Simplifying surgery in haemophilia B: Low factor IX consumption and infrequent infusions in surgical procedures with rIX-FP.

Abstract Introduction Long-acting recombinant factor IX (FIX) products may simplify the surgical treatment of haemophilia B patients. The impact of rIX-FP, a recombinant FIX fused to recombinant albumin, on FIX consumption and surgical management was assessed in patients with haemophilia B. Materials and methods Male patients, ≤65 years old with severe haemophilia B (FIX activity ≤2%) requiring non-emergency surgery were enrolled in the surgical substudy of PROLONG-9FP. Dosing was based on World Federation of Hemophilia guidelines and patients' pharmacokinetics. Haemostatic efficacy was assessed on a 4-point scale. rIX-FP consumption and safety were monitored throughout the perioperative period. Results This updated dataset reports on thirty (8 minor and 22 major) surgeries conducted in 21 patients. A single preoperative bolus was used in 96.7% (n = 29) of surgeries. After minor surgery, patients received a median (range) of 0 (0–3) infusions with a median (range) consumption of 0 (0–178.89) IU/kg in the 14-day postoperative period. In patients who underwent major surgery (including 15 patients undergoing joint replacement surgery), the median (range) number of infusions in the 14-day postoperative period was 5 (0−11) and median consumption was 221.7 (0–444.07) IU/kg. Haemostatic efficacy was rated as excellent or good in 87.5% (7/8) of minor surgeries and 95.5% (21/22) of major surgeries. Conclusion Surgical procedures can be performed using a single preoperative bolus of rIX-FP in nearly all patients. During postoperative care, use of rIX-FP necessitated infrequent infusions and low FIX consumption. Overall, data suggest rIX-FP simplifies perioperative care in patients with haemophilia B

Flow cytometric analysis of platelets mepacrine-labelled dense granules among individuals with mild bleeding symptoms

Introduction: Mild bleeding symptoms are commonly encountered in the general population & amongst individuals with platelet disorders. One of the possible causes is due to reduced number of dense granules synthesis in platelets and defective release of its contents. This study was aimed to evaluate platelets mepacrine-labelled dense granules storage and release using flow cytometry in healthy individuals and those presenting with mild bleeding symptoms. Methods: This study was conducted at the National Blood Centre (NBC) and Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM). Thirty- four individuals were recruited as controls (n=24) and patients (n=10). ADP-activated platelets and mepacrine-labelled dense granules was detected using flow cytometry. Results were expressed as mean fluorescent intensity (MFI) of mepacrine in resting and activated platelets; representing dense granules storage and release, respectively. Statistical analysis was considered significant if p ≤ 0.05. Results: There was a significant difference of mean MFI between resting (1284.3 ± 91.8) and activated platelets (1233.8 ± 107.8) of overall respondents with mean difference of 50.5 (p<0.01). However, there was no significant difference of mean MFI in resting and activated platelets between controls and patients was observed. Conclusion: Results indicated there is no secretion defects in platelet dense granules among patients in comparison with controls. Flow cytometry provides alternative way of dense granule assessment in patients presented with mild bleeding symptoms

Platelet aggregation pattern on light transmission aggregometry among Malaysian healthy individuals

Introduction: Platelet aggregation test using light transmission aggregometry (LTA) is considered as the gold standard for evaluation of platelet function. Variations of platelet aggregation had been reported in apparently healthy individuals whereby a normal cut–off value established locally is highly recommended. This study aims to determine the platelet aggregation pattern and the preliminary findings on reference values for multiple agonists–induced platelet aggregation among Malaysian healthy individuals in a single centre. Method: A total number of 63 informed consented healthy individuals consisted of Malay, Chinese and Indian were recruited among staff and blood donors at National Blood Centre, Kuala Lumpur. Platelet aggregation was measured using LTA against adenosine diphosphate 10 µM (ADP10), collagen 0.19 mg/mL (COL), ristocetin 1.5 mg/mL (RIS), arachidonic acid 1 mM (AA) and epinephrine 10 µM (EPI). Results were expressed as percent final aggregation (%FA). Reference values were calculated from mean±2SD. Results: Age, gender and ethnic groups had no significant effect on platelet aggregation. A variability of platelet aggregation response to EPI was observed among the healthy individuals. Ten of 33 respondents (30%) had impaired aggregation with <20% FA in response to EPI. The local population showed a slightly higher aggregation pattern in response to COL, RIS, AA and EPI (excluding non-responders) compared to manufacturer’s reference values. Conclusion: This study has provided a glimpse of the aggregation pattern of the local nationality showing considerable differences in the reference values from manufacturer’s; thus highlighting the need of establishing local reference values

Report on von Willebrand Disease in Malaysia

BACKGROUND: Von Willebrand disease (vWD) is an inherited hemostatic disorder that affects the hemostasis pathway. The worldwide prevalence of vWD is estimated to be 1% of the general population but only 0.002% in Malaysia.AIM: Our present paper has been written to disclose the statistical counts on the number of vWD cases reported from 2011 to 2013.MATERIAL AND METHODS: This article is based on sociodemographic data, diagnoses and laboratory findings of vWD in Malaysia. A total of 92 patients were reported to have vWD in Malaysia from 2011 to 2013.RESULTS: Sociodemographic-analysis revealed that 60% were females, 63% were of the Malay ethnicity, 41.3% were in the 19-44 year old age group and 15.2% were from Sabah, with the East region having the highest registered number of vWD cases. In Malaysia, most patients are predominately affected by vWD type 1 (77.2%). Factor 8, von Willebrand factor: Antigen and vWF: Collagen-Binding was the strongest determinants in the laboratory profiles of vWD.CONCLUSION: This report has been done with great interest to provide an immense contribution from Malaysia, by revealing the statistical counts on vWD from 2011-2013

A study on the frequency of iron deficiency and thalassaemia in blood donors at Pusat Darah Negara, Kuala Lumpur

This study was done to identify lood donors with thalassaemia and iron deficiency. A cross sectional study was carried out at Pusat Darah Negara (PDN), Kuala Lumpur in November 2003. Methods: Full blood counts were done on 242 blood donors (166 males and 76 females) Hb analysis and serum ferritin assay were done for all the samples. The first time donors were used as controls. Results: Only 20 (8.3%) donors had MCV Ferritin done for their iron status and if their MCV and MCH are low, Hb analysis for thalassaemia or haemoglobinopathy

Factor VIII activity and bleeding risk during prophylaxis for severe hemophilia A : a population pharmacokinetic model

Copyright © 2020, Ferrata Storti Foundation.During factor VIII prophylaxis for severe hemophilia A, bleeding risk increases with time when factor VIII activity is below 1%. Maintaining trough activity above 1% does not protect all patients from bleeding. The relationship between factor VIII activity during prophylaxis and bleeding risk has not been thoroughly studied. We investigated factor VIII activity and annualized bleeding rate for spontaneous bleeds during prophylaxis. A population pharmacokinetic model derived from three clinical trials was combined with dosing data and bleed information from patient diaries. Each patients' time on prophylaxis was divided into five categories of predicted activity (0-1%, >1-5%, >5-15%, >15-50%, and >50%). Exposure time, mean factor VIII activity, and bleed number (from patient diaries) were calculated for each activity category, and annualized bleeding rates estimated using negative binomial regression and a parametric model. Relationships between these bleeding rates and factor VIII activity were evaluated by trial phase (pivotal vs. extension) and age (adults/adolescents [≥12 years] vs. children [0-1% for 85.64% of the time. Annualized bleeding rate decreased as factor VIII activity increased in each trial phase and age group. However, for a given activity level, bleeding rate differed substantially by trial phase, and age. This suggests that bleeding risk can change over time and is influenced by factors independent of factor VIII pharmacokinetics and trough levels. Target trough and prophylactic regimen should consider patient age, joint disease activity, and other bleeding risk determinants.publishersversionPeer reviewe

First report of safety and efficacy of a glycoPEGylated FVIII (N8-GP) in previously treated pediatric patients with severe hemophilia A-results from the international phase 3 pathfinder (TM) 5 trial

WOS: 00037994090017

Once-Weekly Prophylactic Treatment Versus on-Demand Treatment of Nonacog Alfa in Patients with Moderately Severe to Severe Hemophilia B

56th Annual Meeting of the American-Society-of-Hematology -- DEC 06-09, 2014 -- San Francisco, CAWOS: 000349233806027Amer Soc Hemato