In vitro inhibition of factor XIII retards clot formation, reduces clot firmness, and increases fibrinolytic effects in whole blood.
BACKGROUND
Thrombelastography has received renewed interest in the perioperative setting. The main determinants of thrombelastographic results are coagulation factor concentrations (various zymogens and fibrinogen) and platelet count; thus, platelet inhibition renders these assays mainly coagulation factor dependent. Assays with and without platelet inhibition are thus increasingly used to trigger and monitor replacement therapy with blood products. In this study, we evaluated the effect of factor XIII inhibition and additional glycoprotein (GP) IIb/IIIa blockade on (platelet-inhibited) whole blood thrombelastography and whether a modified routine assay (using factor XIII antibody) can be used to detect factor XIII deficiency.


METHODS
Normal whole blood was incubated with increasing amounts of a nonspecific antibody, an anti-GPIIb/IIIa antibody, or a neutralizing anti-factor XIII antibody; samples were analyzed with a tissue factor-activated and platelet-inhibited whole blood thrombelastographic assay. Clotting time, clot formation time, maximum clot firmness, and clot lysis at 60 min were evaluated in triplicate. Also, 25 whole blood routine samples were evaluated for factor XIII deficiency using a new thrombelastographic assay incorporating a factor XIII antibody and using a standard factor XIII assay for comparison.


RESULTS
Although GPIIb/IIIa inhibition did not alter the results of the platelet-inhibited whole blood thrombelastography, factor XIII inhibition significantly reduced maximum clot firmness (P = 0.020) and increased clot formation time (P = 0.025) and clot lysis (P = 0.007), leaving clotting time unchanged; a ceiling effect seemed to be present with increasing antibody concentrations in whole blood (but not plasma). The thrombelastographic assay for factor XIII deficiency (<70% activity) had a 90% sensitivity and negative predictive value (area under receiver operating characteristic curve 0.803, P = 0.0015); for a deficiency <60%, sensitivity and negative predictive value were 100% (area under receiver operating characteristic curve 0.84, P = 0.0037).


CONCLUSIONS
Factor XIII has significant impact on platelet-inhibited activated whole blood thrombelastography. This phenomenon should be considered when interpreting thrombelastographic results in the bleeding patient, especially when the results trigger procoagulant therapy. Antibody-mediated factor XIII inhibition can be used to establish thrombelastography-based assays to detect factor XIII deficiency.
Jámbor
Csilla
C
Institute for Clinical Chemistry and Hematology, Kantonsspital, St. Gallen, 9007 Switzerland.
Reul
Viviane
V
Schnider
Thomas W
TW
Degiacomi
Priska
P
Metzner
Hubert
H
Korte
Wolfgang C
WC
D000077284:Abciximab; D000906:Antibodies / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D005176:Factor XIII / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005177:Factor XIII Deficiency / Q000097:blood / Q000175:diagnosis*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D011237:Predictive Value of Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013916:Thrombelastography; D013925:Thromboplastin / Q000378:metabolism; D013997:Time Factors
D000906:Antibodies; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D005176:Factor XIII; D013925:Thromboplastin; D000077284:Abciximab