Editors

Eeva-RiittaSavolainen

SakariKakko

Haemolytic Anaemia

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.

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.

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.

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.

Erythrocyte defects
Cell membrane defects Hereditary spherocytosis http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=3252 Hereditary elliptocytosis http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=3655
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

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 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.