Systemic Therapy In Acquired Haemophilia - A Single Institute Experience

Overview

Journal Ulster Med J

Specialty General Medicine

Date 2016 Oct 5

PMID 27698522

Authors

Lawless Sarah

Das Prantik

Benson Gary

Affiliations

Soon will be listed here.

Abstract

A cornerstone of the management of Acquired Haemophilia A (AHA) involves inhibitor eradication. First line immunosuppressive agents are usually steroids, either alone or in combination with cyclophosphamide. We present the use of Rituximab, cyclophosphamide, vincristine and prednisolone (RCVP) combination as immunosuppressant in AHA in a small cohort of patients in order to control their symptoms and eradicate inhibitors. This was a retrospective analysis of all AHA patients treated at the Northern Ireland Haemophilia centre over a six year period. During this time, a total of six patients were newly diagnosed with AHA. Four of these patients failed to respond conventional therapy of steroids and cyclophosphamide, they were however successfully treated with RCVP/ RCV. All patients achieved complete remission with this regimen after 1 to 2 cycles of treatment. Remission has been maintained for an extended time period (range 33-69 months). As AHA is related to immune modulation and, in some cases, underlying malignancy we decided to use this regime as it is effective in either condition. From our experience, we demonstrate that RCVP combination is a promising treatment in patients with AHA who fail to respond to steroids alone or who have been on pre-existing immunosuppression.

References

Green D, Lechner K . A survey of 215 non-hemophilic patients with inhibitors to Factor VIII. Thromb Haemost. 1981; 45(3):200-3. View

Franchini M . Rituximab in the treatment of adult acquired hemophilia A: a systematic review. Crit Rev Oncol Hematol. 2007; 63(1):47-52. DOI: 10.1016/j.critrevonc.2006.11.004. View

Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J . CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2004; 105(4):1417-23. DOI: 10.1182/blood-2004-08-3175. View

Lian E, Larcada A, Chiu A . Combination immunosuppressive therapy after factor VIII infusion for acquired factor VIII inhibitor. Ann Intern Med. 1989; 110(10):774-8. DOI: 10.7326/0003-4819-110-10-774. View

Villar M, Noy L, Ruiz-Dayao Z . Acquired factor VIII inhibitor treated with cyclophosphamide, vincristine, and prednisone. Am J Hematol. 2002; 69(4):294-5. DOI: 10.1002/ajh.10070. View

Collins P, Hirsch S, Baglin T, Dolan G, Hanley J, Makris M . Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2006; 109(5):1870-7. DOI: 10.1182/blood-2006-06-029850. View

Collins P, Chalmers E, Hart D, Jennings I, Liesner R, Rangarajan S . Diagnosis and management of acquired coagulation inhibitors: a guideline from UKHCDO. Br J Haematol. 2013; 162(6):758-73. DOI: 10.1111/bjh.12463. View

Hasan A, Michel M, Patel V, Stasi R, Cunningham-Rundles S, Leonard J . Repeated courses of rituximab in chronic ITP: Three different regimens. Am J Hematol. 2009; 84(10):661-5. PMC: 2783818. DOI: 10.1002/ajh.21512. View

Green D, Rademaker A, Briet E . A prospective, randomized trial of prednisone and cyclophosphamide in the treatment of patients with factor VIII autoantibodies. Thromb Haemost. 1993; 70(5):753-7. View

10.

Ma A, Carrizosa D . Acquired factor VIII inhibitors: pathophysiology and treatment. Hematology Am Soc Hematol Educ Program. 2006; :432-7. DOI: 10.1182/asheducation-2006.1.432. View

11.

Delgado J, Jimenez-Yuste V, Hernandez-Navarro F, Villar A . Acquired haemophilia: review and meta-analysis focused on therapy and prognostic factors. Br J Haematol. 2003; 121(1):21-35. DOI: 10.1046/j.1365-2141.2003.04162.x. View

12.

McMillan R . Long-term outcomes after treatment for refractory immune thrombocytopenic purpura. N Engl J Med. 2001; 344(18):1402-3. DOI: 10.1056/NEJM200105033441815. View

13.

Spero J, Lewis J, Hasiba U . Corticosteroid therapy for acquired F VIII:C inhibitors. Br J Haematol. 1981; 48(4):635-42. DOI: 10.1111/j.1365-2141.1981.00635.x. View

14.

Stasi R, Brunetti M, Stipa E, Amadori S . Selective B-cell depletion with rituximab for the treatment of patients with acquired hemophilia. Blood. 2004; 103(12):4424-8. DOI: 10.1182/blood-2003-11-4075. View

15.

Collins P, Baudo F, Knoebl P, Levesque H, Nemes L, Pellegrini F . Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). Blood. 2012; 120(1):47-55. PMC: 3390961. DOI: 10.1182/blood-2012-02-409185. View

16.

Field J, Fenske T, Blinder M . Rituximab for the treatment of patients with very high-titre acquired factor VIII inhibitors refractory to conventional chemotherapy. Haemophilia. 2007; 13(1):46-50. DOI: 10.1111/j.1365-2516.2006.01342.x. View

17.

Franchini M, Lippi G . Acquired factor VIII inhibitors. Blood. 2008; 112(2):250-5. DOI: 10.1182/blood-2008-03-143586. View

18.

Shaffer L, Phillips M . Successful treatment of acquired hemophilia with oral immunosuppressive therapy. Ann Intern Med. 1997; 127(3):206-9. DOI: 10.7326/0003-4819-127-3-199708010-00005. View