Changes in Factor VIII Proteins After Cardiopulmonary Bypass in Man Suggest Endothelial Damage

Summary

16 patients undergoing coronary artery bypass grafting using cardiopulmonary bypass (CPB) had blood samples taken at various times before, during and up to 1 week after surgery for estimation of beta-thromboglobulin (BTG), alpha- 1-antichymo- trypsin (ACT), factor VIII procoagulant protein (VIII:C), von Willebrand factor antigen (vWF:Ag) and ristocetin co-factor (vWFiRiCoF). vWF:Ag and vWF:RiCoF rose during and following surgery in a different manner to ACT. At 1 week there was a significantly disproportionate rise in vWF: Ag compared to vWFiRiCoF which suggested a degree of pulmonary endothelial damage.

Prostacyclin, which was administered to 8 of the patients during CPB, reduced platelet activation as measured by a reduction in the release of BTG and also attenuated the consumption of VIII: C. It had no effect on pulmonary endothelial damage as measured by the ratio of vWF: Ag to vWF: RiCoF.

Keywords

Factor VIII - Cardiopulmonary bypass - Prostacyclin - Endothelium

• References

• 1 Peake IR. The nature of factor VIII.. Clin Sci 1984; 67: 561-567
• 2 Stel HV, van der KwastTH, Veerman ECI. Detection of factor VUI/coagulant antigen in human liver tissue. Nature 1983; 303: 530-532
• 3 Bontempo FA, Lewis JH, Gorenc TJ, Spero JA, Ragni MV, Scott JP, Starzl TE. Liver transplantation in Haemophilia A.. Blood 1987; 69: 1721-1724
• 4 Shearn SAM, Peake IR, Giddings JC, Humphrys J, Bloom AL. The characterisation and synthesis of antigens related to factor VIII in vascular endothelium. Thromb Res 1977; 11: 43-56
• 5 Hoyer LW. Molecular pathology and immunology of factor VIII (Haemophilia A and factor VIII inhibitors).. Hum Pathol. 1987: 18
• 6 Grant K, Rodvien R, Mielke CH. Altered factor VIII complexes in patients with acute respiratory insufficiency. Thromb Haemostas 1978; 40: 326-334
• 7 Carvalho ACA, Bellman SM, Saullo VJ, Guinn D, Zapol WM. Altered factor VIII in acute respiratory failure. N Engl J Med 1982; 307: 1113-1119
• 8 Ratliff NB, Young WG, Hackel DB, Mikat E, Wilson JW. Pulmonary injury secondary to extracorporeal circulation. An ultrastructural study. J Thorac Cardiovasc Surg 1973; 65: 425-432
• 9 Anyanwu E, Dittrich H, Giesking R, Enders HJ. Ultrastructural changes in the human lung following cardiopulmonary bypass.. Basic Res Cardiol 1982; 77: 309-322
• 10 Fowler AA, Hammann RF, Good JT, Benson KN, Baird M, Eberle DJ, Petty TL, Hyers TM. Adult respiratory distress syndrome: risks with common predispositions. Ann Intern Med 1983; 98: 593-597
• 11 Williams WG, Manley RW, Drew C. Pulmonary circulatory arrest. Thorax 1965; 20: 523-527
• 12 Westaby S. Complement and the damaging effects of cardiopulmonary bypass. Thorax 1983; 38: 321-325
• 13 Jones DK, Higenbottam TW, Wheeldon D, Kneeshaw J, Bethune D, Wallwork J. Prostacyclin, cardiopulmonary bypass and the alveolar capillary membrane. Perfusion 1986; 1: 165-173
• 14 Jones DK, Higenbottam TW, Wallwork J. Treatment of primary pulmonary hypertension with intravenous epoprostenol (prostacyclin). Br Heart J 1987; 57: 270-278
• 15 Ubatuba FB, Moncada S, Vane JR. The effect of prostacyclin on platelet behaviour, thrombus formation in vivo and bleeding time. Thromb Haemostas 1979; 41: 425-435
• 16 Jones G, Hurley JV. The effect of prostacyclin on the adhesion of leucocytes to injured vascular endothelium. J Pathol 1984; 142: 51-59
• 17 Araki H, Lefer AM. Cytoprotective actions of prostacyclin during hypoxia in the isolated perfused cat liver.. Am J Physiol 1980; 238H: 176-181
• 18 Monden M, Fortner JG. Twenty-four and 48-hour canine liver preservation by simple hypothermia with prostacyclin. Ann Surg 1982; 196: 37-42
• 19 Lefer AM, Ogletree ML, Smith JB, Silver MJ, Nicolaou KC, Barnette WE, Gasic GP. Prostacyclin: a potentially valuable agent for preserving myocardial tissue in acute myocardial ischaemia.. Science 1978; 200: 52-54
• 20 Calvin J, Price CP. Measurement of serum alpha- 1-antichymotrypsin by immunoturbidimetry.. Ann Clin Biochem 1986; 23: 206-209
• 21 Hardisty RM, MacPherson JC. A one-stage factor VIII (antihaemophilia globulin) assay and its use on venous and capillary plasma.. Thromb Diath Haemorrh 1962; 7: 215-229
• 22 Weiss HJ, Hoyer LW, Rickless FR, Varma A, Rogers J. Quantitative assay of a plasma factor deficient in von Willebrand’s disease that is necessary for platelet aggregation: relationship to factor VIII procoagulant activity and antigen content.. J Clin Invest 1973; 52: 2708-2716
• 23 Laurell CB. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Ann Biochem 1966; 15: 45-52
• 24 Enayat MS, Hill FG H. Analysis of the complexity of the multimeric structure of Factor VIII related antigen/von Willebrand protein using a modified electrophoretic technique. J Clin Pathol 1983; 36: 915-919
• 25 Armitage P. (ed) Statistical Methods in Medical Research.. 1st ed Blackwell; Oxford: 1971. pp 253-259
• 26 Weibel ER. Morphological basis of alveolar-capillary gas exchange. Physiol Rev 1973; 53: 419-495
• 27 Tilney NL, Hester WJ. Physiologic and histological changes in the lungs of patients dying after prolonged cardiopulmonary bypass.. Ann Surg 1967; 166: 759-766
• 28 Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults.. Lancet 1967; ii: 319-323
• 29 Nahas RA, Melrose DG, Sykes MK, Robinson B. Post perfusion lung syndrome. The role of circulatory exclusion.. Lancet 1965; ii: 251-254
• 30 Young JA. Coagulation abnormalities with cardiopulmonary bypass.. In: Pathophysiology and Techniques of Cardiopulmonary Bypass (Vol; 1). Utley JR. (ed) Williams and Wilkins; London : 1982. pp 88-105
• 31 van Oeveren W, Kazatchkine MD, Descamps-Latscha B, Maillet F, Fischer E, Carpentier A, Wildevuur CRH. Deleterious effects of cardiopulmonary bypass. A prospective study of bubble versus membrane oxygenation.. J Thorac Cardiovasc Surg 1985; 89: 888-899
• 32 Braude S, Nolop KB, Fleming JS, Krausz T, Taylor KM, Royston D. Increased pulmonary transvascular protein flux after canine cardiopulmonary bypass. Association with lung neutrophil sequestration and tissue peroxidation.. Am Rev Respir Dis 1986; 134: 867-872
• 33 Connell RS, Page US, Bartley TD, Bigelow JC, Webb MC. The effect on pulmonary ultrastructure of Dacron-wool filtration during cardiopulmonary bypass.. Ann Thorac Surg 1973; 15: 217-229
• 34 Rak K, Beck P, Udvardy M, Pfliegler G, Misz M, Boda Z. Plasma levels of beta-thromboglobulin and factor VUI-related antigen in diabetic children and adults.. Thromb Res 1983; 29: 155-162
• 35 Brown Z, Neild GH, Willoughby JJ, Somia NV, Cameron SJ. Increased factor VIII as an index of vascular injury in cyclosporine nephrotoxicity.. Transplantation 1986; 42: 150-153
• 36 Losito R, Beaudry P, Valderrama JC, Cousineau L, Longpre B. Antithrombin III and factor VIII in patients with neoplasms.. Am J Clin Pathol 1977; 68: 258-263
• 37 Lombardi R, Mannucci PM, Segatchian MJ, Vicente GarciaV, Coppola R. Alterations of factor VIII von Willebrand factor in clinical conditions associated with an increase in its plasma concentration.. Br J Haematol 1981; 49: 61-68
• 38 Langley PG, Hughes RD, Williams R. Increased factor VIII complex in fulminant hepatic failure.. Thromb Haemostas 1985; 54: 693-696
• 39 Heinrich D, Schleussner E, Wagner WL, Sellmann-Richter R, Hehrlein FW. Prostacyclin in aortocoronary bypass surgery: a double blind, placebo-controlled study.. Thromb Res 1983; 32: 409-426
• 40 Brody JI, Pickering NJ, Fink GB. Concentrations of factor VIII- related antigen and factor XIII during open heart surgery.. Transfusion 1986; 26: 478-480
• 41 Hawkey CJ, Stirling Y, Charkrabati R, Brozovic M, Cox AG, Meade TW. Haemostatic changes following surgery.. Thromb Res 1983; 32: 223-227