What are the mechanisms leading to thrombocytopenia (low platelet count)?

From the Guidelines

Thrombocytopenia occurs through several distinct mechanisms, including decreased platelet production, increased platelet destruction, and abnormal platelet sequestration, with immune thrombocytopenia (ITP) being a primary cause of increased destruction, as supported by the American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia 1.

Mechanisms of Thrombocytopenia

The primary mechanisms of thrombocytopenia include:

• Decreased platelet production in the bone marrow, which can result from medications, infections, nutritional deficiencies, or bone marrow disorders, as noted in the international consensus report on the investigation and management of primary immune thrombocytopenia 1.
• Increased platelet destruction in peripheral circulation, which occurs in immune thrombocytopenia (ITP) where autoantibodies target platelets, as well as in drug-induced immune thrombocytopenia and non-immune destruction in conditions like disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), and hemolytic uremic syndrome (HUS) 1.
• Abnormal platelet sequestration in the spleen, which occurs in conditions causing splenomegaly like liver cirrhosis or portal hypertension.

Diagnosis and Treatment

Proper diagnosis of thrombocytopenia requires identifying the underlying mechanism through careful history-taking, physical examination, and appropriate laboratory testing to guide effective treatment, as emphasized by the American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia 1.

Key Considerations

• The severity of thrombocytopenia correlates to some extent but not completely with the bleeding risk, and additional factors such as age, lifestyle factors, and uremia affect the risk and should be evaluated before determining the appropriate management, as noted in the international consensus report on the investigation and management of primary immune thrombocytopenia 1.
• The incidence of ITP in adults is approximately equal for the sexes except in the mid-adult years (30-60 years), when the disease is more prevalent in women, and ITP is classified by duration into newly diagnosed, persistent (3-12 months’ duration), and chronic (≥ 12 months’ duration) 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Mechanisms of Thrombocytopenia

Thrombocytopenia can occur due to several mechanisms, including:

• Decreased platelet production 2, 3, 4
• Increased destruction of platelets 2, 3, 4, 5
• Splenic sequestration 2, 4
• Dilution or clumping of platelets 2

Causes of Thrombocytopenia

The causes of thrombocytopenia can be varied, including:

• Infections 3
• Malignancy 3, 6
• Liver disease 3, 2
• Autoimmune disorders 3, 5
• Disseminated intravascular coagulation 3
• Pregnancy 3
• Medications 2, 3
• Coagulation disorders 3

Pathogenesis of Chronic Immune Thrombocytopenia

Chronic immune thrombocytopenia (ITP) is a haematological disorder characterized by:

• Increased platelet destruction 5
• Decreased platelet production 5
• Autoantibody-mediated platelet destruction 5
• Cytotoxic T lymphocyte-mediated platelet lysis 5