Combined Factor VIII And Plasma Exchange Therapy In The Management Of Patients With Factor VIII Inhibitors

1981 ◽  
Author(s):  
R T Wensley ◽  
R F Stevens ◽  
A M Burn
Keyword(s):  
Factor Viii ◽  
Clinical Response ◽  
Plasma Exchange ◽  
Anticoagulant Activity ◽  
Response To Therapy ◽  
Response To Treatment ◽  
High Dose ◽  
Haemophilia A ◽  
Human Factor Viii ◽  
Plasma Factor

Five patients with Haemophilia A and Factor VIII inhibitors and three patients with spontaneous Factor VIII inhibitors presented with severe or life-threatening haemorrhage. All, except one, received intermittent high dose human Factor VIII therapy combined with one or more plasma exchanges. The exception was a patient with spontaneous Factor VIII inhibitors who was plasma-exchanged without receiving Factor VIII. The five Haemophilia A patients showed a uniformly good clinical response to treatment with complete resolution of their bleeding episodes. Their inhibitors were reduced to a level approaching zero and adequate plasma Factor VIII levels were achieved. In contrast, the three patients with spontaneous Factor VIII inhibitors failed to show any clinical response to therapy. They had measurable plasma Factor VIII levels before the Factor VIII therapy, but the administered Factor VIII produced no additional increment. Their inhibitor levels were only minimally altered by therapy. Studies of the inhibitors from the haemophiliacs showed complete Factor VIII neutralisation in incubation mixtures, but inhibitor plasmas from the spontaneous cases failed to completely neutralise the admixed Factor VIII. It is postulated that in haemophiliacs with antibodies, replacement therapy is associated with the formation of stable imnune complexes which remain in the intravascular space and are removed at subsequent plasma exchange. These complexes do not show coagulant or anticoagulant activity. However, in non-haemophiliacs with acquired Factor VIII inhibitors, weaker association of Factor VIII and antibody in the immune complexes may account for the measurable plasma Factor VIII activity, and also enable the dissociated antibody to diffuse out of the intravascular space and hence be unavailable for removal by plasma exchange.

scholarly journals Plasma exchange and human factor VIII concentrate in managing haemophilia A with factor VIII inhibitors.

BMJ ◽  
1980 ◽  
Vol 281 (6252) ◽  
pp. 1388-1389 ◽  
Author(s):  
R T Wensley ◽  
R F Stevens ◽  
A M Burn ◽  
I W Delamore
Keyword(s):  
Factor Viii ◽  
Plasma Exchange ◽  
Human Factor ◽  
Haemophilia A ◽  
Human Factor Viii

Studies on the Characterization of Factor VIII and a Co-factor VIII

1974 ◽  
Vol 31 (02) ◽  
pp. 328-338
Author(s):  
M. M. P Paulssen ◽  
H. L. M. A Vandenbussche-Scheffers ◽  
P. B Spaan ◽  
T de Jong ◽  
M. C Planje
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
The Body ◽  
Haemophilia A ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Polysaccharide Content ◽  
Plasma Factor ◽  
Two Factors

SummaryFactor VIII occurs in the body in two different forms. In lymph factor VIII is bound to chylomicra. In plasma, factor VIII is bound to a protein.After delipidation of chylomicra we obtained a glycoprotein with a high polysaccharide content and a molecular weight of approx. 160,000.In plasma, factor VIII is attached to a protein which is present in normal concentrations in plasma of patients with haemophilia A and in serum (co-factor VIII).This factor is deficient in both the plasma and the serum of patients with von Willebrand’s disease.The binding between factor VIII and co-factor VIII is reversible.Some properties of these two factors are described.

The Fractionation Properties of Human Factor VIII (Antihaemophilic Factor)

1960 ◽  
Vol 04 (02) ◽  
pp. 253-260 ◽  
Author(s):  
Franco Gobbi
Keyword(s):  
Factor Viii ◽  
Human Factor ◽  
Maximum Yield ◽  
Factor Vii ◽  
Precipitation Method ◽  
Salting Out ◽  
Human Factor Viii ◽  
Plasma Factor ◽  
Two Factors ◽  
Thromboplastic Activity

SummaryThe fractionation properties of human Factor VIII (antihaemophilic factor, AHF, antihaemophilic globulin) have been studied using a plasma of congenital afibrinogenaemia as a starting material.From a fibrinogen-free plasma, Factor VIII does not precipitate with ethanol at a final concentration of 8%; on the contrary the maximum yield is reached at an ethanol concentration of 25%.With a precipitation method carried out by a one to ten dilution of plasma with distilled water and acidification by N/10 hydrochloric acid to a pFI 5.2, Factor VIII does not precipitate with the euglobulin fraction; when normal plasma is used, such a precipitation is almost complete.With the salting-out fractionation method by ammonium sulphate, Factor VIII precipitates at a concentration between 25 and 33% of saturation either from fibrinogen-free and from normal human plasma.A non-specific thromboplastic activity appears in the fractions prepared by every method. This activity, which is probably due to the activation of seric accelerators, is easily removed by Al(OH)s adsorption. Thus, in order to insure the specificity of Factor VIII assays, the preliminary adsorption of the fractions is indispensable before testing their antihaemophilic activity.Fibrinogen and Factor VIII have different and definite precipitation patterns. When these two factors are associated the fractionation properties of AHF appear quite modified, showing a close similarity to those of fibrinogen. This fact can explain the technical difficulties encountered in the attempt to purify the antihaemophilic factor, and the lack of reproducible procedures for removing fibrinogen without affecting Factor VII.

scholarly journals Factor VIII/von Willebrand factor in subendothelium mediates platelet adhesion

Blood ◽  
1985 ◽  
Vol 65 (4) ◽  
pp. 823-831 ◽  
Author(s):  
VT Turitto ◽  
HJ Weiss ◽  
TS Zimmerman ◽  
II Sussman
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Vessel Wall ◽  
Platelet Adhesion ◽  
Human Factor ◽  
Rabbit Aorta ◽  
Human Factor Viii ◽  
Plasma Factor ◽  
Von Willebrand ◽  
Willebrand Factor

The present studies were undertaken to determine whether factor VIII/von Willebrand factor (vWF) present in the vessel wall (in addition to that in plasma) may mediate the attachment of platelets to subendothelium. Subendothelium from everted rabbit aorta was exposed to human citrated blood flowing through an annular perfusion chamber at 40 mL/min (wall shear rate of 2,600 s-1 for five minutes). The vessel segments were incubated at 37 degrees C for one hour with various dilutions of either goat-anti-rabbit factor VIII/vWF serum or an IgG fraction prepared from the serum. Control segments were incubated with serum or IgG from a nonimmunized goat. Values of platelet contact (C), platelet adhesion (C + S), and thrombus formation (T) on the subendothelium were evaluated by a morphometric technique. Compared with vessels incubated with fractions prepared from a normal goat, a significant decrease in platelet adhesion (C + S), ranging from 45% to 65%, was observed on vessels incubated with various dilutions (1:5 to 1:50) of either serum or IgG fractions of goat-anti-rabbit factor VIII/vWF. A similar decrease in platelet adhesion was observed with vessels incubated with an F(ab')2 fragment against rabbit factor VIII/vWF prepared in the goat. When goat-anti-rabbit factor VIII/vWF IgG was added to rabbit blood (1:75 dilution), platelet adhesion was reduced to the same extent (65%) on normal rabbit vessels and on vessels pre-incubated with goat-anti-rabbit factor VIII/vWF. Immunofluorescence studies revealed the presence of rabbit factor VIII/vWF in the subendothelium of rabbit aorta and the continued binding of the goat-anti-factor VIII/vWF antibodies on subendothelium during the perfusion studies. No uptake of human factor VIII/vWF on the rabbit subendothelium was observed by this immunologic technique; human factor VIII/vWF was found to be entirely associated with the attached human platelets. Thus, factor VIII/vWF in the vessel wall may mediate platelet attachment to subendothelium in a manner similar to that of plasma factor VIII/vWF.

scholarly journals Sustained expression of therapeutic levels of human factor VIII in mice

Blood ◽  
1996 ◽  
Vol 87 (11) ◽  
pp. 4671-4677 ◽  
Author(s):  
S Connelly ◽  
JM Gardner ◽  
RM Lyons ◽  
A McClelland ◽  
M Kaleko
Keyword(s):  
Factor Viii ◽  
Adenoviral Vector ◽  
Human Factor ◽  
Hemophilia A ◽  
Coagulation Factor ◽  
High Dose ◽  
Specific Enzyme ◽  
Adult Mice ◽  
Human Factor Viii

Deficiency of coagulation factor VIII (FVIII) results in hemophilia A, a common hereditary bleeding disorder. Using a human FVIII-encoding adenoviral vector, Av1ALAPH81, we have demonstrated expression of therapeutic levels of human FVIII in mice sustained for more than 5 months after vector administration. Administration of a high dose (4 x 10(9) plaque-forming units [pfu]) of Av1ALAPH81 to mice resulted in a peak expression of 2,063 ng/mL of human FVIII in the mouse plasma, with levels decreasing to background by weeks 15 to 17. Normal FVIII levels in humans range from 100 to 200 ng/mL and therapeutic levels are as low as 10 ng/mL. Alternatively, administration of 8- to 80-fold lower vector doses (5 x 10(8) pfu to 5 x 10(7) pfu) to normal adult mice resulted in expression of FVIII at therapeutic levels sustained for at least 22 weeks. Detailed analysis of vector toxicity indicated that the high vector dose caused a dramatic elevation of liver-specific enzyme levels, whereas an eight-fold lower vector dose was significantly less hepatotoxic. The data presented here demonstrate that administration of lower, less toxic vector doses allow long-term persistence of FVIII expression.

scholarly journals Use of porcine factor VIII in the treatment of patients with acquired hemophilia

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1513-1520 ◽  
Author(s):  
AE Morrison ◽  
CA Ludlam ◽  
C Kessler
Keyword(s):  
Factor Viii ◽  
Acquired Hemophilia ◽  
First Line Therapy ◽  
Human Factor Viii ◽  
Plasma Factor ◽  
Inhibitor Level ◽  
Clinical Responses ◽  
Bleeding Episodes ◽  
Antibody Levels ◽  
Auto Antibody

Abstract Data have been collected from 47 centers in Europe and North America on the treatment with porcine factor VIII concentrate of 74 acute bleeding episodes in 65 patients with acquired hemophilia. The median initial anti-human factor VIII auto-antibody inhibitor level was 38 Bethesda unit (BU)/mL (range 1.2 to 1,024) whereas that against porcine was 1 BU/mL (range 0 to 15). The mean initial dose of porcine factor VIII infused was 84 IU/kg, which increased the plasma factor VIII:C activity by 0.85 IU/mL. Therapy was continued for a mean of 8.5 days during which time the average number of infusions was 11. Objective clinical responses were rated as good or excellent in 78% of recipients. Side effects were uncommon; only one patient experienced a severe anaphylactic reaction necessitating the discontinuation of porcine FVIII therapy. After therapy, no increase in the median level of anti- human FVIII or anti-porcine antibody was noted in the group as a whole, although 13 patients showed individual increases in either anti-human or anti-porcine antibody levels or both of more than 10 BU/mL. Of the 7 patients who subsequently rebled, 5 were successfully re-treated and 2 did not respond to further porcine factor VIII treatment. Porcine factor VIII is safe and clinically effective treatment for bleeding episodes associated with acquired hemophilia and should be considered as first-line therapy for patients whose acquired anti-factor VIII:C antibody cross-reacts with porcine factor VIII:C at low levels.

scholarly journals Plasmapheresis in neurological disorders: six years experience from University Clinical center Tuzla

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1234 ◽  
Author(s):  
Osman Sinanović ◽  
Sanela Zukić ◽  
Adnan Burina ◽  
Nermina Pirić ◽  
Renata Hodžić ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Clinical Response ◽  
Plasma Exchange ◽  
Neurological Diseases ◽  
Therapeutic Plasma Exchange ◽  
Motor Neuropathy ◽  
Extracorporeal Blood Purification ◽  
Clinical Center ◽  
Plasma Factor ◽  
Neurological Patients

Background: Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique that is designed to remove substances with a large molecular weight. The TPE procedure includes removal of antibodies, alloantibodies, immune complexes, monoclonal protein, toxins or cytokines, and involves the replenishment of a specific plasma factor. The aim of the study was to describe the clinical response to TPE in various neurological patients, and to assess the clinical response to this therapy. Methods: The study was retrospective. We analyzed the medical records of 77 patients who were treated at the Department of Neurology, University Clinical Center (UCC) Tuzla from 2011 to 2016.   Results: 83 therapeutic plasma exchanges were performed in the 77 patients. There was a slight predominance of male patients (54.5%), with an average age of 51±15.9 years. The most common underlying neurological diseases were Guillain–Barré syndrome (GBS) (37.7%), then chronic inflammatory demyelinating polyneuropathy (CIDP) (23.4%), multiple sclerosis (MS) (11.7%) and myasthenia gravis (10.4%). Less frequent neurological diseases that were encountered were paraneoplastic polyneuropathies (5.2%), neuromyelitis optica (also known as Devic’s disease) (3.9%), motor neuron disease (3.9%), polymyositis (2.6%) and multifocal motor neuropathy (1.2%). Conclusions: Six years experience of therapeutic plasma exchange in neurological patients in our department have shown that, following evidence-based guidelines for plasmapheresis, the procedure was most effective in patients with GBS, CIDP and myasthenia gravis.

Systemic Steroids Suppress Antimelanocyte Antibodies in Vitiligo

1997 ◽  
Vol 1 (4) ◽  
pp. 193-195 ◽  
Author(s):  
Seung-Kyung Hann ◽  
Dunlu Chen ◽  
Jean-Claude Bystryn
Keyword(s):  
Clinical Response ◽  
Steroid Treatment ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Systemic Steroid ◽  
Good Clinical Response ◽  
Systemic Steroid Therapy ◽  
Initiation Of Therapy ◽  
Antibody Levels

Background: Vitiligo is associated with autoantibodies to melanocytes. The role of these antibodies in the pathogenesis of the disease is still unknown. Objective: The purpose of this study was to examine the role of vitiligo antibodies in the pathogenesis of the disease by studying whether or not there is a correlation between changes in their level and response to therapy with systemic steroid. Methods: Antibodies to the 40 to 45 kD, 75 kD, and 90 kD vitiligo antigens were measured prior to and following systemic steroid therapy in 10 patients with active vitiligo. Results: Four months following initiation of therapy, seven (78%) of nine patients with good clinical response to steroid treatment had a significant decrease in the level of vitiligo antibodies. By contrast, one patient who had no response to treatment had a slight increase in antibody levels. Conclusion: These findings suggest that one mechanism by which corticosteroids can cause repigmentation in vitiligo is by decreasing the level of vitiligo antibodies, and support the notion that vitiligo antibodies are involved in the pathogenesis of this disease.

High-dose cytosine arabinoside: Clinical response to therapy in acute leukemia

1982 ◽  
Vol 10 (S1) ◽  
pp. 239-250 ◽  
Author(s):  
A. P. Early ◽  
H. D. Preisler ◽  
D. J. Higby ◽  
M. Brecher ◽  
G. Browman ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Clinical Response ◽  
Cytosine Arabinoside ◽  
Response To Therapy ◽  
High Dose

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

Blood ◽  
2000 ◽  
Vol 95 (9) ◽  
pp. 2799-2805 ◽  
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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