A specific and sensitive activated partial thromboplastin time (APTT)-based factor VIII inhibitor screening assay

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.

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

Case Reports in Hematology ◽

10.1155/2013/521785 ◽

2013 ◽

Vol 2013 ◽

pp. 1-3 ◽

Cited By ~ 2

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.

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Prothrombin-Complex Concentrates, Thromboses, and Factor VIII Inhibitors: Evidence for a Coagulant Formed by the Interaction of Factors X and II

10.1055/s-0039-1689419 ◽

1975 ◽

Cited By ~ 1

Author(s):

G. H. Tishkoff

Keyword(s):

Factor Viii ◽

Human Factor ◽

Factor Xa ◽

Activated Partial Thromboplastin Time ◽

Factor Viii Inhibitor ◽

Factor V ◽

Prothrombin Complex Concentrates ◽

Corrective Effect ◽

Viii Inhibitor

Kurcyznski and Penner have reported on the use of prothrombin concentrates in the management of bleeding in hemophilia patients with Factor VIII inhibitor. Several commercial concentrates showed marked ability to shorten the activated partial thromboplastin time (APTT) of Factor VIII inhibitor plasma after 40 min preincubation. Significantly, purified human Factor Xa and thrombin did not evidence corrective effect. Highly purified human Factors X and II, isolated by affinity chromatography from partially activated prothrombin complex, effectively corrected the APTT when combined, but were inactive when tested separately. Preliminary studies suggest that Factor V is essential. This study indicates that the thrombogenic properties of prothrombin concentrates in vivo may be due in part to a coagulant complex formed by the interaction of X, V, and a prothrombin intermediate.

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An 89-Year-Old Man with COVID-19-Associated Coagulopathy Presenting with a Prolonged Partial Thromboplastin Time, Lupus Anticoagulant, and a High Titer of Factor VIII Inhibitor

American Journal of Case Reports ◽

10.12659/ajcr.926728 ◽

2020 ◽

Vol 21 ◽

Author(s):

Sanaz Ghafouri ◽

Matthew Rettig ◽

Kanwarpal S. Kahlon

Keyword(s):

Factor Viii ◽

Partial Thromboplastin Time ◽

Lupus Anticoagulant ◽

High Titer ◽

Factor Viii Inhibitor ◽

Viii Inhibitor

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Acquired Haemophilia: Functional Study of Antibodies to Factor VIII

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650189 ◽

1981 ◽

Vol 45 (03) ◽

pp. 285-289 ◽

Cited By ~ 14

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.

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A Higher than Expected Incidence of Factor VIII Inhibitors in Multitransfused Haemophilia A Patients Treated with an Intermediate Purity Pasteurized Factor VIII Concentrate

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651565 ◽

1993 ◽

Vol 69 (02) ◽

pp. 115-118 ◽

Cited By ~ 131

Author(s):

Kathelijne Peerlinck ◽

Jef Arnout ◽

Jean Guy Gilles ◽

Jean-Marie Saint-Remy ◽

Jos Vermylen

Keyword(s):

Factor Viii ◽

Randomized Trials ◽

Specific Factor ◽

Factor Viii Inhibitor ◽

Haemophilia A ◽

Viral Inactivation ◽

Gradual Decline ◽

Inhibitor Level ◽

Factor Viii Concentrates ◽

Viii Inhibitor

SummaryIn May 1990, 218 patients with haemophilia A regularly attending the Leuven Haemophilia Center were randomly assigned to a group receiving either of two newly introduced factor VIII concentrates: factor VIII-P, an intermediate purity pasteurized concentrate, or factor VIII-SD, a high purity concentrate treated with solvent-detergent for viral inactivation.Patients were followed from May 1990 until October 1991. Between August 1991 and October 1991 a clinically important factor VIII inhibitor was detected in five out of the 109 patients receiving factor VIII-P while none of the 109 patients receiving factor VIII-SD developed such antibodies. All patients acquiring an inhibitor had previously been clinically tolerant to transfused factor VIII with 200 to more than 1,000 days of exposure to factor VIII prior to May 1990. Patients with inhibitors were transfused daily with 30 U factor VIII-SD per kg body weight, which was associated with a gradual decline of the inhibitor level. In all patients the antibodies were relatively slow-acting and predominantly directed towards the light chain of factor VIII.This study demonstrates a higher than expected incidence of factor VIII inhibitors associated with the use of a specific factor VIII concentrate in multitransfused haemophilia A patients. It indicates the usefulness of evaluating newly introduced concentrates in prospective, randomized trials.

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Pemphigus Vulgaris Associated with Acquired Hemophilia due to Factor VIII Inhibitor

Nishi Nihon Hifuka ◽

10.2336/nishinihonhifu.65.223 ◽

2003 ◽

Vol 65 (3) ◽

pp. 223-226 ◽

Cited By ~ 2

Author(s):

Masahide YAMAGUCHI ◽

Mamoru KOHDA ◽

Hiroaki UEKI ◽

Wataru FUJIMOTO

Keyword(s):

Factor Viii ◽

Pemphigus Vulgaris ◽

Factor Viii Inhibitor ◽

Acquired Hemophilia ◽

Viii Inhibitor

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Factor-VIII Inhibitor in Less Severely Affected Haemophilic Patients

10.1055/s-0039-1689668 ◽

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.

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Eptacog-alfa/factor-VIII-inhibitor-bypassing-fraction

Reactions Weekly ◽

10.1007/s40278-021-98750-8 ◽

2021 ◽

Vol 1863 (1) ◽

pp. 146-146

Keyword(s):

Factor Viii ◽

Factor Viii Inhibitor ◽

Viii Inhibitor

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A Clinical and Experimental Study of Acquired Inhibitors to Factor VIII

Blood ◽

10.1182/blood.v26.6.805.805 ◽

1965 ◽

Vol 26 (6) ◽

pp. 805-818 ◽

Cited By ~ 33

Author(s):

HAROLD R. ROBERTS ◽

MARGARET B. SCALES ◽

JOHN T. MADISON ◽

WILLIAM P. WEBSTER ◽

GEORGE D. PENICK

Keyword(s):

Experimental Study ◽

Factor Viii ◽

Mode Of Action ◽

Exchange Transfusion ◽

Hemophilia A ◽

Retroperitoneal Hematoma ◽

Factor Viii Inhibitor ◽

Viii Inhibitor ◽

Potent Factor

Abstract Factor VIII inhibitors which developed in four patients with hemophilia A are described. These inhibitors are apparently specific for Factor VIII and are capable of inducing a transient hemophilic state when injected into dogs. The genesis, properties, and mode of action of these inhibitors can be explained on an immunologic basis and it seems most likely that they represent an antibody to Factor VIII. One hemophilia A patient, with retroperitoneal hematoma and a potent Factor VIII inhibitor, was successfully treated by an exchange transfusion followed by administration of purified porcine Factor VIII.

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