Congenital fibrinogen disorders: a retrospective clinical and genetic analysis of the Prospective Rare Bleeding Disorders Database.

ABSTRACT: Congenital fibrinogen deficiency (CFD) is a rare bleeding disorder caused by mutations in FGA, FGB, and FGG. We sought to comprehensively characterize patients with CFD using PRO-RBDD (Prospective Rare Bleeding Disorders Database). Clinical phenotypes, laboratory, and genetic features were investigated using retrospective data from the PRO-RBDD. Patients were classified from asymptomatic to grade 3 based on their bleeding severity. In addition, FGA, FGB, and FGG were sequenced to find causative variants. A total of 166 CFD cases from 16 countries were included, of whom 123 (30 afibrinogenemia, 33 hypofibrinogenemia, 55 dysfibrinogenemia, and 5 hypodysfibrinogenemia) were well characterized. Considering the previously established factor activity and antigen level thresholds, bleeding severity was correctly identified in 58% of the cases. The rates of thrombotic events among afibrinogenemic and hypofibrinogenemic patients were relatively similar (11% and 10%, respectively) and surprisingly higher than in dysfibrinogenemic cases. The rate of spontaneous abortions among 68 pregnancies was 31%, including 86% in dysfibrinogenemic women and 14% with hypofibrinogenemia. Eighty-six patients received treatment (69 on-demand and/or 17 on prophylaxis), with fibrinogen concentrates being the most frequently used product. Genetic analysis was available for 91 cases and 41 distinct variants were identified. Hotspot variants (FGG, p.Arg301Cys/His and FGA, p.Arg35Cys/His) were present in 51% of dysfibrinogenemia. Obstetric complications were commonly observed in dysfibrinogenemia. This large multicenter study provided a comprehensive insight into the clinical, laboratory, and genetic history of patients with CFDs. We conclude that bleeding severity grades were in agreement with the established factor activity threshold in nearly half of the cases with quantitative defects.

Emicizumab Prophylaxis in Patients with Severe Hemophilia A: Insights from A Resource Limited Country.

METHODS: In this prospective study, severe HA patients were recruited from January 2022 to June 2023. Inhibitor positive and inhibitor negative patients with annual bleeding rate (ABR) 8 or greater and past histories of bleeding like intra-cranial, intra-abdominal, and pseudo-tumors were included. Emicizumab loading dose was 3 mg/kg in the first 4 weeks, and the maintenance dose was started at week 5 at 6 mg/kg/month. Patients' detailed bleeding history and demographics were recorded. The five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) was used to evaluate patients' HRQoL. Furthermore, Hemophilia Joint Health Score (HJHS) and Functional Independence score in Hemophilia (FISH) were applied for the assessment of joints at different time points. Results were analyzed by SPSS version 21. RESULTS: A total of 36 HA male patients with the mean age of 19.7 ± 14.42 years were recruited in the study; among them, 19 patients were inhibitor positive, while 17 were negative. Patients clinically presented with bleeding symptoms which included: hemarthrosis 95%, GI bleeding 13.8%, and bruises and gums bleeding 13.8%. Significant reduction was observed in the bleeding episodes after the therapeutic intervention, and joints assessment and Euro-Quality-of-life Visual Analog Scale showed a significant improvement in health after treatment. Similarly, there was a remarkable reduction in bleeding episodes and improved quality of life among HA patients. The ABR decreased from 53.6% episodes per year prior to treatment to 2.4% during Emicizumab therapy. Prior to initiating Emicizumab therapy, participants exhibited an average FISH score of 16 and HJHS score of 10, indicating moderate limitations due to joint-related issues. After treatment, the mean FISH score improved to 9 and HJHS score to 4 reflecting a substantial enhancement in participants' ability to perform daily activities (P < 0.057). CONCLUSION: Our results showed that HA patients on prophylactic treatment with Emicizumab were less restricted and had improved quality of life due to marked decrease in bleeding episodes which resulted in improved health and social lives. In addition, it was well tolerated, and no participant discontinued treatment because of adverse events.

The Impact of ABO Incompatibility on the Outcomes of Hematopoietic Stem Cell Transplantation: A Single-Center Study From Pakistan.

Background and objective Allogeneic hematopoietic stem cell transplantation (alloHSCT) provides curative treatment for several hematological illnesses. In this study, we evaluated the impact of ABO compatibility and incompatibility on outcomes and complications related to hematopoietic stem cell transplantation (HSCT) performed for various hematological disorders at our center. Methodology This was a retrospective, single-center, cohort study in which patients were categorized according to the ABO match and mismatch status. The mismatch group was further subcategorized into major, minor, and bidirectional groups. Results A total of 117 patients underwent alloHSCT, out of which 82 (70.1%) were male and 35 (30%) were female. The median age of the patients was 9.5 years (range: 46 years). The most common indications for stem cell transplant were beta-thalassemia major (BTM; n=58, 49%) and aplastic anemia (AA; n=42, 35.8%). However, the outcomes in match and mismatch groups showed significant results for positive direct Coombs test (DCT), indicating the occurrence of hemolysis. Despite the increased need for blood transfusions, ABO blood group incompatibility (ABOi) had no negative impact on the clinical results. Conclusion Based on our findings, ABO incompatibility does not affect the outcomes in patients undergoing alloHSCT. Patient monitoring can aid in early detection and treatment, thereby minimizing the frequency of fatal events.

Correlation Between Serum Ferritin and Degree of Hepatic Fibrosis on Fibroscan in Thalassemic Patients.

Aim and objective This study aimed to examine the relationship between serum ferritin levels and the degree of hepatic fibrosis as detected on Fibroscan in thalassemia patients. Materials and methods This was a single-center and cross-sectional study conducted from April 2021 to December 2022. The sample population comprised 55 beta-thalassemia patients receiving treatment at the National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan. The data was compiled through a series of patient interviews, an examination of medical records and was analyzed to obtain the results. Descriptive statistics were used for several variables, including diagnosis, Fibroscan score, blood group, comorbidity, visceromegaly, consanguinity, serum glutamate pyruvate transaminase (SGPT), viral markers, and C reactive protein (CRP). The correlation analysis was done using Spearman's correlation test. Results There were 55 participants in the study, 40 of whom were male and 15 of whom were female. The mean age of the patients was eight years, while the average age at diagnosis was nine months with a transfusion frequency of every 20 days. Spearman's rho (r = 0.287), and the significant value of (p = 0.033) confirmed a statistically significant positive correlation between serum ferritin levels and hepatic fibrosis. On Fibroscan, 74.5% of patients had F0-F1 stage fibrosis followed by 14.5% of the patients having F2 stage fibrosis. HCV seropositivity was the most prevalent comorbidity among the patients. 80% of patients had serum ferritin levels greater than 1000 ug/mL. Hepatosplenomegaly was present in 43.6% of the patients. 78.2% of patients were born out of consanguineous marriages. Conclusion In conclusion, this study found a statistically significant positive correlation between serum ferritin levels and hepatic fibrosis in beta-thalassemia patients. The study emphasizes the significance of monitoring serum ferritin levels in thalassemia patients to prevent hepatic fibrosis.

Management of Severe Hemophilia A: Low-Dose Prophylaxis vs. On-Demand Treatment.

INTRODUCTION: Prophylactic clotting factor infusion regimens to prevent bleeding and joint deformity has become the standard of care in severe hemophilia A patients. AIM: To assess low-dose factor prophylaxis in our population as an alternative approach to managing severe hemophilia A. METHODS: A prospective cohort study that included 68 hemophilia A patients divided into two groups, i.e., Prophylaxis and on-demand. The two groups were compared for annualized bleeding rate (ABR), hospitalization, units of factor VIII (FVIII) infused, or plasma products transfused, i.e., fresh frozen plasma (FFP) and cryoprecipitate (CP), and development of FVIII inhibitors. RESULTS: Of the 68 patients recruited in this study, 25 (36.7%) were in the prophylaxis group, and 43(63.3%) were in the on-demand group. The on-demand group presented a higher median-IQR ABR [8(20-3) vs. 5(10-1.5), p-value 0.024], several hospitalizations (39.7% vs. 0, p-value 0.001), and inhibitor development (9.3% vs. 0, p-value 0.289) compared to the prophylaxis group. The prophylaxis approach demonstrated a significant negative correlation of ABR with FVIII prophylaxis (r=-0484, p=value=0.014). Moreover, no hospitalizations or inhibitor development was observed in the prophylaxis group. The estimated annual consumption of FVIII was 328 IU/kg/year in the on-demand group and 1662.6 IU/kg/year in the prophylaxis group. However, a highly significant difference in plasma product utilization was observed between the two groups, i.e., p-value <0.001 and 0.038 for FFP and CP, respectively. CONCLUSION: Low-dose factor prophylaxis resulted in improved outcomes compared to on-demand treatment in terms of ABR, joint bleeding, hospitalization, and the development of inhibitors. This treatment approach should be adopted as an economically feasible alternative to high-dose Prophylaxis in resource-constrained countries.

Assessment of Hepatic Profile in Acquired Aplastic Anemia: An Experience From Pakistan.

INTRODUCTION:  Aplastic anemia (AA) is characterized by pancytopenia and hypocellular marrow in the absence of an abnormal infiltrate or increase in reticulin fibrosis. The diagnosis of AA is challenging at times due to decreased cellularity and overlapping morphological features with other bone marrow failure syndromes. Hepatitis-associated aplastic anemia (HAAA) is a rare variant in which patients typically present with jaundice and hepatitis followed by pancytopenia almost within 6 months. Post-hepatitis AA accounts for approximately 1-5% of cases, and invariably such cases are negative for the known hepatitis virus as well. There is limited literature available to understand the correlation of AA with hepatitis with none reported at the national level in our region. As AA is relatively more prevalent in Southeast Asia as compared to the western world and hepatitis is a prevalent disease in our population, the main purpose of this study was to assess the hepatic profile and determine the association of hepatitis in AA at the time of diagnosis. MATERIALS AND METHODS:  A cross-sectional study was carried out at the National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, from November 2019 to December 2020 after the informed consent from patients. The study included all treatment-naïve patients of acquired AA with no prior history of taking steroids, immunosuppressive treatment, or chemoradiation therapy. Liver function tests, complete blood count, prothrombin time (PT), and activated partial thromboplastin time were performed, along with viral profiles (HAV, Hep B, Hep C, and HIV). SPSS version 23 (IBM Corp., Armonk, NY) was used for statistical analysis. Mean and standard deviations were computed for quantitative variables while percentages and frequencies were reported for qualitative variables. T-test was used to observe the main difference between groups and a p-value <0.05 was considered to be significant. RESULTS:  Out of a total of 351 patients, 29 (8.2%) patients with AA tested positive for viral hepatitis. Hepatitis A was the most prevalent hepatitis (4.0%), followed by hepatitis C (3.7%). The comparison of platelet counts in patients with and without hepatitis was reported to be of statistical significance (p-value < 0.05). A significant statistical difference (p-value < 0.0001) was found in platelet count and PT in patients of AA with and without hepatitis. CONCLUSION:  Overall, this study revealed that <10% of patients of AA had a positive screening for hepatitis A, B, and C and low platelet count, and PT was statistically significant when compared between the patients with and without hepatitis. Hepatitis being prevalent in our part of the world might have an important causal association with AA. Patients with AA should be screened for liver functions and viral hepatitis at the time of diagnosis. In addition to hepatitis A, B, and C and HIV, other causes of hepatitis should also be screened such as parvovirus B19, human herpes virus 16, and adenovirus which are not included in routine diagnostic viral testing panel.

Frequency of Intron 22 Inversion in Severe Hemophilia A Patients.

OBJECTIVE: The aim of our study was to find the frequency of Intron 22 inversion (Inv22) in severe hemophilia A (HA) patients and to evaluate the association between Inv22 and FVIII inhibitor formation. METHOD: Data analysis was carried out on IBM SPSS Statistics Version 23.00 (IBM Corp, Armonk, NY). Descriptive statistics were applied to measure the frequencies, percentages, and mean ± SD of the clinical and general history of HA patients, including age, family history, inhibitor status, intron22 inversion, and FVIII levels. Chi-square was applied to evaluate the association between Inv22 and F8 inhibitor formation. RESULTS: A total of 62 HA patients were enrolled in the study with mean±SD age of (14.39±13.2) years. A family history of HA was observed in 36 (58.1%) patients. Out of 62 patients, 28(45.2%) were reported as Inv22 positive while inhibitor status was observed as positive in three (4.83%) patients. However, an insignificant association was observed between the inhibitor and Inv22 positive patients with a p-value=0.443. CONCLUSION: In our study, Inv22 was found to be the major cause of severe HA in our patients, i.e., 45.1%. However, no significant relation was computed between Inv22 and inhibitor formation.

The Outcome of Hodgkin Lymphoma With Reference to Prognostic Markers.

OBJECTIVES: This study aimed to determine the impact of prognostic markers on the outcomes of Hodgkin lymphoma. METHODS: It is a cross-sectional, single-center study. A total of 60 patients diagnosed with Hodgkin lymphoma were recruited for the study over five years between 2016 to 2020. The study setting was the National Institute of Blood and Bone Marrow Transplant in Pakistan. The Statistical Package for Social Sciences (SPSS) version 23 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. RESULTS: In the study population, 63.3% of the patients were male (38/60), and 36.7% were female (22/60). Hodgkin lymphoma was divided into four stages: stage I (18.3%), stage II (18.3%), stage III (46.7%), and stage IV (16.7%). Patients in stage III had a higher value of hemoglobin (Hb) than in other stages of the disease. The erythrocyte sedimentation rate was high in 56.7% of stage III patients than in patients of the other stages. The lactate dehydrogenase (LDH) levels were not under the normal range in 51.6% of patients. Only 20% of patients in stage III had LDH values within the normal range, whereas 26.6% did not. CONCLUSION: There was a significant impact of prognostic factors on the survival of patients with Hodgkin lymphoma.

Frequency of Extended Red Cell Antigen Phenotype Among Patients of Hematological Diseases: A Single Center Study.

Background Alloimmunization of erythrocytes is a major problem in patients with hematological diseases that require frequent blood transfusions. Matching of extended red cell antigens of Kell, MNS, Kidd, and Duffy can decrease the risk of alloimmunization. Hence, in this study, the frequencies of the extended red cell phenotypes were explored. Objective To find out the frequency of extended red blood cell antigen phenotypes among patients with hematological diseases. Methods This cross-sectional research study was performed on 488 patients diagnosed with hematological diseases who required blood transfusion at the National Institute of Blood Disease and Bone Marrow Transplantation Karachi for a period of 1.42 years from November 2019 to March 2021. The blood of patients was analyzed for antigen phenotypes of different blood group systems including Kell, MNS, Kidd, and Duffy. The data obtained were interpreted. Results Among the 488 patients, 284 (58.20%) patients were male, and 204 (41.80%) patients were female with a mean age of 8.1 years. Beta thalassemia was the most common hematological disease reported in 354 (72.5%) of the patients. The most common blood group was O positive reported in 182 (37.3%) of the patients followed by B positive blood group in 124 (25.4%). The frequencies of extended red cell antigen phenotypes in the patients were K antigen 14 (2.9%), Kpa antigen 26 (5.3%), Kpb antigen 424 (86.9%), Fya antigen 360 (73.8%), Fyb antigen 260 (53.3%), Jka antigen 294 (60.2%), Jkb antigen 326 (66.8%), M antigen 410 (84.0%) and N antigen 306 (62.7%). Conclusion Beta thalassemia was the most common hematological disease followed by iron deficiency anemia, aplastic anemia, and acute leukemia. Patients with hematological diseases had a higher prevalence of Kpb antigen followed by M, Fya, Jkb, N, Jka, Fyb, Kpa, and K antigen. O positive was the most frequent blood group followed by B positive, A positive and AB positive blood group.

Frequency of Hepatitis B, C, and Human Immunodeficiency Virus in Blood Donors.

INTRODUCTION: Blood donation is considered an important source of infection transmitted through transfusion, especially in developing countries like Pakistan. OBJECTIVE: To find out the frequency of seroprevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) among blood donors in the blood bank. METHODS: A prospective cohort study was carried out on blood donors at the National Institute of Blood Disease and Bone Marrow Transplant, Karachi, during the period of January 1, 2019 to December 31, 2020. The descriptive statistical analysis to find out the percentages and frequencies was implemented using SPSS version 23 (IBM Corp., Armonk, NY). RESULTS: During the study duration, a total of 23,656 blood donors visited and donated blood, including 12,234 blood donors in the year 2019 and 11,422 blood donors in the year 2020. According to the analysis, only 1.4% of patients with HBV, 1.5% with HCV, and 0.03% were seropositive in the year 2020. In 2019, 1.6% HBV, 2.07% HCV, and 0.09% HIV blood donors were seropositive with a significant 0.00 p-value. CONCLUSION: It is concluded that hepatitis C is the most commonly occurring in donors compared to HBV and HIV. HBV vaccines are available in Pakistan, which is why cases are fewer than HCV.

Frequency of Specific and Non-specific Inhibitors in Haemophilia A Patients.

OBJECTIVE: To determine the frequency of specific and non-specific inhibitors in haemophilia A patients. STUDY DESIGN: This is a cross-sectional study. PATIENTS AND METHODS: A total of 150 male haemophilia A patients were included in this cross-sectional study at the National Institute of Blood Diseases and Bone Marrow Transplant (NIBD), Karachi, Pakistan, from September 2019 to January 2022. RESULTS: Among 150 patients included in this study, 23 (15.3%) had an inhibitor and 127 (84.6%) did not. All patients had specific inhibitors against Factor VIII (FVIII). Non-specific inhibitors were not identified in our population. Among the patients in the inhibitor group, there were 13 (56.5%) in the severe (<1%) category. There were 10 (43.5%) patients in the moderate (1-5%) category. There were no patients in the mild category. The median inhibitor level was 15.4 Bethesda unit (BU). CONCLUSION: The development of inhibitors has not been identified as a major problem in our population. However, it is noteworthy that only 15.3% of patients with haemophilia A developed inhibitors in this data set. They were essentially treated with plasma and its products.

Coagulation Abnormalities and Risk Assessment in Acute Promyelocytic Leukemia: An Experience From a Resource-Constraint Country.

Introduction The objective of the study was to assess the impact of coagulopathy in risk-stratified acute promyelocytic leukemia (APML) patients irrespective of bleeding manifestation. Patients and methods This was a cross-sectional study design conducted at the National Institute of Blood Diseases and Bone Marrow Transplantation (NIBD & BMT) from November 2019 to December 2021. A total of 62 patients between three years to 74 years of age of either gender and treatment-naive cases of APML were included in the study. Morphological diagnosis was made on bone marrow samples, and confirmation was done by karyotyping/fluorescence in situ hybridization (FISH) and/or polymerase chain reaction (PCR). Complete blood count (CBC), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, and fibrinogen levels were done for bleeding risk assessment. Cases other than APML and cases on treatment were excluded from the study. Results A total of 85 APML patients were registered at our institute. Among them, 62 (73%) were included in the analysis as per the inclusion criteria of the study. The median age was 32 (3-74) years, with a male predominance of 34 (55%). According to the Sanz score, 18 (29%) patients were noted to have low risk; however, 22 (35.4%) patients were found to have an intermediate-risk disease and 22 (35.4%) patients had high-risk disease. There was positive bleeding history among 44 (71%) patients, followed by fever in 28 (45%) patients. Raised PT, APTT, and D-dimer were found in 46 (74%), 38 (61%), and 52(83.8%) patients, respectively. Low fibrinogen levels were observed among 16 (26%) patients. The association of risk stratification and bleeding history with CBC and coagulation parameters was observed. Platelet count and total leucocyte count were noted to be significantly associated with risk stratification. However, there was no association observed between the rest of the parameters with risk stratification and bleeding. Conclusion The results of our study suggest that regardless of bleeding symptoms, coagulation parameters must be investigated at the time of diagnosis in patients with suspected APML, and in addition to all-trans-retinoic acid (ATRA), transfusion of fresh frozen plasma should be done. It has clinical value, and adding it to the algorithm of treatment would be beneficial to the patients in the developing world, where resources are already meager.

The Frequency of Rh Phenotype and Its Probable Genotype.

AIMS AND OBJECTIVES: Our goal is to disseminate data on the distribution pattern of Rh antigen, its phenotypes, and the likely genotypes of these genetic variants in the Pakistani population. METHODOLOGY: This study was a cross-sectional research project. Patients' demographic statistics, such as age and gender, were gathered from their medical information. Blood group, disease, RhD, and other antigen frequency, phenotype, and probable genotype were considered variables. All blood samples were phenotyped for Rhesus antigens (D, C, c, E, and e), and the test was carried out using the tubing technique. RESULTS: According to gender distribution, most of the patients were males, with 131 frequencies (57.7%), while females had 42.35%. The most common phenotype was DCCee, with its probable genotype DCe/DCe (R1 R1) (34%), followed by DCcee, with probable genotype DCe/ce (R1 r) (29.1%); the least common phenotype was ddCcee, with its probable genotype Ce/ce (r ' r) (0.4%). CONCLUSION: It is concluded that the DCCee phenotype was the most common with its probable genotype DCe/DCe, while the least common phenotype was ddCcee with its probable genotype Ce/ce.

Thrombocytopenia in Pregnancy: Identification and Management at a Reference Center in Pakistan.

OBJECTIVE: The study aimed to evaluate the causes of thrombocytopenia in pregnancy and its management along with the outcome in the COVID-19 era. METHODS: Recruitment for this prospective, cross-sectional observational study of thrombocytopenia in pregnancy (platelet counts <100x109/L) was done from January 2017 to August 2020 at the National Institute of Blood Diseases (NIBD) after taking the patients' informed consent. Complete clinical and lab profile of patients was also collected. RESULTS: A total of 150 pregnant women with thrombocytopenia were enrolled, with the mean age being 27.3±4.64 years. Mean platelet counts at baseline were 48.0±24. Main clinical manifestations at baseline included: anemia 65.9%, bruises 23.25%, and edema 9.3%. Causes of thrombocytopenia were gestational thrombocytopenia (GT) 72 (48%), acute fatty liver five (3.3%), pre-eclampsia in 11 (7.3%), and eclampsia seven (4.6%). Causes not specific to pregnancy included 30 (20%) cases of ITP, hepatitis C, and nutritional deficiency was reported in nine (6%) patients each. 72/150 received supportive care treatment to manage thrombocytopenia and were closely monitored and given supplements. Twenty (66.6%) ITP patients received treatment with steroids, with complete response in 70% of them seen. Overall, 38 (25.3%) women with bleeding symptoms and platelet count <50x109/L received platelet transfusions. CONCLUSION: The study shows that pre-eclampsia and eclampsia are serious conditions with a high risk for complications, while GT is a benign and the most common cause of thrombocytopenia in pregnancy which requires no active treatment. The other causes such as ITP and infections require individualized management.

Blood Ordering and Transfusion Practices: An Insight Toward Better Utility of Blood Products.

Background An adequate supply of quality blood products is the backbone of any hospital. To maintain it, the utilization and wastage of the products should be closely monitored. Objective To determine the crossmatch to transfusion (C/T) ratio, transfusion probability (%T), and transfusion index (Ti) of packed red blood cells and to review the use of platelets. Materials and methods A total of 6,326 hematological patients receiving packed red blood cells were included in the study. The random donor platelets that were prepared during this period were also included to know the actual utilization of platelets. Results A total of 26,146 crossmatches were requested for these 6,326 patients in three years. Out of these, 26,024 units were issued and transfused to the patients. The CT ratio of our data was calculated to be 1.00, the transfusion probability was found to be 98.1%, and the transfusion index was computed to be 0.99. For random donor platelets, 37,162 were prepared from whole blood during this period, while 30,971 platelets were transfused to the patients. Conclusion The overall results of our analysis showed proper utilization of blood products at our institution. The wastage was considered to be minimal.

Quality of life in a large multinational haemophilia B cohort (The B-Natural study) - Unmet needs remain.

INTRODUCTION: The B-Natural study is a multicentre, multinational, observational study of haemophilia B (HB) designed to increase understanding of clinical manifestations, treatment and quality of life (QoL). AIM: To characterise and compare QoL in HB across disease severity groups and individuals with inhibitors to identify gaps in treatment. METHODS: A total of 224 individuals from 107 families were enrolled from a total of 24 centres in North America (n = 16), Europe (n = 7) and Asia (n = 1). Of these, 68 (30.4%) subjects had severe (<1 IU/dL), median age 15.6 years, 114 (50.9%) moderate (1-5 IU/dL), age 13.3 years, and 42 (18.8%) mild (>5-< 40 IU/dL), age 12.1 years, disease. Twenty-nine participants had inhibitors or a history of inhibitors. Three versions of the EQ-5D instrument were used as a measure of QoL: proxy (ages 4-7), youth (ages 8-15) and self (age 16+). Each instrument included a visual analogue scale ranging from 100 (best health) to 0 (worst health) to assess current day's health (EQ VAS). Range-of-motion (ROM) for elbows, knees and ankles was assessed using a four-point scale, from which a composite score was calculated. RESULTS: In all severity groups, a proportion of subjects showed less than optimal QoL. The majority of the mild and moderate severe participants reported a normal EQ-5D health profile (79% and 72%, respectively), whereas about half (47%) of the severe participants and only 13% of the inhibitor participants reported this profile. CONCLUSION: The B-Natural study reveals impacted QoL in all disease severities of HB including those with inhibitors. Unmet needs remain and include nonsevere HB.

The ISTH bleeding assessment tool as predictor of bleeding events in inherited platelet disorders: Communication from the ISTH SSC Subcommittee on Platelet Physiology.

BACKGROUND: The ISTH Bleeding Assessment Tool (ISTH-BAT) has been validated for clinical screening of suspected von Willebrand disease (VWD) and for bleeding prediction. Recently it has been validated for subjects with inherited platelet disorders (IPD) (BAT-VAL study). OBJECTIVES: To determine whether the ISTH-BAT bleeding score (BS) predicts subsequent bleeding events requiring treatment in IPD patients. METHODS: Patients with IPD, type 1 VWD (VWD-1) and age- and sex-matched healthy controls enrolled in the BAT-VAL study were prospectively followed-up for 2 years and bleeding episodes requiring treatment were recorded. RESULTS: Of the 1098 subjects initially enrolled, 955 were followed-up and 124 suffered hemorrhages during follow-up, 60% of whom had inherited platelet function disorders (IPFD). Total number of events was significantly higher in IPFD (n = 235) than VWD-1 (n = 52) or inherited thrombocytopenia (IT; n = 20). Events requiring transfusions were 66% in IPFD, 5.7% in VWD-1, and 3% in IT. Baseline BS was significantly higher in IPFD patients with a bleeding event at follow-up than in those without (p < .01) and the percentage of subjects suffering a bleeding event increased proportionally to baseline BS quartile. A significant association between the BS and the chance of suffering severe bleeding was found in the overall, IPFD, and VWD-1 populations. Similar results were obtained for the pediatric population. CONCLUSIONS: Inherited platelet function disorder patients with high BS at enrollment are more likely to suffer from bleeding events requiring treatment at follow-up. Moreover, the higher the baseline BS quartile the greater the incidence of subsequent events, suggesting that independently from diagnosis a high BS is associated with a greater risk of subsequent hemorrhage.

Utilisation of blood products at a centre in Pakistan. Is donating better than wasting?

The study was designed to investigate the quantity and reasons of wastage of blood products. This was an observational study conducted from February 2018 to February 2019 at the National Institute of Blood Disease and Bone Marrow Transplantation (NIBD and BMT), PECHS campus. The study was approved by the institutional review board. Wastage and reasons of wastage for all the blood products were evaluated. Frequencies were calculated by using SPSS version 23.0. A total of 2,880 bags of blood products were available, including 960 each of platelets, packed red cells and fresh frozen plasma. The overall wastage rate was 3.5%. Packed red cells and platelets were fully consumed, yet shortage of supply was observed. However, highest wastage was observed in fresh frozen plasma i.e. 102 bags. Expiry of unused products 60 (59%) followed by broken bags 30 (29%) were two common modes of wastage. Wastage of blood products is a genuine issue in a hospital setup, strategies and plan of action should be discussed and implemented to ensure that they are available when and where they are needed most.

Natural history study of factor IX deficiency with focus on treatment and complications (B-Natural).

INTRODUCTION: Haemophilia B (HB) is less well studied than haemophilia A (HA); despite similarities between the two inherited bleeding disorders, important differences remain that require further research. AIM: B-Natural is a multi-centre, prospective, observational study of HB, designed to increase understanding of clinical manifestations, treatment, quality-of-life (QoL), inhibitor development, immune tolerance induction (ITI) outcome, renal function and create a biorepository for future investigations. METHODS: Participants include sibling pairs/groups without a current/history of inhibitors and singletons or siblings with a current/history of inhibitors followed for six months. Demographics, medical, social history and treatment were recorded. A physical examination including joint range of motion (ROM) was performed; QoL was assessed. Samples were collected for F9 gene mutation, HLA typing, non-inhibitory antibodies and renal function testing. RESULTS: Twenty-four centres enrolled 224 individuals from 107 families including 29 with current/history of inhibitors. Of these, 68, 30.4%, had severe (<1% FIX level of normal); 114, 50.9%, moderate (1%-5%); and 42, 18.8%, mild (>5-<40%) disease. At enrolment, 53.1% had 50 + exposure days to exogenous FIX. Comparison of joint scores showed significant (P < .05) differences between those with severe (with/without inhibitors), and those with moderate/mild disease. The majority with severe disease, 80.0% with current/history of inhibitors and 64.3% of those without, were treated with prophylaxis. CONCLUSION: B-Natural provides data supporting an increased understanding of HB and its impact throughout life. The need for optimal disease control to normalize physical and psychosocial outcomes is underscored, and further analyses will contribute to an increased understanding of critical issues in HB.

Chromosomal Breakage in Fanconi Anemia and Consanguineous Marriages: A Social Dilemma for Developing Countries.

Introduction A clear picture of the prevalence of Fanconi anemia is not known due to limited studies and research of the subject. This study will detect the frequency of positive chromosomal breakage in pediatric aplastic patients and provide the evidence-based guidelines which help in consideration of appropriate treatment and awareness to the society. Methods A total of 104 aplastic anemia patients were recruited of age <18 years whose samples were tested for chromosomal breakage with mitomycin C (MMC). History of consanguinity between parents were documented for all the patients referred to us. Result Out of 104 diagnosed aplastic anemia patients, 35 (33.7%) patients were found to be Fanconi positive. Mean age of all hypoplastic patients for aplastic anemia and Fanconi anemia was 10.7 ± 4.5 and 10.6 ± 3.5, respectively. Male preponderance was found to be higher (64, 61.5%) as compared to females (40, 38.5%) in aplastic patients. The male to female ratio was observed as 2.5:1 in Fanconi patients while 1.3:1 in non-Fanconi aplastic patients. Parental consanguinity was observed in 33 (94.2%) with Fanconi anemia. Conclusion Fanconi anemia accounts for significant number of patients with hypoplastic bone marrow, therefore consanguineous marriages should be avoided through mass education in Pakistan.