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.

scholarly journals An Unusual Etiology for Elevation of Activated Partial Thromboplastin Time (aPTT) in SLE: Acquired Hemophilia and Lupus Anticoagulant

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Srikanth Seethala ◽  
Nathaniel P. Collins ◽  
George Comerci
Keyword(s):  
Factor Viii ◽  
Partial Thromboplastin Time ◽  
Lupus Anticoagulant ◽  
Activated Partial Thromboplastin Time ◽  
Factor Viii Inhibitor ◽  
Activity Levels ◽  
First Line ◽  
Acquired Hemophilia ◽  
Viii Inhibitor ◽  
Work Up

A 60-year-old female who has a history significant for diabetes, depression, and rheumatoid arthritis presented with a progressively enlarging hematoma of the left upper extremity. She was found to have an enlarging hematoma and an isolated elevation of activated partial thromboplastin time (aPTT). Lab work-up revealed low factor VIII activity levels and inhibitor titers at 13.38 Bethesda units (BU). Dilute Russell’s viper venom time (dRVVT) revealed a lupus anticoagulant. Hemostasis was achieved with factor VIII inhibitor bypassing activity (FEIBA) and inhibitor eradication with-rituxan after the failure of first-line treatment with cyclophosphamide and prednisone.

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: Functional Study of Antibodies to Factor VIII

1981 ◽  
Vol 45 (03) ◽  
pp. 285-289 ◽  
Author(s):  
J P Allain ◽  
A Gaillandre ◽  
D Frommel
Keyword(s):  
Factor Viii ◽  
Functional Study ◽  
Factor Viii Inhibitor ◽  
Acquired Haemophilia ◽  
Viii Inhibitor ◽  
Kinetics Of ◽  
Antibody Function ◽  
Native Plasma

SummaryFactor VIII complex and its interaction with antibodies to factor VIII have been studied in 17 non-haemophilic patients with factor VIII inhibitor. Low VIII:C and high VIIIR.Ag levels were found in all patients. VIII:WF levels were 50% of those of VTIIRrAg, possibly related to an increase of poorly aggregated and electrophoretically fast moving VIIIR:Ag oligomers.Antibody function has been characterized by kinetics of VIII :C inactivation, saturability by normal plasma and the slope of the affinity curve. Two major patterns were observed:1) Antibodies from 6 patients behaved similarly to those from haemophiliacs by showing second order inhibition kinetics, easy saturability and steep affinity slope (> 1).2) Antibodies from other patients, usually with lower titres, inactivated VIII :C according to complex order kinetics, were not saturable, and had a less steep affinity slope (< 0.7). In native plasma, or after mixing with factor VIII concentrate, antibodies of the second group did not form immune complexes with the whole factor VIII molecular complex. However, dissociation procedures did release some antibodies from apparently low molecular weight complexes formed in vivo or in vitro. For appropriate management of non-haemophilic patients with factor VIII inhibitor, it is important to determine the functional properties of their antibodies to factor VIII.

Factor-VIII Inhibitor in Less Severely Affected Haemophilic Patients

1975 ◽  
Author(s):  
E. G. D. Tuddenham ◽  
A. L. Bloom ◽  
J. C. Giddings ◽  
C. A. Barrett
Keyword(s):  
Factor Viii ◽  
Factor Viii Inhibitor ◽  
Factor Viii Level ◽  
Replacement Treatment ◽  
Viii Level ◽  
Viii Inhibitor ◽  
In Vivo Recovery ◽  
Better Than

The occurrence of factor VIII inhibitor in five mild or moderately affected liaemophilic patients is described. In four patients the inhibitor inactivated endogenous factor VIII an dtemporarily converted them to severely affected haemophiliacs with factor VIII level of 0%. In the fifth patient, a brother of one of the others, the inhibitor although more potent did not inactivate the patient’s own factor VIII and did not completely inactivate normal factor VIII in vitro. This patient responded to treatment with factor-VIII concentrate but the in-vivo recovery was reduced. The patient’s plasma was tested against a panel of normal donors but it inactivated factor VIII in each to a similar extent and no evidence for normal factor-VIII groups was obtained. In the other patients the response to replacement treatment was also better than that usually seen in severely affected haemophilic patients with inhibitor. In the two related patients the inhibitors have so far persisted but in the unrelated patients the inhibitors eventually disappeared and did not always recur with subsequent therapy. The incidence of factor- VIII inhibitor in less severe haemophiliacs (factor VIII > 3% ) in this centre is 6% suggesting that the complication is more frequent in this type of patient than hitherto recognised.

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

A Non-Stasis Rabbit Model for the Detection of Factor IX Concentrate Thrombogenicity.

1979 ◽  
Author(s):  
C.V. Prowse ◽  
A.R. Williams
Keyword(s):  
Platelet Count ◽  
Factor Viii ◽  
Partial Thromboplastin Time ◽  
Rabbit Model ◽  
Factor Ix ◽  
In Vitro Activity ◽  
Blood Samples ◽  
Intravascular Coagulation

A method has been developed whereby aerial blood samples can be obtained from a rabbit over a period of four hours following infusion of potentially thrombogenic solutions. Infusion of 50 uAg thrombin over JO minutes produced intravascular coagulation for up to three hours after infusion as demonstrated by a decrease in factor VIII, increase in partial thromboplastin time and fibrin(ogen) degradation producta and a positive ethanol gelation teat. No change in fibrinogen, factor DC or platelet count was found. Saline infusion produced no change in any of these parameters.Infusion of a variety of factor IX concentrates at 100 u/kg shewed that those concentrates active in in vitro thrombogenicity teste produced a similar effect to thrombin in vivo and in addition may result in a drop in platelet count. Infesion of concentrates with low in vitro activity did not induce intravascular coagulation.

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 Feiba Immuno: A Preparation with Factor Eight Inhibitor Bypassing Activity

1977 ◽  
Author(s):  
F. Elsinger
Keyword(s):  
Factor Viii ◽  
Factor Xa ◽  
Coagulation Factors ◽  
Active Principle ◽  
Factor Viii Inhibitor ◽  
Factor V ◽  
In Vitro Experiments ◽  
Factor X ◽  
Viii Inhibitor

FEIBA IMMUNO is a preparation in which a new activity is generated capable of bypassing factor VIII. The preparation which is used to treat patients with inhibitors (especially inhibitors to factor VIII) is standardized in FEIBA units, i.e. in terms of its in vitro capacity to shorten the activated PTT of a factor VIII inhibitor plasma.It could be concluded from different in vitro experiments that none of the classic’ activated coagulation factors is responsible for the factor VIII bypassing reaction; FEIB-activity seems to be correlated to a new complex of coagulation factors.To get an answer to the question which coagulation factors are essential for FEIB-activity, we tried to generate this activity from different deficient plasmas; from these experiments the following conclusions could be drawn:, the presence of at least factors VII, IX, and X is essential for the generation of the molecular species responsible for factor VIII as well as factor X bypassing activity, but factor V is not bypassed. This activity is not factor Xa itself. Factors VIII and V are not necessary for the generation of this active principle, but factor V is finally needed for its bypassing action.

Sign in / Sign up

Export Citation Format

Share Document