Aspirin sensitivity of platelet aggregation in diabetes mellitus.

Although aspirin is cardioprotective in high-risk populations, many with diabetes mellitus (DM) are unresponsive to these benefits. We questioned whether cardiovascular unresponsiveness might be demonstrated by lack of aspirin sensitivity to in vitro platelet functions especially in subjects with poorly controlled diabetes. Six women and 4 men (48+/-8 years [mean+/-S.

A multicenter clinical evaluation of the Clot Signature Analyzer.

Background: The Clot Signature Analyzer (CSA) was designed to assess global hemostasis as a screening assay using non-anticoagulated whole blood. Three different measurements are produced by the instrument: platelet hemostasis time (PHT), clot time (CT), and collagen-induced thrombus formation (CITF).

Objectives: The purpose of the present study was to determine normal ranges for these measurements and assess the performance of the CSA in patients with well-characterized hemostatic disorders and in normal subjects.

Recombinant factor VIIa: a universal hemostatic agent?

Recombinant factor VIIa (rVIIa) has proved effective for the treatment and prevention of hemorrhage in patients with inherited hemophilia A and B who develop inhibitors to factor VIII or IX, and patients with acquired hemophilia A. More recently, there is evidence that rVIIa may also be effective in the control of abnormal bleeding in a variety of other conditions, such as inherited factor VII deficiency, thrombocytopenia, Glanzmann's thrombasthenia, and liver disease. In some of the reports, rVIIa appeared to be effective in controlling massive hemorrhage in which there was no response to conventional measures.

Massive retroperitoneal pseudotumour in a patient with type 3 von Willebrand disease.

Formation of destructive haemorrhagic pseudocysts or pseudotumours thought to arise from unresolved, encapsulated haematomas is a well-recognized, rare complication of severe haemophilia A or B, and has been reported in a single patient with von Willebrand disease (vWD). We report a 41-year-old patient with type 3 vWD who underwent incomplete resection of a large retroperitoneal pseudocyst in 1995 and presented with a recurrent, extensive right abdominal and flank mass and signs and symptoms of large bowel obstruction. He required emergency partial colectomy for bowel ischaemia and removal of his right kidney, which was hydronephrotic due to prolonged ureteral obstruction by the pseudocyst.

Pharmacokinetic analysis of plasma-derived and recombinant F IX concentrates in previously treated patients with moderate or severe hemophilia B.

Background: Hemophilia B is an X-linked bleeding disorder that affects approximately 1 in 25,000 males. Therapy for acute bleeding episodes consists of transfusions of plasma-derived (pd-F IX) or recombinant (r-F IX) concentrates.

Study Design And Methods: A double-blind, two-period crossover study was initiated to assess the pharmacokinetics of pd-F IX and r-F IX and to address patient-specific variables that might influence in vivo recovery.

The relationship between hirudin and activated clotting time: implications for patients with heparin-induced thrombocytopenia undergoing cardiac surgery.

Unlabelled: Anticoagulation with recombinant hirudin (r-hirudin) (Refludan) has been suggested as an alternative to heparin for patients with heparin-induced thrombocytopenia requiring cardiac surgery. We sought to develop a modified activated coagulation time (ACT) that would allow quantification of the levels of r-hirudin required during cardiopulmonary bypass (CPB). Twenty-one patients scheduled for elective cardiac surgical procedures requiring CPB were enrolled in this IRB-approved study.

New insights into how blood clots: implications for the use of APTT and PT as coagulation screening tests and in monitoring of anticoagulant therapy.

Blood coagulation occurs efficiently on cell surfaces such as activated platelets and monocytes, and fibroblasts. It is initiated by limited amounts of tissue factor (TF) exposed at the sites of vascular injury that complexes with trace amounts of circulating factor VIIa (FVIIa). Additional FVIIa-TF complexes are formed from FVII-TF involving positive feedback loops, including FVIIa-TF as well as factors Xa and IXa as they are formed in subsequent steps.

Anticoagulation and anticoagulation reversal with cardiac surgery involving cardiopulmonary bypass: an update.

Accelerated thrombin generation is central to the development of hemostatic abnormalities during cardiopulmonary bypass (CPB) that are associated with both thromboembolic complications and serious, abnormal bleeding. Thrombin not only converts fibrinogen to fibrin, but also activates platelets and coagulation factors V, VIII, and XI and causes release of von Willebrand factor from vascular endothelium. Thrombin can also downregulate the hemostatic system by inducing formation of platelet inhibitory agents, such as nitric oxide and prostacyclin, and release of tissue plasminogen activator, facilitating activation of protein C, and releasing tissue factor pathway inhibitor.

Use of point-of-care test in identification of patients who can benefit from desmopressin during cardiac surgery: a randomised controlled trial.

Background: Platelet dysfunction is a major cause of excessive microvascular bleeding after cardiac surgery. A new point-of-care test (hemoSTATUS) can identify patients at risk of excessive bleeding. We aimed to find out whether patients who can benefit from desmopressin during cardiac surgery can be identified by this test.

A randomized, double-blind comparison of two dosage levels of recombinant factor VIIa in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B, with and without inhibitors. rFVIIa Study Group.

Recombinant factor VIIa (rFVIIa) was developed to provide an improved procoagulant component capable of 'by-passing' inhibitor antibodies in the treatment of haemophilic patients. The primary objective of this study was to compare the efficacy of two dosage regimens of rFVIIa (given intravenously at periodic intervals) in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B with and without inhibitors. The study was designed as a randomized, double-blind, parallel group, international multicenter trial.

Platelet adhesion and aggregation in pulsatile shear flow: effects of red blood cells.

An in vitro test system was developed to examine the effects of red blood cells (RBC) on shear-induced platelet adhesion (SIPAD) and platelet aggregation (SIPAG). Suspensions of human platelets labeled with Mepacrine and suspended in citrated plasma were exposed to single, continuous or repetitive (120-300x) one second shear stress pulses of varying amplitude (15-100 dyn/cm2) in a cone-plate viscometer in the presence or absence of fresh, untreated (intact) RBC or glutaraldehyde (GLA)-fixed, rigid, adenosine diphosphate (ADP)-depleted (GLA)-RBC. SIPAG was expressed as percent loss of single platelets.

A comparison between continuous infusion versus standard bolus administration of heparin based on monitoring in cardiac surgery.

This study was designed to determine prospectively if stable heparin concentrations can be maintained during extracorporeal circulation by using a continuous infusion technique, compared with a bolus regimen based on whole blood heparin concentration monitoring. Forty patients were assigned randomly to either an infusion or a monitoring group. The reference heparin concentration was defined as the whole blood heparin concentration associated with a kaolin activated clotting time (ACT) of approximately 480 s prior to institution of cardiopulmonary bypass (CPB) for both cohorts.

Monitoring of hemostasis in cardiac surgical patients: impact of point-of-care testing on blood loss and transfusion outcomes.

Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are at increased risk for excessive perioperative blood loss requiring transfusion of blood products. Strategies to optimize administration of heparin and protamine and the assessment of their effects on coagulation are evolving in cardiac surgical patients. Two recent evaluations have focused on the use of multiple point-of-care (POC) coagulation assays for patient-specific adjustment of heparin and protamine dosage.

Antithrombin III during cardiac surgery: effect on response of activated clotting time to heparin and relationship to markers of hemostatic activation.

Unlabelled: This study was designed to determine if, and to what extent, antithrombin III (AT) levels affect the response of the activated clotting time (ACT) to heparin in concentrations used during cardiac surgery, and to characterize the relationship between AT levels and markers of activation of coagulation during cardiopulmonary bypass (CPB). After informed consent, blood specimens obtained from eight normal volunteers (Phase I) were used to measure the response of the kaolin and celite ACT to heparin after in vitro addition of AT (200 U/dL) and after dilution with AT-deficient plasma to yield AT concentrations of 20, 40, 60, 80, and 100 U/dL. In Phase II, blood specimens collected before the administration of heparin and prior to discontinuation of CPB, were used to measure the response of the kaolin ACT to heparin (preheparin only), AT concentration, and a battery of coagulation assays in 31 patients undergoing repeat or combined cardiac surgical procedures.

Effects of platelets and white blood cells and antiplatelet agent C7E3 (Reopro) on a new test of PAF procoagulant activity of whole blood.

This study was designed to evaluate the effects of varying concentrations of platelets, white blood cells (WBC) and Fab fragments of a monoclonal antibody (c7E3, Reopro) directed at the platelet GpIIb-IIIa receptor complex on ACT-based clot ratio values (hemoSTATUS assay) in healthy volunteers. These measurements were made in heparinized whole blood from 10 normal volunteers in which either platelet or WBC concentrations had been varied by differential centrifugation. In addition, blood collected in either heparin or argatroban was incubated with varying concentrations of c7E3 (Reopro).

Hemofiltration during cardiopulmonary bypass: the effect on anti-Xa and anti-IIa heparin activity.

Previous studies have demonstrated that heparin concentrations during cardiopulmonary bypass (CPB) may vary considerably, which may be related to variability in redistribution, cellular and plasma protein binding, and clearance of heparin. The purpose of this study was to determine whether hemofiltration removes lower molecular weight fractions of heparin from plasma and thus contributes to variability of blood levels of heparin. Twenty patients undergoing cardiac surgery with CPB were enrolled in this study after informed consent was obtained.

More effective suppression of hemostatic system activation in patients undergoing cardiac surgery by heparin dosing based on heparin blood concentrations rather than ACT.

This study was designed to determine whether the maintenance of higher than usual patient-specific heparin concentrations during cardiopulmonary bypass (CPB) was associated with more effective suppression of hemostasis system activation. Thirty-one patients scheduled for repeat cardiac surgery or combined procedures (i.e.

Evaluation of a new point-of-care test that measures PAF-mediated acceleration of coagulation in cardiac surgical patients.

Background: This study was designed to evaluate a new point-of-care test (HemoSTATUS) that assesses acceleration of kaolin-activated clotting time (ACT) by platelet activating factor (PAF) in patients undergoing cardiac surgery. Our specific objectives were to determine whether HemoSTATUS-derived measurements correlate with postoperative blood loss and identify patients at risk for excessive blood loss and to characterize the effect of desmopressin acetate (DDAVP) and/or platelet transfusion on these measurements.

Methods: Demographic, operative, blood loss and hematologic data were recorded in 150 patients.

Effect of heparin on whole blood activated partial thromboplastin time using a portable, whole blood coagulation monitor.

Objectives: To evaluate the responsiveness of whole blood activated partial thromboplastin time (aPTT) to varying heparin doses in vitro and to examine the ex vivo relationship of whole blood aPTT to plasma heparin concentration.

Design: Prospective, controlled laboratory study.

Setting: Surgical suites and laboratory at a tertiary center.

The impact of heparin concentration and activated clotting time monitoring on blood conservation. A prospective, randomized evaluation in patients undergoing cardiac operation.

A whole blood hemostasis system (Hepcon) provides both activated clotting time and accurate whole blood heparin concentration measurements via an automated protamine titration method. This study was designed to prospectively evaluate the impact of heparin and protamine administration using this system on the incidence and treatment of bleeding after cardiopulmonary bypass. Two hundred fifty-four patients requiring cardiopulmonary bypass were enrolled in this prospective study over a 7-month period.