Procoagulant microparticles promote coagulation in a factor XI-dependent manner in human endotoxemia.

UNLABELLED: Essentials The procoagulant effects of microparticles (MPs) on coagulation in endotoxemia are not known. MPs from endotoxemia volunteers were evaluated for procoagulant activity in a plasma milieu. MPs from endotoxemia volunteers shortened clotting times and enhanced thrombin generation. MP procoagulant effects were mediated in a factor XI-dependent manner. SUMMARY: Background Human endotoxemia is characterized by acute inflammation and activation of coagulation, as well as increased numbers of circulating microparticles (MPs). Whether these MPs directly promote coagulation and through which pathway their actions are mediated, however, has not been fully explored. Objectives In this study, we aimed to further characterize endotoxin-induced MPs and their procoagulant properties using several approaches. Methods Enumeration and characterization of MPs were performed using a new-generation flow cytometer. Relative contributions of the extrinsic and intrinsic pathways in MP-mediated procoagulant activity were assessed using plasmas deficient in factor (F) VII or FXI or with blocking antibodies to tissue factor (TF) or FXIa. Results Total MPs and platelet MPs were significantly elevated in plasma at 6 h after infusion of endotoxin in healthy human subjects. MPs isolated from plasma following endotoxin infusion also demonstrated increased TF activity in a reconstituted buffer system. When added to recalcified platelet-poor plasma, these MPs also promoted coagulation, as judged by a decreased clotting time with shortening of the lag time and time to peak thrombin using calibrated automated thrombography (CAT). However, the use of FVII-deficient plasma or blocking antibody to TF did not inhibit these procoagulant effects. In contrast, plasma clotting time was prolonged in FXI-deficient plasma and a blocking antibody to FXIa inhibited all MP-mediated parameters in the CAT assay. Conclusions The initiation of coagulation by cellular TF in endotoxemia is in contrast to (and presumably complemented by) the intrinsic pathway-mediated procoagulant effects of circulating MPs.

Decreased renal function in hypertensive emergencies.

Data about acute renal function in hypertensive crises are scarce. We hypothesised that acute kidney damage could result from hypertensive emergency (HE), as indicated by the earliest biomarker of kidney injury, neutrophil gelatinase-associated lipocalin (NGAL). Thus, we compared renal function between patients with HE, patients with urgencies and normotensive controls. Sixty emergency department patients were enroled in a prospective, cross-sectional study. Creatinine, blood urea nitrogen (BUN), NGAL and cystatin C were measured and estimated glomerular filtration rate was calculated (eGFR). Creatinine and BUN were significantly higher and eGFR was significantly lower in HE as compared with urgencies or controls (P < 0.01). Similarly, cystatin C and NGAL levels were significantly higher in emergencies compared with the other groups (P < 0.001). All renal function parameters were similar between urgencies and controls. Among HE, NGAL was significantly higher (61%) in patients with pulmonary oedema than in those with cerebral events (P = 0.008), whereas the other parameters were not significantly different. In conclusion, this cross-sectional investigation showed that markers of acute and chronic kidney injury were higher in patients with HE than in urgencies or controls. These results should encourage further studies to better characterise the role of acute kidney damage in hypertensive pulmonary oedema, and HE in general.

[The importance of house dust mites and stored food mites as house dust allergens in the rural population]. / Die Bedeutung der Hausstaub-und Vorratsmilben als Hausstaub-Allergen bei der ländlichen Bevölkerung.

House dust samples from rural districts contain more mite species (in particular stored food mites) than samples from urban areas, and the total number of mites is also approximately three times greater. 77 patients from rural districts, 48 of whom allergic to their own house dust, and 29 controls, were tested with mite extracts from Dermatophagoides pteronyssimus, D. farinae, Chortoglyphus arcuatus, Acarus siro, Glycyphagus destructor and Tyrophagus putrescentiae, and a house dust extract. Out of 32 patients who showed positive scratch tests to one or more mite extracts, 29 (90,6 percent) reacted positively to D. pteronyssimus, 25 (78.1 percent) to D. farinae and from 7 to 12 (20-40 percent) to the stored food mites. Out of the 48 patients allergic to their own house dust, 27 (56.2 percent showed positive reactions to D. pteronyssinus, 24 (50.0 percent) to the house dust extract and 21 (43.7 percent) to D. farinae. Only 5 (17.2 percent) out of the 29 controls reacted positively to one or more of the solutions tested. The stored food mites showed 2.5 to 4.5 times more positive reactions in the rural patients compared with the results obtained in urban patients. The importance of these mites in the sensitization of patients from rural districts is discussed.