Adrenal Infarction in Pregnancy Secondary to Elevated Plasma Factor VIII Activity

Further Experience on the Effect of High Pre-Donation Factor VIII Levels in Blood Donors on the Factor VIII Content of Small-Pool Fractions

10.1055/s-0039-1682568 ◽

1977 ◽

Author(s):

H. Beeser ◽

H. Eqli

Keyword(s):

Factor Viii ◽

High Plasma ◽

Activity Levels ◽

Factor Viii Activity ◽

Factor Viii Level ◽

Plasma Factor ◽

Viii Level ◽

Factor Viii Concentrates ◽

Small Pool ◽

Concentrate Preparation

Because of the well known wide normal range of the factor VIII activity between 60 to 170% I man, selecting of donors with high activity levels would be of advantaae for the preparation of factor VIII concentrates. This is especially true for preparing small-pool fractions, as for technical reasons the final product cannot be controlled for its factor VIII content. In preliminary investigations, we reported on elsewhere, high factor VIII activity in donors estimated before a donation had been rarely reproducible before a second donation after 8-12 weeks. So as a preliminary result of finding a donor’s factor VIII level varying from donation to donation selecting of plasmas with high factor VIII content for concentrate preparation could only be establishedby re-estimating the activity before each donation. Proceeding in this way would be much too troublesome. To get more reliable information whether a healthy subject’s high factor VIII plasma level is distinctly varying or rather constant we assayed the plasma of 200 donors with factor VIII activity > 120% two times more before donation. The results confirmed our preliminary findings, especially the fact that a high plasma factor VIII activity in experienced donors was rarely reproducible when re-estimated before a second and third donation. As a consequence selecting of donors with high factor VIII procoaqulant activity for preparing small-pool factor VIII concentrates is impracticable.

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Presence Of Receptor For Activated Factor VIII On The Surface Of Released Platelets

10.1055/s-0038-1652900 ◽

1981 ◽

Author(s):

K Brodén ◽

L-O Andersson

Keyword(s):

Factor Viii ◽

Von Willebrand Factor ◽

Factor X ◽

Factor Viii Activity ◽

Platelet Receptor ◽

Plasma Factor ◽

Centrifuge Tube ◽

Dilute Suspension ◽

Von Willebrand ◽

Willebrand Factor

In normal plasma Factor VIII activity is associated with a series of high molecular weight glycoprotein complexes also containing von Willebrand Factor related activities. To study the possible binding of various forms of Factor VIII to released platelets, a solution containing Factor VIII was mixed with a dilute suspension of platelets, which were released by addition of collagen. After 10 minutes of incubation the mixture was layered over 1.5 ml of 30% human serum albumin solution in a centrifuge tube and subjected to centrifugation at 7,000xg. Fractions were collected and analyzed for Factor VIII activity and phospholipid-related procoagulant activity. When purified Factor VUI/von Willebrand Factor complex was studied no significant association between the Factor VIII activity and the platelets were found. When purified Factor VUI/von Willebrand Factor complex was activated with 10-3 units/ml of thrombin and then tested, the main part of the Factor VIII activity became associated with the platelets. Even at very low platelet counts this binding was clearly detectable. The binding occurred both in the presence and in the absence of Ca2+. Thus released platelets bind thrombin-activated Factor VIII but not the Factor VUI/von Willebrand Factor complex. It is known that activation of Factor VIII by thrombin causes dissociation of the Factor VIII from the von Willebrand Factor part of the complex. The data obtained indicate that this dissociation is necessary in order to get the Factor VIII to bind to the platelet receptor. It may work as an amplification mechanism where the first traces of Thrombin formed upon initiation of coagulation dissociates Factor VIII from von Willebrand Factor, followed by binding to receptor on released platelets and formation of Factor X activator complex on the surface of the platelets.

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An Improved Method of Making Factor VIII Concentrates

10.1055/s-0039-1684434 ◽

1979 ◽

Author(s):

G. Rock ◽

D.S. Palmer ◽

E.S. Tackaberry ◽

M. Wickerhauser

Keyword(s):

Factor Viii ◽

Present Method ◽

Batch Preparation ◽

Improved Method ◽

Factor Viii Activity ◽

Peg 4000 ◽

Plasma Factor ◽

Factor Viii Concentrates ◽

The Cost ◽

Plasma Activity

The yields from batch preparation of Factor VIII concentrates can be substantially improved by collecting the blood into heparin rather than into CPD as anticoagulant. The resultant cryoprecipitate contains 78 ± 9% of the original plasma activity if 20 mls of supernatant per litre of starting plasma are left with the cryoprecipitate to maintain heparin levels. This cryoprecipitate was further purified by solubilization at 37°C for 5 minutes using 40 cc of saline per litre of starting plasma. This preparation was adjusted to pH 6.3 and 4.5% PEG 4000. Then, after removal of the precipitate by centrifugaron, the 4.5% PEG supernatant is adjusted to pH 6.0 and 11% PEG. The 11% PEG precipitate obtained after centrifugation is resolubilized in 1/100th the original plasma volume with buffer (0.1 M glycine, 20 mM citrate, 0.15 H saline) containing 1 unit of heparin per ml. Experiments using plasma pools containing 1-15 donor units gave yields ranging from 390-490 plasma Factor VIII equivalents per litre of the starting plasma. The final product retains an average of 90% of the initial Factor VIII activity after 24 hours at 22°C. It is believed that the present method could substantially reduce the cost of producing Factor VIII concentrates.

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Correction of the coagulation defect in hemophilia A mice through factor VIII expression in skin

Blood ◽

10.1182/blood.v95.9.2799.009k23_2799_2805 ◽

2000 ◽

Vol 95 (9) ◽

pp. 2799-2805 ◽

Cited By ~ 42

Author(s):

Steven S. Fakharzadeh ◽

Yue Zhang ◽

Rita Sarkar ◽

Haig H. Kazazian

Keyword(s):

Transgenic Mice ◽

Factor Viii ◽

Hemophilia A ◽

Systemic Disease ◽

Factor Viii Activity ◽

Human Factor Viii ◽

Plasma Factor ◽

Transgenic Lines ◽

Rag 1 ◽

Involucrin Promoter

To test the hypothesis that factor VIII expressed in the epidermis can correct hemophilia A, we generated transgenic mice in a factor VIII–deficient background that express human factor VIII under control of the involucrin promoter. Mice from 5 transgenic lines had both phenotypic correction and plasma factor VIII activity. In addition to the skin, however, some factor VIII expression was detected in other tissues that have stratified squamous epithelia. To determine whether an exclusively cutaneous source of factor VIII could correct factor VIII deficiency, we grafted skin explants from transgenic mice onto mice that are double knockouts for the factor VIII and RAG-1 genes. Two graft recipients had plasma factor VIII activity of 4% to 20% of normal and improved whole blood clotting compared with factor VIII–deficient mice. Thus, expression of factor VIII from the epidermis can correct hemophilia A mice, thereby supporting the feasibility of cutaneous gene therapy for systemic disease.

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Thrombotic stroke associated with elevated plasma factor VIII

Annals of Neurology ◽

10.1002/ana.410080416 ◽

1980 ◽

Vol 8 (4) ◽

pp. 435-437 ◽

Cited By ~ 17

Author(s):

Kenneth S. Kosik ◽

Bruce Furie

Keyword(s):

Factor Viii ◽

Elevated Plasma ◽

Plasma Factor

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Rabbit Antibodies Against the Procoagulant Activity (VIII:C) of Human Factor VIII

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653456 ◽

1981 ◽

Vol 46 (04) ◽

pp. 699-705 ◽

Cited By ~ 1

Author(s):

T H Tran ◽

G A Marbet ◽

F Duckert

Keyword(s):

Factor Viii ◽

Human Factor ◽

Gel Filtration ◽

Procoagulant Activity ◽

Solid Matrix ◽

Factor Viii Activity ◽

Physiological Conditions ◽

Human Factor Viii ◽

Plasma Factor ◽

Factor Viii Antigen

SummaryThe procoagulant activity VIII:C was separated from factor VIII antigen (VIIIR:Ag) by gel filtration in the presence of 0.25 mol/l calcium chloride. Antibodies (anti-VIII:C) were obtained by immunization of rabbits with VIII:C. The last step of the purification procedure of antibodies consists of an adsorption on VIIIR:Ag-Sepharose 2 BCL as immunoadsorbent to remove contaminating traces of antibodies against VIIIR:Ag. The anti- VIII:C titer remains unchanged during this adsorption (29 Bethesda units per mg). In solution, anti-VIII:C neutralies factor VIII activity (in plasma, cryoprecipitate or in purified form) and the fragment VIII:C without reacting with VIIIR:Ag. Once immobilized on a solid matrix, i.e.2% agarose, it loses over 95% of its inhibitory capacity. The immobilized anti-VIIIR:Ag binds stoichiometrically the antigen and the activity of plasma factor VIII. These results together suggest that factor VIII is composed of 2 different entities, but undissociated under physiological conditions. Immunophysical analyses as a function of pH and temperature of anti-VIII:C and its complex with factor VIII show properties similar to those of homologous antibodies. The antigen determinants of VIII:C (VIII:CAg) are destroyed at low pHs or high temperatures, and VIII:C can no more form a complex with anti-VIII:C. Purified anti-VIII:C is also used in a two-stage assay to detect VIII:CAg or cross-reacting material in some severe haemophiliacs.

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Elevated Plasma Factor VIII and d-Dimer Levels as Predictors of Poor Outcomes of Thrombosis in Children

Yearbook of Vascular Surgery ◽

10.1016/s0749-4041(08)70298-7 ◽

2006 ◽

Vol 2006 ◽

pp. 385-386

Author(s):

G.L. Moneta

Keyword(s):

Factor Viii ◽

Elevated Plasma ◽

Plasma Factor ◽

Poor Outcomes ◽

D Dimer

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Factor VIII expression in liver disease

Thrombosis and Haemostasis ◽

10.1160/th03-05-0310 ◽

2004 ◽

Vol 91 (02) ◽

pp. 267-275 ◽

Cited By ~ 120

Author(s):

Martine Hollestelle ◽

Hendrika Geertzen ◽

Irene Straatsburg ◽

Thomas van Gulik ◽

Jan van Mourik

Keyword(s):

Liver Cirrhosis ◽

Liver Disease ◽

Factor Viii ◽

Rna Extraction ◽

Control Group ◽

Mrna Levels ◽

Protein Distribution ◽

Elevated Plasma ◽

Cirrhotic Tissue ◽

Plasma Factor

SummaryLiver disease is associated with markedly elevated plasma factor VIII (FVIII) levels, whereas the synthesis of many other coagulation factors and proteins is reduced. In order to define the mechanism of FVIII increase, we have determined the expression levels of FVIII, both at mRNA and protein level, in patients with liver disease who underwent partial liver resection. In addition, the expression of von Willebrand factor (VWF) and low density lipoprotein receptor-related protein (LRP), proteins known for their ability to modulate FVIII plasma levels, were examined. Tissue samples for RNA extraction were obtained from 4 patients with cirrhosis, 9 patients with liver failure without cirrhosis and 6 patients with liver metastasis of a colon or rectum carcinoma (control group). In patients with liver cirrhosis hepatic FVIII and LRP mRNA levels were significantly lower than controls (p ≤ 0.010), while VWF mRNA was significantly higher (p ≤ 0.050). Immunohistochemical analysis revealed that cellular VWF protein distribution was also increased in cirrhotic livers compared to liver tissue from patients with non-cirrhotic liver disease. In cirrhotic tissue enlarged portal veins appeared to overgrow FVIII producing sinusoidal endothelial cells. Similarly, the number of LRP-producing cells appeared to be lower in cirrhotic tissue than in controls. The plasma concentration of both FVIII and VWF was significantly higher in patients with cirrhosis than control subjects (p = 0.038 and 0.010 respectively). These results demonstrate that elevated plasma FVIII levels in liver cirrhosis are associated with increased hepatic biosynthesis of VWF and decreased expression of LRP, rather than increased FVIII synthesis.

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Suppression of an Antibody to Factor VIII by a Combination of Factor VIII and Cyclophosphamide

Blood ◽

10.1182/blood.v37.4.381.381 ◽

1971 ◽

Vol 37 (4) ◽

pp. 381-387 ◽

Cited By ~ 65

Author(s):

DAVID GREEN

Keyword(s):

Factor Viii ◽

Vaginal Bleeding ◽

Blood Clotting ◽

Intravenous Dose ◽

Clotting Time ◽

Factor Viii Activity ◽

Plasma Factor ◽

History Of ◽

Blood Clotting Time

Abstract A 54-year-old woman with a 20-year history of generalized, severe psoriasis presented with diffuse ecchymoses, melena, and vaginal bleeding. The whole blood clotting time was 59 minutes and the plasma factor VIII concentration was less than 1 per cent of normal. Incubation of the patient’s plasma with cryoprecipitate containing one unit of factor VIII resulted in the rapid disappearance of factor VIII activity from the mixture. The major antifactor VIII activity of the patient’s plasma was associated with an immunoglobulin of the IgG class. The patient was initially treated with a combination of methotrexate, azathioprine, and cyclophosphamide. No improvement occurred, and after 6 weeks of therapy the drugs were discontinued. Eight months later, she presented with an expanding sublingual hematoma. Bleeding was controlled by the rapid administration of 10,000 units of factor VIII, and an intravenous dose of cyclophosphamide given concurrently resulted in a prompt decline in antibody titer. Factor VIII levels subsequently became normal and have remained normal during 7 months of follow-up observation.

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