Thrombosis: A Study of Coagulation Parameters and Mechanisms during Allograft Rejection

Summary

Thrombosis of the microvasculature has been recognized as the end product of organ rejection, but the exact biological pathway through which this occurs has not been clarified. Normal, factor VII deficient and heterozygous hemophilic (factor VIII) dogs were grouped to study the intrinsic and extrinsic clotting and platelet mechanisms during unmodified renal allograft rejection. The observed alterations of the hemostatic mechanisms are related to the changes observed in the microvasculature. Six groups of donor-recipient animals were studied: Group I - autografts (control); Group II - normal to normal allografts with bilateral nephrectomy; Group III - heterozygotes for factor VIII deficiency; Group IV - normal to normal allografts with unilateral nephrectomy; Group V - normal to factor VII deficiency without nephrectomy; and Group VI - normal to normal allografts with unilateral nephrectomy and dipyridamole. Each engrafted animal was followed pre- and posttransplantation for change in the blood clotting factors, fibrin split products, platelets, white blood cells, renal function and microvasculature. The animals with factor VII deficiency rejected in a similar fashion as the control animals. The group with impaired factor VIII synthesis and platelet function had longer survival times. These data suggest that the intrinsic clotting pathway and platelets are the primary mechanism through which thrombosis occurs secondary to immune injury.

• References

• 1 Brecher G, Cronkite EP. 1964. Estimation of the number of platelets by phase microscopy. In: Tocantins Kazal (eds.) Blood Coagulation Hemorrhage and Thrombosis Grune and Stratton; New York: p 52
• 2 Busch GJ, Braun WE, Carpenter CB, Corson JM, Galvanek ER, Reynolds ES, Merrill JP, Dammin GJ. 1969; Intravascular coagulation (IVC) in human renal allograft rejection. Transplantation Proceedings 1: 267
• 3 Busch GJ, Galvanek EG, Reynolds ES. 1971; a Human renal allografts: analysis of lesions in long-term survivors. Human Pathology 2: 253
• 4 Busch GJ, Reynolds ES, Galvanek EG, Braun WE, Dammin GJ. 1971; b Human renal allografts. Medicine 50: 29
• 5 Claes G. 1972; Studies on platelets and fibrinogen during rejection of canine renal allografts. Scandinavian Journal of Urology and Nephrology. Supp (Suppl. 01) 10: 5
• 6 Colman RW, Braun WE, Busch GJ, Dammin GJ, Merrill JP. 1969; Coagulation studies in hyperacute and other formsof renal allograft rejection. New England Journal of Medicine 281-685
• 7 Garvey MG, Black JM. 1972; The detection of fibrinogen/fibrin degradation products by means of a new antibody-coated latex particle. Journal of Clinical Pathology 25: 680
• 8 George CR P, Slichter SJ, Quadracci LJ, Striker GE, Harker LA. 1974; A kinetic evaluation of hemostasis in renal disease. New England Journal of Medicine 291: 1111
• 9 Graham JB, Buckwalter JA, Hartley LJ, Brinkhous KM. 1949; Canine hemophilia: observations of the course, the clotting anomaly, and the effect of blood transfusions. Journal of Experimental Medicine 90: 97
• 10 Huseby RM, Bang NU. 1971. Fibrinogen. In: Bang Beller Deutsch Mammen (eds.) Thrombosis and Bleeding. Academic Press; New York: p 233
• 11 Ingram GI C. 1973. The control of the Factor VIII level in the nonhemophilic subject. In: Ala Denson eds Haemophilia. Excerpta Medica; Amsterdam: p 3
• 12 Langdell RD, Wagner RH, Brinkhous KM. 1953; Effect of antihemophilic factor on one-stage clotting tests. Journal of Laboratory and Clinical Medicine 41: 637
• 13 Marsh WH, Fingerhut B, Miller H. 1965; Automated and manual direct methods for the determination of blood urea. Clinical Chemistry 11: 624
• 14 Mckee PA, Coussons RT, Buckner RG, Williams GR, Hampton JW. 1970; Effects of the spleen on canine factor VIII levels. Journal of Laboratory and Clinical Medicine 75: 391
• 15 Penick GD, Roberts HR, Webster WP, Brinkhous KM. 1958; Hemorrhagic states secondary to intravascular clotting: an experimental study of their evaluation and prevention. Archives of Pathology 66: 708
• 16 Starzl TE, Boehmig HJ, Ameniya H, Wilson CB, Dixon FJ, Giles GR, Simpson KM, Halgrimson CG. 1970; Clotting changes, including disseminated intravascular coagulation during rapid renal-homograft rejection. New England Journal of Medicine 283: 383
• 17 Webster WP, Zukoski CF, Hutchin P, Reddick RL, Mandel SR, Penick GD. 1971; Plasma factor VIII synthesis and control as revealed by canine organ transplantation. American Journal of Physiology 220: 1147
• 18 Webster WP, Mandel SR, Reddick RL, Wagner JL, Penick GD. 1974; Orthotopic liver transplantation in canine hemophilia B. American Journal of Physiology 226: 496
• Webster WP, Mandel SR, Strike LE, Penick GD, Griggs TR, Brinkhous KM. 1976; Factor VIII synthesis: hepatic and renal allografts in swine with von Willebrand’s disease. American Journal of Physiology 230: 1342