxis. A high-risk group of TEs in MM patients receiving IMiDs was identified, and a larger study is needed to confirm these findings.

Normal D-dimer levels in cancer patients with radiologic evidence of pulmonary embolism Abstract Accurate and expeditious diagnosis and treatment of pulmonary embolism in cancer patients improves patient outcomes. D-dimer is often used to rule out pulmonary embolism. However, this test is less accurate in cancer patients, and it is unclear whether cancer patients with normal D-dimer levels can present with pulmonary embolism. All consecutive patients who presented to The University of Texas MD Anderson Cancer Center in Houston, Texas, USA, between May 2009 and November 2015 who underwent computed tomography pulmonary angiography and plasma D-dimer level measurement were retrospectively reviewed. Patients with suspected pulmonary embolism and normal D-dimer levels were identified. Among the 8023 cancer patients identified, 1156 (14%) had pulmonary embolism. Only 35 patients with pulmonary embolism (3%) had normal plasma D-dimer levels. Twenty-six of these patients had acute pulmonary embolism and the other nine had subacute or chronic pulmonary embolism. Thirteen of the 26 acute cases were in patients with hematological cancer. Most patients (23/35, 66%) had subsegmental or segmental pulmonary embolism. Only one patient had pulmonary embolism in the main pulmonary arteries. Although it is uncommon (3%), cancer patients with radiologic evidence of pulmonary embolism can present with normal D-dimer levels. Recognizing the possibility of this uncommon occurrence is critical in the decision process for ordering diagnostic tests for evaluation of suspected pulmonary embolism.

A direct oral anticoagulant edoxaban accelerated fibrinolysis via enhancement of plasmin generation in human plasma: dependent on thrombin-activatable fibrinolysis inhibitor Abstract A direct oral anticoagulant, edoxaban, is as effective as vitamin K antagonists for the treatment of venous thromboembolism (VTE). However, the mechanism underlying the treatment effect on VTE remains to be determined. The aims of this study were to evaluate the effect of edoxaban on tissue plasminogen activator (t-PA)-induced clot lysis in human plasma and to determine the roles of plasmin and thrombin-activatable fibrinolysis inhibitor (TAFI) in the profibrinolytic effect by edoxaban. Pooled human normal plasma or TAFI-deficient plasma (containing 180 ng/mL t-PA and 0.1 nM thrombomodulin) was mixed with edoxaban or an activated TAFI inhibitor, potato tuber carboxypeptidase inhibitor (PCI). Clot was induced by adding tissue factor and phospholipids. Clot lysis time and plasma plasmin-α2 antiplasmin complex (PAP) concentration were determined. Clot structure was imaged with a scanning electron microscope. In normal plasma, edoxaban at clinically relevant concentrations (75, 150, and 300 ng/mL) and PCI significantly shortened clot lysis time. PCI increased PAP concentration and a correlation between PAP concentration and percent of clot lysis was observed. Edoxaban also dose-dependently elevated PAP concentration. In TAFI-deficient plasma, the effects of edoxaban and PCI on clot lysis and PAP concentration were markedly diminished as compared with normal plasma. Fibrin fibers were thinner in clots formed in the presence of edoxaban. In conclusion, edoxaban at clinically relevant concentrations accelerates t-PA-induced fibrinolysis via increasing plasmin generation in human plasma. The effects of edoxaban is mainly dependent on TAFI. The profibrinolytic effect of edoxaban might contribute to the efficacy for the treatment of VTE.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com