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Aspirin-Induced Bilateral Renal Hemorrhage After Extracorporeal Shock Wave Lithotripsy Therapy: Implications and Conclusions
0022-534 '7 /90 /1434-0/S l $02.00/0 THE JOLJRNAL OF UROLOG'/
Copyright
143, Printed in
1990 by AMERICAN UROLOGICAL ASSOCIATION, lNC.
ASPIRIN-INDUCED BILAT~RAL RENAL HEMORRHAGE AFTER EXTRACORPOREAL SHOCK WA VE LITHOTRIPSY THERAPY: IMPLICATIONS AND CONCLUSIONS HENRY RUIZ
BRIAN SALTZMAN*
AND
From the Department of Urology, Mount Sinai Medical Center, New York, New York
ABSTRACT
We report a case of bilateral intrarenal, subcapsular and perirenal hematomas after extracorporeal shock wave lithotripsy. Following treatment chest pain developed necessitating monitoring in the intensive care unit and cardiac evaluation. Serial hematocrit levels during the next 2 days revealed a decrease from 48 to 23%, requiring multiple transfusions. After therapy it was recognized that the patient had taken aspirin on a daily basis within 1 week before lithotripsy. We postulate that the aspirin ingestions acted as a potential predisposing factor in the formation of the bilateral renal hematoma. (J. Ural., 143: 791-792, 1990) Extracorporeal shock wave lithotripsy (ESWL t) rapidly is becoming the treatment of choice for renal and proximal ureteral calculi. Its wide acceptance stems from the effectiveness and low complication rate. Most complications are related to obstruction from stone fragments lodged within the ureter, with accompanying colic and/or infection. Significant hemorrhage has been documented sporadically in the literature.'· 2 The most common signs and symptoms include severe flank pain, a decrease in hematocrit and, rarely, the development of a Gray-Turner sign. Hematuria after ESWL is not a reliable indication of parenchymal hemorrhage, since most patients who undergo ESWL experience hematuria. CASE REPORT
M. D., a 65-year-old white man, had a long history of nephrolithiasis and spontaneous passage of calculi. Diagnostic evaluation for flank pain elsewhere revealed bilateral nonobstructing caliceal stones. The patient was referred to our institution for ESWL. A preoperative review of systems elicited no personal or family history of bleeding abnormalities. All preoper-ative parameters, including chemistry studies, prothrombin time, partial thromboplastin time, template bleeding time and platelet count, were normal. The patient had been taking aspirin and was advised to stop 2 weeks before ESWL, A total of 2,400 shock waves at 20 kv. was administered bilaterally with the Dornier HM3 lithotriptor. Postoperative chest pain necessitated monitoring in the intensive care unit and cardiac evaluation, Serial hematocrit levels during the next 2 days revealed a decrease from 48 to 23% (normal 42 to The patient received 2 units of packed red blood cells and large flank ecchymosis eventually developed. The hematocrit stabilized at 30%. After postoperative day 2 the gross hematuria resolved. A computerized tomography (CT) scan revealed large bilateral intrarenal, subcapsular and perirenal hematomas (see figure). The patient continued to improve and was discharged from the hospital in stable condition 10 days after treatment. He has been asymptomatic since then. An excretory urogram 3 months later showed small 1 to 2 mm. stone fragments bilaterally without any obstruction, with incomplete resolution of the bilateral hematoma. DISCUSSION
The activity of aspirin is mediated by its irreversible inhibition of platelet function by acetylating the active site of the Accepted for publication October 13, 1989. * Current address: Division of Urology, Beth Israel Hospital, 330 Brookline Ave., Boston, Massachusetts 02215. t Dornier Medical Systems, Inc., Marietta, Georgia.
791
platelet enzyme cyclo-oxygenase. 3 Inactivation of this enzyme prevents the formation of cyclic endoperoxides and thromboxane A2 necessary for the platelet release reaction. 4 The acetylation reaction is irreversible and affects function of the platelets abnormally for the duration of their life-span. Platelet halflife, normally 5 to 7 days, is unchanged in patients undergoing aspirin therapy. 5 Thus, patients who have taken aspirin within 7 days of the operation have impaired hemostasis with an increased liability to bleeding postoperatively. Discontinuation of aspirin therapy more than 7 days preoperatively may provide patients with the ability to produce enough functional platelets so that hemostatic activity is normalized." Some studies have found that aspirin causes increased perioperative blood loss, while others have found that it does not. 7 Amrein and associates found that aspirin caused a slight increase in perioperative blood loss, approximately 400 ml., which they concluded was not of great clinical importance. 8 Rubin found that a history of aspirin ingestion within 1 week preoperatively was predictive of increased postoperative blood loss. 9 However, it also was noted that abnormal platelet function did not predict or correlate with increased bleeding, The template bleeding time commonly is used to evaluate the in vivo physiological function of platelets, and to assess the selectivity of aspirin on platelets and vessel wall cyclo-oxygenase.8 Its use to predict postoperative blood loss remains controversial. Three recent studies could find no correlation between prolonged bleeding times induced by aspirin and increased operative blood loss. 9 · 11 Others have found that a prolonged bleeding time preoperatively was predictive of increased postoperative blood loss. 12 Thus, a normal bleeding time after aspirin therapy in no way guarantees normal platelet function. However, an abnormal bleeding time apparently does not reliably indicate ineffective perioperative hemostasis after aspirin therapy. The recent report of the United States Cooperative Study of ESWL recommended that ESWL not be performed unless patients are in a normal clotting state and have ceased taking aspirin for at least 2 weeks before treatment. 1 We observe this recommendation and routinely advise our patients to discon tinue the use of aspirin 2 weeks before therapy. It was only upon intense questioning that the patient admitted to taking aspirin within 1 week of treatment. Interestingly, in this situation all coagulation and hematological parameters, including prothrombin time, partial thromboplastin time, platelet count and template bleeding time, were normal. Therefore, we recommend that more specific platelet function studies with aden osine diphosphate, epinephrine, collagen and ristocetin be im-
792
RUIZ AND SALTZMAN
normalities that would preclude safe treatment. Of primary importance is the recognition that these tests do have diagnostic limitation in their sensitivity and even patients with normal values may be at risk for a parenchymal hematoma. The only method to exclude the possibility of an aspirin-induced coagulopathic condition remains waiting 14 days so that a normal number of platelets can be generated. REFERENCES
CT scan reveals bilateral subcapsular hematoma
plemented to evaluate platelet function further in patients with a history of recent aspirin ingestion. Our case demonstrates the great difficulties that currently exist in determining the status of aspirin-induced platelet dysfunction preoperatively. It also raises the issue as to whether aspirin-induced platelet dysfunction is of major hemostatic importance. The need for further investigation is clear, since the list of drugs that affect platelet function and bleeding time is extensive (dipyridamole, propanolol, nitroglycerin, calcium channel blockers, nonsteroidal anti-inflammatory agents, antibiotics and halothane) .13 It is clear that certain patients undergoing ESWL will have parenchymal hematoma. To date there is no effective means to predict which patients will have symptomatic bleeding. However, patients with known coagulopathic conditions or those who ingest medications that are recognized to interfere with normal coagulation are at high risk for this morbidity. Our case documents the importance of elucidating, during the preoperative assessment, patients who have been consuming aspirin or aspirin-like medications. This subgroup of patients should undergo appropriate hematological evaluation to elucidate ab-
1. Papanicolaou, N., Stafford, 8. A., Pfister, R. C., Althausen, A. F, and Dretler, 8. P.: Significant renal hemorrhage following extracorporeal shock wave lithotripsy: imaging and clinical features. Radiology, 163: 661, 1987. 2. Baumgartner, B. R., Dickey K. W., Ambrose, 8. 8., Walton, K. N., Nelson, R. C. and Bernardino, M. E.: Kidney changes after extracorporeal shock wave lithotripsy: appearance on MR imaging. Radiology, 163: 531, 1987. 3. Roth, G. J., Stanford, N. and Majerus, P. W.: Acetylation of prostaglandin synthetase by aspirin. Proc. Natl. Acad. Sci., 72: 3073, 1975. 4. Needleman, P., Minkes, M. and Raz, A.: Thromboxanes: selective biosynthesis and distinct biological properties. Science, 193: 163, 1976. 5. Torosian, M., Michelson, E. L., Morganroth, J. and MacVaugh, H., III: Aspirin- and coumadin-related bleeding after coronaryartery bypass graft surgery. Ann. Intern. Med., 89: 325, 1978. 6. Aster, R. H., and Jandl, J. H.: Platelet sequestration in man. I. Methods. J. Clin. Invest., 43: 843, 1964. 7. Kennedy, B. M.: Aspirin and surgery: a review. Irish Med. J., 77: 363, 1984. 8. Amrein, P. C., Ellman, L. and Harris, W. H.: Aspirin-induced prolongation of bleeding time and perioperative blood loss. J.A.M.A., 245: 1825, 1981. 9. Rubin, R. N.: Aspirin and postsurgery bleeding. Ann. Intern. Med., 89: 1006, 1978. 10. Ferraris, V. A. and Swanson, E.: Aspirin usage and perioperative blood loss in patients undergoing unexpected operations. Surg., Gynec. & Obst., 156: 439, 1983. 11. Ramsey, G., Arvan, D. A., Steward, 8. and Blumberg, N.: Do preoperative laboratory tests predict blood transfusion needs in cardiac operations? J. Thorac. Cardiovasc. Surg., 85: 564, 1983. 12. Bick, R. L.: Alterations of hemostasis associated with cardiopulmonary bypass: pathophysiology, prevention, diagnosis, and management. Sem. Thromb. Hemostas., 3: 59, 1976. 13. Hindman, B. J. and Koka, V. B.: Usefulness of the post-aspirin bleeding time. Anesthesiology, 64: 368, 1986.
Copyright
143, Printed in
1990 by AMERICAN UROLOGICAL ASSOCIATION, lNC.
ASPIRIN-INDUCED BILAT~RAL RENAL HEMORRHAGE AFTER EXTRACORPOREAL SHOCK WA VE LITHOTRIPSY THERAPY: IMPLICATIONS AND CONCLUSIONS HENRY RUIZ
BRIAN SALTZMAN*
AND
From the Department of Urology, Mount Sinai Medical Center, New York, New York
ABSTRACT
We report a case of bilateral intrarenal, subcapsular and perirenal hematomas after extracorporeal shock wave lithotripsy. Following treatment chest pain developed necessitating monitoring in the intensive care unit and cardiac evaluation. Serial hematocrit levels during the next 2 days revealed a decrease from 48 to 23%, requiring multiple transfusions. After therapy it was recognized that the patient had taken aspirin on a daily basis within 1 week before lithotripsy. We postulate that the aspirin ingestions acted as a potential predisposing factor in the formation of the bilateral renal hematoma. (J. Ural., 143: 791-792, 1990) Extracorporeal shock wave lithotripsy (ESWL t) rapidly is becoming the treatment of choice for renal and proximal ureteral calculi. Its wide acceptance stems from the effectiveness and low complication rate. Most complications are related to obstruction from stone fragments lodged within the ureter, with accompanying colic and/or infection. Significant hemorrhage has been documented sporadically in the literature.'· 2 The most common signs and symptoms include severe flank pain, a decrease in hematocrit and, rarely, the development of a Gray-Turner sign. Hematuria after ESWL is not a reliable indication of parenchymal hemorrhage, since most patients who undergo ESWL experience hematuria. CASE REPORT
M. D., a 65-year-old white man, had a long history of nephrolithiasis and spontaneous passage of calculi. Diagnostic evaluation for flank pain elsewhere revealed bilateral nonobstructing caliceal stones. The patient was referred to our institution for ESWL. A preoperative review of systems elicited no personal or family history of bleeding abnormalities. All preoper-ative parameters, including chemistry studies, prothrombin time, partial thromboplastin time, template bleeding time and platelet count, were normal. The patient had been taking aspirin and was advised to stop 2 weeks before ESWL, A total of 2,400 shock waves at 20 kv. was administered bilaterally with the Dornier HM3 lithotriptor. Postoperative chest pain necessitated monitoring in the intensive care unit and cardiac evaluation, Serial hematocrit levels during the next 2 days revealed a decrease from 48 to 23% (normal 42 to The patient received 2 units of packed red blood cells and large flank ecchymosis eventually developed. The hematocrit stabilized at 30%. After postoperative day 2 the gross hematuria resolved. A computerized tomography (CT) scan revealed large bilateral intrarenal, subcapsular and perirenal hematomas (see figure). The patient continued to improve and was discharged from the hospital in stable condition 10 days after treatment. He has been asymptomatic since then. An excretory urogram 3 months later showed small 1 to 2 mm. stone fragments bilaterally without any obstruction, with incomplete resolution of the bilateral hematoma. DISCUSSION
The activity of aspirin is mediated by its irreversible inhibition of platelet function by acetylating the active site of the Accepted for publication October 13, 1989. * Current address: Division of Urology, Beth Israel Hospital, 330 Brookline Ave., Boston, Massachusetts 02215. t Dornier Medical Systems, Inc., Marietta, Georgia.
791
platelet enzyme cyclo-oxygenase. 3 Inactivation of this enzyme prevents the formation of cyclic endoperoxides and thromboxane A2 necessary for the platelet release reaction. 4 The acetylation reaction is irreversible and affects function of the platelets abnormally for the duration of their life-span. Platelet halflife, normally 5 to 7 days, is unchanged in patients undergoing aspirin therapy. 5 Thus, patients who have taken aspirin within 7 days of the operation have impaired hemostasis with an increased liability to bleeding postoperatively. Discontinuation of aspirin therapy more than 7 days preoperatively may provide patients with the ability to produce enough functional platelets so that hemostatic activity is normalized." Some studies have found that aspirin causes increased perioperative blood loss, while others have found that it does not. 7 Amrein and associates found that aspirin caused a slight increase in perioperative blood loss, approximately 400 ml., which they concluded was not of great clinical importance. 8 Rubin found that a history of aspirin ingestion within 1 week preoperatively was predictive of increased postoperative blood loss. 9 However, it also was noted that abnormal platelet function did not predict or correlate with increased bleeding, The template bleeding time commonly is used to evaluate the in vivo physiological function of platelets, and to assess the selectivity of aspirin on platelets and vessel wall cyclo-oxygenase.8 Its use to predict postoperative blood loss remains controversial. Three recent studies could find no correlation between prolonged bleeding times induced by aspirin and increased operative blood loss. 9 · 11 Others have found that a prolonged bleeding time preoperatively was predictive of increased postoperative blood loss. 12 Thus, a normal bleeding time after aspirin therapy in no way guarantees normal platelet function. However, an abnormal bleeding time apparently does not reliably indicate ineffective perioperative hemostasis after aspirin therapy. The recent report of the United States Cooperative Study of ESWL recommended that ESWL not be performed unless patients are in a normal clotting state and have ceased taking aspirin for at least 2 weeks before treatment. 1 We observe this recommendation and routinely advise our patients to discon tinue the use of aspirin 2 weeks before therapy. It was only upon intense questioning that the patient admitted to taking aspirin within 1 week of treatment. Interestingly, in this situation all coagulation and hematological parameters, including prothrombin time, partial thromboplastin time, platelet count and template bleeding time, were normal. Therefore, we recommend that more specific platelet function studies with aden osine diphosphate, epinephrine, collagen and ristocetin be im-
792
RUIZ AND SALTZMAN
normalities that would preclude safe treatment. Of primary importance is the recognition that these tests do have diagnostic limitation in their sensitivity and even patients with normal values may be at risk for a parenchymal hematoma. The only method to exclude the possibility of an aspirin-induced coagulopathic condition remains waiting 14 days so that a normal number of platelets can be generated. REFERENCES
CT scan reveals bilateral subcapsular hematoma
plemented to evaluate platelet function further in patients with a history of recent aspirin ingestion. Our case demonstrates the great difficulties that currently exist in determining the status of aspirin-induced platelet dysfunction preoperatively. It also raises the issue as to whether aspirin-induced platelet dysfunction is of major hemostatic importance. The need for further investigation is clear, since the list of drugs that affect platelet function and bleeding time is extensive (dipyridamole, propanolol, nitroglycerin, calcium channel blockers, nonsteroidal anti-inflammatory agents, antibiotics and halothane) .13 It is clear that certain patients undergoing ESWL will have parenchymal hematoma. To date there is no effective means to predict which patients will have symptomatic bleeding. However, patients with known coagulopathic conditions or those who ingest medications that are recognized to interfere with normal coagulation are at high risk for this morbidity. Our case documents the importance of elucidating, during the preoperative assessment, patients who have been consuming aspirin or aspirin-like medications. This subgroup of patients should undergo appropriate hematological evaluation to elucidate ab-
1. Papanicolaou, N., Stafford, 8. A., Pfister, R. C., Althausen, A. F, and Dretler, 8. P.: Significant renal hemorrhage following extracorporeal shock wave lithotripsy: imaging and clinical features. Radiology, 163: 661, 1987. 2. Baumgartner, B. R., Dickey K. W., Ambrose, 8. 8., Walton, K. N., Nelson, R. C. and Bernardino, M. E.: Kidney changes after extracorporeal shock wave lithotripsy: appearance on MR imaging. Radiology, 163: 531, 1987. 3. Roth, G. J., Stanford, N. and Majerus, P. W.: Acetylation of prostaglandin synthetase by aspirin. Proc. Natl. Acad. Sci., 72: 3073, 1975. 4. Needleman, P., Minkes, M. and Raz, A.: Thromboxanes: selective biosynthesis and distinct biological properties. Science, 193: 163, 1976. 5. Torosian, M., Michelson, E. L., Morganroth, J. and MacVaugh, H., III: Aspirin- and coumadin-related bleeding after coronaryartery bypass graft surgery. Ann. Intern. Med., 89: 325, 1978. 6. Aster, R. H., and Jandl, J. H.: Platelet sequestration in man. I. Methods. J. Clin. Invest., 43: 843, 1964. 7. Kennedy, B. M.: Aspirin and surgery: a review. Irish Med. J., 77: 363, 1984. 8. Amrein, P. C., Ellman, L. and Harris, W. H.: Aspirin-induced prolongation of bleeding time and perioperative blood loss. J.A.M.A., 245: 1825, 1981. 9. Rubin, R. N.: Aspirin and postsurgery bleeding. Ann. Intern. Med., 89: 1006, 1978. 10. Ferraris, V. A. and Swanson, E.: Aspirin usage and perioperative blood loss in patients undergoing unexpected operations. Surg., Gynec. & Obst., 156: 439, 1983. 11. Ramsey, G., Arvan, D. A., Steward, 8. and Blumberg, N.: Do preoperative laboratory tests predict blood transfusion needs in cardiac operations? J. Thorac. Cardiovasc. Surg., 85: 564, 1983. 12. Bick, R. L.: Alterations of hemostasis associated with cardiopulmonary bypass: pathophysiology, prevention, diagnosis, and management. Sem. Thromb. Hemostas., 3: 59, 1976. 13. Hindman, B. J. and Koka, V. B.: Usefulness of the post-aspirin bleeding time. Anesthesiology, 64: 368, 1986.