The Endothelial Cell and the Factor VIII Bypassing Activity of Prothrombin Complex Concentrate

Summary

Some classical hemophiliacs have a paradoxical hemostatic response to prothrombin complex concentrate (PCC). We hypothesized that vascular endothelial cells (EC) may contribute to this “factor VIII bypassing activity”. When PCC were incubated with suspensions or monolayer cultures of EC, they acquired the ability to partially bypass the defect of factor VIII deficient plasma. This factor VIII bypassing activity distributed with EC and not with the supernatant PCC, and was not a general property of intravascular cells. The effect of PCC was even more dramatic on fixed EC monolayers, which became procoagulant after incubation with PCC. The time courses of association and dissociation of the PCC-derived factor VIII bypassing activity of fixed and viable EC monolayers were both rapid. We conclude that EC may provide a privileged site for sequestration of constituents of PCC which express coagulant activity and which bypass the abnormality of factor VIII deficient plasma.

Keywords

Endothelial cells - Factor VIII - Prothrombin complex concentrates

• References

• 1 Lusher JM, Shapiro SS, Palascak JE, Vijaya RaoA, Levine PH, Blatt PM. and the Hemophilia Study Group. Efficacy of prothrombin-complex concentrates in hemophiliacs with antibodies to factor VIII.. N Engl J Med 1980; 303: 421-425
• 2 Blatt PM, White GC, McMillan CW, Roberts HR. Treatment of anti-factor VIII antibodies.. Thromb Haemostas 1977; 38: 514-523
• 3 Jaffe EA, Levin RI, Weksler BB, Marcus AJ. Synthesis of prostacyclin by cultured endothelial cells.. In: Pathobiology of the Endothelial Cell. Nossel HJ, Vogel HJ. (eds) Academic Press; New York : 1982. pp 301-309
• 4 Levin EG, Loskutoff DJ. Cultured bovine endothelial cells produce both urokinase and tissue-type plasminogen activators.. J Cell Biol 1982; 94: 631-636
• 5 Fair DS, Marlar RA, Levin EG. Human endothelial cells synthesize protein S.. Blood 1986; 67: 1168-1171
• 6 Busch C, Owen WG. Identification in vitro of an endothelial cell surface cofactor for antithrombin III.. J Clin Invest 1982; 69: 726-729
• 7 Esmon CT, Owen WG. Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C.. Proc Natl Acad Sci USA 1981; 78: 2249-2252
• 8 Jaffe EA, Hoyer LW, Nachman RL. Synthesis of antihemophilic factor antigen by cultured human endothelial cells.. J Clin Invest 1973; 52: 2757-2764
• 9 Cerveny T, Fass D, Mann K. Synthesis of factor V by cultured bovine endothelial cells.. Blood 1984; 63: 1467-1474
• 10 Sprengers ED, Kluft C. Plasminogen activator inhibitors.. Blood 1987; 69: 381-387
• 11 Nawroth PP, Handley D, Stern DM. The multiple levels of endothelial cell-coagulation factor interactions.. Clin Haematol 1986; 15: 293-321
• 12 Shore AS, Leary P, Teitel JM. Comparison of accessory cell functions of endothelial cells and monocytes: IL-2 production by T cells and PFC generation.. Cell Immunol 1986; 100: 210-223
• 13 White GC, Roberts HR, Kingdon HS, Lundblad RL. Prothrombin complex concentrates: portentially thrombogenic materials and clues to the mechanism of thrombosis in vivo.. Blood 1977; 49: 159-170
• 14 Bull HA, Machin SJ. The haemostatic function of the vascular endothelial cell.. Blut 1987; 55: 71-80
• 15 Rosenberg RD, Rosenberg JS. Natural anticoagulant mechanisms.. J Clin Invest 1984; 74: 1-6
• 16 Walker FJ, Esmon CT. The effects of phospholipid and factor Va on the inhibition of factor Xa by antithrombin III.. Biochem Biophys Res Commun 1979; 90: 641-647
• 17 Teitel JM, Rosenberg RD. Protection of factor Xa from neutralization by the heparin-antithrombin complex.. J Clin Invest 1983; 71: 1383-1391
• 18 Nesheim ME, Giles AR. Rapid changes associated with hemostasis or bleeding induced in dogs by various combinations of factor Xa plus phosphatidylcholine phosphatidyl serine vesicles. Circulation 1986; 74 (supp II): 1166