Hematological Morbidity Research Articles

Long-Term Hematologic Outcomes of Offspring Born to Mothers with G6PD deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most prevalent enzyme deficiency in the world, can cause hemolytic episodes in response to stressors. The aim of this study was to investigate whether infants born to mothers with G6PD deficiency have higher long-term risk for hematological morbidity compared to infants born to mothers without G6PD deficiency.

The Role of epigenetic modifications of DNA and histones in the treatment of oncohematological diseases

Introduction. Current knowledge of tumour biology attests a dual genetic and epigenetic nature of cancer cell abnormalities. Tumour epigenetics research provided insights into the key pathways mediating oncogenesis and facilitated novel epigenetic therapies.Aim — an overview of intricate involvement of epigenetic change in haematological morbidity and current therapeutic approaches to target the related mechanisms.Main findings. We review the best known epigenetic marks in tumour cells, e.g. DNA cytosine methylation, methylation and acetylation of histone proteins, the underlying enzymatic machinery and its role in oncogenesis. The epigenetic profile-changing drugs are described, including DNA hypomethylating agents, histone deacetylase and methylase inhibitors. A particular focus is made on substances currently approved in haematological therapy or undergoing clinical trial phases for future clinical availability.

Prenatal exposure to maternal β-thalassemia minor and the risk for long-term hematologic morbidity in the offspring: A population-based cohort study

Objectiveβ-Thalassemia has been shown to be associated with adverse short-term perinatal outcomes including low birth weight and preterm labor. The aim of this study was to assess whether in-utero exposure of maternal β-thalassemia minor is a risk factor for offspring hematological morbidity. Study designA population-based retrospective cohort study was conducted, including all infants born between the years 1991–2014 at a tertiary medical center. Long-term hospitalizations with hematologic morbidities were compared between offspring of mothers with or without β-thalassemia minor. Multiple gestations, perinatal mortality, chromosomal disorders and congenital malformations were excluded. Both study groups were followed until 18 years of age for hospitalization with hematological morbidities. Kaplan-Meier survival curve was used to compare the cumulative hematological morbidity incidence between both groups, and a Cox proportional hazard model was used to control for confounders. ResultsDuring the study period, 243,682 deliveries met the inclusion criteria, of them 0.3% (n = 677) were of mothers with β-thalassemia minor. Among offspring to thalassemic versus non-thalassemic mothers, hospitalization rates involving hematological morbidity, were higher (3.3% vs. 0.7%, p < 0.001) a finding that was consistent with the Kaplan-Meier survival curve (log rank p < 0.001). Using Cox regression model, which adjusted for maternal age, SGA, gestational age and birth weight, maternal β-thalassemia minor was found to be an independent risk factor for long-term offspring hematological (aHR = 5.54; 95% CI 3.63–8.44, p < 0.001, 5.56; 95% CI 3.65–8.47, p < 0.001, and 5.49; 95% CI 3.60–8.36, p < 0.001, respectively). ConclusionPrenatal maternal β-thalassemia minor is independently associated with offspring long-term hematological morbidity.

Optimal delivery timing for dizygotic twins - the short- and long-term perspective.

Major obstetrics and gynecology societies offer inconsistent recommendation regarding optimal delivery timing in uncomplicated dizygotic twins. We sought to investigate the impact of delivery timing within term gestation, in dizygotic twins, on the short- and long-term offspring morbidity. A prospectively analyzed cohort of dizygotic twin deliveries was conducted. All women delivered at a regional tertiary medical center, at term (≥37 0/7), between the years 1991 and 2014, were included. The primary exposure was delivery at 37 0/7-37 + 6/7 weeks, while delivery at ≥38 0/7 weeks' gestation was considered the reference. Neonatal short- and long-term outcomes according to hospitalizations of offspring up to 18 years of age due to cardiac, respiratory, hematological, neurological, and infectious morbidity were compared. Kaplan-Meier survival curves were used to compare cumulative incidences per each major-system hospitalization. Cox regression models were used to estimate the adjusted hazard ratios, while adjusting for variables with clinical importance. During the study period, 612 dizygotic twin deliveries met the inclusion criteria. Of them, 200 (31.3%) occurred at 37-37 6/7 weeks, and 412 (68.7%) occurred at ≥38 0/7 weeks' gestation. In the long-term analysis, rates of hospitalizations involving several major morbidity categories exhibited comparable rates in both groups. The Cox regression models did not demonstrate an independent association between gestational age within term and later major pediatric morbidity in offspring (total long-term morbidity: adjusted hazard ratio 1.33, 95% confidence interval 0.77-2.29). Dizygotic twin deliveries occurring at different gestational ages within term do not appear to significantly impact on major short- and long-term outcomes.

A CASE-CONTROL STUDY ABOUT HEMATOLOGICAL PROFILE AND MORBIDITY OF NEWBORNS AT BIRTH, BORN TO MOTHERS WITH HYPERTENSION IN PREGNANCY.

Background: Hypertensive disorders of pregnancy complicate about 8% of all gestations. Hypertensive disorders are responsible for significant maternal and perinatal morbidity and mortality.&#x0D; AIMS: To determine the hematological parameters and morbidity in neonates born to mothers with gestational hypertension, pre-eclampsia or eclampsia syndrome and in neonates born to normotensive mothers without any maternal complications or medical illness with special reference to platelet count and neutrophil count.&#x0D; Methods and Material: The study was a prospective study conducted on neonates born to pregnant women complicated with gestational hypertension, pre-eclampsia or eclampsia syndrome and neonates born to normotensive mothers recruited at Neonatal Intensive Care Unit and Post natal wards who were delivered at Ananta Hospital and AIMS &amp; RC, Rajsamand (Raj.) from October 2018 to September 2019 and the hematological parameters of these babies were studied.&#x0D; Results: In our study we observed that the mean value of platelet count were significantly lower in study group compared to control group which was highly Statistical significant (p&lt;0.001). The mean value of PT, aPTT, Bleeding Time and Clotting time were significantly higher in study group, as compared to control group. The statistical analytic differences were highly significant in all parameters i.e. PT, aPTT, Bleeding Time and Clotting time (P&lt;0.001).&#x0D; Conclusion: To conclude early hematological screening of babies are recommended to facilitate early detection and management of serious neonatal complications describes above, to decrease morbidity and improved growth, development and survival.&#x0D; Keywords: Pre-eclampsia, Eclampsia, Gestational Hypertension, Newborns.

Long-term pediatric hematological morbidity of the early-term newborn.

Children born at early term (37 0/7 to 38 6/7weeks' gestation) are at an increased risk for long-term respiratory, cardiovascular, neurological, and developmental morbidities as compared with children born at full term (39 0/7 to 40 6/7weeks' gestation). In this population-based cohort analysis, we sought to evaluate the long-term hematological morbidity of early-term born children. The cohort consisted of 223,242 term singleton deliveries. Hospitalizations of the offspring up to 18years of age involving hematological morbidity were evaluated, including hereditary and acquired anemias, immunodeficiency disorders, coagulation disorders, white blood cell disorders, cytopenias, polycythemia, and myelodysplastic syndrome. Hematological hospitalizations were significantly more common in children delivered at early term as compared with those born at later gestational ages. A Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of hematological-related hospitalizations in the early-term born group (logrank p< 0.001). Using a Cox regression model, early-term delivery was found to be an independent risk factor for childhood hematological morbidity with an adjusted hazard ratio of 1.15 (95%CI 1.01-1.30, p=0.027).Conclusion: Early-term delivery appears to be independently associated with pediatric long-term hematological morbidity of the offspring. What is Known? • It has been shown that children born at early term are at increased risk for short-term adverse outcomes including perinatal mortality. • Early-term infants are also at increased risk for long-term morbidity, mainly respiratory. What is New? • Early-term delivery is also independently associated with long-term hematological morbidity of the offspring.

800: Offspring of women following bariatric surgery are at an increased risk for long-term pediatric hematological morbidity

To investigate whether offspring of women following bariatric surgery, as well as these suffering from obesity during their pregnancy, are at an increased risk for long-term pediatric hematological morbidity. A population based cohort study was performed comparing the risk of long-term hematological morbidity (up to the age of 18 years) of children of patients following bariatric surgery and obese women (as compared with non-obese parturients). Deliveries occurred between the years 1991-2013 in a tertiary medical center. Multiple pregnancies and fetal congenital malformations were excluded. Kaplan-Meier survival curves were constructed in order to compare cumulative hematological morbidity. Cox proportional hazards model was used to control for confounders. During the study period 253,808 newborns met the inclusion criteria; 961 were delivered to patients following bariatric surgery, 2473 were delivered to obese women and 250,374 were delivered to non-obese, non-post bariatric patients. Long-term total hematological morbidity was non-significantly higher in children delivered to patients following bariatric surgery (p=0.07, Table; Log rank p=0.07, Figure). Nevertheless, in a Cox proportional hazards model, controlling for important confounders such as maternal age, gestational age at birth, pregnant number, diabetes, hypertension, caesarian delivery, nation, smoking and low APGAR score at 5 minutes; Children delivered to women following bariatric surgery had higher rates of long term total hematological morbidity (adjusted HR=2.12, 95% CI 1.3-3.5; P<0.01). Using the same model, no association was noted between obesity and long term pediatric hematological morbidity (adjusted HR=0.89 95% CI 0.6-1.3; P=0.54). Specifically, bariatric surgery was independently associated with pediatric anemia (adjusted HR=2.02, 95% CI 1.1-3.8 P=0.03) and with thrombocytopenia (adjusted HR=2.6, 95% CI 1.2-5.9 P=0.02). Offspring of women following bariatric surgery are at an increased risk for long-term pediatric hematological morbidity.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

593: Long term hematological morbidity in children ollowing assisted reproductive technology (ART) pregnancies compared to spontaneous pregnancies

593: Long term hematological morbidity in children ollowing assisted reproductive technology (ART) pregnancies compared to spontaneous pregnancies

Haemorrhagic and thrombotic complications in pregnant women with acquired and congenital cardiac disease.

Pregnant patients with cardiac disease have significantly higher predicted maternal morbidity and mortality compared to the general obstetric population. Published guidelines on optimal management of these patients recommend multidisciplinary care provision. There are few published data on the incidence of haematological complications in pregnant women with cardiac disease, although the data that does exist suggests a relatively high rate of bleeding and thrombotic events. To determine the outcomes in terms of haematological morbidity occurring within a cohort of pregnant women with cardiac disease in the setting of multidisciplinary care provision. Patients were identified from a database compiled by the obstetric cardiology service listing all cardiac patients managed in the Rotunda maternity hospital during the period from 2004 to 2011. Data were obtained from the medical and obstetric case notes relating to details of perinatal care and the occurrence of antenatal and postnatal complications. During the 8-year review period, 451 women with cardiac disease were assessed. Fifty-nine were determined to have moderate to high-risk disease. Each received consultant-delivered multidisciplinary care, where written management strategies were agreed by collaborating senior colleagues either preconceptually or in early pregnancy. No venous thromboembolic events occurred and a modest rate of post-partum haemorrhage (approximately 5%) was recorded. There were no maternal deaths. The relatively favourable outcomes observed within our institution highlight the importance of a multidisciplinary approach to the management of pregnant women with cardiac disease, particularly in scenarios where limited published evidence exists to guide management.

The Value of Vaginal Packing in Pelvic Floor Surgery

The objective of this study was to evaluate the effect of vaginal packing following pelvic floor surgery with regard to post-operative pain, bleeding and infection. This was a double-blind randomised study of women undergoing vaginal hysterectomy and/or pelvic floor repair at a tertiary urogynaecology unit. The primary outcome of day 1 post-operative pain was assessed using the short-form McGill Pain score. Secondary outcomes were haematological and infective morbidity, evaluated using changes in full blood count, and cultures of midstream urine and high vaginal swabs. A transvaginal ultrasound scan to exclude pelvic haematoma was performed at 6 weeks in all women who underwent vaginal hysterectomy with or without a pelvic floor repair. In total, 190 women were recruited: mean age 58.3 years (27–91 years), mean body mass index 27.4 kg/m2 and median parity 3. Women were randomised into the ‘pack’ (n = 86) and ‘no pack’ (n = 87) arms with no demographic differences between the groups. No statistically significant differences in the post-operative pain scores or secondary outcome measures were demonstrated. Incidence of haematoma formation (14.8 % no pack, 7.3 % pack, p = 0.204) was not statistically significant. There were three clinically significant complications in the no pack group and none in the pack group. This is the first study to examine pain in association with post-operative vaginal packing. There is no evidence to suggest that packing increases pain scores or post-operative morbidity. A trend towards increased haematoma and significant complications was seen in the no pack group. As vaginal packing does no harm and may be of some benefit it may be argued that packing should be recommended as routine clinical practice.

Cerebral Injury and Neurodevelopmental Outcome in Twin-Twin Transfusion Syndrome

Twin-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies associated with high perinatal mortality and morbidity rates. Management in TTTS is a major challenge for obstetricians and neonatologists. Twins with TTTS often are born prematurely after an extremely distressing and highly hazardous fetal period. In addition to complications associated with prematurity, surviving twins with TTTS are at increased risk for other complications, including neurological, cardiovascular, renal, and hematologic morbidity. Follow-up studies report varying rates of cerebral palsy and long-term neurodevelopmental impairment. This review focuses on the cerebral injury during the neonatal period as well as long-term neurodevelopmental outcome of TTTS survivors.

Adjuvant radiotherapy and/or chemotherapy after surgery for uterine carcinosarcoma

Uterine carcinosarcomas are uncommon with about 35% not confined to the uterus at diagnosis. The survival of women with advanced uterine carcinosarcoma is poor with a pattern of failure indicating greater likelihood of upper abdominal and distant metastatic recurrence. To evaluate the effectiveness and safety of adjuvant radiotherapy and/or systemic chemotherapy in the management of uterine carcinosarcoma. We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), 2012, Issue 10, MEDLINE and EMBASE up to November 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Randomised controlled trials (RCTs) comparing adjuvant radiotherapy and/or chemotherapy in women with uterine carcinosarcoma. Two review authors independently abstracted data and assessed risk of bias. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and risk ratios (RRs) comparing adverse events in women who received radiotherapy and/or chemotherapy were pooled in random-effects meta-analyses. Three trials met the inclusion criteria and these randomised 579 women, of whom all were assessed at the end of the trials. Two trials assessing 373 participants with stage III to IV persistent or recurrent disease, found that women who received combination therapy had a significantly lower risk of death and disease progression than women who received single agent ifosfamide, after adjustment for performance status (HR = 0.75, 95% confidence interval (CI): 0.60 to 0.94 and HR = 0.72, 95% CI: 0.58 to 0.90 for OS and PFS respectively). There was no statistically significant difference in all reported adverse events, with the exception of nausea and vomiting, where significantly more women experienced these ailments in the combination therapy group than the Ifosamide group (RR = 3.53, 95% CI: 1.33 to 9.37).In one trial there was no statistically significant difference in the risk of death and disease progression in women who received whole body irradiation and chemotherapy, after adjustment for age and FIGO stage (HR = 0.71, 95% CI: 0.48 to 1.05 and HR = 0.79, 95% CI: 0.53 to 1.18 for OS and PFS respectively). There was no statistically significant difference in all reported adverse events, with the exception of haematological and neuropathy morbidities, where significantly less women experienced these morbidities in the whole body irradiation group than the chemotherapy group (RR= 0.02, 95% CI: 0.00 to 0.16) for haematological morbidity and all nine women in the trial experiencing neuropathy morbidity were in the chemotherapy group). In advanced stage metastatic uterine carcinosarcoma as well as recurrent disease adjuvant combination, chemotherapy with ifosfamide should be considered. Combination chemotherapy with ifosfamide and paclitaxel is associated with lower risk of death compared with ifosfamide alone. In addition, radiotherapy to the abdomen is not associated with improved survival.

The Role of Macrophage Migration Inhibitory Factor (MIF) Genetic Polymorphisms in Predicting the Development of Macrocytic Anemia in HIV+ Patients.

Anemia is the most common hematologic morbidity in HIV+ patients and is associated with increased mortality. In previous studies, we have examined anemia-associated mortality in over 30,000 HIV+ men cared for within the VA system, and have confirmed the increased mortality previously shown to be associated with anemia. Most strikingly, however, we have demonstrated that macrocytosis in particular is an independent risk factor for early mortality even after correcting for alcohol abuse, liver disease, or therapy with AZT. We hypothesize that macrocytosis reflects a proinflammatory state associated with HIV and magnified by co-morbidities. We have therefore sought to link anemia with known markers of underlying inflammation. Genetic variants that affect the level of cytokine gene expression have been shown to influence the development of anemia associated with a variety of illnesses. One such polymorphism occurs in the macrophage migration inhibitory factor (MIF) gene, a cytokine secreted by macrophages and T-cells that induces release of TNF and IL-6 from macrophages. Our group has defined two polymorphisms in the promoter of the human MIF gene that affect the level of MIF expression. The first, a tetranucleotide CATT repeat, occurs 5-8 times within a Pit-1transcription factor binding site, and increased numbers of repeats are associated with higher levels of MIF expression. The second, a single-nucleotide polymorphism (SNP), has been identified at −173 bp (G/C), although its significance in predicting cytokine levels has been hard to separate from the associated CATT repeat polymorphism. High expression MIF polymorphisms have been shown to correlate with the development of anemia in the setting of malaria, to influence recovery from community acquired pneumonia, and to increase the severity of manifestations of rheumatoid arthritis. We therefore undertook to examine whether MIF polymorphisms might influence the development of anemia in the setting of HIV. We wished to test the hypothesis that the presence of high-expressing alleles of MIF predisposes to the development of anemia in the setting of HIV, particularly in association with other co-morbid conditions. In order to address this question, genomic DNA isolated/extracted from blood collected as part of the Veterans Aging Cohort Study (VACS) has been genotyped for the polymorphisms using a PCR based method. These data are being correlated with anemia, mean corpuscular volume, and CD4 count. We are using Cox proportional hazards models stratified by age, race, HIV severity, and co-morbid disease to examine associations between anemia type/severity and MIF gene polymorphisms. We are currently analyzing the prevalence of high-expressing MIF alleles in non-anemic and anemic patients with and without HIV, using multivariate analysis to identify correlations of genotype with markers of morbidity. It is hoped that these studies will provide insight into the etiology of anemia in HIV+ patients in general, and of macrocytic anemia in particular.

Efficacy of Splenectomy for Patients with Mantle Cell Non-Hodgkin's Lymphoma

The purpose of this study was to define the role of splenectomy in patients (pts) with mantle cell lymphoma (MCL) with regard to improving cytopenias and symptoms of splenomegaly. 26 pts with MCL underwent splenectomy between January 1987 and October 1999 and were followed prospectively for hematologic response and operative morbidity and mortality. A positive response was defined at 1 month of follow-up as: a hemoglobin of ≥11.0 g/dl in a pt with a preoperative value < 11.0 g/dl; or a platelet count of ≥ 100 × 109/L in a pt with a preoperative value < 100 × 109/L. A positive hematologic response was achieved in 69.2% of pts with preoperative anemia, 90% with thrombocytopenia, and 50% with both anemia and thrombocytopenia. The peri-and post-operative morbidity were 3.8 and 19.2%, respectively, the operative mortality was 0%. The median duration of hospitalization was six days. Four (15.4%) pts have not required chemotherapy after splenectomy. Three of these four were previously untreated and they have maintained stable disease for eight years after splenectomy without chemotherapy. Eight additional pts did not require chemotherapy for > 13 months after splenectomy. These results suggest that splenectomy may provide durable remission in selected pts with refractory cytopenias or symptoms related to splenomegaly in pts with MCL. There is a subset of pts that have prolonged disease stabilization without the requirement for immediate chemotherapy after splenectomy.

Haematological toxicity of radiotherapy following high-dose chemotherapy and autologous bone marrow transplantation in patients with recurrent Hodgkin's disease

17 patients with recurrent Hodgkin's disease received 21 courses of radiotherapy (RT) 1–23 months after high-dose chemotherapy and autologous bone marrow transplantation. WHO grade III–IV haematological toxicity, of median duration 38 days (range 4–236), was observed following 10 courses of radiotherapy in 9 patients. This haematological morbidity could be predicted with an 80.0% sensitivity when the pre-RT white cell count was < 5 × 10 9/l or the platelet count < 100 × 10 9/l. It occurred in 9 11 patients wth initial stage III–IV disease, including all 6 given extended radiotherapy fields, but in no patients with initial stage II disease ( χ 2 = 9.35, P < 0.005). Age, histology, the presence of B symptoms, performance status, previous radiotherapy or chemotherapy, the interval between autologous bone marrow transplantation and radiotherapy, the high-dose regimen used, and the radiotherapy dose or field size, did not appear to affect haematological toxicity. The median survival was 18 months from the date of starting radiotherapy. 7 patients remain alive and progression-free 8–51 months (median 21 months) after radiotherapy. Radiotherapy may contribute to durable remissions in patients with relapsed or residual Hodgkin's disease after autologous bone marrow transplantation, but significant haematological toxicity may be expected in those with mild pancytopaenia prior to radiotherapy, particularly with initial stage III or IV disease.

Haematological morbidity in patients with Hodgkin's disease treated with radiotherapy following autologous bone marrow transplantation

Haematological morbidity in patients with Hodgkin's disease treated with radiotherapy following autologous bone marrow transplantation

Perioperative mortality and morbidity of coronary artery bypass grafting

This paper reviews literature from the past year on mortality and on cardiac, neurologic, gastrointestinal, hematologic, and endocrine morbidity after coronary artery bypass grafting.

Factors affecting blood stem cell collections following high-dose cyclophosphamide mobilization in lymphoma, myeloma and solid tumors

Sixty patients with malignancy were enrolled in a study of high dose chemotherapy and peripheral blood stem cell transplantation (PBSCT). The International Journal of Cell Cloning were harvested prior to PBSCT using 75 cycles of high-dose Cyclophosphamide (Cy) mobilization (4 or 7 G/m2) with collection of a median of 4.6 × 108/kg mononuclear cells (MNC) (range 0.2 - 9.5) and 21.6 × 104/kg colony forming unit - granulocyte /macrophage (CFU-GM) (range 0.1 -220). Forty seven patients were mobilized once, 11 required 2 cycles and 2 required 3 cycles. Eight patients (13%) failed to reach the optimim CFU-GM target (total of > 15 × 104 CFU-GM/kg) following Cy mobilization. In a multivariate regression analysis, a number of factors identified those patients who were likely to achieve optimum stem cell collections. These included the use of the higher Cy mobilization dose (P <0.02), a longer interval from last chemotherapy cycle to mobilization(P <0.01) and a higher pre-mobilization bone marrow CFU-GM level (P <0.005). Patient's age, the degree of bone marrow infiltration, the kind of disease or the number of premobillzation chemotherapeutic cycles did not affect the ability to collect adequate stem cell numbers. The mobilization procedure was associated with moderate non-hematologic toxicity and significant hematological morbidity was observed primarily in patients mobilized using the 7 G/m2 dose. Patients mobilized at the higher Cy dose experienced significantly prolonged median days with ANC < 500 (10 vs. 6.6) and platelets < 50,000 (7 vs. 1.4), deeper neutropenic and thrombocytopenic nadirs, more febrile days and bacteremic episodes (P for all < 0.0001). Refinements to the protocol, in particular the use of hematopoietic colony-stimulating growth factors, are currently under investigation.