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Revision as of 07:46, 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

Thrombocytopenia in COVID-19 infection is more common is patients with severe infection and it has been reported that thrombocytopenia upon admission for COVID-19 infection is associated with poor outcome and mortality.

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]
Decrease in platelets may also be due to a cytokine storm caused by the COVID-19 infection which results in the destruction of bone marrow progenitor cells.^[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

The causes of thrombocytopenia in COVID-19 infection are:^[11]

Attack on hematopoietic stem cells (HSCs)
Abnormal bone marrow microenvironment
Decreased production of thrombopoietin (TPO)
Cellular immunity and cytokine storm
Lung damage
Increased platelet consumption
Increased platelet clearance
Drug-induced thrombocytopenia (antiviral drugs)

Differentiating Thrombocytopenia from other Diseases

The differential diagnosis to consider in thrombocytopenia include:^[12]

Pseudothrombocytopenia
Splenomegaly
Infections (Epstein-Barr virus, cytomegalovirus, hepatitis C, HIV, parvovirus B19, H pylori)
Drugs (antibiotics, alcohol, chemotherapy, radiation)
Folate deficiency or vitamin B12 deficiency
Liver disease
Bone marrow failure (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 36.2% of all patients with COVID-19 infection.^[13]
Thrombocytopeniais seen in 57.7% of patients with severe COVID-19 infection compared to 31.6 % of patients with non-severe infection.^[13]

Risk Factors

Thrombocytopenia in COVID-19 infection is more common is patients with severe infection compared to patients with non-severe infection.^[13]

Screening

It has been reported that thrombocytopenia upon admission for COVID-19 infection is associated with severe disease and mortality.^[14]
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.^[11]

Natural History, Complications, and Prognosis

Natural History

Thrombocytopenia is associated with an increased risk for severe COVID-19 infection (threefold).^[15]

Complications

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

Prognosis

It has been reported that thrombocytopenia upon admission for COVID-19 infection is independently and strongly associated with poor outcome and mortality.^[14]

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]
The median platelet count in COVID-19 patients with thrombocytopenia is 137,500 and 172,000 x <math>10^9</math>/L in severe and non-severe infection, respectively.^[13]

History and Symptoms

The median platelet count in COVID-19 patients with thrombocytopenia is 137,500 and 172,000 x <math>10^9</math>/L in severe and non-severe infection, respectively.^[13]
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
- Immunization history
- Changes in vision
- Rash
- Fever
- Recent travel
- Transfusion history

Physical Examination

The median platelet count in COVID-19 patients with thrombocytopenia is 137,500 and 172,000 x <math>10^9</math>/L in severe and non-severe infection, respectively.^[13]
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^[16] (epistaxis, bloody sputum, gingival bleeding, menorrhagia, heavy bleeding after invasive procedures or childbirth)^[17]
- Unexplained bruising (petechiae, purpura, ecchymosis)
- Hepatosplenomegaly
- Abdominal tenderness
- Urinary tract (check for hematuria)^[18]
- Stool for occult blood (evaluation of gastrointestinal and rectal bleeding)
- Retinal hemorrhage on fundoscopic exam (evaluation of central nervous system bleeding)^[18]
- Neurologic examination (check for intracranial bleeding)^[18]
- Soft tissue or joint bleeding is not associated with thrombocytopenia and other coagulation disorders such as DIC should be checked.^[16]^[18]

Laboratory Findings

Compelete blood count (CBC): Thrombocytopenia is defined by platelet count <150 x <math>10^9</math>/L on CBC.^[3]
- The median platelet count in COVID-19 patients with thrombocytopenia is 137,500 and 172,000 x <math>10^9</math>/L in severe and non-severe infection, respectively.^[13]

Peripheral blood smear: Peripheral blood smear may be helpful if there is suspicion of other disorders that cause thrombocytopenia.
Other laboratory testings (such as HIV, HCV testing, antibody testing, liver enzymes and liver function testing) are performed if there is suspicion of other disorders that cause thrombocytopenia.

Electrocardiogram

There are no ECG findings associated with thrombocytopenia in COVID-19 infection.

X-ray

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

Echocardiography or Ultrasound

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

CT scan

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

MRI

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

Other Imaging Findings

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

Other Diagnostic Studies

There are no other diagnostic studies associated with thrombocytopenia in COVID-19 infection. However, bone marrow biopsy may be helpful if there is suspicion of other disorders that cause thrombocytopenia.

Treatment

Medical Therapy

The treatment options for thrombocytopenia in COVID-19 infection include:^[19]

Rituximab,
Thrombopoietin receptor agonists (eltrombopag, avatrombopag, romiplostim)
High-dose dexamethasone as an alternative to prednisone
Intravenous immunoglobulins (IVIg) (1 g/kg on 1 or 2 consecutive days or 0.4 g/kg per day for 5 days)
Intravenous anti-D (50–75 mg/kg once) (consider potential triggering of DIC or hemolysis)
Platelet growth factors in patients with bleeding, high risk for bleeding, unresponsive to prednisone (carefully evaluate due to the potential thrombotic events in coronavirus infection)
Platelet transfusion in refractory visceral or cerebral meningeal hemorrhage

Surgery

The mainstay of treatment for severe thrombocytopenia in COVID-19 infection is medical therapy. Surgery has not been reported to be indicated in thrombocytopenia in COVID-19 infection.

Primary Prevention

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

Secondary Prevention

There are no established measures for the secondary prevention of thrombocytopenia in COVID-19 infection. However, it may include avoidance of antiviral medications.

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 ^5.4 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 ^11.2 ^11.3 ^11.4 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).
↑ Lee EJ, Lee AI (2016). "Thrombocytopenia". Prim Care. 43 (4): 543–557. doi:10.1016/j.pop.2016.07.008. PMID 27866576.
↑ ^13.0 ^13.1 ^13.2 ^13.3 ^13.4 ^13.5 ^13.6 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).
↑ ^14.0 ^14.1 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).
↑ 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).
↑ ^16.0 ^16.1 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.
↑ ^18.0 ^18.1 ^18.2 ^18.3 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.
↑ Lorenzo-Villalba N, Zulfiqar AA, Auburtin M, Schuhmacher MH, Meyer A, Maouche Y; et al. (2020). "Thrombocytopenia in the Course of COVID-19 Infection". Eur J Case Rep Intern Med. 7 (6): 001702. doi:10.12890/2020_001702. PMC 7279909 Check |pmc= value (help). PMID 32523922 Check |pmid= value (help).

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 ^5.4 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).

[pmid32535232-11] 11.0 ^11.1 ^11.2 ^11.3 ^11.4 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).

[pmid27866576-12] Lee EJ, Lee AI (2016). "Thrombocytopenia". Prim Care. 43 (4): 543–557. doi:10.1016/j.pop.2016.07.008. PMID 27866576.

[pmid32109013-13] 13.0 ^13.1 ^13.2 ^13.3 ^13.4 ^13.5 ^13.6 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).

[pmid32557535-14] 14.0 ^14.1 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).

[pmid32178975-15] 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).

[pmid23233580-16] 16.0 ^16.1 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.

[pmid24729754-17] 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.

[pmid16711312-18] 18.0 ^18.1 ^18.2 ^18.3 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.

[pmid32523922-19] Lorenzo-Villalba N, Zulfiqar AA, Auburtin M, Schuhmacher MH, Meyer A, Maouche Y; et al. (2020). "Thrombocytopenia in the Course of COVID-19 Infection". Eur J Case Rep Intern Med. 7 (6): 001702. doi:10.12890/2020_001702. PMC 7279909 Check |pmc= value (help). PMID 32523922 Check |pmid= value (help).

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@@ Line 7: / Line 7: @@
 ==Overview==
-There is an association between severe [[COVID-19]] infection and [[thrombocytopenia]].
+[[Thrombocytopenia]] in [[COVID-19]] infection is more common is patients with severe infection and it has been reported that [[thrombocytopenia]] upon admission for [[COVID-19]] infection is associated with poor outcome and mortality.
 ==Historical Perspective==
@@ Line 19: / Line 19: @@
 *[[Thrombocytopenia]] is defined by platelet count <150 x <math>10^9</math>/L on CBC.<ref name="pmid28030481" />
-*Classification of thrombocytopenia by platelet count is:<ref name="pmid22534274">{{cite journal| author=Gauer RL, Braun MM| title=Thrombocytopenia. | journal=Am Fam Physician | year= 2012 | volume= 85 | issue= 6 | pages= 612-22 | pmid=22534274 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22534274  }} </ref>
+*Classification of [[thrombocytopenia]] by platelet count is:<ref name="pmid22534274">{{cite journal| author=Gauer RL, Braun MM| title=Thrombocytopenia. | journal=Am Fam Physician | year= 2012 | volume= 85 | issue= 6 | pages= 612-22 | pmid=22534274 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22534274  }} </ref>
 **Mild: between 70,000 and 150,000 x <math>10^9</math>/L
 **Severe: less than 20,000 x <math>10^9</math>/L
@@ Line 31: / Line 31: @@
 The [[pathogenesis]] of [[thrombocytopenia]] in [[COVID-19]] infection is due to several factors:<ref name="pmid32296910">{{cite journal| author=Xu P, Zhou Q, Xu J| title=Mechanism of thrombocytopenia in COVID-19 patients. | journal=Ann Hematol | year= 2020 | volume= 99 | issue= 6 | pages= 1205-1208 | pmid=32296910 | doi=10.1007/s00277-020-04019-0 | pmc=7156897 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32296910  }} </ref>
-* Decrease in primary platelet production due to infection of bone marrow cells by [[Coronavirus|coronaviruses]]<ref name="pmid16019455">{{cite journal| author=Yang M, Ng MH, Li CK| title=Thrombocytopenia in patients with severe acute respiratory syndrome (review). | journal=Hematology | year= 2005 | volume= 10 | issue= 2 | pages= 101-5 | pmid=16019455 | doi=10.1080/10245330400026170 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16019455  }} </ref> and inhibition of bone marrow growth,<ref name="pmid1350662">{{cite journal| author=Yeager CL, Ashmun RA, Williams RK, Cardellichio CB, Shapiro LH, Look AT | display-authors=etal| title=Human aminopeptidase N is a receptor for human coronavirus 229E. | journal=Nature | year= 1992 | volume= 357 | issue= 6377 | pages= 420-2 | pmid=1350662 | doi=10.1038/357420a0 | pmc=7095410 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1350662  }} </ref> which lead to abnormal [[hematopoietic]] function.<ref name="pmid32296910" />
+* Decrease in primary platelet production due to infection of bone marrow cells by [[Coronavirus|coronaviruses]]<ref name="pmid16019455">{{cite journal| author=Yang M, Ng MH, Li CK| title=Thrombocytopenia in patients with severe acute respiratory syndrome (review). | journal=Hematology | year= 2005 | volume= 10 | issue= 2 | pages= 101-5 | pmid=16019455 | doi=10.1080/10245330400026170 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16019455  }} </ref> and inhibition of [[bone marrow]] growth,<ref name="pmid1350662">{{cite journal| author=Yeager CL, Ashmun RA, Williams RK, Cardellichio CB, Shapiro LH, Look AT | display-authors=etal| title=Human aminopeptidase N is a receptor for human coronavirus 229E. | journal=Nature | year= 1992 | volume= 357 | issue= 6377 | pages= 420-2 | pmid=1350662 | doi=10.1038/357420a0 | pmc=7095410 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1350662  }} </ref> which lead to abnormal [[hematopoietic]] function.<ref name="pmid32296910" />
 *Decrease in platelets may also be due to a [[cytokine storm]] caused by the [[COVID-19]] infection which results in the destruction of bone marrow [[Progenitor cell|progenitor cells]].<ref name="pmid32296910" />
 * Increase in [[platelet]] destruction due to increase in auto-antibodies and immune complexes.<ref name="pmid11551503">{{cite journal| author=Nardi M, Tomlinson S, Greco MA, Karpatkin S| title=Complement-independent, peroxide-induced antibody lysis of platelets in HIV-1-related immune thrombocytopenia. | journal=Cell | year= 2001 | volume= 106 | issue= 5 | pages= 551-61 | pmid=11551503 | doi=10.1016/s0092-8674(01)00477-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11551503  }} </ref>
-* 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.<ref name="pmid32296910" /><ref name="pmid28329764">{{cite journal| author=Lefrançais E, Ortiz-Muñoz G, Caudrillier A, Mallavia B, Liu F, Sayah DM | display-authors=etal| title=The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. | journal=Nature | year= 2017 | volume= 544 | issue= 7648 | pages= 105-109 | pmid=28329764 | doi=10.1038/nature21706 | pmc=5663284 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28329764  }} </ref>
+* 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.<ref name="pmid32296910" /><ref name="pmid28329764">{{cite journal| author=Lefrançais E, Ortiz-Muñoz G, Caudrillier A, Mallavia B, Liu F, Sayah DM | display-authors=etal| title=The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. | journal=Nature | year= 2017 | volume= 544 | issue= 7648 | pages= 105-109 | pmid=28329764 | doi=10.1038/nature21706 | pmc=5663284 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28329764  }} </ref>
 *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.<ref name="pmid32296910" /><ref name="pmid32495027">{{cite journal| author=Liu X, Zhang R, He G| title=Hematological findings in coronavirus disease 2019: indications of progression of disease. | journal=Ann Hematol | year= 2020 | volume=  | issue=  | pages=  | pmid=32495027 | doi=10.1007/s00277-020-04103-5 | pmc=7266734 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32495027  }} </ref>
@@ Line 74: / Line 74: @@
 ==Epidemiology and Demographics==
-*[[Thrombocytopenia]] is seen in 36% of patients with COVID-19 infection.<ref name="pmid32109013" />
+*[[Thrombocytopenia]] is seen in 36.2% of all patients with COVID-19 infection.<ref name="pmid32109013" />
-* Thrombocytopenia is seen in 57.7% of patients with severe [[COVID-19]] infection compared to 31.6 % of patients with non-severe infection.<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>
+*[[Thrombocytopenia]]<nowiki/>is seen in 57.7% of patients with severe [[COVID-19]] infection compared to 31.6 % of patients with non-severe infection.<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==
@@ Line 106: / Line 106: @@
 *[[Thrombocytopenia]] is defined by platelet count <150 x <math>10^9</math>/L on CBC.<ref name="pmid28030481" />
-*<s>[[Thrombocytopenia]]</s> <s>in patients with [[COVID-19]] is usually moderate (>100× <math>10^9</math>/L), however in patients with multi-organ failure with [[Acute respiratory distress syndrome|ARDS]] or [[capillary leak syndrome]] platelet count is >50×<math>10^9</math>.<ref name="pmid32178975" /></s>
+*The median [[platelet]] count in [[COVID-19]] patients with [[thrombocytopenia]] is 137,500 and 172,000 x <math>10^9</math>/L in severe and non-severe infection, respectively.<ref name="pmid32109013" />
 ===History and Symptoms===
-*<s>[[Thrombocytopenia]]</s> <s>in patients with [[COVID-19]] is usually moderate (>100× <math>10^9</math>/L), however in patients with multi-organ failure with [[Acute respiratory distress syndrome|ARDS]] or [[capillary leak syndrome]] platelet count is >50×<math>10^9</math>.<ref name="pmid32178975" /></s>
+*The median [[platelet]] count in [[COVID-19]] patients with [[thrombocytopenia]] is 137,500 and 172,000 x <math>10^9</math>/L in severe and non-severe infection, respectively.<ref name="pmid32109013" />
 * Most patients are asymptomatic if the platelet count is 50,000 x <math>10^9</math>/L or greater.<ref name="pmid22534274" />
@@ Line 119: / Line 119: @@
 ** Family history
 ** Medications history
-** Immunization history
+**[[Vaccination|Immunization]] history
 ** Changes in vision
 ** Rash
@@ Line 131: / Line 131: @@
 ===Physical Examination===
-* <s>[[Thrombocytopenia]] in patients with [[COVID-19]] is usually moderate (>100× <math>10^9</math>/L), however in patients with multi-organ failure with [[Acute respiratory distress syndrome|ARDS]] or [[capillary leak syndrome]] platelet count is >50×<math>10^9</math>.<ref name="pmid32178975" /></s>
+* The median [[platelet]] count in [[COVID-19]] patients with [[thrombocytopenia]] is 137,500 and 172,000 x <math>10^9</math>/L in severe and non-severe infection, respectively.<ref name="pmid32109013" />
-* Most patients are asymptomatic if the platelet count is 50,000 x <math>10^9</math>/L or greater.<ref name="pmid22534274" />
+* Most patients are asymptomatic if the [[platelet]] count is 50,000 x <math>10^9</math>/L or greater.<ref name="pmid22534274" />
-* 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>
+* 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, [[Gingiva|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>
@@ Line 141: / Line 141: @@
 ** Abdominal tenderness
 ** Urinary tract (check for [[hematuria]])<ref name="pmid16711312" />
-** Stool for occult blood (evaluation of [[Gastrointestinal tract|gastrointestinal]] and [[rectal]] bleeding)
+** Stool for [[occult blood]] (evaluation of [[Gastrointestinal tract|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 hemorrhage|intracranial bleeding]])<ref name="pmid16711312" />
-** Soft tissue or joint bleeding is not associated with thrombocytopenia and other [[Coagulopathy|coagulation disorders]] such as [[Disseminated intravascular coagulation|DIC]] should be checked.<ref name="pmid23233580" /><ref name="pmid16711312" />
+** Soft tissue or joint bleeding is not associated with [[thrombocytopenia]] and other [[Coagulopathy|coagulation disorders]] such as [[Disseminated intravascular coagulation|DIC]] should be checked.<ref name="pmid23233580" /><ref name="pmid16711312" />
 === 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]]</s> <s>in patients with [[COVID-19]] is usually moderate (>100× <math>10^9</math>/L), however in patients with multi-organ failure with [[Acute respiratory distress syndrome|ARDS]] or [[capillary leak syndrome]] platelet count is >50×<math>10^9</math>.<ref name="pmid32178975" /></s>
+**The median [[platelet]] count in [[COVID-19]] patients with [[thrombocytopenia]] is 137,500 and 172,000 x <math>10^9</math>/L in severe and non-severe infection, respectively.<ref name="pmid32109013" />
-* '''Peripheral blood smear:'''
+*[[Blood film|Peripheral blood smear]]: Peripheral blood smear may be helpful if there is suspicion of other disorders that cause [[thrombocytopenia]].
+*Other [[laboratory]] testings (such as [[Human Immunodeficiency Virus (HIV)|HIV]], [[Hepatitis C|HCV]] testing, antibody testing, liver [[enzymes]] and [[Liver function tests|liver function testing]]) are performed if there is suspicion of other disorders that cause [[thrombocytopenia]].
 *
-===<s>Electrocardiogram</s>===
+===Electrocardiogram===
-<s>There are no ECG findings associated with [disease name].</s>
+There are no ECG findings associated with [[thrombocytopenia]] in [[COVID-19]] infection.
-<s>OR</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>===
-<s>There are no x-ray findings associated with [disease name].</s>
-<s>OR</s>
+===X-ray===
+There are no x-ray findings associated with [[thrombocytopenia]] in [[COVID-19]] infection.
-<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>
+===Echocardiography or Ultrasound===
+There are no echocardiography/ultrasound  findings associated with [[thrombocytopenia]] in [[COVID-19]] infection.
-<s>OR</s>
+===CT scan===
+There are no CT scan findings associated with [[thrombocytopenia]] in [[COVID-19]] infection.
-<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>
+===MRI===
+There are no MRI findings associated with [[thrombocytopenia]] in [[COVID-19]] infection.
-===<s>Echocardiography or Ultrasound</s>===
+===Other Imaging Findings===
-<s>There are no echocardiography/ultrasound  findings associated with [disease name].</s>
+There are no other imaging findings associated with [[thrombocytopenia]] in [[COVID-19]] infection.
-<s>OR</s>
+===Other Diagnostic Studies===
+There are no other diagnostic studies associated with [[thrombocytopenia]] in [[COVID-19]] infection. However, [[bone marrow biopsy]] may be helpful if there is suspicion of other disorders that cause thrombocytopenia.
-<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>
-===<s>CT scan</s>===
-<s>There are no CT scan findings associated with [disease name].</s>
-<s>OR</s>
-<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>
-<s>OR</s>
-<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>
-===<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==
 ===Medical Therapy===
-The treatment options for [[thrombocytopenia]] in [[COVID-19]] include:<ref name="pmid32523922">{{cite journal| author=Lorenzo-Villalba N, Zulfiqar AA, Auburtin M, Schuhmacher MH, Meyer A, Maouche Y | display-authors=etal| title=Thrombocytopenia in the Course of COVID-19 Infection. | journal=Eur J Case Rep Intern Med | year= 2020 | volume= 7 | issue= 6 | pages= 001702 | pmid=32523922 | doi=10.12890/2020_001702 | pmc=7279909 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32523922  }} </ref>
+The treatment options for [[thrombocytopenia]] in [[COVID-19]] infection include:<ref name="pmid32523922">{{cite journal| author=Lorenzo-Villalba N, Zulfiqar AA, Auburtin M, Schuhmacher MH, Meyer A, Maouche Y | display-authors=etal| title=Thrombocytopenia in the Course of COVID-19 Infection. | journal=Eur J Case Rep Intern Med | year= 2020 | volume= 7 | issue= 6 | pages= 001702 | pmid=32523922 | doi=10.12890/2020_001702 | pmc=7279909 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32523922  }} </ref>
 * [[Rituximab]],
@@ Line 233: / Line 186: @@
 * Intravenous immunoglobulins (IVIg) (1 g/kg on 1 or 2 consecutive days or 0.4 g/kg per day for 5 days)
 * Intravenous anti-D (50–75 mg/kg once) (consider potential triggering of [[Disseminated intravascular coagulation|DIC]] or [[hemolysis]])
-* Platelet growth factors in patients with bleeding, high risk for bleeding, unresponsive to [[prednisone]] (carefully evaluate due to the potential thrombotic events during coronavirus infection)
+* Platelet growth factors in patients with bleeding, high risk for bleeding, unresponsive to [[prednisone]] (carefully evaluate due to the potential thrombotic events in coronavirus infection)
 * Platelet transfusion in refractory visceral or cerebral meningeal hemorrhage
 ===Surgery===
-Surgical intervention is not recommended for the management of [disease name].
+The mainstay of treatment for severe [[thrombocytopenia]] in [[COVID-19]] infection is medical therapy. Surgery has not been reported to be indicated in [[thrombocytopenia]] in [[COVID-19]] infection.
-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].
+There are no established measures for the primary [[Prevention (medical)|prevention]] of [[thrombocytopenia]] in [[COVID-19]] infection.
-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].
+There are no established measures for the secondary [[Prevention (medical)|prevention]] of [[thrombocytopenia]] in [[COVID-19]] infection. However, it may include avoidance of antiviral medications.
-OR
-Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].
 ==References==