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      Drugs & Diseases > Hematology

      Hemolytic Anemia Clinical Presentation

      Updated: Nov 10, 2022
      • Author: Srikanth Nagalla, MD, MS, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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      Presentation

      History

      Signs and symptoms of hemolytic anemia are diverse and are due to anemia, the extent of compensation, previous treatment, and the underlying disorder. Patients with minimal or long-standing hemolytic anemia may be asymptomatic, and hemolysis is often found incidentally during routine laboratory testing. Clinical manifestations may include the following:

      • Dark urine may occur in patients with intravascular hemolysis, due to hemoglobinuria; chronic intravascular hemolysis may result in iron deficiency.

      • Tachycardia, dyspnea, angina, and weakness occur in patients with severe anemia, as cardiac function is sensitive to anoxia.

      • Persistent hemolysis may result in the development of bilirubin gallstones; these patients may present with abdominal pain.

      • Bronze skin color and diabetes occur in hematosiderosis; iron overload may occur in patients who have received multiple transfusions or those who have been administered iron therapy erroneously.

      • In addition to hemolysis, patients with thrombotic thrombocytopenic purpura (TTP) may experience fever, neurologic signs, kidney failure, and thrombocytopenia.

      • Leg ulcers may develop in patients with sickle cell anemia, thalassemia major, and other hemolytic disorders, as a result of decreased red blood cell (RBC) deformability, endothelial changes, and chronic hypoxia.

      • Venous thromboembolism occurs in 15% to 33% of adults with warm autoimmune hemolytic anemia, especially in the first few weeks after onset. [33]  Children with hereditary spherocytosis (HS) are also at increased risk for thrombosis. Hypercoagulability is especially marked in children with HS who are experiencing a hemolytic crisis. [34]

      Patients may report recent use of medications that can cause immune hemolysis. These include penicillin, quinine, quinidine, and L-dopa. Dimethyl fumarate, which used in the treatment of relapsing forms of multiple sclerosis, has recently been shown to cause a hemolytic anemia. [35]

      In patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, hemolysis can be triggered by oxidant drugs and stress from infections. Fava beans can induce hemolysis in susceptible individuals with the Mediterranean variant of G6PD deficiency.

      Next:

      Physical Examination

      The physical examination in an individual with hemolytic anemia can reveal signs of anemia, complications of hemolysis, and evidence of an underlying disease. General pallor and pale conjunctivae and fingernails indicate anemia but are not specific for hemolytic anemias. Tachycardia, tachypnea, and hypotension due to anoxia and decreased vascular volume can occur in severe anemias but are not specific for hemolytic anemias.

      Jaundice may occur because of a modest increase in indirect bilirubin in hemolysis. The rise is not specific for hemolytic disorders and may occur in liver disease and biliary obstruction. Bilirubin levels are rarely greater than 3 mg/dL in hemolysis, unless complicated by liver disease or cholelithiasis.

      Splenomegaly occurs in hereditary spherocytosis and other hemolytic anemias, but it is not present in all hemolytic disorders. For example, splenomegaly usually is not present in G6PD deficiency. The presence of splenomegaly could suggest an underlying disorder such as chronic lymphocytic leukemia (CLL), some lymphomas, or systemic lupus erythematosus (SLE). Butterfly malar rash and arthritis also symptoms suggestive of SLE. Lymphadenopathy along with splenomegaly is consistent with CLL.

      Splenomegaly sometimes is not evident on physical examination, and ultrasonic imaging or CT scanning may be necessary to define spleen size. When evaluating spleen size, it is important to avoid unnecessary pressure in order to avoid splenic rupture.

      Leg ulcers may be present.

      Right upper abdominal quadrant tenderness may indicate cholelithiasis (bilirubin gallstones) and gallbladder disease.

      Tachycardia and dyspnea may be evident when the onset of hemolysis is abrupt and the anemia is severe. Angina and heart failure symptoms can occur in patients with underlying cardiovascular disease.

      In patients with chronic hemolytic anemia, increased folate consumption may lead to folate deficiency. Clinical manifestations may include patchy hyperpigmentation, sore tongue, and gastrointestinal symptoms.

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