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Gross Hematuria Associated with Sickle Cell Trait and Von Willebrand’S Disease
0022-5347/79/1221-0136$02.00/0
THE
Vol. 122, July Printed in U.S.A.
JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
GROSS HEMATURIA ASSOCIATED WITH SICKLE CELL TRAIT AND VON WILLEBRAND'S DISEASE RONALD S. WEINGER, GEORGE S. BENSON
AND
SANTIAGO VILLARREAL
From the Department of Medicine, Division of Hematology, Department of Surgery, Division of Urology and the Gulf States Hemophilia Center, The University of Texas Medical School at Houston, Houston, Texas
ABSTRACT
A case of recurrent gross hematuria, sickle cell trait and von Wille brand's disease is reported. The gross hematuria abated promptly after the institution of cryoprecipitate therapy. The importance of considering von Willebrand's disease in the differential diagnosis in patients with sickle cell trait and hematuria is discussed. Gross hematuria is a well recognized occurrence in patients with sickle cell trait. 1- 3 In addition, Brody and associates recently reported the association among von Willebrand's disease, gross hematuria and sickle cell trait. 4 Herein we describe the detection of von Willebrand's disease in a young black woman with sickle cell trait and significant gross hematuria. The hematuria ceased within 24 hours after the institution of cryoprecipitate infusions. CASE REPORT
An 18-year-old black woman was hospitalized with gross painless hematuria 1 day in duration. She had experienced hematuria 4 times previously and the most recent episode had occurred 1 year ago. Cystoscopy at that time revealed no significant bladder or urethral pathology but blood was observed to be effluxing from the right ureteral orifice. The bleeding ceased after administration of 2 units of blood. The patient denied any other personal or family history of bleeding. During the current episode she was afebrile and normotensive. There was no costovertebral angle or abdominal tenderness. No abdominal masses or bruits were present. Laboratory evaluation included a normal prothrombin time, activated partial thromboplastin time, fibrinogen level, platelet count and complete blood count. The urine was grossly bloody and had a specific gravity of 1.011. Hemoglobin electrophoresis once again revealed hemoglobin AS. An excretory urogram demonstrated minimal blunting of the right upper pole calix and a small caliceal diverticulum in the upper pole of the left kidney. Despite intravenous fluid and diuretic therapy, the hematuria persisted until 10 days after hospitalization when studies that had been obtained on the third hospital day were completed and 6 units of cryoprecipitate were infused. The gross hematuria improved greatly within 9 hours. At 2 subsequent 12-hour intervals 4 units of cryoprecipitate were infused. Gross hematuria was not present after the second cryoprecipitate infusion. The patient was discharged 12 days after hospitalization completely asymptomatic. Family members were not available for study. MATERIALS AND METHODS
Blood was collected in plastic syringes and anticoagulated with 1/10 volume of 3.8 per cent sodium citrate. Platelet poor plasma was obtained by centrifuging blood for 20 minutes at 1,800 g, and either tested immediately or stored at -70C for subsequent assays. Standard techniques were used for measurement of activated partial thromboplastin time, prothromAccepted for publication October 27, 1978. Supported in part by a grant from the United States Public Health Service, No. MC-B-480001-01-0.
136
bin time, fibrinogen and 1-stage assays of factor VIII coagulant activity (FVIIhHG), 5• * Bleeding times were by template. 6 Ristocetin cofactor activity (FVIIIvwF) was measured using formalin-fixed platelets. 7 Factor VIII antigen (FVIIIAGN) was quantified in plasma by Laurell electroimmunoassay,8 using rabbit anti-human FVIII antibody.t RESULTS
The history of recurrent episodes of hematuria prompted a search for von Willebrand's disease. The patient had a bleeding time of 2 minutes (normal <8 minutes) 3 days after hospitalization. FVIIhHG was 0.67 U./ml. (normal 0.60 to 1.50 U./ml.), FVIIIAGN was 0.36 U./ml. (normal 0.60 to 1.50 U./ml.) and FVIIIvwF was 0.30 U./ml. (normal 0.60 to 1.50 U./ml.). The results oflaboratory studies done 10 days after hospitalization pertinent to von Willebrand's disease and those following the first infusion of cryoprecipitate are shown in the table. Of significance is the prolonged increase of FVIIhHG which followed transfusion. FVIIIvwF increased transiently but had returned almost to the pre-transfusion level 11 hours later. FVIIhGN remained within the normal range during that same post-transfusion period. DISCUSSION
Abel and Brown described hematuria in patients with sickle cell trait. 1 The mechanism(s) responsible for this phenomenon remains obscure but may be related to the environmental conditions in the renal medulla, which favor intravascular sickling.9-11 An alternate explanation, involving the development of immune complex nephritis, has been proposed recently by Pardo and associates in patients with sickle cell anemia. 12 The normal human von Willebrand factor is composed of disulfide-linked, 230,000 molecular weight subunits 13 and induces platelet agglutination in the presence of the antibiotic, ristocetin (FVIIIvwF) .14 Also, FVIIIvwF reacts with antisera to FVIII produced in animals (FVIIIAGN). 15 Additional subunits that possess FVIIIAHG are derived from an as yet unknown site and are attached to the circulating FVIIIvwF/FVIIIAGN molecules by non-covalent bonds. 16 von Willebrand's disease is a heterogeneous disorder that involves defects in the factor VIII molecular complex. Some patients have absent or reduced FVIIIvwF, FVIIhGN and FVIIIAHG activities. 14' 15 The bleeding time, although prolonged in the classical form of the disorder, may be normal. 17 In other patients a defect in FVIIIvwF is associated with normal FVIIhGN * Factor VIII-deficient plasma substrates, George King Biomedical, Inc., Salem, New Hampshire. t Behring Diagnostics, Sommerville, New Jersey.
GROSS HEMATURIA WITH SICKLE CELL TRAIT AND VON WILLEBRAND'S DISEASE
Laboratory results (10th hospital day)
Before infusion 1 hr. after infusion 11 brs. after infusion
FVII1AHG' (U./ml.)
FVIIlvWFt (U./ml.)
FVIIIAGN+ (U./ml.)
B.T.§ (min.)
0.29 0.67 0.87
0.12 0.28 0.18
0.39 1.01 0.85
2 Not done Not done
' Factor VIII coagulant activity, normal 0.60 to 1.50 U./ml.
t Ristocetin cofactor activity, normal 0.60 to 1.50 U./ml. :j: Factor VIII related antigen, normal 0.60 to 1.50 U./ml. § Template bleeding time, normal <8 minutes.
and FVIIhHG levels. 18 Our patient demonstrated variable but low levels of FVIIIAHG, FVIIlvwF and FVIIIAGN, Although the bleeding time was within the normal range she responded to cryoprecipitate infusions with the prolonged increase in FVIIIAHG characteristic of von Willebrand's disease. 19 Massive hematuria in sickle trait patients is often a difficult management problem. Therapy has included bed rest,2 hypotonic fluids in conjunction with alkalization of the urine, 20 epsilon aminocaproic acid, 21 • 22 renal pelvic lavage with silver nitrate 2:i and nephrectomy. 9 Our case and those reported previously4 suggest that when von •Nillebrand's disease coexists with sickle cell trait hematuria can be managed successfully with specific plasma product therapy. It is interesting to speculate that the coexistence of von Willebrand's disease with sickle trait accentuates the severity of clinical bleeding. Whether an increased incidence of von Wille brand's disease exists in individuals heterozygous for sickle hemoglobin is unknown. Of importance is that our patient and those of Brody and associates 4 had no additional personal or family bleeding history other than hematuria. This suggests that in patients with sickle cell trait who have protracted or severe bleeding episodes a search for von Willebrand's disease should be undertaken before more radical therapy (that is epsilon aminocaproic acid, silver nitrate lavage or nephrectomy) is instituted. REFERENCES
1. Abel, M. S. and Brown, C. R.: Sickle cell diseases with severe hematuria simulating renal neoplasm. J. A. M. A., 136: 624, 1948. 2. Lucas, W. M. and Bullock, W. H.: Hematuria in sickle cell disease. J. Urol., 83: 733, 1960. 3. Bennett, M. A., Heslop, R. W. and Meynell, M. J.: Massive haematuria associated with sickle-cell trait. Brit. Med. J., 1: 677, 1967. 4. Brody, J. I., Levison, S. P. and Jung, C. J.: Sickle cell trait and hematuria associated with von Willebrand syndromes. Ann. Intern. Med., 86: 529, 1977. 5. Bowie, E. J. W., Thompson, J. H., Jr., Owen, C. A., Jr. and Didisheim, P.: Mayo Clinic Laboratory Manual of Hemostasis. Philadelphia: W. B. Saunders Co., 1971. 6. Mielke, C. H., Kaneshiro, M. M., Maher, I. A., Weiner, J.M. and Rapaport, S. I.: The standardized normal Ivy bleeding time and its prolongation by aspirin. Blood, 34: 204, 1969. 7. Macfarlane, D. E., Stibbe, J., Kirby, E. P., Zucker, M. B., Grant, R. A. and McPherson, J. A.: A method for assaying von Willebrand factor (ristocetin cofactor). Thromb. Diath. Haemorrh., 34: 306, 1975.
137
8. Laurel!, C. B.: Electroimmuno assay. Scand. J. Clin. Lab. Invest. (8124), 29: 21, 1972. 9. Mostofi, F. K., Vorder Bruegge, C. F. and Diggs, L. W.: Lesions in kidneys removed for unilateral hematuria in sickle cell disease. A.M.A. Arch. Path., 63: 336, 1957. 10. Hong, S. K., Boylan, J. W., Tannenberg, A. M. and Rahn, H.: Total and partial gas tensions of human bladder urine. J. Appl. Physiol., 15: 115, 1960. 11. Perillie, P. E. and Epstein, F. H.: Sickling phenomenon produced by hypertonic solution. Clin. Res., 9: 332, 1961. 12. Pardo, V., Strauss, J., Kramer, H., Ozawa, T. and McIntosh, R. W.: Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. II. Clinicopathologic study of seven patients. Amer. J. Med., 59: 650, 1975. 13. Legaz, M. E., Schmer, G., Counts, R. B. and Davie, E.W.: Isolation and characterization of human factor VIII (antihemophiliac factor). J. Biol. Chem., 248: 3946, 1973. 14. Weiss, H.J., Rogers, J. and Brand, H.: Defective ristocetin-induced platelet aggregation in von Willebrand's disease and its correction by factor VIII. J. Clin. Invest., 52: 2697, 1973. 15. Zimmerman, T. S., Ratnoff, 0. D. and Powell, A. E.: Immunologic differentiation of classic hemophilia (factor 8 deficiency) and von Willebrand's disease, with observations on combined deficiencies of antihemophilic factor and proaccelerin (factor V) and on an acquired circulating anticoagulant against antihernophilic factor. J. Clin. Invest., 50: 244, 1971. 16. Brockway, W. J. and Fass, D. N.: The nature of the interaction between ristocetin-Willebrand factor VIII coagulant activity molecule. J. Lab. Clin. Med., 89: 1295, 1977. 17. Veltkamp, J. J. and Tilburg, N. H., van: "Autosomal haemophilia": a variant of von Wille brand's disease. Brit. J. Haematol., 26: 141, 1974. 18. Gralnick, H. R., Coller, B. S. and Sultan, Y.: Studies of the human factor VIII/von Wille brand factor protein. III. Qualitative defects in von Willebrand's disease. J. Clin. Invest., 56: 814, 1975. 19. Sultan, Y., Simeon, J., Maisonneuve, P. and Caen, J. P.: Immunologic studies in von Willebrand's disease: alteration of factor VIII/von Willebrand protein after transfusion with plasma concentrates in patients with von Willebrand's disease. Thrornbos. Haemostas., 35: 110, 1976. 20. Marynick, S. P., Ramsey, E. J. and Knochel, J. P.: The effect of bicarbonate and distilled water on sickle cell trait hematuria and in vitro studies on the interaction of osmolality and pH on erythrocyte sickling in sickle cell trait. J. Urol., 118: 793, 1977. 21. Bilinsky, R. T., Kandel, G. L. and Rabiner, S. F.: Epsilon aminocaproic acid therapy of hematuria due to heterozygous sickle cell diseases. J. Uro!., 102: 93, 1969. 22. Vega, R., Shanberg, A. M. and Malloy, T. R.: The use of epsilon aminocaproic acid in sickle cell trait hernaturia. J. Urol., 105: 552, 1971. 23. Allen, T. D.: Sickle cell disease and hematuria: a report of 29 cases. J. Urol., 91: 177, 1964. EDITORIAL COMMENT Hematuria associated with sickle cell trait has constituted a therapeutic impasse characterized by treatments ranging from nephrectomy to silver nitrate infusions to furosemide to epsilon aminocaproic acid. Recognition of the bleeding dysplasia (van Willebrand's) as a contributing factor allows a specific therapeutic manipulation to correct the problem. The frequency of such a convergence is unknown since coagulation evaluation has not been part of the study of the sickle cell trait even when it has been complicated by bleeding. T.P.D.
THE
Vol. 122, July Printed in U.S.A.
JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
GROSS HEMATURIA ASSOCIATED WITH SICKLE CELL TRAIT AND VON WILLEBRAND'S DISEASE RONALD S. WEINGER, GEORGE S. BENSON
AND
SANTIAGO VILLARREAL
From the Department of Medicine, Division of Hematology, Department of Surgery, Division of Urology and the Gulf States Hemophilia Center, The University of Texas Medical School at Houston, Houston, Texas
ABSTRACT
A case of recurrent gross hematuria, sickle cell trait and von Wille brand's disease is reported. The gross hematuria abated promptly after the institution of cryoprecipitate therapy. The importance of considering von Willebrand's disease in the differential diagnosis in patients with sickle cell trait and hematuria is discussed. Gross hematuria is a well recognized occurrence in patients with sickle cell trait. 1- 3 In addition, Brody and associates recently reported the association among von Willebrand's disease, gross hematuria and sickle cell trait. 4 Herein we describe the detection of von Willebrand's disease in a young black woman with sickle cell trait and significant gross hematuria. The hematuria ceased within 24 hours after the institution of cryoprecipitate infusions. CASE REPORT
An 18-year-old black woman was hospitalized with gross painless hematuria 1 day in duration. She had experienced hematuria 4 times previously and the most recent episode had occurred 1 year ago. Cystoscopy at that time revealed no significant bladder or urethral pathology but blood was observed to be effluxing from the right ureteral orifice. The bleeding ceased after administration of 2 units of blood. The patient denied any other personal or family history of bleeding. During the current episode she was afebrile and normotensive. There was no costovertebral angle or abdominal tenderness. No abdominal masses or bruits were present. Laboratory evaluation included a normal prothrombin time, activated partial thromboplastin time, fibrinogen level, platelet count and complete blood count. The urine was grossly bloody and had a specific gravity of 1.011. Hemoglobin electrophoresis once again revealed hemoglobin AS. An excretory urogram demonstrated minimal blunting of the right upper pole calix and a small caliceal diverticulum in the upper pole of the left kidney. Despite intravenous fluid and diuretic therapy, the hematuria persisted until 10 days after hospitalization when studies that had been obtained on the third hospital day were completed and 6 units of cryoprecipitate were infused. The gross hematuria improved greatly within 9 hours. At 2 subsequent 12-hour intervals 4 units of cryoprecipitate were infused. Gross hematuria was not present after the second cryoprecipitate infusion. The patient was discharged 12 days after hospitalization completely asymptomatic. Family members were not available for study. MATERIALS AND METHODS
Blood was collected in plastic syringes and anticoagulated with 1/10 volume of 3.8 per cent sodium citrate. Platelet poor plasma was obtained by centrifuging blood for 20 minutes at 1,800 g, and either tested immediately or stored at -70C for subsequent assays. Standard techniques were used for measurement of activated partial thromboplastin time, prothromAccepted for publication October 27, 1978. Supported in part by a grant from the United States Public Health Service, No. MC-B-480001-01-0.
136
bin time, fibrinogen and 1-stage assays of factor VIII coagulant activity (FVIIhHG), 5• * Bleeding times were by template. 6 Ristocetin cofactor activity (FVIIIvwF) was measured using formalin-fixed platelets. 7 Factor VIII antigen (FVIIIAGN) was quantified in plasma by Laurell electroimmunoassay,8 using rabbit anti-human FVIII antibody.t RESULTS
The history of recurrent episodes of hematuria prompted a search for von Willebrand's disease. The patient had a bleeding time of 2 minutes (normal <8 minutes) 3 days after hospitalization. FVIIhHG was 0.67 U./ml. (normal 0.60 to 1.50 U./ml.), FVIIIAGN was 0.36 U./ml. (normal 0.60 to 1.50 U./ml.) and FVIIIvwF was 0.30 U./ml. (normal 0.60 to 1.50 U./ml.). The results oflaboratory studies done 10 days after hospitalization pertinent to von Willebrand's disease and those following the first infusion of cryoprecipitate are shown in the table. Of significance is the prolonged increase of FVIIhHG which followed transfusion. FVIIIvwF increased transiently but had returned almost to the pre-transfusion level 11 hours later. FVIIhGN remained within the normal range during that same post-transfusion period. DISCUSSION
Abel and Brown described hematuria in patients with sickle cell trait. 1 The mechanism(s) responsible for this phenomenon remains obscure but may be related to the environmental conditions in the renal medulla, which favor intravascular sickling.9-11 An alternate explanation, involving the development of immune complex nephritis, has been proposed recently by Pardo and associates in patients with sickle cell anemia. 12 The normal human von Willebrand factor is composed of disulfide-linked, 230,000 molecular weight subunits 13 and induces platelet agglutination in the presence of the antibiotic, ristocetin (FVIIIvwF) .14 Also, FVIIIvwF reacts with antisera to FVIII produced in animals (FVIIIAGN). 15 Additional subunits that possess FVIIIAHG are derived from an as yet unknown site and are attached to the circulating FVIIIvwF/FVIIIAGN molecules by non-covalent bonds. 16 von Willebrand's disease is a heterogeneous disorder that involves defects in the factor VIII molecular complex. Some patients have absent or reduced FVIIIvwF, FVIIhGN and FVIIIAHG activities. 14' 15 The bleeding time, although prolonged in the classical form of the disorder, may be normal. 17 In other patients a defect in FVIIIvwF is associated with normal FVIIhGN * Factor VIII-deficient plasma substrates, George King Biomedical, Inc., Salem, New Hampshire. t Behring Diagnostics, Sommerville, New Jersey.
GROSS HEMATURIA WITH SICKLE CELL TRAIT AND VON WILLEBRAND'S DISEASE
Laboratory results (10th hospital day)
Before infusion 1 hr. after infusion 11 brs. after infusion
FVII1AHG' (U./ml.)
FVIIlvWFt (U./ml.)
FVIIIAGN+ (U./ml.)
B.T.§ (min.)
0.29 0.67 0.87
0.12 0.28 0.18
0.39 1.01 0.85
2 Not done Not done
' Factor VIII coagulant activity, normal 0.60 to 1.50 U./ml.
t Ristocetin cofactor activity, normal 0.60 to 1.50 U./ml. :j: Factor VIII related antigen, normal 0.60 to 1.50 U./ml. § Template bleeding time, normal <8 minutes.
and FVIIhHG levels. 18 Our patient demonstrated variable but low levels of FVIIIAHG, FVIIlvwF and FVIIIAGN, Although the bleeding time was within the normal range she responded to cryoprecipitate infusions with the prolonged increase in FVIIIAHG characteristic of von Willebrand's disease. 19 Massive hematuria in sickle trait patients is often a difficult management problem. Therapy has included bed rest,2 hypotonic fluids in conjunction with alkalization of the urine, 20 epsilon aminocaproic acid, 21 • 22 renal pelvic lavage with silver nitrate 2:i and nephrectomy. 9 Our case and those reported previously4 suggest that when von •Nillebrand's disease coexists with sickle cell trait hematuria can be managed successfully with specific plasma product therapy. It is interesting to speculate that the coexistence of von Willebrand's disease with sickle trait accentuates the severity of clinical bleeding. Whether an increased incidence of von Wille brand's disease exists in individuals heterozygous for sickle hemoglobin is unknown. Of importance is that our patient and those of Brody and associates 4 had no additional personal or family bleeding history other than hematuria. This suggests that in patients with sickle cell trait who have protracted or severe bleeding episodes a search for von Willebrand's disease should be undertaken before more radical therapy (that is epsilon aminocaproic acid, silver nitrate lavage or nephrectomy) is instituted. REFERENCES
1. Abel, M. S. and Brown, C. R.: Sickle cell diseases with severe hematuria simulating renal neoplasm. J. A. M. A., 136: 624, 1948. 2. Lucas, W. M. and Bullock, W. H.: Hematuria in sickle cell disease. J. Urol., 83: 733, 1960. 3. Bennett, M. A., Heslop, R. W. and Meynell, M. J.: Massive haematuria associated with sickle-cell trait. Brit. Med. J., 1: 677, 1967. 4. Brody, J. I., Levison, S. P. and Jung, C. J.: Sickle cell trait and hematuria associated with von Willebrand syndromes. Ann. Intern. Med., 86: 529, 1977. 5. Bowie, E. J. W., Thompson, J. H., Jr., Owen, C. A., Jr. and Didisheim, P.: Mayo Clinic Laboratory Manual of Hemostasis. Philadelphia: W. B. Saunders Co., 1971. 6. Mielke, C. H., Kaneshiro, M. M., Maher, I. A., Weiner, J.M. and Rapaport, S. I.: The standardized normal Ivy bleeding time and its prolongation by aspirin. Blood, 34: 204, 1969. 7. Macfarlane, D. E., Stibbe, J., Kirby, E. P., Zucker, M. B., Grant, R. A. and McPherson, J. A.: A method for assaying von Willebrand factor (ristocetin cofactor). Thromb. Diath. Haemorrh., 34: 306, 1975.
137
8. Laurel!, C. B.: Electroimmuno assay. Scand. J. Clin. Lab. Invest. (8124), 29: 21, 1972. 9. Mostofi, F. K., Vorder Bruegge, C. F. and Diggs, L. W.: Lesions in kidneys removed for unilateral hematuria in sickle cell disease. A.M.A. Arch. Path., 63: 336, 1957. 10. Hong, S. K., Boylan, J. W., Tannenberg, A. M. and Rahn, H.: Total and partial gas tensions of human bladder urine. J. Appl. Physiol., 15: 115, 1960. 11. Perillie, P. E. and Epstein, F. H.: Sickling phenomenon produced by hypertonic solution. Clin. Res., 9: 332, 1961. 12. Pardo, V., Strauss, J., Kramer, H., Ozawa, T. and McIntosh, R. W.: Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. II. Clinicopathologic study of seven patients. Amer. J. Med., 59: 650, 1975. 13. Legaz, M. E., Schmer, G., Counts, R. B. and Davie, E.W.: Isolation and characterization of human factor VIII (antihemophiliac factor). J. Biol. Chem., 248: 3946, 1973. 14. Weiss, H.J., Rogers, J. and Brand, H.: Defective ristocetin-induced platelet aggregation in von Willebrand's disease and its correction by factor VIII. J. Clin. Invest., 52: 2697, 1973. 15. Zimmerman, T. S., Ratnoff, 0. D. and Powell, A. E.: Immunologic differentiation of classic hemophilia (factor 8 deficiency) and von Willebrand's disease, with observations on combined deficiencies of antihemophilic factor and proaccelerin (factor V) and on an acquired circulating anticoagulant against antihernophilic factor. J. Clin. Invest., 50: 244, 1971. 16. Brockway, W. J. and Fass, D. N.: The nature of the interaction between ristocetin-Willebrand factor VIII coagulant activity molecule. J. Lab. Clin. Med., 89: 1295, 1977. 17. Veltkamp, J. J. and Tilburg, N. H., van: "Autosomal haemophilia": a variant of von Wille brand's disease. Brit. J. Haematol., 26: 141, 1974. 18. Gralnick, H. R., Coller, B. S. and Sultan, Y.: Studies of the human factor VIII/von Wille brand factor protein. III. Qualitative defects in von Willebrand's disease. J. Clin. Invest., 56: 814, 1975. 19. Sultan, Y., Simeon, J., Maisonneuve, P. and Caen, J. P.: Immunologic studies in von Willebrand's disease: alteration of factor VIII/von Willebrand protein after transfusion with plasma concentrates in patients with von Willebrand's disease. Thrornbos. Haemostas., 35: 110, 1976. 20. Marynick, S. P., Ramsey, E. J. and Knochel, J. P.: The effect of bicarbonate and distilled water on sickle cell trait hematuria and in vitro studies on the interaction of osmolality and pH on erythrocyte sickling in sickle cell trait. J. Urol., 118: 793, 1977. 21. Bilinsky, R. T., Kandel, G. L. and Rabiner, S. F.: Epsilon aminocaproic acid therapy of hematuria due to heterozygous sickle cell diseases. J. Uro!., 102: 93, 1969. 22. Vega, R., Shanberg, A. M. and Malloy, T. R.: The use of epsilon aminocaproic acid in sickle cell trait hernaturia. J. Urol., 105: 552, 1971. 23. Allen, T. D.: Sickle cell disease and hematuria: a report of 29 cases. J. Urol., 91: 177, 1964. EDITORIAL COMMENT Hematuria associated with sickle cell trait has constituted a therapeutic impasse characterized by treatments ranging from nephrectomy to silver nitrate infusions to furosemide to epsilon aminocaproic acid. Recognition of the bleeding dysplasia (van Willebrand's) as a contributing factor allows a specific therapeutic manipulation to correct the problem. The frequency of such a convergence is unknown since coagulation evaluation has not been part of the study of the sickle cell trait even when it has been complicated by bleeding. T.P.D.