Immune Thrombocytopenic Purpura: Understanding Causes, Mechanisms, and Modern Treatment Approaches

Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder characterized by the immune-mediated destruction of platelets, leading to a significantly reduced platelet count in peripheral blood. This condition can result in easy bruising, petechiae, and in severe cases, life-threatening hemorrhages. While the exact cause varies among individuals, common triggers include viral or bacterial infections, dysregulation of the immune system, splenic and hepatic involvement, and genetic predisposition. Management typically involves a combination of supportive care, corticosteroids, immunosuppressive agents, and in select cases, surgical or interventional procedures.

Understanding the Causes and Pathophysiology of ITP

The development of immune thrombocytopenic purpura is multifactorial, involving complex interactions between environmental triggers and the body's immune response. Research has identified several key contributors that play a role in the onset and progression of this condition.

1. Infections as Triggers

Infectious agents—particularly viruses such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), HIV, and hepatitis C—are frequently linked to the initiation of ITP, especially in children. Bacterial infections may also act as catalysts. These pathogens are thought to induce molecular mimicry, where the immune system mistakenly targets platelet surface antigens due to structural similarities between microbial proteins and host platelet components. This cross-reactivity leads to antibody production against platelets, marking them for destruction.

2. Immune System Dysregulation

While infections may initiate the process, it is the aberrant immune response that drives the pathology of ITP. Autoantibodies, primarily IgG type, bind to glycoproteins on the platelet membrane (such as GPIIb/IIIa). Once coated with antibodies, platelets are recognized as foreign by macrophages in the reticuloendothelial system—especially in the spleen—and are prematurely destroyed. Additionally, recent studies suggest impaired function of regulatory T cells (Tregs) and overactivity of autoreactive B cells contribute to loss of immune tolerance, perpetuating platelet clearance.

3. Role of the Spleen and Liver

The spleen plays a central role in both the production of antiplatelet antibodies (PAIg) and the removal of antibody-coated platelets. Ex vivo studies confirm that splenic tissue in ITP patients produces pathogenic immunoglobulins. Platelets opsonized with PAIg or immune complexes (IC) undergo conformational changes that increase their adhesion to sinusoidal walls within the spleen, prolonging retention time and enhancing phagocytosis by mononuclear phagocytes. The liver contributes similarly through Kupffer cells, which engulf damaged platelets, making it a secondary site of platelet destruction—particularly when splenomegaly or chronic liver disease is present.

4. Genetic Predisposition

Evidence suggests a hereditary component in ITP susceptibility. Specific human leukocyte antigen (HLA) alleles—such as HLA-DRB104 and HLA-DQB103—have been associated with increased risk, indicating that genetic regulation of immune responses may influence disease onset. These findings support the hypothesis that certain individuals possess an inherited tendency toward autoimmunity, which, when combined with environmental triggers, can lead to clinical manifestations of ITP.

Comprehensive Treatment Strategies for ITP

Management of immune thrombocytopenic purpura must be tailored to the individual, considering age, severity of thrombocytopenia, bleeding symptoms, and response to prior therapies. The primary goals are to prevent serious bleeding, maintain adequate platelet counts, and minimize treatment-related side effects.

1. Supportive and General Care

Patients with severe bleeding or platelet counts below 20×10⁹/L require immediate intervention. Strict bed rest is recommended to reduce the risk of traumatic injury. Activities involving physical contact or high impact should be avoided. Local measures such as nasal packing or antifibrinolytic agents (e.g., tranexamic acid) can help control mucosal bleeding. Concurrent use of medications that impair hemostasis—like aspirin or NSAIDs—should be discontinued unless medically necessary.

2. First-Line Therapy: Corticosteroids

Corticosteroids remain the cornerstone of initial treatment, achieving response rates of up to 80% in newly diagnosed cases. Oral prednisone acetate (typically 1 mg/kg/day) is commonly prescribed. In acute or severe presentations, intravenous administration of dexamethasone sodium phosphate or methylprednisolone sodium succinate provides rapid suppression of immune activity. Once bleeding is controlled and platelet counts begin to rise—usually within days to two weeks—gradual tapering begins, reducing the dose by approximately 5 mg per week to avoid adrenal insufficiency and minimize long-term complications such as osteoporosis, hyperglycemia, and mood disturbances.

3. Second-Line and Adjunctive Pharmacological Treatments

For patients who do not respond adequately to steroids or experience relapse, alternative pharmacotherapies are available. Immunosuppressants such as azathioprine, cyclophosphamide, or mycophenolate mofetil may be used to modulate the overactive immune system. Danazol, a synthetic androgen, has shown efficacy in some refractory cases by stabilizing platelet membranes and suppressing autoantibody production. Emerging evidence also supports the use of certain traditional herbal formulations as complementary treatments, though further clinical trials are needed to validate their safety and effectiveness.

4. Surgical and Interventional Options

Splenectomy, once considered a standard second-line treatment, offers sustained remission in 70–90% of eligible patients. By removing the primary site of antibody production and platelet destruction, splenectomy can lead to durable responses. However, due to surgical risks and lifelong susceptibility to encapsulated bacteria, many clinicians now reserve this option for persistent or refractory cases. As a less invasive alternative, radiologically guided splenic artery embolization has gained attention in recent years. This procedure reduces splenic blood flow and function, mimicking the effects of splenectomy without complete organ removal, and has demonstrated promising outcomes in pilot studies.

Ongoing research continues to explore novel biologics—including thrombopoietin receptor agonists (TPO-RAs) like eltrombopag and romiplostim—as well as monoclonal antibodies such as rituximab, offering hope for more targeted, effective, and safer therapies in the future. With a multidisciplinary approach and personalized treatment plans, most patients with ITP can achieve good symptom control and maintain a high quality of life.