Use of a TGA and TEM in the Assessment of the Efficacy of Treatment With APCC or rFVIIa (Thrombus)

Use of a TGA and TEM in the Assessment of the Efficacy of Treatment With APCC or rFVIIa Concentrate in Patients With Acquired Haemophilia and in Patients With Haemophilia A With Inhibitors

Occurrence of inhibitors to coagulation factor VIII is diagnosed in ~30% patients with haemophilia A. Presence of inhibitor with a titre >5 BU/ml requires the use of by-passing agents: recombinant activated Factor VIIa concentrate (rFVIIa) and/or activated prothrombin complex concentrate (APCC). Similarly, haemorrhagic complications in patients with acquired haemophilia and inhibitor titre >5 BU/ml should be treated with by-passing agents.

Response to treatment with by-passing agents is patient-specific, and can vary in the same patient during subsequent bleedings. Some patients have good response to both products, however in other patients a better bleeding control is provided by one of the mentioned above agents (APCC or rFVIIa). There are clinical situations when severe bleedings requires an alternate use of both these agents.

Traditional methods of laboratory tests used post-treatment in patients with haemophilia without inhibitors are useless in the presence of inhibitor. Laboratory monitoring of therapy with by-passing agents is possible with the use of global tests for the coagulation process assessment, which are as follows: thrombin generation assay (TGA) and thromboelastometry (TEM).

Several studies revealed that TGA allows a monitoring of therapy with by-passing agents in patients with haemophilia A and inhibitor - the choice of the most effective treatment option - agent type and its dose, as well as laboratory assessment of treatment efficacy.

Up to date, laboratory tests assessing the efficacy of by-passing agents in patients with acquired haemophilia were not conducted.

In Factor VIII or IX deficiency conditions, fibrin's fibres generated by thrombin are morphologically thicker, and blood clots have increased susceptibility to fibrinolytic enzymes. Blood clot stability may be assessed with the use of thromboelastometry (TEM). We can hypothesize that simultaneous use of TGA and TEM methods may allow for an assessment of patient's individual response to therapy with by-passing agents. Clinical significance of the minimal dose of APCC and rFVIIa, needed to TGA and TEM normalization, requires further studies.

Tests' purpose: Examination of the hypothesis that simultaneous use of thrombin generation assay (TGA) and thromboelastometry (TEM) may facilitate the choice of optimal therapy with by-passing agents and laboratory monitoring of efficacy of those agents in patients with acquired haemophilia or haemophilia A with inhibitor.

Study Overview

• Status: Unknown
• Conditions: Haemophilia

Detailed Description

This section is Not applicable

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

Study Locations

• Poland
  • Gdansk, Poland, 80-952
    • Recruiting
    • Katedra i Klinika Hematologii i Transplantologii Gdanski Uniwersytet Medyczny
    • Contact: Andrzej Mital, MD, PhD
  • Krakow, Poland, 31-501
    • Recruiting
    • Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Alergii i Immunologii
    • Contact: Jacek Musial, MD, PhD
  • Lodz, Poland, 93-510
    • Recruiting
    • Klinika Hematologii Uniwersytetu Medycznego w Lodzi Wojewodzki Szpital Specjalistyczny im. M. Kopernika
    • Contact: Krzysztof Chojnowski, MD, PhD
  • Poznan, Poland, 61-505
    • Recruiting
    • Centrum Diagnostyczno - Lecznicze INTERLAB
    • Contact: Krystyna Zawilska, MD,PhD
  • Warszawa, Poland, 02-776
    • Recruiting
    • Instytut Hematologii i Transfuzjologii w Warszawie
    • Contact: Jerzy Windyga, MD, PhD
  • Wroclaw, Poland, 50-367
    • Recruiting
    • Katedra i Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku, Akademia Medyczna
    • Contact: Maria Podolak-Dawidziak, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

60 patients with acquired haemophilia 20 patients with congenital haemophilia A with inhibitor

Description

Inclusion Criteria:

• patients with acquired haemophilia
• patients with congenital haemophilia A with inhibitor

Exclusion Criteria:

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
haemophilia; Patients with acquired haemophilia. Patients with haemophilia A with inhibitor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of patient's individual response to therapy with by-passing agents by simultaneous use of TGA and TEM methods.	This is non-inverventional study as the protocol will not assign specific treatment to the particular subjects of the study. Patients will be treated with APCC or rFVIIa based on the experience of the study site. Patients are prescribed a treatment according to their physician's judgement or local clinical practice. This is observation of the everyday clinical practise on site.	48 hours

Collaborators and Investigators

• Sponsor: Stowarzyszenie Pomocy Chorym na Zakrzepicę i Skazy Krwotoczne Thrombus
• Investigators: Principal Investigator: Krystyna Zawilska, MD, PhD, Centrum Diagnostyczno - Lecznicze INTERLAB; Principal Investigator: Maria Podolak-Dawidziak, MD,PhD, Katedra i Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku, Akademia Medyczna; Principal Investigator: Andrzej Mital, MD, PhD, Katedra i Klinika Hematologii i Transplantologii Gdanski Uniwersytet Medyczny; Principal Investigator: Jerzy Windyga, MD, PhD, Instytut Hematologii i Transfuzjologii w Warszawie; Principal Investigator: Krzysztof Chojnowski, MD, PhD, Klinika Hematologii Uniwersytetu Medycznego w Lodzi Wojewodzki Szpital Specjalistyczny im. M. Kopernika; Principal Investigator: Jacek Musial, MD, PhD, Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Alergii i Immunologii

Publications and helpful links

General Publications

• Dargaud Y, Negrier C. Thrombin generation testing in haemophilia comprehensive care centres. Haemophilia. 2010 Mar;16(2):223-30. doi: 10.1111/j.1365-2516.2009.02082.x. Epub 2009 Aug 27.
• Berntorp E. Differential response to bypassing agents complicates treatment in patients with haemophilia and inhibitors. Haemophilia. 2009 Jan;15(1):3-10. doi: 10.1111/j.1365-2516.2008.01931.x. Epub 2008 Nov 10.
• Dargaud Y, Bordet JC, Lienhart A, Negrier C. Use of the thrombin generation test to evaluate response to treatment with recombinant activated factor VII. Semin Hematol. 2008 Apr;45(2 Suppl 1):S72-3. doi: 10.1053/j.seminhematol.2008.03.008. No abstract available.
• Livnat T, Martinowitz U, Zivelin A, Seligsohn U. Effects of factor VIII inhibitor bypassing activity (FEIBA), recombinant factor VIIa or both on thrombin generation in normal and haemophilia A plasma. Haemophilia. 2008 Jul;14(4):782-6. doi: 10.1111/j.1365-2516.2008.01688.x. Epub 2008 Mar 21.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Anticipated): April 1, 2016
• Study Completion (Anticipated): June 1, 2016

Study Registration Dates

• First Submitted: May 14, 2013
• First Submitted That Met QC Criteria: May 16, 2013
• First Posted (Estimate): May 17, 2013

Study Record Updates

• Last Update Posted (Estimate): December 18, 2015
• Last Update Submitted That Met QC Criteria: December 17, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Haemophilia; TGA; TEM
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: TGA-TEM