Hemolytic anemia causes
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Shyam Patel [2]
Overview
The causes for hemolytic anemia can be divided into intracorpuscular or extracorpuscular causes. The intrinsic causes are commonly due to hereditary causes whereas the extrinsic causes are commonly acquired. Drugs are another major cause of hemolysis. In the era of immunotherapy for cancer, drug-related causes are becoming increasingly important to recognize.
Causes
The causes of hemolytic anemia can be divided into etiologies that are intrinsic to red blood cell biology or extrinsic to red blood cell biology. Intrinsic, or intracorpuscular, causes include red blood cell membrane defects or enzyme deficiencies. Extrinsic causes include infections, autoimmune conditions, or drugs.
Intrinsic or Intracorpuscular Factors
Red blood cell membrane defects
- Paroxysmal nocturnal hemoglobinuria
- Alpha thalassemia
- Hereditary spherocytosis: This is the most common hereditary form of hemolytic anemia.[1] It is caused by mutations in red blood cell cytoskeletal proteins, such as:
- Hereditary elliptocytosis
- Unstable hemoglobin variants and hemoglobinopathies
Red blood cell enzyme deficiencies
- Glucose-6-phosphate dehydrogenase deficiency
- Pyruvate kinase deficiency
- Triose phosphate isomerase deficiency
Extrinsic Factors
Extrinsic factors refers to those that are commonly acquired in nature and have an adverse effect on red blood cells.
Infections
- Shiga-toxin from enterohemorrhagic E. coli strain O157:H&
- Parvovirus
- Malaria
- Babesia
- Clostridium perfringens
Autoimmune or rheumatologic conditions
Systemic activation of the immune system due to underlying rheumatologic conditions can result in a predisposition for hemolysis.
Drugs
These are important causes of hemolysis, especially in the era of immunotherapy for cancer. As more immunotherapeutic agents reach the market, it is likely that there will be more cases of iatrogenic hemolytic anemia.
- Pembrolizumab
- Nivolumab
- Ipilimumab
- Durvalumab
- Avelumab
- Dapsone
- Quinines
Causes by Organ System
| Cardiovascular | Artificial valves (mechanical or bioprosthetic) that cause shear stress to red blood cells |
| Chemical/Poisoning | Snake venom |
| Dental | No underlying causes |
| Dermatologic | No underlying causes, but microangiopathy can present with dermatologic manifestations |
| Drug Side Effect | Acetaminophen and Oxycodone, Amoxicillin, Cefadroxil, Cefaclor, Cefotaxime sodium, Cefotetan disodium, Ceftazidime, Chlorpromazine, Chlorpropamide, Clemastine, Dexchlorpheniramine, Diflunisal, Doxycycline, Flurbiprofen, Indinavir,Imipenem-Cilastatin, Rifampin, Mafenide, Meropenem, Metaxalone, Micafungin sodium, Minocycline hydrochloride, Nitrofurantoin, Olsalazine, Oxaprozin, Oxytetracycline, Penicillin G , Primaquine phosphate (in G-6-PD deficiency and in favism), Pegademase, Piperacillin, Piperacillin/tazobactam, Procarbazine, Probenecid,Rasburicase, Repaglinide, Sulindac, tolbutamide, Tolazamide, Thiothixene, Tolmetin, |
| Ear Nose Throat | No underlying causes |
| Endocrine | Grave's disease and other conditions characterized by antibodies against endocrine organs can rarely cause inadvertent hemolysis |
| Environmental | No underlying causes |
| Gastroenterologic | No underlying causes |
| Genetic | Hereditary spherocytosis, hereditary elliptocytosis, thalassemias, glucose-6 phosphate deficiency, pyruvate kinase deficiency, triose phosphate deficiency |
| Hematologic | Microangiopathic hemolytic anemia, thrombotic thrombocytopenia purpura, disseminated intravascular coagulation |
| Iatrogenic | Immunotherapy drugs used to treat cancer, such as pembrolizumab, nivolumab, ipilimumab, avelumab, and durvalumab |
| Infectious Disease | Babesia, malaria, Clostridium perfringens, enterohemorrhagic E.coli (hemolytic uremia syndrome), parvovirus |
| Musculoskeletal/Orthopedic | No underlying causes |
| Neurologic | No underlying causes |
| Nutritional/Metabolic | No underlying causes |
| Obstetric/Gynecologic | HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) syndrome and pre-eclampsia |
| Oncologic | Anti-PD-1 agents (immunotherapeutic drugs for cancer), chronic lymphocytic leukemia (causes autoimmune hemolytic anemia) |
| Ophthalmologic | No underlying causes |
| Overdose/Toxicity | No underlying causes |
| Psychiatric | No underlying causes |
| Pulmonary | No underlying causes |
| Renal/Electrolyte | No underlying causes |
| Rheumatology/Immunology/Allergy | Systemic lupus erythematosis |
| Sexual | No underlying causes |
| Trauma | Capillary damage can result in shear stress and hemolysis |
| Urologic | No underlying causes |
| Miscellaneous | No underlying causes |
References
- ↑ Jung HL (2013). "A new paradigm in the diagnosis of hereditary hemolytic anemia". Blood Res. 48 (4): 237–9. doi:10.5045/br.2013.48.4.237. PMC 3894378. PMID 24466544.