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FATAL HEMOLYSIS FOLLOWING BALL VALVE REPLACEMENT OF THE AORTIC VALVE
FATAL HEMOLYSIS FOLLOWING BALL VALVE REPLACEMENT OF THE AORTIC VALVE William
N
A, Reed, M.D., and Marvin Dunn, M.D., Kansas City, Kans.
artificial materials, including silicon rubber and Dacron, have been used to partially or totally replace the aortic valve. Since 1960, use of the ball valve prosthesis, as designed by Starr and Edwards, has been more extensive. The present report describes a case in which replacement of the aortic valve with the Starr-Edwards prosthesis resulted in continued severe hemolysis and eventually led to the patient's death from renal failure. Attention is directed to a discussion of the possible causes and means of prevention of this complication in the future. UMEROUS
CASE REPORT
A 32-year-old man was first seen in the outpatient clinic of the University of Kansas Medical Center on May 11, 1961, for evaluation of a heart murmur first noted in 1950. He denied chest pain, shortness of breath, exertional dyspnea, orthopnea, syncope, or pedal edema. There was no history suggesting rheumatic fever. The past history, family history, and system review were noncontributory. Examination revealed a blood pressure of 85/60 mm. H g with a pulse rate of 80. Systolic thrills and bruits were present over both carotids. The apex beat was at the sixth inter costal space at the anterior axillary line. A marked left ventricular thrust was present. A systolic thrill was present at the aortic area and transmitted along the left sternal border. Auscultatory findings included a Grade 4 aortic systolic ejection murmur which transmitted into the neck and to the apex. A Grade 2 aortic diastolic regurgitant murmur was present at the left sternal border and an Austin-Flint murmur at the apex. The aortic component of the second sound was absent. A loud third sound was audible at the apex. The remainder of the physical examination was within normal limits. The electrocardiogram showed ventricular hypertrophy of the systolic overload type. The phonocardiogram confirmed the auscultatory findings. The total ejection time corrected for the heart rate was prolonged to 0.39 seconds. The chest x-ray examination showed left ventricular and left auricular enlargement. Calcification of the aortic valve was noted on fluoroscopy and there was typical post-stenotie dilatation of the aorta. He was seen at intervals in the outpatient clinic until May, 1962. He had then devel oped dyspnea, palpitation, tachycardia with exertion, and had noted decreased exercise tolerance. He was admitted to the hospital on Dec. 1, 1962, for evaluation. Right heart catheterization was within normal limits. The left ventricle was catheterized by the Brockenbrough technique. Cardiac output was determined by the Fick principle. A 100 mm. systolic gradient was measured across the aortic valve (left ventricular pressure Prom the Department of Surgery and Department of Medicine, University of Kansas Medical Center, Kansas City, Kans. < Received for publication Feb. 8, 1964. 436
Vol. 48, No. 3 F A T A L HEMOLYSIS A F T E R BALL VALVE R E P L A C E M E N T September, 1964
437 ^° '
was 180/24 mm. H g and aortic pressure 80/40). The mean left atrial pressure was normal but the " A " waves were noted to peak at 24 mm. H g (the left ventricular end diastolic pres sure). Aortic insufficiency was estimated by injecting Cardio-green stain at various levels in the aorta while sampling from the left brachial artery. Dye was recovered at the level of the seventh thoracic vertebra, which was compatible with moderate aortic insufficiency. The findings were thought to be compatible with severe aortic stenosis and moderate in sufficiency. Following the cardiac catheterization, the patient was digitalized and placed on a low sodium diet. He was re-admitted to the hospital on April 29, 1963, for operation on the aortic valve. Operation was performed on May 2, 1963, the heart being exposed through a median sternotomy. A disc-type oxygenator system was used in the extracorporeal circulatory system, there was a flow rate of 2.2 L. per square meter per minute. After the body temperature had been reduced to 80° C. and the heart packed in normal saline ice slush, the aorta was cross-clamped and opened by a vertical incision curved into the noncoronary sinus. The left ventricular chamber was decompressed by a catheter passed through the apex of the left ventricle. The extensive calcification involved all cusps of the aortic valve with ex tension of the calcium deposits into the aorta. The left coronary artery was perfused with blood at 30° C. A flow of 200 ml. per minute was maintained throughout the intracardiac portion of the procedure. Total valve replacement was elected as the technique of choice. Incisions were made at the junction of the valve with aorta and the valve was removed by sharp and blunt dissection. I t was necessary to use bone rongeurs along the attachment of the noncoronary leaflet to remove calcified material in this area. An 11A Starr-Edwards valve was then inserted with the use of interrupted 2-0 Dacron sutures through the aortic annulus. The aortotomy was closed by means of an everting mattress stitch. Ventricular fibrillation was converted to normal sinus rhythm with a single electric shock. The heart resumed satisfactory function and extracorporeal support was discontinued. Prior to the insertion of the valve, the systolic gradient was 120 mm. H g and after valve replacement was 24 mm. Hg. The procedure was completed uneventfully; the patient had been perfused one hour and thirty minutes. The immediate postoperative course was entirely uneventful. By the third postopera tive day, the blood pressure and pulse were stable, the patient was af ebrile, and the mediastinal drainage tubes were removed. The blood pressure at this time was 110/70 with a heart rate of 80 to 100. A Grade 2 aortic systolic ejection murmur was noted. The postoperative medi cations included digitoxin (0.1 mg. daily), penicillin (600,000 units intramuscularly four times daily), and streptomycin (0.5 Gm. intramuscularly twice daily). On the fourth postoperative day, a decrease in hemoglobin and hematocrit was noted. The Coombs' test was negative, the total bilirubin was 1.0 mg. per cent, and the plasma hemoglobin was 4 mg. per cent. On the sixth postoperative day, anticoagulant therapy was instituted with the use of Coumadin. Convalescence continued uneventfully. On the twelfth postoperative day, the urine became dark red. I t was found to be hematest positive but contained very few red blood cells. (Prothrombin time at this time was 59 per cent.) The total bilirubin was 1.7 mg. per cent. Tests for myoglobulinuria and prophyria were nega tive. Spectrophotometric examination of the serum and urine showed the presence of methemoglobinemia and methemoglobinuria as well as methemalbuminemia and methemalbuminuria. There were no iso-agglutinins present. Concomitant with the onset of hemoglobinuria, the patient developed an aortic diastolic regurgitant murmur and the blood pressure was noted to have changed from 110/70 to 90/45 mm. Hg. The patient was encouraged to drink large volumes of fluid to maintain a high urine output. Frequent determinations were made of the plasma hemoglobin, blood urea nitrogen, and creatinine. Values for these determinations are depicted in Figs. 1 through 3. In spite of maintaining a large urine output (Fig. 4 ) , the patient had gradual increase in the blood urea nitrogen and creatinine. He remained essentially unchanged clinically, although quite weak and rather dyspneic, when the hemoglobin fell below 10 grams. Packed red cell trans fusions were given as shown in Fig. 2. The patient was started on prednisone, 10 mg. every 6 hours, on the twenty-sixth postoperative day and this was continued until his death on
J. Thoracic and Cardiovas. Surg.
R E E D AND D U N N
438
10 12
14 16 18 2 0 22 24 26 28 30 32 34 36 DAYS POST-OPERATIVE
Fig:. 1.—The blood urea nitrogen and creatinine are demonstrated in milligrams per cent. There was a slow increase until the thirty-second postoperative day at which time a rapid in crease occurred to the time of death.
0
_i
2
i ii_
4
6
8
H WM H M * * _1 1_ _ 1 _ _i_ _1_ i i_ 10 12 14 16 18 2 0 2 2 24 26 28 3 0 32 34 3 6 DAYS POST OPERATIVE
_i
Pig. 2.—The drop in hemoglobin and hematocrit which persisted through the postoperative period is demonstrated with a return to normal levels immediately after the second operative procedure. A rapid decline then occurred to the time of death.
the thirty-seventh postoperative day. The plasma hemoglobin continued to rise and it was concluded that the hemolysis was most likely due to red cell destruction secondary to the partial detachment of the prosthetic valve. On the twenty-ninth postoperative day, retrograde aortic eatheterization and angiocardiogram were performed by the Seldinger aortic technique. Begurgitation was noted in the area of the noncoronary sinus. Reoperation was recommended to correct the regurgitation. '
Vol. 48, No. 3
September, 1964
F A T A L HEMOLYSIS A F T E R BALL VALVE R E P L A C E M E N T
5
7
9
II
13
15
17
19 21 2 3 25 DAYS POST-OPERATIVE
27
29
31 3 3
439
35
Fig. 3.—This figure demonstrates the slow increase in plasma hemoglobin up to the second operation. Decrease to 50 mg. per cent occurred immediately following the second operation. A rapid increase then occurred until the patient's death.
5600
2
4
6
8
10 12 14 16 18 2 0 22 24 26 28 30 32 34 36 DAYS POST-OPERATIVE
Fig. 4.—This figure demonstrates the daily urine output during the entire postoperative period.
On the thirty-first postoperative day, with the use of the operative technique and ap paratus previously described, the aorta was cross-clamped and opened transversely in order to obtain better visualization of the site of regurgitation. This was noted along the noncoronary eusp margin which was the point of maximum calcification. The valve was re-at tached by placing through-and-through aortic sutures tied over Teflon plegets. The valve did not appear displaced. The systolic gradient was 90 mm. before repair and 40 mm. fol lowing correction of the regurgitation.
B E E D AND D U N N
440
J. Thoracic and Cardiovas. Surg.
Following the procedure, the urine cleared 4 hours postoperatively and the plasma hemoglobin was 50 mg. per cent. Eight hours after operation, the urine again became the color of port wine. Plasma hemoglobin increased rapidly (Fig. 3 ) . Renal function deteriorated rapidly in spite of good urine volume and the fluid intake (Fig. 2 ) . Renal shutdown oc curred on the thirty-sixth postoperative day. The patient developed pulmonary edema and died on the thirty-seventh postoperative day. Postmortem examination revealed evidence of lower nephron nephrosis with deposits of hemoglobin pigment in all tissues. A reactive bone marrow was present. The aortic valve prosthesis was positioned 6 to 8 mm. below both coronary artery orifices. The cuff of the valve was securely attached around the circumference of the aorta. Viewing the valve from the left ventricle, the prosthesis appeared to be in an excellent position. When viewed from above, the aorta encroached upon the superior aspect of the cage of the prosthesis. With the ball in the open position, the aorta was severely obstructed with very little clearance for blood flow around the ball. No other significant pathologic condition was noted. DISCUSSION
This case represents a previously unreported complication of aortic valve replacement with a ball valve prosthesis. Stohlman and associates7 first reported the occurrence of traumatic hemolytic anemia in dogs in which a Lucite ball valve prosthesis was placed in a conduit between the left ventricular apex and the thoracic aorta. Since canine red blood cells are more fragile than human red blood cells, a direct comparison cannot be made. However, Neill 3 ' 5 reported severe hemolysis in man following the surgical repair of an endocardial cushion defect in which a Teflon patch was used in the repair. Sayed and co-workers4 studied a similar case and postulated that hemolysis was produced by a jet stream of blood striking an unendothelized portion of the Teflon patch. Hemoly sis was corrected by covering the unendothelized portion of the Teflon patch with endocardium. Verdon and associates8 have reported the cases of 2 patients with endocardial cushion defects who developed traumatic intravascular hemoly sis postoperatively. All of the patients had endocardial cushion defects which were repaired by means of a Teflon patch to close the atrial septal defect. In each case a portion of the patch either lacked an endothelial cover at the site where it was struck by a regurgitant jet or a portion of the patch was detached and was not covered by endothelium. Turbulence of blood flow and reaction to the Teflon are other factors which might contribute to the intravascular hemolysis. Starr 6 found hemolysis in a few patients following replacement of the aortic valve; this either cleared spontaneously or after steroid therapy. Our patient had a normal plasma hemoglobin on the fifth postoperative day. However, on the twelfth postoperative day there was marked elevation of plasma hemoglobin which indicated severe intravascular hemolysis. Since an aortic diastolic murmur occurred coincident with the onset of massive hemolysis, a cause and effect relationship was postulated. The second operation was per formed to correct the regurgitation with the hope that this would terminate the hemolysis. The temporary disappearance of the hemoglobinurina and re duction in plasma hemoglobin was probably due to the exchange transfusion performed at the time of extracorporeal circulation. After the second operation the aortic diastolic murmur disappeared which indicated secure placement of the aortic valve prosthesis. Postmortem examina-
Vol. 48, No. 3 FATAL HEMOLYSIS AFTER BALL VALVE EEPLACEMENT
441
September, 1964
tion confirmed the correct placement of the prosthesis below the coronary orifices. No thrombus was present. The continuation of the hemolytic process after the second operation indicates that aortic regurgitation was not the principal cause of the hemolysis. The absence of blood incompatibility, negative Coombs' test, and lack of response to corticosteroids constitute evidence against an antigen-antibody or autoimmune reaction as the cause of the hemolysis. Although Starr has noted some improvement in the hemolytic process with steroid therapy, this has failed to be of benefit in other cases.8 Dextran and heparin have also failed to produce significant improvement. 1 ' 2 Hemolysis due to a foreign body reaction does not appear too likely. Intravascular hemolysis is rare in comparison with the widespread use of prosthetic materials. Materials used in the Starr-Edwards valves are relatively inert in human tissues. Traumatic destruction of red cells appears to offer the most logical ex planation for the hemolytic process noted. Trauma to the red blood cells could occur when the valve opens, when it closes, or as blood flows around the ball during the systolic ejection phase. The degree of traumatic destruction is also related to the red cell fragility, cardiac output, valve size, and turbulence of flow. Previous studies have shown that red cells transfused into patients with traumatic hemolysis have a markedly shortened life span. 8 Increased red cell fragmentation also occurs as a sign of traumatic destruction of red cells. Significant hemoglobinemia and hemoglobinuria does not develop until about 8 to 10 days following the operation. The exact mechanism for this delay is un known, nor is there a good explanation for the apparent increase in the rate of hemolysis. These problems may be related to the carrying capacity of the haptoglobin system. The hemoglobin binding capacity of the haptoglobin sys tem probably does not exceed 1,400 mg. per 100 ml. When this is exceeded, hemoglobinemia and hemoglobinuria occur. The carrying capacity of the haptoglobins, the regeneration of haptoglobin, and the rate of intravascular hemolysis are interrelated factors determining the degree of hemoglobinuria and hemo globinemia. Since haptoglobin regeneration is slow, its capacity is easily ex ceeded by rapid intravascular hemolysis. We are uncertain whether the hemolysis occurred as a result of valve open ing, valve closure, or turbulent blood flow. If the trauma of valve opening and closing were a significant factor, the occurrence of traumatic hemolysis should be a much more frequent complication of aortic valve replacement. It seems more likely that the red cell trauma occurred during the actual phase of systolic ejection due to partial obstruction and severe blood turbulence. Sig nificant obstruction may result when the aortic circumference is relatively small at the level of the distal portion of the valve cage. The proximity of the aortic wall to the cage is dependent upon the distance from the aortic annulus to the superior margin of the sinus of Valsalva and the size of the valve used. Starr indicated that when in doubt the smaller size valve should be used. His reason dealt primarily with the relationship of the circumference at the base of the valve but a similar problem may also occur at the distal end of the valve prosthe-
442
R E E D AND DUNN
J. Thoracic and Cardiovas. Surg.
sis. Persistence of a significant systolic gradient across the aortie valve is testi mony to the fact that obstruction was present. At postmortem examination the site of obstruction appeared to be at the area where the aorta encroached upon the distal portion of the valve cage. This type of obstruction could have been prevented by a smaller prosthesis, a shorter prosthesis, deeper placement of the prosthesis, or by enlargement of the aorta by use of a prosthetic patch. Since the structure of the prosthetic valve and cardiac anatomy are relatively fixed factors, aortic enlargement or the use of a smaller prosthesis might offer a solution to similar problems in the future. Transverse rather than vertical in cision of the aorta will also prevent narrowing following closure. SUMMARY
A case of fatal traumatic hemolysis is reported following the insertion of a Starr-Edwards aortic ball valve prosthesis. Reasons for the traumatic hemolysis are discussed and possible methods of prevention are presented. REFERENCES
1. Crosby, W. H., and Benjamin, N. R.: Paroxysmal Nocturnal Hemoglobinuria: Effect of Dextran on Hemolysis I n Vitro, Acta Haemat. 19: 193, 1958. 2. McFarland, W., Galbraith, R. G., and Miale, A., J r . : Heparin Therapy in Autoimmune Hemolytic Anemia, Blood 15: 741, 1960. 3. Neill, C. A., Farman, E. N., Sigler, A. T., and Bahnsen, H. T.: Hemolytic Anemia Fol lowing Surgical Repair of Endocardial Cushion Defects. Presented a t Thirty-First Annual Meeting of Society for Pediatric Research Program, Atlantic City, New Jersey, May 4, 1961. 4. Sayed, H. M., Dacie, J . V., Handley, D. A., Lewis, S. M., and Cleland, W. P . : Hemolytic Anemia of Mechanical Origin After Open Heart Surgery, Thorax 16: 356, 1961. 5. Sigles, A. T., Farman, E . N., Linkham, W. H., Neill, C. A., and Bahnson, H. T.: The Waring Blendor Syndrome. Seventy-Second Annual Meeting, American Pediatric Society, May, 1962, page 24. 6. Starr, A . : Personal communication. 7. Stahlman, F., Jr., Sarnoff, S. J., Case, R. B., and Ness, A. T.: Hemolytic Syndrome Fol lowing Insertion of Lucite Ball Valve Prosthesis Into Cardiovascular System, Circulation 13: 586, 1956. 8. Verdon, T. A., Jr., Forrester, R. H., and Crosby, W. H . : Hemolytic Anemia After Open Heart Repair of Ostium Primum Defects, New England J . Med. 269: 444, 1963.
N
A, Reed, M.D., and Marvin Dunn, M.D., Kansas City, Kans.
artificial materials, including silicon rubber and Dacron, have been used to partially or totally replace the aortic valve. Since 1960, use of the ball valve prosthesis, as designed by Starr and Edwards, has been more extensive. The present report describes a case in which replacement of the aortic valve with the Starr-Edwards prosthesis resulted in continued severe hemolysis and eventually led to the patient's death from renal failure. Attention is directed to a discussion of the possible causes and means of prevention of this complication in the future. UMEROUS
CASE REPORT
A 32-year-old man was first seen in the outpatient clinic of the University of Kansas Medical Center on May 11, 1961, for evaluation of a heart murmur first noted in 1950. He denied chest pain, shortness of breath, exertional dyspnea, orthopnea, syncope, or pedal edema. There was no history suggesting rheumatic fever. The past history, family history, and system review were noncontributory. Examination revealed a blood pressure of 85/60 mm. H g with a pulse rate of 80. Systolic thrills and bruits were present over both carotids. The apex beat was at the sixth inter costal space at the anterior axillary line. A marked left ventricular thrust was present. A systolic thrill was present at the aortic area and transmitted along the left sternal border. Auscultatory findings included a Grade 4 aortic systolic ejection murmur which transmitted into the neck and to the apex. A Grade 2 aortic diastolic regurgitant murmur was present at the left sternal border and an Austin-Flint murmur at the apex. The aortic component of the second sound was absent. A loud third sound was audible at the apex. The remainder of the physical examination was within normal limits. The electrocardiogram showed ventricular hypertrophy of the systolic overload type. The phonocardiogram confirmed the auscultatory findings. The total ejection time corrected for the heart rate was prolonged to 0.39 seconds. The chest x-ray examination showed left ventricular and left auricular enlargement. Calcification of the aortic valve was noted on fluoroscopy and there was typical post-stenotie dilatation of the aorta. He was seen at intervals in the outpatient clinic until May, 1962. He had then devel oped dyspnea, palpitation, tachycardia with exertion, and had noted decreased exercise tolerance. He was admitted to the hospital on Dec. 1, 1962, for evaluation. Right heart catheterization was within normal limits. The left ventricle was catheterized by the Brockenbrough technique. Cardiac output was determined by the Fick principle. A 100 mm. systolic gradient was measured across the aortic valve (left ventricular pressure Prom the Department of Surgery and Department of Medicine, University of Kansas Medical Center, Kansas City, Kans. < Received for publication Feb. 8, 1964. 436
Vol. 48, No. 3 F A T A L HEMOLYSIS A F T E R BALL VALVE R E P L A C E M E N T September, 1964
437 ^° '
was 180/24 mm. H g and aortic pressure 80/40). The mean left atrial pressure was normal but the " A " waves were noted to peak at 24 mm. H g (the left ventricular end diastolic pres sure). Aortic insufficiency was estimated by injecting Cardio-green stain at various levels in the aorta while sampling from the left brachial artery. Dye was recovered at the level of the seventh thoracic vertebra, which was compatible with moderate aortic insufficiency. The findings were thought to be compatible with severe aortic stenosis and moderate in sufficiency. Following the cardiac catheterization, the patient was digitalized and placed on a low sodium diet. He was re-admitted to the hospital on April 29, 1963, for operation on the aortic valve. Operation was performed on May 2, 1963, the heart being exposed through a median sternotomy. A disc-type oxygenator system was used in the extracorporeal circulatory system, there was a flow rate of 2.2 L. per square meter per minute. After the body temperature had been reduced to 80° C. and the heart packed in normal saline ice slush, the aorta was cross-clamped and opened by a vertical incision curved into the noncoronary sinus. The left ventricular chamber was decompressed by a catheter passed through the apex of the left ventricle. The extensive calcification involved all cusps of the aortic valve with ex tension of the calcium deposits into the aorta. The left coronary artery was perfused with blood at 30° C. A flow of 200 ml. per minute was maintained throughout the intracardiac portion of the procedure. Total valve replacement was elected as the technique of choice. Incisions were made at the junction of the valve with aorta and the valve was removed by sharp and blunt dissection. I t was necessary to use bone rongeurs along the attachment of the noncoronary leaflet to remove calcified material in this area. An 11A Starr-Edwards valve was then inserted with the use of interrupted 2-0 Dacron sutures through the aortic annulus. The aortotomy was closed by means of an everting mattress stitch. Ventricular fibrillation was converted to normal sinus rhythm with a single electric shock. The heart resumed satisfactory function and extracorporeal support was discontinued. Prior to the insertion of the valve, the systolic gradient was 120 mm. H g and after valve replacement was 24 mm. Hg. The procedure was completed uneventfully; the patient had been perfused one hour and thirty minutes. The immediate postoperative course was entirely uneventful. By the third postopera tive day, the blood pressure and pulse were stable, the patient was af ebrile, and the mediastinal drainage tubes were removed. The blood pressure at this time was 110/70 with a heart rate of 80 to 100. A Grade 2 aortic systolic ejection murmur was noted. The postoperative medi cations included digitoxin (0.1 mg. daily), penicillin (600,000 units intramuscularly four times daily), and streptomycin (0.5 Gm. intramuscularly twice daily). On the fourth postoperative day, a decrease in hemoglobin and hematocrit was noted. The Coombs' test was negative, the total bilirubin was 1.0 mg. per cent, and the plasma hemoglobin was 4 mg. per cent. On the sixth postoperative day, anticoagulant therapy was instituted with the use of Coumadin. Convalescence continued uneventfully. On the twelfth postoperative day, the urine became dark red. I t was found to be hematest positive but contained very few red blood cells. (Prothrombin time at this time was 59 per cent.) The total bilirubin was 1.7 mg. per cent. Tests for myoglobulinuria and prophyria were nega tive. Spectrophotometric examination of the serum and urine showed the presence of methemoglobinemia and methemoglobinuria as well as methemalbuminemia and methemalbuminuria. There were no iso-agglutinins present. Concomitant with the onset of hemoglobinuria, the patient developed an aortic diastolic regurgitant murmur and the blood pressure was noted to have changed from 110/70 to 90/45 mm. Hg. The patient was encouraged to drink large volumes of fluid to maintain a high urine output. Frequent determinations were made of the plasma hemoglobin, blood urea nitrogen, and creatinine. Values for these determinations are depicted in Figs. 1 through 3. In spite of maintaining a large urine output (Fig. 4 ) , the patient had gradual increase in the blood urea nitrogen and creatinine. He remained essentially unchanged clinically, although quite weak and rather dyspneic, when the hemoglobin fell below 10 grams. Packed red cell trans fusions were given as shown in Fig. 2. The patient was started on prednisone, 10 mg. every 6 hours, on the twenty-sixth postoperative day and this was continued until his death on
J. Thoracic and Cardiovas. Surg.
R E E D AND D U N N
438
10 12
14 16 18 2 0 22 24 26 28 30 32 34 36 DAYS POST-OPERATIVE
Fig:. 1.—The blood urea nitrogen and creatinine are demonstrated in milligrams per cent. There was a slow increase until the thirty-second postoperative day at which time a rapid in crease occurred to the time of death.
0
_i
2
i ii_
4
6
8
H WM H M * * _1 1_ _ 1 _ _i_ _1_ i i_ 10 12 14 16 18 2 0 2 2 24 26 28 3 0 32 34 3 6 DAYS POST OPERATIVE
_i
Pig. 2.—The drop in hemoglobin and hematocrit which persisted through the postoperative period is demonstrated with a return to normal levels immediately after the second operative procedure. A rapid decline then occurred to the time of death.
the thirty-seventh postoperative day. The plasma hemoglobin continued to rise and it was concluded that the hemolysis was most likely due to red cell destruction secondary to the partial detachment of the prosthetic valve. On the twenty-ninth postoperative day, retrograde aortic eatheterization and angiocardiogram were performed by the Seldinger aortic technique. Begurgitation was noted in the area of the noncoronary sinus. Reoperation was recommended to correct the regurgitation. '
Vol. 48, No. 3
September, 1964
F A T A L HEMOLYSIS A F T E R BALL VALVE R E P L A C E M E N T
5
7
9
II
13
15
17
19 21 2 3 25 DAYS POST-OPERATIVE
27
29
31 3 3
439
35
Fig. 3.—This figure demonstrates the slow increase in plasma hemoglobin up to the second operation. Decrease to 50 mg. per cent occurred immediately following the second operation. A rapid increase then occurred until the patient's death.
5600
2
4
6
8
10 12 14 16 18 2 0 22 24 26 28 30 32 34 36 DAYS POST-OPERATIVE
Fig. 4.—This figure demonstrates the daily urine output during the entire postoperative period.
On the thirty-first postoperative day, with the use of the operative technique and ap paratus previously described, the aorta was cross-clamped and opened transversely in order to obtain better visualization of the site of regurgitation. This was noted along the noncoronary eusp margin which was the point of maximum calcification. The valve was re-at tached by placing through-and-through aortic sutures tied over Teflon plegets. The valve did not appear displaced. The systolic gradient was 90 mm. before repair and 40 mm. fol lowing correction of the regurgitation.
B E E D AND D U N N
440
J. Thoracic and Cardiovas. Surg.
Following the procedure, the urine cleared 4 hours postoperatively and the plasma hemoglobin was 50 mg. per cent. Eight hours after operation, the urine again became the color of port wine. Plasma hemoglobin increased rapidly (Fig. 3 ) . Renal function deteriorated rapidly in spite of good urine volume and the fluid intake (Fig. 2 ) . Renal shutdown oc curred on the thirty-sixth postoperative day. The patient developed pulmonary edema and died on the thirty-seventh postoperative day. Postmortem examination revealed evidence of lower nephron nephrosis with deposits of hemoglobin pigment in all tissues. A reactive bone marrow was present. The aortic valve prosthesis was positioned 6 to 8 mm. below both coronary artery orifices. The cuff of the valve was securely attached around the circumference of the aorta. Viewing the valve from the left ventricle, the prosthesis appeared to be in an excellent position. When viewed from above, the aorta encroached upon the superior aspect of the cage of the prosthesis. With the ball in the open position, the aorta was severely obstructed with very little clearance for blood flow around the ball. No other significant pathologic condition was noted. DISCUSSION
This case represents a previously unreported complication of aortic valve replacement with a ball valve prosthesis. Stohlman and associates7 first reported the occurrence of traumatic hemolytic anemia in dogs in which a Lucite ball valve prosthesis was placed in a conduit between the left ventricular apex and the thoracic aorta. Since canine red blood cells are more fragile than human red blood cells, a direct comparison cannot be made. However, Neill 3 ' 5 reported severe hemolysis in man following the surgical repair of an endocardial cushion defect in which a Teflon patch was used in the repair. Sayed and co-workers4 studied a similar case and postulated that hemolysis was produced by a jet stream of blood striking an unendothelized portion of the Teflon patch. Hemoly sis was corrected by covering the unendothelized portion of the Teflon patch with endocardium. Verdon and associates8 have reported the cases of 2 patients with endocardial cushion defects who developed traumatic intravascular hemoly sis postoperatively. All of the patients had endocardial cushion defects which were repaired by means of a Teflon patch to close the atrial septal defect. In each case a portion of the patch either lacked an endothelial cover at the site where it was struck by a regurgitant jet or a portion of the patch was detached and was not covered by endothelium. Turbulence of blood flow and reaction to the Teflon are other factors which might contribute to the intravascular hemolysis. Starr 6 found hemolysis in a few patients following replacement of the aortic valve; this either cleared spontaneously or after steroid therapy. Our patient had a normal plasma hemoglobin on the fifth postoperative day. However, on the twelfth postoperative day there was marked elevation of plasma hemoglobin which indicated severe intravascular hemolysis. Since an aortic diastolic murmur occurred coincident with the onset of massive hemolysis, a cause and effect relationship was postulated. The second operation was per formed to correct the regurgitation with the hope that this would terminate the hemolysis. The temporary disappearance of the hemoglobinurina and re duction in plasma hemoglobin was probably due to the exchange transfusion performed at the time of extracorporeal circulation. After the second operation the aortic diastolic murmur disappeared which indicated secure placement of the aortic valve prosthesis. Postmortem examina-
Vol. 48, No. 3 FATAL HEMOLYSIS AFTER BALL VALVE EEPLACEMENT
441
September, 1964
tion confirmed the correct placement of the prosthesis below the coronary orifices. No thrombus was present. The continuation of the hemolytic process after the second operation indicates that aortic regurgitation was not the principal cause of the hemolysis. The absence of blood incompatibility, negative Coombs' test, and lack of response to corticosteroids constitute evidence against an antigen-antibody or autoimmune reaction as the cause of the hemolysis. Although Starr has noted some improvement in the hemolytic process with steroid therapy, this has failed to be of benefit in other cases.8 Dextran and heparin have also failed to produce significant improvement. 1 ' 2 Hemolysis due to a foreign body reaction does not appear too likely. Intravascular hemolysis is rare in comparison with the widespread use of prosthetic materials. Materials used in the Starr-Edwards valves are relatively inert in human tissues. Traumatic destruction of red cells appears to offer the most logical ex planation for the hemolytic process noted. Trauma to the red blood cells could occur when the valve opens, when it closes, or as blood flows around the ball during the systolic ejection phase. The degree of traumatic destruction is also related to the red cell fragility, cardiac output, valve size, and turbulence of flow. Previous studies have shown that red cells transfused into patients with traumatic hemolysis have a markedly shortened life span. 8 Increased red cell fragmentation also occurs as a sign of traumatic destruction of red cells. Significant hemoglobinemia and hemoglobinuria does not develop until about 8 to 10 days following the operation. The exact mechanism for this delay is un known, nor is there a good explanation for the apparent increase in the rate of hemolysis. These problems may be related to the carrying capacity of the haptoglobin system. The hemoglobin binding capacity of the haptoglobin sys tem probably does not exceed 1,400 mg. per 100 ml. When this is exceeded, hemoglobinemia and hemoglobinuria occur. The carrying capacity of the haptoglobins, the regeneration of haptoglobin, and the rate of intravascular hemolysis are interrelated factors determining the degree of hemoglobinuria and hemo globinemia. Since haptoglobin regeneration is slow, its capacity is easily ex ceeded by rapid intravascular hemolysis. We are uncertain whether the hemolysis occurred as a result of valve open ing, valve closure, or turbulent blood flow. If the trauma of valve opening and closing were a significant factor, the occurrence of traumatic hemolysis should be a much more frequent complication of aortic valve replacement. It seems more likely that the red cell trauma occurred during the actual phase of systolic ejection due to partial obstruction and severe blood turbulence. Sig nificant obstruction may result when the aortic circumference is relatively small at the level of the distal portion of the valve cage. The proximity of the aortic wall to the cage is dependent upon the distance from the aortic annulus to the superior margin of the sinus of Valsalva and the size of the valve used. Starr indicated that when in doubt the smaller size valve should be used. His reason dealt primarily with the relationship of the circumference at the base of the valve but a similar problem may also occur at the distal end of the valve prosthe-
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sis. Persistence of a significant systolic gradient across the aortie valve is testi mony to the fact that obstruction was present. At postmortem examination the site of obstruction appeared to be at the area where the aorta encroached upon the distal portion of the valve cage. This type of obstruction could have been prevented by a smaller prosthesis, a shorter prosthesis, deeper placement of the prosthesis, or by enlargement of the aorta by use of a prosthetic patch. Since the structure of the prosthetic valve and cardiac anatomy are relatively fixed factors, aortic enlargement or the use of a smaller prosthesis might offer a solution to similar problems in the future. Transverse rather than vertical in cision of the aorta will also prevent narrowing following closure. SUMMARY
A case of fatal traumatic hemolysis is reported following the insertion of a Starr-Edwards aortic ball valve prosthesis. Reasons for the traumatic hemolysis are discussed and possible methods of prevention are presented. REFERENCES
1. Crosby, W. H., and Benjamin, N. R.: Paroxysmal Nocturnal Hemoglobinuria: Effect of Dextran on Hemolysis I n Vitro, Acta Haemat. 19: 193, 1958. 2. McFarland, W., Galbraith, R. G., and Miale, A., J r . : Heparin Therapy in Autoimmune Hemolytic Anemia, Blood 15: 741, 1960. 3. Neill, C. A., Farman, E. N., Sigler, A. T., and Bahnsen, H. T.: Hemolytic Anemia Fol lowing Surgical Repair of Endocardial Cushion Defects. Presented a t Thirty-First Annual Meeting of Society for Pediatric Research Program, Atlantic City, New Jersey, May 4, 1961. 4. Sayed, H. M., Dacie, J . V., Handley, D. A., Lewis, S. M., and Cleland, W. P . : Hemolytic Anemia of Mechanical Origin After Open Heart Surgery, Thorax 16: 356, 1961. 5. Sigles, A. T., Farman, E . N., Linkham, W. H., Neill, C. A., and Bahnson, H. T.: The Waring Blendor Syndrome. Seventy-Second Annual Meeting, American Pediatric Society, May, 1962, page 24. 6. Starr, A . : Personal communication. 7. Stahlman, F., Jr., Sarnoff, S. J., Case, R. B., and Ness, A. T.: Hemolytic Syndrome Fol lowing Insertion of Lucite Ball Valve Prosthesis Into Cardiovascular System, Circulation 13: 586, 1956. 8. Verdon, T. A., Jr., Forrester, R. H., and Crosby, W. H . : Hemolytic Anemia After Open Heart Repair of Ostium Primum Defects, New England J . Med. 269: 444, 1963.