Thrombotic Thrombocytopenic Purpura (TTP): Targeted Therapy with Caplacizumab

Thrombotic Thrombocytopenic Purpura (TTP) is a rare and life-threatening hematologic disorder characterized by widespread microvascular thrombosis due to severely reduced activity of the enzyme ADAMTS13. This deficiency leads to the accumulation of ultra-large von Willebrand factor (vWF) multimers, which cause abnormal platelet aggregation and the formation of microthrombi in small vessels throughout the body.

TTP is classified into acquired (immune-mediated) and hereditary (congenital) forms. The acquired type is far more common and caused by autoantibodies that inhibit ADAMTS13 activity. TTP presents abruptly and can lead to rapid organ damage—most commonly affecting the brain, heart, and kidneys—if not treated promptly.

Targeted Therapy: Cablivi (caplacizumab)

Cablivi® (caplacizumab) is a first-in-class nanobody targeting the A1 domain of vWF, blocking its interaction with platelets and thereby preventing microthrombus formation. It is FDA-approved for use in combination with plasma exchange and immunosuppressive therapy in adults with acquired TTP.

Administered as a daily subcutaneous injection following an initial intravenous dose, Cablivi has demonstrated significant benefits in shortening the time to platelet normalization, reducing the incidence of TTP-related death or recurrence, and preventing major thrombotic events.

Key data from the HERCULES trial showed that patients receiving Cablivi experienced:

• ●  Faster platelet count recovery
• ●  Fewer recurrences of TTP
• ●  Lower rates of thromboembolic complications
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Cablivi is generally well tolerated, with the most common side effects being epistaxis, headache, and gingival bleeding. Because of its antiplatelet mechanism, careful monitoring is necessary, particularly in patients at risk of bleeding.

Diagnostic Considerations

TTP is a medical emergency. Early recognition and treatment initiation are critical. Diagnostic hallmarks include:

• ●  Microangiopathic hemolytic anemia (MAHA)
• ●  Severe thrombocytopenia (platelet count often <30,000/μL)
• ●  Neurologic symptoms (confusion, seizures, stroke)
• ●  Renal involvement
• ●  Fever (in some cases)
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A markedly reduced ADAMTS13 activity (<10%) confirms the diagnosis of TTP. However, treatment with plasma exchange and corticosteroids should not be delayed while awaiting test results due to the disease's rapid progression.

Future Directions in TTP Treatment

The introduction of Cablivi has significantly improved the frontline management of acquired TTP, reducing mortality and relapse risk when used alongside standard therapies. Moving forward, research is focusing on:

• ●  Optimizing duration of caplacizumab therapy
• ●  Earlier identification of ADAMTS13 autoantibodies
• ●  Personalized strategies to reduce treatment resistance and relapse
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Long-term monitoring of patients with acquired TTP remains essential due to the potential for relapse and ongoing autoimmune activity. With emerging targeted therapies like Cablivi, the outlook for patients with TTP continues to improve, shifting from crisis management to sustained remission and recovery.