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Severe Hemoglobinuria Masquerading as Gross Hematuria Following Mitral Valve Replacement
0022-5347/95/1535-1639$03.00/0 JOIlllNAL OF UROLOGY
Vol. 153,1639-1640,May 1995 Printed in U.S.A.
Copyright 0 1995 by AMEHICAN UROLOCICAL ASSOCIATION, INC
SEVERE HEMOGLOBINURIA MASQUERADING AS GROSS HEMATURIA FOLLOWING MITRAL VALVE REPLACEMENT ELLIOT B. LANDER From the Department of Urology, Southern California Permanente Medical Group, Orange County, California
ABSTRACT
Gross hemoglobinuria following mitral valve replacement can represent a rare form of hemolytic anemia. This condition can masquerade as gross hematuria i n the post-valve replacement patient. It is commonly associated with valvular dysfunction, specifically, perivalvular leakage. The leakage may not be apparent on routine echocardiography but it may be documented with trans-esophageal echocardiography. KEY WOFDS: hemoglobinuria;hematuria; anemia, hemolytic; mitral valve; heart valve prosthesis
A case of gross hemoglobinuria following mitral valve replacement with the St. Jude prosthesis is reported. Severe gross hemoglobinuria masquerades as gross hematuria and can result in red, black or chocolate colored urine. Perivalvular leakage in prosthetic heart valves can result in a rare form of macro-angiopathic hemolytic anemia. It is important to recognize this condition with careful examination of urinary sediment to avoid invasive and extensive evaluation of gross hematuria and, perhaps more importantly, to alert the physician to early prosthetic valvular dysfunction.
The patient was treated conservatively with fluids and multiple blood transfusions (approximately 4 units per month for 3 months). The mild high output congestive heart failure subsequently improved, as did the appearance of the urine. In January 1994 the patient received the final transfusion and the hematocrit remained stable at 30 mg./dl. Total bilirubin and serum creatinine levels normalized. The clinical manifestations of jaundice resolved. The perivalvular leakage is presumed to have improved. DISCUSSION
CASE REPORT
A 72-year-old man with a history of inferior wall myocardial infarction and previous coronary artery bypass graft surgery underwent mitral valve replacement for severe mitral regurgitation with a St. Jude prosthetic valve in July 1993. The patient was immediately anticoagulated with warfarin. Urine was chocolate colored postoperatively and he was rehospitalized for severe anemia. He denied voiding symptoms, flank pain and passage of clots or tissue in the urine but continued to pass dark colored urine. He denied a history of nephrolithiasis, urinary tract infections, urological disease, family members with sickle cell disease and tobacco use. Physical examination revealed a thin, slightly jaundiced white man with icteric sclerae. Cardiovascular examination was consistent with mild congestive heart failure. Abdominal, genital and rectal examinations were unremarkable. The urine was dark but without clots. Laboratory analysis revealed a hematocrit of 21 mg./dl. (normal 42 to 52%) and numerous schistocytes on peripheral smear. Serum creatinine was 1.2 mg./dl. (normal 0.7 to 1.3). Total, indirect and direct bilirubin levels were 3.4 mg./dl. (normal less than 11, 3.1 mg./dl. (normal 0 to 0.2) and 0.3 mg./dl. (normal 0 to 0.25), respectively. Urinalysis dipstick showed 3 + bacteria, positive nitrite (normal negative) and “very large” blood (normal negative). Laboratory microscopic analysis demonstrated 15 to 20 white blood cells per high power field (normal 0 to 5 ) and 3 to 6 red blood cells per high power field (normal 0 to 2). Cultures yielded more than lo5 Enterobacter species, which were pansensitive. An excretory urogram was remarkable only for prostatic enlargement. Personal office examination of the urinary d lfield of hemoglobin casts. There was sediment revealed a f notable absence of red blood cells and red blood cell casts. The urinary tract infection was treated with oral flouroquinolone. Routine echocardiography demonstrated left mild to moderate dilatation of the heart with a normally functioning prosthetic mitral valve. Trans-esophageal echocardiography revealed perivalvular leakage at the prosthetic valve. Accepted for publication October 14,1994.
Clinical anemia due to intravascular hemolysis associated with valvular dysfunction has been termed macro-angiopathic hemolytic anemia.’ When intravascular hemolysis is severe, hemoglobinuria results. Hemoglobinuria is a well documented complication of perivalvular leakage with the St. Jude mitral valve replacement.13 Chronic intravascular hemolysis with anemia is noted with other types of valve prosthesis as well, including the Starr-Edwards, Bjork-Shiley, Beall, Magovern and the Cutter-Smelloff prostheses.4-7 Mechanical hemolysis has been noted to appear 1 to 44 days after valve replacement and is associated with some degree of hepatorenal insufficiency.2 In the most severe cases patients died of renal and multiorgan failure before valve repair.3 In patients undergoing reoperation leakages were noted to be slight and hemoglobinuria resolved after valve repair. Not all patients in these previous series were diagnosed with valve malfunction or perivalvular leakage.3 In light of these findings, an exhaustive search for valvular dysfunction is warranted in cases of hemoglobinuria. It is noteworthy that in our case routine echocardiography failed to identify the leakage noted on trans-esophageal echocardiography. To evaluate more fully the etiology of the hemolysis, electron microscopy has been performed on the St. Jude prosthesis. The sewing cuff reveals an irregular shaggy surface that may create greater shearing forces against erythrocytes if there is perivalvular leakage.2 Red blood cell destruction has been attributed to turbulent flow and shearing forces rather than direct mechanical impact.’.’ The red blood cell has a critical tolerance to shearing stress that, when increased, causes stretching of the cell membrane with subsequent tearing and cell fi-agmentation.l0 This fragmentation results in release of free hemoglobin, which is bound to haptoglobin and cleared by the reticuloendothelial system. When the plasmafree hemoglobin level exceeds the haptoglobin binding capacity, the hemoglobin is filtered a t the gl~merulus.~ When small quantities of hemoglobin (20 to 60 mg./100 ml.) are filtered by the kidneys the proximal tubules absorb it, and convert it to ferritin and hemosiderin. When larger quantities of hemoglobin are presented to the proximal tubule, the
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SEVERE HEMOGLOBINURIA FOLLOWING MITR4L VALVE REPLACEMENT
transport mechanism capacity is exceeded and hemoglobinuria occurs.4 Thus, the clinical pigmenturia may be secondary either to hemosiderin or hemoglobin, depending on the degree of the underlying pathological condition. CONCLUSIONS
Our case underscores the importance of careful examination of the urinary sediment. The clinical anemia, positive urinary dipstick result and gross appearance of the urine may have led to a routine hematuria evaluation. However, appropriate evaluation of the urine by the clinician led to a high index of suspicion for hemolysis. In this case, the congestive heart failure and anemia improved but many cases require valvular repair. The proper investigation of dark urine in the valve replacement patient may prevent needless radiographic and endoscopic studies for sources of hematuria, and may alert the medical team to a significant cardiac pathological condition. REFERENCES
1. Park, C. H., Maytin, 0. and Rubini, J.: Postperfusion and macroangiopathic hemolytic syndromes after cardiac surgery. South. Med. J., 6 2 348,1969. 2. Okita, Y., Miki, S., Kusuhara, K, Ueda, Y., Tahata, T., Tsukamoto, Y., Yamanaka, K, and Shiraishi, S.: Intractable hemolysis caused by perivalvular leakage following mitral &. Thovalve replacement G t h S t . Jude Medical prosthesis. A
rac. Surg., 46:89, 1988. 3. Taggart, D. P., Spyt, T. J., Wheatley, D. J. and Fisher, J.: Severe hemolysis with the St. Jude Medical prosthesis. Eur. J . Cardiothorac. Surg., 2 137, 1988. 4. Eyster, E., Mayer, K. and McKenzie, S.: Traumatic hemolysis with iron deficiency anemia in patients with aortic valve lesions. Ann. Intern. Med., 68: 995,1968. 5. Eyster, E., Rothchild, J . and Mychajliw, 0.:Chronic intravascular hemolysis after aortic valve replacement. Long-term study comparing different types of ball-valve prostheses. Circulation, 1 4 657,1971. 6. Williams, J. C., Jr., Vernon, C. R, Daicoff, G. R., Bartley, T., Wheat, M. and Ramsey, H.: Hemolysis following mitral valve replacement with the Beall valve prosthesis. J. Thorac. Cardiovasc. Surg., 61: 393,1971. 7. Allard, J. R., Fraser, G. and Dobell, R. A.: Sudden hemolysis indicating prosthetic valve dysfunction. Canad. J. Surg., 1 9 272, 1976. 8. Rubinson, R. M., Morrow, A. G. and Gebel, P.: Mechanical destruction of erythrocytes by incompetent aortic valvular prosthesis; clinical, hemodynamic, and hematologic findings. h e r . Heart. J., 71: 179, 1966. 9. Rose, J. C., Hufnagel, C., Freis, E., Harvey, W. and Partenope, E.: The hemodynamic alterations produced by a plastic valvular prosthesis for severe aortic insufficiency in man. J . Clin. Invest., 3 3 891,1954. 10. Laurell, C.and Nyman, M.: Studies on the serum haptoglobin level in hemoglobinemiaand its influence on renal excretion of hemoglobin. Blood, 12: 493, 1957.
Vol. 153,1639-1640,May 1995 Printed in U.S.A.
Copyright 0 1995 by AMEHICAN UROLOCICAL ASSOCIATION, INC
SEVERE HEMOGLOBINURIA MASQUERADING AS GROSS HEMATURIA FOLLOWING MITRAL VALVE REPLACEMENT ELLIOT B. LANDER From the Department of Urology, Southern California Permanente Medical Group, Orange County, California
ABSTRACT
Gross hemoglobinuria following mitral valve replacement can represent a rare form of hemolytic anemia. This condition can masquerade as gross hematuria i n the post-valve replacement patient. It is commonly associated with valvular dysfunction, specifically, perivalvular leakage. The leakage may not be apparent on routine echocardiography but it may be documented with trans-esophageal echocardiography. KEY WOFDS: hemoglobinuria;hematuria; anemia, hemolytic; mitral valve; heart valve prosthesis
A case of gross hemoglobinuria following mitral valve replacement with the St. Jude prosthesis is reported. Severe gross hemoglobinuria masquerades as gross hematuria and can result in red, black or chocolate colored urine. Perivalvular leakage in prosthetic heart valves can result in a rare form of macro-angiopathic hemolytic anemia. It is important to recognize this condition with careful examination of urinary sediment to avoid invasive and extensive evaluation of gross hematuria and, perhaps more importantly, to alert the physician to early prosthetic valvular dysfunction.
The patient was treated conservatively with fluids and multiple blood transfusions (approximately 4 units per month for 3 months). The mild high output congestive heart failure subsequently improved, as did the appearance of the urine. In January 1994 the patient received the final transfusion and the hematocrit remained stable at 30 mg./dl. Total bilirubin and serum creatinine levels normalized. The clinical manifestations of jaundice resolved. The perivalvular leakage is presumed to have improved. DISCUSSION
CASE REPORT
A 72-year-old man with a history of inferior wall myocardial infarction and previous coronary artery bypass graft surgery underwent mitral valve replacement for severe mitral regurgitation with a St. Jude prosthetic valve in July 1993. The patient was immediately anticoagulated with warfarin. Urine was chocolate colored postoperatively and he was rehospitalized for severe anemia. He denied voiding symptoms, flank pain and passage of clots or tissue in the urine but continued to pass dark colored urine. He denied a history of nephrolithiasis, urinary tract infections, urological disease, family members with sickle cell disease and tobacco use. Physical examination revealed a thin, slightly jaundiced white man with icteric sclerae. Cardiovascular examination was consistent with mild congestive heart failure. Abdominal, genital and rectal examinations were unremarkable. The urine was dark but without clots. Laboratory analysis revealed a hematocrit of 21 mg./dl. (normal 42 to 52%) and numerous schistocytes on peripheral smear. Serum creatinine was 1.2 mg./dl. (normal 0.7 to 1.3). Total, indirect and direct bilirubin levels were 3.4 mg./dl. (normal less than 11, 3.1 mg./dl. (normal 0 to 0.2) and 0.3 mg./dl. (normal 0 to 0.25), respectively. Urinalysis dipstick showed 3 + bacteria, positive nitrite (normal negative) and “very large” blood (normal negative). Laboratory microscopic analysis demonstrated 15 to 20 white blood cells per high power field (normal 0 to 5 ) and 3 to 6 red blood cells per high power field (normal 0 to 2). Cultures yielded more than lo5 Enterobacter species, which were pansensitive. An excretory urogram was remarkable only for prostatic enlargement. Personal office examination of the urinary d lfield of hemoglobin casts. There was sediment revealed a f notable absence of red blood cells and red blood cell casts. The urinary tract infection was treated with oral flouroquinolone. Routine echocardiography demonstrated left mild to moderate dilatation of the heart with a normally functioning prosthetic mitral valve. Trans-esophageal echocardiography revealed perivalvular leakage at the prosthetic valve. Accepted for publication October 14,1994.
Clinical anemia due to intravascular hemolysis associated with valvular dysfunction has been termed macro-angiopathic hemolytic anemia.’ When intravascular hemolysis is severe, hemoglobinuria results. Hemoglobinuria is a well documented complication of perivalvular leakage with the St. Jude mitral valve replacement.13 Chronic intravascular hemolysis with anemia is noted with other types of valve prosthesis as well, including the Starr-Edwards, Bjork-Shiley, Beall, Magovern and the Cutter-Smelloff prostheses.4-7 Mechanical hemolysis has been noted to appear 1 to 44 days after valve replacement and is associated with some degree of hepatorenal insufficiency.2 In the most severe cases patients died of renal and multiorgan failure before valve repair.3 In patients undergoing reoperation leakages were noted to be slight and hemoglobinuria resolved after valve repair. Not all patients in these previous series were diagnosed with valve malfunction or perivalvular leakage.3 In light of these findings, an exhaustive search for valvular dysfunction is warranted in cases of hemoglobinuria. It is noteworthy that in our case routine echocardiography failed to identify the leakage noted on trans-esophageal echocardiography. To evaluate more fully the etiology of the hemolysis, electron microscopy has been performed on the St. Jude prosthesis. The sewing cuff reveals an irregular shaggy surface that may create greater shearing forces against erythrocytes if there is perivalvular leakage.2 Red blood cell destruction has been attributed to turbulent flow and shearing forces rather than direct mechanical impact.’.’ The red blood cell has a critical tolerance to shearing stress that, when increased, causes stretching of the cell membrane with subsequent tearing and cell fi-agmentation.l0 This fragmentation results in release of free hemoglobin, which is bound to haptoglobin and cleared by the reticuloendothelial system. When the plasmafree hemoglobin level exceeds the haptoglobin binding capacity, the hemoglobin is filtered a t the gl~merulus.~ When small quantities of hemoglobin (20 to 60 mg./100 ml.) are filtered by the kidneys the proximal tubules absorb it, and convert it to ferritin and hemosiderin. When larger quantities of hemoglobin are presented to the proximal tubule, the
1639
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SEVERE HEMOGLOBINURIA FOLLOWING MITR4L VALVE REPLACEMENT
transport mechanism capacity is exceeded and hemoglobinuria occurs.4 Thus, the clinical pigmenturia may be secondary either to hemosiderin or hemoglobin, depending on the degree of the underlying pathological condition. CONCLUSIONS
Our case underscores the importance of careful examination of the urinary sediment. The clinical anemia, positive urinary dipstick result and gross appearance of the urine may have led to a routine hematuria evaluation. However, appropriate evaluation of the urine by the clinician led to a high index of suspicion for hemolysis. In this case, the congestive heart failure and anemia improved but many cases require valvular repair. The proper investigation of dark urine in the valve replacement patient may prevent needless radiographic and endoscopic studies for sources of hematuria, and may alert the medical team to a significant cardiac pathological condition. REFERENCES
1. Park, C. H., Maytin, 0. and Rubini, J.: Postperfusion and macroangiopathic hemolytic syndromes after cardiac surgery. South. Med. J., 6 2 348,1969. 2. Okita, Y., Miki, S., Kusuhara, K, Ueda, Y., Tahata, T., Tsukamoto, Y., Yamanaka, K, and Shiraishi, S.: Intractable hemolysis caused by perivalvular leakage following mitral &. Thovalve replacement G t h S t . Jude Medical prosthesis. A
rac. Surg., 46:89, 1988. 3. Taggart, D. P., Spyt, T. J., Wheatley, D. J. and Fisher, J.: Severe hemolysis with the St. Jude Medical prosthesis. Eur. J . Cardiothorac. Surg., 2 137, 1988. 4. Eyster, E., Mayer, K. and McKenzie, S.: Traumatic hemolysis with iron deficiency anemia in patients with aortic valve lesions. Ann. Intern. Med., 68: 995,1968. 5. Eyster, E., Rothchild, J . and Mychajliw, 0.:Chronic intravascular hemolysis after aortic valve replacement. Long-term study comparing different types of ball-valve prostheses. Circulation, 1 4 657,1971. 6. Williams, J. C., Jr., Vernon, C. R, Daicoff, G. R., Bartley, T., Wheat, M. and Ramsey, H.: Hemolysis following mitral valve replacement with the Beall valve prosthesis. J. Thorac. Cardiovasc. Surg., 61: 393,1971. 7. Allard, J. R., Fraser, G. and Dobell, R. A.: Sudden hemolysis indicating prosthetic valve dysfunction. Canad. J. Surg., 1 9 272, 1976. 8. Rubinson, R. M., Morrow, A. G. and Gebel, P.: Mechanical destruction of erythrocytes by incompetent aortic valvular prosthesis; clinical, hemodynamic, and hematologic findings. h e r . Heart. J., 71: 179, 1966. 9. Rose, J. C., Hufnagel, C., Freis, E., Harvey, W. and Partenope, E.: The hemodynamic alterations produced by a plastic valvular prosthesis for severe aortic insufficiency in man. J . Clin. Invest., 3 3 891,1954. 10. Laurell, C.and Nyman, M.: Studies on the serum haptoglobin level in hemoglobinemiaand its influence on renal excretion of hemoglobin. Blood, 12: 493, 1957.