Kaolin-Activated Thromboelastography in Hemophilia Patients Discriminates Responses to rFVIIa Better Than Tissue Factor.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2277-2277
Author(s):  
Ru Zhang ◽  
Dena Yassin ◽  
Lingyun Ji ◽  
Robert Miller ◽  
Diane J. Nugent ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Ex Vivo ◽  
Geometric Mean ◽  
Clotting Factor ◽  
Clinical Settings ◽  
Collection Method ◽  
Significant Difference ◽  
Increased Sensitivity ◽  
Type Factor ◽  
Clotting Factor Concentrates

Abstract Thromboelastography (TEG) is a leading candidate for monitoring bypassing agent therapy in hemophilia. It is not clear, however, which pre-analytic methods provide the most sensitivity in assessing the response to clotting factor concentrates. Previous studies have utilized kaolin (K) or recombinant human tissue factor (TF) as activators, and native blood (NB) or citrated blood (CB) as the collection method. Utilizing blood samples from 16 hemophiliacs (8 with and 8 without inhibitors), we compared NB to CB and K to 2 dilutions of TF [1:17,000(TF1) and 1:42,000(TF2)] with and without ex vivo addition of recombinant FVIIa (rFVIIa) and recombinant factor VIII (rFVIII). For patients with inhibitors, 3 experiments were performed for each of the above comparisons: no added factor and addition of rFVIIa 1.5mcg/ml and 4.5 mcg/ml. For patients without inhibitors (all FVIII deficient), 5 experiments were performed: no added factor, rFVIII 0.5 units/ml, rFVIII 1 units/ml, and rFVIIa 1.5 and 4.5mcg/ml. This initial analysis focused on the R parameter (reaction time) which is the time to initial fibrin formation and is the parameter that is most sensitive to the addition of clotting factor concentrates. The R values were analyzed via log transformed random effects ANOVA. All R values are expressed as geometric means. See table for results. There was no significant difference in the R time of NB and CB for any of the experiments. For inhibitor patients following the addition of rFVIIa, the R time was significantly longer for K than for TF1 and TF2 allowing a clearer distinction in response to various concentrations of rFVIIa. This is demonstrated as a significant difference between the 2 concentrations of rFVIIa with the higher concentration demonstrating a shorter R. For patients without inhibitors, activation with K led to a significantly longer R relative to TF1 and TF2 as well with both placebo and rFVIIa. Importantly, when adding a non-activated factor such as rFVIII, R was equivalent for K and TF2 both of which were significantly longer than TF1. In conclusion, 1) we recommend CB as the collection method as it is more practical in clinical settings, and 2) activation with K demonstrates a longer R than TF1 or TF2, resulting in increased sensitivity to addition of 2 clinically relevant concentrations of rFVIIa in both the inhibitor and non-inhibitor patients. Thus we suggest that K is the best activator when analyzing response to rFVIIa in hemophilia patients. Observed (Predicted) Geometric Mean R (mins) for CB Patient Type Factor Kaolin TF1 TF2 *p<0.001 for K versus TF1, K versus TF2, and TF1 versus TF2. *p<0.001 for rFVIIa 1.5 mcg/ml versus 4.5 mcg/ml for all activation methods. #p<0.03 for K versus TF1 for all factors. #p<0.001 for K versus TF2 for placebo and both concentrations of rFVIIa Inhibitor* rFVIIa 1.5 mcg/ml 50.6 (50.1) 14.7 (14.7) 25.1 (25.3) rFVIIa 4.5 mcg/ml 37.3 (32.1) 11.1 (9.4) 19.4 (16.2) No Inhibitor # Placebo 18.2 (17.6) 9.1 (9.1) 13.6 (13.9) rFVIII 0.5 U/ml 7.7 (7.7) 6.0 (6.0) 8.1 (8.1) rFVIII 1.0 U/ml 7.1 (7.1) 5.8 (5.8) 7.6 (7.6) rFVIIa 1.5 mcg/ml 12.7 (11.3) 5.8 (5.9) 10.3 (8.9) rFVIIa 4.5 mcg/ml 9.8 (11.0) 5.8 (5.7) 8.3 (8.7)

Clinical Factors Associated with Progression to AIDS in the Italian Cohort of HIV-Positive Hemophiliacs

1994 ◽  
Vol 72 (01) ◽  
pp. 033-038 ◽  
Author(s):  
N Schinaia ◽  
A M G Ghirardini ◽  
M G Mazzucconi ◽  
G Tagariello ◽  
M Morfini ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
National Registry ◽  
Factor Ix ◽  
Clotting Factor ◽  
Coagulation Disorders ◽  
Factors Associated ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Congenital Coagulation Disorders ◽  
Clotting Factor Concentrates

SummaryThis study updates estimates of the cumulative incidence of AIDS among Italian patients with congenital coagulation disorders (mostly hemophiliacs), and elucidates the role of age at seroconversion, type and amount of replacement therapy, and HBV co-infection in progression. Information was collected both retrospectively and prospectively on 767 HIV-1 positive patients enrolled in the on-going national registry of patients with congenital coagulation disorders. The seroconversion date was estimated as the median point of each patient’s seroconversion interval, under a Weibull distribution applied to the overall interval. The independence of factors associated to faster progression was assessed by multivariate analysis. The cumulative incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 17.0% (95% Cl = 14.1-19.9%) over an 8-year period for Italian hemophiliacs. Patients with age greater than or equal to 35 years exhibited the highest cumulative incidence of AIDS over the same time period, 32.5% (95% Cl = 22.2-42.8%). Factor IX recipients (i.e. severe B hemophiliacs) had higher cumulative incidence of AIDS (23.3% vs 14.2%, p = 0.01) than factor VIII recipients (i.e. severe A hemophiliacs), as did severe A hemophiliacs on less-than-20,000 IU/yearly of plasma-derived clotting factor concentrates, as opposed to A hemophiliacs using an average of more than 20,000 IU (18.8% vs 10.9%, p = 0.02). No statistically significant difference in progression was observed between HBsAg-positive vs HBsAg-negative hemophiliacs (10.5% vs 16.4%, p = 0.10). Virological, immunological or both reasons can account for such findings, and should be investigated from the laboratory standpoint.

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.

Acute Hepatitis C in Haemophiliacs Due to “Virus-Inactivated” Clotting Factor Concentrates

1992 ◽  
Vol 68 (06) ◽  
pp. 781-781 ◽  
Author(s):  
A Gerritzen ◽  
B Scholt ◽  
R Kaiser ◽  
K E Schneweis ◽  
H-H Brackmann ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Acute Hepatitis ◽  
Clotting Factor ◽  
Acute Hepatitis C ◽  
Clotting Factor Concentrates

Recombinant Tissue Factor as Substitute for Conventional Thromboplastin in the Prothrombin Time Test

1992 ◽  
Vol 67 (01) ◽  
pp. 042-045 ◽  
Author(s):  
Armando Tripodi ◽  
Arnaldo Arbini ◽  
Veena Chantarangkul ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Prothrombin Time ◽  
Tissue Factor ◽  
Oral Anticoagulant Therapy ◽  
Clotting Factor ◽  
Rabbit Brain ◽  
Sensitivity Index ◽  
Clotting Factors ◽  
Wide Range ◽  
Reference Preparation ◽  
Time Test

SummaryRelipidated recombinant tissue factor (r-TF) has been assessed in comparison with conventional rabbit brain thromboplastin (Manchester Reagent) for its suitability for measurement of prothrombin time (PT). The International Sensitivity Index (ISI) of r-TF calibrated against the International Reference Preparation BCT/253 (human plain) was found to be 0.96 and 1.12 with instrumental and manual techniques. Our study of plasmas from patients with congenital deficiencies of clotting factors covering a wide range of severity demonstrates that r-TF is able to detect even minor deficiencies of factors involved in the extrinsic and common coagulation pathways. Patients with liver diseases were correctly diagnosed with a prevalence of abnormal results comparable for both reagents. Between-assay reproducibility expressed as coefficient of variation was 2.3 % and 3.9 % at normal and abnormal PT levels.In conclusion, our evaluation shows that relipidated r-TF possesses the necessary requisites of sensitivity, diagnostic accuracy and reproducibility which make it a suitable candidate for PT determination both for monitoring oral anticoagulant therapy and diagnosing congenital and acquired clotting factor deficiencies. Moreover, being a highly defined reagent it may constitute a step forward in the standardization of PT testing.

Detection of Circulating Tissue Factor and Factor VII in a Normal Population

1996 ◽  
Vol 75 (05) ◽  
pp. 772-777 ◽  
Author(s):  
Sybille Albrecht ◽  
Matthias Kotzsch ◽  
Gabriele Siegert ◽  
Thomas Luther ◽  
Heinz Großmann ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Normal Population ◽  
Mean Value ◽  
Factor Vii ◽  
Significant Difference ◽  
Age Dependent ◽  
The Mean ◽  
Highly Correlated ◽  
And Gender

SummaryThe plasma tissue factor (TF) concentration was correlated to factor VII concentration (FVIIag) and factor VII activity (FVIIc) in 498 healthy volunteers ranging in age from 17 to 64 years. Immunoassays using monoclonal antibodies (mAbs) were developed for the determination of TF and FVIIag in plasma. The mAbs and the test systems were characterized. The mean value of the TF concentration was 172 ± 135 pg/ml. TF showed no age- and gender-related differences. For the total population, FVIIc, determined by a clotting test, was 110 ± 15% and the factor VIlag was 0.77 ± 0.19 μg/ml. FVII activity was significantly increased with age, whereas the concentration demonstrated no correlation to age in this population. FVII concentration is highly correlated with the activity as measured by clotting assay using rabbit thromboplastin. The ratio between FVIIc and FVIIag was not age-dependent, but demonstrated a significant difference between men and women. Between TF and FVII we could not detect a correlation.

Hepatitis-Free Interval After Clotting Factor Therapy in First Infused Haemophiliacs

1986 ◽  
Vol 56 (03) ◽  
pp. 268-270 ◽  
Author(s):  
M Morfini ◽  
D Rafanelli ◽  
G Longo ◽  
A Messori ◽  
P Rossi Ferrini
Keyword(s):  
Life Table ◽  
Lower Risk ◽  
Clotting Factor ◽  
Rank Test ◽  
Life Table Method ◽  
Table Method ◽  
Log Rank Test ◽  
Free Interval ◽  
Post Infusion ◽  
Clotting Factor Concentrates

SummaryPost-infusion hepatitis is known to occur very frequently in haemophiliacs after treatment with unheated commercial clotting factor concentrates, obtained from large plasma donation pool. On the contrary, single-donor cryoprecipitate is likely to carry a lower risk of transmitting hepatitis.To evaluate this hypothesis, we retrospectively reviewed the medical records of 25 first infused haemophiliacs (from 1981 to 1984) treated with unheated commercial clotting factor concentrates (n = 19) or cryoprecipitate (n = 6).The hepatitis-free interval after the beginning of therapy was expressed as exposure days. The end point of each patient, i.e. the hepatitis occurrence, was defined as an increase of aminotransferases (ALT and AST) and/or the seroconversion of HBV-markers, which were checked every three months.The life-table method and log-rank test showed that cryo-precipitates had a significantly longer hepatitis-free interval (p = 0.0131, log-rank test) and a lower risk of transmitting hepatitis (p = 0.01-0.05, life-table method) than the commercial concentrates. However, the safety of cryoprecipitate therapy was shown to cover only a few exposure days, and so the real advantage of this product depends on the bleeding frequency of the patient concerned.We believe that these methods and our findings may be useful to assess and compare the safety of the new “heat-treated” clotting factor concentrates.

Aerosol generation through pars plana vitrectomy

2020 ◽  
pp. bjophthalmol-2020-317214
Author(s):  
Hasan Naveed ◽  
Fong May Chew ◽  
Hanbin Lee ◽  
Edward Hughes ◽  
Mayank A Nanavaty
Keyword(s):  
Pars Plana Vitrectomy ◽  
Ex Vivo ◽  
Dynamic Changes ◽  
Aerosol Generation ◽  
Significant Difference ◽  
Optical Particle Counter ◽  
Pars Plana ◽  
23 Gauge ◽  
Set Up ◽  
Ex Vivo Study

PurposeTo assess whether pars plana vitrectomy (PPV) is an aerosol-generating procedure (AGP) in an ex vivo experimental model.MethodsIn this ex vivo study on 10 porcine eyes, optical particle counter was used to measure particles ≤10 μm using cumulative mode in the six in-built channels: 0.3 μm, 0.5 μm, 1 μm, 2.5 μm, 5 μm and 10 μm aerosols during PPV. Two parts of the study were as follows: (1) to assess the pre-experimental baseline aerosol count in the theatre environment where there are dynamic changes in temperature and humidity and (2) to measure aerosol generation with 23-gauge and 25-gauge set-up. For each porcine eye, five measurements were taken for each consecutive step in the experiment including pre-PPV, during PPV, fluid–air exchange (FAX) and venting using a flute with 23-gauge set-up and a chimney with 25-gauge set-up. Therefore, a total of 200 measurements were recorded.ResultsWith 23-gauge and 25-gauge PPV, there was no significant difference in aerosol generation in all six channels comparing pre-PPV versus PPV or pre-PPV versus FAX. Venting using flute with 23-gauge PPV showed significant reduction of aerosol ≤1 μm. Air venting using chimney with 25-gauge set-up showed no significant difference in aerosol of ≤1 μm. For cumulative aerosol counts of all particles measuring ≤5 μm, compared with pre-PPV, PPV or FAX, flute venting in 23-gauge set-up showed significant reduction unlike the same comparison for chimney venting in 25-gauge set-up.ConclusionPPV and its associate steps do not generate aerosols ≤10 μm with 23-gauge and 25-gauge set-ups.

The Influence of Force Direction on the Fracture Pattern and Fracture Resistance of Canine Teeth in Dogs

2017 ◽  
Vol 34 (1) ◽  
pp. 8-17 ◽  
Author(s):  
Stephanie Goldschmidt ◽  
Catherine Zimmerman ◽  
Caitlyn Collins ◽  
Scott Hetzel ◽  
Heidi-Lynn Ploeg ◽  
...  
Keyword(s):  
Fracture Resistance ◽  
Ex Vivo ◽  
Testing Machine ◽  
Fracture Pattern ◽  
Hard Tissue ◽  
Canine Tooth ◽  
Cross Sectional ◽  
Significant Difference ◽  
Force Direction ◽  
Testing Group

Biomechanical studies of the elongated canine tooth of animals are few, and thus our understanding of mechanical and physical properties of animal teeth is limited. The objective of the present study was to evaluate the influence of force direction on fracture resistance and fracture pattern of canine teeth in an ex vivo dog cadaver model. Forty-five extracted canine teeth from laboratory beagle dogs were standardized by hard tissue volume and randomly distributed among 3 force direction groups. The teeth were secured within a universal testing machine and a load was applied at different directions based on testing group. The maximum force to fracture and the fracture pattern classification were recorded for each tooth. After correcting for hard tissue cross-sectional area in a multivariate analysis, no significant difference in the amount of force required for fracture was apparent between the different force direction groups. However, the influence of force direction on fracture pattern was significant. The results of this study may allow the clinician to educate clients on possible causal force directions in clinically fractured teeth and, thus, help prevent any contributing behavior in the future.

Sign in / Sign up

Export Citation Format

Share Document