PFA-100 System: A New Method for Assessment of Platelet Dysfunction.

This is a celebratory reprint of a historical paper published in STH in 1998. The original Abstract follows.The PFA-100 system is a platelet function analyzer designed to measure platelet-related primary hemostasis.

Prospective evaluation of protein C and factor VIII in prediction of cancer-associated thrombosis.

Venous thromboembolism (VTE) is a preventable disease, yet it is one of the leading causes of death among patients with cancer. Improving risk stratification mechanisms will allow us to personalize thrombo-prophylaxis strategies. We sought to evaluate Collagen and Thrombin Activated Platelets (COAT-platelets) as well as protein C and factor VIII as biomarkers predictive of cancer-associated thrombosis in a prospective cohort of patients with cancer.

Accuracy and safety of (99m)Tc-labeled anti-D-dimer (DI-80B3) Fab' fragments (ThromboView®) in the diagnosis of deep vein thrombosis: a phase II study.

Background: The assessment of patients with suspected deep vein thrombosis (DVT) remains challenging despite current diagnostic algorithms. (99m)Tc-labelled DI-DD3B6/22-80B3 Fab´ fragments ((99m)Tc-DI-80B3, ThromboView®) is a novel diagnostic test that uses a radiolabelled humanized monoclonal antibody fragment specific for the D-dimer region of cross-linked fibrin to detect DVT. This test has an anatomic component to locate DVT and a functional component to differentiate acute (newly formed) thrombus from inactive (old) thrombus.

Phosphofructokinase deficiency and portal and mesenteric vein thrombosis.

Phosphofructokinase deficiency is a rare disorder with less than 100 reported cases; the contribution of altered glucose metabolism in other tissues to the pathogenesis of the disease is not fully understood. The authors present a unique case of portal and mesenteric vein thrombosis in a 43-year-old man with a known case of phosphofructokinase deficiency.

Venous thromboembolism clinically detected after hip fracture surgery with prophylaxis in a clinical practice setting.

Clinical trials have shown differences in efficacy among anticoagulants used for venous thromboembolism (VTE) prophylaxis after hip fracture surgery, but the applicability of their results is limited by constraints of the clinical trial setting. We conducted this retrospective cohort study to assess VTE after hip fracture surgery in patients who received prophylaxis with dalteparin, enoxaparin, fondaparinux, or unfractionated heparin in a hospital setting. After adjustments were made for demographic differences, risk for VTE was significantly higher for dalteparin (odds ratio [OR], 1.

Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery.

Dabigatran, an oral once-daily unmonitored thrombin inhibitor, has been tested elsewhere using enoxaparin 40 mg once daily. We used the North American enoxaparin 30 mg BID regimen as the comparator. This was a double-blind, centrally randomized trial.

Fondaparinux combined with intermittent pneumatic compression vs. intermittent pneumatic compression alone for prevention of venous thromboembolism after abdominal surgery: a randomized, double-blind comparison.

Background: The benefit of combined mechanical and pharmacologic methods for venous thromboembolism prevention after abdominal surgery has not been clearly established.

Objectives: To compare the efficacy and safety of fondaparinux in conjunction with intermittent pneumatic compression vs. intermittent pneumatic compression alone in this context.

The influence of obesity on calf blood flow and vascular reactivity in older adults.

Objective: To determine whether differences in vascular reactivity existed among normal weight, overweight, and obese older men and women, and to examine the association between abdominal fat distribution and vascular reactivity.

Methods: Eighty-seven individuals who were 60 years of age or older (age = 69 +/- 7 yrs; mean +/- SD) were grouped into normal weight (BMI < 25; n = 30), overweight (BMI > or = 25 and < 30; n = 28), or obese (BMI > or = 30; n = 29) categories. Calf blood flow (BF) was assessed by venous occlusion strain-gauge plethysmography at rest and post-occlusive reactive hyperemia.

The relationship between arterial elasticity and metabolic syndrome features.

The purpose of this study was to examine the effects of metabolic syndrome (MS) features on arterial elasticity of the large and small arteries in apparently healthy adults, to examine the effect of clustered features of MS, and to determine which features are most predictive of large and small artery elasticity. The subjects for this study consisted of 126 men and women, age 45 years and older. The subjects rested supine while pulse contour analysis was measured from the radial artery by using an HDI/Pulsewave CR-2000 instrument (Hypertension Diagnostic, Inc) to assess arterial elasticity in the large and small arteries.

Abnormal melt curve profile during prothrombin 20210G --> A analysis due to the 20209C --> T variant.

The common factor II 20210G --> A mutation, located in the 3'-untranslated region, is an important risk factor for the development of thromboembolic disorders, especially in Caucasians. A number of methods are employed for clinical laboratory diagnosis of this mutation, some of which are capable of detecting adjacent 3'-end sequence variations. We present results from an African deep vein thrombosis patient tested for the 20210G --> A mutation by real-time polymerase chain reaction and melt-curve analysis using hybridization probes that incidentally detected an adjacent 3'-untranslated region variant.

Traces of factor VIIa modulate thromboplastin sensitivity to factors V, VII, X, and prothrombin.

Background: Thromboplastin reagents are used to conduct prothrombin time (PT) clotting tests to monitor oral anticoagulant therapy and screen for clotting factor deficiencies. Thromboplastins made from purified, recombinant tissue factor are generally more sensitive to changes in plasma factor (F) VII levels than are thromboplastins prepared from tissue extracts. This may be problematic as FVII's short plasma half-life can result in day-to-day fluctuation during oral anticoagulant therapy.

Phospholipid composition controls thromboplastin sensitivity to individual clotting factors.

Background: Tissue factor is the active ingredient in thromboplastin reagents used to perform prothrombin time (PT) clotting tests to monitor oral anticoagulant therapy and to screen for clotting factor deficiencies. Thromboplastins are complex mixtures prepared from extracts of brain or placenta, although newer thromboplastins contain recombinant tissue factor incorporated into phospholipid vesicles. Thromboplastins can vary widely in their sensitivity to reductions in the levels of vitamin K-dependent clotting factors.

Oral direct thrombin inhibitor ximelagatran compared with warfarin for the prevention of venous thromboembolism after total knee arthroplasty.

Background: Warfarin, which requires coagulation monitoring, is associated with relatively high rates of thromboembolism despite providing adequate prophylaxis. This study compared an oral direct thrombin inhibitor, ximelagatran, with warfarin in order to evaluate the safety and efficacy of the medication for the prevention of venous thromboembolism in patients undergoing total knee arthroplasty.

Methods: Following surgery, patients were randomly assigned to fixed-dose oral ximelagatran (36 mg twice daily) or warfarin (target international normalized ratio, 2.

Dose-response study of recombinant human soluble thrombomodulin (ART-123) in the prevention of venous thromboembolism after total hip replacement.

Background: Recombinant human soluble thrombomodulin (ART-123) is composed of the active, extracellular, domain of thrombomodulin. ART-123 binds to thrombin and this complex converts protein C into the natural anticoagulant activated protein C. This study was performed to identify an effective and safe dose of ART-123 for prevention of venous thromboembolism after elective, unilateral total hip replacement.

Early lymphoid progenitors in mouse and man are highly sensitive to glucocorticoids.

Glucocorticoids are extensively used in anti-inflammatory therapy and may contribute to the normal regulation of lymphopoiesis. This study utilized new information about the early stages of lymphopoiesis in mouse and man to determine precisely which cell types are hormone sensitive. Cycling B lineage precursors were depleted in dexamethasone-treated mice, while mature, non-dividing CD45R(Hi) CD19(Hi) lymphocytes, myeloid progenitors and stem cells with the potential for lymphocyte generation on transplantation were spared.

Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569].

Introduction: PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) was a phase III, randomized, double blind, placebo controlled, multicenter trial conducted in patients with severe sepsis from 164 medical centers. Here we report data collected at study entry for 1690 patients and over the following 7 days for the 840 patients who received placebo (in addition to usual standard of care).

Methods: Nineteen biomarkers of coagulation activation, anticoagulation, fibrinolysis, endothelial injury, and inflammation were analyzed to determine the relationships between baseline values and their change over time, with 28-day survival, and type of infecting causative micro-organism.

New perspectives on vitamin E: gamma-tocopherol and carboxyelthylhydroxychroman metabolites in biology and medicine.

Vitamin E (alpha-tocopherol or alphaT) has long been recognized as a classic free radical scavenging antioxidant whose deficiency impairs mammalian fertility. In actuality, alpha-tocopherol is one member of a class of phytochemicals that are distinguished by varying methylation of a chroman head group. Early studies conducted between 1922 and 1950 indicated that alpha-tocopherol was specific among the tocopherols in allowing fertility of laboratory animals.

Treatment and management of acute venous thromboembolic disease.

Venous thromboembolic (VTE) disease consists of deep vein thrombosis and/or pulmonary embolism. Either low molecular weight heparin given subcutaneously or unfractionated heparin administered intravenously are used for the initial treatment. Simultaneously, warfarin therapy is initiated.

Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement.

Background: In a previous study of the prevention of venous thromboembolism after total knee replacement, the efficacy of ximelagatran, an oral direct thrombin inhibitor that does not require monitoring of coagulation or dose adjustment, was found to be similar to that of warfarin at a dose of 24 mg of ximelagatran twice daily. The purpose of the present study was to determine whether a higher dose of ximelagatran is superior to warfarin.

Methods: This randomized, double-blind trial compared a regimen of 7 to 12 days of oral ximelagatran, at a dose of 24 or 36 mg twice daily, starting the morning after surgery, with warfarin therapy started the evening of the day of surgery.

Selective factor Xa inhibition improves efficacy of venous thromboembolism prophylaxis in orthopedic surgery.

Venous thromboembolism is a serious, frequent, and potentially fatal complication of major orthopedic surgery. Currently available pharmacologic agents for the prevention of venous thromboembolism in this high-risk population consist of the oral anticoagulants and the heparin family of antithrombotic agents (unfractionated heparin, low-molecular-weight heparin, heparinoids). These classes of agents interfere with the activity of both thrombin and factor Xa (or their respective zymogens) to varying degrees.

Laboratory issues in diagnosing abnormalities of protein C, thrombomodulin, and endothelial cell protein C receptor.

Objective: To review the current understanding of the pathophysiology of protein C deficiency and its role in congenital thrombophilia. Recommendations for diagnostic testing for protein C function and concentration, derived from the medical literature and consensus opinions of recognized experts in the field, are included, specifying whom, how, and when to test. The role of related proteins, such as thrombomodulin and endothelial protein C receptor, is also reviewed.

B lymphopoiesis is active throughout human life, but there are developmental age-related changes.

This study addressed several questions concerning age-related changes in human B lymphopoiesis. The relative abundance of pro-B, pre-B, immature, naive, and mature B cells among the CD19(+) lymphocyte fraction of human bone marrow was found not to change appreciably over the interval between 24 and 88 years of age. Moreover, proliferation of pro-B and large pre-B cells in adult marrow equaled that observed with fetal marrow specimens.