COVID-19-associated thrombocytopenia: Difference between revisions
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* 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, 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> | ** 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) | ** Unexplained bruising (petechiae, purpura, ecchymosis) | ||
| Line 145: | Line 144: | ||
** Abdominal tenderness | ** Abdominal tenderness | ||
** Urinary tract (check for hematuria)<ref name="pmid16711312" /> | ** Urinary tract (check for hematuria)<ref name="pmid16711312" /> | ||
** Stool for occult blood (evaluation of gastrointestinal and rectal bleeding) | ** 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> | ** 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" /> | ** Neurologic examination (check for intracranial bleeding)<ref name="pmid16711312" /> | ||
| Line 152: | Line 151: | ||
=== Laboratory Findings === | === 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:''' | |||
* | * | ||
Revision as of 18:57, 26 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]
- Initially, the 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.[3][4]
- 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.[5]
- Classification of thrombocytopenia by platelet count is:[6]
- 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.[6]
- Patients with platelet count between 30 and 50 x <math>10^9</math>/L rarely have purpura, but may have excessive bleeding with trauma.[6]
- Patients with platelet count between 10 and 30 x <math>10^3</math>/L may have bleeding with minor trauma.[6]
- Patients with platelet count less than 10 x <math>10^3</math>/L have increased risk for spontaneous bleeding, petechiae, and bruising.[6]
- Spontaneous bleeding, which is an emergency, usually occurs in patients with platelet counts less than 5 x <math>10^3</math>/L .[6]
Pathophysiology
The pathogenesis of thrombocytopenia in COVID-19 infection is due to several factors:[7]
- Decrease in primary platelet production due to infection of bone marrow cells by coronaviruses[8] and inhibition of bone marrow growth,[9] which lead to abnormal hematopoietic function.[7]
- 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.[7][11]
- 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.[7][12]
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 ((Page name)) from other Diseases
[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].
OR
[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].
Epidemiology and Demographics
- Thrombocytopenia is seen in 36% of patients with COVID-19 infection.[13]
- Thrombocytopenia is seen in 57.7% of patients with severe COVID-19 infection compared to 31.6 % of patients with non-severe infection.[13]
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.[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.[15]
Natural History, Complications, and Prognosis
Natural History
Thrombocytopenia is associated with an increased risk for severe COVID-19 infection (threefold).[16]
Complications
Complications of thrombocytopenia in patients with severe COVID-19 infection may include:
- Intravascular coagulopathy
- Disseminated intravascular coagulation (DIC)[15]
- Multiple organ dysfunction syndrome[15]
- Death[15]
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.[5]
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>.[16]
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>.[16]- Most patients are asymptomatic if the platelet count is 50,000 x <math>10^9</math>/L or greater.[6]
- Patients should be questioned about:[5][6]
- 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>.[16]- Most patients are asymptomatic if the platelet count is 50,000 x <math>10^9</math>/L or greater.[6]
- The physical examination in patients with thrombocytopenia should include checking for:[5]
- Bleeding[17] (epistaxis, bloody sputum, gingival bleeding, menorrhagia, heavy bleeding after invasive procedures or childbirth)[18]
- Unexplained bruising (petechiae, purpura, ecchymosis)
- Hepatosplenomegaly
- Abdominal tenderness
- Urinary tract (check for hematuria)[19]
- Stool for occult blood (evaluation of gastrointestinal and rectal bleeding)
- Retinal hemorrhage on fundoscopic exam (evaluation of central nervous system bleeding)[19]
- Neurologic examination (check for intracranial bleeding)[19]
- Soft tissue or joint bleeding is not associated with thrombocytopenia and other coagulation disorders such as DIC should be checked.[17][19]
Laboratory Findings
- Compelete blood count (CBC): Thrombocytopenia is defined by platelet count <150 x <math>10^9</math>/L on CBC.[5]
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>.[16]
- Peripheral blood smear:
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.
- ↑ Huang, Chaolin; Wang, Yeming; Li, Xingwang; Ren, Lili; Zhao, Jianping; Hu, Yi; Zhang, Li; Fan, Guohui; Xu, Jiuyang; Gu, Xiaoying; Cheng, Zhenshun; Yu, Ting; Xia, Jiaan; Wei, Yuan; Wu, Wenjuan; Xie, Xuelei; Yin, Wen; Li, Hui; Liu, Min; Xiao, Yan; Gao, Hong; Guo, Li; Xie, Jungang; Wang, Guangfa; Jiang, Rongmeng; Gao, Zhancheng; Jin, Qi; Wang, Jianwei; Cao, Bin (2020). "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China". The Lancet. 395 (10223): 497–506. doi:10.1016/S0140-6736(20)30183-5. ISSN 0140-6736.
- ↑ https://www.cdc.gov/coronavirus/2019-ncov/about/transmission.html. Missing or empty
|title=(help) - ↑ 5.0 5.1 5.2 5.3 5.4 Greenberg EM (2017). "Thrombocytopenia: A Destruction of Platelets". J Infus Nurs. 40 (1): 41–50. doi:10.1097/NAN.0000000000000204. PMID 28030481.
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 Gauer RL, Braun MM (2012). "Thrombocytopenia". Am Fam Physician. 85 (6): 612–22. PMID 22534274.
- ↑ 7.0 7.1 7.2 7.3 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). - ↑ 13.0 13.1 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). - ↑ 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). - ↑ 15.0 15.1 15.2 15.3 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). - ↑ 16.0 16.1 16.2 16.3 16.4 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). - ↑ 17.0 17.1 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.
- ↑ 19.0 19.1 19.2 19.3 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.