Evaluation of an automated von Willebrand factor glycoprotein IbM activity assay compared with 3 alternative von Willebrand factor activity assays.

Background: To overcome deficiencies of the traditional von Willebrand factor (VWF) ristocetin cofactor activity assay (VWF:RCo), several automated assays for VWF platelet-binding activity have been developed. Information on the performance of these assays and their diagnostic utility remains limited.

Objectives: To validate the VWF:glycoprotein IbM assay INNOVANCE VWF Ac and compare it with an automated VWF:RCo assay as well as with an automated assay and a manual VWF:Ab assay and to generate reference ranges and analyze reproducibility of the VWF:glycoprotein IbM assay.

Effect of 6% hydroxyethyl starch 130/0.4 on kidney and haemostatic function in cardiac surgical patients: a randomised controlled trial.

Whether third-generation hydroxyethyl starch solutions provoke kidney injury or haemostatic abnormalities in patients having cardiac surgery remains unclear. We tested the hypotheses that intra-operative administration of a third-generation starch does not worsen postoperative kidney function or haemostasis in cardiac surgical patients compared with human albumin 5%. This triple-blind, non-inferiority, clinical trial randomly allocated patients aged 40-85 who underwent elective aortic valve replacement, with or without coronary artery bypass grafting, to plasma volume replacement with 6% starch 130/0.

The relation between ABO blood types and clinical and platelet function parameters in patients who underwent percutaneous coronary intervention.

Background: ABO blood groups have been associated with venous thromboembolism and arterial thrombosis. Although platelets play key roles in thrombogenesis, the relation between ABO groups and platelets is not well known and was investigated in this study.

Patients And Methods: ABO blood type information was retrospectively obtained for 206 patients who underwent percutaneous coronary intervention (PCI) and received dual antiplatelet therapy with aspirin and clopidogrel.

Establishing a Clinical Laboratory in a Tertiary/Quaternary Care Greenfield Hospital in the Middle East: Recounting the Cleveland Clinic Abu Dhabi Experience.

Context: - This review chronicles the establishment of a clinical laboratory in Cleveland Clinic Abu Dhabi, a greenfield tertiary/quaternary care hospital in the United Arab Emirates. It discusses the challenges faced, solutions sought, and lessons learned and shares insights and pitfalls that may be encountered in such an undertaking.

Objectives: - To share our experience in building a clinical laboratory in a start-up, multispecialty hospital and how we provided support and managed people, processes, and technology for building and making operational the Cleveland Clinic Abu Dhabi.

The Impact of an Electronic Expensive Test Notification.

Objectives: The impact of clinical decision support tools (CDSTs) that display test cost information has been variable.

Methods: We retrospectively analyzed the 3-year impact of a passive CDST that notified providers when the test order cost was $1,000 or more. We determined the most common expensive tests ordered, the frequency with which providers abandoned the order after notification, and the costs saved through this intervention.

Diagnostic approach to microangiopathic hemolytic disorders.

Thrombotic micro-angiopathies (TMA) are a group of related disorders that are characterized by thrombosis of the microvasculature and associated organ dysfunction, and encompass congenital, acquired, and infectious etiologies. A hall mark of TMAs is the fragmentation of erythrocytes by the microvascular thrombi, resulting in a hemolytic anemia. There are several distinct pathophysiologies leading to microangiopathic hemolysis, ranging from decreased degradation of von Willebrand factor as seen in thrombotic thrombocytopenic purpura (TTP) to endothelial damage facilitated by Escherichia coli shiga toxin or complement dysregulation, seen in shiga toxin-related hemolytic-uremic syndrome (Stx-HUS) and complement-mediated TMA (also called atypical hemolytic-uremic syndrome), respectively.

Validation of a panel of ADAMTS13 assays for diagnosis of thrombotic thrombocytopenic purpura: activity, functional inhibitor, and autoantibody test.

Introduction: Quantitation of ADAMTS13 activity, functional inhibitors, and autoantibodies is crucial in diagnosis and management of thrombotic thrombocytopenic purpura. We compared and optimized commercial assay kits and validated a testing panel.

Methods: Citrated plasma specimens from healthy volunteers and residual samples submitted for clinical testing were used in the study.

Dual biofunctional polymer modifications to address endothelialization and smooth muscle cell integration of ePTFE vascular grafts.

Expanded polytetrafluoroethylene (ePTFE) grafts were coated on the luminal surface with a cell-adhesive fluorosurfactant (FSP) polymer to promote endothelialization, followed by ethanol hydration to degas the pores and subsequent cell-adhesive, enzymatically degradable poly(ethylene glycol)-based hydrogel incorporation into the graft interstices to accommodate potential smooth muscle cell integration in the graft wall. The FSP coating on ePTFE was stable as demonstrated by a significantly reduced receding water contact angle on FSP-coated ePTFE (14.5 ± 6.

Reducing duplicate testing: a comparison of two clinical decision support tools.

Objectives: Unnecessary duplicate laboratory testing is common and costly. Systems-based means to avert unnecessary testing should be investigated and employed.

Methods: We compared the effectiveness and cost savings associated with two clinical decision support tools to stop duplicate testing.

In vivo evaluation of biomimetic fluorosurfactant polymer-coated expanded polytetrafluoroethylene vascular grafts in a porcine carotid artery bypass model.

Objective: The objective of this study was to evaluate the potential for biomimetic self-assembling fluorosurfactant polymer (FSP) coatings incorporating heptamaltose (M7-FSP) to block nonspecific protein adsorption, the cell adhesive RGD peptide (RGD-FSP), or the endothelial cell-selective CRRETAWAC peptide (cRRE-FSP) to improve patency and endothelialization in small-diameter expanded polytetrafluoroethylene (ePTFE) vascular graft implants.

Methods: ePTFE vascular grafts (4 mm in diameter, 5 cm in length) were coated with M7-FSP, RGD-FSP, or cRRE-FSP by dissolving FSPs in distilled water and flowing solution through the graft lumen for 24 hours. Coatings were confirmed by receding water contact angle measurements on the lumen surface.

Improving Molecular Genetic Test Utilization through Order Restriction, Test Review, and Guidance.

The ordering of molecular genetic tests by health providers not well trained in genetics may have a variety of untoward effects. These include the selection of inappropriate tests, the ordering of panels when the assessment of individual or fewer genes would be more appropriate, inaccurate result interpretation and inappropriate patient guidance, and significant unwarranted cost expenditure. We sought to improve the utilization of molecular genetic tests by requiring providers without specialty training in genetics to use genetic counselors and molecular genetic pathologists to assist in test selection.

Photoinitiator-free synthesis of endothelial cell-adhesive and enzymatically degradable hydrogels.

We report on a photoinitiator-free synthetic method of incorporating bioactivity into poly(ethylene glycol) (PEG) hydrogels in order to control physical properties, enzymatic biodegradability and cell-specific adhesiveness of the polymer network, while eliminating the need for UV-mediated photopolymerization. To accomplish this, hydrogel networks were polymerized using Michael addition with four-arm PEG acrylate (10 kDa), using a collagenase-sensitive peptide (CSP) as a crosslinker, and introducing an endothelial cell-adhesive peptide either terminally (RGD) or attached to the crosslinking peptide sequence (CSP-RGD). The efficiency of the Michael addition reactions were determined by nuclear magnetic resonance and Ellman's assay.

Extracellular matrix-mimetic poly(ethylene glycol) hydrogels engineered to regulate smooth muscle cell proliferation in 3-D.

The goal of this project is to engineer a defined, synthetic poly(ethylene glycol) (PEG) hydrogel as a model system to investigate smooth muscle cell (SMC) proliferation in three-dimensions (3-D). To mimic the properties of extracellular matrix, both cell-adhesive peptide (GRGDSP) and matrix metalloproteinase (MMP) sensitive peptide (VPMSMRGG or GPQGIAGQ) were incorporated into the PEG macromer chain. Copolymerization of the biomimetic macromers results in the formation of bioactive hydrogels with the dual properties of cell adhesion and proteolytic degradation.

Multi-parameter assessment of platelet inhibition and its stability during aspirin and clopidogrel therapy.

Introduction: Poor response to antiplatelet drugs is associated with adverse outcomes. We assessed platelet inhibition and its stability and tested correlation and agreement between platelet function assays.

Methods: Peripheral blood from 58 patients on both aspirin and clopidogrel who underwent percutaneous coronary intervention (PCI) was collected at hospital discharge (visit-1) and at 30-90 days (visit-2).

Duplicate laboratory test reduction using a clinical decision support tool.

Objectives: Duplicate laboratory tests that are unwarranted increase unnecessary phlebotomy, which contributes to iatrogenic anemia, decreased patient satisfaction, and increased health care costs.

Materials And Methods: We employed a clinical decision support tool (CDST) to block unnecessary duplicate test orders during the computerized physician order entry (CPOE) process. We assessed laboratory cost savings after 2 years and searched for untoward patient events associated with this intervention.

Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci.

Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry.

Algorithmic approaches to hemostasis testing.

There are many unique issues that may make a pathologist's consultation helpful in hemostasis testing. Besides the rapidly expanding knowledge of both bleeding and thrombotic disorders and a wide test menu, hemostasis testing is very sensitive to preanalytical issues (hemolysis, fill volume, time, temperature, storage conditions) and the interference of many commonly prescribed drugs. The pathologist can serve an important role in the evaluation of a patient for a bleeding or thrombotic disorder.

Cross-reactivity of cell-selective CRRETAWAC peptide with human and porcine endothelial cells.

We report on the cross-reactivity of the cell adhesive peptide CRRETAWAC between human and porcine endothelial cells (ECs). CRRETAWAC is a phage display derived peptide which has been shown to bind the α5 β1 receptor on human ECs, but does not bind platelets and thus could be incorporated into a coating for cardiovascular biomaterials that resists platelet adhesion and thrombosis, while allowing for endothelialization. To determine the cross-reactivity of the peptide, attachment and growth of human and porcine ECs on CRRETAWAC fluorosurfactant polymer (FSP) coated surfaces was explored.

Biomimetic-engineered poly (ethylene glycol) hydrogel for smooth muscle cell migration.

We report on a biomimetic scaffold as a model system to evaluate smooth muscle cell (SMC) migration in three dimensions. To accomplish this, bio-inert poly (ethylene glycol) (PEG)-based hydrogels were designed as the scaffold substrate. To mimic properties of the extracellular matrix, cell-adhesive peptide (GRGDSP) derived from fibronectin and collagenase-sensitive peptide (GPQGIAGQ) derived from collagen type I were incorporated into the PEG macromer chain.

Loci influencing blood pressure identified using a cardiovascular gene-centric array.

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ∼50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ∼2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.

Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes.

External quality assurance of fibrinogen assays using normal plasma: results of the 2008 College of American Pathologists proficiency testing program in coagulation.

Context: Proper diagnosis and therapy of fibrinogen deficiency requires high-quality fibrinogen assays.

Objective: To assess the interlaboratory bias, precision, and grading of fibrinogen assays used by laboratories participating in the United States College of American Pathologists proficiency testing program in coagulation.

Design: Two identical vials of normal plasma were sent to more than 3500 laboratories.

Clinical outcomes using a platelet function-guided approach for secondary prevention in patients with ischemic stroke or transient ischemic attack.

Background And Purpose: Antiplatelet therapy nonresponse is associated with worse clinical outcomes. We studied the clinical outcomes associated with platelet function-guided modifications in antiplatelet therapy in patients with ischemic stroke or transient ischemic attack.

Methods: From January 2005 to August 2007, 324 patients with ischemic stroke underwent platelet function testing using platelet aggregometry.