Mechanism of Disease

In ITP, immune dysregulation lowers platelet counts through multiple pathways. Autoreactive B cells produce autoantibodies that target platelets for destruction by macrophages and impair megakaryocyte maturation, reducing platelet production. Autoantibodies may also destroy platelets through other mechanisms.

Immune system activity can also lead to elevated levels of inflammatory markers.^1-6

Adapted from Kashiwagi H, et al. Int J Hematol. 2013;98(1):24-33. © Japanese Society of Hematology (JSH).¹

Watch the mechanism of disease (MOD) video to learn more about the multiple dimensions of ITP

Bruton’s tyrosine kinase (BTK) plays a pivotal role in complex immune dysregulation^9,10

B cells are responsible for the production of autoantibodies; macrophages are essential for phagocytosis; and the NLRP3 inflammasome plays a key role in systemic inflammation. All of these processes are regulated by BTK.^9,10

• In B cells: The BTK pathway is crucial for proliferation, differentiation, and autoantibody production
• In macrophages: Various signalling pathways dependent on BTK drive phagocytosis, degranulation, and the production of inflammatory cytokines
• Systemically: BTK drives the production of mediators of inflammation like NLRP3 inflammasome, which can contribute to platelet destruction and systemic inflammation

Patients living with ITP have elevated inflammatory markers, including¹⁰:

• TNF-α and IFN-γ
• IL-2 and IL-6
• NLRP3 inflammasome cytokines IL-1β and IL-18

BTK is implicated in the production or activation of these inflammatory markers and is a critical driver of inflammation.¹⁰

Other signalling pathways involved in the pathogenesis of ITP⁸

With incremental understanding of molecular mechanisms driving ITP pathology, it is becoming increasingly clear that multiple signalling pathways are involved in the pathogenesis and manifestation of the disease.⁸

BCR, B-cell receptor; Fc, fragment crystallisable; IFN, interferon; IL, interleukin; NLRP3, nucleotide-binding domain, leucine-rich repeat and pyrin domain-containing protein 3; TNF, tumour necrosis factor.

Causes and pathophysiology of ITP^1-4,8,11,12

ITP has an estimated prevalence of up to 9.5 per 100,000 people. The causes and pathophysiology of immune thrombocytopenia (ITP), historically called idiopathic thrombocytopenic purpura or immune thrombocytopenic purpura, are multifactorial and trigger a wide range of symptoms.

The pathophysiology of ITP is complex, involving various immune cells and different organs. Platelet destruction and inhibition of thrombopoiesis (platelet production) are key drivers of the disease. Current treatments for ITP aim to target these mechanisms of immune thrombocytopenia.

Our understanding of the pathophysiology of ITP is expanding and opening up new treatment possibilities for more targeted therapies and overall disease control.

What are the causes of ITP^12-14

The cause of ITP in adults can be differentiated by whether the disease is primary or secondary ITP. 

In primary ITP, the underlying causes remain unidentified—this is why it was previously known as idiopathic thrombocytopenic purpura. This is the most common cause of ITP, with approximately 80% of ITP patients diagnosed with primary ITP. 

In contrast, secondary ITP is caused by known factors such as certain medications, infections, or cancers. 

It is often associated with persistent autoimmunity and underlying autoimmune diseases including systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). 

Chronic ITP is characterised by the persistence of symptoms for more than 12 months after the initial diagnosis. Chronic ITP is more common in adults than in children. Recent studies suggest genetic factors, including polymorphisms in cytokine receptor genes and genes regulating T cell activity, may influence the susceptibility for chronic ITP. However, more research is needed to fully understand the causes of chronic ITP.