Factor Eight Inhibitor Bypassing Activity Research Articles

Reversing Dabigatran in Life-Threatening Bleeding Occurring During Cardiac Ablation With Factor Eight Inhibitor Bypassing Activity

We report a case of a patient receiving dabigatran who developed a life-threatening bleeding complication during cardiac ablation that rapidly resolved after administration of Factor Eight Inhibitor Bypassing Activity (FEIBA). Therapeutic anticoagulation with warfarin during cardiac ablation has been shown to reduce the risk of stroke and systemic embolism. Cardiac tamponade is a potentially life-threatening procedural complication requiring emergent reversal of anticoagulation and pericardiocentesis. Dabigatran is superior to warfarin in preventing stroke and systemic embolism in nonvalvular atrial fibrillation, but has not been evaluated for use during cardiac ablation. Dabigatran is without a known reversal agent and, should tamponade occur during ablation, it is unclear what reversal strategy could be used to establish hemostasis. A 67-year-old man with history of atrial fibrillation with rapid ventricular rate, two previous atrial fibrillation ablations, and prescribed dabigatran 150 mg bid was admitted for an atrial fibrillation ablation procedure. The last dabigatran dose was 7 hours prior to procedure. During the procedure, a transseptal perforation occurred, requiring an emergent pericardiocentesis. Within 60 minutes, approximately 4.5 L of blood was removed via the pericardiocentesis. Low-dose FEIBA (3159 units, 26 U/kg actual body weight) over 15 minutes was administered. Hemostasis was noted within minutes of initiating the infusion with cessation of bleeding after administration was complete. This case report describes the potential ability of a low dose of the activated prothrombin complex concentrate, FEIBA, to reestablish hemostasis independent of the pharmacologic effects of dabigatran. Additional studies are warranted to confirm the findings of our observation.

Factor VIII Bypassing Activity (FEIBA) assays: standardization and development of the 1st NIBSC Working Standard for FEIBA – results from a collaborative study

Factor-Eight-Inhibitor-Bypassing-Activity (FEIBA) is a bypassing-agent used to control spontaneous bleeding or cover surgical interventions in Haemophiliacs who develop neutralizing antibodies against FVIII/FIX. The market lot-release of FEIBA is dependent on specific clot-based assays, carried out by both the manufacturer and regulatory authorities, relative to manufacturer's in-house standards, which are produced on a small-scale and are replaced frequently. We sought to standardize the FEIBA assay by developing a FEIBA primary standard which would be internationally available in sufficiently large quantities, with a predicted lifetime of many years. A collaborative study involving the manufacturer and three regulatory authorities, was carried out in which a candidate material, sample B (06/172), was calibrated by assays relative to the manufacturer's in-house FEIBA standards (C and D). All laboratories used their routine validated methods (16 APTT-assays, 8 ACTIN-FS-assays and 27 DAPTTIN-assays). Intra-laboratory geometric coefficients of variation (GCVs) for candidate B ranged from 3% to 29% (GCVs <9% from majority of labs). Assessment of inter-laboratory variability gave overall GCV values of 6.9% and 4.4% relative to standards C and D, respectively, for all methods. There was good agreement in potency estimation between laboratories using each of the three methods, with the overall potencies by the three methods differing by less than 10% of the overall mean, giving an overall combined potency of 28.0 units per ampoule. All participants agreed that candidate B (06/172) be established as the 1st NIBSC Working Standard for FEIBA with an assigned potency of 28.0units per ampoule, based on combined results for both methods, relative to either standard C or D.

FEIBA: A Prohemostatic Agent

Factor eight inhibitor bypassing activity (FEIBA), Anti-Inhibitor Coagulation Complex has been used for over 30 years in hemophiliac patients with inhibitors. The history of its use is reviewed here, including issues related to thrombosis, efficacy, and comparison to alternative bypassing agents. The need for surrogate assays to monitor effective hemostasis with the use of FEIBA remains.

New direct oral anticoagulants – current therapeutic options and treatment recommendations for bleeding complications

To date, clinical studies show that the incidence of spontaneous bleeding with new direct oral anticoagulants (DOAs) is comparable to that of established anticoagulants. However, unlike vitamin K antagonists, there are currently no clinically available antidotes or approved reversal agents for new DOAs. Restoring normal coagulation is important in many cases, such as emergency surgeries, serious bleedings, or anticoagulant overdosing. Attempts have been made to restore normal coagulation after treatment with new DOAs using compounds such as recombinant activated factor VII (rFVIIa), prothrombin complex concentrate (PCC), or FEIBA (factor eight inhibitor bypassing activity). Limited pre-clinical data and even less clinical evidence are available on the usefulness of these methods in restoring normal coagulation for the emergency management of critical bleeding episodes. Evaluating the utility of DOAs is further complicated by the fact that it is unknown how predictive established test systems are of the bleeding risks. Clinical practice requires further evaluation of the emergency management options for the new DOAs to define the agents and the doses that are most useful. Furthermore, patients receiving long-term treatment with a DOA are likely to undergo elective surgery at some point, and there is lack of evidence regarding perioperative treatment regimens under such conditions. This review summarises potential bleeding management options and available data on the new DOAs.

Efficacy of FEIBA for acute bleeding and surgical haemostasis in haemophilia A patients with inhibitors: a multicentre registry in Turkey

Long used in established industrialized nations to treat patients with haemophilia and inhibitors, factor eight inhibitor bypassing activity (FEIBA) has, in recent years, been introduced into more geographically diverse settings. Data are needed on how successfully FEIBA therapy has been implemented in new regions. To determine the efficacy and safety of FEIBA for the treatment of acute bleeding and surgical haemostasis in a newly industrialized country. A multicentre registry of haemophilia A patients with inhibitors receiving FEIBA treatment was established in Turkey. With a standardized case report form, data were collected retrospectively on: patient demographics; characteristics of acute bleeding episodes and surgical interventions; FEIBA regimen; and treatment outcomes. Thirty-seven patients received a total of 112 FEIBA treatment courses, 90 for acute bleeding and 22 for surgical haemostasis. The median FEIBA dose per infusion for acute bleeding was 50 IU kg(-1), and for surgery was 100 IU kg(-1). For both acute joint and muscle/soft tissue bleeding and in surgery, haemostasis was attained in a median of two FEIBA infusions. FEIBA was judged effective in 92% of treatment courses for acute bleeding, with a 95% confidence interval (CI) of 85-97%. Rates of haemostatic efficacy did not differ significantly between anatomical sites of acute bleeding. The haemostatic efficacy rate of FEIBA in surgery was 86% (CI, 65-97%). No thromboembolic complications or other adverse events occurred during any treatment course. FEIBA has been successfully integrated into clinical practice in Turkey, with rates of haemostatic efficacy comparable to those reported in countries with a longer history of FEIBA usage.

190Factor VIII inhibitor bypassing activity (FEIBA) as an adjunct in post-cardiotomy bleeding

Refractory bleeding after cardiac surgery continues to be a significant challenge. Post-bypass coagulopathy requiring multiple transfusions is associated with higher levels of morbidity and mortality. This problem has been exacerbated in recent years by the increased use of antiplatelet agents and the loss of aprotinin. Factor eight inhibitor bypassing activity (FEIBA) is a coagulation factor concentrate commonly used in haemophelia, but it has also shown some promise in postoperative hemostasis. We report on the largest known series of its use in post-cardiotomy coagulopathy. A retrospective review of 81 consecutive cases involving the use of FEIBA at a provincial cardiac surgical program was performed. From Jan 1, 2008 to Sep 30, 2010, a total of 81 patients received FEIBA for bleeding refractory to routine adjunct therapy such as platelets, fresh frozen plasma (FFP) and cryoprecipitate administration. 28 patients received intra-operative doses only, 44 received postoperative doses only, and 9 received both intra- and post-operative doses. Average age was 66.5 years, with 50 males and 31 females. 18 cases were isolated CABG with all other cases being concomitant procedures or complex urgent cases. For the 37 patients who received intra-operative FEIBA, average CPB time was 237 minutes (S.D. ± 82) and all patients were still bleeding after receiving standard coagulation factors. The average FEIBA dose was 939 Units (S.D. ± 203) and adequate hemostasis allowed for sternal closure in all patients. 28 patients did not receive additional FEIBA, average blood loss over first 12 hours was 677 mls (S.D. ± 314), and only 1 patient required re-exploration. 9 patients were given a second dose postoperatively and 4 patients required re-exploration (4/37, 10.8%). For patients receiving post-operative FEIBA only, average CPB time was 139 minutes (S.D. ± 57), average blood loss was 1271 mls ( ± 455) before FEIBA and 121 mls in the first hour after FEIBA. 9 of those patients required re-exploration. In all 81 patients, there were no strokes or perioperative myocardial infarctions, and 1 mortality (1.2%). Renal insufficiency developed in 12 patients (14.8%). Intra- or post-operative use of FEIBA appears to be effective in controlling refractory bleeding post-cardiotomy, with acceptable rates of complications in a high risk surgical cohort. A prospective randomized trial to further determine this drug's efficacy may be warranted.

Successful major and minor surgery using factor VIII inhibitor bypassing activity in patients with haemophilia A and inhibitors

Surgeries are being increasingly performed in patients with haemophilia A and high-titre inhibitors. Optimal bypassing agent regimens need further delineation. Data pertaining to surgeries from 1989 to 2004 at a single centre were retrospectively analysed. Patients received a standardized factor eight inhibitor bypassing activity (FEIBA) dose for both major and minor elective or emergency surgeries. The standard FEIBA dose was 70 U kg(-1) per infusion. FEIBA was infused at 9 and 1 h before and 8 h after operation. Infusions were routinely repeated every 8 h afterward. Haemostatic efficacy was assessed on the basis of blood loss, occurrence of haematoma and transfusion requirements. Seven adult patients underwent a total of 12 operations: 10 major and two minor. Ten procedures were elective. The median cumulative numbers of infusions and days of therapy were 46 and 17, respectively. Cumulative total FEIBA consumption was a median of 3185 U kg(-1). Observed blood losses, haematoma incidence and transfusion requirements were comparable to those expected for noncoagulopathic patients undergoing similar procedures. The only large haematoma occurred after a hip prosthesis operation and resolved under continuing FEIBA treatment. There were no cases of disseminated intravascular coagulation or other thromboembolic complications. FEIBA provides an effective and safe first-line peri- and postoperative haemostatic therapy for patients with haemophilia A and inhibitors, allowing both major and minor operations to be successfully performed.

FEIBA®in treatment of acute bleeding episodes in patients with haemophilia A and factor VIII inhibitors: a retrospective survey in regional haemophilia centre

FEIBA (factor eight inhibitor by-passing activity) is used to achieve haemostasis in haemophiliacs with inhibitor. The aim of this study was to evaluate efficacy and consumption of the product in treatment of haemorrhages in haemophiliacs with factor VIII inhibitor, and determine factors that can influence the results of treatment. We used data from our haemophilia centre from years 2000-2008. Six haemophiliacs with factor VIII inhibitor were treated on demand with FEIBA for 61 bleeding episodes (45 haemarthroses, six muscle bleeds, six other sites bleeds and four multiple sites bleeds). The median cumulative dose of FEIBA per bleeding episode was 205 U kg(-1). Bleeding was stopped in 96.7% (59 of 61) of events but re-bleeding occurred in 3 events (4.9%) within 48 h after cessation of bleeding. In home treatment (20 of 61) bleeding stopped in 90% (18 of 20) without recurrence and the median consumption per event was reduced to 153 U kg(-1). Without the use of home treatment the median consumption was 250 U kg(-1) per event and bleeding ceased definitely in 92.7% (38 of 41) of cases. The cumulative dose of FEIBA was lower for three episodes with re-bleeding: median 96 U kg(-1) but not in the two cases of ineffective treatment: 361 U kg(-1). FEIBA in management of bleeding episodes completely resolved the haemorrhage in 91.8% of events and in a further 4.9% if treatment was restarted. Using home treatment saved expenditure due to the lower cumulative dose needed for treatment of haemorrhage.

Differential response to bypassing agents complicates treatment in patients with haemophilia and inhibitors

The bypassing agents factor eight inhibitor bypassing activity (FEIBA) anti-inhibitor coagulant complex and recombinant activated factor VII (rFVIIa) have been established as safe and effective therapies for treating bleeding episodes in haemophilia patients with inhibitors. However, the efficacy of each bypassing agent can vary, and neither agent is universally effective. The reasons for such variability have yet to be confirmed, but may involve patient-specific factors and the mechanisms of action (MOAs) and pharmacokinetic profiles of these two agents. This issue underscores the necessity of both products in the comprehensive care of patients with haemophilia and inhibitors. The objective of this review is to discuss the evidence of a differential haemostatic response to bypassing agents and the potential roles of MOA and patient-specific factors in contributing to the differences in response.

Factor Eight Inhibitor Bypassing Activity (FEIBA) for Refractory Bleeding in Cardiac Surgery: Review of Clinical Outcomes

Refractory postoperative bleeding complicates a significant number of cardiac surgical procedures and results in both morbidity and mortality. Conventional strategies to effect hemostasis include surgical reexploration and administration of blood products. In some cases, bleeding remains intractable despite these methods, and alternatives are needed. Herein, we report our experience with the use of factor eight inhibitor bypassing activity (FEIBA), a coagulation factor concentrate, for refractory postoperative bleeding. A retrospective review of the experience with FEIBA at a university-affiliated cardiac surgery program between February 2004 and January 2007 was performed. Sixteen patients received FEIBA for refractory postoperative bleeding. The majority (69%) received a single dose, either intraoperatively or postoperatively. The recipients of multiple doses were more likely to undergo operative reexploration. Blood product utilization and hourly chest tube output were decreased significantly following administration of FEIBA. Three deaths occurred (19%), two from multisystem organ failure and one from respiratory failure. Thrombotic events included the development of a clotted hemothorax in one patient and distal extremity ischemia in another. FEIBA administration is associated with decreased blood product utilization and chest tube output in patients with refractory postoperative bleeding.

Some recent developments regarding arthropathy and inhibitors in haemophilia

In this paper, the most recent developments on arthropathy and inhibitors in haemophilia are reviewed. Firstly, early long-term prophylaxis is strongly recommended in children with severe haemophilia. Secondly, in joint bleeds not responding to substitution of factor VIII to normal factor VIII levels angiographic embolization might be considered as a promising therapeutic option. Thirdly, recent data indicate disruption of normal development for adolescents with inhibitors. Fourthly, some case reports indicate the benefit of secondary prophylaxis with recombinant factor VIIa (rFVIIa) or factor eight inhibitor bypassing activity (FEIBA) in patients with severe haemophilia A and inhibitors. Finally, surgical procedures in haemophilia patients with factor inhibitors can be accomplished safely and effectively with FEIBA and/or rFVIIa, although the risk of complications is higher than in haemophilia patients without inhibitors.

Short‐term oral corticosteroid therapy for acute haemarthrosis in haemophilia patients with high‐titre inhibitors

Treatment of acute bleeding events is unsatisfactory in patients with haemophilia and high-titre factor VIII (FVIII) inhibitors. In order to determine whether short-term corticosteroid therapy enhances resolution of the signs and symptoms of acute haemarthrosis, we performed a randomized, double-blind, placebo-controlled study in children with FVIII deficiency and high-titre inhibitors receiving Factor Eight Inhibitor Bypass Activity (FEIBA) for acute haemorrhagic events. At each haemarthrosis, patients were randomized to receive either prednisolone 2 mg kg(-1) day(-1) or placebo-divided t.i.d. for 2 days (six doses) in addition to FEIBA. The primary endpoint was the number of subsequent doses of FEIBA required. The effect of the study medication was also assessed subjectively by patients or parents, by physical examination and by repeated haemorrhages into the joint. During the study period, seven patients were enrolled with 45 evaluable events, 24 treated with prednisolone and 21 with placebo. An average of 2.08 and 1.86 doses of FEIBA were infused in the prednisolone- and placebo-treated patients, respectively. By Wilcoxon Rank Sum Test, there was no statistically significant difference in number of additional infusions of FEIBA or duration of symptoms between the corticosteroid and placebo arms. We conclude that there is no significant benefit of a 2-day course of oral corticosteroids as adjunctive therapy for haemarthrosis in patients with haemophilia and a high-titre inhibitor.

Antidotal Effects of rFVIIa and FEIBA on Anticoagulant-Induced Inhibition of Thrombin Generation.

Recombinant FVIIa (NovoSeven®, N7) has been demonstrated to antagonize the antihemostatic effects of anticoagulants such as anti-Xa-agents like LMWH or Fondaparinux. Whether this effect, which can be monitored using cell-based in vitro assays including platelets, can also be observed when trying to antagonize thrombin inhibitors and heparinoids, is still insufficiently known. We used a fluorometric thrombin generation test (TGT) to assay N7 efficacy in platelet-rich plasma (PRP) on eight concentrations of Argatroban (Argatra®), Lepirudin (Refludan®) and Danaparoid (Orgaran®) between 0 and 10 μg/ml resp. 0–10 anti-Xa units/ml) including their therapeutic ranges. Blood samples used for spiking were taken from eight healthy male volunteers who had taken no antihemostatic medication 14 days before sampling. TF was used as initiator of coagulation (final conc. 60 fM). FEIBA (factor eight inhibitor bypassing activity) was also tested as a potential antidote in this experimental setting. N7 doses used for in-vitro spiking of PRP samples were betweeen 2.4 (corresponding to clinically used high doses) and 9.6 (Argatroban, Fondaparinux) resp. 24 μg/ml (Lepirudin), FEIBA doses were 0.5, 1 and 2 U/ml. The TGT parameters evaluated were ETP, PEAK, LAG TIME (LT) and TIME TO PEAK (TTP). While the Argatroban effect on thrombin generation could not be reversed up to 9.6 μg/ml of N7, for FEIBA the thrombin activity increased half-logarithmic-like with linear rises for doubled FEIBA doses. The inhibitory effect of Lepirudin on TGT parameters was neutralized by 2.4 μg/ml rFVIIa, and the lowest FEIBA concentration (0.5 U/ml) was also sufficient. For Danaparoid, the reversal of its inhibitory effects in the TGT was more marked for supratherapeutical concentrations, but 2.4 μg N7/ml worked as well as 24. The antidote effect of FEIBA on Danaparoid concentrations increased with FEIBA concentrations, but seemed to be less strong than that of N7. Fondaparinux (Arixtra®), which was run as control substance in our assay and antagonized with N7 2.4 μg/ml (9.6 μg/ml had no stronger effect) and FEIBA in the intermediate concentration of 1U/ml, showed analogous changes to the results published by Lisman et al., JTH 2003. Regarding the TGT parameters, there seem to be “cut-offs” between 2 and 5μg/ml for the inhibitors without antidotes where ETP and PEAK are reduced to zero. Inhibitor-induced prolongation of LT and TTP showed similar characteristics with and without antidotes, but on different levels, i. e. the antidotes shortened these time values over the whole inhibitor concentration range. Higher concentrations of antidotes were more effective on high inhibitor concentrations. Argatroban could be antagonized with FEIBA only, whereas N7 was also effective on Lepirudin and Fondaparinux, and even better on Danaparoid. The N7 reversal of Lepirudin-induced irreversible thrombin inhibition seems to be contradictory to the missing effect on the reversible Argatroban-induced effect but could be due to the (slow) binding kinetics (Elg et al Thromb Haemost 1997) of the recombinant hirudin. The assay could be used to determine or predict the antihemostatic effects of anticoagulants over a dose range and the potential efficacy of antidotes for overdosing with anticoagulants. Furthermore, it may be a tool for a personalized medicine approach.

Individualization of bypassing agent treatment for haemophilic patients with inhibitors utilizing thromboelastography

The treatment of bleeding for haemophilic patients with inhibitors relies on the use of the bypassing agents, recombinant factor VIIa and factor eight inhibitor bypass activity (FEIBA). While both therapies are effective in the majority of bleeding episodes, there is a significant amount of interindividual variability when it comes to the response to therapy. As of yet, there is no reliable laboratory parameter that can predict the response to therapy in the same manner that factor VIII and factor IX levels predict response in non-inhibitor patients. Developing such a laboratory parameter is vital in order to maximize the clinical efficacy of these agents. Thromboelastography (TEG) is a device, which assesses clot formation over time in whole blood and has several characteristics which suggest it may be an effective way to monitor bypass agent therapy. We studied the ability of TEG to individualize the treatment regimens of three patients with high titre inhibitors assessing the response to recombinant factor VIIa, FEIBA, and when both were used sequentially. The TEG allowed for individualization of treatment for each of the three patients and resulted in more effective, convenient and less expensive treatment regimens. We thus believe that TEG is a promising device for monitoring of bypass agent therapy and should be studied further.

Acquired Hemophilia A: A Single Institution's Experience.

Background: Acquired Hemophilia A (AH) due to factor VIII inhibitor is a rare life threatening disorder. If not diagnosed and treated urgently, significant mortality and morbidity results. AH can occur in setting of old age, autoimmune diseases, pregnancy, medication, malignancy, and lymphoproliferatve disorders. In majority of cases it is idiopathic.Objective: Review the treatment modalities and outcome of AH patients at our institution.Methods: A retrospective review of the data pertaining to patients who were diagnosed with AH at our institution between 1993–2004.Results: There were 5 patients diagnosed with AH, 3 female and 2 male. The median age was 67 years (range 30–84 years) the setting for development of AH in these patients was as follows: 1- postpartum, 1-HIV, 3 idiopathic. All patients presented with varying degree of spontaneous hemorrhage. The median Factor VIII inhibitor level was 16 Bethesda Unit (BU)(range 7. 2–31). Acute control of hemorrhage was achieved in all patients using either FEIBA (Factor eight inhibitor bypass activity) alone (1 patient), FEIBA and Novo seven (VIIa)(4 patients). Chronic immunosuppressive therapy was given as follows: Steroid alone (2 patients), Steroid and IVIG (1 patients), Steroid and Cyclophospamide (1 patient) and Steroid, Cyclophospamide and Rituximab (1 patient). Complete remission (CR) was obtained in 4 patients and with the final patient still receiving treatment. In one patient, the dose of Cyclophospamide was decreased due to Leucopenia. The median time to elimination of inhibitors was 5 month (range 1–10 month). There have been no mortalities.Conclusions: AH is a life threatening condition if not promptly diagnosed and treated, mortality remains significantly high. Treatment with factors replacement and immunosuppressive therapy was effective in all our patients

FEIBA: mode of action.

FEIBA (factor eight inhibitor bypassing activity) has a history of more than 30 years of successful use in controlling bleeding in haemophilic patients who have developed inhibitory antibodies against factor (F)VIII or FIX. Recently it was shown that FEIBA contains the proenzymes of the prothrombin complex factors, prothrombin, FVII, FIX and FX, but only very small amounts of their activation products, with the exception of FVIIa, which is contained in FEIBA in greater amounts. FEIBA controls bleeding by induction and facilitation of thrombin generation, a process for which FV is crucial. A number of biochemical in vitro and in vivo studies have shown that FXa and prothrombin play a critical role in the activity of FEIBA. Consequently, they are considered to be key components of this product. The prothrombinase complex has been found to be a major target site for FEIBA. Apart from prothrombin and FXa, FEIBA contains other proteins of the prothrombin complex, which could also facilitate haemostasis in haemophilia patients with inhibitors.

Treatment of acquired haemophilia with factor eight inhibitor bypassing activity.

Haemorrhagic manifestations in patients with acquired haemophilia can be fatal if not recognized and treated appropriately. A retrospective analysis of the efficacy of factor eight inhibitor bypassing activity (FEIBA) in patients with acquired haemophilia treated in three medical centres in the past 10 years was conducted. The median inhibitor titre at treatment was 128 Bethesda Units (BU) in patients with severe and 34 BU in patients with moderate bleeding; P = 0.001. The majority of patients received FEIBA at a dose of 75 u kg-1 every 8-12 h. The number of FEIBA doses administered was higher in patients with severe compared with moderate haemorrhage, 10 vs. 6 doses per bleeding episode; P = 0.001. Complete response (CR) was achieved in 76% of severe and 100% of moderate bleeding episodes with a total CR of 86%. When compared with patients with human inhibitor titre <50 BU, those with titre >51 BU at treatment had lower median porcine titre, 1 vs. 9.5 BU; P < 0.05, fewer doses of FEIBA, 6 vs. 8.5 doses; P < 0.05, and shorter time to CR, 29 vs. 42 h; P < 0.05. Patients exposed to factor VIII concentrates prior to FEIBA had significantly higher maximum recorded human inhibitor titre compared with patients without such exposure, 273 vs. 38 BU; P = 0.0001. Treatment with FEIBA was very well tolerated and with very few side effects. This study provides evidence that FEIBA is an effective agent in acquired haemophilia and suitable for all types of patients regardless of severity of haemorrhage, underlying disease or inhibitor titre.

Failure of Activated Prothrombin Complex Concentrates in a Hemophiliac With an Anti-Factor VIII Antibody

IN APPROXIMATELY 15% of patients with severe hemophilia A who receive multiple transfusions, anti— factor VIII antibodies develop (C. W. McMillan, MD, S. S. Shapiro, MD, J. Lazerson, MD, unpublished data, 1983). Control of hemorrhagic episodes in these patients is often difficult and unsatisfactory. Various methods of treatment have been developed for such patients.^1,2Most recently, activated prothrombin complex concentrates (PCCs) have been described as efficacious in controlling hemorrhage in patients with an inhibitor. Two preparations of activated PCC have been developed: Autoplex (anti-inhibitor coagulant complex) and FEIBA (factor eight inhibitor bypassing activity). In published trials, response to treatment with Autoplex for major and minor bleeds ranged from excellent to fair with no treatment failures,²while FEIBA was judged to be effective in control of joint and muscle bleeding in 64% of treatment episodes.³The purpose of this report is to describe the failure of Autoplex to

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

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.