COVID-19-associated thrombocytopenia
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]
- 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]
- 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% 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
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]
Thrombocytopeniain 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>.[15]
History and Symptoms
Thrombocytopeniain 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>.[15]- 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
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>.[15]- 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]
Thrombocytopeniain 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>.[15]
- 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.
- ↑ 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 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 15.4 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). - ↑ 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.