The pathophysiology of acquired/immune-mediated thrombotic thrombocytopenic purpura (aTTP/iTTP) poses a triple threat2-7:

Autoantibody symbol

Autoantibody formation

ADAMTS13 symbol

Autoantibody formation leading to ADAMTS13 inhibition resulting in uncleaved vWF (ULvWF)

Arterial thrombosis symbol

Microthrombi-driven risks caused by ULvWF binding to platelets to form ULvWF-platelet aggregates

PEX and immunosuppressive therapy directly address only 2 of the 3 aspects of the disease.2,4,5,6,8

The triple threat of aTTP/iTTP deserves a triple therapy regimen with CABLIVI, PEX, and immunosuppressive therapy1-8

CABLIVI (caplacizumab-yhdp) mechanism of action: Immunosuppressive therapy (eg, steroids): Intended to inhibit ADAMTS13 autoantibody formation PEX: Removes autoantibodies and replaces ADAMTS13 CABLIVI (caplacizumab-yhdp): Blocks vWF-mediated platelet aggregation, inhibiting microthrombi formation

CABLIVI MOA: The first of its kind

    Acquired thrombotic thrombocytopenic purpura, or aTTP, is a rare, rapidly progressing, life-threatening autoimmune disease. Left untreated, up to 90% of aTTP patients die.

    Historical treatment includes plasma exchange and immunosuppressive therapy, which has improved prognosis. However, despite these treatments, the mortality rate remains high at 8 to 20%. In a large retrospective study, the median time from diagnosis to death was 9 days despite treatment with plasma exchange.

    Symptoms of aTTP can be complex and variable. Most common signs include thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia, resulting from microvascular occlusion. Clinical manifestations of organ ischemia can include strokes, transient ischemic attacks, myocardial infarction, and renal and mesenteric ischemia.

    aTTP is caused by the severe deficiency of a von Willebrand factor-cleaving protease, ADAMTS13. This deficiency is due to formation of autoantibodies directed against ADAMTS13. Normally, ADAMTS13 breaks apart ultra-large strings of von Willebrand factor, known as vWF, into smaller pieces. In aTTP patients, however, ADAMTS13 is blocked by autoantibodies, thereby greatly increasing the amount of ultra-large vWF in circulation. Thousands of circulating platelets bind to these ultra-large vWF strings, forming platelet-rich blood clots within small blood vessels throughout the body. These small clots are known as microthrombi.

    As of February 2019, CABLIVI became the newest treatment approved by the FDA for aTTP in combination with plasma exchange and immunosuppressive therapy. Plasma exchange removes vWF and autoantibodies and replenishes ADAMTS13. Immunosuppressive therapies are intended to inhibit anti-ADAMTS13 autoantibody production. Neither directly affects the binding of platelets to vWF.

    CABLIVI is a monoclonal antibody fragment that was developed to inhibit microthrombi formation in aTTP by binding specifically to the A1 domain of vWF. CABLIVI blocks the interaction between vWF and platelets, thereby reducing both vWF-mediated platelet adhesion and platelet consumption. This inhibits the formation of microthrombi while the underlying autoimmune disease is treated with immunosuppressive therapy.

Day 1 clock symbol

Choose CABLIVI on day 1 in combination with PEX and immunosuppressive therapy

Guidelines checkmarks

ISTH Guideline recommendations*

Who should not start CABLIVI?

  • CABLIVI is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of its excipients
  • Withhold CABLIVI treatment 7 days prior to elective surgery, dental procedures, or other invasive interventions

*A conditional recommendation defined as desirable effects of the recommendation probably outweighing the undesirable effects. Assumes timely access to ADAMTS13 testing and clinical diagnosis based on high likelihood of aTTP/iTTP. In de novo patients where no reasonable access to ADAMTS13 activity testing is available, the Guidelines do not recommend CABLIVI; however, treatment of a patient previously diagnosed with aTTP/iTTP could be safely undertaken on clinical grounds without the need for a confirmatory ADAMTS13 test.9

ADAMTS13=a disintegrin and metalloproteinase with a thrombospondin type 1 motif, 13; ISTH=International Society on Thrombosis and Haemostasis; MOA=mechanism of action; PEX=plasma exchange; TTP=thrombotic thrombocytopenic purpura; ULvWF=ultra-large von Willebrand factor; vWF=von Willebrand factor.