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Cryoprecipitate-topical thrombin glue
J
THORAC CARDIOVASC SURG
90:502-505, 1985
Cryoprecipitate-topical thrombin glue Initial experience in patients undergoing cardiac operations The me of fibrin glues as topical hemostatic agents is reported in the European literature. We have composed an analogous compound in our operating rooms using cryoprecipitate and topical thrombin (1000 unitsfml) in equal volumes applied directly to the bleeding site. We have used cryoprecipitatetopical thrombin glue in 26 patients undergoing cardiac operations. Severe bleeding not responding to ~ methods of control was encountered during or after coronary artery bypass (n = 17), valve replacement (n = 3~ bypass plus valve replacement (n = 5), or repair of postinfarction ventricular septal defect (n = 1). Five patients were operated on emergently and four were undergoing their second cardiac operation. The glue was used in four patients while on bypassand fullyheparinized and in 17 patients who continued to bleed after separation from bypass and administration of protamine. Hemostasis was achieved in all patients and none required reexploration for bleeding. In five patients undergoing reexploration for postoperative hemorrhage (none having received cryoprecipitate-topical thrombin glue during the initial operation), the glue provided hemostasis when other measures failed, and no additional reexplorations were needed. No patient exhibited hypersensitivity, fibrinolysis, or coagulopathyfollowing the use of this glue. In 16 patients followed for 9 to 12 months postoperatively, no hepatitis has occurred. The highly concentrated fibrinogen in cryoprecipitate is activated by thrombin to form fibrin and bring about rapid hemostasis. Cryoprecipitate-topical thrombin glue is a readily available, reliable, and inexpensive topical hemostatic agent in the patient undergoing a cardiac operation.
F1avian M. Lupinetti, M.D. (by invitation), William S. Stoney, M.D., William C. Alford, Jr., M.D., George R. Burrus, M.D. (by invitation), David M. Glassford, Jr., M.D. (by invitation), Michael R. Petracek, M.D. (by invitation), and Clarence S. Thomas, M.D., Nashville, Tenn.
Esistent hemorrhage refractory to usual methods of control remains a potentially life-threatening complication to the patient undergoing a cardiac operation, and it is a frustrating problem for the surgeon. This problem is encountered with increased frequency as cardiac surgeons more commonly undertake reoperative and emergency procedures, operations on poor-risk patients, and treatment of individuals who have or develop coagulopathic conditions. Optimal control of bleeding may require a combination of direct suture control, electroFrom the Departments of Cardiac and Thoracic Surgery, Vanderbilt University Hospital and St. Thomas Hospital, Nashville, Tennessee Read at the Sixty-fifth Annual Meeting of The American Association for Thoracic Surgery, New Orleans, La., April 29-May I, 1985. Address for reprints: William S. Stoney, M.D., St. Thomas Hospital, 4220 Harding Rd. Nashville, Tenn. 37202.
502
cautery, topical collagen hemostatic agents, and other techniques. Even these may be inadequate or inappropriate at times. The experimental use of fibrin glues has been welldocumented in the European literature.!" and these compounds have been used clinically for over 10 years.':" In the United States, fibrin glue has been used experimentally 15, 16 but is not approved for clinical use. The ready availability of fibrinogen-rich cryprecipitate and topical thrombin, however, allows the simple manufacture of an analogous substance that achieves reliable and safe hemostasis.
Patients and methods In patients undergoing cardiac operations who demonstrated bleeding that could not be safely controlled by placement of suture material, cautery, and surface application of collagen hemostats, consideration was
Volume 90 Number 4 October, 1985
given to the use of cryoprecipitate-topical thrombin glue. Cryoprecipitate in single-donor units, 1 to 10 ml each, was obtained from the blood bank and drawn into a syringe on the operating field. Topical thrombin was reconstituted in normal saline to a concentration of 1,000 units/ml and placed in a separate syringe. The cryoprecipitate and thrombin were then simultaneously injected directly onto the bleeding site in approximately equal volumes. A dense gel formed almost instantaneously, and this rapidly became a firm clot. In cases in which hemostasis was not controlled, the coagulum was removed to permit more accurate and direct reapplication. Cryoprecipitate-topical thrombin glue was used in 26 patients between April 1 and June 30, 1984. These patients were the first in whom this glue was used in this institution. They included all patients during this period in whom refractory hemorrhage was encountered. There were 14 men and 12 women. The patients' ages ranged from 30 to 79 years, with a mean of 61 years. No patient had a derangement of clotting function preoperatively as evaluated by routine measurement of prothrombin time, partial thromboplastin time, platelet count, and bleeding time when indicated. No attempt was made to discontinue aspirin use in advance in the 12 patients who routinely received aspirin while awaiting operation. Follow-up was established in all surviving patients by telephone contact with the patients, family members, or personal physicians. Operations performed included coronary artery bypass in 17 patients, valve replacement in three patients, coronary bypass and valve replacement in five patients, and repair of a postinfarction ventricular septal defect in one patient. Two coronary bypass operations were second-time operations for progression of disease, and two aortic valve replacements were reoperations because of valve deterioration. Five operations were performed emergently. Cryoprecipitate-topical thrombin glue was used while the patient was on bypass and fully heparinized in four cases and after separation from bypass and administration of protamine in 17 cases. The glue was used in five patients who required reexploration for persistent postoperative bleeding; none of these patients had received the glue during the initial operation. Two patients required cryoprecipitate-topical thrombin glue for disseminated intravascular coagulopathy that developed intraoperatively before the administration of the glue. The sites of administration of the glue included the aortic and coronary artery suture lines of saphenous vein and internal mammary bypass grafts,
Cryoprecipitate-topical thrombin glue 5 0 3
the aortic suture line after valve replacement, ventriculotomy closures, and superficial epicardial bleeding points. Results From 2 to 20 ml of cryoprecipitate-topical thrombin glue was used to control bleeding. Hemorrhage was stopped in all 21 patients who received the glue during their cardiac operation, and none required reexploration at a later time. In the five patients who required reexploration for bleeding, none having received cryoprecipitate-topical thrombin glue during the initial procedure, bleeding was also controlled by the glue and no further reexploration was necessary. Four of the five patients who required reexploration for bleeding were among the first six patients in our series. There were nine deaths, five on the first postoperative day. Four deaths, including both patients with disseminated intravascular coagulopathy, occurred between postoperative days 10 and 34. No death could be attributed to hemorrhage alone, although the complications associated with hemorrhage were contributory in some cases. There was no evidence of hypersensitivity, fibrinolysis, or coagulopathy occurring. after the use of cryoprecipitate-topical thrombin glue. Of the 17 patients discharged alive, 16 are alive 9 months to 1 year postoperatively. The cause of death in the one nonsurvivor is not known. No cases of hepatitis developed during this period. Discussion Cryoprecipitate was first used by Pool and Shannon" in 1965 in the treatment of classic hemophilia. It is produced by slow thawing of plasma at low temperatures. In addition to having 20% to 85% of the factor VIII present in the original unit of plasma, cryoprecipitate contains enough factor XIII to be of use in treating factor XIII deficiency. It also contains small amounts of factors II, V, and IX plus the bulk of fibrinogen present in the plasma with a concentration of fibrinogen of 150 to 200 mg/unit of cryoprecipitate. Thrombin interacts with fibrinogen to produce fibrin monomers, which undergo hydrogen bonding to form strands of polymeric fibrin. These strands are then stabilized by factor XIII, also activated by thrombin, to establish the stable cross-linking necessary for clot formation." These reactions are catalyzed by calcium, and some proponents of fibrin glues add calcium to their solutions." We have not found this necessary, as the calcium content in autologous serum appears adequate
The Journal of Thoracic and Cardiovascular Surgery
5 0 4 Lupinetti et al.
to permit the necessary reactions to occur. Similarly, we have omitted aprotinin, used by some investigators to stabilize the clot and prevent fibrinolysis,":" with no apparent adverse consequences. Fibrin glues do not require an intact coagulation system and can therefore be used despite systemic heparinization. This allows the surgeon to obtain a considerable degree of hemostasis prior to reversing heparin with protamine. Although no complications of intravascular coagulation have been described following the use of fibrin glue, it seems a reasonable precaution to avoid depositing the fibrinogen or the thrombin components into the intravascular space or into the suction port of the cardiopulmonary bypass pump. Another reasonable precaution is selective and judicious use of these glues. On the one hand, they will not control vigorous arterial bleeding that properly requires suture ligation. On the other hand, excessive application of fibrin glue may theoretically contribute to tamponade or to excessive adhesion formation. Fibrin adhesives have been shown to be effective in cardiac and vascular operations in adults.':'? pulmonary resection and treatment of pneumothorax, II pediatric cardiac operations," splenic salvage," and skin grafting." In addition, these substances have been used experimentally in cardiac valve implants.i lymphovenous anastomoses,' colon anastomoses,' and repair of liver injuries. 16 We have found cryoprecipitate-topical thrombin glue to be most valuable in securing hemostasis in the distal suture line of coronary bypass grafts. This is especially true with internal mammary artery bypasses, which provide superior long-term patency but require greater caution in manipulation. In these delicate vessels, this glue may be far safer than additional suture. Four of the five patients requiring reoperation in our series were among the initial six patients to receive cryoprecipitate-topical thrombin glue, whereas reexploration was required only once in the last 17 patients. This demonstrates that additional experience with the use of this glue has made us more ready to use it when the chances of postoperative bleeding appear greater than usual. Cryoprecipitate-topical thrombin glue is a safe and reliable topical hemostatic agent in the patient undergoing a cardiac operation. It is easily made, readily available, and is more economical than other hemostatic agents." The risk of hepatitis, while present, is low" and is perhaps lower than the risk of multiple repeated transfusions of blood products required in the treatment of unremitting hemorrhage.
We wish to acknowledge the assistance of Dr. Charles Wallace for his recommendations in our use of cryoprecipitate. REFERENCES Haverich A, Maatz W, Walterbusch G: Evaluation of fibrin seal in animal experiments. Thorac Cardiovasc Surg 30:215-222, 1982 2 Saggau W, Hatipoglu 0, Mittman U, Spath J, Storch HH, Schmitz W, Wurster K: Tissue glue for sealing plastic valves and bioprosthesis in the canine aorta. Scand J Thorac Cardiovasc Surg 16: 129-135, 1982 3 Milingos S, Tassopoulos J, Vrachnos P: Experimental remarks on the utilization of biological tissue adhesives in Iymphovenous anastomosis. J Cardiovasc Surg 25: 130133, 1984 4 Oka H, Harrison RC, Burhenne HJ: Effect of a biologic glue on the leakage rate fo experimental rectal anastomoses. Am J Surg 143:561-564, 1982 5 Wolner E: Fibrin gluing in cardiovascular surgery. Thorac Cardiovasc Surg 30:236-237, 1982 6 Borst HG, Haverich A, Walterbusch G, Maatz W: Fibrin adhesive. An important hemostatic adjunct in cardiovascular operations. J THoRAc CARDIOVASC SURG 84:548-553, 1982 7 Walterbusch G, Haverich A, Borst HG: Borst HG: Clinical experience with fibrin glue for local bleeding control and sealing of vascular prostheses. Thorac Cardiovase Surg 30:234-235, 1982 8 Koveker G, de Vivie ER, Hellberg KD: Clinical experience with fibrin glue in cardiac surgery. Thorac Cardiovasc Surg 29:287-289, 1981 9 Kalmar P, Krebber HJ, Pokar H, Tilsner V: Bioadhesives in cardiac and vascular surgery. Thorac Cardiovasc Surg 30:230-231,1982 10 Koveker G: Clinical application of fibrin glue in cardiovascular surgery. Thorac Cardiovasc Surg 30:228-229, 1982 11 Thetter 0: Fibrin adhesive and its application in thoracic surgery. Thorac Cardiovasc Surg 29:290-292, /981 12 Stark J, de Leval M: Experience with fibrin seal (Tisseel) in operations for congenital heart defects. Ann Thorac Surg 38:411-413, 1984 13 Scheele J, Gentsch HH, Matteson E: Splenic repair by fibrin tissue adhesive and collagen fleece. Surgery 95:6-13, 1984 14 Vibe P, Pleas J: A new method of skin graft adhesion. Scand J Plast Reconstr Surg 17:263-264, 1983 15 Jakob H, Campbell CD, Qiu ZK, Pick R, Replogle RL: Evaluation of fibrin sealing for cardiovascular surgery. Circulation 70:Suppl I: 138-146, 1984 16 Jakob H, Campbell CD, Sternberger A, Wriedt-Lubbe I, Blumel G, Replogle RL: Combined application of heterologous collagen and fibrin sealant for live injuries. J Surg Res 36:571-577, 1984 17 Pool JG, Shannon AE: Production of high-potency con-
Volume 90 Number 4 October, 1985
centrates of antihemophilic globulin in a close-bag system. Assay in vitro and in vivo. N Engl J Med 273:1443-1447, 1965 18 Sternberger A, Blumel G: Fibrinogen-fibrin conversion and inhibition of fibrinolysis. Thorac Cardiovasc Surg 30:209-214, 1982 19 Redl H, Schlag G, Dinges HP: Methods of fibrin seal application. Thorac Cardiovasc Surg 30:223-227, 1982 20 Rousou JA, Engelman RM, Breyer RH: Fibrin glue. An effective hemostatic agent for nonsuturable intraoperative bleeding. Ann Thorac Surg 38:409-410, 1984 21 Scheele J, Schricker KT, Goy RD, Lampe I, Panis R: Hepatitisrisiko der Fibrinklebung in der Allgemeichirurgie. Med Welt 32:783-788, 1981
Discussion DR. HANS G. BORST Hannover, Federal Republic of German)'
Our experience with hemostatic fibrin sealing now comprises close to 1,000 applications both in the high-pressure and in the low-pressure system, with a failure rate of 3.4% in the former and 1.9% in the latter. Fibrin sealing, therefore, has become an integral part of our cardiovascular practice and we surely could not do without it anymore. Perhaps of interest are our results with fibrin sealing of vascular prostheses. We used sealed woven grafts in the ascending aortic and arch positions in 74 patients without any failures. We had the same success in 25 right ventricularpulmonary arterial conduits and right ventricular patches. Knitted grafts were employed in 14 patients undergoing ascending aortic replacement, with one failure occurring in the only graft made of nonvelour fabric. The impression was gained that this prosthesis could not be loaded with a sufficient
Cryoprecipitate-topical thrombin glue 5 0 5
amount of fibrin adhesive because of the absence of the velour. Knitted right ventricular-pulmonary arterial conduits and patches were sealed in 20 instances without failure, and knitted left ventricular patches were successfully sealed in five cases. Finally, we replaced the descending, the thoracoabdominal, and the infrarenal aorta with knitted grafts in 204 patients who had received a heparin dose of I mg/kg. There were six failures in this group, all of which occurred in patients with perforated aneurysms, profound shock, and acidosis. The possible mechanism of the observed failure to seal was thought to be fibrinolysis in these patients. We conclude that fibrin sealing of woven and knitted double velour grafts is a highly reliable method for closing the pores of the fabric. Fibrin-sealed knitted grafts probably should not be used under the conditions of severe circulatory impairment. Importantly, the sealant does not impede the handling qualities of a graft. I would like to ask the authors which concentration of the fibrinogen they are using. In our experience a high concentration of 90 mg/rnl appears mandatory. DR. LUPINETTI (Closing) I would like to thank Professor Borst not only for his kind comments but for his many contributions in the field of adhesives in surgical technique. The concentration of fibrinogen in cryoprecipitate is quite variable and depends partly on ~he vagaries of the blood bank manufacture of this substance. Normally there is 150 to 200 mg of fibrinogen per unit of cryoprecipitate, which is anywhere from I to 10 ml. That would equal a minimum of 15 mg/rnl, as Dr. Borst recommends. We have not made any efforts, however, to quantitate the precise amount of fibrinogen in our cryoprecipitate.
THORAC CARDIOVASC SURG
90:502-505, 1985
Cryoprecipitate-topical thrombin glue Initial experience in patients undergoing cardiac operations The me of fibrin glues as topical hemostatic agents is reported in the European literature. We have composed an analogous compound in our operating rooms using cryoprecipitate and topical thrombin (1000 unitsfml) in equal volumes applied directly to the bleeding site. We have used cryoprecipitatetopical thrombin glue in 26 patients undergoing cardiac operations. Severe bleeding not responding to ~ methods of control was encountered during or after coronary artery bypass (n = 17), valve replacement (n = 3~ bypass plus valve replacement (n = 5), or repair of postinfarction ventricular septal defect (n = 1). Five patients were operated on emergently and four were undergoing their second cardiac operation. The glue was used in four patients while on bypassand fullyheparinized and in 17 patients who continued to bleed after separation from bypass and administration of protamine. Hemostasis was achieved in all patients and none required reexploration for bleeding. In five patients undergoing reexploration for postoperative hemorrhage (none having received cryoprecipitate-topical thrombin glue during the initial operation), the glue provided hemostasis when other measures failed, and no additional reexplorations were needed. No patient exhibited hypersensitivity, fibrinolysis, or coagulopathyfollowing the use of this glue. In 16 patients followed for 9 to 12 months postoperatively, no hepatitis has occurred. The highly concentrated fibrinogen in cryoprecipitate is activated by thrombin to form fibrin and bring about rapid hemostasis. Cryoprecipitate-topical thrombin glue is a readily available, reliable, and inexpensive topical hemostatic agent in the patient undergoing a cardiac operation.
F1avian M. Lupinetti, M.D. (by invitation), William S. Stoney, M.D., William C. Alford, Jr., M.D., George R. Burrus, M.D. (by invitation), David M. Glassford, Jr., M.D. (by invitation), Michael R. Petracek, M.D. (by invitation), and Clarence S. Thomas, M.D., Nashville, Tenn.
Esistent hemorrhage refractory to usual methods of control remains a potentially life-threatening complication to the patient undergoing a cardiac operation, and it is a frustrating problem for the surgeon. This problem is encountered with increased frequency as cardiac surgeons more commonly undertake reoperative and emergency procedures, operations on poor-risk patients, and treatment of individuals who have or develop coagulopathic conditions. Optimal control of bleeding may require a combination of direct suture control, electroFrom the Departments of Cardiac and Thoracic Surgery, Vanderbilt University Hospital and St. Thomas Hospital, Nashville, Tennessee Read at the Sixty-fifth Annual Meeting of The American Association for Thoracic Surgery, New Orleans, La., April 29-May I, 1985. Address for reprints: William S. Stoney, M.D., St. Thomas Hospital, 4220 Harding Rd. Nashville, Tenn. 37202.
502
cautery, topical collagen hemostatic agents, and other techniques. Even these may be inadequate or inappropriate at times. The experimental use of fibrin glues has been welldocumented in the European literature.!" and these compounds have been used clinically for over 10 years.':" In the United States, fibrin glue has been used experimentally 15, 16 but is not approved for clinical use. The ready availability of fibrinogen-rich cryprecipitate and topical thrombin, however, allows the simple manufacture of an analogous substance that achieves reliable and safe hemostasis.
Patients and methods In patients undergoing cardiac operations who demonstrated bleeding that could not be safely controlled by placement of suture material, cautery, and surface application of collagen hemostats, consideration was
Volume 90 Number 4 October, 1985
given to the use of cryoprecipitate-topical thrombin glue. Cryoprecipitate in single-donor units, 1 to 10 ml each, was obtained from the blood bank and drawn into a syringe on the operating field. Topical thrombin was reconstituted in normal saline to a concentration of 1,000 units/ml and placed in a separate syringe. The cryoprecipitate and thrombin were then simultaneously injected directly onto the bleeding site in approximately equal volumes. A dense gel formed almost instantaneously, and this rapidly became a firm clot. In cases in which hemostasis was not controlled, the coagulum was removed to permit more accurate and direct reapplication. Cryoprecipitate-topical thrombin glue was used in 26 patients between April 1 and June 30, 1984. These patients were the first in whom this glue was used in this institution. They included all patients during this period in whom refractory hemorrhage was encountered. There were 14 men and 12 women. The patients' ages ranged from 30 to 79 years, with a mean of 61 years. No patient had a derangement of clotting function preoperatively as evaluated by routine measurement of prothrombin time, partial thromboplastin time, platelet count, and bleeding time when indicated. No attempt was made to discontinue aspirin use in advance in the 12 patients who routinely received aspirin while awaiting operation. Follow-up was established in all surviving patients by telephone contact with the patients, family members, or personal physicians. Operations performed included coronary artery bypass in 17 patients, valve replacement in three patients, coronary bypass and valve replacement in five patients, and repair of a postinfarction ventricular septal defect in one patient. Two coronary bypass operations were second-time operations for progression of disease, and two aortic valve replacements were reoperations because of valve deterioration. Five operations were performed emergently. Cryoprecipitate-topical thrombin glue was used while the patient was on bypass and fully heparinized in four cases and after separation from bypass and administration of protamine in 17 cases. The glue was used in five patients who required reexploration for persistent postoperative bleeding; none of these patients had received the glue during the initial operation. Two patients required cryoprecipitate-topical thrombin glue for disseminated intravascular coagulopathy that developed intraoperatively before the administration of the glue. The sites of administration of the glue included the aortic and coronary artery suture lines of saphenous vein and internal mammary bypass grafts,
Cryoprecipitate-topical thrombin glue 5 0 3
the aortic suture line after valve replacement, ventriculotomy closures, and superficial epicardial bleeding points. Results From 2 to 20 ml of cryoprecipitate-topical thrombin glue was used to control bleeding. Hemorrhage was stopped in all 21 patients who received the glue during their cardiac operation, and none required reexploration at a later time. In the five patients who required reexploration for bleeding, none having received cryoprecipitate-topical thrombin glue during the initial procedure, bleeding was also controlled by the glue and no further reexploration was necessary. Four of the five patients who required reexploration for bleeding were among the first six patients in our series. There were nine deaths, five on the first postoperative day. Four deaths, including both patients with disseminated intravascular coagulopathy, occurred between postoperative days 10 and 34. No death could be attributed to hemorrhage alone, although the complications associated with hemorrhage were contributory in some cases. There was no evidence of hypersensitivity, fibrinolysis, or coagulopathy occurring. after the use of cryoprecipitate-topical thrombin glue. Of the 17 patients discharged alive, 16 are alive 9 months to 1 year postoperatively. The cause of death in the one nonsurvivor is not known. No cases of hepatitis developed during this period. Discussion Cryoprecipitate was first used by Pool and Shannon" in 1965 in the treatment of classic hemophilia. It is produced by slow thawing of plasma at low temperatures. In addition to having 20% to 85% of the factor VIII present in the original unit of plasma, cryoprecipitate contains enough factor XIII to be of use in treating factor XIII deficiency. It also contains small amounts of factors II, V, and IX plus the bulk of fibrinogen present in the plasma with a concentration of fibrinogen of 150 to 200 mg/unit of cryoprecipitate. Thrombin interacts with fibrinogen to produce fibrin monomers, which undergo hydrogen bonding to form strands of polymeric fibrin. These strands are then stabilized by factor XIII, also activated by thrombin, to establish the stable cross-linking necessary for clot formation." These reactions are catalyzed by calcium, and some proponents of fibrin glues add calcium to their solutions." We have not found this necessary, as the calcium content in autologous serum appears adequate
The Journal of Thoracic and Cardiovascular Surgery
5 0 4 Lupinetti et al.
to permit the necessary reactions to occur. Similarly, we have omitted aprotinin, used by some investigators to stabilize the clot and prevent fibrinolysis,":" with no apparent adverse consequences. Fibrin glues do not require an intact coagulation system and can therefore be used despite systemic heparinization. This allows the surgeon to obtain a considerable degree of hemostasis prior to reversing heparin with protamine. Although no complications of intravascular coagulation have been described following the use of fibrin glue, it seems a reasonable precaution to avoid depositing the fibrinogen or the thrombin components into the intravascular space or into the suction port of the cardiopulmonary bypass pump. Another reasonable precaution is selective and judicious use of these glues. On the one hand, they will not control vigorous arterial bleeding that properly requires suture ligation. On the other hand, excessive application of fibrin glue may theoretically contribute to tamponade or to excessive adhesion formation. Fibrin adhesives have been shown to be effective in cardiac and vascular operations in adults.':'? pulmonary resection and treatment of pneumothorax, II pediatric cardiac operations," splenic salvage," and skin grafting." In addition, these substances have been used experimentally in cardiac valve implants.i lymphovenous anastomoses,' colon anastomoses,' and repair of liver injuries. 16 We have found cryoprecipitate-topical thrombin glue to be most valuable in securing hemostasis in the distal suture line of coronary bypass grafts. This is especially true with internal mammary artery bypasses, which provide superior long-term patency but require greater caution in manipulation. In these delicate vessels, this glue may be far safer than additional suture. Four of the five patients requiring reoperation in our series were among the initial six patients to receive cryoprecipitate-topical thrombin glue, whereas reexploration was required only once in the last 17 patients. This demonstrates that additional experience with the use of this glue has made us more ready to use it when the chances of postoperative bleeding appear greater than usual. Cryoprecipitate-topical thrombin glue is a safe and reliable topical hemostatic agent in the patient undergoing a cardiac operation. It is easily made, readily available, and is more economical than other hemostatic agents." The risk of hepatitis, while present, is low" and is perhaps lower than the risk of multiple repeated transfusions of blood products required in the treatment of unremitting hemorrhage.
We wish to acknowledge the assistance of Dr. Charles Wallace for his recommendations in our use of cryoprecipitate. REFERENCES Haverich A, Maatz W, Walterbusch G: Evaluation of fibrin seal in animal experiments. Thorac Cardiovasc Surg 30:215-222, 1982 2 Saggau W, Hatipoglu 0, Mittman U, Spath J, Storch HH, Schmitz W, Wurster K: Tissue glue for sealing plastic valves and bioprosthesis in the canine aorta. Scand J Thorac Cardiovasc Surg 16: 129-135, 1982 3 Milingos S, Tassopoulos J, Vrachnos P: Experimental remarks on the utilization of biological tissue adhesives in Iymphovenous anastomosis. J Cardiovasc Surg 25: 130133, 1984 4 Oka H, Harrison RC, Burhenne HJ: Effect of a biologic glue on the leakage rate fo experimental rectal anastomoses. Am J Surg 143:561-564, 1982 5 Wolner E: Fibrin gluing in cardiovascular surgery. Thorac Cardiovasc Surg 30:236-237, 1982 6 Borst HG, Haverich A, Walterbusch G, Maatz W: Fibrin adhesive. An important hemostatic adjunct in cardiovascular operations. J THoRAc CARDIOVASC SURG 84:548-553, 1982 7 Walterbusch G, Haverich A, Borst HG: Borst HG: Clinical experience with fibrin glue for local bleeding control and sealing of vascular prostheses. Thorac Cardiovase Surg 30:234-235, 1982 8 Koveker G, de Vivie ER, Hellberg KD: Clinical experience with fibrin glue in cardiac surgery. Thorac Cardiovasc Surg 29:287-289, 1981 9 Kalmar P, Krebber HJ, Pokar H, Tilsner V: Bioadhesives in cardiac and vascular surgery. Thorac Cardiovasc Surg 30:230-231,1982 10 Koveker G: Clinical application of fibrin glue in cardiovascular surgery. Thorac Cardiovasc Surg 30:228-229, 1982 11 Thetter 0: Fibrin adhesive and its application in thoracic surgery. Thorac Cardiovasc Surg 29:290-292, /981 12 Stark J, de Leval M: Experience with fibrin seal (Tisseel) in operations for congenital heart defects. Ann Thorac Surg 38:411-413, 1984 13 Scheele J, Gentsch HH, Matteson E: Splenic repair by fibrin tissue adhesive and collagen fleece. Surgery 95:6-13, 1984 14 Vibe P, Pleas J: A new method of skin graft adhesion. Scand J Plast Reconstr Surg 17:263-264, 1983 15 Jakob H, Campbell CD, Qiu ZK, Pick R, Replogle RL: Evaluation of fibrin sealing for cardiovascular surgery. Circulation 70:Suppl I: 138-146, 1984 16 Jakob H, Campbell CD, Sternberger A, Wriedt-Lubbe I, Blumel G, Replogle RL: Combined application of heterologous collagen and fibrin sealant for live injuries. J Surg Res 36:571-577, 1984 17 Pool JG, Shannon AE: Production of high-potency con-
Volume 90 Number 4 October, 1985
centrates of antihemophilic globulin in a close-bag system. Assay in vitro and in vivo. N Engl J Med 273:1443-1447, 1965 18 Sternberger A, Blumel G: Fibrinogen-fibrin conversion and inhibition of fibrinolysis. Thorac Cardiovasc Surg 30:209-214, 1982 19 Redl H, Schlag G, Dinges HP: Methods of fibrin seal application. Thorac Cardiovasc Surg 30:223-227, 1982 20 Rousou JA, Engelman RM, Breyer RH: Fibrin glue. An effective hemostatic agent for nonsuturable intraoperative bleeding. Ann Thorac Surg 38:409-410, 1984 21 Scheele J, Schricker KT, Goy RD, Lampe I, Panis R: Hepatitisrisiko der Fibrinklebung in der Allgemeichirurgie. Med Welt 32:783-788, 1981
Discussion DR. HANS G. BORST Hannover, Federal Republic of German)'
Our experience with hemostatic fibrin sealing now comprises close to 1,000 applications both in the high-pressure and in the low-pressure system, with a failure rate of 3.4% in the former and 1.9% in the latter. Fibrin sealing, therefore, has become an integral part of our cardiovascular practice and we surely could not do without it anymore. Perhaps of interest are our results with fibrin sealing of vascular prostheses. We used sealed woven grafts in the ascending aortic and arch positions in 74 patients without any failures. We had the same success in 25 right ventricularpulmonary arterial conduits and right ventricular patches. Knitted grafts were employed in 14 patients undergoing ascending aortic replacement, with one failure occurring in the only graft made of nonvelour fabric. The impression was gained that this prosthesis could not be loaded with a sufficient
Cryoprecipitate-topical thrombin glue 5 0 5
amount of fibrin adhesive because of the absence of the velour. Knitted right ventricular-pulmonary arterial conduits and patches were sealed in 20 instances without failure, and knitted left ventricular patches were successfully sealed in five cases. Finally, we replaced the descending, the thoracoabdominal, and the infrarenal aorta with knitted grafts in 204 patients who had received a heparin dose of I mg/kg. There were six failures in this group, all of which occurred in patients with perforated aneurysms, profound shock, and acidosis. The possible mechanism of the observed failure to seal was thought to be fibrinolysis in these patients. We conclude that fibrin sealing of woven and knitted double velour grafts is a highly reliable method for closing the pores of the fabric. Fibrin-sealed knitted grafts probably should not be used under the conditions of severe circulatory impairment. Importantly, the sealant does not impede the handling qualities of a graft. I would like to ask the authors which concentration of the fibrinogen they are using. In our experience a high concentration of 90 mg/rnl appears mandatory. DR. LUPINETTI (Closing) I would like to thank Professor Borst not only for his kind comments but for his many contributions in the field of adhesives in surgical technique. The concentration of fibrinogen in cryoprecipitate is quite variable and depends partly on ~he vagaries of the blood bank manufacture of this substance. Normally there is 150 to 200 mg of fibrinogen per unit of cryoprecipitate, which is anywhere from I to 10 ml. That would equal a minimum of 15 mg/rnl, as Dr. Borst recommends. We have not made any efforts, however, to quantitate the precise amount of fibrinogen in our cryoprecipitate.