Pathogenesis (disease development)
Sickle cell disease refers to a hereditary form of anemia (anemia) that is relatively common in the black population (see “Ethnicity” below).
In this autosomal recessive disease, a point mutation on chromosome 11 results in the production of an altered hemoglobin (sickle cell hemoglobin, HbS). In this pathological (diseased) HbS, instead of glutamate, there is a valine at the sixth position of the β-chain.
Hemoglobin HbS causes erythrocytes (red blood cells) to lose their shape and deformability. Thus, vaso-occlusions (vascular occlusion) and subsequent infarctions (sudden death of a tissue or organ part, due to a prolonged interruption of the blood supply) occur in the various organs.
Etiology (causes)
Biographic causes
- Genetic burden
- By parents, grandparents – point mutation on chromosome 11.
- Persons from the Mediterranean region are mostly homozygous for the Benin haplotype, persons from Central Africa are mostly homozygous for the Bantu type
- Ethnic origin
- Three-quarters of sickle cell anemia cases occur in Africa (carrier frequency (heterozygous trait carriers): 10-40% in equatorial Africa; north African coast 1-2%; South Africa
- Eastern Mediterranean
- Near East
- African Americans: sickle cell anemia is the most common inherited disease in African Americans in the United States (carrier frequency: 5-10%).
Medications
Anemia
- Antiprotozoal drugs
- Analogue of the azo dye trypan blue (suramin).
- Pentamidine
- Alpha-methyldopa (antihypertensive).
- Antimalarials, such as primaquine or dapsone.
- Chelating agents (D-penicillamine, trieethylenetetramine dihydrochloride (Trien), tetrathiomolybdenum).
- Quinidine
- Direct Factor Xa inhibitor (rivaroxaban).
- Immunosuppressants (thalidomide).
- Janus kinase inhibitors (ruxolitinib).
- Monoclonal antibodies – pertuzumab
- MTOR inhibitors (everolimus, temsirolimus).
- Neomycin
- P-aminosalicylic acid (mesalazine)
- Phenytoin [megaoblastic anemia]
- Thrombin inhibitor (dabigatran)
- Tuberculostatics (isoniazid, INH; rifampicin, RMF).
- Antivirals
- Nucleoside analogues (ribavirin) [hemolytic anemia.]
- NS5A inhibitors (daclatasvir).
- Protease inhibitors (boceprevir, telaprevir).
Aplastic anemia
- Allopurinol*
- Alpha-methyldopa*
- Antibiotics – drugs such as streptomycin* , tetracycline* or methicillin* .
- Antidiabetic drugs – tolbutamide and chlorpropamide.
- Antihistamines – cimetidine
- Anticonvulsants – carbomazepine
- Carboanhydrase inhibitors (CAH, CAI) – acetazolamide, dichlorophenamide, methazolamide.
- Quinidine*
- Chloramphenicol
- Colchicine
- D-penicillamine – drug used in the therapy of rheumatoid arthritis.
- Lithium*
- Medicines for protozoan infections such as chloroquine or mepacrine.
- Non-steroidal anti-inflammatory drugs (NSAIDs) – phenylbutazone, ibuprofen, or acetylsalicylic acid (ASA).
- Estrogens
- Sedatives – such as chlorpromazine* or meprobamate* .
- Sulfonamides
- Tuberculostatics (isoniazid, INH)
- Thyrostatic drugs – such as methylthiouracil or carbimazole.
- Cytostatics
- Alkylants such as chlorambucil or cyclophosphamide.
- Antimetabolites such as mercaptopurine, fluorouracil or methotrexate.
- Mitosis inhibitors such as vincristine or paclitaxel.
Note: For drugs marked with an asterisk (* ), the association with aplastic anemia is poorly established.
