Mef Cammunicatian
Does sulphinpyrazone reduce haemolysis from prosthetic heart valves? Intravascular haemolysis is a recognised complication of prosthetic heart valves but is rarely severe enough to cause significant anaemia. Recommended treatment of the anaemia is iron and folate supplementation with blood transfusion in severe cases. Anaemias uncontrolled by such measures may necessitate either repair or replacement of the prosthesis. Other therapies have been used attempting to control the anaemia and avoid further cardiac surgery. Neither steroids nor splenectomy have been found to help. Sulphinpyrazone has also been tried.’.’ We report the outcome of using sulphinpyrazone in four patients with haemolytic anaemia arising from prosthetic valve dysfunction. Four patients with haemolytic anaemia arising from prosthetic valve regurgitation were studied. Their clinical details are given in Table 1. Haemodynamic data were obtained by echocardiography alone in Patient 2 and in conjunction with cardiac catheterisation in Patients 1,3 and 4. Severity ofleak is graded according to accepted ~riteria.~ Patient 1 had a longstanding stable paraprosthetic leak, Patient 2 had a recently discovered stable paraprosthetic leak, Patients 3 and 4 had new prosthetic leaks. Intravascular haemolytic anaemia was confirmed by low haemoglobin and serum haptoglobins, elevated lactic dehydrogenase (urea stable LDH) and methaemalbumin, with detectable red cell fragments and urine haemosiderin. Testing for autoimmune haemolysis including Coomb’s tests were negative. Iron and folate deficiencies were excluded. No biochemical evidence of renal or hepatic dysfunction was found. Sulphinpyrazone was given at 400 mg daily for two weeks, 600 mg daily for four weeks then 800 mg daily
for eight weeks in Patients 1, 2 and 3. Patient 4 was started at 800 mg daily. Baseline haemolysis was quantified twice before drug treatment commenced, eight weeks apart in Patients 1, 2 and 3 and three weeks apart in Patient 4. The measurements of Hb and LDH before and after sulphinpyrazone are given in Figure 1. At the initiation of the drug all patients had significant haemolytic anaemia with Hb 9.0 to 9.6 gldL and LDH elevated six to ten times normal. During drug treatment only Patient 3 showed a fall in LDH but this was not associated with a significant rise in haemoglobin count. In the other patients the LDH and Hb remained static or, especially in Patient 4, deteriorated. This patient had worsening haemolytic anaemia requiring multiple blood transfusions such that urgent mitral prosthetic valve replacement was undertaken after three weeks of sulphinpyrazone. There was no objective improvement in cardiac function or subjective symptomatic improvement in any patient with the drug. We evaluated the effect of sulphinpyrazone on the haemolytic anaemia arising from various types of bioprosthetic valve dysfunction in four patients. These patients were typical of those which it is claimed have most to benefit from sulphinpyrazone.1,2No significant improvement was observed in any patient. One of the patients with severe haemolysis from a prosthetic cusp rupture required urgent prosthetic valve replacement despite being on s~lphinpyrazone.~ Improvements in haemolytic anaemia have been described in five cases with mechanical prosthetic valves during sulphinpyrazone.’,’ We studied bioprostheses to broaden the experience with the drug. There is no reason to suggest that haemolysis arising
TABLE 1 Patients with Haemolytic Anaemia Resultant from Prosthetic Valve Regurgitation
Sex
Age
Valve
Position
F F
3 4
M F
78 77 71
W W I-s
M
2
A A
55
H
M
Patient
1
Age prosthesis at onset leak (months)
Duration leak before drug (months)
Leak severity (grade)
1
24
1 72 108
5
2 2 3 3
2 1
W = Wessex; I-S= lonescu-Shiley;H = Hancock; M = Mitral; A =Aortic. Gnrespondence to: Dr M. Errington, Registrar, Department of Medical Radiology, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW Scotland.
382
Aust NZ J Med 1992; 22
ERRINGTON AND BLOOMFIELD
improves when recognised and avoided.6 Third, concomitant medical conditions which may cause haemolytic anaemia must be excluded. In two of the reported cases markedly elevated levels of serum glutamic oxaloacetic transaminase were unexplained despite liver disease being a recognised cause of haemolytic anaemia. Having selected our patients to avoid these possibilities we saw no resolution of the anaemias. In conclusion, we found no evidence to recommend the use of sulphinpyrazone in the treatment of haemolytic anaemia arising from bioprosthetic valve dyshnction. We recommend that the medical management of such patients remains iron and folate supplementation, blood transfusion when necessary and carehl exclusion of contributory causes of anaemia.
3wo
ZDW
1O
W
0
1
2
3
M. ERRINGTON, Registrar, Department of Medical Radiology, P. BLOOMFIELD, Consultant, Department of Cardiology, Royal Infirmary, Lauriston Place, Edinburgh, Scotland.
4
Patlenti
Figure 1: Results of LDH and Hb for each patient before and after Sulphinpyrazone Treatment.
from mechanical or bioprosthetic valves, whether competent or not, is other than through turbulent trauma to erythrocytes. Had sulphinpyrazone beneficially altered erythrocyte deformability to reduce such trauma, which has been claimed,2 we would expect to have detected it. For several reasons caution must be exercised before concluding that an improvement in haemolytic anaemia in the previously reported patients was due to sulphinpyrazone. First, spontaneous resolution of such haemolytic anaemia without drug treatment has been documented and has been attributed to endothelialisation of foreign material.5Second, haemolysis in patients with prosthetic valve dyshnction does not always arise from mechanical trauma. Unusual blood group incompatibility may cause profound haemolytic anaemia following valve surgery which
SULPHINPYRAZONE AND HAEMOLYTIC ANAEMIA
Date of submission: 27 January 1992
References 1. WoodruffRK, Goble AJ. Control of cardiac valve related haemclytic anaemia by sulphinpyrazone. Aust NZ J Med 1985; 15: 645-6. 2. Owen J, Seidenfeld AM, Glynn MFX. Amelioration of cardiac haemolytic anaemia by sulphinpyrazone therapy. Can Med Assoc J 1980; 122: 5546. 3. Miller GAH. Invasive investigation of the heart: valvar heart disease. 1st edition. Oxford, UK: Blackwell Scientific Publications, 1989; 269-92. 4. Bloomfield P, Wheatley DJ, Prescott RJ, Miller HC. Twelve year comparison of a Bjork Shiley mechanical heart valve with porcine bioprostheses. N Engl J Med 1991; 324: 573-9. 5. Myers TJ, Hild DH, Rinaldi MJ. Haemolytic anaemia associated with heterograft replacement of the mitral valve. J Thorac Cardiovasc Surg 1978; 76: 214-5. 6. Feld H, Roth J. Severe haemolytic anaemia after replacement of the mitral valve by a St Jude medical prosthesis. Br Heart J 1989; 62: 475-6.
Aust NZ J Med 1992; 22
383
Does sulphinpyrazone reduce haemolysis from prosthetic heart valves? Intravascular haemolysis is a recognised complication of prosthetic heart valves but is rarely severe enough to cause significant anaemia. Recommended treatment of the anaemia is iron and folate supplementation with blood transfusion in severe cases. Anaemias uncontrolled by such measures may necessitate either repair or replacement of the prosthesis. Other therapies have been used attempting to control the anaemia and avoid further cardiac surgery. Neither steroids nor splenectomy have been found to help. Sulphinpyrazone has also been tried.’.’ We report the outcome of using sulphinpyrazone in four patients with haemolytic anaemia arising from prosthetic valve dysfunction. Four patients with haemolytic anaemia arising from prosthetic valve regurgitation were studied. Their clinical details are given in Table 1. Haemodynamic data were obtained by echocardiography alone in Patient 2 and in conjunction with cardiac catheterisation in Patients 1,3 and 4. Severity ofleak is graded according to accepted ~riteria.~ Patient 1 had a longstanding stable paraprosthetic leak, Patient 2 had a recently discovered stable paraprosthetic leak, Patients 3 and 4 had new prosthetic leaks. Intravascular haemolytic anaemia was confirmed by low haemoglobin and serum haptoglobins, elevated lactic dehydrogenase (urea stable LDH) and methaemalbumin, with detectable red cell fragments and urine haemosiderin. Testing for autoimmune haemolysis including Coomb’s tests were negative. Iron and folate deficiencies were excluded. No biochemical evidence of renal or hepatic dysfunction was found. Sulphinpyrazone was given at 400 mg daily for two weeks, 600 mg daily for four weeks then 800 mg daily
for eight weeks in Patients 1, 2 and 3. Patient 4 was started at 800 mg daily. Baseline haemolysis was quantified twice before drug treatment commenced, eight weeks apart in Patients 1, 2 and 3 and three weeks apart in Patient 4. The measurements of Hb and LDH before and after sulphinpyrazone are given in Figure 1. At the initiation of the drug all patients had significant haemolytic anaemia with Hb 9.0 to 9.6 gldL and LDH elevated six to ten times normal. During drug treatment only Patient 3 showed a fall in LDH but this was not associated with a significant rise in haemoglobin count. In the other patients the LDH and Hb remained static or, especially in Patient 4, deteriorated. This patient had worsening haemolytic anaemia requiring multiple blood transfusions such that urgent mitral prosthetic valve replacement was undertaken after three weeks of sulphinpyrazone. There was no objective improvement in cardiac function or subjective symptomatic improvement in any patient with the drug. We evaluated the effect of sulphinpyrazone on the haemolytic anaemia arising from various types of bioprosthetic valve dysfunction in four patients. These patients were typical of those which it is claimed have most to benefit from sulphinpyrazone.1,2No significant improvement was observed in any patient. One of the patients with severe haemolysis from a prosthetic cusp rupture required urgent prosthetic valve replacement despite being on s~lphinpyrazone.~ Improvements in haemolytic anaemia have been described in five cases with mechanical prosthetic valves during sulphinpyrazone.’,’ We studied bioprostheses to broaden the experience with the drug. There is no reason to suggest that haemolysis arising
TABLE 1 Patients with Haemolytic Anaemia Resultant from Prosthetic Valve Regurgitation
Sex
Age
Valve
Position
F F
3 4
M F
78 77 71
W W I-s
M
2
A A
55
H
M
Patient
1
Age prosthesis at onset leak (months)
Duration leak before drug (months)
Leak severity (grade)
1
24
1 72 108
5
2 2 3 3
2 1
W = Wessex; I-S= lonescu-Shiley;H = Hancock; M = Mitral; A =Aortic. Gnrespondence to: Dr M. Errington, Registrar, Department of Medical Radiology, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW Scotland.
382
Aust NZ J Med 1992; 22
ERRINGTON AND BLOOMFIELD
improves when recognised and avoided.6 Third, concomitant medical conditions which may cause haemolytic anaemia must be excluded. In two of the reported cases markedly elevated levels of serum glutamic oxaloacetic transaminase were unexplained despite liver disease being a recognised cause of haemolytic anaemia. Having selected our patients to avoid these possibilities we saw no resolution of the anaemias. In conclusion, we found no evidence to recommend the use of sulphinpyrazone in the treatment of haemolytic anaemia arising from bioprosthetic valve dyshnction. We recommend that the medical management of such patients remains iron and folate supplementation, blood transfusion when necessary and carehl exclusion of contributory causes of anaemia.
3wo
ZDW
1O
W
0
1
2
3
M. ERRINGTON, Registrar, Department of Medical Radiology, P. BLOOMFIELD, Consultant, Department of Cardiology, Royal Infirmary, Lauriston Place, Edinburgh, Scotland.
4
Patlenti
Figure 1: Results of LDH and Hb for each patient before and after Sulphinpyrazone Treatment.
from mechanical or bioprosthetic valves, whether competent or not, is other than through turbulent trauma to erythrocytes. Had sulphinpyrazone beneficially altered erythrocyte deformability to reduce such trauma, which has been claimed,2 we would expect to have detected it. For several reasons caution must be exercised before concluding that an improvement in haemolytic anaemia in the previously reported patients was due to sulphinpyrazone. First, spontaneous resolution of such haemolytic anaemia without drug treatment has been documented and has been attributed to endothelialisation of foreign material.5Second, haemolysis in patients with prosthetic valve dyshnction does not always arise from mechanical trauma. Unusual blood group incompatibility may cause profound haemolytic anaemia following valve surgery which
SULPHINPYRAZONE AND HAEMOLYTIC ANAEMIA
Date of submission: 27 January 1992
References 1. WoodruffRK, Goble AJ. Control of cardiac valve related haemclytic anaemia by sulphinpyrazone. Aust NZ J Med 1985; 15: 645-6. 2. Owen J, Seidenfeld AM, Glynn MFX. Amelioration of cardiac haemolytic anaemia by sulphinpyrazone therapy. Can Med Assoc J 1980; 122: 5546. 3. Miller GAH. Invasive investigation of the heart: valvar heart disease. 1st edition. Oxford, UK: Blackwell Scientific Publications, 1989; 269-92. 4. Bloomfield P, Wheatley DJ, Prescott RJ, Miller HC. Twelve year comparison of a Bjork Shiley mechanical heart valve with porcine bioprostheses. N Engl J Med 1991; 324: 573-9. 5. Myers TJ, Hild DH, Rinaldi MJ. Haemolytic anaemia associated with heterograft replacement of the mitral valve. J Thorac Cardiovasc Surg 1978; 76: 214-5. 6. Feld H, Roth J. Severe haemolytic anaemia after replacement of the mitral valve by a St Jude medical prosthesis. Br Heart J 1989; 62: 475-6.
Aust NZ J Med 1992; 22
383
