Multicenter Retrospective Study on the Utilization of FEIBA in France in Patients with Factor VIII and Factor IX Inhibitors

1997 ◽  
Vol 77 (06) ◽  
pp. 1113-1119 ◽  
Author(s):  
C Negrier ◽  
J Goudemand ◽  
Y Sultan ◽  
M Bertrand ◽  
C Rothschild ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Factor Viii ◽  
Surgical Procedures ◽  
Factor Ix ◽  
Care Providers ◽  
Substitution Product ◽  
Anamnestic Response ◽  
Hiv Seroprevalence ◽  
Bleeding Episodes ◽  
Activated Prothrombin Complex Concentrates

SummaryFactor VIII or factor IX replacement is frequently impossible in inhibitor-developing hemophiliacs, because of the level of the inhibitor titer. Activated prothrombin complex concentrates are one of the available options to treat the bleeding episodes in such patients. However, the efficacy of these products and the associated thrombogenic risk, particularly in prolonged administration such as employed during surgeries, are important concerns for hemophilia care providers. We performed a multicenter retrospective study to evaluate the use of FEIBA (Factor Eight Bypassing Activity) in France, and data is presented on 433 bleeding episodes, including surgical procedures, concerning 60 patients from 15 hemophilia centers.The efficacy was judged as good or excellent in 352 episodes (81.3%), poor in 73 episodes (16.9%) and non-existent in 8 episodes (1.8%). Minor and major surgical procedures were successfully performed using FEIBA as a second-line therapy after human or porcine factor VIII, and in some occasions FEIBA was utilized as the only substitution product. The tolerance was assessed as good in 428 episodes (98.8%), but in 5 cases adverse effects were reported. Only 3 patients out of 52 regularly evaluated (5.8%) were HIV-seropositive, and for two of them the seroconversion occurred prior to the first use of FEIBA. In contrast, 80.4% of the patients were HCV-seropositive. An anamnestic response after the administration of FEIBA was noted in 31.5% of cases. This study points out the main features of the use of FEIBA in France, and particularly the low HIV seroprevalence in the patients treated. The good efficacy and the excellent tolerance still confer to this product a place to consider in the therapeutic options for the treatment of inhibitor-developing hemophiliacs or in acquired hemophilia.

scholarly journals The use of factor eight inhibitor by-passing activity (FEIBA immuno) product for treatment of bleeding episodes in hemophiliacs with inhibitors

Blood ◽  
1983 ◽  
Vol 61 (1) ◽  
pp. 36-40 ◽  
Author(s):  
MW Hilgartner ◽  
GL Knatterud
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Side Effects ◽  
Soft Tissue ◽  
Factor Viii ◽  
Surgical Procedures ◽  
Factor Ix ◽  
Mucous Membranes ◽  
Bleeding Episodes ◽  
Inhibitor Titer

FEIBA (factor eight inhibitor by-passing activity) Immuno was used to achieve hemostasis in 46 patients with factor VIII inhibitors with titers greater than 4 Bethesda units, and 3 patients with factor IX inhibitors. One-hundred and sixty-five bleeding episodes were treated with 50–70 U/kg; 102 of these episodes occurred in joints. 20 in mucous membranes, 33 muscle and soft tissue, and 10 were emergency episodes including 3 central nervous system and 4 surgical procedures. Ninety- three percent of the bleeding episodes were controlled, while 7% were not controlled: 36% were controlled by one infusion in 12 hr, another 42% with 1 or more infusions in 36 hrs and an additional 14% were controlled in more than 36 hr. There were no serious side effects, and while the inhibitor titer rose in 10 of the patients, the product continued to be efficacious.

scholarly journals The use of factor eight inhibitor by-passing activity (FEIBA immuno) product for treatment of bleeding episodes in hemophiliacs with inhibitors

Blood ◽  
1983 ◽  
Vol 61 (1) ◽  
pp. 36-40 ◽  
Author(s):  
MW Hilgartner ◽  
GL Knatterud
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Side Effects ◽  
Soft Tissue ◽  
Factor Viii ◽  
Surgical Procedures ◽  
Factor Ix ◽  
Mucous Membranes ◽  
Bleeding Episodes ◽  
Inhibitor Titer

Abstract FEIBA (factor eight inhibitor by-passing activity) Immuno was used to achieve hemostasis in 46 patients with factor VIII inhibitors with titers greater than 4 Bethesda units, and 3 patients with factor IX inhibitors. One-hundred and sixty-five bleeding episodes were treated with 50–70 U/kg; 102 of these episodes occurred in joints. 20 in mucous membranes, 33 muscle and soft tissue, and 10 were emergency episodes including 3 central nervous system and 4 surgical procedures. Ninety- three percent of the bleeding episodes were controlled, while 7% were not controlled: 36% were controlled by one infusion in 12 hr, another 42% with 1 or more infusions in 36 hrs and an additional 14% were controlled in more than 36 hr. There were no serious side effects, and while the inhibitor titer rose in 10 of the patients, the product continued to be efficacious.

Management of Haemophilia A with Antibodies - The Effect of Combined Treatment with Factor VIII, Hydrocortisone and Cyclophosphamide

1985 ◽  
Vol 54 (04) ◽  
pp. 776-779 ◽  
Author(s):  
U Hedner ◽  
L Tengborn
Keyword(s):  
Factor Viii ◽  
Combined Treatment ◽  
Factor Ix ◽  
Treatment Schedule ◽  
High Antibody ◽  
Anamnestic Response ◽  
Short Intervals ◽  
Low Responders ◽  
Antibody Levels ◽  
High Responders

SummaryImmune tolerance has by several methods been induced in haemophiliacs with antibodies. A conversion of “high responders” into “low responders” was previously reported after repeated moderate factor IX doses over periods of 7-10 days in combination with cyclophosphamide and steroids in two patients with haemophilia B and inhibitors. This paper reports similar results in a heamophilia A patient by giving factor VIII, cyclophosphamide, and steroids during relatively short periods of time (7-8 days). The anamnestic response markedly decreased already following the first treatment and never exceeded a level of 1 u/ml (˜ 3 BU/ml) even when boosted with ordinary factor VIII doses for only 3 days. It is concluded that the markedly decreased secondary antibody response is most probably the result of factor VIII given at short intervals (twice a day) for periods of up to about one week when given in combination with cyclophosphamide and steroids. The same effect may be achieved by other methods. The treatment schedule suggested in the present paper is, however, simple and avoids long periods of high antibody levels. Furthermore, the total factor VIII dose used is lower than suggested in most other treatment schedules, which makes the treatment substantially less expensive.

Use of an Activated Prothrombin Complex Concentrate (Auto Factor IX-Hyland) in the Control of Bleeding of Haemophilic (A) Patients with Inhibitor of Factor VIII

1979 ◽  
Author(s):  
E.J. Watson-Williams ◽  
C.F. Abildgaard ◽  
E. A. Turner
Keyword(s):  
Soft Tissue ◽  
Factor Viii ◽  
Prothrombin Complex Concentrate ◽  
Factor Ix ◽  
Factor Viii Inhibitor ◽  
Activated Prothrombin Complex Concentrate ◽  
Prolonged Aptt ◽  
Bleeding Episodes ◽  
Viii Inhibitor ◽  
Flow Study

One of us (C.F.A.) has previously reported the successful use of one of the commercially available prothrombin complex concentrates for the control of bleeding episodes of haemophiltc patients with factor VIII inhibitors. Subsequent batches of these concentrates have not proved consistently effective even in doses of 150 factor IX units/kg every 24 hours. Recently an investigational preparation, Auto Factor IX, has been made available to us. This has a stated factor VIII correctional unit assay for each batch, (based on the ability to correct the prolonged APTT of plasma containing an inhibitor of factor VIII). We used 60-120 units/kg as an IV dose every 12 or 24 hours in the treatment of 24 bleeding episodes in 8 patients with factor VIII Inhibitor. The bleeding episodes were haemarthrosis (12) soft-tissue (6) intralingual (2) lacerations (2) retroperitoneal (1) and epidural (1). Rapid easing of pain and reduction of swelling was noted in all joints and soft tissue bleeds. In the retroperitoneal bleed cessation of bleeding was demonstrated by Technetium 99 Sulfur-colloid flow study, in the patient with epidural bleeding the hematoma was shown to reduce by serial CAT scans. Response was as good as we have come to expect from similar levels of factor VIII concentrate given to patients without an inhibitor. In 23 of the 24 episodes there was a marked reduction of APTT 10 minutes after the completion of the infusion.

scholarly journals Clinical Use of Factor IX Concentrates

1977 ◽  
Author(s):  
D. Ménaché
Keyword(s):  
Beneficial Effect ◽  
Factor Viii ◽  
Radical Change ◽  
Factor Ix ◽  
Severe Bleeding ◽  
Factor Viii Inhibitor ◽  
Anamnestic Response ◽  
Viii Inhibitor ◽  
Factor Ix Deficiency

The clinical efficacy of Factor IX concentrates in the treatment of patients with Factor IX deficiency is well recognized. The availability of such concentrates has brought a radical change in the management of these patients. The basis for treatment is to obtain an effective Factor IX hemostatic level in vivo. In these conditions, concentrates have been used to reduce the incidence of hemorrhagic episodes in patients particularly exposed and more often to control hemorrhagic episodes or to prevent hemorrhage in the post operative period. Although thromboembolic complications have occured in some instances the major indication of Factor IX concentrates still remains replacement therapy in patients with Factor IX deficiency.More recently Factor IX concentrates have been used for the treatment of patients with antibody to Factor VIII. Although the therapeutic principle(s) responsible for the Factor VIII inhibitor bypassing activity has not yet been characterized several beneficial effect of both “activated” and non activated Factor IX concentrates have been observed in such patients experiencing minor or severe bleeding episodes. On the other hand we are aware of some cases without beneficial effect of Factor IX concentrates in patients with Factor VIII inhibitor. The major complication would seem to be an anamnestic response in some patients resulting in either a moderate or a considerable increase of the Factor VIII inhibitor titer when compared to the initial level before Factor IX concentrates therapy. If Factor IX concentrates prove to be efficacious in the treatment of patients with Factor VIII antibody special attention would be required in the manufacturing processing in order to avoid an anamnestic response.

Use of Prothrombin Complex Concentrates in Hemophiliacs with Inhibitors: Clinical and Laboratory Studies

PEDIATRICS ◽  
1978 ◽  
Vol 62 (5) ◽  
pp. 767-774
Author(s):  
George R. Buchanan ◽  
Sherwin V. Kevy
Keyword(s):  
Factor Viii ◽  
High Titer ◽  
Factor Ix ◽  
Laboratory Studies ◽  
Clotting Factors ◽  
Prothrombin Complex Concentrates ◽  
Prolonged Incubation ◽  
Plasma Factor ◽  
Bleeding Episodes ◽  
Proven Benefit

Nine patients with severe classic hemophilia and inhibitors against factor VIII were treated for 156 bleeding episodes with 503 infusions of Proplex, Konyne, or Auto-Factor IX, three preparations of prothrombin complex concentrates (PCCs). Approximately two thirds of the bleeding episodes were managed successfully. Although the prothrombin time (PT) and partial thromboplastin time (PTT) were shortened after most PCC infusions, there was no evidence of disseminated intravascular coagulation. The degree of shortening of PT or PTT was not related to the particular PCC preparation used, dose, or cessation of hemorrhage. All PCC preparations contained activated clotting factors, as manifested by their ability to shorten the PTT of normal plasma, factor-VIII-deficient plasma, and factor-IX-deficient plasma. Shortening, which was greater with Auto-Factor IX than with the other products, was inhibited partially by a factor IX antibody and blocked completely by prolonged incubation with plasma. Although the nature of the procoagulant material in PCCs is uncertain, these products are of proven benefit to hemophilic patients with high-titer inhibitors. Side effects have been minimal and inhibitor titers have not risen.

scholarly journals Incidence of immune responses following 102 infusions of autoplex in 18 hemophilic patients with antibody to factor VIII

Blood ◽  
1984 ◽  
Vol 63 (2) ◽  
pp. 457-462
Author(s):  
Y Laurian ◽  
JP Girma ◽  
T Lambert ◽  
D Meyer ◽  
MJ Larrieu
Keyword(s):  
Immune Responses ◽  
Factor Viii ◽  
Prothrombin Complex Concentrate ◽  
Hemophilia A ◽  
Significant Rise ◽  
Predisposing Factor ◽  
Anamnestic Response ◽  
Activated Prothrombin Complex Concentrate ◽  
Bleeding Episodes ◽  
High Responders

An activated prothrombin complex concentrate (Autoplex) was infused for the treatment of 102 bleeding episodes in 18 hemophilia A patients with antibody to factor VIII who were previously known as high responders. Among 95 bleeding episodes treated with a single infusion of the concentrate [43–107 factor VIII correcting units (FECU)/kg], only 1 anamnestic response was observed. On the contrary, a significant rise in antibody titer occurred following 2 of 4 double (at 8–12 hr interval) and all 3 multiple (over3 –10 days) infusions of Autoplex. The occurrence of immune responses may be explained by the presence of factor VIII coagulant antigen (VIII:CAg) in the 26 batches of Autoplex tested by two-site immunoradiometric assay (10-–36 U/vial). The anamnestic response was not correlated to the batch used nor to the amount (0.6–7.8 U/kg/day) of VIII:CAg infused per day. However, exposure to the concentrate over several days appeared to be the major predisposing factor for an immune response.

Failure of Immunosuppression in a Severe Haemophilia B Patient with Specific Antibody

1976 ◽  
Vol 36 (01) ◽  
pp. 086-089 ◽  
Author(s):  
Jean-Pierre Allain ◽  
Dominique Frommel
Keyword(s):  
Factor Viii ◽  
Immunosuppressive Therapy ◽  
Specific Antibody ◽  
Factor Ix ◽  
Secondary Response ◽  
Severe Haemophilia ◽  
Anamnestic Response ◽  
Haemophilia B

SummaryPrevention of a secondary response to factor IX by cyclophosphamide was attempted in an 11 year old patient with severe Christmas disease. An antibody to factor IX had been present for 4 years before immunosuppressive therapy was tried. Despite profound lymphopenia, synthesis of factor IX antibody was not depressed. The difficulties of modifying the anamnestic response to factor IX by chemical immunosuppression may be as real as has been reported for factor VIII in classical haemophilia.

Activated Factor IX Complex in Treatment of Surgical Cases of Hemophilia A with Inhibitors

1981 ◽  
Vol 46 (03) ◽  
pp. 638-641 ◽  
Author(s):  
Wahid T Hanna ◽  
Robert R Madigan ◽  
Marian A Miles ◽  
Robert D Lange
Keyword(s):  
Factor Viii ◽  
Surgical Procedures ◽  
Hemophilia A ◽  
Aminocaproic Acid ◽  
Factor Ix ◽  
Severe Hemophilia ◽  
Thrombotic Complications ◽  
Normal Hemostasis ◽  
Epsilon Aminocaproic Acid

SummaryThree patients with severe hemophilia A with inhibitors to factor VIII were treated with activated factor IX complex. Bleeiling was controlled adequately during surgical procedures involving each of the three. Partial thromboplastin times showed a variable shortening and prothrombin times were significantly shortened to values less than normal. Hemostasis was substantiated by the use of epsilon aminocaproic acid. Neither anamnestic responses nor thrombotic complications were observed. A transient hypertension developed in two patients shortly after infusion with the activated factor IX complex.

Recombinant Factor VIIa Does not Induce Hypercoagulability In Vitro

1999 ◽  
Vol 81 (02) ◽  
pp. 245-249 ◽  
Author(s):  
Gerhard Cvirn ◽  
Wolfgang Muntean ◽  
Siegfried Gallistl
Keyword(s):  
Factor Viii ◽  
Thrombin Generation ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Factor Ix ◽  
Control Factor ◽  
Prothrombin Complex Concentrates ◽  
Thrombotic Complications ◽  
Activated Prothrombin Complex Concentrates

SummaryRecombinant factor VIIa (rVIIa) has been reported to be clinically effective and safe in haemophilic patients with inhibitor antibodies. Compared to activated prothrombin complex concentrates the risk of thrombotic complications seems to be very low after rVIIa administration. Determination of free thrombin generation has been shown to identify hypercoagulability. Therefore, free thrombin and prothrombinase activity (Xa generation) were assessed after extrinsic activation of rVIIa supplemented factor VIII and factor IX deficient plasma. Free thrombin generation was also determined after supplementation of (activated) prothrombin complex concentrates. Addition of 150 U rVIIa/ml shortened the clotting times markedly in control, factor VIII, and factor IX deficient plasma. In contrast, free thrombin and Xa generation were not different in the absence or presence of 150 U rVIIa/ml. Addition of (activated) prothrombin complex concentrates resulted in a marked increase of free thrombin generation in all investigated plasmas. Although in vitro studies cannot reflect specific clinical circumstances our results support the notion that rVIIa does not induce a hypercoagulable state as sporadically observed after administration of (activated) prothrombin complex concentrates.

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