What causes severe thrombocytopenia (low platelet count)?

From the Guidelines

Severe thrombocytopenia is primarily caused by immune thrombocytopenic purpura (ITP), where the immune system destroys platelets, as well as other conditions such as drug-induced thrombocytopenia, bone marrow disorders, and viral infections. According to the American Society of Hematology 2019 guidelines for immune thrombocytopenia 1, ITP is an acquired autoimmune disorder characterized by a low platelet count resulting from platelet destruction and impaired platelet production. The guidelines highlight that ITP has an incidence of 2 to 5 per 100 000 and can be an isolated primary condition or secondary to other conditions.

Some of the key causes of severe thrombocytopenia include:

• Immune thrombocytopenic purpura (ITP)
• Drug-induced thrombocytopenia from medications like heparin, quinine, and certain antibiotics
• Bone marrow disorders such as leukemia, aplastic anemia, and myelodysplastic syndromes
• Viral infections including HIV, hepatitis C, and COVID-19
• Disseminated intravascular coagulation (DIC)
• Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS)
• Severe vitamin B12 or folate deficiency
• Chemotherapy and radiation therapy
• Hypersplenism

The diagnosis and management of these conditions can be complex, and treatment depends on identifying and addressing the underlying cause, with options ranging from corticosteroids and immunoglobulins for immune-mediated cases to platelet transfusions for severe bleeding risk, as discussed in the international consensus report on the investigation and management of primary immune thrombocytopenia 1 and the diagnosis and management of heparin-induced thrombocytopenia 1. It is essential to prioritize the most recent and highest quality study, which in this case is the American Society of Hematology 2019 guidelines for immune thrombocytopenia 1, to guide clinical decision-making and ensure the best possible outcomes for patients with severe thrombocytopenia.

From the FDA Drug Label

1. 3 Heparin-Induced Thrombocytopenia and Heparin-Induced Thrombocytopenia and Thrombosis

Heparin-induced thrombocytopenia (HIT) is a serious antibody-mediated reaction. HIT occurs in patients treated with heparin and is due to the development of antibodies to a platelet Factor 4-heparin complex that induce in vivo platelet aggregation 5. 5 Thrombocytopenia Thrombocytopenia in patients receiving heparin has been reported at frequencies up to 30%. It can occur 2 to 20 days (average 5 to 9) following the onset of heparin therapy.

Severe thrombocytopenia can be caused by heparin-induced thrombocytopenia (HIT), an antibody-mediated reaction that occurs in patients treated with heparin. This condition is due to the development of antibodies to a platelet Factor 4-heparin complex that induce in vivo platelet aggregation. Thrombocytopenia can also occur in patients receiving heparin, with frequencies reported up to 30%, and can happen 2 to 20 days after the onset of heparin therapy 2.

Additionally, quinine can also cause severe thrombocytopenia, which is an immune-mediated disorder. Severe cases of thrombocytopenia that are fatal or life-threatening have been reported, including cases of hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) 3.

From the Research

Causes of Severe Thrombocytopenia

Severe thrombocytopenia can be caused by various factors, including:

• Autoimmune disorders, such as immune thrombocytopenia (ITP) 4, 5, 6, 7, 8
• Viral infections, such as hepatitis B virus, hepatitis C virus, cytomegalovirus, HIV, and severe acute respiratory syndrome coronavirus 2 5
• Vaccines, including the COVID-19 vaccine 5
• Impaired platelet production, which can occur in combination with antibody-mediated platelet destruction 6

Immune Thrombocytopenia (ITP)

ITP is a heterogeneous disease with an unpredictable evolution, and its pathogenesis is complex, involving alterations in humoral and cellular immunity 4, 7, 8. The management of ITP is based on immune suppression, such as corticosteroids and intravenous immunoglobulins, or the use of thrombopoietin receptor agonists (TPO-RAs), rituximab, or spleen tyrosine kinase (Syk) inhibitors 4, 7.

Risk Factors for Severe Thrombocytopenia

Risk factors for severe thrombocytopenia include:

• Age, with peaks during childhood and in the elderly 8
• Underlying medical conditions, such as viral infections or autoimmune disorders 5, 8
• Use of certain medications, such as vaccines or immunosuppressive agents 5