RSS-Feed abonnieren
DOI: 10.1055/s-0038-1665434
The Treatment of Bleeding in Acquired Haemophilia with Recombinant Factor VIIa: A Multicentre Study
Publikationsverlauf
Received 21. 1997
Accepted after resubmission 17. Juli 1997
Publikationsdatum:
30. Juli 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199701/lookinside/thumbnails/10-1055-s-0038-1665434-1.jpg)
Summary
Recombinant factor Vila was used to treat 38 patients with acquired haemophilia participating in the Novoseven compassionate-use program. 19 were male, median age 59, range 2-89 years. The median pre-treatment anti-human (H) and anti-porcine (P) inhibitor titre was H 43 BU/ml (range 1-4500) and P 4.5 BU/ml (range 0-1600). Recombinant factor VIIa was used as first-line therapy for 14 bleeding episodes and as salvage-therapy for 60 episodes which failed to respond to blood-product therapy given for a median of four days (range 1-21 days) prior to treatment with rVIIa. Pre-rVIIa treatment was not reported for four episodes. The indications for treatment were 7 haemarthroses, 40 muscle haematomas, 20 urinary or GI haemorrhages and 3 surgical interventions. The median starting dose of rVIIa was 90.4 ug/kg (range 45-181). A median of 28 doses (range 1-541) were given per episode, over a median 3.9 days (range 0-43).
Efficacy was assessed clinically 8 and 24 h after the start of rVIIa and at the end of treatment. A good response was obtained in all 14 bleeds for which rVIIa was used as first-line therapy. The response after 24 h of rVIIa salvage-therapy for 60 bleeds was good in 75%, partial in 17% and poor in 8%. Efficacy was unreported in 4 cases. The median prothrombin time (PTT) shortened from 12 s (range 9.3-20) pre-treatment to 8.8 s (range 6-14) during treatment. The clinical response did not correlate with the dose of rVIIa used, the type of bleed or the degree of shortening of the PTT following rVIIa infusion.
Three patients died from haemorrhagic complications of acquired haemophilia. This mortality of 7.9% is lower than previously reported for this condition. Although one patient developed DIC during treatment with rVIIa, this was probably attributable to hypovolaemic shock, massive transfusion and the use of PCCs. This study demonstrates that rVIIa is a safe, useful and effective treatment for bleeding in patients with acquired haemophilia.
-
References
- 1 Shapiro SS, Hultin M. Acquired inhibitors to the blood coagulation factors. Sem Thromb and Hemostas 1975; 1: 336-385
- 2 Lottenburg R, Kentro TB, Kitchins CS. Acquired haemophilia: a natural history study of 16 patients with factor VIII inhibitor receiving little or no therapy. Arch Intern Med 1987; 147: 1077-1081
- 3 Green D, Lechner KA. A survey of 215 non-haemophiliac patients with inhibitors to factor VIII. Thromb Haemost 1981; 45: 200-203
- 4 Green D, Rademaker AW, Briët E. A randomised trial of prednisolone and cyclophosphamide in the treatment of patients with factor VIII autoantibodies. Thromb Haemost 1993; 70: 753-757
- 5 Nilsson IM, Skanse B, Gydell K. Circulating anticoagulant after pregnancy and its response to ACTH. Acta Haemat 1958; 19: 40-50
- 6 Hauser I, Gisslinger H, Locker G. et al Postpartum factor VIII inhibitors: report of two cases with special reference to the efficacy of various treatments. Wiener Klin Wochenschrift 1993 105 (012) 1993; 40-50
- 7 Sherman LA, Goldstein MA, Sise HS. Circulating anticoagulant (antifactor Vni) treated with immunosuppressive drugs. Thrombosis et Diathesis Haemorrhagica 1969; 21: 249-258
- 8 Spero JA, Lewis JH, Hasiba U. Corticosteroid therapy for acquired FVIII:C inhibitors. Br J Haematol 1981; 48: 635-642
- 9 Hultin MB. Acquired inhibitors in malignant and non-malignant disease states. Am J Med 1991; 91 (supp 05A) 09S-13S
- 10 Morrison AE, Ludlam CA, Kessler CM. Use of porcine factor VIII in the treatment of patients with acquired hemophilia. Blood 1993; 81: 1513-1520
- 11 Gringeri A, Santagostino E, Tradati F, Giangrande PLF, Mannucci PM. Adverse effects of treatment with porcine factor VIII. Thromb Haemost 1991; 65: 245-247
- 12 Hay CRM, Lozier JN, Lee CA, Laffan M, Tradati F, Santagostino E, Ciava-rella N, Schiavoni M, Fukui H, Yoshioka A, Teitel J, Mannucci PM, Kasper CK. Safety profile of porcine factor VIII and its use as hospital and home-therapy for patients with haemophilia A and inhibitors: the results of an international survey. Thromb Haemost 1996; 75: 25-29
- 13 Lusher JM, Shapiro SS, Palacak JE, Rao AV, Levine PH, Blatt PM. and the Haemophilia study Group. Efficacy of prothrombin complex concentrates in hemophiliacs with antibodies to factor VIII: a multicenter therapeutic trial. N Eng J Med 1980; 303: 421-425
- 14 Lusher JM. Use of prothrombin complex concentrates in the management of bleeding in hemophiliacs with inhibitors benefits and limitations. Semin Haematol 1994; 31: 49-52
- 15 Chavin SI, Siegel DM, Rocco TA, Olsen JF. Acute myocardial infarction during treatment with an activated prothrombin complex concentrate in a patient with factor VIII deficiency and a factor VIII inhibitor. Am J Med 1988; 85: 244-249
- 16 Hay CRM, Colvin BT, Ludlam CA, Hill FGH, Preston FE. Recommendations for the treatment of factor VIII inhibitors: from the UK Haemophilia Centre Directors Organisation Inhibitor Working Party. Blood Coagulation and Fibrinolysis 1996; 7: 134-138
- 17 Hedner U, Feldstedt M, Glazer S. Recombinant FVIIa in hemophilia treatment. In: Hemophilia and von Willebrand’s disease in the 1990s. Lusher JM, Kessler CM. eds Amsterdam: Elsevier Science Publishers BV. 1991: 283-292
- 18 Hedner U, Glazer S, Falch J. Recombinant activated factor VII in the treatment of bleeding episodes in patients with inherited and acquired bleeding disorders. Trans Med Rev 1993; 7 (02) 78-83
- 19 Macik BG, Lindley CM, Lusher J, et al. Safety and initial efficacy of three dose-levels of recombinant activated factor VII (rFVIIa): results of a phase 1 study. Blood Coagulation and Fibrinolysis 1993; 4: 521-527
- 20 Hedner U. Factor Vila in the treatment of haemophilia. Blood Coagulation and Fibrinolysis 1990; 1 (03) 307-17
- 21 Kasper CK, Aledort LM, Counts RB. et al A more uniform measurement of factor VIII inhibitors. Thrombosis et Diathesis Haemorrhagica 1975; 34: 869-872
- 22 Cooper HA, Hoots WK, Shapiro A. Comparison of two doses of recombin- at factor Vila (rVIIa) for producing hemostasis during and after surgery in patients (PTS) with hemophilia A or B and inhibitors and PTS with acquired inhibitors. Thromb Haemost 1997; suppl 167-168
- 23 Marder VJ, Shulman NR. Clinical aspects of congenital factor VII deficiency. Am J Med 1964; 37: 182-186
- 24 Dike GWR, Griffiths D, Bidwell E, Snape TJ, Rizza CR. A factor VII concentrate for therapeutic use. B J Haematol 1980; 45: 107-118
- 25 Novo Nordisk. unpublished manufacturers information.
- 26 Shulman S, Bech Jensen M, Varon D, Keller N, Gitel S, Horozowski H, Heim M, Martinowitz U. Feasability of using recombinant factor Vila in continuous infusion. Thromb Haemost 1996; 75 (03) 432-436