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.

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.

A distinct molecular mutational profile and its clinical impact in essential thrombocythemia and primary myelofibrosis patients.

BACKGROUND: Classical MPNs including ET and PMF have a chronic course and potential for leukaemic transformation. Timely diagnosis is obligatory to ensure appropriate management and positive outcomes. The aim of this study was to determine the mutational profile, clinical characteristics and outcome of ET and PMF patients in Pakistani population. METHODS: This was a prospective observational study conducted between 2012 and 2017 at NIBD. Patients were diagnosed and risk stratified according to international recommendations. Response to treatment was assessed by IWG criteria. RESULTS: Of the total 137 patients analysed, 75 were ET and 62 were PMF. JAK2 positivity was seen in 51 cases (37.2%), CALR in 41 cases (29.9%), while triple-negative in 17 (12.4%) cases. None of the patients in the present study were MPL positive. Overall survival for patients with ET and PMF was 92.5 and 86.0% respectively and leukaemia free survival was 100 and 91.6% respectively, at a median follow-up of 12 months. Leukaemic transformation occurred in 6.5% of MF patients; among them, JAK2 mutation was frequently found. Molecular mutations did not influence the OS in ET whereas in PMF, OS was shortest in the triple-negative PMF group as compared to the JAK2 and CALR positive patient groups. CONCLUSION: This study shows a different spectrum of molecular mutations in ET and PMF patients in Pakistani population as compared to other Asian countries. Similarly, the risk of leukaemic transformation in ET and PMF is relatively lower in our population of patients. The factors responsible for these phenotypic and genotypic differences need to be analysed in large scale studies with longer follow-up of patients.

Gγ-Xmn I polymorphism: a significant determinant of ß-thalassemia treatment without blood transfusion.

ß-thalassemia is characterized by impaired ß-chain synthesis leading to ineffective erythropoiesis, severe anemia, and a need for blood transfusion. Presence of Xmn I polymorphism (-158 C-T nucleotide change) in γ-globin gene is associated with a higher fetal hemoglobin and a lesser clinical severity. This prospective study attempted to find out the effect of hydroxyurea (HU) on ß-thalassemia patients in the presence or absence of Xmn I polymorphism. A total of 143 consecutive ß-thalassemia patients received HU (16 mg/kg/d). Sixty-four (44.7%) had Xmn I polymorphism (either homozygous or heterozygous). Patients were evaluated at a median duration of 3 years (range, 6 mo to 9 y). Responders became transfusion independent after 6 months, partial responders had a least 50% reduction in transfusion requirement and nonresponders had no significant reduction. Of the 64 patients with Xmn I polymorphism, 44 (69%) showed response (P<0.01), whereas in those who lacked Xmn I polymorphism (n=79), only 17 (21%) were responders. This study showed that the presence of Xmn I polymorphism in ß-thalassemia is a predictor of response to HU and highlights the possibility of managing this subset of patients without blood transfusion.