Ann Hematol (2015) 94:1755–1756 DOI 10.1007/s00277-015-2432-x
LETTER TO THE EDITOR
Renal siderosis and serum ferritin Prasad R. Koduri 1 & Sashidhar Kaza 2
Received: 28 May 2015 / Accepted: 11 June 2015 / Published online: 20 June 2015 # Springer-Verlag Berlin Heidelberg 2015
Dear Editor, Patients with chronic intravascular hemolysis may develop persistent hemosiderinuria and renal siderosis [1]. Renal iron deposits have very slow turnover and are unavailable for erythropoiesis [1, 2]. Iron deficiency can develop pari passu with renal siderosis in patients with chronic intravascular hemolysis [1]; data on serum ferritin values in such patients is sparse [3–6]. We report the case of a patient who developed mitral regurgitation with intravascular hemolysis following mitral valve repair for myxomatous mitral valve disease. He was found to have renal siderosis and iron deficiency anemia. His serum ferritin was 13 ng/mL. The low serum ferritin value, despite renal siderosis, suggests that serum ferritin may not reflect the Bsequestered^ stores of iron in the kidneys. Case: A 67-year-old man presented with shortness of breath on exertion of 4-week duration. He had undergone mitral valve repair 4 years previously for myxomatous mitral valve disease. He appeared pale and had a grade 3/6 holosystolic murmur at the cardiac apex. His Hb was 8.9 g/dL and reticulocytes 1.2 %. Blood smear examination showed anisocytosis, anisochromia, and fragmented red cells (Fig. 1). The serum ferritin was 13 ng/mL, total serum bilirubin 1.8 mg/dL, direct bilirubin 0.2 mg/dL, and lactate dehydrogenase 1200 U/L. Urine sediment was strongly positive for hemosiderin. The direct Coombs’ test result was negative. Stool was repeatedly
negative for occult blood. Esophagogastroduodenoscopy and colonoscopy showed normal findings. Transthoracic echocardiography showed severe mitral regurgitation with an eccentric jet. Magnetic resonance imaging showed symmetric diffusely reduced signal intensity of the renal cortices on both T1- and T2-weighted sequences diagnostic of renal hemosiderosis (Fig. 2). He was treated with intravenous ferric carboxymaltose and folic acid. Three months later, he was asymptomatic. His clinical examination was normal except for the apical systolic murmur. His Hb was 12.3 g/dL, reticulocytes 3.6 %, serum total bilirubin 2.3 mg/dL, direct bilirubin 0.4 mg/dL, lactate dehydrogenase 2012 U/L, and serum ferritin 81 ng/mL. Serum haptoglobin was undetectable. Blood smear examination continued to show schistocytes. The clinical, laboratory, and imaging data together with the response to iron therapy establish the diagnosis of mechanical hemolytic anemia, renal siderosis, and iron deficiency anemia in our patient. Hemolytic anemia following mitral valve repair is rare with only 70 cases reported up to 2012 [7]. In the Cleveland Clinic series, the median time to diagnosis of
* Prasad R. Koduri [email protected] 1
The Division of Hematology-Oncology, Mediciti Hospital, Secretariat Road, Hyderabad, India 500063
2
The Department of Radiology, Mediciti Hospital, Secretariat Road, Hyderabad, India 500063
Fig. 1 Blood smear shows anisochromia and fragmented red cells (Leishman stain, ×400)
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Ann Hematol (2015) 94:1755–1756
the low serum ferritin values in iron-deficient patients with chronic intravascular hemolysis and renal siderosis remains unclear.
Conflict of interest The authors declare that they have no competing interests.
References 1. Fig. 2 T1-weighted MR image of abdomen (coronal view) shows diffuse decrease in signal intensity of the renal cortices
hemolytic anemia after mitral valve repair was 30 days [8], and nearly all required reoperation. A Medline™ search revealed only a single case of iron deficiency related to mechanical hemolytic anemia following mitral valve repair [6]. This may be due to the short interval between the mitral valve repair and the onset of hemolysis, transfusions of packed erythrocytes, and early reoperation resulting in resolution of hemolytic anemia in nearly all affected patients [8]. There are no systematic studies of serum ferritin in patients with cardiac hemolytic anemia with renal siderosis. Serum ferritin is secreted primarily from macrophages through a nonclassical lysosomal secretory pathway; increases in serum ferritin levels following macrophage-specific and total ablation of iron regulatory protein-2 suggest that macrophages are not the sole source of serum ferritin [9]. Macrophages and proximal tubule cells in the kidney are the likely the major cellular sources for serum ferritin [9]. The pathophysiologic basis for
Roberts WC, Morrow AG (1966) Renal hemosiderosis in patients with prosthetic aortic valves. Circulation 33:390–398 2. Bunn HR, Jandl H (1969) The renal handling of hemoglobin: II. Catabolism. J Exp Med 129:925–934 3. Rao KR, Ray VH, Patel AR (1983) Serum ferritin and sequestered stores of body iron. Am J Clin Pathol 80:743–745 4. Rao KR, Patel AR (1983) Paroxysmal nocturnal hemoglobinuria. Arch Intern Med 143:183 5. Risitano AM, Imbriaco M, Marando L et al (2012) From perpetual haemosiderinuria to possible iron overload: iron redistribution in paroxysmal nocturnal haemoglobinuria patients on eculizumab by magnetic resonance imaging. Br J Haematol 158:415–429 6. Gungunes A, Akpinar I, Dogan M, Baser K, Yildirim S, Haznedaroglu IC (2010) Do all hemolytic anemias that occur after mitral valve repair require surgical treatment? Clin Cardiol 33:E76– E78 7. Abourjaili G, Torbey E, Alsaghir T, Olkovski Y, Costantino T (2012) Hemolytic anemia following mitral valve repair: a case presentation and literature review. Exp Clin Cardiol 17:248–250 8. Dumont E, Gillinov AM, Blackstone EH et al (2007) Reoperation after mitral valve repair for degenerative disease. Ann Thorac Surg 84:444–450 9. Cohen LA, Gutierrez L, Weiss A et al (2010) Serum ferritin is derived primarily from macrophages through nonclassical secretory pathway. Blood 16:1574–1584
LETTER TO THE EDITOR
Renal siderosis and serum ferritin Prasad R. Koduri 1 & Sashidhar Kaza 2
Received: 28 May 2015 / Accepted: 11 June 2015 / Published online: 20 June 2015 # Springer-Verlag Berlin Heidelberg 2015
Dear Editor, Patients with chronic intravascular hemolysis may develop persistent hemosiderinuria and renal siderosis [1]. Renal iron deposits have very slow turnover and are unavailable for erythropoiesis [1, 2]. Iron deficiency can develop pari passu with renal siderosis in patients with chronic intravascular hemolysis [1]; data on serum ferritin values in such patients is sparse [3–6]. We report the case of a patient who developed mitral regurgitation with intravascular hemolysis following mitral valve repair for myxomatous mitral valve disease. He was found to have renal siderosis and iron deficiency anemia. His serum ferritin was 13 ng/mL. The low serum ferritin value, despite renal siderosis, suggests that serum ferritin may not reflect the Bsequestered^ stores of iron in the kidneys. Case: A 67-year-old man presented with shortness of breath on exertion of 4-week duration. He had undergone mitral valve repair 4 years previously for myxomatous mitral valve disease. He appeared pale and had a grade 3/6 holosystolic murmur at the cardiac apex. His Hb was 8.9 g/dL and reticulocytes 1.2 %. Blood smear examination showed anisocytosis, anisochromia, and fragmented red cells (Fig. 1). The serum ferritin was 13 ng/mL, total serum bilirubin 1.8 mg/dL, direct bilirubin 0.2 mg/dL, and lactate dehydrogenase 1200 U/L. Urine sediment was strongly positive for hemosiderin. The direct Coombs’ test result was negative. Stool was repeatedly
negative for occult blood. Esophagogastroduodenoscopy and colonoscopy showed normal findings. Transthoracic echocardiography showed severe mitral regurgitation with an eccentric jet. Magnetic resonance imaging showed symmetric diffusely reduced signal intensity of the renal cortices on both T1- and T2-weighted sequences diagnostic of renal hemosiderosis (Fig. 2). He was treated with intravenous ferric carboxymaltose and folic acid. Three months later, he was asymptomatic. His clinical examination was normal except for the apical systolic murmur. His Hb was 12.3 g/dL, reticulocytes 3.6 %, serum total bilirubin 2.3 mg/dL, direct bilirubin 0.4 mg/dL, lactate dehydrogenase 2012 U/L, and serum ferritin 81 ng/mL. Serum haptoglobin was undetectable. Blood smear examination continued to show schistocytes. The clinical, laboratory, and imaging data together with the response to iron therapy establish the diagnosis of mechanical hemolytic anemia, renal siderosis, and iron deficiency anemia in our patient. Hemolytic anemia following mitral valve repair is rare with only 70 cases reported up to 2012 [7]. In the Cleveland Clinic series, the median time to diagnosis of
* Prasad R. Koduri [email protected] 1
The Division of Hematology-Oncology, Mediciti Hospital, Secretariat Road, Hyderabad, India 500063
2
The Department of Radiology, Mediciti Hospital, Secretariat Road, Hyderabad, India 500063
Fig. 1 Blood smear shows anisochromia and fragmented red cells (Leishman stain, ×400)
1756
Ann Hematol (2015) 94:1755–1756
the low serum ferritin values in iron-deficient patients with chronic intravascular hemolysis and renal siderosis remains unclear.
Conflict of interest The authors declare that they have no competing interests.
References 1. Fig. 2 T1-weighted MR image of abdomen (coronal view) shows diffuse decrease in signal intensity of the renal cortices
hemolytic anemia after mitral valve repair was 30 days [8], and nearly all required reoperation. A Medline™ search revealed only a single case of iron deficiency related to mechanical hemolytic anemia following mitral valve repair [6]. This may be due to the short interval between the mitral valve repair and the onset of hemolysis, transfusions of packed erythrocytes, and early reoperation resulting in resolution of hemolytic anemia in nearly all affected patients [8]. There are no systematic studies of serum ferritin in patients with cardiac hemolytic anemia with renal siderosis. Serum ferritin is secreted primarily from macrophages through a nonclassical lysosomal secretory pathway; increases in serum ferritin levels following macrophage-specific and total ablation of iron regulatory protein-2 suggest that macrophages are not the sole source of serum ferritin [9]. Macrophages and proximal tubule cells in the kidney are the likely the major cellular sources for serum ferritin [9]. The pathophysiologic basis for
Roberts WC, Morrow AG (1966) Renal hemosiderosis in patients with prosthetic aortic valves. Circulation 33:390–398 2. Bunn HR, Jandl H (1969) The renal handling of hemoglobin: II. Catabolism. J Exp Med 129:925–934 3. Rao KR, Ray VH, Patel AR (1983) Serum ferritin and sequestered stores of body iron. Am J Clin Pathol 80:743–745 4. Rao KR, Patel AR (1983) Paroxysmal nocturnal hemoglobinuria. Arch Intern Med 143:183 5. Risitano AM, Imbriaco M, Marando L et al (2012) From perpetual haemosiderinuria to possible iron overload: iron redistribution in paroxysmal nocturnal haemoglobinuria patients on eculizumab by magnetic resonance imaging. Br J Haematol 158:415–429 6. Gungunes A, Akpinar I, Dogan M, Baser K, Yildirim S, Haznedaroglu IC (2010) Do all hemolytic anemias that occur after mitral valve repair require surgical treatment? Clin Cardiol 33:E76– E78 7. Abourjaili G, Torbey E, Alsaghir T, Olkovski Y, Costantino T (2012) Hemolytic anemia following mitral valve repair: a case presentation and literature review. Exp Clin Cardiol 17:248–250 8. Dumont E, Gillinov AM, Blackstone EH et al (2007) Reoperation after mitral valve repair for degenerative disease. Ann Thorac Surg 84:444–450 9. Cohen LA, Gutierrez L, Weiss A et al (2010) Serum ferritin is derived primarily from macrophages through nonclassical secretory pathway. Blood 16:1574–1584
