Transfusion-Induced Iron Overload Clinical Presentation

Updated: May 07, 2021
  • Author: Geneva E Guarin, MD, MBA; Chief Editor: Emmanuel C Besa, MD  more...
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Presentation

History

Patients with transfusion-induced iron overload typically have underlying anemia and transfusion dependence. The clinician should ask about the following:

  • Duration of transfusion dependenc
  • Number of transfusions each year
  • Chelation history and compliance

Patients may complain of weight loss, fatigue, and arthralgia, along with cardiac, gastrointestinal, and endocrine manifestations.

Cardiac manifestations (related to heart failure) may include the following:

  • Dyspnea
  • Orthopnea
  • Paroxysmal nocturnal dyspnea
  • Swelling of lower extremities

Gastrointestinal signs and symptoms (related to cirrhosis) may include the following:

  • Abdominal distention
  • Abdominal pain
  • Hematemesis
  • Melena
  • Encephalopathy

Endocrine manifestations may include the following:

  • Stunted growth
  • Delayed puberty
  • Decreased libido
  • Delayed menarche
  • Diabetes mellitus (ie, polyuria, polydipsia, polyphagia)
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Physical

General physical examination findings in patients with transfusion-induced iron overload may include the following:

  • Bronze/gray skin color
  • Bruising
  • Cachexia
  • Dwarfism
  • Delayed breast development in pubertal girls
  • Soft, small testes in males

Cardiac findings may include the following:

  • Jugular venous distention
  • S3 rhythm
  • Pleural effusion
  • Peripheral edema

Pulmonary findings may include the following:

  • Lung crepitations
  • Loud P 2

Abdominal findings may include the following:

  • Ascites
  • Tenderness
  • Hepatomegaly
  • Splenomegaly
  • Caput medusa
  • Umbilical hernia

Neurologic findings related to cirrhosis may include the following:

  • Asterixis
  • Encephalopathy
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Causes

Transfusion dependence due to the following are among the causes of transfusion-induced iron overload:

  • Sickle cell disease
  • β-thalassemia major
  • Aplastic anemia
  • Hemolytic anemia
  • Blackfan-Diamond syndrome
  • Myelodysplastic syndrome
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Complications

Cardiac involvement is a major determinant of the prognosis in iron-overload states. [25]  Hypertrophy and dilatation are common. Abnormal cardiac function can be observed in the absence of overt heart failure. [26]  The average time for the development of heart failure in transfused, unchelated patients is 10 years. [27]

Iron chelation can reverse cardiac changes and improve performance. [28]  In a murine model of beta-thalassemia, the myocardial damage with increased interstitial fibrosis and remodelling appears to start before any significant myocardial iron deposits can be demonstrated, suggesting additional mechanisms of cardiac failure pathogenesis in thalassemia. [29]

Pulmonary hypertension appears to be less common in thalassemia major patients who undergo transfusion, probably due to the correction of hypoxia, and it is more common in the less transfused thalassemia intermedia patients. [30]  More than one third of transfusion-dependent patients with β-thalassemia major exhibit a restrictive lung function defect, which may improve with chelation therapy. [31]

Liver involvement is common in those who undergo long-term transfusions. Early cirrhotic changes can be observed as early as age 7 years in some people with thalassemia. [32]  Upregulation of the transport of NTBI is observed in cultured hepatocytes and is likely to occur in vivo. [33]  Once cirrhosis develops, the risk of hepatocellular carcinoma (HCC) is increased.

Endocrine dysfunction affects virtually all glands. Pituitary involvement causes delayed puberty in more than 50% of patients. [34]  Destruction of pancreatic beta cells, insulin resistance, or both may result in diabetes mellitus. [35]  Even those without diabetes may have abnormal glucose metabolism. [35]  Thyroid, parathyroid, and exocrine pancreas are also affected. [36]  In one study involving patients with chronic anemia with transfusion-induced iron overload, free T3 and free T4 were decreased and thyrotropin-stimulating hormone was higher than normal. [37]  

Neutrophils from patients with secondary iron overload have an increased iron and ferritin content and a phagocytosis defect. [38] Yersinia enterocolitica seems to have affinity for those loaded with iron, causing abdominal infections [39]  and hepatic abscesses. [40]  Deferoxamine seems to worsen the infection and should be discontinued in cases in which active abdominal symptoms are present. [41]

Degenerative arthropathy in thalassemia is also a sequela of iron overload. [42]

Complications of iron overload as manifested in va Complications of iron overload as manifested in various organs in the body
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