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Editors

Eeva-RiittaSavolainen
SakariKakko

Haemolytic Anaemia

Essentials

  • A reticulocyte count is a first-line investigation in anaemia; it differentiates anaemia caused by excessive consumption (= haemorrhage or haemolysis) from deficiency anaemias and myelogenous anaemias (e.g. malignant haematological diseases).
  • The aetiology of haemolysis must be investigated whenever possible.

Epidemiology

  • Haemolytic anaemias are rare in some countries (e.g. the Nordic countries), but rare cases occur, caused by e.g. autoimmune haemolytic anaemia (AIHA) http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=13392.
  • In certain geographic regions haemolytic anaemias present a more frequently encountered problem (sickle cell anaemia, thalassaemias, abnormal haemoglobins etc.), and this must be borne in mind when treating patients originating from such regions.

Background

  • The normal life span of red blood cells is 120 days. In haemolysis, the life span may be shortened down to a few minutes.
  • Haemolysis may be
    • compensated, which is a state in which the increased erythrocyte production is able to compensate for the accelerated consumption, thus averting anaemia.
    • uncompensated, i.e. the patient develops anaemia.
  • The reticulocyte count is raised in both conditions, indicating increased erythrocyte production.
  • Erythrocytes are destroyed either
    • extravascularly in the reticuloendothelial system, particularly in the spleen
    • intravascularly (in the blood stream) or
    • as precursor cells in the bone marrow.
  • Signs of haemolysis include:
    • enhanced erythropoiesis in the bone marrow, resulting in reticulocytosis
    • an increase in haemoglobin breakdown products
    • in intravascular haemolysis, increased plasma haemoglobin concentration and occasionally haemoglobinuria as well as haemosiderinuria.

Causes of haemolytic anaemia

  • The premature destruction of erythrocytes may be caused by:
    • defects in the erythrocytes themselves (hereditary haemolytic anaemias and paroxysmal nocturnal haemoglobinuria, i.e. PNH).
  • Specific disease forms are listed in table T1.

Causes of haemolysis

Erythrocyte defects
Cell membrane defects
Enzymopathies
  • Haemoglobin abnormalities
  • Thalassaemias
  • Haemoglobinopathies
Paroxysmal nocturnal haemoglobinuria (PNH)
External causes
Immunohaemolysis
  • Autoimmune haemolysis
  • Cold haemagglutination syndrome
  • Drug-induced immunohaemolysis
  • Transfusion reaction
  • Mother-child immunisation
Fragmentation haemolysis
  • Prosthetic valves, other prostheses, haemoperfusion
  • March haemoglobinuria
  • Vasculitis
  • Disseminated intravascular coagulation (DIC)
  • Thrombotic thrombocytopenic purpura (TTP)
Other external causes
  • Infections, toxins, burns, hypersplenism

Diagnostic assessment

  • The assessment should aim to
    1. ascertain the presence of haemolysis
    2. uncover the cause and mechanism of the haemolytic condition.
  • The general practitioner can fairly easily exclude the possibility of significant haemolysis.
  • The first-line investigations in anaemia include basic blood count with platelet count, reticulocytes, ESR and CRP.
  • Anaemia and reticulocytosis can be signs of haemorrhage or haemolysis.
  • Co-existing deficiency anaemia is also possible. Consequently, check transcobalamin II-bound vitamin B12, folate and ferritin levels.
  • Other investigations to be carried out in order to verify haemolysis and its mechanism include:
    • direct Coombs' test
      • Positive in autoimmune haemolytic anaemia (AIHA)
    • lactate dehydrogenase
      • A very sensitive indicator of haemolysis, but it also increases in many other conditions.
    • haptoglobin
      • Decreases in haemolysis, but it may also be decreased in liver diseases.
    • bilirubin
      • The concentration of unconjugated bilirubin, in particular, increases.
    • urinary haemosiderine
      • indicative of intravascular haemolysis of long duration, and it will remain positive several weeks after the cessation of haemolysis.
    • blood cell morphology studies and bone marrow examination if indicated.
  • A careful history should be taken regarding current medication, including both regular and temporary drugs.
  • Family history, immigrant populations

Treatment

  • Treatment depends on the specific condition and is mostly carried out in collaboration with a specialist physician.
  • Patients with severe anaemia that needs blood transfusion (blood haemoglobin < 70 g/l) and patients with symptomatic anaemia should be referred as an emergency case to hospital for treatment.