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{{Hemolytic anemia}}
{{Hemolytic anemia}}
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==Overview==
==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.
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==
==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.
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===
===Intrinsic or Intracorpuscular Factors===
====Red blood cell membrane defects====
====Red blood cell membrane defects====
*[[Paroxysmal nocturnal hemoglobinuria]]  
*[[Paroxysmal nocturnal hemoglobinuria]]  
*[[Alpha thalassemia]]
*[[Alpha thalassemia]]
*[[Hereditary spherocytosis]]
*[[Hereditary spherocytosis]]: This is the most common hereditary form of hemolytic anemia.<ref name="pmid24466544">{{cite journal| author=Jung HL| title=A new paradigm in the diagnosis of hereditary hemolytic anemia. | journal=Blood Res | year= 2013 | volume= 48 | issue= 4 | pages= 237-9 | pmid=24466544 | doi=10.5045/br.2013.48.4.237 | pmc=3894378 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24466544  }} </ref> It is caused by [[mutations]] in [[red blood cell]] [[cytoskeletal]] [[proteins]], such as:
**[[Spectrin]]
**[[Ankyrin]]
**[[Band 3]]
**[[Band 4.1]]
**[[Glycophorin]]
*[[Hereditary elliptocytosis]]
*[[Hereditary elliptocytosis]]
*Unstable [[hemoglobin]] variants and [[hemoglobinopathies]]
*Unstable [[hemoglobin]] variants and [[hemoglobinopathies]]


====Red Blood Cell Enzyme Deficiencies====
====Red blood cell enzyme deficiencies====
*[[Glucose-6-phosphate dehydrogenase deficiency]]
*[[Glucose-6-phosphate dehydrogenase deficiency]]
*[[Pyruvate kinase deficiency]]
*[[Pyruvate kinase deficiency]]
*[[Triose phosphate isomerase deficiency]]
*[[Triosephosphate isomerase|Triose phosphate isomerase]] [[deficiency]]


===Extrinsic Factors===
===Extrinsic Factors===
Extrinsic factors refers to those that are commonly acquired in nature and have an adverse effect on red blood cells.
Extrinsic factors refers to those that are commonly acquired in nature and have an adverse effect on [[Red blood cell|red blood cells]].


====Infections====
====Infections====
*[[Shiga-toxin]] from [[enterohemorrhagic ''E. coli'' strain O157:H&]]
*Shiga-toxin from [[EHEC|enterohemorrhagic E. coli]] strain O157:H&
*[[Parvovirus]]
*[[Parvovirus]]
*[[Malaria]]
*[[Malaria]]
*[[Babesia]]
*[[Babesia]]
*[[''Clostridium perfringens'']]  
*[[Clostridium perfringens]]


====Autoimmune Conditions====
====Autoimmune or rheumatologic conditions====
Systemic activation of the immune system due to underlying rheumatologic conditions can result in a predisposition for hemolysis.
Systemic activation of the [[immune system]] due to underlying [[Rheumatologic disease|rheumatologic]] conditions can result in a predisposition for [[hemolysis]].
*Systemic lupus erythematosus
*[[Systemic lupus erythematosus]]


====Drugs====
====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.
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]]
*[[Pembrolizumab]]
*[[Nivolumab]]
*[[Nivolumab]]
*[[Ipilimumab]]
*[[Ipilimumab]]
*[[Durvalumab]]
*Durvalumab
*[[Avelumab]]
*Avelumab
*[[Dapsone]]
*[[Dapsone]]
*[[Quinines]]
*[[Quinine|Quinines]]


===Causes by Organ System===
===Causes by Organ System===


{|style="width:80%; height:100px" border="1"
{| style="width:80%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" |'''Cardiovascular'''
| style="width:25%" bgcolor="LightSteelBlue" ; border="1" |'''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | No underlying causes
| style="width:75%" bgcolor="Beige" ; border="1" | [[Artificial heart valve|Artificial valves]] (mechanical or bioprosthetic) that cause shear stress to [[red blood cells]]
|-
|-
|bgcolor="LightSteelBlue"| '''Chemical/Poisoning'''
| bgcolor="LightSteelBlue" | '''Chemical/Poisoning'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | [[Snake venoms|Snake venom]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Dental'''
| '''Dental'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Dermatologic'''
| '''Dermatologic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes, but [[microangiopathy]] can present with [[Dermatological|dermatologic]] manifestations
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
| '''Drug Side Effect'''
|bgcolor="Beige"| [[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]],  
| bgcolor="Beige" | [[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]],  
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
| '''Ear Nose Throat'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Endocrine'''
| '''Endocrine'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | [[Grave's disease]] and other conditions characterized by [[antibodies]] against [[endocrine organs]] can rarely cause inadvertent [[hemolysis]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Environmental'''
| '''Environmental'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
| '''Gastroenterologic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Genetic'''
| '''Genetic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | [[Hereditary spherocytosis]], [[hereditary elliptocytosis]], [[Thalassemia|thalassemias]], [[glucose-6 phosphate deficiency]], [[pyruvate kinase deficiency]], [[Triose phosphate isomerase|triose phosphate]] deficiency
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Hematologic'''
| '''Hematologic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | [[Microangiopathic hemolytic anemia]], [[Thrombotic thrombocytopenic purpura|thrombotic thrombocytopenia purpura]], [[disseminated intravascular coagulation]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Iatrogenic'''
| '''Iatrogenic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | [[Immunotherapy]] drugs used to treat [[cancer]], such as [[pembrolizumab]], [[nivolumab]], [[ipilimumab]], avelumab, and  durvalumab
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Infectious Disease'''
| '''Infectious Disease'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | [[Babesia]], [[malaria]], ''[[Clostridium perfringens]]'', [[EHEC|enterohemorrhagic ''E.coli'']] ([[Hemolytic-uremic syndrome|hemolytic uremia syndrome]]), [[parvovirus]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Musculoskeletal/Orthopedic'''
| '''Musculoskeletal/Orthopedic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Neurologic'''
| '''Neurologic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Nutritional/Metabolic'''
| '''Nutritional/Metabolic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | [[HELLP syndrome]] ([[Hemolysis|'''h'''emolysis]], '''e'''levated '''l'''iver enzymes, [[Thrombocytopenia|'''l'''ow '''p'''latelets]]) syndrome and [[Preeclampsia|pre-eclampsia]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Oncologic'''
| '''Oncologic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | Anti-PD-1 agents (immunotherapeutic drugs for cancer), [[chronic lymphocytic leukemia]] (causes [[autoimmune hemolytic anemia]])
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Ophthalmologic'''
| '''Ophthalmologic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Overdose/Toxicity'''
| '''Overdose/Toxicity'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Psychiatric'''
| '''Psychiatric'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Pulmonary'''
| '''Pulmonary'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Renal/Electrolyte'''
| '''Renal/Electrolyte'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Rheumatology/Immunology/Allergy'''
| '''Rheumatology/Immunology/Allergy'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | [[Systemic lupus erythematosus|Systemic lupus erythematosis]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Sexual'''
| '''Sexual'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Trauma'''
| '''Trauma'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | [[Capillary]] damage can result in [[shear stress]] and [[hemolysis]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Urologic'''
| '''Urologic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Miscellaneous'''
| '''Miscellaneous'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|}
|}
===Causes in Alphabetical Order===
{{col-begin|width=80%}}
{{col-break|width=33%}}
*[[Amoxicillin]]
*[[Cefadroxil]]
*[[Cefotetan disodium]]
*[[Ceftazidime]]
*[[Chlorpropamide]]
*[[Flurbiprofen]]
*[[Indinavir]]
*[[Micafungin sodium]]
*[[Oxaprozin]]
*[[Probenecid]]
{{col-break|width=33%}}
{{col-break|width=33%}}
{{col-end}}


==References==
==References==

Latest revision as of 18:46, 30 October 2017

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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

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.

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 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

  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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