Von Willebrand Disease (VWD) is associated with significant morbidity as a result of excessive mucocutaneous bleeding symptoms. Patients with VWD can experience easy bruising, epistaxis, gastrointestinal and oral cavity bleeding, as well as heavy menstrual bleeding and bleeding after dental work, surgical procedures, and childbirth. Early diagnosis and treatment is important to prevent and treat these symptoms. We systematically reviewed the accuracy of diagnostic tests using different cut-off values of VWF:Ag and platelet-dependent VWF activity assays in the diagnosis of VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. Two investigators screened and abstracted data. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity and reported patient important outcomes when relevant. This review included 21 studies that evaluated VWD diagnosis, including the approach to patients with VWF levels that have normalized with age (6 studies), VWF cut-off levels for the diagnosis of Type 1 VWD (9 studies), and platelet-dependent VWF activity/VWF:Ag ratio cut-off levels for the diagnosis of Type 2 VWD (6 studies). The results showed low certainty in the evidence for a net health benefit from reconsidering the diagnosis of VWD versus simply removing the disease in patients with VWF levels that have normalized with age. For the diagnosis of Type 1 VWD, in patients with VWF:Ag <0.30 IU/mL, VWF sequence variants were detected in 75-82% of patients in 2 studies, and for VWF:Ag between 0.30-0.50 IU/mL, VWF sequence variants were detected in 44-60% of patients in 3 studies. A sensitivity of 0.90 (95% CI: 0.83 to 0.94), and a specificity of 0.91 (95% CI: 0.76 to 0.97) were observed for a platelet-dependent VWF activity /VWF:Ag ratio of <0.7 in detecting type 2 VWD (moderate certainty in the test accuracy results). VWF antigen and platelet-dependent activity are continuous variables with an increase in bleeding risk with decreasing levels. This systematic review shows that using a VWF activity/VWF:Ag ratio of <0.7 versus lower cutoff levels in patients with an abnormal initial VWD screen is more accurate for the diagnosis of type 2 VWD.

Von Willebrand Disease (VWD) is associated with significant morbidity because of excessive bleeding. Early diagnosis and treatment is important to prevent and treat these symptoms. We systematically reviewed the accuracy of any VWF activity assay in the diagnosis and classification of patients for VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity. The review included 77 studies that evaluated the use of newer tests of VWF platelet binding activity (VWF:GPIbR , VWF:GPIbM) and VWF:RCo for the diagnosis of VWD (13 studies), VWF propeptide to VWF:Ag ratio and desmopressin trial for the diagnosis of type 1C VWD (5 studies), VWF multimer analysis and VWF:CB/VWF:Ag ratio for the classification of type 2 VWD (11 studies), genetic testing and ristocetin-induced platelet aggregation to diagnose type 2B VWD (14 studies), genetic testing and FVIII:VWF binding to diagnose type 2N VWD (17 studies). Based on available diagnostic test accuracy, there appears to be comparable test accuracy results between newer tests of platelet binding activity of VWF function and VWF:RCo. The findings of these reviews support VWF multimer analysis or VWF:CB/VWF:Ag to diagnose type 2 VWD. The desmopressin trial test with 1- and 4-hour postinfusion blood work is the test of choice to confirm increased VWF clearance in patients with VWD suspected of type 1C. Additionally, genetic testing is most useful in diagnosing type 2B VWD and has a role in the diagnostic algorithm of suspected type 2N VWD.

Background: Von Willebrand Disease (VWD) can be associated with significant morbidity. Patients with VWD can experience bruising, mucocutaneous bleeding, and bleeding after dental and surgical procedures. Early diagnosis and treatment are important to minimize the risk of these complications. Several bleeding assessment tools (BATs) have been used to quantify bleeding symptoms as a screening tool for VWD. Objective: We systematically reviewed diagnostic test accuracy results of bleeding assessment tools (BATs) to screen patients for VWD. Methods: We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity. Results: The review included 7 cohort studies that evaluated the use of BATs to screen adult and pediatric patients for VWD. The pooled estimates for sensitivity and specificity were 75% (95% confidence interval [CI] 66%-83%) and 54% (29%-77%), respectively. Certainty of evidence varied from moderate to high. Conclusion: This systematic review provides accuracy estimates for validated BATs as a screening modality for VWD. A BAT is a useful initial screening test to determine who needs specific blood testing. The pretest probability of VWD (often determined by the clinical setting/patient population), along with sensitivity and specificity estimates will influence patient management.

Intra-aortic balloon pump counterpulsation (IABP) has been shown to prolong life in critically ill cardiac patients. However, complications including distal emboli, balloon rupture, bleeding, limb loss, and bowel ischemia continue to be associated with them. We present a case of a 56-year-old male who suffered bowel ischemia as a result of a malpositioned IABP. While the benefit of such devices in critically ill patients is not disputed, patients as well as clinicians should be aware of the potential side effects and patients undergoing IABP placement should be monitored for complications.

e13093 Background: Angiotensin-converting enzyme inhibitors (ACEIs) are commonly prescribed medications for hypertension and heart failure. Generally, ACEIs are well-tolerated medications with reasonable safety profile making them a favorable choice by many clinicians. However, several studies with conflicting results have signaled an association between ACEIs use and the development of lung cancer. We sought to systematically review the literature and perform the first meta-analysis to study the risk of lung cancer among ACEI users. Methods: We performed a literature review by searching multiple databases. A random effect meta-analysis approach was used to pool the data and relative risk was used to calculate the overall effect estimate. Results: A total of 423 articles were identified but only 6 observational studies were included with a total of 872,220 patients (634,672. ACEIs users). The relative risk of lung cancer development among ACEIs users was 1.02 (CI 0.89-1.16) compared to non-ACEIs users. Conclusions: Current systematic review and meta-analysis show no significant association between ACEIs use and the development of lung cancer. The result of our meta-analysis provides further assurance to the health care providers regarding ACEIs use.