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fibrin fragments in uremia
THROMBOSIS RESEARCH 27; 625-626, 1982 0049-3838/82/170625-02$03.00/O Printed in the USA. Copyright (c) 1982 Pergamon Press Ltd. All rights reserved.
LETTER TO THE EDITORS-IN-CHIEF
FIBRINOGEN/FIBRIN FRAGMENTS IN UREMIA
Laurence A. Sherman Washington University School of Medicine St. Louis, Missouri 63110 (Received 13.5.1982; in revised form 6.7.1982. Accepted by Editor-in-Chief A.L. Copley) Kudryk et al in a recent paper (1) noted an increase in immunoreactive material in patients undergoing hemodialysis and postulated changes in heparin concentration as the cause of the phenomena. However, they appropriately noted the fact that predialysis levels in other patients were in the same range and prior data in the literature has shown that chronic kidney failure results in elevated levels of the usually measured fibrinogen/fibrin degradation products. An alternative explanation needs to be commented on, that is, of altered catabolism of degradation products. Some years ago we noted in experimental animal models that the clearance of both fragments D and E were substantially increased in either acute (2) or chronic renal failure (3). The changes were specifically related to a loss of functioning renal tissue rather than a change in excretion, in that ureteral obstruction had no effect, whereas surgical removal of part or all of the kidnesy substantially impaired blood clearance (3). It is worth commenting that we were unable in the same animal model (rabbit), used for the acute studies, to show any effect of subtotal hepatectomy or reticuloendothelial system blockade. We then concluded that elevated levels of fibrinogen/fibrin degradation products in the blood of patients with acute or chronic renal failure could not be interpreted as indicating a coagulopathy as being a cause or related to the renal disorder. Rather, that the elevated levels of fibrinogen/fibrin degradation products was, at least in part, a non-specific event as the result of removal of catabolically active tissues. Other serum proteins, such as beta microglobulin, have also been noted to be directly catabolized in the kidneys and are similarly elevated during renal failure. I With increasing use of immunoassays of various "markers" of coagulation processes it is important to consider potential changes in catabolism of the "marker" in disease states. Decreased catabolism can elevate blood levels as readily as increased generation of the marker. Unfortunately, our knowledge of specific organ systems involved in the catabolism of coagulation proteins is far from complete and many further studies will be necessary. Key-words: Uremia, fibrin fragments.
625
626
FIBRIN(OGEN) FRAGMENTS IN UREMIA
Vo1.27, No.5
REFERENCES KUDRYK, B., ROBINSON, D., NETRE, C., HESSEL, B., BLOMBACK, M.and BLAKBACK, B. Measurement in human blood of fibrinogen/fibrin fragments containing the BH 15-42 sequence. Thrombosis Research, 25, 277-291, 1982 2. HAYNE, O.A. and SHERMAN, L.A. The _in vivo behavior of fibrinogen fragment D in experimental renal, hepatic, and reticuloendothelial dysfunction. Am. J. Pathol., 71, 219-236, 1973. 3. 110, A., RUTHERFORD, E., WOCHNER, R.D., and SHERMAN, L.A. Catabolic and excretory role of the kidney in the metabolism of fibrinogen fragments D and E. J. Lab. Clin. Med., 87, 934-946, 1976.
1.
LETTER TO THE EDITORS-IN-CHIEF
FIBRINOGEN/FIBRIN FRAGMENTS IN UREMIA
Laurence A. Sherman Washington University School of Medicine St. Louis, Missouri 63110 (Received 13.5.1982; in revised form 6.7.1982. Accepted by Editor-in-Chief A.L. Copley) Kudryk et al in a recent paper (1) noted an increase in immunoreactive material in patients undergoing hemodialysis and postulated changes in heparin concentration as the cause of the phenomena. However, they appropriately noted the fact that predialysis levels in other patients were in the same range and prior data in the literature has shown that chronic kidney failure results in elevated levels of the usually measured fibrinogen/fibrin degradation products. An alternative explanation needs to be commented on, that is, of altered catabolism of degradation products. Some years ago we noted in experimental animal models that the clearance of both fragments D and E were substantially increased in either acute (2) or chronic renal failure (3). The changes were specifically related to a loss of functioning renal tissue rather than a change in excretion, in that ureteral obstruction had no effect, whereas surgical removal of part or all of the kidnesy substantially impaired blood clearance (3). It is worth commenting that we were unable in the same animal model (rabbit), used for the acute studies, to show any effect of subtotal hepatectomy or reticuloendothelial system blockade. We then concluded that elevated levels of fibrinogen/fibrin degradation products in the blood of patients with acute or chronic renal failure could not be interpreted as indicating a coagulopathy as being a cause or related to the renal disorder. Rather, that the elevated levels of fibrinogen/fibrin degradation products was, at least in part, a non-specific event as the result of removal of catabolically active tissues. Other serum proteins, such as beta microglobulin, have also been noted to be directly catabolized in the kidneys and are similarly elevated during renal failure. I With increasing use of immunoassays of various "markers" of coagulation processes it is important to consider potential changes in catabolism of the "marker" in disease states. Decreased catabolism can elevate blood levels as readily as increased generation of the marker. Unfortunately, our knowledge of specific organ systems involved in the catabolism of coagulation proteins is far from complete and many further studies will be necessary. Key-words: Uremia, fibrin fragments.
625
626
FIBRIN(OGEN) FRAGMENTS IN UREMIA
Vo1.27, No.5
REFERENCES KUDRYK, B., ROBINSON, D., NETRE, C., HESSEL, B., BLOMBACK, M.and BLAKBACK, B. Measurement in human blood of fibrinogen/fibrin fragments containing the BH 15-42 sequence. Thrombosis Research, 25, 277-291, 1982 2. HAYNE, O.A. and SHERMAN, L.A. The _in vivo behavior of fibrinogen fragment D in experimental renal, hepatic, and reticuloendothelial dysfunction. Am. J. Pathol., 71, 219-236, 1973. 3. 110, A., RUTHERFORD, E., WOCHNER, R.D., and SHERMAN, L.A. Catabolic and excretory role of the kidney in the metabolism of fibrinogen fragments D and E. J. Lab. Clin. Med., 87, 934-946, 1976.
1.