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Revision as of 05:09, 27 June 2020

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

Synonyms and keywords:

Overview

There is an association between severe COVID-19 infection and thrombocytopenia.

Historical Perspective

Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus called SARS-CoV-2, which caused a respiratory illness outbreak that was first detected in Wuhan, China.^[1]^[2]

On January 30, 2020, the outbreak was declared a Public Health Emergency of International Concern.
On March 12, 2020, the COVID-19 outbreak was declared a pandemic by the World Health Organization (WHO).

Classification

Thrombocytopenia is defined by platelet count <150 x <math>10^9</math>/L on CBC.^[3]
Classification of thrombocytopenia by platelet count is:^[4]
- Mild: between 70,000 and 150,000 x <math>10^9</math>/L
- Severe: less than 20,000 x <math>10^9</math>/L
Most patients are asymptomatic if the platelet count is 50,000 x <math>10^9</math>/L or greater.^[4]
Patients with platelet count between 30 and 50 x <math>10^9</math>/L rarely have purpura, but may have excessive bleeding with trauma.^[4]
Patients with platelet count between 10 and 30 x <math>10^3</math>/L may have bleeding with minor trauma.^[4]
Patients with platelet count less than 10 x <math>10^3</math>/L have increased risk for spontaneous bleeding, petechiae, and bruising.^[4]
Spontaneous bleeding, which is an emergency, usually occurs in patients with platelet counts less than 5 x <math>10^3</math>/L .^[4]

Pathophysiology

The pathogenesis of thrombocytopenia in COVID-19 infection is due to several factors:^[5]

Decrease in primary platelet production due to infection of bone marrow cells by coronaviruses^[6] and inhibition of bone marrow growth,^[7] which lead to abnormal hematopoietic function.^[5]

Increase in platelet destruction due to increase in auto-antibodies and immune complexes.^[8]

Decrease in circulating platelet due to lung injury which causes megakaryocyte fragmentation and decreases platelet production, because lung is a reservoir for megakaryocyte and hematopoieitic progenitor cells and has a role in platelet production.^[5]^[9]
In addition, decrease in platelets may be due to activation of platelets that result in platelet aggregation and formation of micro-thrombus which increase platelet consumption.^[5]^[10]

Causes

~~Disease name] may be caused by [cause1], [cause2], or [cause3].~~

OR

~~Common causes of [disease] include [cause1], [cause2], and [cause3].~~

OR

~~The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].~~

OR

~~The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click here.~~

Differentiating Thrombocytopenia from other Diseases

The differential diagnosis to consider in thrombocytopenia include:

Infections (Epstein-Barr virus, cytomegalovirus, hepatitis C, human immunodeficiency virus, parvovirus B19, H pylori)
Medications (antibiotics, alcohol, chemotherapy, radiation)
Folate or vitamin B12 deficiencies
Liver disease
Bone marrow failure syndromes (such as aplastic anemia, Fanconi anemia, and Diamond-Blackfan anemia)
Hematologic disorders (lymphoma, leukemia, myelodysplastic syndrome)
Tumor infiltration of bone marrow
Inherited thrombocytopenias (Bernard-Soulier syndrome, Wiskott-Aldrich syndrome, and thrombocytopenia with absent radii)

Immune thrombocytopenic purpura (ITP) and drug-induced ITP (such as quinine, NSAIDs, glycoprotein IIb/IIIa inhibitors)
Heparin-induced thrombocytopenia (HIT)
Thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS)
Drug-induced TTP (such as mitomycin C, gemcitabine, oxaliplatin)
Disseminated intravascular coagulation (DIC)
Posttransfusion purpura
Autoimmune-related thrombocytopenia (such as systemic lupus erythematosus (SLE), common variable immunodeficiency (CVID), antiphospholipid antibody syndrome,thyroid disease)
Mechanical destruction (such as cardiopulmonary bypass, intra-aortic balloon pump)

Epidemiology and Demographics

Thrombocytopenia is seen in 36% of patients with COVID-19 infection.^[11]
Thrombocytopenia is seen in 57.7% of patients with severe COVID-19 infection compared to 31.6 % of patients with non-severe infection.^[11]

Risk Factors

~~There are no established risk factors for [disease name].~~

OR

~~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].~~

OR

~~Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].~~

OR

~~Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.~~

Screening

It has been reported that thrombocytopenia upon admission for COVID-19 infection is associated with severe disease and mortality.^[12]
However, there is insufficient evidence to recommend routine screening and monitoring of thrombocytopenia for predicting disease progression in patients with COVID-19 infection and further studies are required.^[13]

Natural History, Complications, and Prognosis

Natural History

Thrombocytopenia is associated with an increased risk for severe COVID-19 infection (threefold).^[14]

Complications

Complications of thrombocytopenia in patients with severe COVID-19 infection may include:

Intravascular coagulopathy

Disseminated intravascular coagulation (DIC)^[13]
Multiple organ dysfunction syndrome^[13]
Death^[13]

Prognosis

It has been reported that thrombocytopenia upon admission for COVID-19 infection is independently and strongly associated with poor outcome and mortality.^[12]

Diagnosis

Diagnostic Study of Choice

The diagnostic study of choice for thrombocytopenia is compelete blood count (CBC).

Thrombocytopenia is defined by platelet count <150 x <math>10^9</math>/L on CBC.^[3]
Thrombocytopenia in patients with COVID-19 is usually moderate (>100× <math>10^9</math>/L), however in patients with multi-organ failure with ARDS or capillary leak syndrome platelet count is >50×<math>10^9</math>.^[14]

History and Symptoms

Thrombocytopenia in patients with COVID-19 is usually moderate (>100× <math>10^9</math>/L), however in patients with multi-organ failure with ARDS or capillary leak syndrome platelet count is >50×<math>10^9</math>.^[14]
Most patients are asymptomatic if the platelet count is 50,000 x <math>10^9</math>/L or greater.^[4]

Patients should be questioned about:^[3]^[4]
- Bruising or petechiae
- Bleeding (melena, epistaxis, menorrhagia,hematuria, prolonged bleeding after procedures, gingival bleeding and blood in sputum)
- Past medical history
- Family history
- Medications history
- Immunizations history
- Changes in vision
- Rash
- Fever
- Recent travel
- Transfusion history

Physical Examination

Thrombocytopenia in patients with COVID-19 is usually moderate (>100× <math>10^9</math>/L), however in patients with multi-organ failure with ARDS or capillary leak syndrome platelet count is >50×<math>10^9</math>.^[14]
Most patients are asymptomatic if the platelet count is 50,000 x <math>10^9</math>/L or greater.^[4]

The physical examination in patients with thrombocytopenia should include checking for:^[3]

- Bleeding^[15] (epistaxis, bloody sputum, gingival bleeding, menorrhagia, heavy bleeding after invasive procedures or childbirth)^[16]
- Unexplained bruising (petechiae, purpura, ecchymosis)
- Hepatosplenomegaly
- Abdominal tenderness
- Urinary tract (check for hematuria)^[17]
- Stool for occult blood (evaluation of gastrointestinal and rectal bleeding)
- Retinal hemorrhage on fundoscopic exam (evaluation of central nervous system bleeding)^[17]
- Neurologic examination (check for intracranial bleeding)^[17]
- Soft tissue or joint bleeding is not associated with thrombocytopenia and other coagulation disorders such as DIC should be checked.^[15]^[17]

Laboratory Findings

Compelete blood count (CBC): Thrombocytopenia is defined by platelet count <150 x <math>10^9</math>/L on CBC.^[3]
Thrombocytopenia in patients with COVID-19 is usually moderate (>100× <math>10^9</math>/L), however in patients with multi-organ failure with ARDS or capillary leak syndrome platelet count is >50×<math>10^9</math>.^[14]

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 [disease name].~~

OR

~~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].~~

OR

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].

Echocardiography or Ultrasound

~~There are no echocardiography/ultrasound findings associated with [disease name].~~

OR

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].

OR

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].

CT scan

~~There are no CT scan findings associated with [disease name].~~

OR

~~[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].~~

OR

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].

MRI

~~There are no MRI findings associated with [disease name].~~

OR

~~[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].~~

OR

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].

Other Imaging Findings

~~There are no other imaging findings associated with [disease name].~~

OR

~~[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].~~

Other Diagnostic Studies

~~There are no other diagnostic studies associated with [disease name].~~

OR

~~[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].~~

OR

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].

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 [disease name].

OR

There are no available vaccines against [disease name].

OR

Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

OR

[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].

Secondary Prevention

There are no established measures for the secondary prevention of [disease name].

OR

Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].

References

↑ https://www.cdc.gov/coronavirus/2019-ncov/about/index.html. Missing or empty |title= (help)
↑ 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.
↑ ^3.0 ^3.1 ^3.2 ^3.3 ^3.4 Greenberg EM (2017). "Thrombocytopenia: A Destruction of Platelets". J Infus Nurs. 40 (1): 41–50. doi:10.1097/NAN.0000000000000204. PMID 28030481.
↑ ^4.0 ^4.1 ^4.2 ^4.3 ^4.4 ^4.5 ^4.6 ^4.7 ^4.8 Gauer RL, Braun MM (2012). "Thrombocytopenia". Am Fam Physician. 85 (6): 612–22. PMID 22534274.
↑ ^5.0 ^5.1 ^5.2 ^5.3 Xu P, Zhou Q, Xu J (2020). "Mechanism of thrombocytopenia in COVID-19 patients". Ann Hematol. 99 (6): 1205–1208. doi:10.1007/s00277-020-04019-0. PMC 7156897 Check |pmc= value (help). PMID 32296910 Check |pmid= value (help).
↑ Yang M, Ng MH, Li CK (2005). "Thrombocytopenia in patients with severe acute respiratory syndrome (review)". Hematology. 10 (2): 101–5. doi:10.1080/10245330400026170. PMID 16019455.
↑ Yeager CL, Ashmun RA, Williams RK, Cardellichio CB, Shapiro LH, Look AT; et al. (1992). "Human aminopeptidase N is a receptor for human coronavirus 229E". Nature. 357 (6377): 420–2. doi:10.1038/357420a0. PMC 7095410 Check |pmc= value (help). PMID 1350662.
↑ Nardi M, Tomlinson S, Greco MA, Karpatkin S (2001). "Complement-independent, peroxide-induced antibody lysis of platelets in HIV-1-related immune thrombocytopenia". Cell. 106 (5): 551–61. doi:10.1016/s0092-8674(01)00477-9. PMID 11551503.
↑ Lefrançais E, Ortiz-Muñoz G, Caudrillier A, Mallavia B, Liu F, Sayah DM; et al. (2017). "The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors". Nature. 544 (7648): 105–109. doi:10.1038/nature21706. PMC 5663284. PMID 28329764.
↑ 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).
↑ ^11.0 ^11.1 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).
↑ ^12.0 ^12.1 Maquet J, Lafaurie M, Sommet A, Moulis G, Covid-Clinic-Toul investigators group. Alvarez M; et al. (2020). "Thrombocytopenia is independently associated with poor outcome in patients hospitalized for COVID-19". Br J Haematol. doi:10.1111/bjh.16950. PMID 32557535 Check |pmid= value (help).
↑ ^13.0 ^13.1 ^13.2 ^13.3 Zhang Y, Zeng X, Jiao Y, Li Z, Liu Q, Ye J; et al. (2020). "Mechanisms involved in the development of thrombocytopenia in patients with COVID-19". Thromb Res. 193: 110–115. doi:10.1016/j.thromres.2020.06.008. PMC 7274097 Check |pmc= value (help). PMID 32535232 Check |pmid= value (help).
↑ ^14.0 ^14.1 ^14.2 ^14.3 ^14.4 Lippi G, Plebani M, Henry BM (2020). "Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis". Clin Chim Acta. 506: 145–148. doi:10.1016/j.cca.2020.03.022. PMC 7102663 Check |pmc= value (help). PMID 32178975 Check |pmid= value (help).
↑ ^15.0 ^15.1 Stasi R (2012). "How to approach thrombocytopenia". Hematology Am Soc Hematol Educ Program. 2012: 191–7. doi:10.1182/asheducation-2012.1.191. PMID 23233580.
↑ Ghoshal K, Bhattacharyya M (2014). "Overview of platelet physiology: its hemostatic and nonhemostatic role in disease pathogenesis". ScientificWorldJournal. 2014: 781857. doi:10.1155/2014/781857. PMC 3960550. PMID 24729754.
↑ ^17.0 ^17.1 ^17.2 ^17.3 Sekhon SS, Roy V (2006). "Thrombocytopenia in adults: A practical approach to evaluation and management". South Med J. 99 (5): 491–8, quiz 499-500, 533. doi:10.1097/01.smj.0000209275.75045.d4. PMID 16711312.

Template:WikiDoc Sources

[1] ttps://www.cdc.gov/coronavirus/2019-ncov/about/index.html. Missing or empty |title= (help)

[LuCui2020-2] 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.

[pmid28030481-3] 3.0 ^3.1 ^3.2 ^3.3 ^3.4 Greenberg EM (2017). "Thrombocytopenia: A Destruction of Platelets". J Infus Nurs. 40 (1): 41–50. doi:10.1097/NAN.0000000000000204. PMID 28030481.

[pmid22534274-4] 4.0 ^4.1 ^4.2 ^4.3 ^4.4 ^4.5 ^4.6 ^4.7 ^4.8 Gauer RL, Braun MM (2012). "Thrombocytopenia". Am Fam Physician. 85 (6): 612–22. PMID 22534274.

[pmid32296910-5] 5.0 ^5.1 ^5.2 ^5.3 Xu P, Zhou Q, Xu J (2020). "Mechanism of thrombocytopenia in COVID-19 patients". Ann Hematol. 99 (6): 1205–1208. doi:10.1007/s00277-020-04019-0. PMC 7156897 Check |pmc= value (help). PMID 32296910 Check |pmid= value (help).

[pmid16019455-6] Yang M, Ng MH, Li CK (2005). "Thrombocytopenia in patients with severe acute respiratory syndrome (review)". Hematology. 10 (2): 101–5. doi:10.1080/10245330400026170. PMID 16019455.

[pmid1350662-7] Yeager CL, Ashmun RA, Williams RK, Cardellichio CB, Shapiro LH, Look AT; et al. (1992). "Human aminopeptidase N is a receptor for human coronavirus 229E". Nature. 357 (6377): 420–2. doi:10.1038/357420a0. PMC 7095410 Check |pmc= value (help). PMID 1350662.

[pmid11551503-8] Nardi M, Tomlinson S, Greco MA, Karpatkin S (2001). "Complement-independent, peroxide-induced antibody lysis of platelets in HIV-1-related immune thrombocytopenia". Cell. 106 (5): 551–61. doi:10.1016/s0092-8674(01)00477-9. PMID 11551503.

[pmid28329764-9] Lefrançais E, Ortiz-Muñoz G, Caudrillier A, Mallavia B, Liu F, Sayah DM; et al. (2017). "The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors". Nature. 544 (7648): 105–109. doi:10.1038/nature21706. PMC 5663284. PMID 28329764.

[pmid32495027-10] 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).

[pmid32109013-11] 11.0 ^11.1 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).

[pmid32557535-12] 12.0 ^12.1 Maquet J, Lafaurie M, Sommet A, Moulis G, Covid-Clinic-Toul investigators group. Alvarez M; et al. (2020). "Thrombocytopenia is independently associated with poor outcome in patients hospitalized for COVID-19". Br J Haematol. doi:10.1111/bjh.16950. PMID 32557535 Check |pmid= value (help).

[pmid32535232-13] 13.0 ^13.1 ^13.2 ^13.3 Zhang Y, Zeng X, Jiao Y, Li Z, Liu Q, Ye J; et al. (2020). "Mechanisms involved in the development of thrombocytopenia in patients with COVID-19". Thromb Res. 193: 110–115. doi:10.1016/j.thromres.2020.06.008. PMC 7274097 Check |pmc= value (help). PMID 32535232 Check |pmid= value (help).

[pmid32178975-14] 14.0 ^14.1 ^14.2 ^14.3 ^14.4 Lippi G, Plebani M, Henry BM (2020). "Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis". Clin Chim Acta. 506: 145–148. doi:10.1016/j.cca.2020.03.022. PMC 7102663 Check |pmc= value (help). PMID 32178975 Check |pmid= value (help).

[pmid23233580-15] 15.0 ^15.1 Stasi R (2012). "How to approach thrombocytopenia". Hematology Am Soc Hematol Educ Program. 2012: 191–7. doi:10.1182/asheducation-2012.1.191. PMID 23233580.

[pmid24729754-16] Ghoshal K, Bhattacharyya M (2014). "Overview of platelet physiology: its hemostatic and nonhemostatic role in disease pathogenesis". ScientificWorldJournal. 2014: 781857. doi:10.1155/2014/781857. PMC 3960550. PMID 24729754.

[pmid16711312-17] 17.0 ^17.1 ^17.2 ^17.3 Sekhon SS, Roy V (2006). "Thrombocytopenia in adults: A practical approach to evaluation and management". South Med J. 99 (5): 491–8, quiz 499-500, 533. doi:10.1097/01.smj.0000209275.75045.d4. PMID 16711312.

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@@ Line 12: / Line 12: @@
 * [[COVID-19|Coronavirus disease 2019 (COVID-19)]] is caused by a novel [[coronavirus]] called [[SARS-CoV-2]], which caused a respiratory illness [[outbreak]] that was first detected in Wuhan, China.<ref>{{Cite web|url=https://www.cdc.gov/coronavirus/2019-ncov/about/index.html|title=|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref name="LuCui2020">{{cite journal|last1=Lu|first1=Jian|last2=Cui|first2=Jie|last3=Qian|first3=Zhaohui|last4=Wang|first4=Yirong|last5=Zhang|first5=Hong|last6=Duan|first6=Yuange|last7=Wu|first7=Xinkai|last8=Yao|first8=Xinmin|last9=Song|first9=Yuhe|last10=Li|first10=Xiang|last11=Wu|first11=Changcheng|last12=Tang|first12=Xiaolu|title=On the origin and continuing evolution of SARS-CoV-2|journal=National Science Review|year=2020|issn=2095-5138|doi=10.1093/nsr/nwaa036}}</ref>
-*Initially, the [[Patient|patients]] were believed to have contracted the [[virus]] from [[seafood]]/animal markets which suggested animal-to-human spread.
-*The growing number of [[patients]] however, suggest that human-to-human transmission is actively occurring.<ref name="HuangWang2020">{{cite journal|last1=Huang|first1=Chaolin|last2=Wang|first2=Yeming|last3=Li|first3=Xingwang|last4=Ren|first4=Lili|last5=Zhao|first5=Jianping|last6=Hu|first6=Yi|last7=Zhang|first7=Li|last8=Fan|first8=Guohui|last9=Xu|first9=Jiuyang|last10=Gu|first10=Xiaoying|last11=Cheng|first11=Zhenshun|last12=Yu|first12=Ting|last13=Xia|first13=Jiaan|last14=Wei|first14=Yuan|last15=Wu|first15=Wenjuan|last16=Xie|first16=Xuelei|last17=Yin|first17=Wen|last18=Li|first18=Hui|last19=Liu|first19=Min|last20=Xiao|first20=Yan|last21=Gao|first21=Hong|last22=Guo|first22=Li|last23=Xie|first23=Jungang|last24=Wang|first24=Guangfa|last25=Jiang|first25=Rongmeng|last26=Gao|first26=Zhancheng|last27=Jin|first27=Qi|last28=Wang|first28=Jianwei|last29=Cao|first29=Bin|title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China|journal=The Lancet|volume=395|issue=10223|year=2020|pages=497–506|issn=01406736|doi=10.1016/S0140-6736(20)30183-5}}</ref><ref>{{Cite web|url=https://www.cdc.gov/coronavirus/2019-ncov/about/transmission.html|title=|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
 * On January 30, 2020, the [[outbreak]] was declared a Public Health Emergency of International Concern.
@@ Line 55: / Line 53: @@
 <s>The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click [[Pericarditis causes#Overview|here]].</s>
-==Differentiating ((Page name)) from other Diseases==
+==Differentiating Thrombocytopenia  from other Diseases==
-<s>[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].</s>
+The differential diagnosis to consider in [[thrombocytopenia]] include:
-<s>OR</s>
+* [[Pseudothrombocytopenia]]
+* [[Splenomegaly]]
+* Infections ([[Epstein Barr virus|Epstein-Barr virus]], cytomegalovirus, hepatitis C, human immunodeficiency virus, parvovirus B19, H pylori)
+* Medications (antibiotics, alcohol, chemotherapy, radiation)
+* Folate or  vitamin B12 deficiencies
+* Liver disease
+* Bone marrow failure syndromes (such as aplastic anemia, Fanconi anemia, and Diamond-Blackfan anemia)
+* Hematologic disorders (lymphoma, leukemia, myelodysplastic syndrome)
+* Tumor infiltration of bone marrow
+* Inherited thrombocytopenias (Bernard-Soulier syndrome, Wiskott-Aldrich syndrome, and thrombocytopenia with absent radii)
-<s>[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].</s>
+* Immune thrombocytopenic purpura (ITP) and drug-induced ITP (such as quinine, NSAIDs, glycoprotein IIb/IIIa inhibitors)
+* Heparin-induced thrombocytopenia (HIT)
+* Thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS)
+* Drug-induced TTP (such as mitomycin C, gemcitabine, oxaliplatin)
+* Disseminated intravascular coagulation (DIC)
+* Posttransfusion purpura
+* Autoimmune-related thrombocytopenia (such as systemic lupus erythematosus (SLE), common variable immunodeficiency (CVID), antiphospholipid antibody syndrome,thyroid disease)
+* Mechanical destruction (such as cardiopulmonary bypass, intra-aortic balloon pump)
 ==Epidemiology and Demographics==
@@ Line 139: / Line 154: @@
 * The physical examination in patients with thrombocytopenia should include checking for:<ref name="pmid28030481">{{cite journal| author=Greenberg EM| title=Thrombocytopenia: A Destruction of Platelets. | journal=J Infus Nurs | year= 2017 | volume= 40 | issue= 1 | pages= 41-50 | pmid=28030481 | doi=10.1097/NAN.0000000000000204 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28030481  }} </ref>
 ** Bleeding<ref name="pmid23233580">{{cite journal| author=Stasi R| title=How to approach thrombocytopenia. | journal=Hematology Am Soc Hematol Educ Program | year= 2012 | volume= 2012 | issue=  | pages= 191-7 | pmid=23233580 | doi=10.1182/asheducation-2012.1.191 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23233580  }} </ref> (epistaxis, bloody sputum, gingival bleeding, menorrhagia, heavy bleeding after invasive procedures or childbirth)<ref name="pmid24729754">{{cite journal| author=Ghoshal K, Bhattacharyya M| title=Overview of platelet physiology: its hemostatic and nonhemostatic role in disease pathogenesis. | journal=ScientificWorldJournal | year= 2014 | volume= 2014 | issue=  | pages= 781857 | pmid=24729754 | doi=10.1155/2014/781857 | pmc=3960550 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24729754  }} </ref>
 ** Unexplained bruising (petechiae, purpura, ecchymosis)
@@ Line 144: / Line 160: @@
 ** Abdominal tenderness
 ** Urinary tract (check for hematuria)<ref name="pmid16711312" />
 ** Stool for occult blood (evaluation of gastrointestinal and rectal bleeding)
 ** Retinal hemorrhage on fundoscopic exam (evaluation of central nervous system bleeding)<ref name="pmid16711312">{{cite journal| author=Sekhon SS, Roy V| title=Thrombocytopenia in adults: A practical approach to evaluation and management. | journal=South Med J | year= 2006 | volume= 99 | issue= 5 | pages= 491-8; quiz 499-500, 533 | pmid=16711312 | doi=10.1097/01.smj.0000209275.75045.d4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16711312  }} </ref>
 ** Neurologic examination (check for intracranial bleeding)<ref name="pmid16711312" />
@@ Line 151: / Line 167: @@
 === Laboratory Findings ===
-*'''Compelete blood count (CBC):''' Thrombocytopenia is defined by platelet count <150 x <math>10^9</math>/L on CBC.<ref name="pmid28030481" />
+* Compelete blood count (CBC): Thrombocytopenia is defined by platelet count <150 x <math>10^9</math>/L on CBC.<ref name="pmid28030481" />
-**<s>Thrombocytopenia in patients with COVID-19 is usually moderate (>100× <math>10^9</math>/L), however in patients with multi-organ failure with ARDS or capillary leak syndrome platelet count is >50×<math>10^9</math>.<ref name="pmid32178975" /></s>
+*<s>Thrombocytopenia in patients with COVID-19 is usually moderate (>100× <math>10^9</math>/L), however in patients with multi-organ failure with ARDS or capillary leak syndrome platelet count is >50×<math>10^9</math>.<ref name="pmid32178975" /></s>
-* '''Peripheral blood smear:'''
 *