Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura

Quyen Bach, Mercer University College of Pharmacy


According to the Guidelines on the Diagnosis and Management of Thrombotic Thrombocytopenic Purpura and other Thrombotic Microangiopathies, acquired thrombotic thrombocytopenic purpura is a potentially life threating thrombotic microangiopathy resulting from systemic microvascular thrombosis and leading to profound thrombocytopenia, hemolytic anemia, and organ failure of varying severity. [1]

Caplacizumab is an anti-von Willebrand factor humanized single-variable-domain immunoglobulin that targets the A1 domain of von Willebrand factor and prevents interaction with the platelet glycoprotein Ib-IX-V receptor. [2]



Caplacizumab for Acquired Thrombotic Thrombocytopenia Purpura (TTP) [3]
Design Single-blind, parallel-design, randomized, placebo-controlled, international; N = 75
Objective To evaluate the potential of caplacizumab for treating acquired TTP
Study Groups Caplacizumab group (n = 36); placebo group (n = 39)
Methods Patients were assigned in a 1:1 ratio to active treatment or placebo. In the treatment group, patients were given caplacizumab 10 mg intravenously (IV) x1, then 10 mg subcutaneously (SQ) daily within 30 minutes after the end of each plasma-exchange treatment. Caplacizumab 10 mg SQ was given for 30 days after the last plasma exchange.
Duration October 2010 to January 2014
Primary Outcome Measure The time to confirmed normalization of the platelet count (i.e. time to a response)
Baseline Characteristics Characteristic Caplacizumab (n = 36) Placebo (n = 39)
Mean age (yr) 41 42
Female sex (no.) 24 20
White (no.) 32 34
Black (no.) 4 5
Initial episode of TTP (no.) 24 27
Recurrent episode of TTP (no.) 12 12
Mean platelet count (per mm3) 21,100 28,000
Mean lactate dehydrogenase (LDH) (U/liter) 1,277 1,270
ADAMTS13 activity < 10% (no.) 28 30
ADAMTS13 activity ≥ 10% 2 6
ADAMTS13 activity – missing data (no.) 6 3
Plasma exchange (PE) tapering (no.) 11 11
Glucocorticoids during daily PE (no.) 32 36
Rituximab during daily PE (no.) 2 9
Results   Caplacizumab 95% CI Placebo 95% CI
Time to response (days)
No plasma-exchange before enrollment 3.0 2.7 – 3.9 4.9 3.2 – 6.6
Plasma-exchange enrollment 2.4 1.9 – 3.0 4.3 2.9 – 5.7
Adverse Events Common Adverse Events: headache (3%); epistaxis (3%)
Serious Adverse Events: bleeding (3%)
Percentage that Discontinued due to Adverse Events: 11%
Study Author Conclusions The results of our study show that caplacizumab immediately inhibits the pathophysiological mediator of the microthrombosis.



This randomized controlled trial showed that caplacizumab, as compared with placebo, resulted in a more rapid resolution of TTP episodes. Treatment of acquired TTP takes time to achieve resolution with plasma exchange and immunosuppressive therapy. Caplacizumab, through its rapid blocking effect, could become a solution for quicker prevention of further platelet aggregation, which could potentially prevent short- and long-term end-organ injury due to ischemia.




  1. Scully M, Hunt BJ, Benjamin S, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158(3):323-35.
  2. Ulrichts H, Silence K, Schoolmeester A, et al. Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared with currently marketed antiplatelet drugs. Blood. 2011;118(3):757-65.
  3. Peyvandi F, Scully M, Kremer hovinga JA, et al. Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2016;374(6):511-22.

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