Genetic Alterations, DNA Methylation, Alloantibodies and Phenotypic Heterogeneity in Type III von Willebrand Disease.

Type III von Willebrand disease is present in the Punjab province of Pakistan along with other inherited bleeding disorders like hemophilia. Cousin marriages are very common in Pakistan so genetic studies help to establish protocols for screening, especially at the antenatal level. Factors behind the phenotypic variation of the severity of bleeding in type III vWD are largely unknown. The study was conducted to determine Mutations/genetic alterations in type III von Willebrand disease and also to determine the association of different mutations, methylation status, ITGA2B/B3 mutations and alloimmunization with the severity of type III vWD. After informed consent and detailed history of the patients, routine tests and DNA extraction from blood, mutational analysis was performed by Next Generation Sequencing on Ion Torrent PGM. DNA methylation status was also checked with the help of PCR. In our cohort, 55 cases were detected with pathogenic mutations. A total of 27 different mutations were identified in 55 solved cases; 16 (59.2%) were novel. The mean bleeding score in truncating mutations and essential splice site mutations was relatively higher than weak and strong missense mutations. The mean bleeding score showed insignificant variation for different DNA methylation statuses of the VWF gene at the cg23551979 CpG site. Mutations in exons 7,10, 25, 28, 31, 43, and intron 41 splice site account for 75% of the mutations.

Wastage of Blood Units at Tertiary Care Hospitals of Lahore.

INTRODUCTION:  Blood and its products are the most valuable resource in every healthcare institution. Judicial use of these limited resources is necessary and important to maintain sufficient supply. Blood products and its transfusion system are being evaluated by the use of several markers. The use of crossmatch to transfusion ratio (C/T) was first proposed by Boral Henry in 1975. Nowadays, the C/T ratio is being used by researchers to assess transfusion practices. Ideally, (C/T) ratio has to be 1.0 but it has been suggested that a ratio of 2.5 or less would indicate effective blood use. OBJECTIVE: To assess crossmatch to transfusion ratio (C/T ratio), transfusion probability (%T), and transfusion index (TI) in patients of medical and surgical wards. To assess the wastage of blood components/whole blood units. METHODS:  A cross-sectional study was conducted at Mayo Hospital/King Edward Medical University, Lahore, Services Hospital Lahore, and Alkhidmat Blood Bank Surrayya Azeem Hospital between January 2019 and June 2019. Nonprobability convenient sampling was performed and all collected data were entered and analyzed by using statistical package for social sciences (SPSS version 20). RESULTS:  The total patients who were ordered to arrange blood were 1322 for which overall 2715 crossmatches had been done. Among these crossmatches, a total of 1536 of the donors were bled for from which only 815 units had been transfused to the patients. Overall C/T ratio was found to be 3.33 and the overall wastage was 38.9%. CONCLUSIONS:  Blood transfusion is considered useful in the management of surgical as well as medical patients. Too many units are ordered out of which the majority are wasted due to nonutilization. There is a need for standard operating procedures for transfusion of blood. There shall be regular audits to improve the blood collection, treatment, delivery, and usage practices of this scarce resource.