Evaluation of euglobulin methods for the study of blood fibrinolytic activity: results for patients with rheumatoid arthritis and in the postoperative period.
Euglobulin fractionation is a frequently employed pretreatment of plasma for the determination of fibrinolytic activity. The fractionation procedure suffers from possible in vitro artifacts, e.g., variable precipitation of C1-inactivator. This is illustrated by the following two situations. It is shown that increased amounts of C1-inactivator not related to an increased plasma concentration are present in euglobulin fractions in cases of classic rheumatoid arthritis. Similarly, postoperatively, a disproportional increase in C1-inactivator in euglobulin fractions occurs. In both cases, an artificially reduced fibrinolytic activity is recorded due to increased inhibition by C1-inactivator. This is circumvented and recognized by adding sodium flufenamate or C1s-esterase to euglobulin fractions to uniformly eliminate C1-inactivator. Two specific assays for tissue-type plasminogen activator activity in euglobulin fractions (as C1-inactivator-resistant activator activity and a parabolic rate assay on a synthetic substrate) correlate excellently (r = 0.8728; p less than 0.001; n = 108). The first mentioned is corrected for variable endogenous C1-inactivator; the latter assay is found to be insensitive to inhibition by C1-inactivator. It is concluded that with euglobulin methods a misinterpretation of blood fibrinolytic activity is possible in rheumatoid arthritis patients. In the postoperative period, the fibrinolytic shutdown concerns tissue-type plasminogen activator activity; the pattern of the shutdown can be misjudged in using traditional euglobulin methods.
D000005:Abdomen / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood*; D005591:Chemical Fractionation; D003174:Complement C1 Inactivator Proteins / Q000032:analysis; D003173:Complement C1s / Q000378:metabolism; D005188:False Negative Reactions; D005342:Fibrinolysis; D005439:Flufenamic Acid / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D010960:Plasminogen Activators / Q000032:analysis*; D011184:Postoperative Period; D012712:Serum Globulins / Q000032:analysis*
D003174:Complement C1 Inactivator Proteins; D012712:Serum Globulins; D005439:Flufenamic Acid; D010960:Plasminogen Activators; D003173:Complement C1s