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 comonly 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

These factors are intrinsic to red blood cell biology. Intracorpuscular refers to "within the body" or "within the cell." It can be divided into red blood cell membrane defects or enzyme deficiencies. Both of these causes lead to red blood cell fragility and predisposition to cell rupture. Most of these causes are genetic (inherited from the germline), but some of these causes are acquired.

Red blood cell membrane defects

Red blood cell enzyme deficiencies

Extrinsic Factors

Extrinsic factors refers to those that are commonly acquired in nature and have an adverse effect on red blood cells.

Infections

Autoimmune or rheumatologic conditions

Systemic activation of the immune system due to underlying rheumatologic conditions can result in a predisposition for hemolysis.

  • Systemic lupus erythematosus

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.

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 pembrolizumab, nivolumab, ipilimumab, avelumab, 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 preeclamsia
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

  1. 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.

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