Yasmin Ayob

Recombinant factor VIIa analog (vatreptacog alfa [activated]) for treatment of joint bleeds in hemophilia patients with inhibitors: A randomized controlled trial

Summary.  Background: A recombinant factor VIIa analog (NN1731; vatreptacog alfa [activated]) was developed to provide safe, rapid and sustained resolution of bleeds in patients with hemophilia and inhibitors. Patients/Methods: This global, prospective, randomized, double‐blinded, active‐controlled, dose‐escalation trial evaluated and compared one to three doses of vatreptacog alfa at 5, 10, 20, 40, and 80 μg kg−1 with one to three doses of recombinant FVIIa (rFVIIa) at 90 μg kg−1 in the treatment of acute joint bleeds in hemophilia patients with inhibitors. The primary endpoint comprised adverse events; secondary endpoints were evaluations of immunogenicity, pharmacokinetics, and efficacy. Results and Conclusions: Overall, 96 joint bleeds in 51 patients (> 12 years of age) were dosed. Vatreptacog alfa was well tolerated, with a low frequency of adverse events. No immunogenic or thrombotic events related to vatreptacog alfa were reported. A high efficacy rate of vatreptacog alfa in controlling acute joint bleeds was observed; 98% of bleeds were controlled within 9 h of the initial dose in a combined evaluation of 20–80 μg kg−1 vatreptacog alfa. The efficacy rate observed for rFVIIa (90%) is consistent with data from published clinical trials. The trial was not powered to compare efficacy, and further trials are needed to investigate the efficacy of vatreptacog alfa as compared with that of rFVIIa. The trial was registered at ClinicalTrials.gov (Registration Number: NCT00486278).

Red cell phenotyping of blood from donors at the National blood center of Malaysia.

Background: Human blood groups are polymorphic and inherited integral structures of the red cell membrane. More than 300 red cell antigens have been identified and further categorized into 30 major discrete systems. Their distribution varies in different communities and ethnic groups. Aims: This work was set to determine the prevalence of red cell phenotypes in donors from the major ethnic groups in Malaysia, namely, Malays, Chinese, and Indians. Materials and Methods: The work utilized the dextran acrylamide gel technique in which four types of gel cards were used to identify the blood groups of 594 subjects collected at the National Blood Transfusion Centre, Malaysia. Results: Blood group O and CDe/CDe (R1R1) were the most common in all ethnic groups. The cde/cde (rr) was more prevalent amongst Indians. The rare phenotypes found were cDE/cDE(R2R2) and cDE/CDE(R2Rz). With the Lewis system, the distribution of Le(a-b+) was similar among the ethnic groups. The rarest phenotype Fy(a-b-) was discovered in two donors. Jk(a-b-) was found in seven Malays and in two Indians. In the MNSs system, MN was common in Malays and Chinese, while the MM was more common among Indians. The rare SS was found in 19 donors. Malay and Chinese subjects had high P1 Negative blood but Indians showed high P1 positive blood. Within the Kell System, the very rare KK type was found in six subjects. Conclusions: The results obtained serve as an established database for the distribution of red cell phenotypes based on the blood group systems of donors from the major ethnic groups in Malaysia.

Quality indicators for discarding blood in the National Blood Center, Kuala Lumpur

Background and Objective: The implementation of quality system and continuous evaluation of all activities of the Blood Transfusion Services (BTS) can help to achieve the maximum quantity and quality of safe blood. Optimizing blood collection and processing would reduce the rate of discard and improve the efficiency of the BTS. The objective of this study is to determine the rate of discard of blood and blood component and identify its reasons at the National Blood Centre (NBC), Kuala Lumpur, during the year of 2007 in order to introduce appropriate intervention. Study Designs and Methods: Data on the number of discarded whole blood units and its components, reasons for discard, and the number of blood components processed as well as the number of collected blood units were obtained from the Blood Bank Information System - NBC database. These were analyzed. Results: The total number of blood units collected in 2007 was 171169 from which 390636 units of components were prepared. The total number of discarded whole blood units and its components was 8968 (2.3%). Platelet concentrate recorded the highest of discard at 6% (3909) followed by whole blood at 3.7% (647), fresh frozen plasma (FFP) at 2.5% (2839), and cryoprecipitate at 2% (620). The rate of discarded packed red blood cells RBCs, plasma aphaeresis, and PLT aphaeresis was less than 1% at 0.6% (902), 0.6% (37), and 0.29% (14), respectively. RBC contamination of PLT and plasma were the major cause of discard at 40% (3558). Other causes include leakage (26% - 2306), lipemia (25% - 2208), and underweight (4% - 353). Conclusion: Good donor selection, training and evaluation of the staff, as well as implementation of automation will help to improve processes and output of BTS. This would reduce discard of blood components and wastage caused by non conformance.

A retrospective review of cryoprecipitate transfusion practice in Kuala Lumpur Hospital

Background: Cryoprecipitate is generally used to treat bleeding patients with hypofibrinogenemia, and the transfusion decision is guided based on published guidelines. Aim: This study aimed to evaluate the practice appropriateness in accordance to cryoprecipitate transfusion guidelines in Hospital Kuala Lumpur. Methodology: This cross-sectional study of 117 cryoprecipitates transfused adult patients was conducted in Kuala Lumpur Hospital from January to June 2012. The compliance of the indication of cryoprecipitate was considered as appropriate if indicated for patients who have hypofibrinogenemia (<1.0 g/L) with bleeding, or otherwise inappropriate if pretransfusion fibrinogen level was more than 1.0 g/L, pretransfusion fibrinogen level was not examined and posttransfusion fibrinogen level more than 1.5 g/L. Results: Most of the cryoprecipitate prescriptions were found to be inappropriate, which read 81.2% (95% confidence interval = 0.740, 0.880). Patients who underwent neurovascular surgery were the major recipient of cryoprecipitate, but majority of the prescription was found not appropriate. The decision to transfuse cryoprecipitate was found mostly appropriate when was guided by fibrinogen (52.2%), but the percentage dropped to 10.6% when pretransfusion fibrinogen test was not performed. Regrettably, only 19.7% of total cryoprecipitate were given based on pretransfusion fibrinogen level. Conclusion: Although this study showed a high rate of inappropriateness, no reduced therapeutic efficacy, and adverse effect were reported. The trigger threshold needs to be revised before enforcing stringent implementation of practice guidelines for ensuring optimal use of cryoprecipitate.

Molecular basis of Rh blood group system in the Malaysian population

Background: Rh molecular studies have been previously mainly conducted in Caucasians and African population. There is a limited data on the molecular basis for Rh genotypes among Asians. Aims: This study aims to characterize the Rh genes and frequency of the various RH genotypes among blood donors in National Blood Centre (NBC), Kuala Lumpur. Materials and Methods: A total of 1014 blood samples were obtained from blood donors from four different ethnic groups (360 Malays, 434 Chinese, 164 Indians and 56 others). Serological and molecular analysis of all 1014 blood samples were performed. An automated deoxyribonucleic acid sequencing analysis was performed. Results: Rh phenotypes and RH genotypes showed heterogeneity and significant association with ethnicities. Discrepancies in allele D, C/c and E/e between phenotypes and genotypes results were observed. Discrepancy results in allele D showed significant association with the ethnic groups of the blood donors in NBC. There were multiple novel mutations (23) and published mutations (5) found in this study. Significant associations between discrepancy results and mutations were found in allele D and C/c. Conclusion: Performing RH molecular analysis in Malaysian population provided the basic database for the distribution of Rh genotypes of donors from major ethnic groups in Malaysia.

WITHDRAWN: Rh genotypes among Malaysian blood donors.

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RH genotypes among Malaysian blood donors

Abstract Background: RH genotyping studies have been conducted mainly in people of Caucasian and African descent. There is limited information regarding the molecular basis for RH genotypes in Malaysia. Objectives: To investigate the prevalence and characteristics of RHCE genotypes among different ethnic groups in Malaysia. Methods: A total of 1014 whole blood samples were obtained from donors from 4 different ethnic groups (360 Malays, 434 Chinese, 164 Indians, and 56 others). All samples were phenotyped for C, c, D, E, and e using standard serologic methods and genotyped using polymerase chain reaction (PCR)-based analysis. Results: In the blood samples that we analyzed, the distribution of RH genotype antigens was significantly different among the various ethnic groups. Our findings showed that CCDee is the most common in Malaysian blood donors; 18.4% (187/1014) compared with other genotypes. The ccDEE genotype is more prevalent in the Chinese: 65.6% (82/125), and the ccee genotype is more prevalent in Indians: 47.1% (65/138). There were discrepancies between phenotypes and genotypes. There were 17 (1.7%) discrepancies in RH C/c genotyping results and of these 47% (8/17) occurred in Malays. Discrepancies in RH E/e results occurred in 3 samples (0.3%). Conclusions: Our study provides a database for the distribution of RH genotypes of donors from the major ethnic groups in Malaysia. Methods used in this study are useful for comparing the phenotypes and genotypes. Further investigation should be conducted to study the causes of these discrepancies using other molecular based techniques.