Last reviewed: June 2019
Last updated: April  2019
09 Apr 2019

FDA approves first therapy specifically for acquired thrombotic thrombocytopenic purpura

Caplacizumab has been approved by the US Food and Drug Administration (FDA) for the treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP) in combination with the standard treatment of plasma exchange and immunosuppression. It is the first therapy specifically indicated for aTTP. The FDA approval means the drug is now available in both the US and the EU, having been approved by the European Medicines Agency in September 2018.

Acquired TTP is a rare, difficult to treat blood-clotting disorder that can be life-threatening. Patients can develop extensive blood clots in small blood vessels, leading to damage to end organs, most commonly the central nervous system and kidneys.

In a phase III randomised placebo-controlled trial of 145 adult patients with aTTP, the addition of caplacizumab to plasma exchange and immunosuppression resulted in: [43]

  • A reduction in the composite of TTP-related death, recurrence, or major thromboembolic event (12% vs. 49% in the placebo group, P <0.001)

  • Reduced TTP recurrence during the study (drug treatment plus 28-day follow-up after treatment discontinuation; 12% vs. 38%, P <0.001)

  • Shorter stay in the intensive care unit (3.4 days vs. 9.7 days) and shorter stay in hospital (9.9 days vs. 14.4 days)

  • More rapid normalisation of platelet count (2.69 days vs. 2.88 days, P = 0.01; rate ratio for normalisation 1.55 [primary outcome]).

Bleeding-related adverse events and serious bleeding adverse events were more common among patients treated with caplacizumab than placebo (65% vs. 48% and 11% vs. 1%, respectively). Nosebleed (epistaxis) was the most commonly reported serious bleeding event. Clinicians are advised to monitor closely for bleeding when administering caplacizumab to any patient who takes anticoagulants.

Caplacizumab is a humanised, bivalent variable-domain-only immunoglobulin fragment that blocks the interaction between von Willebrand factor and platelets.

See Management: approach See Management: treatment algorithm

Original source of update

Summary

Definition

History and exam

Key diagnostic factors

  • non-specific prodrome
  • severe neurological symptoms (coma, focal abnormalities, seizures)
  • mild neurological symptoms (headache, confusion)
  • fever

Other diagnostic factors

  • age 30 to 50 years
  • digestive symptoms (nausea, vomiting, diarrhoea, abdominal pain)
  • weakness
  • bleeding symptoms (purpura, ecchymosis, menorrhagia)

Risk factors

  • black ethnicity
  • female gender
  • obesity
  • pregnancy (near term or post-partum period)
  • cancer therapies
  • HIV infection
  • bone marrow transplantation
  • antiplatelet agents
  • quinine

Diagnostic investigations

1st investigations to order

  • platelet count
  • haemoglobin
  • haptoglobin
  • peripheral smear
  • reticulocyte count
  • urinalysis
  • urea and creatinine
  • direct Coombs' test
Full details

Investigations to consider

  • ADAMTS-13 activity assay and inhibitor titres
Full details

Treatment algorithm

Contributors

Authors VIEW ALL

Associate Professor of Medicine

Division of Hematology and Medical Oncology

The University of Tennessee Health Science Center

Memphis

TN

Disclosures

SKR has received honoraria, speaker's fees, consultancy fees, and research support from Alexion Inc., Biogen, Octapharma, Baxalta, and Kedrion.

Dr Sandeep K. Rajan would like to gratefully acknowledge Dr Rebecca Fischer Connor, a previous contributor to this topic.

Peer reviewers VIEW ALL

George Lynn Cross Professor

Department of Biostatistics and Epidemiology

University of Oklahoma Health Sciences Center

Oklahoma City

OK

Disclosures

JNG declares that he has no competing interests.

Associate Professor of Medicine

Department of Internal Medicine

Innsbruck Medical University

Innsbruck

Austria

Disclosures

CP declares that he has no competing interests.

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