thromboxane-a2 and Wounds-and-Injuries

Platelets contract forcefully after their activation, contributing to the strength and stability of platelet aggregates and fibrin clots during blood coagulation. Viscoelastic approaches can be used to assess platelet-induced clot strengthening, but they require thrombin and fibrin generation and are unable to measure platelet forces directly. Here, we report a rapid, microfluidic approach for measuring the contractile force of platelet aggregates for the detection of platelet dysfunction. We find that platelet forces are significantly reduced when blood samples are treated with inhibitors of myosin, GPIb-IX-V, integrin α

Topics: Adult; Aspirin; Blood Coagulation; Blood Platelets; Computer Simulation; Cross-Sectional Studies; Drug Monitoring; Female; Hemorrhage; Humans; Male; Microfluidics; Middle Aged; Myosins; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIb-IX Complex; Platelet Glycoprotein GPIIb-IIIa Complex; Prognosis; Thromboxane A2; Wounds and Injuries

Of 64 polytraumatized patients with a mean injury severity score of 33.1, 42 showed marked systemic release of thromboxane B2 and granulocyte elastase during the initial 18 hours after trauma, reaching peak arterial levels of greater than 1,000 pg/ml and ng/ml, respectively. If those patients ("responders": plasma TXB2 greater than 250 pg/ml) were compared with the remaining 22 ("non-responders": TXB2 less than 250 pg/ml) the following became obvious: "Late" mortality (greater than 3 d) was 31% in responders, which is significantly higher than in non-responders (9%). No correlation was observed between "early" mortality (less than 3 d) and mediator release. There was no difference in the incidence of the adult respiratory distress syndrome (ARDS) (38% versus 32%) or the late sepsis syndrome (17% versus 18%) between responders and non-responders. Morbidity, however, differed markedly in that ARDS in responders was associated with significantly higher elastase levels, a higher mortality and 10 times higher incidence of sepsis as compared to responders without ARDS. ARDS in non-responders, by contrast, did not change elastase maxima or the mortality rate as compared to non-responders without ARDS. It is concluded that TXB2 is not a predictor of posttraumatic ARDS, but is related to a complicated course, in particular to sepsis and mortality. Elastase with high probability predicts ARDS and/or the late sepsis syndrome. Simultaneous determination of TXB2 further enhances the predictive value of elastase.

Topics: Adult; Female; Humans; Leukocyte Elastase; Male; Middle Aged; Pancreatic Elastase; Prognosis; Thromboxane A2; Thromboxane B2; Wounds and Injuries

Severe trauma results in reversible abnormalities in neutrophil function, but the specific role in the pathogenesis of postoperative sepsis is undetermined. Twenty adult patients undergoing elective surgical procedures were studied. Blood samples were obtained prior to and 24 hours after operation. Blood neutrophils were isolated and incubated (10(7) cells/mL) on bovine vascular endothelial cell monolayers. Untreated plasma or zymosan-activated plasma (ZAP) or 65 C inactivated plasma was added, and TxB2 and 6-keto PGF1 alpha production measured after 2 hours. Endothelial damage was detected by light and scanning electron microscopy beginning 2 and 4 hours after treatment. Preoperatively, neutrophil TxB2 release was less than 200 pg/mL; following ZAP it was 2153 pg/mL (p less than 0.001), with untreated plasma 1055 pg/mL (p less than 0.005) and inactivated plasma 764 pg/mL (p less than 0.01). Neutrophil TxB2 release on a plastic dish was not different from incubation on endothelium. Endothelial 6-keto PGF1 alpha release following addition of untreated plasma preoperatively was 1308 pg/mL (p less than 0.01), and with ZAP 1305 pg/mL (p less than 0.01). Activated neutrophils did not alter 6-keto PGF1 alpha production. Postoperatively, neutrophil TxB2 production in response to ZAP was 1092 pg/mL, which was significantly reduced compared to the preoperative response (p less than 0.01). Endothelial damage by activated neutrophils in the postoperative period demonstrated on scanning electron microscopy was also reduced; 6-keto PGF1 alpha release in the postoperative period inducted by ZAP was 569 pg/mL and by untreated plasma 549 pg/mL, which was significantly lower than in the preoperative period (p less than 0.05 and p less than 0.05, respectively). No difference in chemotaxis was demonstrated. It is concluded that operative trauma is followed by lowered neutrophil TxB2 release, appearance of a plasmatic factor that depresses endothelial 6-keto PGF1 alpha production, as well as decreased neutrophil-induced endothelial damage. The neutrophil-endothelial monolayer system is a sensitive method for detection of neutrophil and plasmatic dysfunction.

Topics: Adult; Aged; Aged, 80 and over; Epoprostenol; Female; Humans; In Vitro Techniques; Male; Microscopy, Electron, Scanning; Middle Aged; Neutrophils; Plasma; Postoperative Period; Thromboxane A2; Wounds and Injuries; Zymosan

Topics: Animals; Bicyclic Monoterpenes; Blood Pressure; Coronary Circulation; Platelet Aggregation; Rats; Thromboxane A2; Wounds and Injuries