From the Guidelines
Severe thrombocytopenia is a condition characterized by an extremely low platelet count, typically below 20,000 platelets per microliter, which can lead to spontaneous bleeding and increased risk of morbidity and mortality, as reported in the 2019 American Society of Hematology guidelines 1. Severe thrombocytopenia causes bleeding disorders due to the essential role of platelets in forming clots to stop bleeding. Without sufficient platelets, even minor trauma can cause significant bleeding, including petechiae, purpura, epistaxis, gingival bleeding, gastrointestinal bleeding, and in severe cases, intracranial hemorrhage. Some key points to consider in the management of severe thrombocytopenia include:
- Decreased platelet production, which can be caused by bone marrow disorders such as leukemia or aplastic anemia
- Increased platelet destruction, which can be caused by immune thrombocytopenia, drug-induced thrombocytopenia, or disseminated intravascular coagulation
- Splenic sequestration, which can also contribute to thrombocytopenia Treatment depends on the underlying cause but may include corticosteroids, intravenous immunoglobulin, thrombopoietin receptor agonists, or platelet transfusions for counts below 10,000/μL or active bleeding, as recommended by the 2019 American Society of Hematology guidelines 1. Patients with severe thrombocytopenia should avoid activities with high bleeding risk and medications that affect platelet function, such as aspirin and NSAIDs, to minimize the risk of bleeding and improve quality of life, as highlighted in the international consensus report on the investigation and management of primary immune thrombocytopenia 1.
From the FDA Drug Label
If severe thrombocytopenia develops during Nplate treatment, assess patients for the formation of neutralizing antibodies.
The causes of severe thrombocytopenia are not directly stated in the provided drug labels. However, it is mentioned that neutralizing antibodies may be a cause of severe thrombocytopenia in patients treated with Nplate 2.
- Other potential causes of thrombocytopenia mentioned in the labels include:
- Immune thrombocytopenia (ITP): a condition where the immune system attacks and destroys platelets 2 3
- Myelosuppressive doses of radiation: which can cause thrombocytopenia as part of the hematopoietic syndrome of acute radiation syndrome (HS-ARS) 2
- Chronic hepatitis C virus (HCV) infection: which can cause thrombocytopenia 3
- Severe aplastic anemia (SAA): a condition where the bone marrow fails to produce enough blood cells, including platelets 3
It is essential to note that these causes are not necessarily directly related to severe thrombocytopenia, but rather to thrombocytopenia in general. The exact causes of severe thrombocytopenia are not explicitly stated in the provided drug labels.
From the Research
Severe Thrombocytopenia Causes
- Severe thrombocytopenia can be caused by immune thrombocytopenia (ITP), a rare condition characterized by antibody-mediated platelet destruction combined with impaired platelet production 4, 5, 6, 7.
- ITP can present as a primary or secondary form and may affect individuals of all ages, with peaks during childhood and in the elderly 5.
- The pathogenesis of ITP is complex, involving alterations in humoral and cellular immunity 5, 7.
- Bleeding is the most common clinical manifestation of ITP, and the risk of bleeding is a major concern in patients with severe thrombocytopenia 5, 6, 7.
- Other causes of severe thrombocytopenia are not mentioned in the provided studies, which primarily focus on ITP.
Immune Thrombocytopenia (ITP)
- ITP is an autoimmune disorder characterized by a low platelet count (<100 × 10^9/L) with an increased risk of bleeding 6.
- The management of ITP is based on immune suppression, the use of thrombopoietin receptor agonists, rituximab, or spleen tyrosine kinase (Syk) inhibitors 6, 7.
- New targeted therapies, such as Bruton's tyrosine kinase inhibitors and newer TPO-RAs, are being developed to improve treatment outcomes for ITP patients 7.