Hemoglobin S
(Hb S; Sickle Cell Disease)
- Method:
- Anticoagulant:
- Recommendation:
- Method:Blood Count
- Anticoagulant:EDTA*
- Recommendation:obligatory
- Method:Hemoglobin Differentiation
- Anticoagulant:EDTA*
- Recommendation:obligatory
- Method:Iron Status
- Anticoagulant:Serum**
- Recommendation:obligatory
- Method:Molecular genetics
- Anticoagulant:Serum**
- Recommendation:once
*3 ml EDTA-Blut (Blutbildröhrchen), **7,5 ml Serum, ***7,5 ml EDTA-Blut (extra Röhrchen)
Hemoglobin S (Hb S; sickle cell disease): Overview
Sickle cell disease includes all hemoglobinopathies caused by abnormal hemoglobin S (Hb S). This includes homozygous HbSS forms as well as Hb S in compound heterozygous form with other β-globin gene mutations. The most common of these are Hb S-β-thalassemia and Hb SC disease. Far less frequently, other compound heterozygous combinations occur, such as HbSD, HbSOArab, HbSLepore, and HbSE. Genetically, Hb S is based on an amino acid exchange at position 7 of the β-globin chain (HBB:c.20A>T p.Glu7Val, HbVar ID 226).
Typically, carriers of hemoglobin S and patients with sickle cell disease come from Africa, countries of the Eastern Mediterranean, Iraq, the Arabian Peninsula, India, North and South America and the Caribbean. It is estimated that there are over 3,000 patients with sickle cell disease in Germany (as of 2017), and since 2021, screening for sickle cell disease has been a part of newborn screening in Germany.
The clinical course is determined in part by the genetic constellation, with patients with HbSS, HbS-β0-thalassemia, HbSD, and HbSOArab showing the most severe course. The cause of the symptoms is the decreased elasticity and sickle-like deformation of the erythrocytes, due to the altered hemoglobin structure and the altered properties of hemoglobin S in the deoxygenated state. As a result, hemolysis and vascular occlusion-related crises occur, which determine the disease pattern of sickle cell disease. Thus, indications for testing for sickle cell disease include the following:
- Hemolytic anemia (normocytic or microcytic, depending on the genotype present).
- Recurrent pain crises, especially in the skeletal system
- Pronounced anemia, possibly shock symptoms, and pronounced splenomegaly
- Pronounced anemia and absent reticulocytosis
- Unclear painful swellings of hands and feet in young children
- Aseptic necrosis of femoral or humeral head
- CNS hemorrhage or infarction
- Unexplained severe infection
- Positive family history
Carriers of Hb S usually have no blood count abnormalities or clinical symptoms. Exceptions include papillary necrosis with painless hematuria in up to 4% of Hb S carriers during life, painful splenic infarcts with vigorous exercise or dehydration at high altitudes, and the very rare renal medullary carcinoma.
Hemoglobin S (Hb S; sickle cell disease): Diagnosis
Since there is no method that represents the sole gold standard in the diagnosis of Burkitt lymphoma or Burkitt leukemia, an integrated diagnostic approach taking into account morphology/histology, immunophenotype, and genetics is central. Due to the frequent CNS involvement, especially in the setting of Burkitt leukemia, an additional cerebrospinal fluid (CSF) examination should be performed.
Hemoglobin S (Hb S; sickle cell disease): Therapy
Because Burkitt lymphoma is an aggressively growing tumor with a proliferation rate of up to 100% (Swerdlow et al. 2017), rapid and consistent therapy is required. Intensive combination chemotherapy results in 5-year survival of 90% for adolescents, 84% for adults, and 62% for elderly patients (Hoelzer et al. 2014).
Risk assessment of patients with Burkitt lymphoma can be assisted by the BL-IPI (BL International Prognostic Index), which analyzes various clinical parameters (Olszewski et al. 2021) that also have prognostic significance in HIV-associated BL (Alderuccio et al. 2021).
Therapeutic options can be found in a recent review by Crombie and LaCasce, among others (Crombie & LaCasce 2021).
Status: April 2024