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Extramedullary Hematopoiesis in β-Thalassemia

  • Or Kalchiem-Dekel
    Correspondence
    Correspondence: Address to Or Kalchiem-Dekel, MD, Department of Medicine B, Soroka University Medical Center, POB 151, Beer-Sheva 8410101, Israel.
    Affiliations
    Department of Medicine B, Soroka University Medical Center, Beer-Sheva, Israel

    Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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  • Uri Greenbaum
    Affiliations
    Department of Hematology, Soroka University Medical Center, Beer-Sheva, Israel

    Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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      A 37-year-old man is being followed up at the hematology clinic at our institution for β-thalassemia intermedia. He was diagnosed with β-thalassemia during infancy and required multiple blood transfusions, resulting in iron overload. At the age of 23 years, he underwent splenectomy, obviating the need for further transfusions. Several years later, pulmonary arterial hypertension (PAH) was diagnosed by means of right heart catheterization. Physical examination of the patient revealed a short stature and a body mass index (calculated as the weight in kilograms divided by the height in meters squared) of 22 kg/m2; frontal bossing and a prominent maxilla were consistent with extramedullary hematopoiesis; bronze-colored skin and marked hepatomegaly were evident as signs of iron overload. Recent hemoglobin and ferritin levels were 8 g/dL and 2502 mg/dL, respectively. Chest radiography in the posterior-anterior projection revealed thickened ribs bilaterally, disruption of the anatomic border of the anterior ribs, as well as narrowing of the intercostal spaces. Along the costovertebral junctions, multiple extrapleural masses were noted (Figure A ). The lateral projection demonstrated additional masses on the anterior chest wall (Figure B). Furthermore, roentgenographic signs of pulmonary hypertension were noted in the form of an enlarged pulmonary trunk, prominent right atrium (Figure A), and opacification of the retrosternal space, indicating an enlarged right ventricle (Figure B). These radiological findings, consistent with extramedullary islets of hematopoietic tissue and signs of pulmonary hypertension, were later confirmed by computed tomography of the chest, which also showed gross trabeculation of the ribs and vertebra (see supplemental Figure, available online at http://www.mayoclinicproceedings.org).
      Figure thumbnail gr1
      FigureA, Chest radiography in the anterior-posterior projection demonstrating bilateral paravertebral islets of extramedullary hematopoietic tissue (arrows) and prominent pulmonary trunk and right atrium (arrowheads). B, In chest radiography in the lateral projection, extramedullary islets of the anterior chest (arrows) and an enlarged right ventricle (asterisk) are evident.
      Extramedullary hematopoiesis is a well-documented manifestation of thalassemia,
      • Rivella S.
      The role of ineffective erythropoiesis in non-transfusion-dependent thalassemia.
      as well as other severe disorders of hematopoiesis. Hematopoietic cell colonies may disrupt the cortex of the bones involved and even form masses of extramedullary hematopoietic material in the thoracic
      • Smith P.R.
      • Manjoney D.L.
      • Teitcher J.B.
      • Choi K.N.
      • Braverman A.S.
      Massive hemothorax due to intrathoracic extramedullary hematopoiesis in a patient with thalassemia intermedia.
      or pelvic
      • Mesurolle B.
      • Sayag E.
      • Meingan P.
      • Lasser P.
      • Duvillard P.
      • Vanel D.
      Retroperitoneal extramedullary hematopoiesis: sonographic, CT, and MR imaging appearance.
      cavities as well as other anatomic regions. These, in turn, can cause a mass effect in their respective anatomical location, thus causing damage to adjacent structures, such as spinal cord compression and vascular occlusions.
      Pulmonary arterial hypertension is a common complication of the more severe forms of thalassemia,
      • Tam D.H.
      • Farber H.W.
      Pulmonary hypertension and beta-thalassemia major: report of a case, its treatment, and a review of the literature.
      with a prevalence of more than 50% in some cohorts.
      • Aessopos A.
      • Farmakis D.
      • Karagiorga M.
      • et al.
      Cardiac involvement in thalassemia intermedia: a multicenter study.
      It is postulated that the excess of free hemoglobin in the blood causes endothelial injury as well as nitric oxide depletion, thus leading to the development of PAH.
      • Kato G.J.
      • Taylor VI, J.G.
      Pleiotropic effects of intravascular haemolysis on vascular homeostasis.
      The condition is often asymptomatic but may cause functional impairment in some of the patients. Splenectomy and older age have been shown to be risk factors for developing PAH.
      • Morris C.R.
      • Kim H.Y.
      • Trachtenberg F.
      • et al.
      Thalassemia Clinical Research Network. Risk factors and mortality associated with an elevated tricuspid regurgitant jet velocity measured by Doppler-echocardiography in thalassemia: a Thalassemia Clinical Research Network report.

      Acknowledgments

      We thank Dr Nimrod Maimon for critical review of the manuscript and Dr Alexander Smoliakov, Dr Rosa Novoa, and Dr Elya Benkovich for interpretation of the radiological images.

      Supplemental Online Material

      Figure thumbnail figs1
      Supplemental FigureAxial computed tomography without contrast enhancement at the level to T6 vertebrae showing paravertebral islets of extramedullary hematopoiesis (arrowheads), gross trabeculation of the ribs and vertebral body, and an enlarged pulmonary trunk (asterisk).

      Supplemental Online Material

      Supplemental material can be found online at http://www.mayoclinicproceedings.org. Supplemental material attached to journal articles has not been edited, and the authors take responsibility for the accuracy of all data.

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