Effect of Treatment with Activated Prothrombin Complex Concentrate (FEIBA) on Factor VIII-Antibody Level

1978 ◽  
Vol 40 (02) ◽  
pp. 478-485 ◽  
Author(s):  
K Lechner ◽  
Ch Nowotny ◽  
B Krinninger ◽  
M Zegner ◽  
E Deutsch
Keyword(s):  
Factor Viii ◽  
Antibody Level ◽  
Prothrombin Complex Concentrate ◽  
Anamnestic Response ◽  
Activated Prothrombin Complex Concentrate ◽  
Inhibitor Level ◽  
Complex Preparation ◽  
Effect Of Treatment ◽  
High Doses ◽  
Stimulation Of

SummaryThe influence of treatment with an activated prothrombin complex preparation (FEIBA) on the antibody level was studied in 10 haemophiliacs with an antibody to factor VIII. The antibody level was observed to rise at least once in five patients, while in the remaining five patients no rise occurred. In all, 6 out of 31 treatments were followed by an anamnestic rise of the antibody level, corresponding to 19.4%. A rise of the inhibitor level following FEIBA treatment is likely to occur in patients who show a marked antibody rise after factor VIII treatment (good responders), but have a low antibody level at the time of treatment. High doses of FEIBA and simultaneous transfusion of red cells may also enhance the likelihood of an anamnestic response. Stimulation of antibody production is probably due to the presence of small amounts of factor VIII in this preparation.

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.

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

Abstract 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.

scholarly journals Treatment of Joint-Bleedings in Hemophiliacs with Antibodies to Factor VIII with High doses of Fraction Feiba.

1977 ◽  
Author(s):  
Kl. Schimpf ◽  
K. Zimmermann ◽  
P. Zeltsch
Keyword(s):  
Knee Joint ◽  
Factor Viii ◽  
Half Life ◽  
Clinical Effect ◽  
Single Injection ◽  
Life Time ◽  
Joint Effusion ◽  
The Third ◽  
Inhibitor Level ◽  
High Doses

Observations in 3 patients demonstrated, that joint-bleedings can be controlled with high doses of fraction FEIBA alone or in combination with factor (f) VIII on out-patient basis. First patient, inhibitor 5-10 units (u) per ml, suffered from 24 joint-bleedings within 392 days. 2o of them could be stopped by a single injection of 150-200 u of fraction FEIBA per kg bodyweight (bw). A combination of 90 u of FEIBA and 36 u of f VIII per kg bw had the same effect. But after 5 injections of this combination within 6 weeks, the inhibitor level had risen from 10 to 240 u per ml. During further treatment with 180 u of fraction FEIBA without addition of f VIII, the inhibitor fell down with a half life time of 50 days. The clinical effect of fraction FEIBA was not influenced by the elevated antibody level. Two further patients, inhibitors 2-4 and 32 u respectively, obtained combined injections of 50-100 u of FEIBA plus 36-42 u of f VIII. One patient was on a prophylaxis of 3 injections weekly for 193 days. After 57 injections the inhibitor had fallen from 2-4 u to unmeasurable values. The third patient obtained the above mentioned dosis twice a day for treatment of a knee joint effusion. After 1 week the inhibitor was diminished from 32 to 13 u.

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 Anti-inhibitor Coagulant Complex (Autoplex) for treatment of factor VIII inhibitors in hemophilia

Blood ◽  
1980 ◽  
Vol 56 (6) ◽  
pp. 978-984 ◽  
Author(s):  
CF Abildgaard ◽  
JA Penner ◽  
EJ Watson-Williams
Keyword(s):  
Soft Tissue ◽  
Factor Viii ◽  
Prothrombin Complex Concentrate ◽  
Activated Partial Thromboplastin Time ◽  
Minor Bleeding ◽  
Puncture Wound ◽  
Monitoring Therapy ◽  
Concurrent Use ◽  
Activated Prothrombin Complex Concentrate ◽  
Bleeding Episodes

Abstract Fourteen individuals with severe hemophilia complicated by factor VIII inhibitors (1 to 132 Bethesda Units) were treated for 33 bleeding episodes with a new activated prothrombin complex concentrate, Anti- Inhibitor Coagulant Complex (Autoplex, Hyland, Glendale, Calif.). Excellent or good results were observed in 21 of 25 minor bleeding episodes treated, which included joint, soft tissue, and mucous membrane hemorrhages. Eight major bleeding problems (an epidural bleed, a puncture wound, 2 serious soft tissue hemorrhages, 2 lacerations, and 2 major surgical procedures) were treated with excellent (6) or good (2) results. No serious complications were encountered, but two children developed transient hypofibrinogenemia following Autoplex infusion. Although some shortening of the prothrombin time and activated partial thromboplastin time was noted after infusion of Autoplex, there is no useful laboratory test for monitoring therapy. Despite the unknown mechanism of action for bypassing factor VIII, Autoplex appears to be a useful and needed interim product and is safe and effective. In view of the possible potentiation of thrombosis concurrent use of fibrinolytic inhibitors should be avoided.

scholarly journals Anti-inhibitor Coagulant Complex (Autoplex) for treatment of factor VIII inhibitors in hemophilia

Blood ◽  
1980 ◽  
Vol 56 (6) ◽  
pp. 978-984 ◽  
Author(s):  
CF Abildgaard ◽  
JA Penner ◽  
EJ Watson-Williams
Keyword(s):  
Soft Tissue ◽  
Factor Viii ◽  
Prothrombin Complex Concentrate ◽  
Activated Partial Thromboplastin Time ◽  
Minor Bleeding ◽  
Puncture Wound ◽  
Monitoring Therapy ◽  
Concurrent Use ◽  
Activated Prothrombin Complex Concentrate ◽  
Bleeding Episodes

Fourteen individuals with severe hemophilia complicated by factor VIII inhibitors (1 to 132 Bethesda Units) were treated for 33 bleeding episodes with a new activated prothrombin complex concentrate, Anti- Inhibitor Coagulant Complex (Autoplex, Hyland, Glendale, Calif.). Excellent or good results were observed in 21 of 25 minor bleeding episodes treated, which included joint, soft tissue, and mucous membrane hemorrhages. Eight major bleeding problems (an epidural bleed, a puncture wound, 2 serious soft tissue hemorrhages, 2 lacerations, and 2 major surgical procedures) were treated with excellent (6) or good (2) results. No serious complications were encountered, but two children developed transient hypofibrinogenemia following Autoplex infusion. Although some shortening of the prothrombin time and activated partial thromboplastin time was noted after infusion of Autoplex, there is no useful laboratory test for monitoring therapy. Despite the unknown mechanism of action for bypassing factor VIII, Autoplex appears to be a useful and needed interim product and is safe and effective. In view of the possible potentiation of thrombosis concurrent use of fibrinolytic inhibitors should be avoided.

Toll-Like Receptor Triggering Modulates Factor VIII-Specific Immune Memory in Murine Hemophilia A with Factor VIII Inhibitors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 214-214 ◽  
Author(s):  
Peter Allacher ◽  
Christina Hausl ◽  
Rafi U. Ahmad ◽  
Hans Peter Schwarz ◽  
Peter L. Turecek ◽  
...  
Keyword(s):  
B Cells ◽  
Factor Viii ◽  
B Cell ◽  
Hemophilia A ◽  
Memory B Cells ◽  
Immune Memory ◽  
Low Doses ◽  
Specific Memory ◽  
High Doses ◽  
Stimulation Of

Abstract The development of inhibitory antibodies against factor VIII (FVIII) is the major complication in the treatment of hemophilia A patients with FVIII products. Immune Tolerance Induction (ITI) therapy using long-term application of high doses of FVIII has evolved as an effective therapy to eradicate the antibodies and induce long-lasting immune tolerance. It is a common observation that infections, particularly central venous catheter infections during ITI cause a rise in anti-FVIII antibody titers that can prolong the course of ITI or possibly even lead to failure of ITI. Based on this observation, we asked the question whether microbial components derived from viruses or bacteria modulate the re-stimulation of FVIII-specific immune memory and disturb the recently described inhibition of memory-B-cell-re-stimulation by high doses of FVIII (Hausl et al.: Blood2005; in press). Microbial components are recognized by toll-like receptors (TLRs) that serve as an important link between innate and adaptive immunity. TLRs can discriminate various microbial components such as lipopeptides derived from bacteria or zymosan derived from yeast (recognized by TLR1/2 or TLR2/6), double-stranded RNA derived from viruses (recognized by TLR3), lipopolysaccharide (LPS) derived from gram-negative bacteria (recognized by TLR4), flagellin derived from bacterial flagella (recognized by TLR5), single-stranded RNA derived from viruses (recognized by TLR7/8) or bacterial DNA containing the unmethylated CpG motif (recognized by TLR9). We analyzed the re-stimulation of FVIII-specific memory-B cells using a murine model of hemophilia A as described previously (Hausl et al.: Blood2004; 104:115–22; Hausl et al.: Blood2005, in press). The following TLR ligands were tested: zymosan for TLR2 (0.1–10,000 ng/ml), poly I:C for TLR3 (1.0–50,000 ng/ml), LPS for TLR4 (0.1–10,000 ng/ml), Flagellin for TLR5 (0.01–1,000 ng/ml), Loxoribine for TLR7 (1.0–50,000 ng/ml) and CpG oligonucleotides for TLR9 (0.1–10,000 ng/ml). Our results indicate that none of the TLR ligands at the concentrations tested induced a significant re-stimulation of FVIII-specific memory B cells in the complete absence of either FVIII or T cells. However, ligands for TLR3, TLR4, TLR7 and TLR9 were able to disturb the inhibition of memory-B-cell-re-stimulation by high doses of FVIII and amplified the re-stimulation induced by low doses of FVIII substantially. We conclude that triggering of TLRs by microbial components that are present during infections amplify the re-stimulation of FVIII-specific memory B-cells induced by low doses of FVIII and disturb the inhibition induced by high doses of FVIII.

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