von Willebrand factor disruption and continuous-flow circulatory devices.

Bleeding events remain a significant and frequent complication of continuous-flow left ventricular assist devices (VADs). von Willebrand factor (VWF) is critical to hemostasis by acting as a bridging molecule at sites of vascular injury for normal platelet adhesion as well as promoting platelet aggregation under conditions of high shear. Clinical and experimental data support a role for acquired von Willebrand disease in VAD bleeding episodes caused by shear-induced qualitative defects in VWF.

An Investigation Into the Effects of In Vitro Dilution With Different Colloid Resuscitation Fluids on Clot Microstructure Formation.

Background: Balancing the beneficial effects of resuscitation fluids against their detrimental effect on hemostasis is an important clinical issue. We aim to compare the in vitro effects of 3 different colloid resuscitation fluids (4.5% albumin, hydroxyethyl starch [Voluven 6%], and gelatin [Geloplasma]) on clot microstructure formation using a novel viscoelastic technique, the gel point.

High Platelet Reactivity in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Randomised Controlled Trial Comparing Prasugrel and Clopidogrel.

Background: Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e.

Fractal dimension: a novel clot microstructure biomarker use in ST elevation myocardial infarction patients.

Objectives: Changes in clot microstructure are increasingly implicated in the pathology of atherosclerosis although most data are from techniques in the remote laboratory using altered blood. We validate the novel biomarker Gel Point in STEMI patients and assess therapeutic interventions. Gel Point marks the transition of blood from a visco-elastic liquid to visco-elastic solid and is rapidly measured using unadulterated blood.

The changes in clot microstructure in patients with ischaemic stroke and the effects of therapeutic intervention: a prospective observational study.

Background: Stroke is the second largest cause of death worldwide. Hypercoagulability is a key feature in ischaemic stroke due to the development of an abnormally dense clot structure but techniques assessing the mechanics and quality of clot microstructure have limited clinical use. We have previously validated a new haemorheological technique using three parameters to reflect clot microstructure (Fractal Dimension (d f )) ex-vivo, real-time clot formation time (T GP ) and blood clot strength (elasticity at the gel point (G'GP)).

A new biomarker quantifies differences in clot microstructure in patients with venous thromboembolism.

This study compared patients with venous thromboembolism (VTE) to non-VTE patients using a biomarker of clot microstructure (df ) and clot formation time (TGP ). df was the only marker that identified a significant difference (P < 0·001) between the VTE (n = 60) and non-VTE cohorts (n = 69). The 'abnormal' clot microstructures in the VTE patients suggests either inadequate response to anticoagulant therapy or the presence of a procoagulant state not detected by other markers of coagulation (i.

A new structural biomarker that quantifies and predicts changes in clot strength and quality in a model of progressive haemodilution.

Introduction: We investigated the effect of progressive haemodilution on the dynamics of fibrin clot formation and clot microstructure using a novel rheological method. The technique measures clotting time (TGP), clot strength (G`GP), and quantifies clot microstructure (df) at the incipient stages of fibrin formation. We use computational modelling to examine the relationship between structure and mass, as well as helium ion microscopy (HIM) to compare morphological changes in the fully formed clot to that of the incipient clot.

Performance of a new, rapid, automated immunoassay for the detection of anti-platelet factor 4/heparin complex antibodies.

Heparin-induced thrombocytopenia (HIT) is a life-threatening adverse reaction to heparin that must be identified quickly to determine appropriate anticoagulant therapy strategies. The most common antibodies involved in HIT are directed against platelet factor 4/heparin (PF4/H) complexes. Many methods for anti-PF4/H detection exist such as enzyme immunoassays (EIAs), which have been shown to exhibit high-negative predictive value allowing for the exclusion of HIT in the majority of suspected patients; however, most EIAs are performed in a batch mode, thereby delaying results to the physician.

Biomarkers of lung injury after one-lung ventilation for lung resection.

Background And Objective: Acute lung injury contributes to the mortality of patients after lung resection and one-lung ventilation (OLV). The objective of this study was to characterise the effect of lung resection and OLV on proposed biomarkers of lung injury in exhaled breath condensate (EBC) and plasma.

Methods: In adults undergoing lung resection, EBC was collected before and at 30-min intervals during OLV.

Anticoagulation of a patient with hypertrophic cardiomyopathy and factor VII deficiency.

A 50-year-old male patient with hypertrophic cardiomyopathy and atrial fibrillation was anticoagulated, with warfarin following insertion of a cardioverter defibrillator. He became markedly over anticoagulated after standard moderate induction doses of warfarin. His baseline prothrombin time was prolonged and further investigation showed the patient to have a mild factor VII deficiency.

Heparin induced thrombocytopenia in a patient with factor V Leiden following cardiac surgery.

We report a patient who died as a result of heparin induced thrombocytopenia (HIT) and arterial thromboses following cardiac surgery. The onset was three days after exposure to low molecular weight heparin on the eighth postoperative day. The patient was heterozygous for the factor V Leiden mutation.

Adult cystic fibrosis patients with and without infective exacerbations and their factor XII levels.

We investigated haemostatic and inflammatory parameters in patients with cystic fibrosis in an attempt to understand a previous finding of low factor XII levels in this patient population. We selected two groups of patients, adults attending outpatient annual review clinic who were well, chronically inflammed and adult patients with an infective exacerbation requiring antibiotics or admission to hospital, acutely inflammed. We measured known positive acute phase haemostatic factors, fibrinogen and factor VIII.

Can ROTEM thromboelastometry predict postoperative bleeding after cardiac surgery?

Objective: To evaluate the predictive ability of ROTEM thromboelastometry (Pentapharm, Basel, Switzerland) to identify patients bleeding more than 200 mL/h in the early postoperative period after cardiac surgery.

Design: A prospective observational study.

Setting: A single university hospital.

Pulmonary arterial thrombosis in eisenmenger syndrome is associated with biventricular dysfunction and decreased pulmonary flow velocity.

Objectives: This study sought to determine what factors are associated with pulmonary artery thrombi in Eisenmenger patients.

Background: Pulmonary artery thrombosis is common in Eisenmenger syndrome, although its underlying pathophysiology is poorly understood.

Methods: Adult patients with Eisenmenger syndrome underwent computed tomography pulmonary angiography, cardiac magnetic resonance imaging, and echocardiography.

Endothelial cell damage in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia type II is a severe complication of heparin treatment that may result in thrombosis. When thrombosis occurs it carries a 50% mortality rate. The exact pathophysiology is not fully understood but in the majority of cases it is associated with the production of heparin/platelet factor 4 antibodies.

Blood viscosity and its relationship to iron deficiency, symptoms, and exercise capacity in adults with cyanotic congenital heart disease.

Objectives: This study sought to determine the relationship between blood viscosity and iron deficiency and their impact on symptoms and exercise function in adults with cyanotic congenital heart disease.

Background: Iron deficiency is believed to raise whole blood viscosity in cyanotic congenital heart disease, although available data are inconsistent.

Methods: Thirty-nine cyanotic adults were prospectively assessed for iron deficiency (transferrin saturation < or =5%), hyperviscosity symptoms, and exercise capacity.

Role of nuclear receptor signaling in platelets: antithrombotic effects of PPARbeta.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that heterodimerize with the retinoid X receptor and then modulate at the transcriptional level the function of many target genes. Three PPARs are known: alpha, beta (sometimes called delta), and gamma. The better studied are PPARalpha and PPARgamma, which are activated by fibrates and thiazolidinediones/glitazones, respectively.

Factor XII auto-antibodies present in a patient with a B-cell lymphoma.

A 64-year-old woman was transferred for investigation of a mediastinal mass, biopsy of which showed a diffuse large B-cell lymphoma. She was also found to have an antiphospholipid antibody. The pre-operative coagulation screen showed a prolonged activated partial thromboplastin time, 71.

Teicoplanin-dependent antibodies: detection and characterization.

There are only a few reports of thrombocytopenia associated with clinical doses of teicoplanin, a glycopeptide antibiotic used against Gram-positive bacteria. We investigated 39 patients receiving teicoplanin; 31 were thrombocytopenic with platelet counts between 1-105 x 10(9)/l and 8 were not thrombocytopenic. We identified 14 thrombocytopenic cases (45%) and two (25%) non-thrombocytopenic cases with IgG teicoplanin-dependent platelet-reactive antibodies.

A multicentre assessment of the endogenous thrombin potential using a continuous monitoring amidolytic technique.

This study assessed the inter-laboratory imprecision associated with the measurement of the endogenous thrombin potential (ETP). The initial studies used techniques that had evolved in each of the participating laboratories. Samples from normal healthy subjects (n = 10), two patients receiving coumarin therapy [International Normalized Ratio approximately 2.

Correlation between thrombin potential and bleeding after cardiac surgery in adults.

We used a sensitive assay to measure thrombin potential in 20 patients who underwent cardiopulmonary bypass surgery for coronary artery bypass grafts. We measured coagulation factors II, V, VII, VIII and X. Blood loss was measured as the total amount in the mediastinal drains in the first 24 h postoperatively.

Abciximab is rapidly effective in preventing and arresting established platelet aggregation.

Background: Abciximab reduces the thrombotic complications of angioplasty. It is also used, as a 'bail out' treatment when angioplasty is complicated by thrombus but its speed of action is not known. This study sought to establish how quickly abciximab blocks the aggregation of both quiescent and activated platelets to explain this rapid efficacy.