COVID-19-associated anemia: Difference between revisions

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==Classification==
==Classification==
The following is the classification of [[anemia]] by red blood cell size with [[Mean corpuscular volume|mean corpuscular volume (MCV)]]:


* [[Macrocytic anemia]] (MCV>100)
* Anemia is defined as a hemoglobin level of less than 13 g/dL in men and less than 12 g/dL in women by the World Health Organization (WHO).
* [[Normocytic anemia]] (80<MCV<100)
** High [[reticulocyte]] count
** Low [[reticulocyte]] count


* [[Microcytic anemia]] (MCV<80)
* The following is the classification of [[anemia]] by red blood cell size with [[Mean corpuscular volume|mean corpuscular volume (MCV)]]:
** [[Macrocytic anemia]] (MCV>100)
**[[Normocytic anemia]] (80<MCV<100)
*** High [[reticulocyte]] count
*** Low [[reticulocyte]] count
 
** [[Microcytic anemia]] (MCV<80)


==Pathophysiology==
==Pathophysiology==
Line 56: Line 58:


==Epidemiology and Demographics==
==Epidemiology and Demographics==
Although [[anemia]] is not a common finding in patients with COVID-19 infection, decrease in [[hemoglobin]] in patients with severe COVID-19 infection has been reported.<ref name="pmid32495027" /><ref name="pmid32109013">{{cite journal| author=Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX | display-authors=etal| title=Clinical Characteristics of Coronavirus Disease 2019 in China. | journal=N Engl J Med | year= 2020 | volume= 382 | issue= 18 | pages= 1708-1720 | pmid=32109013 | doi=10.1056/NEJMoa2002032 | pmc=7092819 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32109013  }} </ref>
Although [[anemia]] is not a common finding in patients with [[COVID-19]] infection, decrease in [[hemoglobin]] in patients with severe [[COVID-19]] infection has been reported.<ref name="pmid32495027" /><ref name="pmid32109013">{{cite journal| author=Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX | display-authors=etal| title=Clinical Characteristics of Coronavirus Disease 2019 in China. | journal=N Engl J Med | year= 2020 | volume= 382 | issue= 18 | pages= 1708-1720 | pmid=32109013 | doi=10.1056/NEJMoa2002032 | pmc=7092819 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32109013  }} </ref>


==Risk Factors==
==Risk Factors==
<s>There are no established risk factors for [disease name].</s>
Although [[anemia]] is not a common finding in patients with [[COVID-19]] infection, but decrease in [[hemoglobin]] in patients with severe [[COVID-19]] infection has been reported.<ref name="pmid32495027" /><ref name="pmid32109013" />
 
<s>OR</s>
 
<s>The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].</s>
 
<s>OR</s>
 
<s>Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].</s>
 
<s>OR</s>
 
<s>Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.</s>


==Screening==
==Screening==
Line 86: Line 76:
==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==


* Although [[anemia]] is not a common finding in patients with COVID-19 infection, but decrease in [[hemoglobin]] in patients with severe COVID-19 infection has been reported.<ref name="pmid32495027" /><ref name="pmid32109013" />
* Although [[anemia]] is not a common finding in patients with [[COVID-19]] infection, but decrease in [[hemoglobin]] in patients with severe [[COVID-19]] infection has been reported.<ref name="pmid32495027" /><ref name="pmid32109013" />
* The median hemoglobin is lower in patients with severe COVID-19 (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).<ref name="pmid32109013" />
* The median [[hemoglobin]] is lower in patients with severe [[COVID-19]] (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).<ref name="pmid32109013" />
* Decrease in hemoglobin is seen more in critically ill patients with severe COVID-19 infection.<ref name="pmid32109013" />
* Decrease in hemoglobin is seen more in critically ill patients with severe [[COVID-19]] infection.<ref name="pmid32109013" />


==Diagnosis==
==Diagnosis==
===Diagnostic Study of Choice===
===Diagnostic Study of Choice===


* The [[diagnostic study of choice]] for [[thrombocytopenia]] is compelete blood count (CBC).
* The [[diagnostic study of choice]] for [[anemia]] is compelete blood count (CBC).
* Anemia is defined by
* Anemia is defined by
* The median hemoglobin is lower in patients with severe COVID-19 (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).<ref name="pmid32109013" />
* The median hemoglobin is lower in patients with severe [[COVID-19]] (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).<ref name="pmid32109013" />


===History and Symptoms===
===History and Symptoms===


* Although [[anemia]] is not a common finding in patients with COVID-19 infection, but decrease in [[hemoglobin]] in patients with severe COVID-19 infection has been reported.<ref name="pmid32495027" /><ref name="pmid32109013" />
* Although [[anemia]] is not a common finding in patients with [[COVID-19]] infection, but decrease in [[hemoglobin]] in patients with severe [[COVID-19]] infection has been reported.<ref name="pmid32495027" /><ref name="pmid32109013" />
* The median hemoglobin is lower in patients with severe COVID-19 (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).<ref name="pmid32109013" />
* The median hemoglobin is lower in patients with severe [[COVID-19]] (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).<ref name="pmid32109013" />
*Anemia is defined as a hemoglobin level of less than 13 g/dL in men and less than 12 g/dL in women by the World Health Organization (WHO).
* Patients with anemia should be asked about:<ref name="pmid27866575">{{cite journal| author=Powell DJ, Achebe MO| title=Anemia for the Primary Care Physician. | journal=Prim Care | year= 2016 | volume= 43 | issue= 4 | pages= 527-542 | pmid=27866575 | doi=10.1016/j.pop.2016.07.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27866575  }} </ref>
* Patients with anemia should be asked about:<ref name="pmid27866575">{{cite journal| author=Powell DJ, Achebe MO| title=Anemia for the Primary Care Physician. | journal=Prim Care | year= 2016 | volume= 43 | issue= 4 | pages= 527-542 | pmid=27866575 | doi=10.1016/j.pop.2016.07.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27866575  }} </ref>
** Blood loss  
** Blood loss  
** Duration of the anemia  
** Duration of the anemia  
** Any associated features  
** Any associated features  
** Infection  
** Infection
** Cancer
**[[Cancer]]
** Comorbidities that cause anemia (such as renal failure, rheumatoid arthritis, and inflammatory bowel disease)  
** Comorbidities that cause anemia (such as [[Renal insufficiency|renal failure]], [[rheumatoid arthritis]], and [[inflammatory bowel disease]])
** Past medical history  
** Past medical history
** Patient’s ethnicity may influence the differential  
** Patient’s ethnicity may influence the differential  
** Family history
** Family history
** Drug history (aspirin and NSAIDs)
** Drug history ([[aspirin]] and [[Non-steroidal anti-inflammatory drug|NSAIDs]])


===Physical Examination===
===Physical Examination===


* Although [[anemia]] is not a common finding in patients with COVID-19 infection, but decrease in [[hemoglobin]] in patients with severe COVID-19 infection has been reported.<ref name="pmid32495027" /><ref name="pmid32109013" />
* Although [[anemia]] is not a common finding in patients with [[COVID-19]] infection, but decrease in [[hemoglobin]] in patients with severe [[COVID-19]] infection has been reported.<ref name="pmid32495027" /><ref name="pmid32109013" />
* The median hemoglobin is lower in patients with severe COVID-19 (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).<ref name="pmid32109013" />
* The median hemoglobin is lower in patients with severe [[COVID-19]] (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).<ref name="pmid32109013" />
* The [[physical examination]] in patients with [[anemia]] may include checking for:
*Anemia is defined as a hemoglobin level of less than 13 g/dL in men and less than 12 g/dL in women by the World Health Organization (WHO).
** Pallor of the conjunctiva 
* The [[physical examination]] in patients with [[anemia]] may include checking for:<ref name="pmid27866575" />
** Lymphadenopathy  
** Pallor of the [[conjunctiva]] 
** Hepatosplenomegaly
**[[Lymphadenopathy]]
**[[Hepatosplenomegaly]]
** Bone tenderness
** Bone tenderness
** Petechiae
**[[Petechia|Petechiae]]
** Ecchymose  
**[[Bruise|Ecchymose]]  


===Laboratory Findings===
===Laboratory Findings<ref name="pmid28189170" />===


* Compelete blood count (CBC)''':'''
* Compelete blood count (CBC)''':'''
** The median hemoglobin is lower in patients with severe COVID-19 (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).<ref name="pmid32109013" />
** The median hemoglobin is lower in patients with severe [[COVID-19]] (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).<ref name="pmid32109013" />


* [[Reticulocyte]] count  
*[[Blood film|Peripheral blood smear]]: May be helpful if there is a suspicion of other causes of [[anemia]].
*[[Reticulocyte]] count : May be helpful if there is a suspicion of other causes of [[anemia]].
*Red cell indices: May be helpful if there is a suspicion of other causes of [[anemia]].
**[[Mean corpuscular volume|MCV]]
**[[Mean corpuscular hemoglobin concentration|Mean corpuscular hemoglobin concentration (MCHC)]]
**[[Mean corpuscular hemoglobin|Mean corpuscular hemoglobin (MCH)]] 


* [[Blood film|Peripheral blood smear]]:
===Electrocardiogram===
 
===<s>Electrocardiogram</s>===
<s>There are no ECG findings associated with [disease name].</s>
<s>There are no ECG findings associated with [disease name].</s>


Line 141: Line 136:
<s>An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].</s>
<s>An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].</s>


===<s>X-ray</s>===
===X-ray===
<s>There are no x-ray findings associated with [disease name].</s>
There are no [[X-rays|x-ray]] findings associated with [[anemia]] in [[COVID-19]] infection.
 
<s>OR</s>
 
<s>An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].</s>
 
<s>OR</s>
 
<s>There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].</s>
 
===<s>Echocardiography or Ultrasound</s>===
<s>There are no echocardiography/ultrasound  findings associated with [disease name].</s>
 
<s>OR</s>
 
<s>Echocardiography/ultrasound  may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].</s>
 
<s>OR</s>


<s>There are no echocardiography/ultrasound  findings associated with [disease name]. However, an echocardiography/ultrasound  may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].</s>
===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound  findings associated with [[anemia]] in [[COVID-19]] infection.


===<s>CT scan</s>===
===CT scan===
<s>There are no CT scan findings associated with [disease name].</s>
There are no [[Computed tomography|CT]] scan findings associated with [[anemia]] in [[COVID-19]] infection.


<s>OR</s>
===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[anemia]] in [[COVID-19]] infection.


<s>[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].</s>
===Other Imaging Findings===
There are no other imaging findings associated with [[anemia]] in [[COVID-19]] infection.


<s>OR</s>
===Other Diagnostic Studies<ref name="pmid28189170" />===


<s>There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].</s>
* [[Bone marrow examination]]: May be helpful if there is a suspicion of other causes of [[anemia]].
 
* [[Cytogenetics|Cytogenetic]] and [[Molecule|molecular]] tests : May be helpful if there is a suspicion of other causes of [[anemia]].
===<s>MRI</s>===
<s>There are no MRI findings associated with [disease name].</s>
 
<s>OR</s>
 
<s>[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].</s>
 
<s>OR</s>
 
<s>There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].</s>
 
===<s>Other Imaging Findings</s>===
<s>There are no other imaging findings associated with [disease name].</s>
 
<s>OR</s>
 
<s>[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].</s>
 
===<s>Other Diagnostic Studies</s>===
<s>There are no other diagnostic studies associated with [disease name].</s>
 
<s>OR</s>
 
<s>[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].</s>
 
<s>OR</s>
 
<s>Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].</s>


==Treatment==
==Treatment==
Line 266: Line 219:
<s>Surgery is the mainstay of treatment for [disease or malignancy].</s>
<s>Surgery is the mainstay of treatment for [disease or malignancy].</s>


===<s>Primary Prevention</s>===
===Primary Prevention===
<s>There are no established measures for the primary prevention of [disease name].</s>
There are no established measures for the primary prevention of [[anemia]] in [[COVID-19]] infection.
 
<s>OR</s>
 
<s>There are no available vaccines against [disease name].</s>
 
<s>OR</s>
 
<s>Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].</s>
 
<s>OR</s>
 
<s>[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].</s>
 
===<s>Secondary Prevention</s>===
<s>There are no established measures for the secondary prevention of [disease name].</s>
 
<s>OR</s>


<s>Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].</s>
===Secondary Prevention===
Minimal amount of blood blood should be drawn for blood tests and only clinically necessary tests should be ordered in order to prevent aggregation of [[anemia]] in [[COVID-19]] infection..


==References==
==References==

Revision as of 12:20, 27 June 2020

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

Synonyms and keywords:

Overview

Although anemia is not a common finding in patients with COVID-19 infection, decrease in hemoglobin in patients with severe COVID-19 infection has been reported.

Historical Perspective

Classification

  • Anemia is defined as a hemoglobin level of less than 13 g/dL in men and less than 12 g/dL in women by the World Health Organization (WHO).

Pathophysiology

The pathophysiology of decrease in hemoglobin and rarity of anemia in patients with COVID-19 infection are as the followings:[3]

Causes

Inflammation caused by COVID-19 infection affects erythropoiesis and decreases hemoglobin.[3]

Differentiating COVID-19-associated Anemia from other Diseases

Epidemiology and Demographics

Although anemia is not a common finding in patients with COVID-19 infection, decrease in hemoglobin in patients with severe COVID-19 infection has been reported.[3][6]

Risk Factors

Although anemia is not a common finding in patients with COVID-19 infection, but decrease in hemoglobin in patients with severe COVID-19 infection has been reported.[3][6]

Screening

There is insufficient evidence to recommend routine screening for [disease/malignancy].

OR

According to the [guideline name], screening for [disease name] is not recommended.

OR

According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].

Natural History, Complications, and Prognosis

  • Although anemia is not a common finding in patients with COVID-19 infection, but decrease in hemoglobin in patients with severe COVID-19 infection has been reported.[3][6]
  • The median hemoglobin is lower in patients with severe COVID-19 (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).[6]
  • Decrease in hemoglobin is seen more in critically ill patients with severe COVID-19 infection.[6]

Diagnosis

Diagnostic Study of Choice

  • The diagnostic study of choice for anemia is compelete blood count (CBC).
  • Anemia is defined by
  • The median hemoglobin is lower in patients with severe COVID-19 (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).[6]

History and Symptoms

  • Although anemia is not a common finding in patients with COVID-19 infection, but decrease in hemoglobin in patients with severe COVID-19 infection has been reported.[3][6]
  • The median hemoglobin is lower in patients with severe COVID-19 (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).[6]
  • Anemia is defined as a hemoglobin level of less than 13 g/dL in men and less than 12 g/dL in women by the World Health Organization (WHO).
  • Patients with anemia should be asked about:[7]

Physical Examination

Laboratory Findings[5]

  • Compelete blood count (CBC):
    • The median hemoglobin is lower in patients with severe COVID-19 (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).[6]

Electrocardiogram

There are no ECG findings associated with [disease name].

OR

An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

X-ray

There are no x-ray findings associated with anemia in COVID-19 infection.

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with anemia in COVID-19 infection.

CT scan

There are no CT scan findings associated with anemia in COVID-19 infection.

MRI

There are no MRI findings associated with anemia in COVID-19 infection.

Other Imaging Findings

There are no other imaging findings associated with anemia in COVID-19 infection.

Other Diagnostic Studies[5]

Treatment

Medical Therapy

There is no treatment for [disease name]; the mainstay of therapy is supportive care.

OR

Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].

OR

The majority of cases of [disease name] are self-limited and require only supportive care.

OR

[Disease name] is a medical emergency and requires prompt treatment.

OR

The mainstay of treatment for [disease name] is [therapy].

OR   The optimal therapy for [malignancy name] depends on the stage at diagnosis.

OR

[Therapy] is recommended among all patients who develop [disease name].

OR

Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].

OR

Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].

OR

Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].

OR

Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].

Surgery

Surgical intervention is not recommended for the management of [disease name].

OR

Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]

OR

The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].

OR

The feasibility of surgery depends on the stage of [malignancy] at diagnosis.

OR

Surgery is the mainstay of treatment for [disease or malignancy].

Primary Prevention

There are no established measures for the primary prevention of anemia in COVID-19 infection.

Secondary Prevention

Minimal amount of blood blood should be drawn for blood tests and only clinically necessary tests should be ordered in order to prevent aggregation of anemia in COVID-19 infection..

References

  1. ↑ https://www.cdc.gov/coronavirus/2019-ncov/about/index.html. Missing or empty |title= (help)
  2. ↑ Lu, Jian; Cui, Jie; Qian, Zhaohui; Wang, Yirong; Zhang, Hong; Duan, Yuange; Wu, Xinkai; Yao, Xinmin; Song, Yuhe; Li, Xiang; Wu, Changcheng; Tang, Xiaolu (2020). "On the origin and continuing evolution of SARS-CoV-2". National Science Review. doi:10.1093/nsr/nwaa036. ISSN 2095-5138.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Liu X, Zhang R, He G (2020). "Hematological findings in coronavirus disease 2019: indications of progression of disease". Ann Hematol. doi:10.1007/s00277-020-04103-5. PMC 7266734 Check |pmc= value (help). PMID 32495027 Check |pmid= value (help).
  4. ↑ Zhou, Fei; Yu, Ting; Du, Ronghui; Fan, Guohui; Liu, Ying; Liu, Zhibo; Xiang, Jie; Wang, Yeming; Song, Bin; Gu, Xiaoying; Guan, Lulu; Wei, Yuan; Li, Hui; Wu, Xudong; Xu, Jiuyang; Tu, Shengjin; Zhang, Yi; Chen, Hua; Cao, Bin (2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". The Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. ISSN 0140-6736.
  5. ↑ 5.0 5.1 5.2 Cascio MJ, DeLoughery TG (2017). "Anemia: Evaluation and Diagnostic Tests". Med Clin North Am. 101 (2): 263–284. doi:10.1016/j.mcna.2016.09.003. PMID 28189170.
  6. ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX; et al. (2020). "Clinical Characteristics of Coronavirus Disease 2019 in China". N Engl J Med. 382 (18): 1708–1720. doi:10.1056/NEJMoa2002032. PMC 7092819 Check |pmc= value (help). PMID 32109013 Check |pmid= value (help).
  7. ↑ 7.0 7.1 Powell DJ, Achebe MO (2016). "Anemia for the Primary Care Physician". Prim Care. 43 (4): 527–542. doi:10.1016/j.pop.2016.07.006. PMID 27866575.


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