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BACKGROUND Prognostication of myeloproliferative neoplasm (MPN) has always been challenging, even with the advent of Janus kinase 2 (JAK2 V617F) molecular studies. The survival pattern of patients diagnosed with MPN in developing countries is still undetermined. MATERIALS AND METHODS The national MPN registry conducted from 2009 to 2015 in Malaysia provided a comprehensive insight into the demographics, clinical characteristics and laboratory parameters of patients diagnosed with MPN nationwide. The study analysed the survival patterns and mortality outcomes and risk among 671 patients diagnosed with essential thrombocythaemia (ET), polycythaemia vera (PV), primary myelofibrosis (PMF) and unclassified MPN (MPN-U). Mortality status was traced and confirmed until the end of December 2018, with right censoring applied to patients alive beyond that. RESULTS The analysed cohort consisted of 283 (42.2%) ET, 269 (40.1%) PV, 62 (9.2%) PMF and 57 (8.5%) MPN-U incident cases with diagnosis made between 2007 and 2015. The majority of patients were male (52.3%) and Malay (48.9%), except for ET, in which the majority of patients were female (60.1%) and of Chinese origin (47.0%). Female patients were found to have significantly better overall survival (OS) rates in ET (p = 0.0285) and MPN-U (p = 0.0070). Patients with JAK2 V617F mutation were found to have marginally inferior OS over time. Multivariable Cox regression identified patients with increased age [hazard ratio (HR) 1.055, 95% CI 1.031; 1.064], reduced haemoglobin (HB) level (HR 0.886, 95% CI 0.831; 0.945, p = 0.0002), being male (HR 1.545, 95% CI 1.077; 2.217, p = 0.0182), and having MPN-U (HR 2.383, 95% CI 1.261; 4.503, p = 0.0075) and PMF (HR 1.975, 95% CI 1.054; 3.701, p = 0.0335) at increased risk for worse mortality outcomes. CONCLUSION Myeloproliferative neoplasm reduces patient survival. The degree of impact on survival varies according to sub-type, sex, bone marrow fibrosis and HB levels. The JAK2 V617F mutation was not found to affect the survival pattern or mortality outcome significantly.

Polycythaemia vera (PV) is a haematological disorder caused by an overproduction of erythroid cells. To date, the molecular mechanisms involved in the disease pathogenesis are still ambiguous. This study aims to identify aberrantly expressed proteins in erythroblasts of PV patients by utilizing mass spectrometry-based proteomic analysis. Haematopoietic stem cells (HSCs) were isolated from newly-diagnosed PV patients, PV patients who have received cytoreductive therapy, and healthy subjects. In vitro erythroblast expansion confirmed that the isolated HSCs recapitulated the disease phenotype as the number of erythroblasts from newly-diagnosed PV patients was significantly higher than those from the other groups. Proteomic comparison revealed 17 proteins that were differentially expressed in the erythroblasts from the newly-diagnosed PV patients compared to those from healthy subjects, but which were restored to normal levels in the patients who had received cytoreductive therapy. One of these proteins was S-methyl-5′-thioadenosine phosphorylase (MTAP), which had reduced expression in PV patients’ erythroblasts. Furthermore, MTAP knockdown in normal erythroblasts was shown to enhance their proliferative capacity. Together, this study identifies differentially expressed proteins in erythroblasts of healthy subjects and those of PV patients, indicating that an alteration of protein expression in erythroblasts may be crucial to the pathology of PV.

Background: Bone marrow myelofibrosis (BMF) that develop on top of Polycythaemia vera (PV) and essential thrombocythemia leads to shortening of the patient’s overall survival. This study aimed to address the impact of miR-146a rs2431697 polymorphism on inflammatory biomarkers and genes expression and the hazards of myelofibrosis progression. Patients and Methods: The study included 88 myeloproliferative neoplasm (40 PV; 27 ET; 21 MF) and 90 healthy controls. For all investigated subjects miR-146a rs2431697 genotypes were identified by sequencing and the expression of miR-146a; IL-1β; NF-κB; a NOD-like receptor family, pyrin domain containing 3 (NLRP3) (NLRP3) genes were estimated by real time PCR. Results: miR146a genotypes revealed that there was significant association between TT and TC genotypes with MF. The degree of miR146a expression was significantly reduced in MF as compared to both PV and ET. In contrast; the levels of IL-1β; NF-κB; NLRP3 genes expression were significantly elevated in MF patients group as compared to PV and ET patients’ group. Multivariate analysis identified TT genotype as poor predictor of MF progression. Conclusion: miR-146a rs2431697 TT genotype is associated with high risk of MF progression in MPN patients. Targeting of IL-1β; NF-κB; NLRP3 genes might help in hindering of MF progression in MPN patients

Key points Humans suffering from polycythaemia undergo multiple circulatory adaptations including changes in blood rheology and structural and functional vascular adaptations to maintain normal blood pressure and vascular shear stresses, despite high blood viscosity. During exercise, several circulatory adaptations are observed, especially involving adrenergic and non-adrenergic mechanisms within non-active and active skeletal muscle to maintain exercise capacity, which is not observed in animal models. Despite profound circulatory stress, i.e., polycythaemia, several adaptations can occur to maintain exercise capacity, therefore making early identification of the disease difficult without overt symptomology. Pharmacological treatment of the background heightened sympathetic activity may impair the adaptive sympathetic response needed to match local oxygen delivery to active skeletal muscle oxygen demand and therefore inadvertently impair exercise capacity. Abstract Excessive haematocrit and blood viscosity can increase blood pressure, cardiac work and reduce aerobic capacity. However, past clinical investigations have demonstrated that certain human high-altitude populations suffering from excessive erythrocytosis, Andeans with chronic mountain sickness, appear to have phenotypically adapted to life with polycythaemia, as their exercise capacity is comparable to healthy Andeans and even with sea level inhabitants residing at high altitude. By studying this unique population, which has adapted thru natural selection, this study aimed to describe how humans can adapt to life with polycythaemia. Experimental studies included Andeans with (n = 19) and without (n = 17) chronic mountain sickness, documenting exercise capacity, and characterizing the transport of oxygen thru blood rheology, including haemoglobin mass, blood and plasma volume & blood viscosity, cardiac output, blood pressure and changes in total and local vascular resistances thru pharmacological dissected of α-adrenergic signalling pathways within non-active and active skeletal muscle. At rest, Andeans with chronic mountain sickness had a substantial plasma volume contraction, which alongside a higher red blood cell volume, caused an increase in blood viscosity yet similar total blood volume. Moreover, both morphological and functional alterations in the periphery normalized vascular shear stress and blood pressure despite high sympathetic nerve activity. During exercise, blood pressure, cardiac work and global oxygen delivery increased similar to healthy Andeans but were sustained by modifications in both non-active and active skeletal muscle vascular function. These findings highlight widespread physiological adaptations that can occur in response to polycythaemia, which allow the maintenance of exercise capacity. This article is protected by copyright. All rights reserved.

Summary Polycythaemia vera is a challenging disease to study given its low prevalence and prolonged time-to-event for important clinical endpoints such as thrombosis, progression, and mortality. Although researchers in this space often rise to meet these challenges, there is considerable room for improvement in the analysis of retrospective data, the development of risk-stratification tools, and the design of randomised controlled trials. In this Viewpoint, we review the evidence behind the contemporary approach to risk stratification and treatment of polycythaemia vera. Frameworks for using data more efficiently, constructing more nuanced prognostic models, and overcoming challenges in clinical trial design are discussed.

Umbilical cord milking (UCM) has been theorized to increase placental blood transfusion then again, the optimal method of cord clamping at birth is still contested. We aimed to analyse the effects of UCM on the neonatal haematological parameters at 72 h and 6 weeks of age and its association with any adverse effects. In this randomized control trial, mothers ≥ 34 weeks were randomized into two arms. Under the intervention group, the cord was milked three times before clamping and cutting whereas the controls had the cord clamped and cut without milking. Haemoglobin and haematocrit levels were measured at 72 h. and at 6 weeks. A total of 170 mothers were enrolled with 85 subjects in each arm. Baseline characteristics were comparable. In the intervention arm, the mean haemoglobin [18.1 (2.4) g/dL] and haematocrit [54 (7) %] were significantly higher as compared to the control arm [16.4 (2.1) g/dL and 48 (6) %], at 72 h of age. There was also significant increase in the mean haemoglobin [11.6 (1.3) g/dL] and haematocrit [34 (4) %] compared to the controls [10.1 (1.1) g/dL and 30 (3) %], at 6 weeks. No statistical difference was found in the incidence of PPH and duration of third stage. There was no significant rise in hyperbilirubinaemia, phototherapy requirement and polycythaemia among neonates in the intervention group. Umbilical cord milking is a sound practical approach to raise the haemoglobin and haematocrit levels up to 6 weeks thereby decreasing the proportion of anaemic infants.

Myeloproliferative neoplasms (MPN) are a heterogeneous group of hematological disorders presenting with an increased proliferation in one or several hematological cell lines. Renal manifestations of MPN have not been fully characterized so far. To morphologically assess the potential renal involvement in MPN patients, we analyzed histomorphological findings of a post-mortem cohort (n = 57) with a disease history of Philadelphia-negative MPN including polycythaemia vera, primary myelofibrosis, essential thrombocythemia, or chronic myelomonocytic leukemia (CMML). Seven (12.2%) patients presented with a pattern of diffuse glomerulosclerosis not attributable to diabetic or hypertensive nephropathy. Weak C4d staining suggestive for chronic thrombotic microangiopathy (TMA) was observed in 4/7 cases. Glomerulonephritis was excluded by light microscopy and immunohistochemistry. Patients with a pattern of diffuse glomerulosclerosis did not differ from the rest of the cohort regarding MPN subtype, disease duration, age, or sex. No significant proteinuria had been observed before death. Further findings attributed to MPNs were extramedullary hematopoiesis (n = 5; 8.8%) and tumor involvement in advanced disease (n = 4; 7.0%). Other common findings included arteriolosclerosis (n = 18; 31.6%) and signs of shock (n = 8; 14.0%). To our knowledge, this study is so far the largest investigating renal findings in MPN patients. There may be a causal relationship between idiopathic diffuse glomerular sclerosis and MPN, although its clinical significance and pathophysiology remain uncertain with TMA probably being relevant in a subgroup of cases. Our findings demonstrate the spectrum of renal findings in MPN from early to terminal disease of which hematologists should be aware of in daily clinical practice.

Erythrocytosis has a diverse background. While polycythaemia vera has well defined criteria, the diagnostic approach and management of other types of erythrocytosis are more challenging. The aim of study was to retrospectively analyse the aetiology and management of non-clonal erythrocytosis patients referred to a haematology outpatient clinic in an 8-year period using a 3-step algorithm. The first step was inclusion of patients with Hb > 185 g/L and/or Hct > 0.52 in men and Hb > 165 g/L and/or Hct > 0.48 in women on two visits ≥ two months apart, thus confirming true erythrocytosis. Secondly, polycythaemia vera was excluded and secondary causes of erythrocytosis (SE) identified. Thirdly, idiopathic erythrocytosis patients (IE) were referred to next-generation sequencing for possible genetic background evaluation. Of the 116 patients, 75 (65%) are men and 41 (35%) women, with non-clonal erythrocytosis 34/116 (29%) had SE, 15/116 (13%) IE and 67/116 (58%) stayed incompletely characterized (ICE). Patients with SE were significantly older and had significantly higher Hb and Hct compared to patients with IE. Most frequently, SE was attributed to obstructive sleep apnoea and smoking. Phlebotomies were performed in 56, 53 and 40% of patients in the SE, IE, and ICE group, respectively. Approx. 70% of patients in each group received aspirin. Thrombotic events were registered in 12, 20 and 15% of SE, IE and ICE patients, respectively. Congenital erythrocytosis type 4 (ECYT4) was diagnosed in one patient. The study demonstrates real-life management of non-clonal erythrocytosis which could be optimized using a 3-step diagnostic algorithm.

Hydroxyurea and ruxolitinib are frequently used to treat myeloproliferative disorders, including polycythaemia vera, and chronic treatment is associated with many cutaneous adverse effects such as the development of aggressive non-melanoma skin cancer (NMSC). We report an 85-year-old man with a history of hydroxyurea- and ruxolitinib-treated polycythaemia vera who was referred for the management of progressively growing tumours on his scalp. Histopathology of the largest scalp lesion revealed a partly desmoplastic cutaneous squamous carcinoma with perineural invasion. Initial imaging revealed metastatic disease in cervical lymph nodes, bones and lungs. The scalp lesions were successfully treated with bleomycin-based electrochemotherapy. Under initial systemic therapy using four cycles of cetuximab, metastatic disease progressed. Following the approval by the health insurance, compassionate use of pembrolizumab monotherapy was initiated. After three cycles of pembrolizumab, however, metastatic disease further progressed and the patient finally died from global respiratory insufficiency. The present case exemplifies the cutaneous adverse effects of long-term hydroxyurea and ruxolitinib therapy, frequently resulting in highly aggressive NMSCs that are usually not responsive to systemic treatments even such as immune checkpoint inhibitors.

Objective: We aimed to demonstrate non-inferiority of delayed cord clamping (DCC) and cord milking (CM) in comparison to early cord clamping (ECC) in the incidence of hyperbilirubinemia requiring phototherapy. Material and methods: 467 of maternal-foetal dyads were screened for eligibility. 389 term infants, of breastfeeding, non-smoking mothers were randomized to receive ECC ( < 40 s), DCC (1–2 min) or CM (4 times towards the neonate). The primary outcome was defined as hyperbilirubinemia requiring phototherapy. Results: 307 patients were included in the analysis. CM did not increase the risk of phototherapy RR 11.27 95% CI (0.80; 2.04). Similar results were achieved when comparing DCC and ECC, RR 1.29 95% CI (0.82; 2.05). This was also true for CM vs DCC, RR 0.99 95% CI (0.64; 1.52). The prevalence of total serum bilirubin (TSB) at 24–48 hours was 10.8 mg/dL; 10.33 mg/dL and 11.39 in ECC, CM and DCC group respectively. Transcutaneous bilirubin (TcB) levels at 24–48 h were 7.58 mg/dL, 7.89 mg/dL and 7.60 mg/dL in the ECC, CM and DCC respectively. None of the neonates met exchange transfusion criteria or symptomatic polycythaemia. Conclusions: Our study suggests that placental transfusion is not associated with hyperbilirubinemia requiring phototherapy or exchange transfusion.

Genetic studies in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) are essential to establish the correct diagnosis and to optimise their management. Recently, it has been demonstrated that it is possible to detect molecular alterations analysing cell-free DNA (cfDNA) in plasma samples, which is known as liquid biopsy. We have assessed the molecular profile of a cohort of 107 MPN patients [33 polycythaemia vera (PV), 56 essential thrombocythaemia (ET), 14 primary myelofibrosis (PMF) and 4 unclassifiable MPN] by next-generation sequencing (NGS) using cfDNA and paired granulocyte DNA. A high concentration of cfDNA in plasma was observed in patients with high molecular complexity, in MPL-mutated cases, and in PMF patients. Targeted sequencing of cfDNA showed a comparable mutational profile (100% accuracy) to the one obtained in granulocytic DNA and a strong correlation was observed between the variant allele frequency (VAF) of gene mutations in both DNA sources. The median VAF detected in cfDNA (29·0%; range: 0·95-91·73%) was significantly higher than the VAF detected in granulocytes (median 25·2%; range: 0·10-95·5%), especially for MPL mutations (44·3% vs. 22·5%). In conclusion, our data support the use of cfDNA as a fast, sensitive and accurate strategy for performing molecular characterisation of MPN patients.

Background: Newborns of mothers with hypertensive disorders in pregnancy have an increased risk of preterm delivery, low birth weight, perinatalasphyxia and haematological derangements such as polycythaemia, thrombocytopenia and neutropenia. These morbidities are associated with uteroplacental insufficiency. The haematological derangements however have not been studied in detail in African neonates. Objective: To determine the clinical and haematological features of newborns of hypertensive mothers Methods: Cross-sectional study involving 250 newborns; 125 newborns each of hypertensive mothers (cases), and normotensive mothers (controls). The babies were examined following delivery, their clinical data were recorded, and umbilical cord blood samples were analysed for haematological indices. Results: Preterm deliveries were significantly higher amongst infants of hypertensive mothers (31.2%)compared with controls (12.0%);p = 0.000. Similarly, the birth weight, length and head circumference of the cases were significantly lower than the controls; p = 0.008, 0.003 and 0.004 respectively. Low fifth minute APGAR scores occurred more frequently in cases (8.0%) than controls (0.8%), p=0.010; whilst the mean haematocrit was also significantly higher in cases than the controls, p = 0.013. The median absolute neutrophil count and platelet count were significantly lower in cases than controls; p=0.023 and 0.047 respectively. Thrombocytopenia was identified in 40.0% of the cases compared to 27.2% of the controls, p = 0.041 Conclusion: The present study has shown that newborns of hypertensive mothers have an increased risk of neonatal morbidities such as preterm birth, LBW and thrombocytopenia compared to the newborns of mothers with normal blood pressure in pregnancy, hence close attention needs to be paid to them with emphasis on their haematological system. Key words: newborn, pregnancy, hypertension, hypertensive disorders, haematological, clinical

The presence of erythrocytosis along with the diagnosis of chronic obstructive pulmonary disease (COPD) may veer a primary care clinician in a busy clinic towards attributing the erythrocytosis to hypoxia secondary to COPD; however, this is not always the case. This case highlights the importance of investigation and the significance not excluding a primary cause in COPD patients with erythrocytosis. A 57-year-old male, presenting with chronic cough, was subsequently diagnosed with COPD clinically and confirmed by spirometry. Erythrocytosis was also incidentally noted. The patient did not have any symptoms of polycythemia or hepatosplenomegaly. Therefore, the erythrocytosis was initially thought to be caused by hypoxia secondary to COPD. However, the JAK2 V617F gene mutation was detected and hence the diagnosis of polycythemia vera was made. Although the erythrocytosis was initially attributed secondary to the underlying pulmonary disease, investigations proved it to be primary in origin. This case report highlights the importance of investigating the underlying cause and to confirm the diagnosis of erythrocytosis as primary and secondary polycythemia differ in their management approach. This will avoid inappropriate diagnosis, treatment, and undesirable outcomes.

Background: Prevalence of polycythaemia amongst patients with COPD and its long term effects are unknown. There is limited information in the current literature describing the distribution of haemoglobin (Hb) and its impact on outcomes in the COPD population. The purpose of the present study was to determine the prevalence of polycythaemia in patients with COPD attending a pulmonary clinic, as well as to explore the associations between Hb levels and clinical outcomes. Materials and Methods: A case series descriptive study was conducted on 50 patients of COPD attending pulmonary OPD of a tertiary care hospital. Results: All subjects were male and were aged between 40-85 years. Mean age among of COPD patients with anaemia was 62.00 10.37yrs and with polycythaemia was 62.86 9.03yrs. Amongst COPD patients with polycythaemia mean BMI was 18.49 3.78. Severity of smoking pack years among the patient group was maximum of 60 pack years and minimum of 20 pack years. Mean value of PCV among patients with polycythaemia and without polycythaemia were 56.292.87 and 41.09 4.18 respectively. Conclusions: Polycythaemia did not seem to be related with either increased COPD severity or with altered outcomes. Keywords: Polycythaemia, Anaemia, COPD tertiary care hospital

Congenital heart diseases are common cause of congenital cyanosis with polycythaemia. Congenital methemoglobinemia is a rare cause of lifelong cyanosis with polycythemia. Congenital methemoglobinemia is caused either by enzyme deficiency or by an abnormal Hb (Hb M). Asymptomatic despite presence of severe cyanosis indicates this rare disorder. We are reporting a rare case of polycythemia with cyanosis due to congenital methemoglobinemia. The patient was referred to our centre and attended Hematology OPD (out-patient department) when his routine CBC revealed erythrocytosis. At that time, we found him severely cyanosed especially apparent on lips, tongue, hands and feet. He was diagnosed as a case of congenital methemoglobinemia with 38% blood methemoglobin level (normal value-0.00-2.00%). On view of life long persistent cyanosis, without any cardiopulmonary and neurological abnormality, consanguinity of parent’s marriage, dark colored blood with high methemoglobin level, a final diagnosis of Type I enzyme deficiency congenital methemoglobinemia was made. He was treated with oral ascorbic acid 250 mg twice daily. At follow up after 6 months his skin color improved and RBC count returned to normal. We are reporting this case of congenital methemoglobinemia for the first time in Bangladesh to emphasize the importance of this rare entity in the differential diagnosis of asymptomatic cyanosis with polycythemia.

(1) Background: Polycythaemia is defined by an increase in haemoglobin (Hb) concentration, haematocrit (Hct) or red blood cell (RBC) count above the reference range adjusted to age, sex and living altitude. JAK2 unmutated polycythaemia is frequent but under-investigated in original publications. In this retrospective cohort study, we investigated the clinical and laboratory data, underlying causes, management and outcomes of JAK2 unmutated polycythaemia patients. (2) Methods: The hospital database was searched to identify JAK2 unmutated patients fulfilling WHO 2016 Hb/Hct criteria for PV (Hb >16.5 g/dL in men and >16 g/dL in women, or Hct > 49% in men and >48% in women, or RBC mass > 25% above mean normal predicted value) between 2008 and 2019. Clinical and laboratory data were collected and analysed. (3) Results: From 727,731 screened patients, 294 (0.04%) were included, the median follow-up time was 47 months. Epo and P50 showed no clear pattern in differentiating causes of polycythaemia. In 30%, the cause remained idiopathic, despite extensive work-up. Sleep apnoea was the primary cause, also in patients under 30. Around 20% had received treatment at any time, half of whom had ongoing treatment at the end of follow-up. During follow-up, 17.2% developed a thromboembolic event, of which 8.5% were venous and 8.8% arterial. The mortality was around 3%. (4) Conclusions: Testing for Epo and P50 did not significantly facilitate identification of underlying causes. The frequency of sleep apnoea stresses the need to investigate this condition. Idiopathic forms are common. A diagnostic flowchart based on our data is proposed here. NGS testing should be considered in young patients with persisting polycythaemia, irrespective of Epo and P50 levels.

Myeloproliferative neoplasms (MPNs) are clonal haematopoietic stem cell disorders characterised by myeloid progenitor proliferation in the bone marrow. Polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) are Philadelphia-chromosome negative classic MPNs defined as per the World Health Organization (WHO) 2016 classification and diagnostic criteria. Thrombosis, comprising of both arterial and venous events, is recognised as a leading cause of morbidity and mortality in ET and PV. Several patient and disease-specific characteristics have been shown to correlate with increased thrombotic risk in MPN. Clinical risk factors include age, history of previous thrombosis, cardiovascular comorbidities, and mutation status. The pathobiology of thrombosis in MPN is multifactorial and results from a complex interplay between blood cells, endothelial cells, coagulation system and inflammatory mediators. Platelets, leukocytes, and erythrocytes exist in a hyperactive and proadhesive state. Furthermore, endothelial dysfunction, haemostatic elements and cytokine dysregulation are implicated in thrombogenesis. MPN driver mutations enhance the thrombotic environment, while the chronic inflammatory state further promotes clonal expansion. Much of the current treatment paradigms for MPN focus on primary prevention of thrombosis with antiplatelet agents and cytoreduction. There is a lack of high-quality data informing the optimal approach to secondary prevention of recurrent thrombosis in MPN. Further advances in the characterisation of the cellular and molecular mechanisms underlying thrombotic tendency in MPN are necessary in order to improve personalised risk prediction/stratification and treatment strategies. This review outlines the incidence, nature, and risk factors for thrombosis in MPN, gives an overview of the mechanisms underlying hypercoagulability and discusses prevention and treatment considerations.

Background: Haematological cancers are clonal diseases of the blood and blood-forming organs, with the distribution pattern not known in our locality. This study aimed to describe the distribution pattern and prevalence of haematological cancers among adults in Abakaliki, Nigeria. Materials and Methods: This was an 8-year retrospective study in which the hospital records/case notes of adult patients diagnosed and managed for haematological cancers from May 2012 to April 2020 were reviewed. Data obtained were analysed with the SPSS software, version 20. Results: One hundred and thirty-five cases of haematological cancers were included in the study, with 72 (53.4%) males and 63 (46.6%) females and male-to-female ratio of 1.1:1. The age range was 18–82 years, with a mean age of 49 ± 17 years. Lymphoid malignancies predominate more than myeloid (101 [74.8%] vs. 34 [25.2%]). The leukaemias were more predominant than the lymphomas and myeloma accounting for 48.2%, 36.3% and 7.4%, respectively. Chronic leukaemias were more common than the acute leukaemias with chronic lymphocytic leukaemia (CLL) being the most common accounting for 24.4% of haematological cancers. In general, non-Hodgkin's lymphoma (NHL) was the most common haematologic cancer accounting for 35 (25.9%), followed by CLL 33 (24.4%), chronic myeloid leukaemia (CML) 17 (12.6%), Hodgkin's lymphoma (HL) 14 (10.4%) and multiple myeloma (MM) 10 (7.4%). Others include acute lymphoblastic leukaemia (ALL) 9 (6.7%) and acute myeloblastic leukaemia (AML) 6 (4.4%). Myelodysplastic syndrome (MDS) and polycythaemia vera (PV), each contributed 3% while myelofibrosis (MF) and essential thrombocythaemia (ET) contributed 1.5% and 0.7%, respectively. Conclusion: This study has shown that haematological cancers are not uncommon in our locality with NHL being the most common, followed by CLL, CML, HL, MM, ALL, AML, MDS, PV. MF and ET in that order. The burden of haematological cancers in Ebonyi State, Nigeria is therefore significant and should be prioritised in health-care policy formulation and management.

Background Tetralogy of Fallot (TOF) is the leading cyanotic congenital heart disease. We commenced open-heart surgery at the Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife, Nigeria in 2016. Objectives To review the incidence, pattern, management and treatment outcomes of TOF at the OAUTHC. Methods A retrospective audit was undertaken of hospital records, including echocardiograms of patients with TOF seen from January 2016 to February 2020 at the Paediatric Cardiology Unit, OAUTHC. Results Seventy-two patients (37 boys and 35 girls) aged 0.17-22 years had TOF. Thirty-three (45.8%) had surgery; 31 (93.9%) corrective surgery and two (6.1%) a modified Blalock-Taussig shunt. Complications following surgery included cardiac dysfunction, post-transfusion malaria, pulmonary regurgitation, pericardial effusion and death (15%). Thirty-nine (54.2%) patients had conservative medical management. Complications included polycythaemia and thrombotic stroke, and 14 (35.9%) patients died. Conclusions TOF is associated with significant morbidity and mortality in developing countries. Early and safe corrective surgery is desirable.

Background Patients with Eisenmenger syndrome are chronically hypoxaemic and should therefore mount a secondary erythrocytosis. This response can be attenuated by iron deficiency. Historically, patients with Eisenmenger-associated erythrocytosis often underwent venesection but recent data have challenged this practice. Case presentation An illustrative case of a 30-year-old female with Eisenmenger syndrome secondary to a ventricular septal defect is discussed. Her resting saturations on room air were 84%. She was receiving pulmonary arterial hypertension targeted therapy with sildenafil 25 mg three times a day and bosentan 125 mg twice daily. Her local haematologist was planning on therapeutic venesection as her haematocrit was elevated at 0.57. Her haemoglobin was 16.7 g/dl, ferritin levels were 15 μg/L and transferrin saturations were 10.5%. What are the indications for venesection? Should she receive iron supplementation instead? Data to help guide decision-making are reviewed and a clinical approach is suggested. Conclusions Iron status should be regularly checked in Eisenmenger syndrome patients and replaced appropriately. There is no role for routine venesection in patients with Eisenmenger syndrome; this should be reserved for the small proportion of patients with symptoms of hyperviscosity in the absence of dehydration.

The aim of this retrospective observational study was to observe the pattern and frequency of haematological disorders among the patients attending in the specialized Haematology outpatient Department (HOPD) in Bangabandhu Sheikh Mujib Medical University. Consecutive 201 patients over the period of one year were enrolled. Their age ranged from 01 to 72 years with a mean age of 36.76 years. Most of the patients (34.3%) were in between the ages of 31 to 45 years followed by 16 to 30 years (27.9%). Male to female ratio was 0.65. Iron deficiency anaemia is the most common (24.9%) followed by chronic myeloid leukaemia (11.9%), Hb E beta thalassaemia (9.5%), idiopathic thrombocytopenic purpura (9.5%), beta thalassaemia trait (7.0%), Hb E trait (5.5 %), aplastic anaemia (5.0%), multiple myeloma (3.5%), acute lymphoblastic leukaemia (3.0%). Acute myeloid leukaemia, autoimmune haemolytic anaemia, chronic lymphocytic leukaemia, anaemia of chronic disease, non-Hodgkin lymphoma, polycythaemia, beta thalassemia major and alpha thalassemia was 2.5%, 2.5%, 2.0%, 1.5%, 1.5%, 1.5%, 1.0% and 1.0%, respectively. In the present study, we observed that iron deficiency anaemia the most common non-malignant disease and chronic myeloid leukaemia is the common haematological malignancy.

The combined incidence of classical Philadelphia-negative myeloproliferative neoplasm (MPN) is 6-9/100 000 with a peak frequency between 50 and 70 years. MPN is less frequent in women of reproductive age. However, for essential thrombocythaemia (ET) in particular there is a second peak in women of reproductive age and 15% of polycythaemia vera (PV) patients are less than 40 years of age at the time of diagnosis. Thus these diseases are encountered in women of reproductive potential and may be diagnosed in pregnancy or in women being investigated for recurrent pregnancy loss. The incidence of MPN pregnancies is 3·2/100 000 maternities per year in the UK. The majority of data regarding Philadelphia-negative MPNs relates to patients with ET, for which the literature suggests significant maternal morbidity and poor fetal outcome; specifically maternal thrombosis and haemorrhage, miscarriage, pre-eclampsia, intrauterine growth restriction (IUGR), stillbirth and premature delivery as summarised in the recent systematic review and meta-analysis in Blood, 2018, 132, 3046. The literature for PV is more sparse but increasing and is concordant with ET pregnancy outcomes. The literature regarding primary myelofibrosis (PMF) is even more scarce. Treatment options include aspirin, venesection, low molecular weight heparin (LMWH) and cytoreductive therapy. Data and management recommendations are often extrapolated from other pro-thrombotic conditions or from ET to PV and PMF. Women of reproductive age with a diagnosis of MPN should receive information and assurance regarding management and outcome of future pregnancies. From pre-conceptual planning to the post-partum period, women should have access to joint care from an obstetrician with experience of high-risk pregnancies and a haematologist in a multidisciplinary setting. This paper provides an update with regards to Philadelphia-negative MPN in pregnancy, details local practise in an internationally recognised centre for patients with MPN and outlines a future research strategy.

Summary Background The PROUD-PV and CONTINUATION-PV trials aimed to compare the novel monopegylated interferon ropeginterferon alfa-2b with hydroxyurea, the standard therapy for patients with polycythaemia vera, over 3 years of treatment. Methods PROUD-PV and its extension study, CONTINUATION-PV, were phase 3, randomised, controlled, open-label, trials done in 48 clinics in Europe. Patients were eligible if 18 years or older with early stage polycythaemia vera (no history of cytoreductive treatment or less than 3 years of previous hydroxyurea treatment) diagnosed by WHO's 2008 criteria. Patients were randomly assigned 1:1 to ropeginterferon alfa-2b (subcutaneously every 2 weeks, starting at 100 μg) or hydroxyurea (orally starting at 500 mg/day). After 1 year, patients could opt to enter the extension part of the trial, CONTINUATION-PV. The primary endpoint in PROUD-PV was non-inferiority of ropeginterferon alfa-2b versus hydroxyurea regarding complete haematological response with normal spleen size (longitudinal diameter of ≤12 cm for women and ≤13 cm for men) at 12 months; in CONTINUATION-PV, the coprimary endpoints were complete haematological response with normalisation of spleen size and with improved disease burden (ie, splenomegaly, microvascular disturbances, pruritus, and headache). We present the final results of PROUD-PV and an interim analysis at 36 months of the CONTINUATION-PV study (per statistical analysis plan). Analyses for safety and efficacy were per-protocol. The trials were registered on EudraCT, 2012-005259-18 (PROUD-PV) and 2014-001357-17 (CONTINUATION-PV, which is ongoing). Findings Patients were recruited from Sept 17, 2013 to March 13, 2015 with 306 enrolled. 257 patients were randomly assigned, 127 were treated in each group (three patients withdrew consent in the hydroxyurea group), and 171 rolled over to the CONTINUATION-PV trial. Median follow-up was 182·1 weeks (IQR 166·3–201·7) in the ropeginterferon alfa-2b and 164·5 weeks (144·4–169·3) in the standard therapy group. In PROUD-PV, 26 (21%) of 122 patients in the ropeginterferon alfa-2b group and 34 (28%) of 123 patients in the standard therapy group met the composite primary endpoint of complete haematological response with normal spleen size. In CONTINUATION-PV, complete haematological response with improved disease burden was met in 50 (53%) of 95 patients in the ropeginterferon alfa-2b group versus 28 (38%) of 74 patients in the hydroxyurea group, p=0·044 at 36 months. Complete haematological response without the spleen criterion in the ropeginterferon alfa-2b group versus standard therapy group were: 53 (43%) of 123 patients versus 57 (46%) of 125 patients, p=0·63 at 12 months (PROUD-PV), and 67 (71%) of 95 patients versus 38 (51%) of 74 patients, p=0·012 at 36 months (CONTINUATION-PV). The most frequently reported grade 3 and grade 4 treatment-related adverse events were increased γ-glutamyltransferase (seven [6%] of 127 patients) and increased alanine aminotransferase (four [3%] of 127 patients) in the ropeginterferon alfa-2b group, and leucopenia (six [5%] of 127 patients) and thrombocytopenia (five [4%] of 127 patients) in the standard therapy group. Treatment-related serious adverse events occurred in three (2%) of 127 patients in the ropeginterferon alfa-2b group and five (4%) of 127 patients in the hydroxyurea group. One treatment-related death was reported in the standard therapy group (acute leukaemia). Interpretation In patients with early polycythaemia vera, who predominantly presented without splenomegaly, ropeginterferon alfa-2b was effective in inducing haematological responses; non-inferiority to hydroxyurea regarding haematological response and normal spleen size was not shown at 12 months. However, response to ropeginterferon alfa-2b continued to increase over time with improved responses compared with hydroxyurea at 36 months. Considering the high and durable haematological and molecular responses and its good tolerability, ropeginterferon alfa-2b offers a valuable and safe long-term treatment option with features distinct from hydroxyurea. Funding AOP Orphan Pharmaceuticals AG.