Prothrombin times on deficient plasma reconstituted with factors IX and X

Abstract

REFERENCES1. Lefkowitz JB, Monroe DM, Kasper CK, Roberts HR: Comparison of the behaviour of normal factor 1X and the factor 1X Bm variant Hils in the prothrombin time test using tissue factor, from bovine, human and rabbit sources. Am J Hematol 43:177-182, 1993. 2. Girolami A, Fabris F, Dal Bo Zanon R, Ghiotto G, Bum1 A: Factor VII Padua: A congenital coagulation disorder due to abnormal factor VI1 with a peculiar activation pattern. J Lab Clin Med 91:387-395, 1978. (abnormal factor IX coagulation disorder). Haematology 59:91-108, 1974. 5. Elodi S: Studies of the prolonged prothrombin time in hemophilia BM. Thromb Diath Haemorrh 29:247-252, 1973. 6. Spitzer SG, Wan-Cramer BJ, Kasper CK, Bajani SP: Replacement of isoleucine 397 by threonina in the clotting proteinase factor IXa (Los Angeles and Long Beach variants) affects macromolecula catalysis but not L-tosylarginine methyl ester hydrolysis. Biochem J 265:219-225, 1990. 7. Usharani P, Wan-Cramer J, Kasper CK, Bajay SP: Characterization of three abnormal factor IX variants (Bm Lake Elsinore, Long Becah and Los Angeles) of hemophilia. Br J Clin Invest 75:7&83, 1985. 8. Girolami A, Dal Bo Zanon R, Saltarin P, Quaino V, Altimier G, Ripa T, Marchetti A, Stocco D: Incidence, significance and subtypes of hemophilia Bm in a large population of hemophilia B patients. Blut 44:41-49, 1982.9. Girolami A, Dal Bo Zanon R, De Marco I, Cappellato G; Hemophilia B with associated factor VII deficiency: A distinct variant for hemophilia B with low factor VII activity and normal factor VII antigen. Professor Girolami and colleagues, Gray et al. in 1968 observed that a hemophilia B patient had a 4-sec prolongation using rabbit brain as the tissue source and a 226-sec prolongation using bovine brain [2]. In addition to their 1967 paper [3], in 1969 Twomey et al.[4] observed a 0-4 sec prolongation using human brain as the thromboplastin source and a 2 5 4 7 -sec prolongation using bovine brain, with intermediate prolongations when the thromboplastin source was dog, pig, sheep, or rat. We were interested in understanding the difference between the extreme prolongation seen with bovine brain and the mild to nonexistent prolongation when rabbit and human brain were used as the source of thromboplastin for the prothrombin time (PT). Our recent studies as well as those of Professor Girolami and colleagues are, of course, predated by the pioneering work of many other researchers. To cite just one example, Warner et al. in 1939 showed that thromboplastins from a wide variety of species have very different abilities to promote thrombin generation [5].We did not claim that Spitzer et al. [6] were the first to correlate ox brain PT and antigen levels. We cited that study because it gave an interesting example of how two hemophilia Bm patients initially classified as having different mutations because of the differences in their ox brain PT values were subsequently shown to have identical defects. That study showed dramatically how important it is to quantitate antigen levels of both factor 1X...