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.

scholarly journals Evaluation of Thrombin Generation Assay in Patients with Hemophilia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5061-5061
Author(s):  
Mehran Karimi ◽  
Sezaneh Haghpanah ◽  
Asghar Bazrafshan ◽  
Peyman Eatemadfar ◽  
Javad Dehghani ◽  
...  
Keyword(s):  
Disease Severity ◽  
Thrombin Generation ◽  
Lag Time ◽  
Activity Level ◽  
Screening Tests ◽  
Control Group ◽  
Factor Activity ◽  
Thrombotic Risk ◽  
Plasma Factor ◽  
Bleeding Score

Abstract Background: Diagnosis of hemophilia is based on detection of factor level and coagulation screening test. These screening tests can not reflect global hemostatic balance. Thrombin generation (TG), as a focal point and key process, is an important step in hemostasis and thrombosis. Recent evidence has indicated that TG assay is a better predictor of the coagulation capacity and subsequently overall assessment of hemostasis compared with traditional coagulation tests. The parameters of the thrombogram are helpful in the evaluation of bleeding or thrombotic risk and also in the management of these situations. Objective: The aim of this study is to evaluate the correlation between TG parameters with bleeding symptoms and disease severity in patients with hemophilia. Methods: In this cross-sectional study, 59 male patients with hemophilia were randomly selected from those already registered at Shiraz Hemophilia Center of southern Iran, from February to December 2012. Also, 38 healthy age-matched men were considered as a control group from those referred for check up. Informed written consent was obtained from all participants. The proposal was approved by the Medical Ethics Committee of Shiraz University of Medical Sciences. Disease severity was defined based on the activity level of deficient factor (severe <1%, moderate from 1 to 5%, and mild >5% IU/dL). Bleeding score (BS) was calculated by performing a clinical evaluation using a modified questionnaire based on Tosetto et al- questionnaire. Correlation of TG parameters with disease severity and BS were determined. Results: From 59 patients with hemophilia (52 hemophilia A and 7 hemophilia B), 40 patients (68%) had severe disease, 14 (24%) moderate and 5 (8%) mild disease. All TG parameters showed statistically significant differences between patients and controls (P<0.001). Only Lag time showed a statistically significant correlation with BS (rs= 0.316, P =0.016). All TG parameters except peak showed association with disease severity (P<0.05). In addition, endogenous thrombin potential showed a significant correlation with factor activity level (rs= 0.459, P <0.001). Both Lag time and start tail showed significant negative correlations with factor activity level (rs= -0.488, P <0.001 and rs=- 0.289, P <0.026 respectively). Conclusion: Based on our results, although most of the TG parameters evaluated were not significantly correlated with bleeding score of hemophilia patients, the majority of TG parameters were significantly associated with factor activity level and disease severity. In patients with hemophilia, plasma factor activity level has a poor predictive value in the evaluation of efficacy of treatment; but it seems that TG assay is an appropriate tool for assessment of global hemostasis and better reflection of clotting function in the management of patients with hemophilia. Disclosures No relevant conflicts of interest to declare.

scholarly journals Haemophilia specialist nurses’ perceptions of haemophilia B

2021 ◽  
Vol 8 (1) ◽  
pp. 119-127
Author(s):  
Steve Chaplin ◽  
Maj Friberg Birkedal ◽  
Erica Crilly ◽  
Simon Fletcher ◽  
Sara Garcia ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Online Survey ◽  
Optimal Treatment ◽  
Haemophilia A ◽  
Current Clinical Practice ◽  
Haemophilia B ◽  
Health Related ◽  
Specialist Nurses ◽  
Nurses Perceptions ◽  
The Impact

Abstract Introduction Some clinicians believe that haemophilia B is associated with less bleeding than haemophilia A, yet there appears to be little difference in health-related outcomes. Current clinical practice reduces the risk of bleeds, making differences difficult to measure. We surveyed specialist haemophilia nurses to discern their opinions about the impact of haemophilia B compared to haemophilia A. Methods Between July and September 2020, European and Canadian nurses were invited to complete an online survey (25 questions) about perceptions of management and treatment of haemophilia B. Results Fifty-nine nurses (46 European, 13 Canadian) completed the survey. Bleeding was reported as different in haemophilia B by 37% of respondents, and treatment as different by over half. Opinions and experience around using extended half-life (EHL) products varied. Self-reported confidence in using EHL products was rated at a mean of 7.1 (range 3–10) with 47% believing these would remain the optimal treatment in 2025. Conclusion Some nurses believe haemophilia A and B are managed differently. Variations in experience and levels of confidence in the use of EHL products, combined with a belief that these products will remain an optimal treatment for haemophilia B for the next five years, indicates a need for education to promote confidence and competence.

Thrombotic Events in Asymptomatic FXII Deficiency versus Symptomatic FXI Deficiency: Surprising Observations

2016 ◽  
Vol 136 (2) ◽  
pp. 118-122 ◽  
Author(s):  
A. Girolami ◽  
E. Cosi ◽  
C. Santarossa ◽  
S. Ferrari ◽  
A.M. Lombardi
Keyword(s):  
Myocardial Infarction ◽  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Activity Level ◽  
Factor Activity ◽  
Pubmed Search ◽  
The Impact ◽  
Combined Defects

Objective: To evaluate the impact of an asymptomatic congenital clotting defect (FXII deficiency) versus that of a similar but symptomatic defect (FXI deficiency) on protection from thrombosis. Patients and Methods: All patients with FXII or FXI deficiency and thrombosis were gathered from a time-unlimited PubMed search that was carried out twice and from personal records. Combined defects were excluded. The defect had to be proven by the demonstration of a suited hereditary pattern and by a specific clotting assay. Only patients with a factor activity level of <30% of normal were selected. Results: Twenty-eight patients with an FXII deficiency presented with arterial thrombosis, mainly myocardial infarction, and 29 showed venous thrombosis; for FXI deficiency, these figures were 43 and 10, respectively. The ratio of arterial and venous thrombosis was 0.96 and 4.3, respectively, for FXII and FXI deficiency. Conclusions: Factor FXII deficiency supplies no protection from arterial or venous thrombosis. FXI deficiency shows no protection from arterial thrombosis but appears to guarantee protection from venous thrombosis. A symptomatic, namely bleeding, condition (FXI deficiency) provides protection from venous thrombosis whereas an asymptomatic one (FXII deficiency) does not.

Translating Principles of Speech Science to Clinical Practice: Current and Future Trends in Craniofacial Disorders

2008 ◽  
Vol 18 (1) ◽  
pp. 31-40 ◽  
Author(s):  
David J. Zajac
Keyword(s):  
Clinical Practice ◽  
Speech Intelligibility ◽  
Current Practice ◽  
Computer Assisted ◽  
Behavioral Management ◽  
Single Word ◽  
Future Directions ◽  
Speech Science ◽  
The Impact ◽  
Opinion Article

Abstract The purpose of this opinion article is to review the impact of the principles and technology of speech science on clinical practice in the area of craniofacial disorders. Current practice relative to (a) speech aerodynamic assessment, (b) computer-assisted single-word speech intelligibility testing, and (c) behavioral management of hypernasal resonance are reviewed. Future directions and/or refinement of each area are also identified. It is suggested that both challenging and rewarding times are in store for clinical researchers in craniofacial disorders.

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.

Clinical Pharmacokinetic Studies in Pregnant Women and the Relevance of Pharmacometric Tools

2019 ◽  
Vol 25 (5) ◽  
pp. 483-495 ◽  
Author(s):  
André Dallmann ◽  
Paola Mian ◽  
Johannes Van den Anker ◽  
Karel Allegaert
Keyword(s):  
Pregnant Women ◽  
Clinical Pharmacokinetic ◽  
Individual Variability ◽  
Current Status ◽  
Pharmacokinetic Studies ◽  
Full Potential ◽  
Pbpk Models ◽  
Pregnancy And Postpartum ◽  
Population Pk ◽  
The Impact

Background: In clinical pharmacokinetic (PK) studies, pregnant women are significantly underrepresented because of ethical and legal reasons which lead to a paucity of information on potential PK changes in this population. As a consequence, pharmacometric tools became instrumental to explore and quantify the impact of PK changes during pregnancy. Methods: We explore and discuss the typical characteristics of population PK and physiologically based pharmacokinetic (PBPK) models with a specific focus on pregnancy and postpartum. Results: Population PK models enable the analysis of dense, sparse or unbalanced data to explore covariates in order to (partly) explain inter-individual variability (including pregnancy) and to individualize dosing. For population PK models, we subsequently used an illustrative approach with ketorolac data to highlight the relevance of enantiomer specific modeling for racemic drugs during pregnancy, while data on antibiotic prophylaxis (cefazolin) during surgery illustrate the specific characteristics of the fetal compartments in the presence of timeconcentration profiles. For PBPK models, an overview on the current status of reports and papers during pregnancy is followed by a PBPK cefuroxime model to illustrate the added benefit of PBPK in evaluating dosing regimens in pregnant women. Conclusions: Pharmacometric tools became very instrumental to improve perinatal pharmacology. However, to reach their full potential, multidisciplinary collaboration and structured efforts are needed to generate more information from already available datasets, to share data and models, and to stimulate cross talk between clinicians and pharmacometricians to generate specific observations (pathophysiology during pregnancy, breastfeeding) needed to further develop the field.

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