What causes thrombocytopenia (low platelet count)?

From the Guidelines

Low platelets, or thrombocytopenia, can be caused by several factors, including bone marrow disorders, increased destruction of platelets, medications, viral infections, and splenic sequestration, with treatment depending on identifying and addressing the underlying cause, as supported by recent clinical guidelines 1. When considering the causes of low platelets, it's essential to evaluate the patient's medical history, current medications, and potential infections.

• Bone marrow disorders, such as leukemia, aplastic anemia, or vitamin B12 deficiency, can decrease platelet production, as noted in the AABB clinical practice guideline 1.
• Increased destruction of platelets can occur in conditions like immune thrombocytopenia, disseminated intravascular coagulation, or thrombotic thrombocytopenic purpura.
• Certain medications, including heparin, quinine, sulfonamides, and specific antibiotics, can also contribute to thrombocytopenia.
• Viral infections, such as HIV, hepatitis C, and COVID-19, have been linked to low platelet counts, highlighting the importance of considering infectious causes in patients with thrombocytopenia.
• Splenic sequestration, where an enlarged spleen traps platelets, can also lead to low platelet counts, as discussed in the context of platelet transfusion recommendations 1. In terms of management, the AABB recommends a platelet count transfusion threshold of 20 × 10^9 cells/L for central venous catheter (CVC) placement and 50 × 10^9 cells/L for lumbar puncture (LP) 1, emphasizing the need for careful consideration of platelet counts in patients undergoing invasive procedures.
• For patients with therapy-induced hypoproliferative thrombocytopenia, prophylactic platelet transfusion is recommended at a platelet count of 10 × 10^9 cells/L or less, consistent with current standard practice 1.
• Clinical judgment should be used when deciding on platelet transfusion for patients with platelet counts between 20 × 10^9 and 50 × 10^9 cells/L requiring LP, taking into account individual risk factors for bleeding 1.

From the FDA Drug Label

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. 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

Low platelets causes include heparin-induced thrombocytopenia (HIT) and thrombocytopenia, which can occur in patients receiving heparin therapy 2.

• Heparin-induced thrombocytopenia (HIT) is a serious antibody-mediated reaction that can lead to low platelet counts.
• Thrombocytopenia can occur in patients receiving heparin, with frequencies reported up to 30%. It is also noted that eltrombopag is used to treat low blood platelet counts due to persistent or chronic immune thrombocytopenia (ITP) 3.

From the Research

Causes of Low Platelets

• Immune thrombocytopenia (ITP) is a rare cause of thrombocytopenia, resulting from antibody-mediated platelet destruction combined with impaired platelet production 4
• Aplastic anemia, a bone marrow failure syndrome, can also lead to low platelet counts due to pancytopenia 5
• Bone marrow failure syndromes, such as myelodysplastic syndromes, can cause thrombocytopenia due to impaired platelet production 5
• Autoantibodies produced by autoreactive B lymphocytes and the phagocytic function of macrophages can contribute to platelet destruction in ITP 6
• Abnormalities in bone marrow B cells and plasma cells, including decreased proportions of total B cells and naive B cells, and elevated frequencies of long-lived plasma cells, can contribute to the development of ITP 7

Pathogenesis of Low Platelets

• The pathogenesis of ITP involves the interplay of immune cells, including autoreactive B lymphocytes, macrophages, T lymphocytes, and follicular helper T-cells 6
• The classical pathway of the complement system can also contribute to platelet destruction in ITP 6
• Low levels of thrombopoietin and an immune response against megakaryocytes in the bone marrow can worsen thrombocytopenia 6
• Dysregulation of B-cell subsets in the bone marrow, including decreased regulatory B cell function, can contribute to the development of ITP 7