Fibrinopeptide-A (FPA) Generation by Factor IX Concentrates (F-IX-C) and Feiba (factor VIII inhibitor bypassing activity)

1979 ◽  
Author(s):  
V. Hofmann ◽  
M. Ermanni ◽  
P.M. Straub
Keyword(s):  
Factor Viii ◽  
Factor Ix ◽  
Time Dependent ◽  
Factor Viii Inhibitor ◽  
Fibrinopeptide A ◽  
Coagulant Activity ◽  
At Iii ◽  
Viii Inhibitor

The increase of FPA from 0.4-2.4 to 5.6-80 mg/ml after infusion of F-I-C in 5 hemophiliacs B prompted a study whether thrombin is present or genera ted in F-IX-C and in FEIBA rasp. Purified dialysed fibrinogen served as substrate, FPA-release was measured by RIA and expressed as % of the total FPA in fibrinogen. F-IX-C + fibrinogen produced only traces of FPA. The addition of Ca++ led to a time-dependent increase of FPA-release. 8 batches F-IX-C from 2 sources (Immuno, SwissRedCross) were preincubated with Ca++ for 2 hrs, added to fibrinogen with and without heparin, and FPA measured after 60 s. In absence of heparin 7 F-IX-C produced 5 to 80% FPA, in its presence no FPA was liberated. FEIBA + fibrinogen produced clotting and an 80% FPA-release in 5 min, prevented by prior heparin addition. Preincubation of FEIBA with Ca++ increased FPA-release from 80 to 100%, however, prevention required an ll-fold heparin conc. Hirudin more effectively blocked FPA-release probably due to low AT III in concentrates. Thus, in F-IX-C thrombin is absent or blocked by heparin added by the manufacturer; however, thrombin is rapidly generated in presence of Ca++. The coagulant activity of FEIBA is due to thrombin rather than to a “factor VIII inhibitor bypassing activity”.

In Vitro Thrombogenicity Tests of Factor IX Concentrates

1979 ◽  
Vol 42 (05) ◽  
pp. 1355-1367 ◽  
Author(s):  
C V Prowse ◽  
A Chirnside ◽  
R A Elton
Keyword(s):  
Factor Viii ◽  
Partial Thromboplastin Time ◽  
Generation Time ◽  
Activated Partial Thromboplastin Time ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Factor Viii Inhibitor ◽  
Factor Ixa ◽  
Viii Inhibitor

SummaryVarious factor IX concentrates have been examined in a number of in vitro tests of thrombogenicity. The results suggest that some tests are superfluous as in concentrates with activity in any of these tests activation is revealed by a combination of the non-activated partial thromboplastin time, the thrombin (or Xa) generation time and factor VIII inhibitor bypassing activity tests. Assay of individual coagulant enzymes revealed that most concentrates contained more factor IXa than Xa. However only a small number of concentrates, chiefly those that had been purposefully activated, contained appreciable amounts of either enzyme.

New Method for Quantifying Lupus Anticoagulant

1996 ◽  
Vol 2 (4) ◽  
pp. 237-240
Author(s):  
Roy Speck
Keyword(s):  
Factor Viii ◽  
Confidence Level ◽  
Lupus Anticoagulant ◽  
Heparin Therapy ◽  
Factor Ix ◽  
New Method ◽  
Factor Viii Inhibitor ◽  
Single Factor ◽  
Viii Inhibitor

A method is presented using a new reagent containing propylgallate for the quantitative determina tion of lupus anticoagulant. The amount of an optimized phospholipid standard required by the clotting reaction was found to be 32-50 μg/ml at a 95% confidence level, with a mean of 41 μg/ml. This method eliminates the ef fect of heparin therapy, coumadin therapy, factor-VIII inhibitor, factor-IX inhibitor, and single-factor deficien cies that afflict presently used lupus anticoagulant screen ing and confirmatory procedures. Using this method, it should be possible to detect lupus anticoagulant in pa tients at a much lower level and follow the effect of ther apy on lupus anticoagulant.

Clinical Profile of Haemophilia in a Tertiary Care Hospital in Pune, Maharashtra, India

2021 ◽  
Vol 8 (15) ◽  
pp. 968-971
Author(s):  
Sadiq Yunus Mulla ◽  
Sachin Sitaram Pandit ◽  
Sachin Kisan Shivnitwar
Keyword(s):  
Factor Viii ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Factor Ix ◽  
Clinical Profile ◽  
Factor Viii Inhibitor ◽  
Haemophilia A ◽  
Care Hospital ◽  
Factor Viii Activity ◽  
Viii Inhibitor

BACKGROUND Haemophilia’s are X-linked hereditary blood clotting disorders due to deficiency of factor VIII (haemophilia A) or factor IX (haemophilia B) & also has identical clinical manifestations, screening tests abnormalities and sex-linked genetic transmission. Haemophilia’s result from defects in the factor VIII / IX gene that lead to decreased amount of factor VIII / IX protein, the presence of a functionally abnormal protein, or combination of both. Haemophilia A is a classic example of an X-linked recessive trait. The severity of their bleeding depends on their factor VIII activity level; and, rarely, a woman can have very low factor VIII activity, and present with symptoms of moderate or even severe haemophilia. We wanted to study the clinical profile of patients of haemophilia admitted in a tertiary care hospital. METHODS This is a cross-sectional study enrolling 60 known cases of haemophilia A & B admitted in wards & ICU / attending OPD of a tertiary care hospital. History was obtained in detail & thorough clinical examination was carried out. Precipitating factors for bleeding (spontaneous / minor trauma / major trauma / surgical operation / dental procedure / others), family h / o bleeding were studied in detail. RESULTS Of the total 60 cases of haemophilia, majority (49) of cases were of haemophilia A and 11 cases were of haemophilia B. In the study, majority (28.33 %) of cases belonged to 12 - 20 years age group and the most common presentation was haemarthrosis (61.67 %). 6 patients had factor VIII inhibitor antibodies and all of them were of haemophilia A. CONCLUSIONS Haemarthrosis is the most common clinical presentation of haemophilia and most common cause for haemarthrosis is spontaneous bleeding. Most common joint involved in bleeding was knee joint (target joint). Presence of factor VIII inhibitor antibodies specially in haemophilia A patients is not uncommon. KEYWORDS Haemophilia, Factor VIII, Factor IX

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 Factors Affecting the Factor X Activator Activity of Human Platelets

1977 ◽  
Author(s):  
J. Vermylen ◽  
N. Semeraro
Keyword(s):  
Factor Viii ◽  
Platelet Rich Plasma ◽  
Human Platelets ◽  
Activate Factor ◽  
Factor Viii Inhibitor ◽  
Factor X ◽  
Factors Affecting ◽  
Coagulant Activity ◽  
Viii Inhibitor

Several recent studies have indicated that patients with a thrombotic tendency have enhanced platelet coagulant activity. It therefore is of importance to attempt to identify factors which modify platelet coagulant activities. Recent work in our laboratory has provided evidence that human platelets possess the capacity to directly activate factor X.Adenosine-5'-diphosphate, collagen, acetylsalicylic acid and prostaglandin E1 do not modify this activity. All endotoxins studied however clearly enhanced this activity.Furthermore, infusion of ‘activated’ prothrombin concentrates in haemophiliacs with or without factor VIII inhibitor enhanced the activity of this platelet activator of factor X. The hypothesis has been put forward that this may be the mechanism through which ‘activated’ prothrombin concentrates ‘bypass’ factor VIII of IX inhibitors. Platelet isolated from platelet-rich plasma to which the ‘activated’ prothrombin concentrate had been added at a concentration approaching the maximal concentration achieved following in vivo infusion, also showed an increase in platelet coagulant activity. Work is in progress to identify the component in ‘activated’ prothrombin concentrates which enhances platelet coagulant activity.

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.

scholarly journals Characterization of Factor VIII-Inhibitor By-Passing Activity (FEIBA)

1977 ◽  
Author(s):  
K. Hess ◽  
N. Shih ◽  
G. Tishkoff
Keyword(s):  
Factor Viii ◽  
Factor Xa ◽  
Factor Ix ◽  
Coagulation Cascade ◽  
Factor Viii Inhibitor ◽  
Factor X ◽  
Clotting Factors ◽  
Human Factor Ix ◽  
Viii Inhibitor

In an attempt to identify the thrombogenic factor in human factor IX concentrates, we have studied the role of trace quantities of activated clotting factors employing an assay that compares the Factor VIII-like activity of IX concentrates with the ability of these products to restore to normal the abnormal activated partial thromboplastin time (APTT) of Factor VIII inhibitor plasma after 1 minute and 40 minute incubation. A coagulant activity (FEIBA) was evident when partially purified Factors X and II were combined in vitro. Factor Xa (4 × 10-4 u) plus Factor II gave negative results. Factor IIa (5.5 × 10-2u), when combined with Factor X, generated FEIBA. Activated clotting factors (Xa, IIa) when tested alone, at comparable levels, were devoid of FEIBA. Our results suggest a mechanism, distinct from activated clotting factors, that can effectively by-pass the Factor VIII defect in the coagulation cascade. The proposed mechanism appears to also by-pass the normal inhibitory properties (i.e., antithrombin III) of human blood.

ACQUIRED HAEMOPHILIA DUE TO FACTOR VIII INHIBITOR WITH SEVERE HAEMORRHAGES IN A 46-YEAR-OLD WOMAN SUCCESSFULLY TREATED WITH CYCLOSPORIN A

1987 ◽  
Author(s):  
Z Boda ◽  
J Hársfalvi ◽  
K Pecze ◽  
K Rak
Keyword(s):  
Factor Viii ◽  
Cyclosporin A ◽  
Factor Viii Inhibitor ◽  
Acquired Haemophilia ◽  
Coagulant Activity ◽  
Recovery Treatment ◽  
History Of ◽  
Viii Inhibitor ◽  
Mucosal Bleeding ◽  
Neurological State

A formerly healthy 46-year-old woman suffering from acquired haemophilia caused by factor VIII antibodies was admitted in an unconscious state following subarachnoid haemorrhage. Treatment with prothrombin complex concentrates (taken as a whole 100 000 U of PCC, home made and 10 OOOUofFEIBA, Immuno) , steroid (Prednison 50 mg/day) and cyclophosphamide (100 mg/day) was only partially successful: neurological state improved but the haemorrhagic tendency remained. Significant haematuria, and skin and mucosal bleeding characterized her clinical picture. In the meantime, signs of non-A non-B hepatitis were observed. After recovery treatment with Cyclosporin A (Sandimmun, Sandoz) was started (250 mg/day per os) together with small dose of Prednison (15 mg/day). No PCC was applied since that time and the partial thromboplastin times (PTT) became gradually shorter. Level of factor VIII inhibitor was 160 Bethesda unit prior and 9 unit after treatment, the duration of that was 60 days till now. Factor VIII coagulant activity (VIIIC) increased from value of less than 1 percent to 13.7 percent.Treatment of acquired haemophilia caused by factor VIII antibodies, particularly in cases with central nervous system bleeding, may be very difficult. History of our patient may indicate that patients resistent to substitution therapy, steroid and cytostatics may response well to Cyclosporin A. Therefore, its use is recommended.

At 90 Micrograms Per Kilogram, Recombinant Factor VIIa Partially Corrects Abnormal Hemostatic Function in Blood from Factor IX Deficient Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1044-1044
Author(s):  
Marcus E. Carr ◽  
Erika J. Martin ◽  
Janice G. Kuhn ◽  
Melinda Nolte
Keyword(s):  
Factor Viii ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Factor Ix ◽  
Recommended Dose ◽  
Factor Viii Inhibitor ◽  
Viii Inhibitor ◽  
Baseline Values ◽  
Factor Ix Deficiency ◽  
Dose Dependent

Abstract Reports of the potential clinical utility of recombinant Factor VIIa (rFVIIa, NovoSeven®, NovoNordisk) in a variety of bleeding disorders have raised the possibility that this agent may have broad spectrum hemostatic properties. We have previously demonstrated that rFVIIa produces dose dependent correction of hemostatic status in patients with Factor VIII deficiency and/or Factor VIII inhibitor. In this study we measured the dose dependent effects of rFVIIa on Platelet Contractile Force (PCF), Clot Elastic Modulus (CEM) and Thrombin Generation Time (TGT) (Hemodyne® Analyzer, Hemodyne, Inc.) in patients with factor IX deficiency. Results were compared to those seen with recombinant factor IX (BeneFIX® [GI, Wyeth]) and factor nine concentrate (Mononine® [Aventis-Behring]). Blood from three patients with factor IX deficiency was collected via aseptic venipuncture into evacuated tubes containing 3.2% sodium citrate. The samples were spiked with increasing amounts of each hemostatic agent so as to yield levels ranging from 25 to 200% of the recommended dose. At baseline, each of the factor IX deficient patients had prolonged TGT, decreased PCF and decreased CEM. Despite the fact that each patient had less than 1% of normal factor IX activity, there was significant variability between the patients in their baseline values. TGT for the three patients varied from 587 to 1200 seconds. Baseline PCF ranged from 0.9 to 1.4 Kdynes, while CEM varied from 1.6 to 5.4 Kdynes/cm2. Normal TGT, PCF and CEM values for asymptomatic controls (mean ± SD, n=25) were 392±100 seconds, 7.8±1.3 Kdynes and 18.8±5.6 Kdynes/cm2 respectively. At the 100% of recommended dose, each of the factor IX agents produced shortening of the TGT, and increases in PCF and CEM. The degree of normalization of these parameters did not appear to depend on the baseline values. The patient with the worst baseline parameters completely normalized his values at 100% doses of BeneFIX® and Mononine®. The patient with the best baseline values also normalized his parameters with BeneFIX® but not with Mononine®. The patient with intermediate baseline abnormalities improved all parameters with both factor IX products but appeared to respond better to BeneFIX® at the 100% dose level. The response to NovoSeven®, at 100% of the dose recommended for treatment of factor VIII inhibitor patients, was detectable but clearly inferior to the response to the factor IX agents. These results indicate significant variability in hemostatic status between factor IX deficient patients both at baseline and in response to factor replacement. While rFVIIa has activity in these patients, the dose previously shown to correct TGT in factor VIII deficient patients may not be appropriate for factor IX deficient patients.

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