Severe Anemia Requiring Blood Transfusion Research Articles

Colorectal cancer in inflammatory bowel diseases in St. Petersburg: results of an analytical study

Introduction. Ulcerative colitis (UC) and Crohn’s disease (CD) belong to the category of inflammatory bowel disease (IBD) and are one of the most pressing problems of gastroenterology worldwide, including due to the development of specific life-threatening complications. Chronic inflammation in the colon in IBD is the cause of the development of one of these complications - colorectal cancer, which requires disabling colectomies and is also one of the leading causes of death among IBD patients. In the Russian population of IBD patients the prevalence of dysplasia and cancer of the colon mucosa has not been previously studied in large epidemiological studies. The aim of the study was to assess the incidence of colorectal cancer in patients with IBD in St. Petersburg. Materials and methods. Within the framework of this publication, the results of three studies were compared: a single-center retrospective cohort study conducted on the basis of the city center of IBD in St. Petersburg (516 patients with IBD who admitted to this medical institution for the period 2020-2023); a multicenter epidemiological study aimed at assessing the clinical features of IBD among the population of St. Petersburg (1072 patients with IBD who admitted to 42 outpatient clinics and 6 city hospitals in 2018-2020); registry study based on the general statistical module of the regional IBD Register of St. Petersburg, operating on the basis of a regional fragment of the unified healthcare state information system (12,858 patients with IBD, data collection period: 2019-2022). Results. As a result of comparing data from three studies, the incidence of IBD-associated colorectal cancer in St. Petersburg was calculated, which was 15.7 cases per 10,000 patients with UC per year and 11.5 cases per 10,000 patients with CD per year. Compared to the population of St. Petersburg as a whole, the likelihood of developing colorectal cancer in patients with UC was 2.9 times higher, in patients with CD - 2.4 times higher. At the same time, in a single-center study, when assessing the prevalence of IBD-associated colorectal cancer, it was found that compared with other life-threatening complications of IBD, it was much less common: toxic dilatation of the intestine occurred 3 times more often, intestinal perforation occurred 20 times more often, decompensated bowel stricture occurred 21 times more often, and severe anemia requiring blood transfusion occurred 36 times more common. Also, as a result of a single-center study, it was found that for 1 case of IBD-associated dysplasia of the colon mucosa, there were 5 cases of sporadic dysplasia. Conclusion. The selection of the most effective therapy and systematic endoscopic examination of patients with IBD will significantly reduce the likelihood of developing colorectal cancer, and systematic observation of the patient with regular endoscopic monitoring of the colon with multifocal biopsy will allow timely detection of dysplasia of the colon mucosa in accordance with current clinical guidelines. It can be assumed that within the framework of cancer prevention measures in the first years of follow-up of a patient with IBD from the onset of the disease, it is advisable to give priority to the risk of developing not only IBD-associated dysplasia, but also sporadic dysplasia of the colon mucosa.

An Observational Study on Impact of COVID-19 in Pregnancy: Clinical Profiles and Foetomaternal Outcomes in Caesarean Section Cases at a Tertiary Care Centre, Gujarat, India

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has resulted in a crippled healthcare system worldwide. In this unprecedented situation, it is important to analyse the impact on the vulnerable population of pregnant women, especially those with high-risk pregnancies and those undergoing a Caesarean section (CS). Aim: To analyse the clinical profile, foetomaternal outcomes, and co-morbidities in COVID-19-affected pregnancy cases undergoing a CS. Materials and Methods: This was a retrospective observational study conducted at the Department of Obstetrics and Gynaecology, Government Medical College, and New Civil Hospital in Surat, Gujarat, India during the first wave of the COVID-19 pandemic from April 2020 to December 2020. The study included a total of 65 cases of COVID-19-positive mothers undergoing a C-section. Demographic parameters such as age, obstetric history, details of the C-section (like gestational age at the time of the procedure, indication, and category of the C-section), associated co-morbidities, severity of COVID-19- related symptoms and treatment, neonatal parameters {such as birth weight, Appearance, Pulse, Grimace, Activity and Respiration (APGAR) score, and COVID-19 status of the baby at birth} were analysed. Additionally, a comparison of the C-section rate and complications such as the development of severe anaemia requiring blood transfusion, postoperative development of urinary tract infections, surgical site infections, and the association of hypertensive disorders of pregnancy was conducted between COVID-19-affected and unaffected pregnancies undergoing a C-section during the study period. Data on COVID-19 negative cases were obtained from the monthly labour room statistics submitted to the department. The Chi-square test and Fisher’sexact test were used to compare parameters of the COVID-19 positive and negative groups and a p-value of less than 0.05 was considered statistically significant. Results: Out of a total of 6246 deliveries conducted at the institute during the study period, the CS rate among affected and non affected women was 44.5% (65 out of 146) vs. 32.8% (2006 out of 6100) {p=0.003, Relative Risk (RR) 1.3, 95% Confidence Interval (CI) 1.12-1.62}. The mean age of women with COVID19 undergoing a CS was 25.3 years. The difference in the rate of blood transfusion requirement in COVID-19-affected cases was 9 out of 65 (13.8%) vs. 120 out of 2006 (6%) in COVID-19 negative pregnancies (RR 2.3, 95% CI: 1.2-4.3). The difference in the rate of urinary tract infections in the postoperative period was statistically significant in COVID-19-infected patients, 5 out of 65 (7.7%) vs. 58 out of 2006 (2.9%) in non infected patients (p=0.0451, RR 2.6, 95% CI 1.1-6.4). The prevalence of hypertensive disorders among COVID-19 positive and negative mothers undergoing CS was very high in the present study (16 out of 65, 24.6% vs. 160 out of 2006, 8.1%, RR 3.08, 95% CI 1.9-4.8). Neonatal parameters like low APGAR score at birth were seen in 5 cases (8%), low birth weight in 20 cases (30%), and 3 babies (4.5%) were COVID-19 positive at birth. Conclusion: Higher rates of caesarean sections, increased prevalence of hypertensive disorders of pregnancy, anaemia requiring blood transfusion, and postoperative development of urinary tract infections among COVID-19-affected mothers undergoing a caesarean section.

Maternal and fetal outcomes in pregnant patients with non-cirrhotic portal hypertension: A systematic review and meta-analysis.

Concerned studies with respect to the outcome of pregnant patients with non-cirrhotic portal hypertension are limited. Thus, a systematic review and meta-analysis of the available literature was conducted. A literature search was conducted from 1999 to December 2021 for studies evaluating pregnancy outcomes in patients with non-cirrhotic portal hypertension. Twelve studies were included in the meta-analysis. The pooled rate of variceal bleeding, ascites and severe anemia requiring blood transfusion were 9.6%, 2.3%, and 14.9%, respectively. The pooled rate of spontaneous miscarriage, gestational hypertension, delivery by cesarean section, and postpartum hemorrhage were 11.9%, 4.5%, 36.7%, and 4.7%, respectively. The pooled stillbirth rate was 2.5% and among the live births, the pooled rates of preterm birth, low birth weight, intensive care unit admission, and neonatal mortality were 21.6%, 18.7%, 15.5%, and 1.8%, respectively. Pregnancy in patients with non-cirrhotic portal hypertension is associated with increased maternal & fetal morbidity but mortality remains low.

Contribution of Environment in Comorbidities in Children with Sickle Cell Disease: A Prospective Observational Study at a Tertiary Care Center in India

Key words -environmental determinants, morbidity, sickle cell disease, children Sickle cell disease (SCD) presents with highly variable clinical consequences, which are noted even among identical twins residing in different geographical areas, but remain unexplained even after extensive genetic studies. India has 2nd largest number of births with SCD, only second to Africa. Different regions in India also have variability in climate and environment which also varies from season to season. Therefore, we aimed to study the contribution of environmental determinants associated with morbidity in children with SCD. We conducted a prospective observational study in hospitalized children diagnosed with SCD in a tertiary care center in Government medical college, Nagpur, Maharashtra in India. Our study included 88 females (41.51%) and 124 males (58.49%) in the age group of 6 months -14 years, but majority were between 5-10 years of age (50.94%). Children living outside a radius of 10 km from the hospital where study is conducted and children with systemic disorders were excluded. Convenience sampling method was used to examine the effect of several environmental factors including temperature, rainfall, relative humidity, wind speed, atmospheric pollutants such as nitrogen dioxide (NO2), sulfur dioxide (SO2) and ozone from 1st January 2020 to 31st December 2021. We correlated the association of these environmental factors with the severity of morbidity related to the duration of hospital stay, infection, vasoocclusive crises (VOC), intensive care utilization (ICU) & number of blood transfusions. In our study population maximum duration of hospital stay was 44 days and minimum of 2 days. The cause of admissions included VOCs (54.25%), severe anemia requiring blood transfusion (41.98%), and infections (34.91%). During our 2 years study period, range of maximum and minimum temperature was 22-46.8 and 0 -30.8degree Celsius, relative humidity of 20-100%, wind speed of 0-28 knots, rainfall of 0-100.3 mm, NO2 levels of 0-95 ug/mm3, SO2 levels of 0-39ug/mm3 & 0zone of 0-148ug/mm3. Maximum number of admissions (62.73%) occurred in the months of June - November. High relative humidity (p value =0.0001) was the most important factor leading to an increase in hospital admissions, followed by rainfall (p value =0.0004). Among air pollutants, increase in NO2(p value =0.0002) and SO2(p value =0.0014) levels were associated with higher number of admissions, whereas ozone levels had no significant impact on number of admissions (p value =0.1499). (More statistical analysis will be provided at the time of presentation). Surprisingly COVID-19 pandemic substantially reduced the number of SCD patients seeking medical attention in our tertiary care center. It is also likely that our results may be influenced by a change in the environmental exposure due to the pandemic. Also, the current observations are from a single city. However, our data provide a 'proof of principle' that the environment contributes to the comorbidities of SCD and offer support to undertake larger studies in different geographic regions of tropical countries. We conclude that environmental factors are important determinants of acute complications in children with SCD. Identification of such environmental factors will help develop strategies to prevent/reduce the comorbidities of SCD and improving the quality of life for children and perhaps adults with SCD.

Study of polyps in female reproductive tract in a tertiary care centre

To study the clinical presentation, management of polyps of female reproductive tract. To know the correlation between ultrasonological finding and Histopathological findings. This was a retrospective hospital based observational study. It was conducted in Cheluvamba hospital, attached to Mysore Medical college and Research Institute, Mysore. Data was collected from hospital registers who underwent surgery for diagnosis of polyp from the year 2018 to 2021 were included in the study. There were 50 cases in the study. They were managed according to their symptoms, age, desire for fertility and type of polyp. Polyps are most common in the age group 31 to 40 years (42%) and in parous women. The most common presenting complaint was heavy menstrual bleeding (82%). Based on USG and HPE the most common type of polyp was leiomyomatous polyp. Heavy menstrual bleeding caused severe anaemia in 44% of women who required blood transfusion for correction anaemia. No cases of malignancy were diagnosed.Polyps are an important cause of AUB. The resulting heavy menstrual bleeding can cause severe anaemia requiring blood transfusion, leading to morbidity. Clinical examination and ultrasound diagnosis correlates with histopathological diagnosis. Using clinical examination and ultrasound one can identify the site and type of polyp and decide on further management.

P-051: ENVIRONMENTAL DETERMINANTS IN MORBIDITY & MORTALITY IN CHILDREN WITH SICKLE CELL DISEASE: A PROSPECTIVE OBSERVATIONAL STUDY AT A TERTIARY CARE CENTRE

Purpose: India has been identified as having the 2nd most number of births with sickle cell anemia in the world, after Africa. Apart from biomarkers, environmental factors play an important role in the clinical severity. As there are no such studies from India,current study attempts to address the effects of environmental factors in children with SCD. Materials and methods: Prospective observational study was conducted in 122 consecutively recruited hospitalized children of 1-12 years of age with SCD diagnosed by HPLC,living within a 10km radius of the tertiary care centre.Convenience sampling method was used.This a hospital based study conducted from 1st January 2020 to 31st December 2021.The severity of morbidity were identified by duration of hospital stay,number of blood transfusions,infections & VOCs and correlated with various environmental factors like temperature,rainfall,humidity,windspeed & particulate matters on the day of admission. Results: The study was conducted in Jan 2020-Dec 2021.A total of 212 admissions from 122 subjects were included, 88 females(41.51%) & 124 males(58.49%).Of this,35.85% of children were under 5 years & 64.15% of children above 5 years.The causes of admission included vasoocclusive crisis(54.25%),severe anemia requiring blood transfusions(41.98%) & infections(34.91%). Various environmental factors recorded during this period were as follows, maximum temp 32.85(22-46.8),min temp 21.46(0-30.8), relative humidity 78.41(20-100),wind speed 5.98(0-28km/hr),rainfall 4.89(0-100.3), atmospheric NO2 levels 27.29(0-95ug/m3),SO2 7.06(0-39ug/m3) & Ozone 41.76(0-148ug/m3). We noted an increase in the admissions as the relative humidity increases.Both extremes of temperature & relative humidity were the 3 important factors in causing VOCs & infections across 3 different seasons(p=0.0001).Among air pollutants, rising NO2 levels were significantly related to VOCs(p=0.0002).Rainfall had a strong correlation with infections(p=0.0035).All the environmental factors, except ozone were found significantly correlated with VOC & severe anemia while Infection was significantly related to all the environmental factors except wind speed,NO2 & Ozone. Conclusion: Studying the effect of environmental factors in SCD is important,as it allow patients and families to be given accurate information on how to reduce the risk of acute complications, because they can be manipulated relatively easy with simple advices,unlike genetic factors.However,further long term studies need to be conducted, to assess the effects on chronic complications and to drive public health policies. The authors do not declare any conflict of interest

Malignant Bowel Obstruction in Ovarian Cancer Recurrence: The Role of Palliative Surgery in a Decision-Making Process

Background: Malignant bowel obstruction (MBO) is often the latest stage in ovarian cancer (OC). The therapy of this condition ranges from medical waiting to surgery. The objective of this pilot study is to compare the two strategies so that we can provide a path forward for future studies. Methods: From 700 women diagnosed with OC in the database of the Division of Gynecologic Oncology we crossed the names of those admitted by the emergency services of the IRCSS Azienda Ospedaliero Universitaria of Bologna, Italy. We selected MBO patients with a history of OC as the only neoplastic condition and compared the results between medical conduct and surgery to restore intestinal transit. Results: Of the 700 women in our database, 36 were eligible for study according to the inclusion and exclusion criteria: 9 in surgery group and 27 in medical group. Surgical conduct (tumor biopsy and stoma) appears to be resolutory for the obstruction and have a better result than medical therapy regarding recurrence of MBO, despite the development of greater complications. Relapses of MBOs occurred in 11% of surgical patients and 44% of medical patients (p = 0.0714). Furthermore, after surgical treatment, five patients (55%) experienced postoperative complications; in four cases, severe anemia requiring blood transfusion, while one patient developed post-surgical sepsis, which evolved into multiple organ failure and death. Of the 9 patients treated surgically, 2 (22%) were given surgery as a first choice. In most cases (78%), surgery was decided upon when medical treatment failed. The only discriminative factor appears to be age. The length of hospitalization increased with the patient’s age (p = 0.0181) as statistically significant factors for a worse outcome in surgery. Conclusions: MBO requires complex and multidisciplinary management where different factors need to be considered before initiating surgical therapy. Future studies are needed to deal with this complex problem.

Hookworm infection presenting as recurrent severe anaemia requiring blood transfusion in a Pakistani migrant to Italy.

We report a case of hookworm infection presenting as recurrent severe anaemia in an adult Pakistani migrant to Italy. Clinicians working in non-endemic countries should be aware of this possible cause of anaemia, approachable by a microscopic stool examination that could avoid invasive and time-consuming diagnostic work-up.

Gynecologic and reproductive outcomes in fibrous dysplasia/McCune-Albright syndrome

BackgroundAutonomous ovarian activation with recurrent estrogen-producing cysts is a hallmark feature of the rare bone and endocrine disorder fibrous dysplasia/McCune-Albright syndrome. Precocious puberty in girls with McCune-Albright syndrome has been well-described, however long-term effects on gynecologic and reproductive function are unknown. Concerningly, case reports have described poor skeletal outcomes associated with pregnancy in women with fibrous dysplasia.MethodsThirty-nine women with fibrous dysplasia/McCune-Albright syndrome were evaluated as part of a natural history study. Clinical, radiographic, and biochemical data were reviewed. Women were contacted to obtain detailed menstrual and reproductive histories.ResultsAbnormal uterine bleeding affected 77% of women (30/39), and was associated with severe anemia requiring blood transfusion in 3 cases. Nine women underwent hysterectomy for management of bleeding, including 67% (6/9) at the unusually young age of less than age 35 years. Infertility affected 43% of women (9/21), including 2 women who developed primary ovarian insufficiency after undergoing surgical treatment of ovarian cysts. Of 25 spontaneous pregnancies in 14 women, 35% (8) were unplanned. Among the 14 pregnancies, pregnancy was associated with no change in bone pain in 7 subjects (53%), increased bone pain in 4 subjects (31%), and decreased bone pain in 2 subjects (15%). No additional skeletal complications were reported during pregnancies.ConclusionsWomen with fibrous dysplasia/McCune-Albright syndrome report a high prevalence of gynecologic morbidity and reduced fertility. There is no clear association between pregnancy and poor skeletal outcomes in this population.

Treatment Modalities in Adolescents Who Present with Heavy Menstrual Bleeding.

On this study we sought to determine the relationship of bleeding disorders to iron deficiency anemia. Additionally, this study was undertaken to examine all current treatment modalities used in a menorrhagia clinic with respect to heavy menstrual bleeding management to identify the most effective options for menstrual management in the setting of an underlying bleeding disorder. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We performed a retrospective chart review of adolescents younger than 21years with heavy menstrual bleeding attending a multidisciplinary hematology-adolescent gynecology clinic. Information including demographic characteristics, bleeding diathesis, hematologic parameters, treatment, and the diagnosis was extracted from each chart. Subjects were grouped into 2 categories on the basis of the diagnosis of a bleeding disorder. Hemoglobin level, iron deficiency anemia, and need for transfusion were compared between a bleeding disorder and no bleeding disorder group. Subjects were grouped into categories depending on hormonal modality and treatment success of the groups were compared. Seventy-three subjects were tested for a bleeding disorder. Of the subjects who completed testing, 34 (46%) were diagnosed with a bleeding disorder. Thirty-nine subjects (54%) had heavy menstrual bleeding because of other causes. There was no significant difference in hemoglobin between those with and without a bleeding disorder. Iron deficiency anemia was significantly higher in subjects without a bleeding disorder. In a comparison of hormone therapy success, the levonorgestrel intrauterine device (89%, 8 out of 9 subjects) had the highest rate of menstrual suppression followed by norethindrone acetate 5-10mg/d (83%, 5 out of 6 subjects), and the transdermal patch (80%, 4 out of 5 subjects). All subjects using tranexamic acid as well as hormonal therapy had 100% achievement of menstrual suppression. A high frequency of bleeding disorders was found in those tested. Subjects with a bleeding disorder were less likely to present with severe anemia requiring blood transfusion and less likely to have iron deficiency anemia. Although combined oral contraceptives were commonly used clinically for menstrual suppression, they were not found to be the most effective option.

Clinical and haematological profile of children with sickle cell anaemia admitted to a rural medical college of Chhattisgarh, India

Background: Sickle cell disease (SCD) is the most common single gene disorder resulting in hemolytic anemia. Aim of the study was to describe the clinico-haematological profile of children with sickle cell anaemia admitted to Paediatric ward/PICU with any acute clinical event and to find out the association between high HbF level, frequency of crises episodes and requirement of blood transfusion in sickle cell anemia.Methods: Hospital based descriptive study. Retrospective data analysis was done from medical records of patients between 0-15 years age group admitted to hospital from March 2014 to August 2017.Results: Total 68 clinical events were recorded in 60 patients during the study period. More than half of the children were in 0-5 years age group. Mean age of diagnosis was 2.79 years. Severe anemia requiring blood transfusion was the most common cause of hospitalization followed by painful crises. Mean Hb level in the children was 6.65(±2.38). More than one third of children had associated nutritional anemia. Children with high HbF level were found to have less number of painful crises episodes.Conclusions: Severe anemia followed by painful crises were the commonest presentations requiring admission in our hospital. Chronic anemia with microcytosis and high HbF level is the hematological profile of the present study group. Children with high HbF level suffered from less number of painful crises episodes when compared to children with low HbF. But the requirement of blood transfusion was similar in both groups.

Unusual Presentation of Gastric Polyp in a Young Child: A Case Report

Gastrointestinal polyps are described as abnormal lesions that originate in the gastric epithelium or sub mucosa and protrude into the stomach lumen. It may present as an isolated lesion, or could be multiple as part of juvenile polyposis. It could be hereditary or acquired; hamartomatous or hyperplastic in structure; sessile or pedunculated in shape and of benign or malignant origin. Rectal lesions are the commonest in children but gastric polyps are rarely described in this age group, especially in those less than five years old. Clinical presentation of gastric polyps in children varies widely, from incidental endoscopic finding to massive gastrointestinal bleeding. We report a case of unusual upper gastrointestinal bleeding causing severe anaemia requiring blood transfusion secondary to gastric polyp in a young child.

Neonatal Screening and the Clinical Outcome in Children with Sickle Cell Disease in Central India.

BackgroundSickle cell disease (SCD) is a major health burden in India. The objective of the study was to establish a neonatal screening program and to understand the clinical course of children with SCD in central India.Methods and FindingsPregnant mothers were screened for sickle hemoglobin using the solubility test. Babies were screened by high performance liquid chromatography if the mother was positive for sickle hemoglobin. The diagnosis was confirmed by molecular analysis. They received early prophylactic treatment and vaccination. Of 2134 newborns screened, 104 were sickle homozygous (SS), seven had sickle β-thalassemia (S-β thal) and 978 were sickle heterozygous (AS). The other hemoglobin abnormalities detected included HbS -δβ thalassemia-1, HbSD disease-2, HbE traits-5, β-thalassemia traits-4, alpha chain variants-3 and HbH disease-1.These babies were followed up regularly for hematological and clinical evaluation. Pain, severe anemia requiring blood transfusions and acute febrile illness were the major complications with 59.7, 45.1 and 42.6 cases per 100 person years. Fetal hemoglobin (HbF) levels were inversely associated with vaso-oclussive crisis (VOC) and severe anemia while presence of alpha thalassemia increased the rate of painful events and sepsis. Six early deaths occurred among the SS babies.ConclusionA systematic follow up of this first newborn SCD cohort in central India showed that 47% of babies presented within 1 year of age. In spite of the presence of the Arab-Indian haplotype many babies had severe manifestations.

A Study of Clinical Profile of Vitamin B12 Deficiency with Special Reference to Dermatologic Manifestations in a Tertiary Care Hospital in Sub-Himalayan Bengal.

Background:Vitamin B12 deficiency is thought to be uncommon in the eastern parts of India including Bengal and the eastern states as compared to the northern and southern parts of India. The importance of cutaneous features in relation to vitamin B12 deficiency is not well described in literature.Aim:To know the clinical profile of vitamin B12 deficiency in this region and to find out if there is any relationship between dermatologic manifestations with vitamin B12 deficiency.Materials and Methods:All symptomatic patients of anemia requiring blood transfusions who had either raised mean corpuscular volume (MCV) or bicytopenia/pancytopenia on complete blood count or were symptomatic in the form of skin hyperpigmentation were screened for vitamin B12 deficiency.Results:Twenty-five patients were tested for vitamin B12 deficiency. Of them 19 patients were found to be having vitamin B12 deficiency.Conclusions:Vitamin B12 deficiency is not uncommon in the eastern parts of India, contrasting the previous thoughts that it was uncommon in this area, though larger studies are required to know it better. This study included only those requiring blood transfusions, thus a much higher prevalence is expected in this area. Patients with vitamin B12 deficiency do present with severe anemia requiring blood transfusions and often have skin hyperpigmentation.

An unusual case of post-renal transplant anemia induced by Parvovirus B19

We report a 43-year-old man, a known case of Autosomal dominant polycystic kidney disease, who underwent a pre-emptive renal transplant with antithymocyte globulin (ATG) induction (3 mg/kg) and triple immunosuppression. Six months after transplant, he developed severe anemia requiring blood transfusions. Bone marrow aspirate revealed maturation arrest of the erythroid series at the stage of proerythroblasts and basophilic erythroblasts, and presence of giant proerythroblasts with viral inclusions. IgM antibodies against Parvovirus B19 (PVB19) were positive. We concluded that this was a case of PVB19 induced anemia. It is an extremely rare disease and should be suspected in the setting of chronic anemia with reticulocytopenia in an immunocompromised host.

Azathioprine can be safely used in HIV-infected individuals

Azathioprine is an immunosuppressive agent used following solid organ transplant and in the treatment of autoimmune diseases [1]; however, adverse events may be severe and, although often nonspecific, may include life-threatening myelosuppression [2–4]. As HIV infection is associated with a decline in CD4+ lymphocyte subset count, the benefits of administration of immunosuppressive agents in HIV-infected individuals need to be assessed carefully [5]. The efficacy and associated toxicity of azathioprine in HIV-infected individuals has not been well described with a single case report of an HIV-infected patient on highly active antiretroviral therapy (HAART) safely administered azathioprine for the treatment of myasthenia gravis [6]. A database of all HIV-infected patients is held within the department and this was cross-referenced with a separate record held by the departmental pharmacy to ensure full case ascertainment of HIV-infected individuals prescribed azathioprine between January 2008 and August 2012. Seven individuals received azathioprine during this period and mean age was 38 years (range 27–53 years). There were four female and three male individuals. Indications for azathioprine treatment included myositis; herpes simplex virus related immune reconstitution inflammatory syndrome (IRIS); myasthenia gravis; ulcerative colitis; cryptococcal meningitis related IRIS; tuberculosis-related IRIS and Mycobacterium avium complex related IRIS. All patients were receiving HAART. The medical notes were reviewed and immune parameters and haemoglobin levels recorded, as well as adverse outcomes including malignancy, infection and severe anaemia requiring blood transfusion. All individuals were tested for thiopurine methyltransferase activity prior to commencing treatment with azathioprine and were assessed as tolerant. The median duration of azathioprine was 12 months (range: 0.1–65 months). Laboratory measurements were taken at baseline, after 1 month of azathioprine treatment and at the end of azathioprine treatment. During the first month of azathioprine treatment, there were no statistically significant falls in haemoglobin, white cell count, platelets, neutrophils, lymphocytes, CD4+ cell counts, CD8+ cell counts, CD4+% or CD8+%. Over the course of the treatment with azathioprine, the total white cell count fell significantly from median 6.8 to 3.6 × 109/l (P = 0.037). There was a trend to significance in the decline in neutrophil count from a median 4.2 to 2.1 × 109/l (P = 0.066), although there was no significant decline in total lymphocyte count or subsets (Table 1).Table 1: Affect of azathioprine therapy on blood parameters.No opportunistic infections occurred during or in the 6 months following cessation of azathioprine. Case 3 developed an Escherichia coli bacteraemia requiring antibiotic therapy. Case 5 developed a urinary tract infection with coagulase-negative Staphylococcus and Clostridium difficile colitis requiring hospital admission. Case 6 developed an upper respiratory tract infection (with no organism isolated) and an E. coli urinary tract infection. Case 6 developed anaemia and neutropaenia and subsequently stopped azathioprine therapy. No malignancies were diagnosed during and following cessation of treatment. Two individuals died during treatment with azathioprine: one due to complications of disseminated MAC-related IRIS with pneumonia after 4 days of treatment with azathioprine and one from cardiorespiratory arrest secondary to pre-existent left ventricular failure and poorly controlled diabetes after 14 days of therapy. Neither death was associated with the azathioprine therapy. Although no serious opportunistic infections or malignancies were reported and neither immune parameters, nor haemoglobin fell below critical levels, further data are needed before conclusions of the safety of azathioprine in the context of HIV-infected individuals are made. Where azathioprine is used in this context, immune parameters should be regularly monitored throughout treatment. Acknowledgements Conflicts of interest There are no conflicts of interest.

Novel treatments for epistaxis in hereditary hemorrhagic telangiectasia: a systematic review of the clinical experience with thalidomide

Hereditary hemorrhagic telangiectasia (HHT) is a rare, autosomal dominant bleeding disorder that affects one in 5,000–8,000 individuals [1, 2]. It is characterized by mucocutaneous telangiectasia and arteriovenous malformations in the pulmonary, cerebral and hepatic circulations [3]. The disorder is primarily caused by mutations in genes involved in vascular development and repair, e.g. the endoglin gene (ENG) located on chromosome 9 and the gene encoding activin receptor-like kinase-1 (ALK-1) located on chromosome 12 [4]. Recurrent and severe epistaxis is the most common presentation of HHT, frequently leading to severe anemia requiring blood transfusions [3]. Several approaches have been tried for the management of nosebleeds in HHT, including compression techniques, bilateral embolization, surgical arterial ligature and other techniques such as laser therapy, sclerosing agents, electrocautery and septodermoplasty [5]. Adjuvant medical treatments include estrogens, progestogens and antifibrinolytic agents such as tranexamic acid [6, 7]. However, most of these therapeutic measures are only palliative and largely unsatisfactory, creating therapeutic challenges and worsening the quality of life of HHT patients, especially those with severe bleeding who experience important impediments to daily activities. Recently, angiogenesis has been implicated in the pathogenesis of HHT [3]. Circulating concentrations of both transforming growth factor-b and vascular endothelial growth factor are significantly increased and anti-angiogenic drugs such as bevacizumab and thalidomide have, therefore, been tried in the treatment of vascular malformations in this disease [8–12]. The clinical experience on the role of thalidomide, a potent immunosuppressive and anti-angiogenic agent, for the pharmacological management of HHTassociated epistaxis is systematically reviewed in this paper. We performed an extensive literature search through MEDLINE, EMBASE, OVID, and SCOPUS using ‘‘Hereditary hemorrhagic telangiectasia’’, ‘‘HHT’’, ‘‘Osler-WeberRendu syndrome’’, ‘‘vascular malformation’’, ‘‘epistaxis’’, ‘‘nosebleeds’’, ‘‘thalidomide’’ and ‘‘antiangiogenic agents’’ as search terms. Further references not initially identified in the search but referenced within these articles were also reviewed. Unpublished works were identified by searching the abstract books of the most important conferences on hematological diseases. Overall, 29 cases from seven studies on the use of thalidomide for epistaxis in HHT patients refractory to standard medical and local surgical treatments were collected [13–19] (Table 1). After the first report by Kurtin [13] of improvement of nosebleed in a patient with epithelioid leiomyosarcoma and concomitant HHT, a few investigators have assessed the potential role of this anti-angiogenic drug in this clinical setting. The largest case series available in the literature is that including the results of an interim analysis of an ongoing prospective trial conducted by Balduini and colleagues and recently published in an abstract format [19]. Thalidomide was administered to eight patients at a starting dose of 50 mg/day and increased by 50 mg/day every 4 weeks until response to a maximum of 200 mg/day. A complete or partial response, defined as cessation or reduction in the severity of epistaxis, was observed in all patients but one, with significant decreases of transfusion requirements and improvement of quality of life. Six of the seven patients who had a clinical response to this drug responded within 1 month of starting treatment. Interestingly, an experimental study conducted by Lebrin and colleagues [17] showed that thalidomide M. Franchini (&) F. Frattini S. Crestani C. Bonfanti Department of Transfusion Medicine and Hematology, Carlo Poma Hospital, Mantua, Italy e-mail: massimo.franchini@aopoma.it

Unexpected reach of a leech

Vaginal bleeding as the result of a leech infestation is rare. Here we present two cases of hypovolemic shock with severe anemia requiring blood transfusion due to leech infestation. We also briefly review sparse literature available on this entity.

The microbiologic safety of umbilical cord blood transfusion for children with severe anemia in Mombasa, Kenya

Severe anemia requiring blood transfusion is common in hospitalized young children in sub-Saharan Africa but blood is often in short supply. Umbilical cord blood may be a useful source of blood if microbiologic safety concerns can be addressed. Cord blood, donated on the labor ward at the provincial hospital in Mombasa, was cultured soon after collection (screening culture) and after a period of storage (poststorage culture). Conventional blood transfused to children at the hospital was cultured only at the time of issue (poststorage culture). Maternal sera (cord blood) and conventional blood donations were also screened for transfusion-transmitted infection. At poststorage culture, the overall contamination rate of cord blood was one-third that of conventional blood (13/449 vs. 38/434; odds ratio [OR], 0.31; 95% confidence interval [CI], 0.15-0.61) and for bacteria of high pathogenic potential it was half that of conventional blood (4/449 vs. 7/434; OR, 0.55; 95% CI, 0.12-2.18). Screening cultures were positive in 50% (2/4) of cord blood packs where an organism of high pathogenic potential was isolated at poststorage culture. Cord blood donors had a lower seroreactivity than conventional donors for human immunodeficiency virus (OR, 0.63; 95% CI, 0.29-1.18), hepatitis B virus (OR, 0.32; 95% CI, 0.16-0.59), and hepatitis C virus (OR, 0.20; 95% CI, 0.24-0.76). For syphilis, initial seroreactivity in cord blood donors was 3.8% compared to 1.8% in conventional blood donors (OR, 2.10; 95% CI, 1.15-3.60) but was 0.5% after retesting. With respect to bacterial contamination and seroreactivity for transfusion-transmitted infection, the safety of cord blood in Mombasa compares favorably with conventional blood. Clinical trials of cord blood transfusion are justified.

White blood cell count as a predictor of the severity of sickle cell disease during pregnancy

Objective Increasing epidemiological evidence implicates leukocytosis as a major risk factor for poor outcome in non-pregnant sickle cell disease (SCD) patients. The aim of this study was to investigate whether steady-state white blood cell (WBC) count can predict SCD-related problems in pregnancy. Design Retrospective observational study of 40 SCD pregnant women who had their antenatal care at Guy's & St Thomas’ NHS Trust, London. Twenty-six women developed clinical complications related to SCD during their pregnancy (painful crisis, chest symptoms, infections, severe anaemia requiring blood transfusion, pre-eclampsia, and/or thromboembolism) and 14 remained asymptomatic. The steady-state leukocyte counts early in pregnancy were compared between the two groups and receiver operator characteristics (ROC) curve was plotted for different values of WBC. Results Compared to asymptomatic patients, women who developed SCD-related complications had significantly higher total WBC count [11.2 × 10 9 L −1 (SD 3.22) versus 8 × 10 9 L −1 (2.8), p < 0.01], higher lymphocyte count [3 × 10 9 L −1 (1.62) versus 1.6 × 10 9 L −1 (0.65), p < 0.01] and higher monocyte count [0.8 × 10 9 L −1 (0.47) versus 0.4 × 10 9 L −1 (0.21), p < 0.01]. The neutrophil count showed a similar trend but the difference did not reach statistical significance [6.6 × 10 9 L −1 (2.29) versus 5.7 × 10 9 L −1 (2.15), p = 0.22]. The area under the ROC curve was 74% (95% CI: 56–92). Conclusion WBC count early in pregnancy was significantly higher in women who subsequently developed clinical problems related to SCD. The WBC may be used as a predictor of the severity of SCD in pregnancy.