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{{Hemolytic anemia}}
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==Overview==
==Overview==
It has numerous possible causes, ranging from relatively harmless to life-threatening.
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==


===Common 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]].
* [[Hemolytic anemia]] occurs when the bone marrow is unable to increase production to make up for the premature destruction of red blood cells.''' If the bone marrow is able to keep up with the early destruction, anemia does not occur (this is sometimes called compensated hemolysis).
 
===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.<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]]
*Unstable [[hemoglobin]] variants and [[hemoglobinopathies]]
 
====Red blood cell enzyme deficiencies====
*[[Glucose-6-phosphate dehydrogenase deficiency]]
*[[Pyruvate kinase deficiency]]
*[[Triosephosphate isomerase|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 cell|red blood cells]].


*There are many types of hemolytic anemia, which are classified by the reason for the premature destruction of red blood cells. The defect may be in the red blood cell itself (intrinsic factors), or outside the red blood cell (extrinsic factors).
====Infections====
*Shiga-toxin from [[EHEC|enterohemorrhagic E. coli]] strain O157:H&
*[[Parvovirus]]
*[[Malaria]]
*[[Babesia]]
*[[Clostridium perfringens]]


:*'''Intrinsic factors are often present at birth (hereditary).''' They include:
====Autoimmune or rheumatologic conditions====
::*Abnormalities in the proteins that build normal red blood cells
Systemic activation of the [[immune system]] due to underlying [[Rheumatologic disease|rheumatologic]] conditions can result in a predisposition for [[hemolysis]].
::*Differences in the protein inside a red blood cell that carries oxygen (hemoglobin)
*[[Systemic lupus erythematosus]]


:*'''Extrinsic factors include:'''
====Drugs====
::*Abnormal immune system responses
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.
::*Blood clots in small blood vessels
*[[Pembrolizumab]]
::*Certain infections
*[[Nivolumab]]
::*Side effects from medications
*[[Ipilimumab]]
*Durvalumab
*Avelumab
*[[Dapsone]]
*[[Quinine|Quinines]]
 
===Causes by Organ System===
 
{| style="width:80%; height:100px" border="1"
| style="width:25%" bgcolor="LightSteelBlue" ; border="1" |'''Cardiovascular'''
| 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="Beige" | [[Snake venoms|Snake venom]]
|-
|- bgcolor="LightSteelBlue"
| '''Dental'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Dermatologic'''
| bgcolor="Beige" | No underlying causes, but [[microangiopathy]] can present with [[Dermatological|dermatologic]] manifestations
|-
|- bgcolor="LightSteelBlue"
| '''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="LightSteelBlue"
| '''Ear Nose Throat'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Endocrine'''
| bgcolor="Beige" | [[Grave's disease]] and other conditions characterized by [[antibodies]] against [[endocrine organs]] can rarely cause inadvertent [[hemolysis]]
|-
|- bgcolor="LightSteelBlue"
| '''Environmental'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Genetic'''
| bgcolor="Beige" | [[Hereditary spherocytosis]], [[hereditary elliptocytosis]], [[Thalassemia|thalassemias]], [[glucose-6 phosphate deficiency]], [[pyruvate kinase deficiency]], [[Triose phosphate isomerase|triose phosphate]] deficiency
|-
|- bgcolor="LightSteelBlue"
| '''Hematologic'''
| bgcolor="Beige" | [[Microangiopathic hemolytic anemia]], [[Thrombotic thrombocytopenic purpura|thrombotic thrombocytopenia purpura]], [[disseminated intravascular coagulation]]
|-
|- bgcolor="LightSteelBlue"
| '''Iatrogenic'''
| bgcolor="Beige" | [[Immunotherapy]] drugs used to treat [[cancer]], such as [[pembrolizumab]], [[nivolumab]], [[ipilimumab]], avelumab, and  durvalumab
|-
|- bgcolor="LightSteelBlue"
| '''Infectious Disease'''
| bgcolor="Beige" | [[Babesia]], [[malaria]], ''[[Clostridium perfringens]]'', [[EHEC|enterohemorrhagic ''E.coli'']] ([[Hemolytic-uremic syndrome|hemolytic uremia syndrome]]), [[parvovirus]]
|-
|- bgcolor="LightSteelBlue"
| '''Musculoskeletal/Orthopedic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Neurologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Nutritional/Metabolic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
| bgcolor="Beige" | [[HELLP syndrome]] ([[Hemolysis|'''h'''emolysis]], '''e'''levated '''l'''iver enzymes, [[Thrombocytopenia|'''l'''ow '''p'''latelets]]) syndrome and [[Preeclampsia|pre-eclampsia]]
|-
|- bgcolor="LightSteelBlue"
| '''Oncologic'''
| bgcolor="Beige" | Anti-PD-1 agents (immunotherapeutic drugs for cancer), [[chronic lymphocytic leukemia]] (causes [[autoimmune hemolytic anemia]])
|-
|- bgcolor="LightSteelBlue"
| '''Ophthalmologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Overdose/Toxicity'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Psychiatric'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Pulmonary'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Renal/Electrolyte'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Rheumatology/Immunology/Allergy'''
| bgcolor="Beige" | [[Systemic lupus erythematosus|Systemic lupus erythematosis]]
|-
|- bgcolor="LightSteelBlue"
| '''Sexual'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Trauma'''
| bgcolor="Beige" | [[Capillary]] damage can result in [[shear stress]] and [[hemolysis]]
|-
|- bgcolor="LightSteelBlue"
| '''Urologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Miscellaneous'''
| bgcolor="Beige" | No underlying causes
|-
|}


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
[[Category:Hematology]]
{{WS}}
{{WH}}

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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