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Advances in the Treatment of Hemophilia: Implications for Laboratory Testing

Armando Tripodi, Veena Chantarangkul, Cristina Novembrino, Flora Peyvandi
DOI: 10.1373/clinchem.2017.284356 Published October 2018
Armando Tripodi
Angelo Bianchi Bonomi Hemophilia and Thrombosis CenterIRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.
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  • For correspondence: armando.tripodi@unimi.it
Veena Chantarangkul
Angelo Bianchi Bonomi Hemophilia and Thrombosis CenterIRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.
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Cristina Novembrino
Angelo Bianchi Bonomi Hemophilia and Thrombosis CenterLaboratory of Clinical Chemistry and MicrobiologyIRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.
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Flora Peyvandi
Angelo Bianchi Bonomi Hemophilia and Thrombosis CenterDepartment of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, ItalyIRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.
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Abstract

Background: Until recently, clinical laboratories have monitored hemophilia treatment by measuring coagulation factors before/after infusion of human-derived or recombinant factors. Substantial changes are expected in the near future based on new therapeutic approaches that have been or are being developed.

Content: Hemophilia treatment includes replacement therapy with human-derived/recombinant factors or treatment with bypassing agents for patients without or with inhibitors, respectively. Accordingly, laboratory methods for monitoring include one-stage clotting or chromogenic assays meant to measure either factor VIII/IX or global coagulation tests to measure the effect of bypassing agents. Recently, modified long-acting coagulation factors have been introduced for which discrepant results may be expected when measurement is performed with one-stage clotting or chromogenic assays. Currently, novel drugs not based on coagulation factors are under development and are being tested in clinical studies. These drugs do require new methods and therefore laboratory evaluation of hemophilia will undergo dramatic changes in the near future.

Summary: From the analysis of the current practice and literature, we draw the following conclusions: (a) Thrombin generation or thromboelastometry are the logical candidate assays to monitor bypassing agents. (b) Considerable differences are expected when measuring modified long-acting coagulation factors, depending on whether one-stage or chromogenic assays are used. Although no definitive conclusions can presently be drawn, chromogenic assays are probably more suitable than one-stage clotting. (c) Novel drugs not based on coagulation factors such as emicizumab, fitusiran, or concizumab that are entering the market do require alternative methods that are not yet well established.

  • Received for publication December 20, 2017.
  • Accepted for publication July 26, 2018.
  • © 2018 American Association for Clinical Chemistry

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Clinical Chemistry: 65 (2)
Vol. 65, Issue 2
February 2019
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Advances in the Treatment of Hemophilia: Implications for Laboratory Testing
Armando Tripodi, Veena Chantarangkul, Cristina Novembrino, Flora Peyvandi
Clinical Chemistry Jan 2018, clinchem.2017.284356; DOI: 10.1373/clinchem.2017.284356
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Advances in the Treatment of Hemophilia: Implications for Laboratory Testing
Armando Tripodi, Veena Chantarangkul, Cristina Novembrino, Flora Peyvandi
Clinical Chemistry Jan 2018, clinchem.2017.284356; DOI: 10.1373/clinchem.2017.284356

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