Hemolytic anemia differential diagnosis: Difference between revisions

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__NOTOC__
__NOTOC__
{{Hemolytic anemia}}
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/Hemolytic_anemia]]
{{CMG}}
{{CMG}}; {{AE}} {{shyam}}


==Overview==
==Overview==
The differential diagnosis for hemolytic anemia is broad and includes a variety of conditions that affect [[red blood cells]]. [[Nutritional deficiencies]] and [[Thalassemia|thalassemias]] are important components of the differentiation. Certain laboratory tests and physical exam features can help to distinguish these conditions. The treatment of these conditions are quite different, so it is important to distinguish hemolytic anemia from other causes of [[anemia]] or other conditions that present similarly.


==Differentiating Hemolytic anemia from other Diseases==
==Differentiating Hemolytic anemia from other Diseases==


{| class="wikitable"
{|
! scope="col" | Characteristic/Parameter
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Characterisitc/Parameter
! scope="col" | '''Hemolytic anemia'''
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! scope="col" | '''Sideroblastic anemia'''
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physical examination
! scope="col" | '''Anemia of chronic disease'''
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Mean corpuscular volume
! scope="col" | '''Thalassemia'''
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Laboratory abnormalities
! scope="col" | '''Iron-deficiency anemia'''
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Treatment
! scope="col" | '''Erythropoietin deficiency'''
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other associated abnormalities
! scope="col" | '''Vitamin B12 deficiency'''
! scope="col" | '''Folate deficiency'''
|-
|-
! scope="row" | Symptoms
! align="center" style="background:#DCDCDC;" |Hemolytic anemia<ref name="pmid26447931">{{cite journal |vauthors=Hill QA |title=Autoimmune hemolytic anemia |journal=Hematology |volume=20 |issue=9 |pages=553–4 |date=October 2015 |pmid=26447931 |doi=10.1179/1024533215Z.000000000401 |url=}}</ref>
| [[Bleeding]], [[thrombosis]], [[Necrosis|skin necrosis]]
| align="left" style="background:#F5F5F5;" |
| [[Bleeding]], [[thrombosis]], [[petechiae]], [[sepsis]]
* [[Drug-induced]]
| [[Renal failure]], [[hematuria]], [[bleeding]], [[microangiopathic hemolytic anemia]]
* [[Immune-mediated disease|Immune-mediated]]  
| [[Renal failure]], [[hematuria]], [[bleeding]], [[microangiopathic hemolytic anemia]]
* Non-immune-mediated
| [[Petechiae]], [[bleeding]], other [[autoimmune diseases]]
* [[Infections]]
| [[Petechia]]<nowiki/>e, [[purpura]], [[ecchymoses]]
* [[Rheumatologic disease]]
| [[Bleeding]], [[photosensitivity]], [[arthritis]], [[malar rash]], discoid rash, [[Renal insufficiency|renal failure]], [[seizures]], [[psychosis]]
| align="left" style="background:#F5F5F5;" |
| [[Bleeding]], [[photosensitivity]], [[arthritis]], [[malar rash]], discoid rash, [[Renal insufficiency|renal failure]], [[seizures]], [[psychosis]]
* [[Pallor]]
* [[Jaundice]]
| align="left" style="background:#F5F5F5;" |
* [[Normocytic anemia|Normocytic]]
| align="left" style="background:#F5F5F5;" |
* Indirect [[hyperbilirubinemia]]  
* [[Reticulocytosis]]  
* Low [[haptoglobin]]
* Elevated [[LDH]]
| align="left" style="background:#F5F5F5;" |  
* Removal of offending agent
* [[Steroids]]
* Alternative [[immunosuppression]]
| align="left" style="background:#F5F5F5;" |
* [[HELLP syndrome]]
* [[TTP]]
* [[Chronic lymphocytic leukemia|CLL]]
|-
|-
! scope="row" | Platelet count
! align="center" style="background:#DCDCDC;" |[[Sideroblastic anemia]]<ref name="pmid25064706">{{cite journal |vauthors=Bottomley SS, Fleming MD |title=Sideroblastic anemia: diagnosis and management |journal=Hematol. Oncol. Clin. North Am. |volume=28 |issue=4 |pages=653–70, v |date=August 2014 |pmid=25064706 |doi=10.1016/j.hoc.2014.04.008 |url=}}</ref>
| Low but usually more than 20000 per microliter
| align="left" style="background:#F5F5F5;" |
| Low
* [[Alcoholism]]
| Low
* [[Lead poisoning]]
| Low
* [[Vitamin B6 deficiency]]
| Low; can be as low as 10000 per microliter
* [[Isoniazid]]
| Low; can be less than 10000 per microliter; sudden onset after [[transfusion]]
* [[Chloramphenicol]]
| Variable; usually low
| align="left" style="background:#F5F5F5;" |
| [[Bleeding]], [[photosensitivity]], [[arthritis]], [[malar rash]], discoid rash, [[Renal insufficiency|renal failure]], [[seizures]], [[psychosis]]
* [[Pallor]]
* [[Muscle weakness|Weakness]]
| align="left" style="background:#F5F5F5;" |
* [[Microcytic anemia|Microcytic]]
* [[Normocytic anemia|Normocytic]]
| align="left" style="background:#F5F5F5;" |
* Ringed sideroblasts in [[bone marrow]]
* Low [[vitamin B6]] level
* High [[lead]] level
| align="left" style="background:#F5F5F5;" |
* Removal of offending [[medication]]
* High-dose [[vitamin B6]] (up to 200mg daily)
* Avoidance of [[splenectomy]]
* Symptomatic [[Blood transfusion|transfusion]] support with [[iron]] [[chelation]] as needed
| align="left" style="background:#F5F5F5;" |
* [[Myelodysplastic syndrome]]  
* [[Myeloproliferative neoplasm]]
* [[Iron overload]]
|-
|-
! scope="row" | PT and PTT
! align="center" style="background:#DCDCDC;" |[[Anemia of chronic disease]]<ref name="pmid21239806">{{cite journal |vauthors=Roy CN |title=Anemia of inflammation |journal=Hematology Am Soc Hematol Educ Program |volume=2010 |issue= |pages=276–80 |date=2010 |pmid=21239806 |doi=10.1182/asheducation-2010.1.276 |url=}}</ref>
| Normal
| align="left" style="background:#F5F5F5;" |
| Elevated
* [[Chronic kidney disease]]
| Normal
* [[Rheumatologic disease]]
| Normal
* [[Cancer]]
| Normal
* [[HIV]]
| Normal
* Chronic infection; excess release of [[IL-1]] and [[IL-6]]
| Usually normal
| align="left" style="background:#F5F5F5;" |
| [[Bleeding]], [[photosensitivity]], [[arthritis]], [[malar rash]], discoid rash, [[Renal insufficiency|renal failure]], [[seizures]], [[psychosis]]
* [[Pallor]]
* [[Weakness]]
| align="left" style="background:#F5F5F5;" |  
* [[Normocytic anemia|Normocytic]]
| align="left" style="background:#F5F5F5;" |  
* Elevated [[ESR]] and [[CRP]]  
* Elevated [[hepcidin]]  
* Low serum [[iron]]  
* Low [[transferrin]]
* Elevated [[ferritin]]
| align="left" style="background:#F5F5F5;" |
* Treatment of the underlying cause; [[erythropoiesis]]-stimulating agents
* Supportive [[Red blood cell transfusion|red blood cell transfusions]]
| align="left" style="background:#F5F5F5;" |
* [[Inflammatory bowel disease]]
|-
|-
! scope="row" | Etiology
! align="center" style="background:#DCDCDC;" |[[Thalassemia]]<ref name="pmid25500521">{{cite journal |vauthors=Zainal NZ, Alauddin H, Ahmad S, Hussin NH |title=α-Thalassemia with Haemoglobin Adana mutation: prenatal diagnosis |journal=Malays J Pathol |volume=36 |issue=3 |pages=207–11 |date=December 2014 |pmid=25500521 |doi= |url=}}</ref>
| [[Heparin]] exposure
| align="left" style="background:#F5F5F5;" |
| [[Sepsis]], delivery of fetus, [[acute promyelocytic leukemia]], other [[malignancy]]
* [[Genetic defect]] with alpha- or [[beta-globin]] production
| [[Escherichia coli O157:H7|E.coli strain O157:H7]]; [[Shiga-like toxin]]
| align="left" style="background:#F5F5F5;" |  
| Dysregulation of [[Complement|complement activation]]; mutation in [[Factor H|complement factor H]]
* [[Irritability]]  
| Idiopathic; can be secondary to [[chronic lymphocytic leukemia]], [[Human Immunodeficiency Virus (HIV)|HIV]], [[Hepatitis|viral hepatitis]], [[H. pylori]]
* [[Growth retardation]]  
| Exposure to transfused products
* [[Jaundice]]
| Autoimmunity with development of [[antibodies]] to [[DNA]]
* [[Hepatomegaly]]
| [[Bleeding]], [[photosensitivity]], [[arthritis]], [[malar rash]], discoid rash, [[Renal insufficiency|renal failure]], [[seizures]], [[psychosis]]
* [[Splenomegaly]]
| align="left" style="background:#F5F5F5;" |
* [[Microcytic]]
| align="left" style="background:#F5F5F5;" |
* Abnormal [[hemoglobin]] [[electrophoresis]] (in [[beta-thalassemia]])
| align="left" style="background:#F5F5F5;" |
* [[Blood transfusion|Transfusion]] support
* [[Iron]] chelation
* [[Gene therapy]] if available
| align="left" style="background:#F5F5F5;" |
* [[Extramedullary hematopoiesis]]
|-
|-
! scope="row" | Drug-related
! align="center" style="background:#DCDCDC;" |[[Iron deficiency anemia]]<ref name="pmid25946282">{{cite journal |vauthors=Camaschella C |title=Iron-deficiency anemia |journal=N. Engl. J. Med. |volume=372 |issue=19 |pages=1832–43 |date=May 2015 |pmid=25946282 |doi=10.1056/NEJMra1401038 |url=}}</ref>
| Yes, always
| align="left" style="background:#F5F5F5;" |
| Possible
* Loss of [[iron]] from [[gastrointestinal]] blood loss or [[menstrual]] [[blood loss]]
| No
| align="left" style="background:#F5F5F5;" |
| No
* [[Pallor]]
| Yes
* [[Weakness]]
| No; transfusion-related
* Positive [[occult blood]] testing (if [[Gastrointestinal bleeding|GI bleeding]])
| Possible; drug-induced lupus can be caused by medications like [[hydralazine]] or [[isoniazid]]
| align="left" style="background:#F5F5F5;" |
| [[Bleeding]], [[photosensitivity]], [[arthritis]], [[malar rash]], discoid rash, [[Renal insufficiency|renal failure]], [[seizures]], [[psychosis]]
* [[Microcytic]]
| align="left" style="background:#F5F5F5;" |
* Low serum [[iron]]  
* Elevated [[transferrin]]  
* Low [[transferrin saturation]]
* Low [[ferritin]]
| align="left" style="background:#F5F5F5;" |
* Intravenous or oral iron supplementation
| align="left" style="background:#F5F5F5;" |
* [[Blood loss|Chronic blood loss]]
|-
|-
! scope="row" | Bleeding
! align="center" style="background:#DCDCDC;" |[[Erythropoietin]] deficiency<ref name="pmid23727690">{{cite journal |vauthors=Yamazaki S, Souma T, Hirano I, Pan X, Minegishi N, Suzuki N, Yamamoto M |title=A mouse model of adult-onset anaemia due to erythropoietin deficiency |journal=Nat Commun |volume=4 |issue= |pages=1950 |date=2013 |pmid=23727690 |doi=10.1038/ncomms2950 |url=}}</ref>
| Possible
| align="left" style="background:#F5F5F5;" |
| Usually
* [[Chronic kidney disease]] or other [[renal dysfunction]]
| Usually
| align="left" style="background:#F5F5F5;" |
| Usually
* [[Pallor]]
| Yes; spontaneous bleeding if [[platelet]] count < 10000 per microliter
* [[Weakness]]
| Yes; spontaneous bleeding if platelet count < 10000 per microliter
* Signs of [[chronic kidney disease]]
| Rare
| align="left" style="background:#F5F5F5;" |
| [[Bleeding]], [[photosensitivity]], [[arthritis]], [[malar rash]], discoid rash, [[Renal insufficiency|renal failure]], [[seizures]], [[psychosis]]
* [[Normocytic anemia|Normocytic]]
| align="left" style="background:#F5F5F5;" |
* Low [[Erythropoietin|erythropoietin level]]
| align="left" style="background:#F5F5F5;" |
* [[Epoetin alfa]] 50-100 units/kg 3 times weekly
* Darbepoietin 0.45 mcg/kg weekly or 0.75 mcg/kg every 2 weeks<ref name="pmid28626220">{{cite journal| author=Platzbecker U, Symeonidis A, Oliva EN, Goede JS, Delforge M, Mayer J et al.| title=A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes. | journal=Leukemia | year= 2017 | volume= 31 | issue= 9 | pages= 1944-1950 | pmid=28626220 | doi=10.1038/leu.2017.192 | pmc=5596208 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28626220  }} </ref>
| align="left" style="background:#F5F5F5;" |
* [[Dialysis]] dependence
* [[Myelodysplastic syndrome]]
|-
! align="center" style="background:#DCDCDC;" |[[Vitamin B12 deficiency|Vitamin B12]] or [[folate deficiency]]<ref name="pmid25189324">{{cite journal |vauthors=Hunt A, Harrington D, Robinson S |title=Vitamin B12 deficiency |journal=BMJ |volume=349 |issue= |pages=g5226 |date=September 2014 |pmid=25189324 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Pernicious anemia]]
* [[Diphyllobothrium latum infection]]
* [[Nutritional deficiency]]
* [[Crohn's disease|Crohn's disease of terminal ileum]]
| align="left" style="background:#F5F5F5;" |
* [[Numbness]]
* [[Weakness]]
* [[Tingling]]
* [[Paresthesias]]
| align="left" style="background:#F5F5F5;" |
* [[Macrocytic anemia|Macrocytic]]
| align="left" style="background:#F5F5F5;" |
* Low vitamin B12 or folate level
* [[Megaloblastic anemia]] with  hypersegmented [[neutrophils]]
| align="left" style="background:#F5F5F5;" |  
* [[Vitamin B12]] 1000mcg daily
* [[Folate]] 1mg daily
| align="left" style="background:#F5F5F5;" |
* [[Neuropathy]]
|}
|}
'''Table legend:''' [[HELLP]], hemolysis/elevated liver enzymes/low platelets; '''TTP''', thrombotic thrombocytopenic purpura; '''CLL''', [[chronic lymphocytic leukemia]]


==References==
==References==

Latest revision as of 20:55, 26 February 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shyam Patel [2]

Overview

The differential diagnosis for hemolytic anemia is broad and includes a variety of conditions that affect red blood cells. Nutritional deficiencies and thalassemias are important components of the differentiation. Certain laboratory tests and physical exam features can help to distinguish these conditions. The treatment of these conditions are quite different, so it is important to distinguish hemolytic anemia from other causes of anemia or other conditions that present similarly.

Differentiating Hemolytic anemia from other Diseases

Characterisitc/Parameter Etiology Physical examination Mean corpuscular volume Laboratory abnormalities Treatment Other associated abnormalities
Hemolytic anemia[1]
Sideroblastic anemia[2]
Anemia of chronic disease[3]
Thalassemia[4]
Iron deficiency anemia[5]
  • Intravenous or oral iron supplementation
Erythropoietin deficiency[6]
  • Epoetin alfa 50-100 units/kg 3 times weekly
  • Darbepoietin 0.45 mcg/kg weekly or 0.75 mcg/kg every 2 weeks[7]
Vitamin B12 or folate deficiency[8]

Table legend: HELLP, hemolysis/elevated liver enzymes/low platelets; TTP, thrombotic thrombocytopenic purpura; CLL, chronic lymphocytic leukemia

References

  1. ↑ Hill QA (October 2015). "Autoimmune hemolytic anemia". Hematology. 20 (9): 553–4. doi:10.1179/1024533215Z.000000000401. PMID 26447931.
  2. ↑ Bottomley SS, Fleming MD (August 2014). "Sideroblastic anemia: diagnosis and management". Hematol. Oncol. Clin. North Am. 28 (4): 653–70, v. doi:10.1016/j.hoc.2014.04.008. PMID 25064706.
  3. ↑ Roy CN (2010). "Anemia of inflammation". Hematology Am Soc Hematol Educ Program. 2010: 276–80. doi:10.1182/asheducation-2010.1.276. PMID 21239806.
  4. ↑ Zainal NZ, Alauddin H, Ahmad S, Hussin NH (December 2014). "α-Thalassemia with Haemoglobin Adana mutation: prenatal diagnosis". Malays J Pathol. 36 (3): 207–11. PMID 25500521.
  5. ↑ Camaschella C (May 2015). "Iron-deficiency anemia". N. Engl. J. Med. 372 (19): 1832–43. doi:10.1056/NEJMra1401038. PMID 25946282.
  6. ↑ Yamazaki S, Souma T, Hirano I, Pan X, Minegishi N, Suzuki N, Yamamoto M (2013). "A mouse model of adult-onset anaemia due to erythropoietin deficiency". Nat Commun. 4: 1950. doi:10.1038/ncomms2950. PMID 23727690.
  7. ↑ Platzbecker U, Symeonidis A, Oliva EN, Goede JS, Delforge M, Mayer J; et al. (2017). "A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes". Leukemia. 31 (9): 1944–1950. doi:10.1038/leu.2017.192. PMC 5596208. PMID 28626220.
  8. ↑ Hunt A, Harrington D, Robinson S (September 2014). "Vitamin B12 deficiency". BMJ. 349: g5226. PMID 25189324.

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