Abstract

BACKGROUND Patients with immune thrombocytopenia are at risk of bleeding during surgery, and intravenous immunoglobulin is commonly used to increase the platelet count. We aimed to establish whether perioperative eltrombopag was non-inferior to intravenous immunoglobulin. METHODS We did a randomised, open-label trial in eight academic hospitals in Canada. Patients were aged at least 18 years, with primary or secondary immune thrombocytopenia and platelet counts less than 100 × 10(9) cells per L before major surgery or less than 50 × 10(9) cells per L before minor surgery. Previous intravenous immunoglobulin within 2 weeks or thrombopoietin receptor agonists within 4 weeks before randomisation were not permitted. Patients were randomly assigned to receive oral daily eltrombopag 50 mg from 21 days preoperatively to postoperative day 7 or intravenous immunoglobulin 1 g/kg or 2 g/kg 7 days before surgery. Eltrombopag dose adjustments were allowed weekly based on platelet counts. The randomisation sequence was generated by a computerised random number generator, concealed and stratified by centre and surgery type (major or minor). The central study statistician was masked to treatment allocation. The primary outcome was achievement of perioperative platelet count targets (90 × 10(9) cells per L before major surgery or 45 × 10(9) cells per L before minor surgery) without rescue treatment. We did intention-to-treat and per-protocol analyses using an absolute non-inferiority margin of -10%. This trial is registered with ClinicalTrials.gov, NCT01621204. FINDINGS Between June 5, 2013, and March 7, 2019, 92 patients with immune thrombocytopenia were screened, of whom 74 (80%) were randomly assigned: 38 to eltrombopag and 36 to intravenous immunoglobulin. Median follow-up was 50 days (IQR 49-55). By intention-to-treat analysis, perioperative platelet targets were achieved for 30 (79%) of 38 patients assigned to eltrombopag and 22 (61%) of 36 patients assigned to intravenous immunoglobulin (absolute risk difference 17·8%, one-sided lower limit of the 95% CI 0·4%; p(non-inferiority)=0·005). In the per-protocol analysis, perioperative platelet targets were achieved for 29 (78%) of 37 patients in the eltrombopag group and 20 (63%) of 32 in the intravenous immunoglobulin group (absolute risk difference 15·9%, one-sided lower limit of the 95% CI -2·1%; p(non-inferiority)=0·009). Two serious adverse events occurred in the eltrombopag group: one treatment-related pulmonary embolism and one vertigo. Five serious adverse events occurred in the intravenous immunoglobulin group (atrial fibrillation, pancreatitis, vulvar pain, chest tube malfunction and conversion to open splenectomy); all were related to complications of surgery. No treatment-related deaths occurred. INTERPRETATION Eltrombopag is an effective alternative to intravenous immunoglobulin for perioperative treatment of immune thrombocytopenia. However, treatment with eltrombopag might increase risk of thrombosis. The decision to choose one treatment over the other will depend on patient preference, resource limitations, cost, and individual risk profiles. FUNDING GlaxoSmithKline and Novartis.

Abstract

Lateral epicondylitis (LE) is difficult to manage and can result in significant patient morbidity. Currently, the clinical use of platelet-rich plasma (PRP) for painful tendons has received attention, but its efficacy remains controversial. This study aimed to investigate the clinical effects of PRP and its biological components. 156 patients with LE were randomly divided into group 1, treated with a single injection of 2-mL autologous PRP, and group 2, treated with a control received only physical therapy without injection. Both groups used a tennis elbow strap and performed stretching and strengthening exercises during 24 weeks' follow-up. Pain and functional improvements were assessed using the visual analog scale (VAS), Modified Mayo Clinic Performance Index for the elbow, and magnetic resonance imaging (MRI). White blood cell count, platelet count, and levels of platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, transforming growth factor-beta (TGF-beta), vascular endothelial growth factor, epithelial growth factor, and interleukin-1 beta in PRP were measured and investigated for statistical correlation with the clinical score. At 24 weeks, all pain and functional variables, including VAS score, Mayo Clinic performance scores, and MRI grade, improved significantly in group 1 (P < 0.05). PDGF-AB, PDGF-BB, and TGF-beta levels were more significantly increased in PRP than in whole blood. TGF-beta level significantly correlated with Mayo Clinic performance score and MRI grade improvement. Thus, TGF-beta level in PRP is considered to play a pivotal role in tendon healing. These results may contribute to identifying the best protocol for PRP application in tendinopathies. This article is protected by copyright. All rights reserved.

Abstract

OBJECTIVE Early and aggressive treatment of trauma-associated coagulopathy through transfusion of high plasma to packed red blood cell ratios is gaining favor. Whether this strategy is associated with improved survival is unclear. We performed a systematic review to determine whether higher plasma to packed red blood cell ratios compared with lower plasma to packed red blood cell ratios were associated with a survival advantage. DATA SOURCES We searched electronic databases MEDLINE, Embase, and Web of Science from 1950 to February 2010 for studies comparing mortality in massively transfused trauma cohorts receiving different plasma to packed red blood cell ratios. STUDY SELECTION Two reviewers independently performed study selection. Discrepancies in study selection were resolved by discussion and consensus. DATA EXTRACTION Two reviewers independently extracted data from each study using a standardized form. Two authors independently assessed study quality using the Newcastle-Ottawa Scale. DATA SYNTHESIS Eleven observational studies and no randomized controlled trials were identified. Three studies found a survival benefit with a 1:1 plasma to packed red blood cell transfusion ratio compared with either higher or lower ratios. Six studies did not examine a 1:1 ratio but concluded that higher plasma to packed red blood cell ratios improved survival. Secondary outcomes, including multiorgan system failure, packed red blood cell transfusion, respiratory outcomes, and coagulation variables, did not uniformly fav or 1:1 or higher plasma to packed red blood cell ratios. CONCLUSIONS Methodological flaws, including survival bias, and heterogeneity between studies preclude statistical comparisons concerning the effects of a 1:1 plasma to packed red blood cell transfusion ratio. There is insufficient evidence to support a survival advantage with a 1:1 plasma to packed red blood cell transfusion strategy. Randomized controlled trials evaluating safety and efficacy are warranted before a high plasma to packed red blood cell transfusion ratio can be recommended.

Abstract

Immune thrombocytopenia (ITP) is commonly encountered in clinical practice. In 1996 the American Society of Hematology published a landmark guidance paper designed to assist clinicians in the management of this disorder. Since 1996 there have been numerous advances in the management of both adult and pediatric ITP. These changes mandated an update in the guidelines. This guideline uses a rigorous, evidence-based approach to the location, interpretation, and presentation of the available evidence. We have endeavored to identify, abstract, and present all available methodologically rigorous data informing the treatment of ITP. We provide evidence-based treatment recommendations using the GRADE system in those areas in which such evidence exists. We do not provide evidence in those areas in which evidence is lacking, or is of lower quality - interested readers are referred to a number of recent, consensus-based recommendations for expert opinion in these clinical areas. Our review identified the need for additional studies in many key areas of the therapy of ITP such as comparative studies of front-linetherapy for ITP, the management of serious bleeding in patients with ITP, and studies that will provide guidance about which therapy should be used as salvage therapy for patients after failure of a first-line intervention. 2011 by The American Society of Hematology.

Abstract

BACKGROUND Minimizing bleeding and transfusion is desirable given its cost, complexity and potential for adverse events. Concerns have been heightened by recent data demonstrating that bleeding events may predict worse outcomes and by warnings about the safety of erythropoietic stimulating agents. Prior small studies suggest that antifibrinolytic agents may reduce bleeding and transfusion need in patients undergoing total hip replacement (THR) or total knee arthroplasty (TKA). However, no single study has been large enough to definitively determine if these agents are safe and effective. To address this issue we performed a systematic review of randomized trials describing the use of tranexamic acid, epsilon aminocaproic acid, or aprotinin administration in the perioperative setting. METHODS MEDLINE, EMBASE, CINAHL and the Cochrane databases were searched for relevant trials. Two independent reviewers abstracted total blood loss, transfusion requirements, and venous thromboembolism (VTE) rates. Data were combined using the Mantel-Haenszel method and dichotomous data expressed as relative risk (RR) with 95% confidence intervals (CI). RESULTS Patients receiving antifibrinolytic agents had reduced transfusion need (RR 0.52; 95% CI, 0.42 to 0.64; P<0.00001), reduced blood loss and no increase in the risk of VTE (RR 0.95% CI, 0.80 to 1.10, I(2)=0%, P=0.531). CONCLUSIONS We conclude that antifibrinolytic agents may reduce bleeding and transfusion in patients undergoing THR or TKA who receive appropriate antithrombotic prophylaxis. There is a need for a large, adequately powered prospective study to carefully examine the safety and efficacy of these agents.