The management of anticoagulation noncardiac operations in patients prosthetic heart valves A Prospective
during with
Study
Richard E. Katholi, M.D.* Stanton P. Nolan, M.D. Lockhart B. MC&ire, M.D., F.A.C.P. Charlottesdle,
Vu.
In a previous study of thromboembolism and hemorrhage among patients with prosthetic heart valves undergoing noncardiac operations, there was significant peri-operative bleeding when anticoagulation was maintained during such operations.’ Also, among patients with mitral valve prostheses there was significant per&operative thromboembolism when anticoagulation was discontinued. The need for some means of managing patients with thrombogenic, caged-ball or caged-disc cardiac valves, who require subsequent noncardisc operations, was the impetus for this prospective study of 45 operative procedures performed among a graup of 235 patients on chronic anticoagulation with prosthetic va1ves.t Because in the earlier study there had been no adverse effect from the interruption of anticoagulants for three to five days among patients with only aortic valve prostheses, simple interruption was employed in the present study for such patients. For patients with mitral caged-disc prostheses, either alone or in combination with an aortic or tricuspid prosthesis, restoration of anticoagulation with hepaFrom the of Virginia
Departments Hospital.
of internal Charlottesville,
Medicine Va.
Received
for publication
June
16, 1977.
Accepted
for publication
Aug.
:31. 1977.
and
Reprint requests. Lockhart B. MC&ire, M.D.. Department uf Internal Medicine. ITniversity (‘harlottesvilte, Va. 22901. “Present
address:
iStarr-Edwards Shilry or Beall
I;nivel-sit?
of Alabama,
Birmingham,
?a 1978
University
Division of Cardiology. of Virginia Hospital,
Modrt l%OO OT Magovern aortic diw valve mitral prostheses.
0002~8703/78/0296-0163$00.30/O
Surgery,
The
Alabama.
prostheses
and
C. V. Mosby
Kay-
Co.
rin was used in the early postoperative period to prevent thromboembolism. Methods
The following protocol for the management of anticoagulation during noncardiac operations was used. For patients with isolated aortic valve prostheses warfarin was discontinued in time to produce a normal prothrombin time on t.he day of operation, and oral anticoagulation was resumed two days after operation. (One patient with an aortic valve prosthesis also received heparin early after operation because of a presumed increased risk of thromboembolism). Patients with mitral or combined prostheses underwent rapid reversal of their warfarin effect with parenteral vitamin K during the 24 hours before operation, and received intravenous heparin beginning 12 hours after operation. Heparin anticoagulation was maintained by either intermittent or continuous intravenous infusion to produce a partial thromboplastin time of one and one-half to two and onehalf times the levels of normal controls. When adequate surgical hemostasis was assured, usually three days after operation, oral anticoagulation with warfarin was resumed and t,he heparin was stopped when the prothrombin time reached a therapeutic level. A noncardiac operation was classified as “major” if a body cavity or bone was entered, and otherwise as “minor.” There were 23 major operations which included: hysterectomy (eight); pulse generator change (five): bowel resection
American
Hmrt
.Jl~umol
163
Katholi,
Nolan,
and
McGuire
I. Thromboembolism or hemorrhage in patients with prosthetic valves during subsequent noncardiac operations Table
Mitral Patient group
Aortic valve only
& combined valves
Number Operations
18
21
Major Minor
10 9*
13 13
Total
Management Thromboembolism Hemorrhage
Stop
19 warfarin
0 1t
26 Stop warfarin, add heparin
0 2
‘Two dental extractions were performed with anticoagulation tained. TThis patient received heparin early after operation.
main-
(four); cholecystectomy (three); subtotal gastrectomy (twq); and craniotomy (one). There were 22 minor operations which included: biopsy or excision (nine); dental extraction (five); arteriography (four); mastectomy (twd); and hemorrhoidectomy (two). Results
Thirty-nine patients have undergone 45 noncardiac operations under this protocol. Table I summarizes the experience in terms of peri-operative thromboembolism and hemorrhage. There were no deaths. Thromboembolism did not occur among the patients with isolated aortic valve prostheses despite the discontinuation of anticoagulation for three to five days. There was an incisional hematoma which occurred in a patient who received heparin early after operation because of an increased risk of thromboembolism. In this case the bleeding was minor and easily controlled. Dental extractions were performed on two patients with prosthetic aqrtic valves without the cessation of anticoagulation and there were no complications. Both had chronic atria1 fibrillation and were the only patients in the aortic group with this arrhythmia. When heparin was administered to patients with mitral or combiqed prosthetic valves early after operation, no thromboemboli occurred. Sixteen of these 21 patients (76 per cent) had chronic atria1 fibrillation. One patient developed an abdominal incisional hematoma, but did not require transfusion or discontinuation of anticoagulant therapy. One patient developed vaginal
164
cuff bleeding after a vaginal hysterectomy and required transfusion, ligation of the bleeding site, and brief interruption of heparin. Discussion
The major problem for patients with mitral caged-ball or caged-disc prostheses undergoing noncardiac operations has been thromboembolism when anticoagulants are discontinued. Under these circumstances, the risk is increased when there is atria1 fibrillation.‘, ? Others have reported that a hypercoagulable state is not associated with the interruption of warfarin therapy.” The absence of thromboembolism during the short-term withdrawal of warfarin from patients with aortic prostheses in this and our previous study’ supports that observation. However, it has also been observed that minor procedures, performed in accessible areas, such as dental extractions, can be safely accomplished with maintenance of warfarin.’ Our experience with the continuation of anticoagulation during dental procedures has also been favorable. In this study heparin was administered to patients with mitral prostheses in the early postoperative period in order to avoid the previously observed problem of thromboembolism. The advantage of heparin when compared to warfarin is the rapid reversal of its anticoagulant effect by protamine sulfate if major bleeding should occur. The result from the use of heparin in these patients was the avoidance of thromboemboli; however, hemorrhage did occur in three patients. This incidence of hemorrhage (10 per cent) in our patients is similar to a previous report,5 in which anticoagulation was started soon after an operative procedure. Since these bleeding episodes occurred when the partial thromboplastin time was in the appropriate therapeutic range,” future consideration might be given to the use of lower doses of heparin. It is probable also that the increasing use of non-thrombogenic mitral xenografts will minimize this difficult management problem in the future. Summary
Based on previous thromboembolic complications associated with the interruption of anticoagulation during subsequent noncardiac operations in patients with nonbiological mitral prostheses, a protocol was developed for this high risk
August,
1978, Vol. 96, No. 2
Noncardiac group. We report the successful management of 26 such operations in which anticoagulation was interrupted for 12 hours and then rapidly restored by means of heparin in the postoperative period. Since an earlier study suggested no adverse effect from the interruption of chronic anticoagulants for three to five days among patients with isolated aortic valve prostheses, simple interruption was again employed during 16 subsequent noncardiac operative procedures in this group with no complications. There were three episodes of hemorrhage observed in patients receiving therapeutic doses of heparin postoperatively, but only one required blood replacement.
American Heart Journal
operations and prosthetic
vcrk~es
REFERENCES 1.
2.
3. 4. 5.
6.
Katholi, K. E.. Nolan, S. I’., and McGurre. L. H.: Living with prosthetic heart valves, AM. HURT J. 92:162, 1976. Kudoh, T.: Surgery of the patient on anticoagulants following prosthetic valve replacement. ,JIm. J. Thorac. Surg. 28:187, 1975. Michaels, L.: Incidence of thromboembolim after stopping anticoagulant therapy, J.A.M.A. 215:595, 1971. McIntyre, H.: Management during dental surgery of patients on anticoagulants, Lancet 2:99. 1966. Coon, W. W., and Willis, P. W.: Hemorrhagic compiications of anticoagulant therapy, Arch Intern. Med. 133286, 1974. Salzman. E. W., Deykin, D., Shapiro. It, M.. et al.: Management of heparin therapy. IV. Engl. J. Med. 292:1046, 1975.
165
during with
Study
Richard E. Katholi, M.D.* Stanton P. Nolan, M.D. Lockhart B. MC&ire, M.D., F.A.C.P. Charlottesdle,
Vu.
In a previous study of thromboembolism and hemorrhage among patients with prosthetic heart valves undergoing noncardiac operations, there was significant peri-operative bleeding when anticoagulation was maintained during such operations.’ Also, among patients with mitral valve prostheses there was significant per&operative thromboembolism when anticoagulation was discontinued. The need for some means of managing patients with thrombogenic, caged-ball or caged-disc cardiac valves, who require subsequent noncardisc operations, was the impetus for this prospective study of 45 operative procedures performed among a graup of 235 patients on chronic anticoagulation with prosthetic va1ves.t Because in the earlier study there had been no adverse effect from the interruption of anticoagulants for three to five days among patients with only aortic valve prostheses, simple interruption was employed in the present study for such patients. For patients with mitral caged-disc prostheses, either alone or in combination with an aortic or tricuspid prosthesis, restoration of anticoagulation with hepaFrom the of Virginia
Departments Hospital.
of internal Charlottesville,
Medicine Va.
Received
for publication
June
16, 1977.
Accepted
for publication
Aug.
:31. 1977.
and
Reprint requests. Lockhart B. MC&ire, M.D.. Department uf Internal Medicine. ITniversity (‘harlottesvilte, Va. 22901. “Present
address:
iStarr-Edwards Shilry or Beall
I;nivel-sit?
of Alabama,
Birmingham,
?a 1978
University
Division of Cardiology. of Virginia Hospital,
Modrt l%OO OT Magovern aortic diw valve mitral prostheses.
0002~8703/78/0296-0163$00.30/O
Surgery,
The
Alabama.
prostheses
and
C. V. Mosby
Kay-
Co.
rin was used in the early postoperative period to prevent thromboembolism. Methods
The following protocol for the management of anticoagulation during noncardiac operations was used. For patients with isolated aortic valve prostheses warfarin was discontinued in time to produce a normal prothrombin time on t.he day of operation, and oral anticoagulation was resumed two days after operation. (One patient with an aortic valve prosthesis also received heparin early after operation because of a presumed increased risk of thromboembolism). Patients with mitral or combined prostheses underwent rapid reversal of their warfarin effect with parenteral vitamin K during the 24 hours before operation, and received intravenous heparin beginning 12 hours after operation. Heparin anticoagulation was maintained by either intermittent or continuous intravenous infusion to produce a partial thromboplastin time of one and one-half to two and onehalf times the levels of normal controls. When adequate surgical hemostasis was assured, usually three days after operation, oral anticoagulation with warfarin was resumed and t,he heparin was stopped when the prothrombin time reached a therapeutic level. A noncardiac operation was classified as “major” if a body cavity or bone was entered, and otherwise as “minor.” There were 23 major operations which included: hysterectomy (eight); pulse generator change (five): bowel resection
American
Hmrt
.Jl~umol
163
Katholi,
Nolan,
and
McGuire
I. Thromboembolism or hemorrhage in patients with prosthetic valves during subsequent noncardiac operations Table
Mitral Patient group
Aortic valve only
& combined valves
Number Operations
18
21
Major Minor
10 9*
13 13
Total
Management Thromboembolism Hemorrhage
Stop
19 warfarin
0 1t
26 Stop warfarin, add heparin
0 2
‘Two dental extractions were performed with anticoagulation tained. TThis patient received heparin early after operation.
main-
(four); cholecystectomy (three); subtotal gastrectomy (twq); and craniotomy (one). There were 22 minor operations which included: biopsy or excision (nine); dental extraction (five); arteriography (four); mastectomy (twd); and hemorrhoidectomy (two). Results
Thirty-nine patients have undergone 45 noncardiac operations under this protocol. Table I summarizes the experience in terms of peri-operative thromboembolism and hemorrhage. There were no deaths. Thromboembolism did not occur among the patients with isolated aortic valve prostheses despite the discontinuation of anticoagulation for three to five days. There was an incisional hematoma which occurred in a patient who received heparin early after operation because of an increased risk of thromboembolism. In this case the bleeding was minor and easily controlled. Dental extractions were performed on two patients with prosthetic aqrtic valves without the cessation of anticoagulation and there were no complications. Both had chronic atria1 fibrillation and were the only patients in the aortic group with this arrhythmia. When heparin was administered to patients with mitral or combiqed prosthetic valves early after operation, no thromboemboli occurred. Sixteen of these 21 patients (76 per cent) had chronic atria1 fibrillation. One patient developed an abdominal incisional hematoma, but did not require transfusion or discontinuation of anticoagulant therapy. One patient developed vaginal
164
cuff bleeding after a vaginal hysterectomy and required transfusion, ligation of the bleeding site, and brief interruption of heparin. Discussion
The major problem for patients with mitral caged-ball or caged-disc prostheses undergoing noncardiac operations has been thromboembolism when anticoagulants are discontinued. Under these circumstances, the risk is increased when there is atria1 fibrillation.‘, ? Others have reported that a hypercoagulable state is not associated with the interruption of warfarin therapy.” The absence of thromboembolism during the short-term withdrawal of warfarin from patients with aortic prostheses in this and our previous study’ supports that observation. However, it has also been observed that minor procedures, performed in accessible areas, such as dental extractions, can be safely accomplished with maintenance of warfarin.’ Our experience with the continuation of anticoagulation during dental procedures has also been favorable. In this study heparin was administered to patients with mitral prostheses in the early postoperative period in order to avoid the previously observed problem of thromboembolism. The advantage of heparin when compared to warfarin is the rapid reversal of its anticoagulant effect by protamine sulfate if major bleeding should occur. The result from the use of heparin in these patients was the avoidance of thromboemboli; however, hemorrhage did occur in three patients. This incidence of hemorrhage (10 per cent) in our patients is similar to a previous report,5 in which anticoagulation was started soon after an operative procedure. Since these bleeding episodes occurred when the partial thromboplastin time was in the appropriate therapeutic range,” future consideration might be given to the use of lower doses of heparin. It is probable also that the increasing use of non-thrombogenic mitral xenografts will minimize this difficult management problem in the future. Summary
Based on previous thromboembolic complications associated with the interruption of anticoagulation during subsequent noncardiac operations in patients with nonbiological mitral prostheses, a protocol was developed for this high risk
August,
1978, Vol. 96, No. 2
Noncardiac group. We report the successful management of 26 such operations in which anticoagulation was interrupted for 12 hours and then rapidly restored by means of heparin in the postoperative period. Since an earlier study suggested no adverse effect from the interruption of chronic anticoagulants for three to five days among patients with isolated aortic valve prostheses, simple interruption was again employed during 16 subsequent noncardiac operative procedures in this group with no complications. There were three episodes of hemorrhage observed in patients receiving therapeutic doses of heparin postoperatively, but only one required blood replacement.
American Heart Journal
operations and prosthetic
vcrk~es
REFERENCES 1.
2.
3. 4. 5.
6.
Katholi, K. E.. Nolan, S. I’., and McGurre. L. H.: Living with prosthetic heart valves, AM. HURT J. 92:162, 1976. Kudoh, T.: Surgery of the patient on anticoagulants following prosthetic valve replacement. ,JIm. J. Thorac. Surg. 28:187, 1975. Michaels, L.: Incidence of thromboembolim after stopping anticoagulant therapy, J.A.M.A. 215:595, 1971. McIntyre, H.: Management during dental surgery of patients on anticoagulants, Lancet 2:99. 1966. Coon, W. W., and Willis, P. W.: Hemorrhagic compiications of anticoagulant therapy, Arch Intern. Med. 133286, 1974. Salzman. E. W., Deykin, D., Shapiro. It, M.. et al.: Management of heparin therapy. IV. Engl. J. Med. 292:1046, 1975.
165
