Chatree Chai-Adisaksopha

The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis

Vitamin K antagonists (VKAs) have been the standard of care for treatment of thromboembolic diseases. Target-specific oral anticoagulants (TSOACs) have been developed and found to be at least noninferior to VKAs with regard to efficacy, but the risk of bleeding with TSOACs remains controversial. We performed a systematic review and meta-analysis of phase-3 randomized controlled trials (RCTs) to assess the bleeding side effects of TSOACs compared with VKAs in patients with venous thromboembolism or atrial fibrillation. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials; conference abstracts; and www.clinicaltrials.gov with no language restriction. Two reviewers independently performed study selection, data extraction, and study quality assessment. Twelve RCTs involving 102 607 patients were retrieved. TSOACs significantly reduced the risk of overall major bleeding (relative risk [RR] 0.72, P < .01), fatal bleeding (RR 0.53, P < .01), intracranial bleeding (RR 0.43, P < .01), clinically relevant nonmajor bleeding (RR 0.78, P < .01), and total bleeding (RR 0.76, P < .01). There was no significant difference in major gastrointestinal bleeding between TSOACs and VKAs (RR 0.94, P = .62). When compared with VKAs, TSOACs are associated with less major bleeding, fatal bleeding, intracranial bleeding, clinically relevant nonmajor bleeding, and total bleeding. Additionally, TSOACs do not increase the risk of gastrointestinal bleeding.

Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials.

Direct oral anticoagulants (DOACs) are widely used as an alternative for warfarin. However, the impact of DOACs on mortality outcomes compared with warfarin remains unclear.

Hemodialysis for the treatment of dabigatran-associated bleeding: a case report and systematic review

Dabigatran, a direct thrombin inhibitor, is effective for the treatment of venous thromboembolism and the prevention of stroke and systemic embolism resulting from atrial fibrillation. The most effective way of reversing the anticoagulant effect of dabigatran in patients who have bleeding complications is unknown.

Thromboembolic events, recurrent bleeding and mortality after resuming anticoagulant following gastrointestinal bleeding

Gastrointestinal (GI) bleeding commonly complicates anticoagulant therapy. We aimed to systematically review the published literature to determine the risk of thromboembolism, recurrent GI bleeding and mortality for patients on long-term anticoagulation who experience GI bleeding based on whether anticoagulation therapy was resumed. We performed a systematic review of phase III randomised controlled trials and cohort studies in patients with atrial fibrillation or venous thromboembolism who received oral anticoagulant. We searched MEDLINE, EMBASE and CENTRAL (from 1996-July 2014), conferences abstracts (from January 2006-July 2014) and www.clinicaltrials.gov (up to the last week of July 2014) with no language restriction. Two reviewers independently performed study selection, data extraction and study quality assessment. A total of three studies were included in the meta-analysis. The resumption of warfarin was associated with a significant reduction in thromboembolic events (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.52 to 0.88, p<0.004, I(²)=82%). There was an increase in recurrent GI bleeding but not statistically significant for patients who restarted warfarin compared to those who did not (HR 1.20, 95% CI 0.97 to 1.48, p = 0.10, I(²) = 0%). Resumption of warfarin was associated with significant reduction in mortality (HR 0.76, 95% CI 0.66 to 0.88, p<0.001, I(²) = 87%). This meta-analysis demonstrates that resumption of warfarin following interruption due to GI bleeding is associated with a reduction in thromboembolic events and mortality without a statistically significant increase in recurrent GI bleeding.

Noninvasive Ventilation With vs Without Early Surfactant to Prevent Chronic Lung Disease in Preterm Infants: A Systematic Review and Meta-analysis

IMPORTANCE Controversy exists regarding which of the 2 major strategies currently used to prevent chronic lung disease (CLD) in preterm infants is optimal: noninvasive continuous positive airway pressure (NCPAP) or intubate-surfactant-extubate (INSURE). Preterm infants often require surfactant administration because of respiratory distress syndrome. OBJECTIVE To evaluate whether early INSURE or NCPAP alone is more effective in preventing CLD, death, or both. DATA SOURCES We searched the MEDLINE, EMBASE, Cochrane Controlled Trials Register, and Cumulative Index to Nursing and Allied Health Literature databases from their inception to January 2, 2015, along with conference proceedings and trial registrations. STUDY SELECTION Randomized clinical trials that compared early INSURE with NCPAP alone in preterm infants who had never been intubated before the study entry were selected. Among 1761 initially identified articles, 9 trials (1551 infants) were included. DATA EXTRACTION AND SYNTHESIS Duplicate study selection and data extraction were performed. Meta-analysis was conducted using random-effects models with quality-of-evidence assessment according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. MAIN OUTCOMES AND MEASURES Seven main outcomes were selected a priori to be assessed according to GRADE, including a composite outcome of CLD and/or death, CLD alone, death alone, air leakage, severe intraventricular hemorrhage, neurodevelopmental impairment, and a composite outcome of death and/or neurodevelopmental impairment. RESULTS There were no statistically significant differences between early INSURE and NCPAP alone for all outcomes assessed. However, the relative risk (RR) estimates appeared to favor early INSURE over NCPAP alone, with a 12% RR reduction in CLD and/or death (RR, 0.88; 95% CI, 0.76-1.02; risk difference [RD], -0.04; 95% CI, -0.08 to 0.01; moderate quality of evidence), a 14% decrease in CLD (RR, 0.86; 95% CI, 0.71-1.03; RD, -0.03; 95% CI, -0.06 to 0.01; moderate quality of evidence), and a 50% decrease in air leakage (RR, 0.50; 95% CI, 0.24-1.07; RD, -0.03; 95% CI, -0.06 to 0.00; very low quality of evidence). The sample size was less than the optimal information size. CONCLUSIONS AND RELEVANCE Currently, no evidence suggests that either early INSURE or NCPAP alone is superior to the other. INSURE does not appear to increase CLD and/or death, CLD alone, and air leakage and may reduce these adverse outcomes compared with NCPAP alone. Further adequately powered trials are required.

Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal. A systematic review and meta-analysis.

Urgent reversal of warfarin is required for patients who experience major bleeding or require urgent surgery. Treatment options include the combination of vitamin K and coagulation factor replacement with either prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP). However, the optimal reversal strategy is unclear based on clinically relevant outcomes. We searched in MEDLINE, EMBASE and Cochrane library to December 2015. Thirteen studies (5 randomised studies and 8 observational studies) were included. PCC use was associated with a significant reduction in all-cause mortality compared to FFP (OR= 0.56, 95 % CI; 0.37-0.84, p=0.006). A higher proportion of patients receiving PCC achieved haemostasis compared to those receiving FFP, but this was not statistically significant (OR 2.00, 95 % CI; 0.85-4.68). PCC use was more likely to achieve normalisation of international normalised ratio (INR) (OR 10.80, 95 % CI; 6.12-19.07) and resulted in a shorter time to INR correction (mean difference -6.50 hours, 95 %CI; -9.75 to -3.24). Red blood cell transfusion was not statistically different between the two groups (OR 0.88, 95 % CI: 0.53-1.43). Patients receiving PCC had a lower risk of post-transfusion volume overload compared to FFP (OR 0.27, 95 % CI; 0.13-0.58). There was no statistically significant difference in the risk of thromboembolism following administration of PCC or FFP (OR 0.91, 95 % CI; 0.44-1.89). In conclusion, as compared to FFP, the use of PCC for warfarin reversal was associated with a significant reduction in all-cause mortality, more rapid INR reduction, and less volume overload without an increased risk of thromboembolic events.

Major arterial events in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a meta-analysis

Abstract There is growing evidence that tyrosine kinase inhibitors (TKIs) may be associated with an increased risk of arterial events. We performed a meta-analysis to estimate the incidence of arterial events in patients with CML treated with TKIs. We identified 29 studies enrolling 15,706 patients. The incidence rates of composite of major arterial events were 0.8 per 100 patient-years for non-TKI treatments, 1.1 per 100 patient-years for dasatinib, 0.1 per 100 patient-years for imatinib, 0.4 per 100 patient-years for bosutinib, 2.8 per 100 patient-years for nilotinib and 10.6 per 100 patient-years for ponatinib. The relative risk (RR) for nilotinib compared with imatinib suggests a significantly increased risk of the composite of major arterial events with nilotinib treatment (RR 5.3; 95%CI 3.0–9.3, p < 0.001). This study demonstrates that, patients who received nilotinib or ponatinib had a greater number of major arterial events when compared to non-TKI-, imatinib-, dasatinib- and bosutinib-treated patients.

The impact of ruxolitinib on thrombosis in patients with polycythemia vera and myelofibrosis: a meta-analysis.

The Food and Drug Administration approval of ruxolitinib for treatment of myelofibrosis and polycythemia vera has changed the management of patients with myeloproliferative neoplasms. Yet the impact of this therapy on risk of thrombosis, a major cause of morbidity and mortality among these patients, remains unknown. The aim of this study was to evaluate the impact of ruxolitinib on the risk of thrombosis among patients with polycythemia vera or myelofibrosis. Following identification of randomized controlled trials comparing ruxolitinib to standard care or placebo, rates of thrombosis, including venous and arterial thrombosis, were analyzed using fixed effects models. Rates of thrombosis were significantly lower among patients treated with ruxolitinib [risk ratio 0.45, 95% confidence interval (CI) 0.23–0.88]. Subgroup analysis of venous and arterial thrombosis demonstrated similar risk ratios, which did not reach statistical significance (risk ratio 0.46, 95% CI 0.14–1.48 and RR 0.42, 95% CI 0.18–1.01, respectively). In conclusion, our analysis suggests that JAK2 inhibition with ruxolitinib decreases the risk of arterial and/or venous thrombosis in patients with polycythemia vera or myelofibrosis. These findings will require confirmation in a prospective study.

Clinical Manifestations and Risk Factors for Complications of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms

BACKGROUND Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid lineages. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical Philadelphia chromosome (Ph)-negative MPN that have a Janus Kinase 2 (JAK2) mutation, especially JAK2V617F in the majority of patients. The major complications of Ph-negative MPNs are thrombosis, hemorrhage, and leukemic transformation. OBJECTIVE To study clinical manifestations including symptoms, signs, laboratory findings, and JAK2V617F mutations of Ph-negative MPN (PV, ET and PMF) as well as their complications. MATERIALS AND METHODS All Ph-negative MPN (PV, ET and PMF) patients who attended the Hematology Clinic at Maharaj Nakorn Chiang Mai Hospital from January, 1 2003 through December, 31 2013 were retrospectively reviewed for demographic data, clinical characteristics, complete blood count, JAK2V617F mutation analysis, treatment, and complications. RESULTS One hundred and fifty seven patients were included in the study. They were classified as PV, ET and PMF for 68, 83 and 6 with median ages of 60, 61, and 68 years, respectively. JAK2V617F mutations were detected in 88%, 69%, and 100% of PV, ET and PMF patients. PV had the highest incidence of thrombosis (PV 29%, ET 14%, and PMF 0%) that occurred in both arterial and venous sites whereas PMF had the highest incidence of bleeding (PMF 17%, ET 11%, and PV 7%). During follow up, there was one ET patient that transformed to acute leukemia and five cases that developed thrombosis (three ET and two PV patients). No secondary myelofibrosis and death cases were encountered. CONCLUSIONS Ph-negative MPNs have various clinical manifestations. JAK2V617F mutations are present in the majority of PV, ET, and PMF patients. This study confirmed that thrombosis and bleeding are the most significant complications in patients with Ph-negative MPN.

A systematic review of definitions and reporting of bleeding outcome measures in haemophilia.

Bleeding frequency is an important outcome commonly used in haemophilia studies. There is a variation in practice in how bleeding is measured and defined.