scholarly journals Using pharmacokinetics to individualize hemophilia therapy

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 595-604 ◽  
Author(s):  
Alfonso Iorio
Keyword(s):  
Population Pharmacokinetics ◽  
Interindividual Variability ◽  
Clinical Care ◽  
Activity Level ◽  
Clotting Factor ◽  
Factor Activity ◽  
Individualized Dosing ◽  
Case Basis ◽  
Individual Pharmacokinetics

Abstract Prevention and treatment of bleeding in hemophilia requires that plasma clotting factor activity of the replaced factor exceeds a defined target level. Most clinical decisions in hemophilia are based on implicit or explicit application of pharmacokinetic measures. The large interindividual variability in pharmacokinetics of factor concentrates suggests that relying on the average pharmacokinetic characteristics of factor concentrates would not allow optimizing the treatment of individual patients; for example, adjusting the frequency of infusions and targeting a specific clotting factor activity level on a case-by-case basis. However, individual pharmacokinetic profiles are seldom assessed as part of routine clinical care. Population pharmacokinetics provide options for precise and convenient characterization of pharmacokinetics characteristics of factor concentrates, simplified individual pharmacokinetic profiling, and individualized dosing. Population pharmacokinetics allow for the incorporation of determinants of interpatient variability and reduces the need for extensive postinfusion plasma sampling. Barriers to the implementation of population pharmacokinetics are the need for concentrate-specific pharmacokinetic models, Bayesian calculation power, and specific expertise for production, validation, and appraisal of forecasted estimates. Population pharmacokinetics provide an important theoretical and practical contribution to tailoring the treatment of hemophilia. The need remains for prospective exploration of the clinical impact of tailoring hemophilia treatment based on individual pharmacokinetics, and for the systematic validation of existing software solutions and concentrate-specific models.

Coagulation Factor Activity Level and Clinical Bleeding Severity in Rare Bleeding Disorders: Results From the European Network of Rare Bleeding Disorders (EN-RBD),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3312-3312
Author(s):  
Flora Peyvandi ◽  
Roberta Palla ◽  
Marzia Menegatti ◽  
Simona M Siboni ◽  
Susan Halimeh ◽  
...  
Keyword(s):  
Research Funding ◽  
Linear Regression Analysis ◽  
Strong Association ◽  
Coagulation Factor ◽  
Activity Level ◽  
Clotting Factor ◽  
Bleeding Disorders ◽  
Factor Activity ◽  
European Network ◽  
Bleeding Severity

Abstract Abstract 3312 The European Network of Rare Bleeding Disorders (EN-RBD) was established to bridge the gap between knowledge and practice in the care of patients with RBDs (rare bleeding disorders frequency <1/0.5-2M). The aim of this first report was to explore the relationship between the coagulation factor activity levels and clinical bleeding severity in patients with RBDs. A total of 592 records on patients with RBDs were cross-sectionally collected over a period of three years. Data on clinical bleeding episodes were available for 495 patients and were classified into four categories according to severity. The mean age of patients was 31 years (range, 7 months-95 years), with 51% being females. On linear regression analysis, there was a strong association between coagulation factor activity level and clinical bleeding severity for fibrinogen, factor (F)FX, FXIII, and combined FV and FVIII deficiencies. A weaker association was present for FV and FVII deficiencies. There was no association between coagulation factor activity level and clinical bleeding severity for FXI. It is of clinical relevance to identify levels that are not associated with spontaneous major bleeding, which was done by constructing receiver operating characteristic curves. These levels were highest for FXIII deficiency (25 U/dl), followed by FV+VII (15 U/dl), FVII (15 U/dl), FX (5 U/dl), and FV (1 U/dl) deficiencies. For fibrinogen deficiency, a factor activity level of 20 mg/dl is needed to ensure absence of major spontaneous bleeding. There is a clear relation between coagulation factor activity level and clinical bleeding severity in RBDs, which is different for the missing clotting factor. Disclosures: Peyvandi: NovoNordisk, CSL Behring: Honoraria. Bidlingmaier:CSL Behring, Bayer Schering: Research Funding; CSL Behring, NovoNordisk, Pfizer, Bayer Schering: Membership on an entity's Board of Directors or advisory committees; Baxter, Biotest, CSL Behring, NovoNordisk, Pfizer, Bayer Schering: Honoraria. Schved:LFB, CSL Behring, Novonordisk, Bayer Schering: Research Funding.

scholarly journals Quantitative Characterization of Geotrichum candidum Growth in Milk

2021 ◽  
Vol 11 (10) ◽  
pp. 4619
Author(s):  
Petra Šipošová ◽  
Martina Koňuchová ◽  
Ľubomír Valík ◽  
Monika Trebichavská ◽  
Alžbeta Medveďová
Keyword(s):  
Growth Parameters ◽  
Mechanistic Model ◽  
Geotrichum Candidum ◽  
Activity Level ◽  
Effect Of Temperature ◽  
Operational Parameters ◽  
Quantitative Characterization ◽  
Essential Knowledge ◽  
Cardinal Temperatures

The study of microbial growth in relation to food environments provides essential knowledge for food quality control. With respect to its significance in the dairy industry, the growth of Geotrichum candidum isolate J in milk without and with 1% NaCl was investigated under isothermal conditions ranging from 6 to 37 °C. The mechanistic model by Baranyi and Roberts was used to fit the fungal counts over time and to estimate the growth parameters of the isolate. The effect of temperature on the growth of G. candidum in milk was modelled with the cardinal models, and the cardinal temperatures were calculated as Tmin = −3.8–0.0 °C, Topt = 28.0–34.6 °C, and Tmax = 35.2–37.2 °C. The growth of G. candidum J was slightly faster in milk with 1% NaCl and in temperature regions under 21 °C. However, in a temperature range that was close to the optimum, its growth was slightly inhibited by the lowered water activity level. The present study provides useful cultivation data for understanding the behaviour of G. candidum in milk and can serve as an effective tool for assessing the risk of fungal spoilage, predicting the shelf life of dairy products, or assessing the optimal conditions for its growth in relation to the operational parameters in dairy practices.

Endogenous Clotting Factor Activity and Long-term Outcome in Patients with Moderate Haemophilia

2000 ◽  
Vol 84 (12) ◽  
pp. 977-980 ◽  
Author(s):  
J. G. van der Bom ◽  
E. P. Mauser-Bunschoten ◽  
G. Roosendaal ◽  
F. J. A. Beek ◽  
P. de Kleijn ◽  
...  
Keyword(s):  
Prophylactic Treatment ◽  
Joint Damage ◽  
Clotting Factor ◽  
Factor Activity ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Percent Increase ◽  
Radiological Score

SummaryIn order to address the question of the optimum target level for prophylactic treatment of severe haemophilia patients, the association between endogenous clotting factor activity and outcome was studied in a cohort of 46 patients with moderate haemophilia. Data on treatment and outcome were collected annually.Median follow-up was 8.0 years (range 1-26). Median joint bleed frequency was 1 per year and median radiological score according to Pettersson was 1 point (max. 78) at the age of 25 years. One percent increase in clotting factor level was associated with a 4 months later onset of joint bleeds (95% Confidence Interval (CI): 2-6 months) and a 16% lower Pettersson score (95% CI: 3-27%). No statistically significant effect of clotting factor activity on joint bleed frequency could be demonstrated.These findings confirm that patients with moderate haemophilia experience only mild arthropathy, and provide evidence for a protective effect of higher clotting factor levels on joint damage.

Use of high-resolution techniques for the characterization of clotting factor VIII

1999 ◽  
Vol 852 (1) ◽  
pp. 175-188 ◽  
Author(s):  
Katharina Pock ◽  
Andreas Rizzi ◽  
Djuro Josic
Keyword(s):  
High Resolution ◽  
Factor Viii ◽  
Clotting Factor

scholarly journals Studies Examining the Efficacy of Ankle Foot Orthoses should Report Activity Level and Mechanical Evidence

2010 ◽  
Vol 34 (3) ◽  
pp. 327-335 ◽  
Author(s):  
Jaap Harlaar ◽  
Merel Brehm ◽  
Jules G. Becher ◽  
Daan J. J. Bregman ◽  
Jaap Buurke ◽  
...  
Keyword(s):  
Treatment Algorithm ◽  
Relevant Information ◽  
Current Treatment ◽  
Activity Level ◽  
Walking Ability ◽  
Foot Orthoses ◽  
Level Of Evidence ◽  
Levels Of Evidence ◽  
Ankle Foot Orthoses

Ankle Foot Orthoses (AFOs) to promote walking ability are a common treatment in patients with neurological or muscular diseases. However, guidelines on the prescription of AFOs are currently based on a low level of evidence regarding their efficacy. Recent studies aiming to demonstrate the efficacy of wearing an AFO in respect to walking ability are not always conclusive. In this paper it is argued to recognize two levels of evidence related to the ICF levels. Activity level evidence expresses the gain in walking ability for the patient, while mechanical evidence expresses the correct functioning of the AFO. Used in combination for the purpose of evaluating the efficacy of orthotic treatment, a conjunct improvement at both levels reinforces the treatment algorithm that is used. Conversely, conflicting outcomes will challenge current treatment algorithms and the supposed working mechanism of the AFO. A treatment algorithm must use relevant information as an input, derived from measurements with a high precision. Its result will be a specific AFO that matches the patient's needs, specified by the mechanical characterization of the AFO footwear combination. It is concluded that research on the efficacy of AFOs should use parameters from two levels of evidence, to prove the efficacy of a treatment algorithm, i.e., how to prescribe a well-matched AFO.

scholarly journals Impact of Adopting Population Pharmacokinetics for Tailoring Prophylaxis in Haemophilia A Patients: A Historically Controlled Observational Study

2019 ◽  
Vol 119 (03) ◽  
pp. 368-376 ◽  
Author(s):  
Michaela Stemberger ◽  
Felix Kallenbach ◽  
Elisabeth Schmit ◽  
Alanna McEneny-King ◽  
Federico Germini ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Activity Level ◽  
Critical Threshold ◽  
Life Questionnaire ◽  
Haemophilia A ◽  
Factor Activity ◽  
Traffic Light ◽  
Plasma Factor ◽  
Population Pk ◽  
The Impact

Background Performing individual pharmacokinetics (PK) studies in clinical practice can be simplified by adopting population PK-based profiling on limited post-infusion samples. The objective of this study was to assess the impact of population PK in tailoring prophylaxis in patients with haemophilia A. Patients and Methods Individual weekly treatment plans were developed considering predicted plasma factor activity levels and patients' lifestyle. Patients were trained using a visual traffic-light scheme to help modulate their level of physical activity with respect to factor infusions timing. Annualized joint bleeding rate (ABJR), haemophilia-specific quality of life questionnaire for adults (Haemo-QoL-A) and factor utilization were measured for 12 months before and after tailoring, compared within patients and analysed separately for those previously on prophylaxis (P), situational prophylaxis (SP) or on-demand (OD). Results Sixteen patients previously on P, 10 on SP and 10 on OD were enrolled in the study. The median (lower, upper quartile) ABJR changed from 2.0 (0, 4.0) to 0 (0, 1.6) for P (p = 0.003), from 2.0 (2.0, 13.6) to 3.0 (1.4, 7.2) for SP (p = 0.183) and from 16.0 (13.0, 25.0) to 2.3 (0, 5.0) for OD (p = 0.003). The Haemo-QoL-A total score improved for 58% of P, 50% of SP and 29% of OD patients. Factor utilization (IU/kg/patient/year) increased by 2,400 (121; 2,586) for P, 1,052 (308; 1,578) for SP and 2,086 (1,498; 2,576) for OD. One of 138 measurements demonstrated a factor activity level below the critical threshold of 0.03 IU/mL while the predicted level was above the threshold. Conclusion Implementing tailored prophylaxis using a Bayesian forecasting approach in a routine clinical practice setting may improve haemophilia clinical outcomes.

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