Physiology of hemostasis: with relevance to current and future laboratory testing.

This article briefly details the physiologic and interdependent mechanisms of vascular hemostasis, with an eye toward how the laboratory can assist in diagnosing and maintaining the balance of procoagulant and anticoagulant functions. These functions include determining characteristics of the blood vessel wall, platelet components and receptor-ligand interactions critical for hemostasis, the regulation of thrombin generation and its effects, and the complex fibrinolytic pathways that complete the coagulation cascade.

Fire safety in the operating room.

Purpose Of Review: Elimination of flammable anesthetic gases has had little effect on operating-room fires except to change their etiology. Electrocautery and lasers, in an oxygen-enriched environment, can ignite even the most fire-resistant materials, including the patient, and the fire triad possibilities in the operating room are nearly limitless. This review will: identify operating room contents capable of acting as ignition/oxidizer/fuel sources, highlight operating room items that are uniquely potent fire triad contributors, and operating room identify settings where fire risk is enhanced by proximity of triad components in time or space.

Monocyte activation in on-pump versus off-pump coronary artery bypass surgery.

Objective: Monocyte activation plays a key role in amplifying both inflammatory and coagulopathic sequelae in patients undergoing on-pump coronary artery bypass graft (CABG) surgery. Off-pump CABG diminishes, but does not eliminate, the systemic inflammatory response and its influence on monocyte activation remains unclear. This study was performed to determine if off-pump CABG suppresses all features of monocyte activation.

Genetic variants in P-selectin and C-reactive protein influence susceptibility to cognitive decline after cardiac surgery.

Objectives: We hypothesized that candidate gene polymorphisms in biologic pathways regulating inflammation, cell matrix adhesion/interaction, coagulation-thrombosis, lipid metabolism, and vascular reactivity are associated with postoperative cognitive deficit (POCD).

Background: Cognitive decline is a common complication of coronary artery bypass graft (CABG) surgery and is associated with a reduced quality of life.

Methods: In a prospective cohort study of 513 patients (86% European American) undergoing CABG surgery with cardiopulmonary bypass, a panel of 37 single-nucleotide polymorphisms (SNPs) was genotyped by mass spectrometry.

Leukocyte effects of C5a-receptor blockade during simulated extracorporeal circulation.

Background: Distinct pathways of leukocyte activation during simulated cardiopulmonary bypass are mediated by the complement C5a anaphylatoxin. We hypothesized that a human C5a receptor antagonist would specifically inhibit the inflammatory response of neutrophils to simulated extracorporeal circulation, while preserving the C5b-9 pathway for innate immunity.

Methods: An in vitro extracorporeal circuit recirculated fresh heparinized whole blood through a membrane oxygenator with and without addition of a small molecule human C5a receptor antagonist.

Antithrombin reduces monocyte and neutrophil CD11b up regulation in addition to blocking platelet activation during extracorporeal circulation.

Background: Patients undergoing cardiac surgery requiring cardiopulmonary bypass develop a systemic inflammatory reaction. Antithrombin III (AT) has anticoagulant effects but also shows evidence of anti-inflammatory activity. The aim of this study was to examine whether exogenous AT could reduce white blood cell activation (CD11b up regulation or elastase release), in addition to inhibiting platelet (PLT) activation and fibrin generation, during simulated cardiopulmonary bypass (sCPB), undertaken in the absence of endothelium.

Transcerebral platelet activation after aortic cross-clamp release is linked to neurocognitive decline.

Background: Neurocognitive decline after cardiac surgery requiring cardiopulmonary bypass (CPB) may be caused in part by highly prothrombotic atheroemboli to the brain; the source of these emboli is likely the ascending aorta and aortic arch. We examined transcerebral platelet activation gradients using simultaneous measurements in arterial and jugular venous blood and then compared gradients with post-CPB-associated neurocognitive injury.

Methods: Eighty-one patients undergoing elective coronary artery bypass graft surgery requiring CPB were studied.

Atrial fibrillation after cardiac surgery/cardiopulmonary bypass is associated with monocyte activation.

Atrial fibrillation (AF) contributes significantly to morbidity and mortality in as many as one-third of patients after cardiac surgery that requires cardiopulmonary bypass (CPB). Recent data suggest that inflammatory infiltration of the myocardium may predispose to AF. We conducted an exploratory pilot study to determine if there was an association between the perioperative leukocyte inflammatory response to cardiac surgery/CPB and postoperative AF.

Effects of epsilon-aminocaproic acid and aprotinin on leukocyte-platelet adhesion in patients undergoing cardiac surgery.

Background: The administration of aprotinin during cardiopulmonary bypass (CPB) is hypothesized to decrease activation of leukocytes and platelets and possibly reduce their adhesion. Although epsilon-aminocaproic acid (EACA) shares the ability of aprotinin to inhibit excessive plasmin activity after CPB, its effect on leukocyte and platelet activation and leukocyte-platelet (heterotypic) adhesion is largely unknown. This study was performed to determine the relative effectiveness of the antifibrinolytics, aprotinin and EACA, at reducing leukocyte and platelet activation and leukocyte-platelet conjugate formation in patients undergoing CPB.

Platelet abnormalities associated with cerebral perfusion defects in cocaine dependence.

Background: This study assessed whether reduced regional cerebral blood flow (rCBF; hypoperfusion) in cocaine-dependent (CD) patients is associated with platelet abnormalities and whether these platelet abnormalities predict improvement in hypoperfusion after 1 month of abstinence.

Methods: We correlated platelet number and aggregation with rCBF hypoperfusion in 54 CD patients at baseline and after a month of abstinence while taking either 325 mg aspirin or placebo. We measured rCBF by (SPECT) with (Tc-HMPAO).

Rofecoxib does not compromise platelet aggregation during anesthesia and surgery.

Purpose: This study was undertaken because, although there is evidence that cyclooxygenase type 2 (COX)-2 inhibitors do not compromise platelets in healthy volunteers, many clinicians remain hesitant to administer them perioperatively without definitive evidence of intact platelet function during anesthesia and surgery.

Methods: In 20 patients scheduled for lower abdominal and pelvic surgery, 5 mL of blood were obtained for baseline platelet aggregometry. One hour prior to surgery, patients received an oral solution of either rofecoxib (ROF) 50 mg or placebo (PLAC) by randomized, double-blinded assignment.

Increased leukocyte-platelet adhesion in patients with graft occlusion after peripheral vascular surgery.

Graft occlusion following peripheral vascular surgery is attributable to some combination of acute thrombosis, and progression of atherosclerosis: interactions between leukocytes and activated platelets may play a role in both of these processes. This investigation measured perioperative leukocyte-platelet conjugate formation, and leukocyte and platelet activation in 46 patients undergoing surgery for lower extremity peripheral vascular disease (PVD). All patients were followed for graft patency over the next 6 months; 27 patients had grafts that remained patent while 19 had graft occlusion.

Aspirin or amiloride for cerebral perfusion defects in cocaine dependence.

Cocaine dependent (CD) patients have regional cerebral blood flow (rCBF) deficits that may be related to occlusion of blood vessels by vasoconstriction and abnormal platelet aggregation. This study determined whether aspirin, which reverses platelet aggregation, or amiloride, a vasodilator, significantly reversed this rCBF hypoperfusion. This 1-month randomized trial compared clusters of voxels with significant hypoperfusion in recently abstinent CD patients after aspirin (325 mg daily), amiloride (10 mg daily) or placebo treatment.

Reversibility of severe metabolic stress in stored platelets after in vitro plasma rescue or in vivo transfusion: restoration of secretory function and maintenance of platelet survival.

Background: Determining reversible aspects of the platelet storage lesion may result in improved function and survival of transfused platelets.

Study Design And Methods: Using a model of high-dose (apheresis-derived) platelet concentrates (PC), functional changes imposed by transient adverse metabolic conditions (pH < 6.0 for 1-2 hr) that could be reversed by autologous plasma rescue followed by standard platelet storage were investigated.

Neutrophil CD11b upregulation during cardiopulmonary bypass is associated with postoperative renal injury.

Background: Renal injury remains a persistent complication of cardiopulmonary bypass (CPB) that, when sufficient to require dialysis, increases mortality eight-fold. The high prevalence of renal failure in sepsis and adult respiratory distress syndrome has been linked to the systemic inflammatory response associated with those disorders. We hypothesized that components of the inflammatory response to CPB may similarly contribute to post-CPB acute renal injury.

Platelet PlA2 polymorphism and platelet activation are associated with increased troponin I release after cardiopulmonary bypass.

Background: The PlA2 polymorphism of platelet glycoprotein IIIa has been identified as a prothrombotic risk factor in a number of cardiovascular settings. The aim of this study was to determine whether the PlA2 polymorphism of platelet glycoprotein IIIa and degree of platelet activation were associated with more severe myocardial injury as indicated by troponin I release following cardiopulmonary bypass.

Methods: The PlA2 genotype was determined in 66 patients undergoing elective coronary artery bypass grafting requiring cardiopulmonary bypass.