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Monocyte tissue factor expression and ongoing complement generation in ventricular assist device patients.

C R Wilhelm·J Ristich·R L Kormos·W R Wagner
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Abstract

BACKGROUND: Ongoing complement activation in patients with a ventricular assist device may contribute to observed hemostatic abnormalities and cellular aggregation by mediating leukocyte and platelet activation, formation of leukocyte-platelet conjugates, and the tissue factor pathway of coagulation. METHODS: Blood from 30 patients was collected before ventricular assist device implantation and during the implantation period. Plasma levels of thrombin-antithrombin III complexes, C3a, and SC5b-9 were measured by commercial enzyme-linked immunosorbent assay. Flow cytometry was used to measure circulating monocyte tissue factor expression and circulating monocyteplatelet and granulocyte-platelet conjugates. RESULTS: Thrombin-antithrombin III complex level and monocyte tissue factor expression peaked in the early postoperative period, with maxima occurring on postoperative days 5 and 3, respectively. Levels of C3a and SC5b-9 remained dramatically elevated over normal values for the duration of the study (6 and 5 times upper normal, respectively). Levels of monocyte-platelet conjugates were normal before implantation, decreased during the first 4 postoperative days, and then increased and remained elevated. Levels of granulocyte-platelet conjugates were elevated over the normal range before implantation and remained elevated from postoperative days 3 to 21. A positive correlation was found between levels of SC5b-9 and granulocyte-platelet conjugates (Spearman R=0.66; p < 0.001), and between levels of C3a and thrombin-antithrombin III complex (Spearman R=0.13; p=0.021). CONCLUSIONS: The data suggest a model in which complement mediates formation of leukocyte-platelet aggregates and may indirectly contribute to thrombin generation through monocyte tissue factor expression.

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AdultAgedAntithrombin IIICell AggregationComplement ActivationComplement C3aComplement Membrane Attack ComplexComplement System ProteinsEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryFollow-Up StudiesGene Expression RegulationGlycoproteinsGranulocytesHeart-Assist DevicesHemostasisHumansLeukocytesMaleMiddle AgedMonocytesPeptide HydrolasesPlatelet ActivationThrombinThromboplastinTime FactorsJournal ArticleResearch Support, Non-U.S. Gov't

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C R Wilhelm, J Ristich, R L Kormos, W R Wagner. 1998. Monocyte tissue factor expression and ongoing complement generation in ventricular assist device patients.. https://doi.org/10.1016/s0003-4975(98)00111-8

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