Rare bleeding disorders: spectrum of disease and clinical manifestations in the Pakistani population

Background@#Rare inherited coagulation factor deficiencies constitute an important group of bleeding disorders. A higher frequency of these disorders is seen in areas of high consanguinity.Our aim was to study the prevalence and spectrum of rare inherited bleeding disorders, characterize the severity of the deficiencies, identify different clinical manifestations, and evaluate different treatments provided. @*Methods@#This cross-sectional study was conducted in the Department of Haematology, Armed Forces Institute of Pathology Rawalpindi, between January 2014 and December 2018.A detailed history was taken, and an examination was performed. The signs and symptoms were noted, and the patients were diagnosed on the basis of a coagulation profile. The disease severity was assessed using factor assays. @*Results@#Among 2,516 patients with suspected coagulation disorders, 774 (30.8%) had an inherited bleeding disorder. Of the 774 patients, 165 (21.3%) had a rare bleeding disorder;91 (55.2%) of them were males, and 74 (44.9%) were females, with a male-to-female ratio of 1.2:1. The median patient age was 9 years 3 months. The most common disorder was factor VII deficiency (46 patients, 27.9%). The most common clinical presentation was bruising in 102 (61.8%) and gum bleeding in 91 (55.2%) patients. @*Conclusion@#The most common rare bleeding disorder in our population is factor VII deficiency. The prevalence of these bleeding disorders is high in our population due to a high number of consanguineous marriages.

Clinico-haematologic association and prognostic relevance of NPM1 and FLT3-ITD mutations in acute myeloid leukaemia

Background and Objectives: Molecular genetic abnormalities have a significant role not only in diagnosis but also in determining the clinical course and prognosis. Nucleophosmin-1 [NPM-1] is associated with good prognosis while internal tandem duplication of the fms-like tyrosine kinase-3 gene [FLT3-ITD] confers a poor prognosis. Knowledge of the status of these mutations in AML patients not only guides treatment decisions but also helps in predicting response to frontline induction and consolidation chemotherapy as well as the risk of relapse and overall survival. Our objectives were to determine the prevalence, clinico-haematological features and immunophenotypic characteristics of AML patients with FLT3-ITD and NPM1 mutation and to evaluate the response to induction therapy [CR] and disease free survival [DFS] in this cohort of patients

Methods: Patients diagnosed as AML from March 2015 to March 2017 at Armed Forces Institute of Pathology Rawalpindi were included in the study. Clinico-haematologic and immunophenotypic parameters were noted and molecular analysis for FLT3-ITD and NPM1 mutation was performed. Any correlation with cytogenetics or other molecular markers was also studied. Response to standard induction chemotherapy and disease-free survival were assessed

Results: A total of 108 cases of AML were analyzed. Median age was 35 years and 64.8% were males. The median age of the study group was 35 years. Of these, 70 [64.8%] were males while 38 [35.2%] were females. Twenty-nine [26.9%] patients were NPM1 positive, twelve [11.1%] were FLT3-ITD positive while eight [7.4%] were positive for both mutations. Patients with NPM1 mutations were associated with female gender, higher haemoglobin level and platelet counts while those with FLT3-ITD mutations were predominantly seen in male patients and had significantly higher WBC counts, bone marrow blasts, biopsy cellularity and LDH levels. CR rates of NPM1 positive, FLT3-ITD positive and both mutation positive groups were 72%, 60% and 71%, respectively. The median disease-free survival was significantly lower in the FLT3-ITD positive group [7.1 months] as compared to the NPM1 positive group [16.1 months]. The median disease-free survival was 12 months and 11.9 months in the NPM1 positive/FLT3-ITD positive and the NPM1 negative/FLT3-ITD negative groups, respectively

Conclusion: AML patients harbouring NPM1 and FLT3-ITD mutations have distinct clinical and haematological characteristics. NPM1 mutations have a better CR and DFS as compared to FLT3-ITD group.

Clinicohematological parameters and outcomes in a cohort of chronic lymphocytic leukemia patients with Deletion 17p from Pakistan

BACKGROUND: Chronic lymphocytic leukemia (CLL) exhibits profound heterogeneity in its clinical course. Its clinicohematological and cytogenetic features play a significant role in determining the clinical course and in predicting the treatment response and prognosis. In this context, 17p deletion is known to predict a poor prognosis, as these cases are refractory to conventional therapy. This study aimed to evaluate the clinicohematological characteristics, outcomes, and prognostic factors among CLL patients with and without del 17p in Pakistan. METHODS: This prospective observational study was conducted at the Department of Haematology, Armed Forces Institute of Pathology (Rawalpindi, Pakistan) between January 2013 and December 2017. Patients were diagnosed based on the International Workshop on Chronic Lymphocytic Leukaemia IWCLL criteria, their clinicohematological parameters were recorded, and cytogenetic analyses were performed. The time from diagnosis to treatment and the 2-year overall survival rate were also evaluated. RESULTS: We evaluated 130 CLL cases, including 24 patients (18.5%) with del 17p, who included 18 men (75%) and 6 women (25%). The median age was 68 years. Binet stage C was detected at the presentation in 16 patients (67%). Treatment was administered to 14 patients (70%) at a median interval of 11 months (range, 0–28 mo) after diagnosis. The overall response rate was 64.3%, the median event-free survival was 9 months (range, 1–23 mo), and the 2-year overall survival rate was 65%. CONCLUSION: Del 17p is relatively common in Pakistan, and patients harboring this deletion had poor treatment response and survival outcomes.

Blood transfusion support in mass disaster and trauma situations an experience at a tertiary care center

Objectives: To assess the blood transfusion support requirements in mass disaster and trauma situations

Study Design: Cross-sectional observational study

Place and Duration of Study: This study was conducted at Combined Military Hospital Quetta from, Jan 2013 to Dec 2015

Material and Methods: Nature of injuries, triage details, details of surgical procedures and duration of hospital stay were noted. Data was analyzed with respect to cross match to transfusion ratio and the number of units of each component transfused. Patients requiring massive transfusion and any associated complications were also studied

Results: A total of 2228 casualties were received during the study period, of these, males were 18 [75 percent] and 6 [25 percent] were females. Mean age was29.7 years. 1636 [73.4 percent] casualties had sustained major injuries. Mean hospital stay was 6.31 days. Only 199 [12.2 percent] patients required blood transfusion with a mean of 2.9 units of RCC, 8.7 bags of FFP and 4.6 bags of platelets. Fifteen [7.5 percent] patients received massive transfusion. Following massive transfusion, one case of metabolic acidosis and two cases of coagulopathy were reported

Conclusion: Mass disasters and trauma casualties pose a serious challenge to any healthcare facility in general and the blood transfusion services in particular. Only a well-organized blood transfusion center and blood transfusion emergency preparedness can result in better patient care and outcome. Not all patients need transfusion and a delicate balance between demand and supply has to be maintained