TT Virus Is Present in a High Frequency of Italian Hemophilic Patients Transfused With Plasma-Derived Clotting Factor Concentrates

Blood ◽  
1999 ◽  
Vol 94 (12) ◽  
pp. 4333-4336 ◽  
Author(s):  
Benjamin P. Chen ◽  
Maria Grazia Rumi ◽  
Massimo Colombo ◽  
Yu-Huei Lin ◽  
Latha Ramaswamy ◽  
...  
Keyword(s):  
Factor Viii ◽  
Odds Ratio ◽  
Causal Effect ◽  
Clotting Factor ◽  
Hepatitis Viruses ◽  
Tt Virus ◽  
Plasma Factor ◽  
Immunodeficiency Virus ◽  
Factor Viii Concentrates ◽  
Clotting Factor Concentrates

The prevalence of the blood-borne TT virus (TTV) in Italian hemophiliacs treated with different preparations of factor VIII was determined. Of the 178 hemophilic patients (mean age, 29 years), TTV-DNA was found in 123 (69%), in comparison to 22 of 100 (22%) blood donors (P < .0001). Of the 123 patients who tested positive for TTV, significant numbers were also infected with human hepatitis viruses and/or human immunodeficiency virus (HIV): 31% had TTV and hepatitis C virus (HCV), 22% had TTV, and at least 2 of the 4 known human blood-borne viruses tested, whereas 15% had TTV alone. The risk of acquiring TTV alone was only slightly higher in recipients of unmodified plasma factor concentrates (78%, odds ratio, 1.24; 95% confidence interval [CI], 0.27 to 5.79) than in patients treated with virus inactivated concentrates (67%), whereas the risk was significantly lower in recipients of recombinant factors (11%, odds ratio, 0.09; 95% CI, 0.01 to 0.52). Serum alanine aminotransferase (ALT) levels were elevated in 2 of 27 patients (7%) with TTV alone compared with 43 of 56 patients (77%) coinfected with TTV and HCV and compared with 16 of 21 patients (76%) with HCV alone. Taken together, these results indicate that TTV frequently infects Italian hemophiliacs treated with plasma-derived factor VIII concentrates, both unmodified and virus-inactivated. Our results do not suggest a causal effect of TTV on chronic liver disease in these patients.

TT Virus Is Present in a High Frequency of Italian Hemophilic Patients Transfused With Plasma-Derived Clotting Factor Concentrates

Blood ◽  
1999 ◽  
Vol 94 (12) ◽  
pp. 4333-4336 ◽  
Author(s):  
Benjamin P. Chen ◽  
Maria Grazia Rumi ◽  
Massimo Colombo ◽  
Yu-Huei Lin ◽  
Latha Ramaswamy ◽  
...  
Keyword(s):  
Factor Viii ◽  
Odds Ratio ◽  
Causal Effect ◽  
Clotting Factor ◽  
Hepatitis Viruses ◽  
Tt Virus ◽  
Plasma Factor ◽  
Immunodeficiency Virus ◽  
Factor Viii Concentrates ◽  
Clotting Factor Concentrates

Abstract The prevalence of the blood-borne TT virus (TTV) in Italian hemophiliacs treated with different preparations of factor VIII was determined. Of the 178 hemophilic patients (mean age, 29 years), TTV-DNA was found in 123 (69%), in comparison to 22 of 100 (22%) blood donors (P &lt; .0001). Of the 123 patients who tested positive for TTV, significant numbers were also infected with human hepatitis viruses and/or human immunodeficiency virus (HIV): 31% had TTV and hepatitis C virus (HCV), 22% had TTV, and at least 2 of the 4 known human blood-borne viruses tested, whereas 15% had TTV alone. The risk of acquiring TTV alone was only slightly higher in recipients of unmodified plasma factor concentrates (78%, odds ratio, 1.24; 95% confidence interval [CI], 0.27 to 5.79) than in patients treated with virus inactivated concentrates (67%), whereas the risk was significantly lower in recipients of recombinant factors (11%, odds ratio, 0.09; 95% CI, 0.01 to 0.52). Serum alanine aminotransferase (ALT) levels were elevated in 2 of 27 patients (7%) with TTV alone compared with 43 of 56 patients (77%) coinfected with TTV and HCV and compared with 16 of 21 patients (76%) with HCV alone. Taken together, these results indicate that TTV frequently infects Italian hemophiliacs treated with plasma-derived factor VIII concentrates, both unmodified and virus-inactivated. Our results do not suggest a causal effect of TTV on chronic liver disease in these patients.

scholarly journals Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1859-1863 ◽  
Author(s):  
DB Brettler ◽  
AD Forsberg ◽  
PH Levine ◽  
J Petillo ◽  
K Lamon ◽  
...  
Keyword(s):  
Factor Viii ◽  
Plasma Proteins ◽  
Coagulation Factor ◽  
Clotting Factor ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Immunodeficiency Virus ◽  
Clotting Factor Concentrates ◽  
Cd4 Cell ◽  
Hiv Seropositive

Abstract Conventional clotting factor concentrates have, until recently, been “of intermediate purity,” containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients.

scholarly journals Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1859-1863
Author(s):  
DB Brettler ◽  
AD Forsberg ◽  
PH Levine ◽  
J Petillo ◽  
K Lamon ◽  
...  
Keyword(s):  
Factor Viii ◽  
Plasma Proteins ◽  
Coagulation Factor ◽  
Clotting Factor ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Immunodeficiency Virus ◽  
Clotting Factor Concentrates ◽  
Cd4 Cell ◽  
Hiv Seropositive

Conventional clotting factor concentrates have, until recently, been “of intermediate purity,” containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients.

Antibody to Hepatitis G Mrus after a Vapour-Heated Factor Vlll Goncentrate

1990 ◽  
Vol 64 (02) ◽  
pp. 232-234 ◽  
Author(s):  
P M Mannucci ◽  
A R Zanetti ◽  
M Colombo ◽  
A Chistolini ◽  
R De Biasi ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B ◽  
Factor Viii ◽  
Alanine Aminotransferase ◽  
Household Contact ◽  
Clotting Factor ◽  
Double Infection ◽  
Marked Elevation ◽  
Clotting Factor Concentrates

SummaryTo evaluate whether or not clotting factor concentrates exposed to virucidal procedures transmitted hepatitis C, sera obtained in 1984–1986 from 27 previously untreated hemophiliacs infused with a vapour-heated factor VIII concentrate were tested retrospectively for the antibody to the hepatitis C virus (anti- HCV). A 2-year-old hemophiliac, negative for anti-HCV before administration of concentrate, seroconverted at week 12 and remained anti-HCV positive thereafter. Both his parents were anti-HCV negative and he had no other household contact. The patient had also become HBsAg positive at week 8 and had at the same time a marked elevation of alanine aminotransferase. His double infection with the hepatitis B and C viruses indicates that hot vapour was not completely effective in inactivating these viruses.

Azidothymidine (AZT) in the Treatment of Symptomatic HIV-1-Infected Hemophiliacs

1990 ◽  
Vol 64 (01) ◽  
pp. 108-112 ◽  
Author(s):  
S Eichinger ◽  
I Pabinger ◽  
H Hartl ◽  
C Stain ◽  
S Mayerhofer ◽  
...  
Keyword(s):  
Risk Groups ◽  
Clotting Factor ◽  
Bleeding Tendency ◽  
Probability Of Survival ◽  
Immunodeficiency Virus ◽  
Progression Of Disease ◽  
Bleeding Episodes ◽  
Clotting Factor Concentrates ◽  
Dose Dependent ◽  
Hiv 1

SummaryTwenty-one immunodeficiency virus 1 (HIV 1)-positive hemophilic patients were treated with Azidothymidine (AZT) for symptomatic HIV infection. The median observation period was 20.5 months.At 25 months the probability of survival was 82%, the probability of progression of disease from CDC III or IV C2 to IV C1 (AIDS) was 20% in patients on continuous AZT treatment and 50% in patients with intermption of treatment. Three patients developed severe leukopenia and 3 patients severe anemii during AZT treatment. In 1 patient a dose-dependent striking increase of transaminases during AZT treatment was observed. In 7 patients treatment was intermpted, in 1 patient because of anemia, in 1 because of pruritus and in 5 patients because of noncompliance.No signiticant changes in the consumption of clotting factor concentrates and number of bleeding episodes before and during AZT treatment were noted.We conclude, that both hematological and non-hematological side effects of AZT in HIV 1-infected hemophilic patientr ur. comparable to those seen in other risk groups . AzT does not increase the bleeding tendency in this patient group.

TT virus contaminates first-generation recombinant factor VIII concentrates

Blood ◽  
2001 ◽  
Vol 98 (8) ◽  
pp. 2571-2573 ◽  
Author(s):  
Alberta Azzi ◽  
Riccardo De Santis ◽  
Massimo Morfini ◽  
Krystyna Zakrzewska ◽  
Roberto Musso ◽  
...  
Keyword(s):  
Factor Viii ◽  
First Generation ◽  
Second Generation ◽  
Human Albumin ◽  
Factor Ix ◽  
Recombinant Factor Viii ◽  
Tt Virus ◽  
Recombinant Product ◽  
Before And After ◽  
Factor Viii Concentrates

Abstract Recombinant factor VIII and factor IX concentrates, human-plasma–derived albumin, and samples from previously untreated patients with hemophilia were examined for the presence of TT virus (TTV) by using polymerase chain reaction testing. Blood samples from the patients were obtained prospectively before and every 3 to 6 months after therapy was begun. TTV was detected in 23.5% of the recombinant-product lots and 55.5% of the albumin lots tested. Only first-generation factor VIII recombinant concentrates stabilized with human albumin were positive for TTV, whereas all second-generation (human protein–free) concentrates were negative for the virus. In 59% of patients treated with either first- or second-generation recombinant factor concentrates, TTV infection developed at some point after the initial infusion. Infection with TTV in these patients before and after treatment did not appear to be clinically important. Thus, first-generation recombinant factor VIII concentrates may contain TTV and the source of the viral contamination may be human albumin.

scholarly journals Desmopressin treatment combined with clotting factor VIII concentrates in patients with non-severe haemophilia A: protocol for a multicentre single-armed trial, the DAVID study

BMJ Open ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. e022719 ◽  
Author(s):  
Lisette M Schütte ◽  
Marjon H Cnossen ◽  
Reinier M van Hest ◽  
Mariette H E Driessens ◽  
Karin Fijnvandraat ◽  
...  
Keyword(s):  
Factor Viii ◽  
Combination Treatment ◽  
Bleeding Risk ◽  
Clotting Factor ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Registration Number ◽  
Concentrate Treatment ◽  
Factor Viii Concentrates ◽  
Von Willebrand

IntroductionHaemophilia A is an inherited bleeding disorder characterised by factor VIII (FVIII) deficiency. In patients with non-severe haemophilia A, surgery and bleeding are the main indications for treatment with FVIII concentrate. A recent study reported that standard dosing frequently results in FVIII levels (FVIII:C) below or above FVIII target ranges, leading to respectively a bleeding risk or excessive costs. In addition, FVIII concentrate treatment carries a risk of development of neutralising antibodies. An alternative is desmopressin, which releases endogenous FVIII and von Willebrand factor. In most patients with non-severe haemophilia A, desmopressin alone is not enough to achieve FVIII target levels during surgery or bleeding. We hypothesise that combined pharmacokinetic (PK)-guided administration of desmopressin and FVIII concentrate may improve dosing accuracy and reduces FVIII concentrate consumption.Methods and analysisIn the DAVID study, 50 patients with non-severe haemophilia A (FVIII:C ≥0.01 IU/mL) with a bleeding episode or undergoing surgery will receive desmopressin and FVIII concentrate combination treatment. The necessary dose of FVIII concentrate to reach FVIII target levels after desmopressin administration will be calculated with a population PK model. The primary endpoint is the proportion of patients reaching FVIII target levels during the first 72 hours after start of the combination treatment. This approach was successfully tested in one pilot patient who received perioperative combination treatment.Ethics and disseminationThe DAVID study was approved by the medical ethics committee of the Erasmus MC. Results of the study will be communicated trough publication in international scientific journals and presentation at (inter)national conferences.Trial registration numberNTR5383; Pre-results.

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

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.

scholarly journals Immune status of human immunodeficiency virus seropositive and seronegative hemophiliacs infused for 3.5 years with recombinant factor VIII. The Kogenate Study Group

Blood ◽  
1994 ◽  
Vol 83 (7) ◽  
pp. 1958-1962
Author(s):  
PM Mannucci ◽  
DB Brettler ◽  
LM Aledort ◽  
JM Lusher ◽  
CF Abildgaard ◽  
...  
Keyword(s):  
Factor Viii ◽  
Recombinant Factor Viii ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Immunodeficiency Virus ◽  
Factor Viii Concentrates ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
Cd4 Cell ◽  
Hiv Seropositive

Recent studies suggest that treatment of hemophiliacs with highly purified factor VIII concentrates may preserve immune function. To test this hypothesis, we prospectively studied 51 hemophilic patients (21 human immunodeficiency virus [HIV] seropositive and 30 seronegative) who were on home therapy exclusively with recombinant factor VIII (Kogenate, Miles Laboratory, Berkeley, CA) for 3.5 years. Patients, all of whom had been previously treated with plasma-derived factor VIII concentrates, were monitored every 6 months with T-lymphocyte subsets and beta 2-microglobulin levels. Mean rate of change in absolute CD4 cell counts, calculated from regression slopes for individual patients, showed a small but statistically significant decrease over the 3.5-year study period for HIV seropositive hemophiliacs. No decrease in CD4 cell counts was seen in HIV seronegative hemophiliacs when the data for children under age 6 years were excluded from the analysis. beta 2- microglobulin levels and CD8 cell counts remained unchanged. These data show stability of immunologic parameters in HIV seronegative hemophiliacs, and a small decrease in CD4 cell counts in HIV seropositive hemophiliacs treated with recombinant factor VIII.

An Improved Method of Making Factor VIII Concentrates

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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