Evaluation of hemolysis following replacement of atrioventricular valves with porcine xenograft (Hancock) valves Twenty-two patients who had undergone valve replacement with the porcine xenograft were studied 6 to 62 months postoperatively (mean 30.5 months) for evidence of intravascular hemolysis. Hemolysis was not detected in any patient and postoperative red cell indices and iron studies were normal for the majority of patients. Five patients had significantly elevated serum lactic dehydrogenase (LDH) values preoperatively which returned to normal following operation. Our evidence suggests that the glutaraldehyde-fixed porcine xenograft valve does not cause detectable hemolysis.
., Ph.D., Bethesda, Md. Glen R. Rhodes, M.D., and Charles L. Mclntosh, M.D.,
.Intravascular hemolysis is a frequent and occasionally serious complication of prosthetic valvular replacements. 1-4 A reduction in thromboembolism and hemolysis has been sought through clinical trials of new and modified prosthetic and tissue valves. Perhaps the most widely used tissue valve has been the glutaraldehyde-fixed porcine xenograft (Hancock) on a Dacron-covered flexible stent. 5-8 In six years of experience, this valve has provided excellent hemodynamic function without significant thromboembolism. Also, it has been our clinical impression that negligible hemolysis occurs with this valve. To test this hypothesis, we performed hematologic studies on 22 patients following replacement of the atrioventricular valve. Methods Twenty-two patients who had undergone porcine xenograft replacement of one or more atrioventricular valves were investigated, either during their admission for postoperative catheterization or during their annual clinic visit. Blood was drawn for measurement of a complete blood count, reticulocyte index, red cell indices, and platelet count. Lactic dehydrogenase (LDH) and total bilirubin concentration were determined by standard methods. Values for serum iron, From the Clinic of Surgery, National Heart and Lung Institute, Bethesda, Md. 20014. Received for publication July 27, 1976. Accepted for publication Sept. 3, 1976.
3 12
total iron binding capacity, and iron saturation were also measured. Results The 22 patients included in this study were investigated 6 to 62 months postoperatively (mean 30.5 months). Sixteen of these 22 patients had only mitral valve replacement. The remaining patients underwent mitral valve replacement accompanied by tricuspid valve replacement (3 cases), tricuspid annuloplasty (2 cases), or aortic valve commissurotomy (one case) (Table I). There have been no thromboembolic events or evidence of valvular dysfunction in this group of patients. Only one of the 22 patients was receiving an oral anticoagulant, for reasons unrelated to valve replacement. The preoperative mean hematologic values (Table II) were as follows: hematocrit 39.5 per cent, reticulocyte index 1.4 per cent, platelet count 219 x 103 per cubic millimeter, and LDH 314 I.U. (international units). The hematocrit value was less than 35 per cent in 2 patients, the reticulocyte index greater than 2 per cent in 2 patients, and the LDH greater than 400 I.U. in 5 patients. The platelet count was never less than 100,000 X 103 per cubic millimeter in any patient. The postoperative mean values (Table II) were as follows: hematocrit 42.6 per cent, reticulocyte index 1.2 per cent, platelet counts 227 x 103 per cubic millimeter, and LDH 204 I.U. The hemolysis studies failed to indicate hemolysis in any patient postoperatively (Table III). The mean serum hemoglobin value was 0.58 mg. per 100 ml. (normal range 0 to 6 mg. per 100 ml.).
Volume 73 Number 2 February, 1977
Thirteen of 22 patients had no serum hemoglobin detected. The mean serum haptoglobin value was 94.0 mg. per 100 ml., and only 2 patients had values of less than 50 mg. per 100 ml. Postoperative iron studies were within normal limits for the majority of patients (Table III). There were 5 patients with iron saturations of less than 20 per cent, and all had normal hematocrit values. The mean red cell indices were within normal limits (Table III). Only one patient had red cell indices suggestive of iron deficiency. Also, 2 patients had mild anemias (hematocrit values of 32 and 34 per cent); however, results of their hemolysis studies were normal. Five patients had significantly elevated LDH values preoperatively which returned to normal following operation (Fig. 1). LDH, decreasing postoperatively, was the only parameter than changed significantly (p < 0.05) from preoperative values. Discussion Chronic intravascular hemolysis following cardiac valve replacement with a prosthesis has been a frequent and occasionally serious complication.1-4 The hemolysis may be severe enough to necessitate intensive iron therapy or even valve replacement. The mechanism of hemolysis is usually related to increased shear stress associated with turbulence around both normal and abnormal prosthetic valves. One report has demonstrated that shear stresses of 3,000 dynes per square centimeter or greater, which are sufficient to cause in vitro hemolysis, may develop across ball valves when the orifice size is either small in relation to the stroke volume or large in relation to outflow diameter.10 Increased diastolic pressure gradients may also produce sufficient shear stress to cause hemolysis. Caged-ball valves, especially the Starr-Edwards Models 1000 and 6000 with exposed metal struts and silicone balls, were employed in a significant majority of the first patients undergoing valve replacement. Hemolysis occurred infrequently with these valves except when ball variance or valvular insufficiency developed.11 Metal balls and cloth-covered valves were introduced in order to reduce the ball variance and thromboembolism of the early valves. These valves, such as the Starr-Edwards Model 2310-2320 (aortic) and 6310-6320 (mitral) prostheses, have frequently caused mild but usually well-compensated hemolysis. 12-14 However, severe hemolytic anemia may develop in valves with small orifices or basilar insufficiency.12' 15 Hemolysis following mitral replacement is usually less than that observed after aortic replacement, but it has been reported to be as high as 37.5 to 85 per cent
Valve replacement with Hancock xenografts
313
1200 c
1000
c o
800
D
'& CO c
k_ CD
_c X Q
600 400 200 Postoperative
Preoperative
Fig. 1. Preoperative and postoperative lactic dehydrogenase (LDH) measurements in 5 patients with abnormal preoperative LDH values. Table I. Profile of 22 patients receiving one or more porcine xenograft cardiac valves
MVR MVR, TVR MVR, aortic commissurotomy MVR, tricuspid annuloplasty Total
No.
Total post op. months
Valve complications
16 3 1
489 96 55
None None None
2
28
None
22
668 (mean 30.36)
Legend: MVR, Mitral valve replacement. TVR, Tricuspid valve replacement.
with the Starr-Edwards 6310-6320 series,14, 16 49 per cent with the Beall prosthesis,17 and 15 to 35 per cent with the Bjork-Shiley valves. 16 ' 18 In recent years, varying types of tissue valves have been investigated as alternatives to currently used prostheses. Although fascia lata, pericardial, and fresh homograft valves have given good short-term hemodynamic function with minimal hemolysis and thromboembolism, the incidence of late postoperative tissue failure has been high. 19-21 Our clinical success employing the porcine xenograft valve in the atrioventricular position prompted us to verify the degree of hemolysis, if any, occurring with its use. Evaluation of 22 patients 6 to 62 months following single or double atrioventricular valve replacement revealed no significant hemolysis. Five patients who had elevated LDH and reticulocyte values preoperatively had normal values postopera-
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Rhodes and
The Journal of Thoracic and Cardiovascular Surgery
Mclntosh
Table II. Preoperative
and postoperative
hematologic
parameters
Preop. mean ±S.D. Hematocrit* (%) Reticulocyte index (%) LDH* (I.U.) Platelet blood (x 103/c.mm.)
39.5 1.40 314 219
Post op. mean ±S.D. 42.6 1.22 204 255
± 4.67 ± 1.03 ± 257 ± 64
± 5.76 ± 0.581 ±52.1 ± 37
Normal value 43.5 ± 3.1 1.64 ± 1.08 130-360 248 ± 50
Legend: LDH, Lactic dehydrogenase. *Normal values are average of male-female values. Table HI. Summary of postoperative
hemolysis, iron, and red cell index studies Postop. mean ± S.D.
Serum haptoglobin* (mg./lOO ml.) Serum hemoglobint (mg./100ml.) Serum iron (jiig%) Total iron binding capacity (p.g%) Iron saturation (%) Mean corpuscular volume:): (/xc.mm./red cell) Mean corpuscular hemoglobin^ (Pg/red cell) Mean corpuscular hemoglobin concentration (Gm./lOO ml./RBC) RBC county (x lOVc.mm. blood)
94.0 0.58 94.1 305 33.0 88.5 30.0 33.5 4.83
Normal value 50-250 0-6 70-170 240-250 33 90.1 ± 4 . 8 30.12 ± 1.9 33.7 ± 1.2 4.81 ± 1.2
±51.8 ± 1.55 ±35.1 ± 54.0 ± 16.8 ± 7.3 ± 2.9 ± 0.8 ± 0.53
*Two patients had serum hepatoglobins values less than 50 mg. per 100 ml. tNo patient had a serum hemoglobin value greater than 6 mg. per 100 ml.; no detectable serum hemoglobin. ^Normal values are average of male-female values. tively. This observation suggests that preoperative hemolysis, perhaps from a deformed stenotic mitral valve, may be abolished in some patients following valve replacement with a porcine xenograft. The red cell indices and iron studies were normal in almost all patients. Two patients had mild anemias postoperatively and an additional patient had a reduced mean corpuscular volume, mean corpuscular hemoglobin concentration, and serum iron saturation suggestive of iron deficiency. The LDH, reticulocyte index, and serum hemoglobin values were unremarkable in these patients. Our evidence suggests that the glutaraldehyde-fixed porcine xenograft provides excellent hemodynamic function without significant thromboembolism or hemolysis. Presently, it is our valve of choice for all cases of atrioventricular valve replacement. REFERENCES 1 Bell, R. E., Petroglu, S., and Fraser, R. S.: Chronic Hemolysis Occurring in Patients Following Cardiac Surgery, Br. Heart J. 29: 327, 1967. 2 Grosse-Boackhoff, R., and Gehrmann, G.: Mechanical Hemolysis in Patients With Valvular Heart Disease and Valvular Prostheses, Am. Heart J. 74: 137, 1967. 3 Crexells, C , Aerichide, M., Bonny, Y., Lepage, G., and
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Campearu, L.: Factors Influencing Hemolysis in Valve Prostheses, Am. Heart J. 84: 161, 1972. Marsh, G. W., and Lewis, S. M.: Cardiac Hemolytic Anemia, Semin Hematol. 6: 133, 1969. Brown, J. W., Myerowitz, P. D., Cann, M. S., Colvin, S. B., Mclntosh, C. L., and Morrow, A. G.: Clinical and Hemodynamic Comparisons of Kay-Shiley, StarrEdwards 6520, and Reis-Hancock Porcine Xenograft Mitral Valve, Surgery 76: 983, 1974. Mclntosh, C. L., Michaelis, L. L., Morrow, A. G., Itscoitz, S. B., Redwood, D. R., and Epstein, S. E.: Atrioventricular Valve Replacement With the Hancock Porcine Xenograft: A Five Year Clinical Experience, Surgery 78: 768, 1975. Pipkin, R. D., Buch, W. S., and Fogarty, T. J.: Evaluation of Aortic Valve Replacement with a Porcine Xenograft Without Long-Term Anticoagulation, J. THORAC. CARDIOVASC. SURG. 71: 179,
1976.
8 Cohn, L. H., Lamberti, J. J., Castaneda, A. R., and Collins, J. J.: Cardiac Valve Replacement With the Stabilized Glutaraldehyde Porcine Aortic Valve: Indications, Operative Results and Followup, Chest 68: 162, 1975. 9 Kastor, J. A., Akbarian, M., Buckley, M. J., Dinsmore, R. E., Sanders, C. A., Scannell, J. G., and Austen, W. G.: Paravalvular Leaks and Hemolytic Anemia Following Insertion of Starr-Edwards Aortic and Mitral Valves, J. THORAC. CARDIOVASC. SURG. 56: 279,
1968.
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Valve replacement with Hancock xenografts
10 Nevaril, C. G., Lynch, E. C , Alfrey, C. P., and Heliums, J. D.: Erythrocyte Damage and Destruction Induced by Shearing Stress, J. Lab. Clin. Med. 71: 784, 1968. 11 Penther, P., Boudarias, J. P., Bensaid, J., Maurice, P., and Lenegre, J.: Long-Term Prognosis of Mitral or Aortic Valve Replacement by Starr-Edwards Prostheses, Chest 58: 129, 1970. 12 Lefemine, A. A., Miller, M., and Pinder, G. C : Chronic Hemolysis Produced by Cloth-Covered Valves, J. THORAC. CARDIOVASC. SURG. 67: 657,
Valves. J. THORAC. CARDIOVASC. SURG. 59: 84,
1970.
16 Ahmad, R., Manohitharajah, S. M., Deverall, P. B., and Watson, D. A.: Chronic Hemolysis Following Mitral Valve Replacement, J. THORAC. CARDIOVASC. SURG. 71:
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18
1974.
13 Hodam, R., Starr, A., Herr, R., and Pierce, W. R.: Early Clinical Experience With Cloth-Covered Valvular Prosthesis, Ann. Surg. 170: 471, 1969. 14 Donnely, R. J., Rahman, A. N., Manohitarajah, S. M., Deverall, P. B., and Watson, R. A.: Chronic Hemolysis Following Mitral Valve Replacement: A Comparison of the Frame-Mounted Aortic Homograft and the Composite-Seat Starr-Edwards Prosthesis, Circulation 48: 823, 1973. 15 Reis, R. L., Glancy, D. L., O'Brine, K., Epstein, S. E., and Morrow, A. G.: Clinical and Hemodynamic Assessments of Fabric-Covered Starr-Edwards Prosthetic
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212, 1976. Henderson, B. J., Mitha, A. S., le Roux, B. T., and Gotsman, M. S.: Hemolysis Related to Mitral Valve Replacement With the Beall Valve Prosthesis, Thorax 28: 488, 1973. Slater, S. D., Sallam, I. A., Bain, W. H., Turner, M. A., and Lawrie, T. D. V.: Hemolysis With Bjork-Shiley and Starr-Edwards Prosthetic Heart Valves: A Comparative Study, Thorax 29: 624, 1974. Edwards, W. S.: Late Results With Autogenous Tissue Heart Valves, Ann. Thorac. Surg. 12: 385-390, 1974. lonescu, I., Pakrashi, B. C , Mary, D., Bartek, I. T., and Wooler, G. H.: Long-Term Evaluation of Tissue Valves, J. THORAC. CARDIOVASC. SURG. 68: 361,
1974.
21 Yarbrough, J. W., Roberts, W. C , and Reis, R. L.: Structural Alterations in Tissue Cardiac Valves Implanted in Patients and in Calves, J. THORAC. CARDIOVASC. SURG. 65: 364,
1973.