Keywords
Acquired hemophilia, inhibitor, bypass agents, FVIII, immunosuppression
How to Cite
Quarchioni, M. (2019). Update in the therapeutic approach of Acquired FVIII Inhibitor (Acquired Hemophilia). Journal of Hematology, 21(1), 49–58. Retrieved from https://revistahematologia.com.ar/index.php/Revista/article/view/132
Abstract
Acquired haemophilia is an auto-immune disease caused by an inhibitory antibody to factor VIII. The pattern of bleeding varies but patients remain at risk of life threatening bleeding until the inhibitor has been eradicated. The cornerstones of management are; rapid and accurate diagnosis, control of bleeding, investigation for an underlying cause and eradication of the inhibitor by immunosuppression.
Patients should always be managed jointly with a specialist centre even if they present without significant bleeding. Despite an extensive literature, few controlled data are available and treatment guidelines are based on expert opinion. To treat bleeds recombinant factor VIIa and activated prothrombin complex concentrate are equally efficacious but both are superior to factor VIII or desmopressin.
Immunosuppression should be started as soon as the diagnosis is made. Commonly used regimens are steroids alone or combined with cytotoxic agents. Rituximab is another recommended therapeutic option in the second line.
References
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(1): 39-46.
2. Coppola A, Favaloro E, Tufano A, et al. Acquired inhibidor of coagulation factors part I: acquired hemophilia. Semin Thromb Hemost, June 2012; 38 (5): 433-66.
3. Collins PW, Hirsch S, Baglin TP, et al. UK Haemophilia Centre Doctors’ Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United
Kingdom Haemophilia Centre Doctors’ Organisation, Blood, March 2007; 109 (5):1870–77.
4. Knoebl P, Marco P, Baudo F, et al. Demographics and clinical data in acquired hemophilia A: results of the European Acquired Heamophilia (EACH2) registry. J Thromb Haemost, April
2012; 10 (4): 622-31.
5. Blanco AN, Grosso S. Fundamentos para el manejo práctico en el laboratorio de hemostasia. Inhibidores neutralizantes: inhibidores anti-FVIII. Grupo CAHT, 2da edición. Buenos Aires, 2013; 525-546.
6. Verbruggen B, Novakova I, Wessels H, et al. The Nijmegen modification of the Bethesda assay for factor VIII: C inhibitors: improved specificity and reliability. Thromb Haemost, Feb 1995; 73 (2): 247-51.
7. Kershaw G, Favaloro EJ. Laboratory identification of factor inhibitors an update. Pathology, June 2012; 44 (4): 293–302.
8. Baudo F, de Cataldo F, Gaidano G. Italian registry of acquired hemophilia. Treatment of acquired factor VIII inhibitor with recombinant activated factor VIIa: data from the Italian registry
of acquired hemophilia. Haematologica, June 2004; 89 (6):759–61.
9. Huth-Kühne A, Baudo F, Collins P, et al. International recommendations on the diagnosis and treatment of patients with acquired hemophilia A. Haematologica, April, 2009; 94 (4): 566–75.
10. Delgado J, Jimenez-Yuste V, Hernandez-Navarro F, et al. Acquired haemophilia: review and meta-analysis focused on therapy and prognostic factors. Br J Haematol, April, 2003; 121 (1):
21–35.
11. Collins PW. Management of acquired haemophilia A. J Thromb Haemost, July 2011; 9 (1):226–35.
12. Sumner MJ, Geldziler BD, Pedersen M, et al. Treatment of acquired haemophilia with recombinant activated FVII: a critical appraisal. Haemophilia, Sep, 2007; 13 (5): 451-61.
13. Collins PW. Therapeutic challenges in acquired factor VIII deficiency ASH. Hematology, Dec, 2012; (1): 369-374.
14. Collins PW, Chalmers E, Hart D, et al. Diagnosis and management of acquired coagulation inhibitors: a guideline from UKHCDO. A United Kingdom Haemophilia
Centre Doctors’ Organization (UKHCDO) guideline approved by the British Committee for Standards in Haematology. B J Haematol, Jul 2013; 162 (6): 758-63.
15. Franchini M. Recombinant factor VIIa: a review on its clinical use. Int J Hematol, feb 2006; 83 (2):126-38.
16. Sallah S. Treatment of acquired haemophilia with factor eight inhibitor bypassing activity. Haemophilia, March 2004; 10 (2):169-73.
17. Kasper CK. Human factor VIII for bleeding in patients with inhibitors. Vox Sang 1999; 77 (1): 47-8.
18. Toschi V. OBI-1, porcine recombinant factor VIII for the potential treatment of patients with congenital hemophilia A and alloantibodies agains human factor VIII. Curr Opin Mol Ther,
Oct 2010; 12 (5): 617-25.
19. Guía de tratamiento de la hemofilia. Consenso de Médicos Especialistas en Hemofilia de la República Argentina. Segunda edición, 2015. http://www.hemofilia.org.ar/archivos/pdfs/
GuiaTratamientoHemofilia.pdf. Último acceso noviembre 2014
20. Franchini M and Lippi G. The use of desmopressin in acquired haemophilia A: a systematic review, Blood Transfus, Oct 2011; 9 (4): 377-82.
21. Franchini M, Sassi M, Dell’ Anna P, et al. Extracorporeal immunoadsorption for the treatment of coagulation inhibitors. Semin Thromb Hemost, Feb 2009; 35 (1): 76-80.
22. Zeitler H, Ulrich Merzenich G, Hess L, et al. Treatment of acquired hemophilia by the Bonn-Malmo Protocol: documentation of an in vivo immunomodulating concept. Blood, March 2005; 105 (6): 2287-93.
23. Aledort LM. Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus factor VIII inhibitor bypass activity. J Thromb Haemost, Oct 2004; 2 (10): 1700–8.
24. Sborov DW and Rodgers GM. How I manage patients with acquired haemophilia A. Br J Haematol, April 2013; 161 (2): 157-165.
25. Collins PW, Baudo F, Knoebl P, et al. Immunosuppression for acquired hemophilia A: results of the European Acquired Haemophilia (EACH2) registry. Blood, July 2012; 120 (1):47-55.
26. Alzate M, Meschengieser S, Blanco A et al. Acquired Hemophilia A. Experince of a Single Center. Blood, Nov, 2013; 122 (21): 4781.
27. Franchini M and Mannuccio PM. Inhibitor eradication with rituximab in haemophilia: where do we stand? Br J Haematol, June 2014; 165 (5): 600-8.
28. Sperr WR, Lechner K and Pabinger I. Rituximab for the treatment of acquired antibodies to factor VIII. Haematologica, Jan 2007; 92 (1): 66-7
29. Pardos-Gea J, Altisent C, Parra R, et al. Acquired haemophilia A. First line treatmnet with calcineurin inhibitors and steroid pulses: a 10 year follows up study. Haemophilia, Sep 2012;
18 (5): 789-93.
30. Franchini M. Postpartum Acquired Factor VIII Inhibitors. Am J Hematol, Oct 2006; 81 (10):768–73.
31. Tengborn L, Baudo F, Huth-Ku¨hne A, et al. Pregnancy-associated acquired haemophilia A: results from the European Acquired Haemophilia (EACH2) registry. BJOG, Nov 2012; 119
(12): 1529–37.
32. Ries M, Wölfel D and Maier-Brandt B. Severe intracranial hemorrhage in a newborn infant with transplacental transfer of an acquired factor VII:C inhibitor. J Pediat, Oct 1995; 127(4):
649-50.
33. Zeitler H, Ulrich-Merzenich G, Marquardt N, et al. Immunoadsorption for pregnancy-associated severe Acquired Hemophilia. Therapeutic Apheresis and Dialysis, Feb 2014; 18 (1):103-10.
34. Baudo F and De Cataldo F. Italian Association of Haemophilia Centres (AICE): Register of acquired factor VIII inhibitors (RIIA). Acquired factor VIII inhibitors in pregnancy: data from the Italian Haemophilia Register relevant to clinical practice. Int J Obst Gynaecol, March 2003; 110 (3): 311-14.
35. L.Tengborn et al. Tranexamic acid- an old still going strong and making a revival. Thrombosis Reserch, 2015; 135: 231-242.
(1): 39-46.
2. Coppola A, Favaloro E, Tufano A, et al. Acquired inhibidor of coagulation factors part I: acquired hemophilia. Semin Thromb Hemost, June 2012; 38 (5): 433-66.
3. Collins PW, Hirsch S, Baglin TP, et al. UK Haemophilia Centre Doctors’ Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United
Kingdom Haemophilia Centre Doctors’ Organisation, Blood, March 2007; 109 (5):1870–77.
4. Knoebl P, Marco P, Baudo F, et al. Demographics and clinical data in acquired hemophilia A: results of the European Acquired Heamophilia (EACH2) registry. J Thromb Haemost, April
2012; 10 (4): 622-31.
5. Blanco AN, Grosso S. Fundamentos para el manejo práctico en el laboratorio de hemostasia. Inhibidores neutralizantes: inhibidores anti-FVIII. Grupo CAHT, 2da edición. Buenos Aires, 2013; 525-546.
6. Verbruggen B, Novakova I, Wessels H, et al. The Nijmegen modification of the Bethesda assay for factor VIII: C inhibitors: improved specificity and reliability. Thromb Haemost, Feb 1995; 73 (2): 247-51.
7. Kershaw G, Favaloro EJ. Laboratory identification of factor inhibitors an update. Pathology, June 2012; 44 (4): 293–302.
8. Baudo F, de Cataldo F, Gaidano G. Italian registry of acquired hemophilia. Treatment of acquired factor VIII inhibitor with recombinant activated factor VIIa: data from the Italian registry
of acquired hemophilia. Haematologica, June 2004; 89 (6):759–61.
9. Huth-Kühne A, Baudo F, Collins P, et al. International recommendations on the diagnosis and treatment of patients with acquired hemophilia A. Haematologica, April, 2009; 94 (4): 566–75.
10. Delgado J, Jimenez-Yuste V, Hernandez-Navarro F, et al. Acquired haemophilia: review and meta-analysis focused on therapy and prognostic factors. Br J Haematol, April, 2003; 121 (1):
21–35.
11. Collins PW. Management of acquired haemophilia A. J Thromb Haemost, July 2011; 9 (1):226–35.
12. Sumner MJ, Geldziler BD, Pedersen M, et al. Treatment of acquired haemophilia with recombinant activated FVII: a critical appraisal. Haemophilia, Sep, 2007; 13 (5): 451-61.
13. Collins PW. Therapeutic challenges in acquired factor VIII deficiency ASH. Hematology, Dec, 2012; (1): 369-374.
14. Collins PW, Chalmers E, Hart D, et al. Diagnosis and management of acquired coagulation inhibitors: a guideline from UKHCDO. A United Kingdom Haemophilia
Centre Doctors’ Organization (UKHCDO) guideline approved by the British Committee for Standards in Haematology. B J Haematol, Jul 2013; 162 (6): 758-63.
15. Franchini M. Recombinant factor VIIa: a review on its clinical use. Int J Hematol, feb 2006; 83 (2):126-38.
16. Sallah S. Treatment of acquired haemophilia with factor eight inhibitor bypassing activity. Haemophilia, March 2004; 10 (2):169-73.
17. Kasper CK. Human factor VIII for bleeding in patients with inhibitors. Vox Sang 1999; 77 (1): 47-8.
18. Toschi V. OBI-1, porcine recombinant factor VIII for the potential treatment of patients with congenital hemophilia A and alloantibodies agains human factor VIII. Curr Opin Mol Ther,
Oct 2010; 12 (5): 617-25.
19. Guía de tratamiento de la hemofilia. Consenso de Médicos Especialistas en Hemofilia de la República Argentina. Segunda edición, 2015. http://www.hemofilia.org.ar/archivos/pdfs/
GuiaTratamientoHemofilia.pdf. Último acceso noviembre 2014
20. Franchini M and Lippi G. The use of desmopressin in acquired haemophilia A: a systematic review, Blood Transfus, Oct 2011; 9 (4): 377-82.
21. Franchini M, Sassi M, Dell’ Anna P, et al. Extracorporeal immunoadsorption for the treatment of coagulation inhibitors. Semin Thromb Hemost, Feb 2009; 35 (1): 76-80.
22. Zeitler H, Ulrich Merzenich G, Hess L, et al. Treatment of acquired hemophilia by the Bonn-Malmo Protocol: documentation of an in vivo immunomodulating concept. Blood, March 2005; 105 (6): 2287-93.
23. Aledort LM. Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus factor VIII inhibitor bypass activity. J Thromb Haemost, Oct 2004; 2 (10): 1700–8.
24. Sborov DW and Rodgers GM. How I manage patients with acquired haemophilia A. Br J Haematol, April 2013; 161 (2): 157-165.
25. Collins PW, Baudo F, Knoebl P, et al. Immunosuppression for acquired hemophilia A: results of the European Acquired Haemophilia (EACH2) registry. Blood, July 2012; 120 (1):47-55.
26. Alzate M, Meschengieser S, Blanco A et al. Acquired Hemophilia A. Experince of a Single Center. Blood, Nov, 2013; 122 (21): 4781.
27. Franchini M and Mannuccio PM. Inhibitor eradication with rituximab in haemophilia: where do we stand? Br J Haematol, June 2014; 165 (5): 600-8.
28. Sperr WR, Lechner K and Pabinger I. Rituximab for the treatment of acquired antibodies to factor VIII. Haematologica, Jan 2007; 92 (1): 66-7
29. Pardos-Gea J, Altisent C, Parra R, et al. Acquired haemophilia A. First line treatmnet with calcineurin inhibitors and steroid pulses: a 10 year follows up study. Haemophilia, Sep 2012;
18 (5): 789-93.
30. Franchini M. Postpartum Acquired Factor VIII Inhibitors. Am J Hematol, Oct 2006; 81 (10):768–73.
31. Tengborn L, Baudo F, Huth-Ku¨hne A, et al. Pregnancy-associated acquired haemophilia A: results from the European Acquired Haemophilia (EACH2) registry. BJOG, Nov 2012; 119
(12): 1529–37.
32. Ries M, Wölfel D and Maier-Brandt B. Severe intracranial hemorrhage in a newborn infant with transplacental transfer of an acquired factor VII:C inhibitor. J Pediat, Oct 1995; 127(4):
649-50.
33. Zeitler H, Ulrich-Merzenich G, Marquardt N, et al. Immunoadsorption for pregnancy-associated severe Acquired Hemophilia. Therapeutic Apheresis and Dialysis, Feb 2014; 18 (1):103-10.
34. Baudo F and De Cataldo F. Italian Association of Haemophilia Centres (AICE): Register of acquired factor VIII inhibitors (RIIA). Acquired factor VIII inhibitors in pregnancy: data from the Italian Haemophilia Register relevant to clinical practice. Int J Obst Gynaecol, March 2003; 110 (3): 311-14.
35. L.Tengborn et al. Tranexamic acid- an old still going strong and making a revival. Thrombosis Reserch, 2015; 135: 231-242.
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