Aims: We addressed the question of whether a previously uncharacterized platelet dysfunction contributes to bleeding diathesis in 2B-VWDMPS patients.Methods: We studied the 2 members (mother and daughter) of the MPS kindred with severe bleeding phenotype and addressed this question by coupling quantitative platelet shotgun proteomics and validating biochemical assays, with the systematic analysis of platelet procoagulant membrane dynamics (PMD).Results: Previously, we showed that membrane ballooning, a principal part of the platelet PMD after collagen stimulation, is driven by the influx of Na+ and Cl-, followed by the entry of water.Here, we report in 2B-VWDMPS platelets, loss of the transmembrane chloride channel-1 (CLIC1), and reduced chloride ion influx after collagen stimulation.This was associated with diminished membrane ballooning, phosphatidylserine externalisation and membrane thrombin formation, as well as a distinct phenotypic composition of platelets over fibrillar collagen.Using N-terminomics/ TAILS (terminal amine isotopic labeling of substrates), we compared changes in proteolysis between healthy and 2B-VWDMPS platelets and identified processing differences of von Willebrand factor (VWF), fibronectin (FN1) and Crk-like protein (CRKL).Conclusion(s): 2B-VWDMPS platelets are basally activated, partially degranulated, and have marked loss of regulatory, cytoskeletal, and contractile proteins that may account for structural disorganization, giant platelet formation and the reduction in the haemostatic response.

With 5,050 Egyptians living with hemophilia (2013), the standard of care management is still on-demand with Recombinant activated factor VII (rFVIIa, eptacog alfa activated), the objective of the analysis is to calculate the budget impact of introducing the anti-Inhibitor coagulant complex (FEIBA) to the public sector formulary in Egypt, for the treatment of acute bleeding episodes and for surgery coverage in patients with hemophilia with inhibitors.

Patients and methods: A longitudinal study was carried out in 255 children from 10 centres in nine developing countries over 5 years to assess the musculoskeletal outcome of children on episodic factor replacement. Outcome was documented by assessment of the annual joint bleeding rate (AJBR), WFH clinical and Pettersson radiological joint scores as well as the FISH score for activities. Of the 203 patients for whom data was available at the end of 5 years, 164 who had received only episodic treatment are included in this report. Results: The median age at the beginning of the study was 10 years (IQR 7-12). The median clotting factor concentrate (CFC) usage was 662 IU kg(-1) year(-1) (IQ range: 280-1437). The median AJBR was 10 (IQ range: 5-17). The median AJBR was higher in the older children with the median being 5 for the 5 year old child, while it was 9 for the 10 year old and 11 for children older than 15. Given the episodic nature of the replacement therapy, those with a higher AJBR used significantly greater annual CFC doses (P < 0.001); The median change in WFH clinical score and Pettersson radiological score over the 5 years was 0.4/year for each, while the FISH deteriorated at a rate of 0.2/year with poor correlation of these changes with CFC dose. WFH and FISH scores were significantly worse in those with an AJBR of >3 per year (P = 0.001). The change in the Pettersson score was significantly more in those with an AJBR of >5 per year (P = 0.020). Significant changes in FISH scores were only noted after 10 years of age. Conclusion: Episodic CFC replacement over a large range of doses does not alter the natural course of bleeding in haemophilia or the musculoskeletal deterioration and should not be recommended as a long term option for treatment. Prophylaxis is the only way to preserve musculoskeletal function in haemophilia.

Haemorrhagic disorders like Postpartum haemorrhage and Dengue haemorrhagic fever are life threatening and requires an active and efficient transfusion service that could provide the most appropriate blood product which could be effective in managing them. This would essentially require prompt identification of the coagulopathy so that the best available product can be given to the bleeding patient to correct the identified haemostatic defect which will help control the bleeding. This would only be possible if the transfusion service has a laboratory to correctly detect the haemostatic defect and that too with an accuracy and precision which is ensured by a good laboratory quality assurance practices. These same processes are necessary for the transfusion services to ensure the quality of the blood products manufactured by them and that it contains adequate amounts of haemostasis factors which will be good to be effective in the management of haemorrhagic disorders. These issues are discussed in detail individually in the management of postpartum haemorrhage and Dengue haemorrhagic fever including when these can help in the use of rFVIIa in Dengue haemorrhagic fever. The requirements to ensure good-quality blood products are made available for the management of these disorders and the same have also been described.

Summaryvon Willebrand disease (VWD) is frequently ignored as a cause of menorrhagia. We investigated Egyptian women complaining of heavy menstrual bleeding (HMB) and/or other bleeding symptoms to detect potential VWD cases. Seventy‐five female patients complaining of HMB and/or bleeding symptoms and 38 age‐matched healthy female controls went through a family history questionnaire, a physical examination and were evaluated for bleeding score, pictorial blood assessment chart (PBAC), complete blood count, serum ferritin, blood group, prothrombin time, activated partial thromboplastin time, factor VIII (FVIII) activity, von Willebrand factor (VWF) ristocetin cofactor (RCo) activity, antigen (Ag), and RCo/Ag ratio. Sixty‐eight of 75 patients presented with HMB, out of which 46 had no organic pathology and 7 presented other bleeding symptoms. Six patients were diagnosed with VWD, three with HMB, two with other bleeding symptoms and one with family history of VWD. Two related VWD patients were diagnosed in the control group. There were significant differences in bleeding and PBAC scores, ferritin level, FVIII activity, VWF:RCo and VWF:Ag between VWD patients and controls. This study indicated a high prevalence of VWD among patients with HMB without organic pathology (6.5%) and demonstrated the sensitivity of diagnostic parameters of VWD patients in an outreach campaign. The inexpensive bleeding and PBAC scoring systems are valuable to exclude cases without objective bleeding symptoms. Raising gynaecologists awareness about hereditary bleeding disorders is important to ensure a proper diagnosis and possible referral of these patients. Management of these patients with comprehensive medical care services under a multidisciplinary team would be ideal.

Background and Objectives  A minipool solvent/detergent (S/D; 1% TnBP/1% Triton X‐45; 31°C) process was developed for viral inactivation of plasma and cryoprecipitate used for transfusion. The goal of this study was to determine the rate and extent of inactivation of dengue virus (DENV) during this process.

BACKGROUND AND OBJECTIVES:Foetal and neonatal alloimmune thrombocytopenia (FNAIT) is studied mainly in Caucasian populations. Severe thrombocytopenia (<50×10(9)/L) gives risk of haemorrhage and the most feared complication is intracranial haemorrhage (ICH). In Caucasian populations anti-human platelet antigen (HPA)-1a antibodies are the cause of FNAIT in >80% of the cases. The aims of this project were to study the gene frequencies of HPA-1-5 and 15 alleles in an Egyptian population (Arabic), and to determine the frequency of HPA-1a and -5b immunisations in a cohort of Egyptian pregnant women. MATERIALS AND METHODS:Altogether 6974 pregnant women were included in the study. Genotyping was performed by polymerase chain reaction and antibodies were detected by flow cytometry and enzyme-linked immunosorbent assay. HPA-1-5 and 15 alleles were studied in 367 individuals. RESULTS:The HPA genotypes differed from genotypes published from different Caucasian and Chinese (Han) populations in HPA-1, -2, -3, and -5 systems with significant higher frequency of HPA-1b, -2b and -5b. The rate of HPA-1a alloimmunisation was found comparable to Caucasian populations. Severe thrombocytopenia was found in two newborns. No bleeding complication was reported. Anti-HPA-5b antibodies were detected in 4.4% of the pregnant women. Clinical consequences of these antibodies were not studied. CONCLUSION:The HPA-1bb and -5bb genotypes are more frequent in the Egyptian Arabic population studied compared to Caucasian populations. FNAIT due to anti-HPA-1a and -5b antibodies must be suspected in cases of neonatal thrombocytopenia. Further large prospective studies are needed to increase the knowledge of clinical complications related to HPA alloantibodies in populations with different genetic backgrounds.

Summary. Eighteen cryoprecipitate minipools, each made of 30 units of low volume, concentrated cryoprecipitate, have been treated by solvent‐detergent and filtration (S/D‐F) in a single‐use CE‐marked bag system. The S/D‐F cryoprecipitate contained a mean of 10.5 IU mL−1 factor VIII (FVIII), 17 mg mL−1 clottable fibrinogen, and >10 IU mL−1 von Willebrand factor ristocetin co‐factor, and anti‐A and anti‐B isoagglutinins were undetectable. The products have been infused in 11 severe (FVIII <1%) haemophilia A patients (mean age: 17.4 years; mean weight: 57.6 kg) at a dose close to 40 IU kg−1. Patients were hospitalized for at least 36 h to determine FVIII recovery, half‐life and clearance. They were also closely monitored for possible adverse events. None of the infused patients demonstrated reactions or adverse events even though they did not receive anti‐allergic drugs or corticosteroids prior to infusion. The mean recovery of FVIII 10 min postinfusion was 69.7%. Mean FVIII half‐life was 14.2 h and clearance was 2.6 mL h−1 kg−1. All patients had a bleeding‐free interval of 8–10 days postS/D‐F cryoprecipitate infusion. The data show that S/D‐F cryoprecipitate FVIII presents a normal pharmacokinetics profile, and support that it could be safely used for the control of acute and chronic bleeding episodes in haemophilia A patients.