Monocyte tissue factor expression and ongoing complement generation in ventricular assist device patients.
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.
Wilhelm
C R
CR
Department of Surgery and Artificial Heart Program, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
Ristich
J
J
Kormos
R L
RL
Wagner
W R
WR
D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000032:analysis; D002449:Cell Aggregation; D003167:Complement Activation; D015926:Complement C3a / Q000032:analysis; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000032:analysis / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000032:analysis; D006098:Granulocytes / Q000502:physiology; D006353:Heart-Assist Devices; D006487:Hemostasis; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D010447:Peptide Hydrolases / Q000032:analysis; D015539:Platelet Activation; D013917:Thrombin / Q000096:biosynthesis; D013925:Thromboplastin / Q000032:analysis* / Q000235:genetics; D013997:Time Factors
D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; C047610:SC5b-9 protein complex; C046193:antithrombin III-protease complex; D015926:Complement C3a; D000990:Antithrombin III; D003165:Complement System Proteins; D013925:Thromboplastin; D010447:Peptide Hydrolases; D013917:Thrombin