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KirsiJahnukainen
UllaWartiovaara-Kautto

Sickle Cell Anaemia

Essentials

  • Sickle cell anaemia is a recessively inherited, serious haemolytic disease. Heterozygous carriers are asymptomatic unless they also carry beta thalassaemia Thalassaemias or HbC http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=19635.
  • All patients with symptomatic sickle cell anaemia must be referred to specialized care. N.B.! Despite the name of the disease, not all patients have significant anaemia.
  • Carriers of the sickle cell anaemia gene mutation who are of fertile age and patients with the disease need genetic counselling.

Aetiology

  • Sickle cell anaemia is caused by a beta globin chain defect inherited from both parents that causes polymerization of sickle haemoglobin (HbS) and breaks up blood cells making them sickle shaped.
  • There are various types of sickle cell anaemia (HbSS, HbSC, HbS-beta, HbSD). The most common type causing the most significant health issues (see below) is HbSS.

Epidemiology

  • Sickle cell anaemia is most common in Africa but also occurs in Asia, the Far East, America, the Mediterranean countries and, due to immigration, even further north in Europe.

Symptoms

  • Sickling of red blood cells activates the vascular endothelium, causing constant asymptomatic or symptomatic circulatory disturbances and oxygen deficiency, which untreated will lead to premature death.
  • HbSS is nearly always associated with significant (haemolytic) anaemia but some patients with sickle cell anaemia only have slightly lowered Hb levels.
  • Sickle cell crises are due to paroxysmally increased sickling of red blood cells, haemolysis, and acute circulatory disturbances and oxygen deficiency in tissues due to sickling. Such crises may be fatal and require active, rapid treatment.
  • Infections, fever, dehydration, pregnancy and changes in partial oxygen pressure and temperature make patients susceptible to sickle cell crises.
  • Crisis symptoms include one or more of the following:
    • Severe pain in any part of the body - most commonly the skeleton, sometimes the abdomen, chest or head.
    • Impaired oxygenation
    • Priapism
    • Fever
    • Cerebrovascular accident (infarction or haemorrhage)
    • Sudden loss of vision or hearing
  • Due to their underlying disease, the patients are hyposplenic and susceptible to infections.

Laboratory findings

  • Most patients suffer from haemolytic anaemia Haemolytic Anaemia (lactate dehydrogenase elevated and 3-20% reticulocytes). The severity of anaemia may vary from mild to severe enough to require red blood cell transfusion (Table T1).
  • Patients with HbSC- or HbS-beta disease is also associated with microcytosis (Table T1). HbSS is a normocytic disease unless the patient has also inherited a globin gene mutation.
  • Diagnostic tests: blood haemoglobin fraction test (Table T1), plasma ferritin test (within range or elevated) and blood count (Table T1)
  • The haemoglobin fraction test usually detects both carriership and the symptomatic form of disease.
  • Genetic tests are performed in specialized care.

Clinical and haematological findings in patients over 5 years of age with sickle cell anomalies, and in sickle cell carriers

Sickle cell anomalyClinical severityHbS (%)HbF (%)HbA2 (%)Hb (g/l)Reticulocytes (%)MCV (fl)
SSSevere> 90< 10< 3.560-1103-20> 80
Sß°Severe to moderately severe> 80< 20> 3.560-1003-20< 80
Sß+Moderately severe> 60< 20> 3.590-1203-10< 75
SCSevere to moderately severe50< 5< 3.5 (50 % HbC)100-1503-1075-95
SA (carrier)Asymptomatic< 40< 1< 3.5Within rangeWithin range
Lyhenteet:
  • SS = homozygous for sickle cell anaemia
  • Sß° = heterozygous for sickle cell anaemia and ß-thalassaemia, no ß-globin production
  • Sß+ = heterozygous for sickle cell anaemia and ß-thalassaemia, partial ß-globin production
  • SC = heterozygous for sickle cell anaemia and the HbC gene
Treatment and follow-up

Treatment of sickle cell crises

  • Effective analgesic medication. Opioids are often needed for the treatment of infarction pain due to lack of oxygen in tissues.
  • Rest, fluid administration, ensuring sufficient oxygenation
  • Active search for and treatment of infections
  • If the pain crisis is particularly severe or prolonged, or if the patient has problems with oxygenation, for example, or disturbances of cerebrovascular circulation, a haematologist should be consulted urgently. Without red blood cell exchange transfusion, the situation will become worse and may rapidly lead to multiple organ dysfunction.
  • N.B.! Red blood cell transfusion must always be done using phenotyped erythrocytes, as far as possible Blood Transfusion: Indications, Administration and Adverse Reactions. The erythrocyte phenotype should be defined as soon as the diagnosis has been confirmed.
  • In paediatric patients, halting of erythropoiesis due to a parvovirus infection may lead to an aplastic crisis, and red blood cell transfusion may be needed. Another type of crisis occurring in small children, particularly, is splenic or hepatic sequestration, where most (or all) of the blood volume is trapped in the spleen or in the liver; the child will need immediate red blood cell transfusion, and splenectomy must be considered later.

Genetic counselling

  • In fertile age, carriers of sickle cell anomalies and patients with sickle cell anaemia need genetic counselling.
  • It is important to identify couples with a risk of having a child with symptomatic sickle cell anaemia.
  • If both parents carry the sickle cell anaemia gene, in each pregnancy they will have a 25% risk of having a child with symptomatic sickle cell anaemia. Beta thalassaemia, HbD or HbC carriership combined with HbS carriership will produce the same risk ratio.