COVID-19-associated thrombocytopenia

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. Thrombocytopenia in COVID-19 infection is more common in patients with severe infection and it has been reported that thrombocytopenia upon admission for COVID-19 infection is associated with poor outcome and mortality. Thrombocytopenia is defined by platelet count <150 x <math>10^9</math>/L on complete blood count (CBC). The pathogenesis of thrombocytopenia in COVID-19 infection is due to several factors such as: infection of bone marrow, cytokine storm caused by the COVID-19 infection, increase in autoantibodies and immune complexes, lung injury which causes megakaryocyte fragmentation, and decrease in platelets which may be due to the activation of platelets that result in platelet aggregation.

• 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).

• Thrombocytopenia in general is defined by platelet count <150 x <math>10^9</math>/L on complete blood count (CBC).^[3]
• Classification of thrombocytopenia in general 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
• In general:^[4]
  • Most thrombocytopenic patients are asymptomatic if the platelet count is 50,000 x <math>10^9</math>/L or greater.
  • Thrombocytopenic patients with platelet count between 30 and 50 x <math>10^9</math>/L rarely have purpura, but may have bleeding with trauma.
  • Thrombocytopenic patients with platelet count between 10 and 30 x <math>10^3</math>/L may have bleeding with minor trauma.
  • Thrombocytopenic patients with platelet count less than 10 x <math>10^3</math>/L have increased risk for spontaneous bleeding, petechiae, and bruising.
  • In thrombocytopenic patients, spontaneous bleeding, which is an emergency, usually occurs in patients with platelet counts less than 5 x <math>10^3</math>/L .

The pathogenesis of thrombocytopenia in COVID-19 infection is due to several factors:^{[5][6][7][8][9][10]}

• Decrease in primary platelet production due to infection of bone marrow cells by coronaviruses and inhibition of bone marrow growth, which lead to abnormal hematopoietic function.
• 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.
• Increase in platelet destruction due to an increase in autoantibodies and immune complexes.
• Decrease in circulating platelet due to lung injury which causes megakaryocyte fragmentation and decreases platelet production, because the lung is a reservoir for megakaryocyte and hematopoietic progenitor cells and has a role in platelet production.
• In addition, a decrease in platelets may be due to the activation of platelets that result in platelet aggregation and formation of micro-thrombus which increase platelet consumption.

Summary of the mechanisms involved in thrombocytopenia in COVID-19 infection:^[5]

• Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus called SARS-CoV-2 and is the cause of thrombocytopenia in COVID-19 infection.

• Coronavirus disease 2019 (COVID-19) may cause thrombocytopenia. The differential diagnosis to consider for thrombocytopenia in general include:^[11]
  • Pseudothrombocytopenia  
  • 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)
  • Hematologic disorders (lymphoma, leukemia, myelodysplastic syndrome)
  • Post-transfusion purpura
  • Autoimmune-related thrombocytopenia (such as systemic lupus erythematosus (SLE), common variable immunodeficiency (CVID), antiphospholipid antibody syndrome,thyroid disease)
  • Tumor infiltration of bone marrow
  • Bone marrow failure (such as aplastic anemia, fanconi anemia, and diamond-Blackfan anemia)
  • Liver disease
  • Splenomegaly
  • Infections (Epstein-Barr virus, cytomegalovirus, hepatitis C, HIV, parvovirus B19, H pylori)
  • Drugs (antibiotics, alcohol, chemotherapy, radiation)
  • Folate deficiency or vitamin B12 deficiency
  • Mechanical destruction (such as cardiopulmonary bypass, intra-aortic balloon pump)  

For detailed differential diagnosis of thrombocytopenia click here

• Thrombocytopenia is seen in 36.2% of all patients with COVID-19 infection.^[12]
• Thrombocytopenia is seen in 57.7% of patients with severe COVID-19 infection compared to 31.6 % of patients with non-severe infection.^[12]

• Thrombocytopenia in COVID-19 infection is more common is patients with severe infection compared to patients with non-severe infection.^[12]

• It has been reported that thrombocytopenia upon admission for COVID-19 infection is associated with severe disease and mortality.^[13]
• 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.^[14]

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

• Complications of thrombocytopenia in patients with severe COVID-19 infection may include:^[14]
  • Disseminated intravascular coagulation (DIC)
  • Multiple organ dysfunction syndromes
  • Death

• It has been reported that thrombocytopenia upon admission for COVID-19 infection is independently and strongly associated with poor outcome and mortality.^[13]

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

• Thrombocytopenia in general 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.^[12]

• 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.^[12]
• In general, in thrombocytopenic patients, most patients are asymptomatic if the platelet count is 50,000 x <math>10^9</math>/L or greater.^[4]

• In general, in thrombocytopenic 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

• 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.^[12]
• In general, in thrombocytopenic patients, 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 in general should include checking for:^[3]
  • Bleeding (epistaxis, bloody sputum, gingival bleeding, menorrhagia, heavy bleeding after invasive procedures or childbirth)^[16][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.^[17][18]

• Complete blood count (CBC): Thrombocytopenia in general 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.^[12]

• Peripheral blood smear: Peripheral blood smear may be helpful if there is suspicion of other disorders that cause thrombocytopenia. However, there is insufficient evidence recommending routine peripheral blood smear in COVID-19 patients.
• 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.

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

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

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

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

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

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

• There are no other diagnostic studies associated with COVID-19-associated-thrombocytopenia.
• However, bone marrow biopsy may be helpful if there is suspicion of other disorders that cause thrombocytopenia, but there is insufficient evidence recommending routine bone marrow biopsy in COVID-19 patients.

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 corona-virus infection)
• Platelet transfusion in refractory visceral or cerebral meningeal hemorrhage

• 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.

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

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

Template:WikiDoc Sources