Latest Research on ABO Blood: April 21

[1] The effect of ABO blood group on the diagnosis of von Willebrand disease

In order to firmly establish a normal range for von Willebrand factor antigen (vWF:Ag), we determined plasma vWF:Ag concentrations in 1,117 volunteer blood donors by quantitative immunoelectrophoresis. The presence of the ABO blood group has a significant influence on vWF:Ag values; individuals with blood group O had the lowest mean vWF:Ag level (74.8 U/dL), followed by group A (105.9 U/dL), then group B (116.9 U/dL), and finally group AB (123.3 U/dL). Multiple regression analysis revealed that age significantly correlated with vWF:Ag levels in each blood group. We then performed reverse ABO typing on stored plasma from 142 patients with the diagnosis of von Willebrand disease (vWd). Of 114 patients with type I vWd, blood group O was found in 88 (77%), group A in 21 (18%), group B in 5 (4%), and group AB in none (0%), whereas the frequency of these blood groups in the normal population is significantly different (45%, 45%, 7% and 3%, respectively) (P less than .001). Patients with type II or III vWd had ABO blood group frequencies that were not different from the expected distribution. There may be a subset of symptomatic vWd patients with decreased concentrations of structurally normal vWf (vWd, type I) on the basis of blood group O. Some individuals of blood group AB with a genetic defect of vWF may have the diagnosis overlooked because vWF levels are elevated due to blood type.

[2] ABO Blood Group and the Risk of Pancreatic Cancer

Background

Other than several rare, highly penetrant familial syndromes, genetic risk factors for sporadic pancreatic cancer are largely unknown. ABO blood type is an inherited characteristic that in previous small studies has been associated with the risk of gastrointestinal malignancies.

Methods

We separately examined the relationship between ABO blood type and the risk of incident pancreatic cancer in two large, independent, prospective cohort studies (the Nurses’ Health Study and Health Professionals Follow-up Study) that collected blood group data on 107 503 US health professionals. Hazard ratios for pancreatic cancer by ABO blood type were calculated using Cox proportional hazards models with adjustment for other known risk factors, including age, tobacco use, body mass index, physical activity, and history of diabetes mellitus. All statistical tests were two-sided.

Results

During 927 995 person-years of follow-up, 316 participants developed pancreatic cancer. ABO blood type was associated with the risk of developing pancreatic cancer ( P = .004; log-rank test). Compared with participants with blood group O, those with blood groups A, AB, or B were more likely to develop pancreatic cancer (adjusted hazard ratios for incident pancreatic cancer were 1.32 [95% confidence interval {CI} = 1.02 to 1.72], 1.51 [95% CI = 1.02 to 2.23], and 1.72 [95% CI = 1.25 to 2.38], respectively). The association between blood type and pancreatic cancer risk was nearly identical in the two cohorts ( Pinteraction  = .97). Overall, 17% of the pancreatic cancer cases were attributable to inheriting a non-O blood group (blood group A, B, or AB). The age-adjusted incidence rates for pancreatic cancer per 100 000 person-years were 27 (95% CI = 23 to 33) for participants with blood type O, 36 (95% CI = 26 to 50) for those with blood type A, 41 (95% CI = 31 to 56) for those with blood type AB, and 46 (95% CI = 32 to 68) for those with blood type B.

Conclusions

In two large, independent populations, ABO blood type was statistically significantly associated with the risk of pancreatic cancer. Further studies are necessary to define the mechanisms by which ABO blood type or closely linked genetic variants may influence pancreatic cancer risk.

[3] Relationship Between the ABO Blood Group and the Coronavirus Disease 2019 (COVID-19) Susceptibility

To explore any relationship between the ABO blood group and the coronavirus disease 2019 (COVID-19) susceptibility, we compared ABO blood group distributions in 2173 COVID-19 patients with local control populations, and found that blood group A was associated with an increased risk of infection, whereas group O was associated with a decreased risk.

[4] Prevalence of Malaria Parasitaemia and Its Association with ABO Blood Grouping among Students of Igbinedion University Okada, Nigeria

This study was carried out to investigate ABO blood groups association with malaria parasitaemia among students of Igbinedion University, Okada located in Mid-Western Nigeria. Two milliliters (2ml) of venous blood was collected by venipuncture using 5ml hypodermic needles and syringes from 104 asymptomatic malaria students between March and June 2012. Blood samples were immediately dispensed into Ethylene Diamine Tetra-Acetic acid (EDTA) anticoagulated containers and mixed appropriately. ABO blood typing using monoclonal Antisera A, B and D was carried out on samples. The malaria Plasmodium falciparumrapid Test Device (whole blood) package insert kit (BDH, England) was used to test for the presence of malaria parasites in the specimens. The 104 samples analyzed were made up of 24(23.1%) rhesus positive males, 76(73.0%) rhesus positive females and 4(3.9%) rhesus negative females. In increasing order, 4(3.9%), 16(15.4%), 32(30.8%) and 52(50.0%) students occurred in blood groups AB, A, B and O respectively.

[5] Prevalence of ABO Blood Groups and Its Relationship with Malaria Parasitemia among Students of Federal University of Technology, Akure, Ondo State

There are different reports on the increasing evidence about the relationship between Plasmodium falciparum malaria and ABO blood group, but the range is yet to be understood. The aim of the study was to investigate the prevalence of malaria parasite and its relationship with ABO blood and rhesus grouping among newly admitted students of FUTA. Two millilitres (2 ml) of venous blood was collected by venipuncture using 5 ml hypodermic needles and syringes from 312 symptomatic and asymptomatic malaria students. Blood samples were immediately dispensed into Ethylene Diamine Tetra-Acetic acid (EDTA) anticoagulated containers and mixed appropriately. ABO blood typing using monoclonal Antisera A, B and D was carried out on samples. The 312 samples analysed were made up of 126 (40.4%) rhesus positive and 10(3.21%) rhesus negative. In decreasing order, 60.0%, 45.3%,39.1% and 37.3% students occurred in blood group AB, O, A and B respectively. On the whole, 136(43.6%) of total samples processed, were positive for malaria parasitaemia out of which Plasmodium falciparum account for 82(60.3%). 97(46.2%) and 39(38.2%) of total male and female subjects were infected. Malaria parasitaemia seemed to be relatively high across all blood groups with groups O and AB subjects more susceptible to malaria infection.

Reference

[1] Gill, J.C., Endres-Brooks, J., Bauer, P.J., Marks, W.J. and Montgomery, R.R., 1987. The effect of ABO blood group on the diagnosis of von Willebrand disease.

[2] Wolpin, B.M., Chan, A.T., Hartge, P., Chanock, S.J., Kraft, P., Hunter, D.J., Giovannucci, E.L. and Fuchs, C.S., 2009. ABO blood group and the risk of pancreatic cancer. Journal of the National Cancer Institute101(6), pp.424-431.

[3] Zhao, J., Yang, Y., Huang, H., Li, D., Gu, D., Lu, X., Zhang, Z., Liu, L., Liu, T., Liu, Y. and He, Y., 2020. Relationship between the ABO Blood Group and the COVID-19 Susceptibility. Clinical Infectious Diseases.

[4] Otajevwo, F.D., 2013. Prevalence of malaria parasitaemia and its association with ABO blood grouping among students of Igbinedion University Okada, Nigeria. Journal of Advances in Medicine and Medical Research, pp.1164-1177.

[5] Simon-Oke, I.A., Afolabi, O.J. and Itansanmi, A.I., 2016. Prevalence of ABO blood groups and its relationship with malaria parasitemia among students of federal university of technology, Akure, Ondo State. International Journal of Tropical Disease & Health, pp.1-8.

Latest News on Blood Donation: Feb 2021

The Psychology of Blood Donation: Current Research and Future Directions

With an ever-increasing demand on blood supplies worldwide, there is an immense need to ensure a safe and sufficient supply of blood products. However, recruiting and retaining blood donors remain key challenges for blood agencies. In an attempt to address these problems, researchers have identified a range of sociodemographic, organizational, physiological, and psychological factors that influence people’s willingness to donate blood. Although past research has largely focused on donor recruitment, in particular, demographic variables associated with blood donation behavior, the issue of donor retention has become increasingly important. A growing number of studies have also highlighted the role of psychological factors in explaining, predicting, and promoting blood donation behavior. In line with recent trends in blood donation research, the present article reviews the contributions of, and current directions in, psychological research on blood donation attitudes and behavior, with special emphasis on donor return and repeat blood donation behavior. Although there is overlap between factors that predict the initiation and the maintenance of blood donation behavior, it is suggested that changes in motivation and the development of self-identity as a blood donor are crucial for understanding the processes whereby first-time donors become repeat donors. [1]

The blood donation experience: self‐reported motives and obstacles for donating blood

Background and Objectives The aim of the study was to investigate motives for donating blood as well as difficulties and obstacles associated with blood donation as perceived by the donors themselves.

Materials and Methods Six hundred consecutive blood donors (i.e. all blood donors with a history of at least one previous whole blood donation attending, during nine working days, the Blood Centre of Umeå University Hospital) received a self‐administered questionnaire that contained questions aimed at elucidating motives for donating blood (general motives for donating blood, specific motives for the first donation and motives for continuing to be an active blood donor). Questions concerning difficulties and obstacles that had to be overcome in order to continue being a blood donor were also included in the questionnaire.

Results Altogether 531 whole blood donors filled in the questionnaire (88·5%; 322 men and 209 women). No statistically significant differences were found between male and female blood donors concerning general reasons and motives related to donating blood. The most frequently reported reasons for giving blood the first time were ‘influence from a friend’ (47·2% of donors) and ‘request via media’ (23·5% of donors). Among general reasons/motives with highest ranking of importance, the most commonly reported motive for donating blood were ‘general altruism’ (40·3%), ‘social responsibility/obligation’ (19·7%) and ‘influence from friends’ (17·9%). General altruism’ and ‘social responsibility/obligation’ were also the most frequent reasons for continuing to donate blood (68·4 and 16·0%, respectively). The most commonly reported obstacle to becoming a regular blood donor was ‘laziness’ (19·1%) followed by ‘fear of needles’ (10·5%).

Conclusions Altruism was the most common general motive for donating blood and also for continuing to be an active blood donor. Yet, for the first blood donation, direct ‘influence from friends/relatives’, ‘media appeal’ and other types of recruitment were more commonly reported as reasons or motives for donating blood than altruism. The findings support the notion that different strategies should be used/adopted to get people to donate blood the first time (e.g. recruitment through other blood donors using, for example, the ‘bring a friend along’ method) and to retain these subjects as active blood donors (e.g. by information and by strengthening their sense of being a blood donor or their self‐efficacy etc.). [2]

Blood donors and factors impacting the blood donation decision

The aging of the US population and the evidence that only about 5% of individuals in the United States donate blood each year raise concerns about the assurance of an adequate, safe supply of blood in the future. Blood donation decision making has been investigated world-wide for decades to understand the process better to increase donation efficiency, safety, retention, collection numbers, and diversity of the donor pool. This review focuses on the characteristics of allogeneic blood donors, the motivational sources in donor decision making, and the research concepts and techniques used to examine these factors. Some historic studies considered pivotal, as well as more recent surveys, may not be pertinent to or representative of the current national donor pool. Interpretation of data related to donor characteristics should examine whether demographics mirror the donor pool to assist in targeted recruitment or if targeted recruitment actually leads to the reported demographics. Few recent studies of donor motivation have been published. Modern sources of positive and negative motivation are worth exploring through scientifically sound investigations involving representative cohorts using multifactorial approaches. Strategies that focus on retaining return donors and transforming first-time donors into repeaters would be beneficial. Investigations are needed also to assess research questions and to develop well-designed interventions to test hypotheses and to produce generalizable findings applicable to future donor decision making. [3]

The Effect of Repeated Blood Donations on the Iron Status of Male Blood Donors in Enugu State, Nigeria

Background: One of the biggest challenges in blood donation particularly in Nigeria is the recruitment and retention of voluntary non-remunerated, low cost blood donors.

Aims: The aim of this study is to determine the effect of repeated blood donations on iron stores and the prevalence of iron deficiency anaemia among the male blood donors in the Enugu State, Nigeria.

Study Design: In this case-control study, two hundred and twenty three randomly selected male blood donors, were grouped into six categories according to the number of units of blood donated in one year, two years, three years and the last group were on their 4th year.

Place and Duration of Study: Haematology and blood bank laboratory unit, Enugu State University of Science and Technology Teaching Hospital, Enugu, Enugu State, Nigeria: April 2012 to December 2012.

Methodology: Prior to blood donation, blood samples of 202 directed/regular male blood donors and twenty one apparently healthy men with no previous history of blood donation (aged 18-40years) were collected. Donors were grouped into 0, ≤ 3, 4-6, 7-9, 10-12 and > 13 categories based on the number of units of blood donated.

Results: Iron depletion was seen in 1.3% in group 2 (1-3 times) and also in 13.3% of group 4 (7-9 times), iron deficiency was present in 4.4% of group 3 (4-6 times) and in 20% of group 6 (13-15 times) and iron deficiency anaemia was discovered in 4.4% of group 3 (4-6 times). Blood donors with more than seven times instances of blood donation (P<0.05) showed a significant relationship between iron depletion and iron deficiency.

Conclusion: This study showed that iron deficiency anaemia in blood donors can occur as a result of increase in number of units of blood donated and also based on iron status of individual at time of donation. Based on findings of this study ferritin test should be done on all male blood donors in Enugu before donating any unit of blood to find out the appropriate time to start iron supplement. [4]

Impact of Some Socio-demographic Characteristics, Motivation and Attitudes towards Blood Donation of Hospital-based Blood Donors as Determinants of Safe Blood in Nigeria

Background: Voluntary non-remunerated blood donors (VNRBD) that provide safe blood needed to save lives and improve health or used as a necessary adjunct to emerging modern Medicare are scarce in Nigeria.

Aim: To assess the contribution of donor socio-demographics characteristics, motivation and attitudes towards blood donation as guide to safe donor identification, recruitment and retention as VNRBD in Nigeria.

Materials and Methods: A total of 440 blood donors who met the minimum criteria to donate blood in Nigeria were enrolled and their serum screened for HIV using a combined HIV antigen-antibody Enzyme Linked Immuno-sorbent Assay (GENSCREEN®PLUS HIV Ag- Ab ELISA). The relevant characteristics were assessed together with their HIV sero-status.

Results: The male/female blood donation and HIV sero-positivity ratio was 379:61 and 39:2 respectively. Blood donors aged 18-35 years donated 77.5% and were 90.2% HIV sero-positive when compared with those aged 36-55 years. Majority of blood donors were of single marital status 46.6% and this group were more unsafe (53.7%) when compared with those married divorced, separated and widowed. Blood donors self-employed or in a form of business, donated more blood (39.3%) and accounted for 51.2% of unsafe blood donations when compared with other categories of occupations. Majority of blood donors attained secondary education 45.7% and were more unsafe donors (48.8%) when compared with tertiary and those with primary or no formal education. Educational attainment showed a statistically significant association with blood safety but age, occupation and marital status did not. Majority of the blood donors were first time 93.2% compared to previous and repeat blood donors who were 6.8% and 6.1% respectively. The FBDs constituted 96.4% and accounted for 100% of unsafe blood when compared with other donors. Altruistic and voluntary blood donors were completely safe donors. Those motivated by pressures (family/friend/relative/peer) to donate their blood were in majority 93.6% and accounted for 95.1% of unsafe blood donors when compared with those motivated to donate for other non-financial reasons. Blood donors with altruistic and self-use motivations were 100% safe. However, the aim, motivation and attitude for blood donation were not statistically significant.

Conclusion: The educational attainment of a predominant youthful blood donor population at hospital-based blood banks in Nigeria is significantly associated with blood safety. There is a need for extensive educational campaign on blood donation at establishments and gatherings where this study group can be found including schools, community/age-group meetings, religious houses and social youth organizations. The medium of communication should be vernacular and languages best understood by these potential blood donors and may include radio, television and advertisements in different social media outlets. It is by these proactive measures that, Nigeria’s target of achieving 100% VNRBD supply by 2020 will be achieved. [5]

Reference

[1] Masser, B.M., White, K.M., Hyde, M.K. and Terry, D.J., 2008. The psychology of blood donation: current research and future directions. Transfusion medicine reviews, 22(3), pp.215-233.

[2] Sojka, B.N. and Sojka, P., 2008. The blood donation experience: self‐reported motives and obstacles for donating blood. Vox sanguinis, 94(1), pp.56-63.

[3] Gillespie, T.W. and Hillyer, C.D., 2002. Blood donors and factors impacting the blood donation decision. Transfusion medicine reviews, 16(2), pp.115-130.

[4] Ositadinma, I. M., Ifeoma, A. G., Martina, N. A., Okorie, O. G., Okechukwu, O. C., Chike James, O. and Chiatogu, I. N. (2014) “The Effect of Repeated Blood Donations on the Iron Status of Male Blood Donors in Enugu State, Nigeria”, Journal of Advances in Medicine and Medical Research, 5(6), pp. 788-793. doi: 10.9734/BJMMR/2015/10442.

[5] Orkuma, J., Gomerep, S., Egesie, J., Orkuma, J., Ejele, A., Ngbea, J., Vhriterhire, R. and Onoja, A. (2015) “Impact of Some Socio-demographic Characteristics, Motivation and Attitudes towards Blood Donation of Hospital-based Blood Donors as Determinants of Safe Blood in Nigeria”, Journal of Education, Society and Behavioural Science, 9(3), pp. 176-185. doi: 10.9734/BJESBS/2015/18263.

Latest News on Bleeding Disorders: Jan 2020

Usefulness of Patient Interview in Bleeding Disorders

Background:  It is not known which questions in a medical interview are most informative for diagnosing mild bleeding disorders, and what the value is of the entire interview in screening for hemostatic disorders.

Methods:  A questionnaire was sent to 222 patients with a proven bleeding disorder, to 134 patients suspected of a bleeding disorder but whose hemostasis proved normal, and to 341 healthy volunteers. A first comparison, between patients with a bleeding disorder and patients with bleeding complaints whose hemostasis proved normal, mimics the situation in a department of hematology where patients are referred because of complaints. The second comparison, between patients with a proven bleeding disorder and healthy volunteers, may serve as a model for the situation where the interview is used as a screening tool to detect patients with a bleeding disorder in a population where there is no prior suspicion, eg, before surgical intervention. For each question we calculated a univariate odds ratio, multivariate odds ratios, and a positive and negative likelihood ratio. With a receiver operating characteristic curve analysis we evaluated the value of a simple vs an elaborate interview.

Results:  Ninety-two percent of the questionnaires were returned. For both comparisons the most informative questions were questions about bleeding disorders in the family and traumatic events, with the exception of delivery. Noninformative questions were frequent gumbleeds and blood in the urine. A receiver operating characteristic curve analysis revealed that a simple interview has a high discriminating power in a screening situation, whereas in a referred situation even an elaborate interview has a low performance.

Conclusions:  A simple interview is useful as a screening tool for the dentist or surgeon. In a specialized hematology center with referred patients, however, the interview is of little value in identifying patients with a bleeding disorder. [1]

Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders

Summary. Background: The European Network of Rare Bleeding Disorders (EN‐RBD) was established to bridge the gap between knowledge and practise in the care of patients with RBDs.

Objectives: To explore the relationship between coagulation factor activity level and bleeding severity in patients with RBDs.

Patients/Methods: Cross‐sectional study using data from 489 patients registered in the EN‐RBD. Coagulation factor activity levels were retrieved. Clinical bleeding episodes were classified into four categories according to severity.

Results: The mean age of patients at data collection was 31 years (range, 7 months to 95 years), with an equal sex distribution. On linear regression analysis, there was a strong association between coagulation factor activity level and clinical bleeding severity for fibrinogen, factor (F) X, FXIII, and combined FV and FVIII deficiencies. A weaker association was present for FV and FVII deficiencies. There was no association between coagulation factor activity level and clinical bleeding severity for FXI. The coagulation factor activity levels that were necessary for patients to remain asymptomatic were: fibrinogen, > 100 mg dL−1; FV, 12 U dL−1; combined FV + VIII, 43 U dL−1; FVII, 25 U dL−1; FX, 56 U dL−1; FXI, 26 U dL−1; FXIII, 31 U dL−1. Moreover, coagulation factor activity levels that corresponded with Grade III bleeding were: undetectable levels for fibrinogen, FV and FXIII, < 15 U dL−1 for combined FV + VIII; < 8 U dL−1 for FVI; < 10 U dL−1 for FX; and < 25 U dL−1 for FXI.

Conclusions: There is a heterogeneous association between coagulation factor activity level and clinical bleeding severity in different RBDs. A strong association is only observed in fibrinogen, FX and FXIII deficiencies. [2]

Coagulation and Bleeding Disorders: Review and Update

Hemostasis is initiated by injury to the vascular wall, leading to the deposition of platelets adhering to components of the subendothelium. Platelet adhesion requires the presence of von Willebrand factor and platelet receptors (IIb/IIIa and Ib/IX). Additional platelets are recruited to the site of injury by release of platelet granular contents, including ADP. The “platelet plug” is stabilized by interaction with fibrinogen. In this review, I consider laboratory tests used to evaluate coagulation, including prothrombin time, activated partial thromboplastin time, thrombin time, and platelet count. I discuss hereditary disorders of platelets and/or coagulation proteins that lead to clinical bleeding as well as acquired disorders, including disseminated intravascular coagulation and acquired circulating anticoagulants. [3]

Etiology of Non-variceal Bleeding of upper Gastrointestinal System: A Brief Review

Upper gastrointestinal bleeding (UGB) has important morbidity and mortality risk and these risk increases when co-morbidities exist. Nonsteroidal anti-inflammatory drugs use and Helicobacter Pylori infection are risk factors for peptic ulcer bleeding. Peptic ulcer disease is the most common cause of non variceal UGB. However, other rare causes should be responsible for UGB especially in treatment resistant cases. [4]

The Prevalence of Menstrual Disorder and Its Association with BMI: A Cross Sectional Study

Introduction: Menstrual disorder is very frequent complain in adolescence age and it can end too many problems .Our purpose of this study was appointed, prevalence the menstrual disorder and relation between it and BMI.

Methods: This cross sectional study was done on 1200   girl’s school that lived in north of Iran (Mazandaran province). We selected our samples randomly. We collected data by questionnaire. Analysis of data was done by spss-19 software and we used descriptive statistics, chi square. Test and in depended T test. Significant level of this study was p< 0.05.

Results: The prevalence of menstrual disturbance was 13.2% (in urban girls) and 8.6% (in rural girls). According to chi- square test, the relation between BMI and hypomenorhea (p= 0.055), polymenorhea (p= 0.384), oligomenorhea (p= 0.757), amenorrhea (p= 0.247), metrorhagia (p= 0.781) and menorrhagia (p=  0.171) was not significant.

Conclusion: Menstrual disorder is common in adolescence age and BMI is not effective on menstrual disturbance. [5]

Reference

[1] Šrámek, A., Eikenboom, J.C., Briet, E., Vandenbroucke, J.P. and Rosendaal, F.R., 1995. Usefulness of patient interview in bleeding disorders. Archives of internal medicine, 155(13), pp.1409-1415.

[2] Peyvandi, F., Palla, R., Menegatti, M., Siboni, S.M., Halimeh, S., Faeser, B., Pergantou, H., Platokouki, H., Giangrande, P., Peerlinck, K. and Celkan, T., 2012. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. Journal of Thrombosis and Haemostasis, 10(4), pp.615-621.

[3] Triplett, D.A., 2000. Coagulation and bleeding disorders: review and update.

[4] Gurler, M. and Aktas, G. (2015) “Etiology of Non-variceal Bleeding of upper Gastrointestinal System: A Brief Review”, Journal of Advances in Medicine and Medical Research, 11(11), pp. 1-4. doi: 10.9734/BJMMR/2016/21716.

[5] Mandana, Z. (2018) “The Prevalence of Menstrual Disorder and Its Association with BMI: A Cross Sectional Study”, Current Journal of Applied Science and Technology, 30(3), pp. 1-5. doi: 10.9734/CJAST/2018/9226.

Latest News on Sickle Cell Disease : Nov 2020

Sickle-cell disease

Sickle-cell disease is one of the most common severe monogenic disorders in the world. Haemoglobin polymerisation, leading to erythrocyte rigidity and vaso-occlusion, is central to the pathophysiology of this disease, although the importance of chronic anaemia, haemolysis, and vasculopathy has been established. Clinical management is basic and few treatments have a robust evidence base. One of the main problems of sickle-cell disease in children is the development of cerebrovascular disease and cognitive impairment, and the role of blood transfusion and hydroxycarbamide for prevention of these complications is starting to be understood. Recurrent episodes of vaso-occlusion and inflammation result in progressive damage to most organs, including the brain, kidneys, lungs, bones, and cardiovascular system, which becomes apparent with increasing age. Most people with sickle-cell disease live in Africa, where little is known about this disease; however, we do know that the disorder follows a more severe clinical course in Africa than for the rest of the world and that infectious diseases have a role in causing this increased severity of sickle-cell disease. More work is needed to develop effective treatments that specifically target pathophysiological changes and clinical complications of sickle-cell disease. [1]

Mortality In Sickle Cell Disease — Life Expectancy and Risk Factors for Early Death

BACKGROUND

Information on life expectancy and risk factors for early death among patients with sickle cell disease (sickle cell anemia, sickle cell-hemoglobin C disease, and the sickle cell-β-thalassemias) is needed to counsel patients, target therapy, and design clinical trials.

METHODS

We followed 3764 patients who ranged from birth to 66 years of age at enrollment to determine the life expectancy and calculate the median age at death. In addition, we investigated the circumstances of death for all 209 adult patients who died during the study, and used proportional-hazards regression analysis to identify risk factors for early death among 964 adults with sickle cell anemia who were followed for at least two years.

RESULTS

Among children and adults with sickle cell anemia (homozygous for sickle hemoglobin), the median age at death was 42 years for males and 48 years for females. Among those with sickle cell-hemoglobin C disease, the median age at death was 60 years for males and 68 years for females. Among adults with sickle cell disease, 18 percent of the deaths occurred in patients with overt organ failure, predominantly renal. Thirty-three percent were clinically free of organ failure but died during an acute sickle crisis (78 percent had pain, the chest syndrome, or both; 22 percent had stroke). Modeling revealed that in patients with sickle cell anemia, the acute chest syndrome, renal failure, seizures, a base-line white-cell count above 15,000 cells per cubic millimeter, and a low level of fetal hemoglobin were associated with an increased risk of early death.

CONCLUSIONS

Fifty percent of patients with sickle cell anemia survived beyond the fifth decade. A large proportion of those who died had no overt chronic organ failure but died during an acute episode of pain, chest syndrome, or stroke. Early mortality was highest among patients whose disease was symptomatic. A high level of fetal hemoglobin predicted improved survival and is probably a reliable childhood forecaster of adult life expectancy. [2]

Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease

Although the deleterious vasoconstrictive effects of cell-free, hemoglobin-based blood substitutes have been appreciated, the systemic effects of chronic hemolysis on nitric oxide bioavailability have not been considered or quantified. Central to this investigation is the understanding that nitric oxide reacts at least 1,000 times more rapidly with free hemoglobin solutions than with erythrocytes. We hypothesized that decompartmentalization of hemoglobin into plasma would divert nitric oxide from homeostatic vascular function. We demonstrate here that plasma from patients with sickle-cell disease contains cell-free ferrous hemoglobin, which stoichiometrically consumes micromolar quantities of nitric oxide and abrogates forearm blood flow responses to nitric oxide donor infusions. Therapies that inactivate plasma hemoglobin by oxidation or nitric oxide ligation restore nitric oxide bioavailability. Decompartmentalization of hemoglobin and subsequent dioxygenation of nitric oxide may explain the vascular complications shared by acute and chronic hemolytic disorders. [3]

Sickle Cell Disease in Pregnancy: Maternal and Fetal Outcome in Port Harcourt, Nigeria

Background: Medical experts for many years have daunted the occurrence of pregnancy in homozygote sickle cell patients. This is because of associated high risk for mother and fetus.

The aim of this study is to determine the prevalence and maternal and fetal outcome of pregnant mothers with sickle cell disease at the University of Port Harcourt Teaching Hospital, Nigeria.

Materials and Methods: This was a retrospective descriptive study of medical case files of all booked pregnant mothers who attended the antenatal clinic of the University of Port Harcourt Teaching Hospital, Nigeria from January 2007 to December 2011. The parameters extracted from the folders included: age, level of education, hemoglobin genotype, full blood count, malaria parasite, urine analysis and culture, complications of pregnancy, Apgar scores and birth weight.

Results: A total of 4,650 mothers were booked for antenatal care. Eight hundred and forty (18.1%) of them were HbAS, five (0.1%) were HbAC, nine (0.2%) were HbSS and 1(0.02%) HbSC. Age and gestation at booking were 18–42 years (mean 28.6± 2.1) and 9–34 weeks gestation (mean 16.6±3.3), respectively. Malaria and vaso-occlusive crisis were the commonest complications encountered in pregnancy. Twenty percent of women had induction of labour and 60% were delivered by emergency caesarean section. Twenty percent had postpartum haemorrhage. Forty four percent of women delivered before 37 completed weeks. Birth weight below 2500 g occurred in 50% of singleton pregnancies. Two neonates developed transient complications related to maternal opiate exposure postnatally. There were 2(20%) maternal and fetal losses from toxaemia of pregnancy.

Conclusion: Pregnancy is uncommon among females with sickle cell disease in Port Harcourt, Nigeria. Sickle cell disease remains a severe complicating factor to pregnancy and associated with increased fetal and maternal losses. [4]

Trace Elements Deficiency in Patients with Homozygous Sickle Cell Disease

Aim: The serum trace elements statuses of sickle cell patients attending at General Hospital Owerri, Nigeria were investigated to determine whether or not the serum levels of these elements were normal.

Materials and Methods: One hundred confirmed sickle cell patients (HbSS) age 5–30 years were selected. One hundred normal subjects (HbAA) age 5–30 years were used as control.

Results: The levels of trace elements were significantly decreased in sickle cell anemia (p<0.05), except copper, when compared with the control.

Conclusion: The result suggests, but not conclusively, that supplementation of sickle cell patients with food and drug containing trace elements might be helpful, particularly if diminished mineral levels predispose patients to crises. [5]

Reference

[1] Rees, D.C., Williams, T.N. and Gladwin, M.T., 2010. Sickle-cell disease. The Lancet, 376(9757), pp.2018-2031.

[2] Platt, O.S., Brambilla, D.J., Rosse, W.F., Milner, P.F., Castro, O., Steinberg, M.H. and Klug, P.P., 1994. Mortality in sickle cell disease–life expectancy and risk factors for early death. New England Journal of Medicine, 330(23), pp.1639-1644.

[3] Reiter, C.D., Wang, X., Tanus-Santos, J.E., Hogg, N., Cannon, R.O., Schechter, A.N. and Gladwin, M.T., 2002. Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nature medicine, 8(12), pp.1383-1389.

[4] Ugboma, H. A. A. and George, I. O. (2015) “Sickle Cell Disease in Pregnancy: Maternal and Fetal Outcome in Port Harcourt, Nigeria”, Journal of Advances in Medicine and Medical Research, 7(1), pp. 40-44. doi: 10.9734/BJMMR/2015/11602.

[5] Nnodim, J., Samuel, M., Dioka, C. E., Onah, C., Ihim, A. and Atuegbu, C. (2014) “Trace Elements Deficiency in Patients with Homozygous Sickle Cell Disease”, Journal of Advances in Medicine and Medical Research, 4(21), pp. 3878-3883. doi: 10.9734/BJMMR/2014/7489.

LATEST RESEARCH NEWS ON BLOOD CANCER : FEB – 2020

Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence

BACKGROUND

Cancers arise from multiple acquired mutations, which presumably occur over many years. Early stages in cancer development might be present years before cancers become clinically apparent.

METHODS

We analyzed data from whole-exome sequencing of DNA in peripheral-blood cells from 12,380 persons, unselected for cancer or hematologic phenotypes. We identified somatic mutations on the basis of unusual allelic fractions. We used data from Swedish national patient registers to follow health outcomes for 2 to 7 years after DNA sampling.[1]

Pancreatic Cancer Risk and ABO Blood Group Alleles: Results from the Pancreatic Cancer Cohort Consortium

A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with risk of pancreatic cancer, but the influence of specific ABO genotypes remains unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, and BB) in 1,534 cases and 1,583 controls from 12 prospective cohorts in PanScan, grouping participants by genotype-derived serologic blood type (O, A, AB, and B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression.[2]

DNA Fragments in the Blood Plasma of Cancer Patients: Quantitations and Evidence for Their Origin from Apoptotic and Necrotic Cells

Increased levels of DNA fragments have frequently been found in the blood plasma of cancer patients. Published data suggest that only a fraction of the DNA in blood plasma is derived from cancer cells. However, it is not known how much of the circulating DNA is from cancer or from noncancer cells. By quantitative methylation-specific PCR of the promoter region of the CDKN2A tumor suppressor gene, we were able to quantify the fraction of plasma DNA derived from tumor cells. In the plasma samples of 30 unselected cancer patients, we detected quantities of tumor DNA from only 3% to as much as 93% of total circulating DNA. [3]

Analysis of O6 -Methylguanine in Cancer Patient Blood during Administration of Cyclophosphamide Using Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry

Aims: To determine O6 -Methylguanine in Cancer Patient Blood during Administration of Cyclophosphamide using Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry.[4]

Visual and Auditory Complications of Chronic Myeloid Leukemia: A Case Report

Hearing loss and visual impairment are not common presentations of Chronic Myeloid Leukemia (CML). We report such a case who presented in the chronic phase with profound hearing loss, visual impairment, progressively enlarging spleen, anaemia, and weight loss. Laboratory evaluation showed Packed Cell Volume – 10%, Total White Cell Count – 1,343 x 109 / L, Platelets – 589 x 109 / L. Blood chemistry showed Uric Acid level of 530mmol/L. Karyotyping showed the Philadelphia chromosome. Chemotherapy was instituted and she improved remarkably with minimal improvement in perception of sound. .[5]

 

Reference

[1] Genovese, G., Kähler, A.K., Handsaker, R.E., Lindberg, J., Rose, S.A., Bakhoum, S.F., Chambert, K., Mick, E., Neale, B.M., Fromer, M. and Purcell, S.M., 2014. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. New England Journal of Medicine, 371(26), pp.2477-2487.

[2] Wolpin, B.M., Kraft, P., Gross, M., Helzlsouer, K., Bueno-de-Mesquita, H.B., Steplowski, E., Stolzenberg-Solomon, R.Z., Arslan, A.A., Jacobs, E.J., LaCroix, A. and Petersen, G., 2010. Pancreatic cancer risk and ABO blood group alleles: results from the pancreatic cancer cohort consortium. Cancer research70(3), pp.1015-1023.

[3] Jahr, S., Hentze, H., Englisch, S., Hardt, D., Fackelmayer, F.O., Hesch, R.D. and Knippers, R., 2001. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer research61(4), pp.1659-1665.

[5] Ejele, O.A., Omunakwe, H.E., Iyalla, C., da Lilly-Tariah, O.B. and Pedro-Egbe, C.N., 2013. Visual and auditory complications of chronic myeloid leukemia: a case report. Journal of Advances in Medicine and Medical Research, pp.566-572.

Latest Research News on Myeloid Leukemia: Jan – 2020

Chronic Myeloid Leukemia

In the past decade clinical and laboratory studies have led to big new insights into the biology of chronic chronic myelocytic leukemia (CML). Basic science has defined the molecular pathogenesis of CML as unregulated signal transduction by a tyrosine kinase. Clinical science has demonstrated that it’s curable through immune-mediated elimination of leukemia cells by allogeneic T lymphocytes.Clinical FeaturesCML may be a malignant clonal disorder of hematopoietic stem cells that leads to increases in not only myeloid cells but also erythroid cells and platelets in peripheral blood and marked myeloid hyperplasia within the bone marrow (Figure 1A, Figure 1B, andFigure 1C). [1]

Age and acute myeloid leukemia

We conducted a retrospective analysis of 968 adults with acute chronic myelocytic leukemia (AML) on 5 recent Southwest Oncology Group trials to know how the character of AML changes with age. Older study patients with AML presented with poorer performance status, lower white blood corpuscle counts, and a lower percentage of marrow blasts. Multidrug resistance was found in 33% of AMLs in patients younger than age 56 compared with 57% in patients older than 75. the share of patients with favorable cytogenetics dropped from 17% in those younger than age 56 to 4% in those older than 75. In contrast, the proportion of patients with unfavorable cytogenetics increased from 35% in those younger than age 56 to 51% in patients older than 75. Particularly striking were the increases in abnormalities of chromosomes 5, 7, and 17 among the elderly. [2]

Acute Myeloid Leukemia

Acute chronic myelocytic leukemia (AML) is characterized by a rise within the number of myeloid cells within the marrow and an arrest in their maturation, frequently leading to hematopoietic insufficiency (granulocytopenia, thrombocytopenia, or anemia), with or without leukocytosis. within the us , the annual incidence of AML is approximately 2.4 per 100,000,1 and it increases progressively with age, to a peak of 12.6 per 100,000 adults 65 years aged or older. Until the 1970s, the diagnosis was based solely on the pathological and cytologic examination of bone marrow and blood. Five-year survival rates during this era were but 15. [3]

Acute myeloid leukemia with isolated del(5q) is associated with IDH1/IDH2 mutations and better prognosis when compared to acute myeloid leukemia with complex karyotype including del(5q)

Myelodysplastic syndrome with isolated del(5q) may be a well-recognized entity with a comparatively favorable prognosis. Isolated del(5q) in acute chronic myelocytic leukemia is rare and acute chronic myelocytic leukemia cases with isolated del(5q) aren’t well characterized. Del(5q) has been shown to be a poor prognostic marker in acute chronic myelocytic leukemia supported multivariable analysis in large cohort studies, which contained mostly cases with del(5q) within the context of multiple chromosomal abnormalities. To further characterize acute chronic myelocytic leukemia with isolated del(5q), clinicopathologic characterization including mutation analysis was performed. [4]

Impact of DNMT3A Gene Mutation on Response of Acute Myeloid Leukemia Patients to Induction Therapy

Aim: to guage the frequency and prognostic impact of DNA methyltransferase 3A (DNMT3A) point mutation on response to induction therapy in newly diagnosed acute chronic myelocytic leukemia patients.

Study Design: Cross-sectional descriptive study.

Place and Duration: Hematology units of Suez Canal and Ain Shams schools of drugs , Egypt. Between September 2016 and July 2017.

Methodology: The study enrolled forty patients (male: female ratio was 1; mean age was 52.4 ± 19.4 years) with newly diagnosed de novo AML before starting induction therapy. DNMT3A mutations were detected using dye terminator sequencing technique for the second a part of DNMT3A, encompassing the PHD and methyltransferase domains and representing exons 11 till the last exon 23. Hematological, cytogenetic studies and DNMT3A mutation results were compared to the patients’ hematological response to induction therapy. [5]

Reference

[1] Sawyers, C.L., 1999. Chronic myeloid leukemia. New England Journal of Medicine, 340(17), (Web Link)

[2] Appelbaum, F.R., Gundacker, H., Head, D.R., Slovak, M.L., Willman, C.L., Godwin, J.E., Anderson, J.E. and Petersdorf, S.H., 2006. Age and acute myeloid leukemia. Blood, 107(9), (Web Link)

[3] Lowenberg, B., Downing, J.R. and Burnett, A., 1999. Acute myeloid leukemia. New England Journal of Medicine, 341(14), (Web Link)

[4] Acute myeloid leukemia with isolated del(5q) is associated with IDH1/IDH2 mutations and better prognosis when compared to acute myeloid leukemia with complex karyotype including del(5q)
Bryan Rea, Nidhi Aggarwal, Svetlana A. Yatsenko, Nathanael Bailey & Yen-Chun Liu
Modern Pathology (2019) (Web Link)

[5] G. Segai, D., Ramsis, N., Fahmy, H. and Kamel, N. (2018) “Impact of DNMT3A Gene Mutation on Response of Acute Myeloid Leukemia Patients to Induction Therapy”, International Blood Research & Reviews, 8(3), (Web Link)

News Update on Lymphoma Research: Jan – 2020

Modern Radiation Therapy for Nodal Non-Hodgkin Lymphoma—Target Definition and Dose Guidelines From the International Lymphoma Radiation Oncology Group

Radiation therapy (RT) is that the best single modality for local control of non-Hodgkin lymphoma (NHL) and is a crucial component of therapy for several patients. Many of the historic concepts of dose and volume have recently been challenged by the arrival of recent imaging and RT planning tools. The International Lymphoma Radiation Oncology Group (ILROG) has developed these guidelines after multinational meetings and analysis of obtainable evidence. the rules represent an agreed consensus view of the ILROG committee on the utilization of RT in NHL within the era . The roles of reduced volume and reduced doses are addressed, integrating modern imaging with 3-dimensional planning and advanced techniques of RT delivery. within the era , during which combined-modality treatment with systemic therapy is acceptable , the previously applied extended-field and involved-field RT techniques that targeted nodal regions have now been replaced by limiting the RT to smaller volumes based solely on detectable nodal involvement at presentation. [1]

Non-Hodgkin’s Lymphoma After Primary Hodgkin’s Disease in the German Hodgkin’s Lymphoma Study Group: Incidence, Treatment, and Prognosis

PURPOSE: The cumulative incidence for non-Hodgkin lymphoma’s (NHL) after primary Hodgkin’s disease (HD) ranges between 1% and 6%. to research the course of disease for secondary NHL, we retrospectively analyzed patients treated within clinical trials of the German Hodgkin’s Lymphoma Study Group (GHSG) since 1981.

PATIENTS AND METHODS: From 1981 to 1998, the GHSG conducted three generations of clinical trials for the treatment of primary HD involving a complete of 5,406 patients. Reference histology by an expert panel was obtained for 4,104 of the patients. Data on incidence, treatment, and outcome of secondary NHL were updated in March 1999. [2]

Testicular lymphoma.

Non-Hodgkin’s lymphoma of the testis is an uncommon disease. It accounts for about 9% of testicular neoplasms. Despite this low overall incidence, however, it’s the foremost common testicular malignancy within the elderly. Testicular lymphoma features a rather high incidence of bilateral involvement and a propensity for extranodal spread to the skin, subcutaneous tissue, CNS, lung, and Waldeyer’s ring. Although intermediate-grade diffuse large B-cell lymphoma is that the commonest histologic pattern among primary testicular lymphoma, secondary infiltration of the testis, especially in high-grade Burkitt’s lymphoma, is more prevalent. Although excellent results with a doxorubicin-containing chemotherapy regimen are achieved in early-stage disease, patients with advanced disease have a grave prognosis. [3]

Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma

Anti-CD19 chimeric antigen receptor (CAR)-expressing T cells are an efficient treatment for B-cell lymphoma, but often cause neurologic toxicity. We treated 20 patients with B-cell lymphoma on a phase I clinical trial , first-in-human clinical test of T cells expressing the new anti-CD19 CAR Hu19-CD828Z (NCT02659943). the first objective was to assess safety and feasibility of Hu19-CD828Z T-cell therapy. Secondary objectives included assessments of blood levels of CAR T cells, anti-lymphoma activity, second infusions and immunogenicity. All objectives were met. Fifty-five percent of patients who received Hu19-CD828Z T cells obtained complete remission. Hu19-CD828Z T cells had clinical anti-lymphoma activity almost like that of T cells expressing FMC63-28Z, an anti-CD19 CAR tested previously by our group, which contains murine binding domains and is employed in axicabtagene ciloleucel. [4]

A Rare Case Report of Duodenal Marginal Zone B-cell Lymphoma Related to Immunoproliferative Small Intestinal Disease and Associated Lymphoma (IPSID)

Marginal zone B-cell lymphoma may be a unique lymphoma of the alimentary canal most ordinarily in developing countries with poor socioeconomic conditions, poor hygiene, malnutrition, and a high degree of intestinal infections where IPSID is common.

We experienced a rare case of extranodal MZBCL in duodenum (sub sort of MALT) during a 14-year-old girl who complained of epigastric pain.

Abdominal computerized tomography (CT) with Intravenous (IV) contrast showed mixed mass infiltrate the intestinal wall with mesenteric lymphadenopathy.

Upper alimentary canal endoscopy had showed obstruction within the 2nd segment of duodenum, biopsies were taken. [5]

Reference

[1] Illidge, T., Specht, L., Yahalom, J., Aleman, B., Berthelsen, A.K., Constine, L., Dabaja, B., Dharmarajan, K., Ng, A., Ricardi, U. and Wirth, A., 2014. Modern radiation therapy for nodal non-Hodgkin lymphoma—target definition and dose guidelines from the International Lymphoma Radiation Oncology Group. International Journal of Radiation Oncology* Biology* Physics, 89(1), (Web Link)

[2] Rueffer, U., Josting, A., Franklin, J., May, M., Sieber, M., Breuer, K., Engert, A. and Diehl for the German Hodgkin’s Lymphoma Study Group, V., 2001. Non-Hodgkin’s lymphoma after primary Hodgkin’s disease in the German Hodgkin’s Lymphoma Study Group: incidence, treatment, and prognosis. Journal of clinical oncology, 19(7), (Web Link)

[3] Shahab, N. and Doll, D.C., 1999, June. Testicular lymphoma. In Seminars in oncology (Web Link)

[4] Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma
Jennifer N. Brudno, Norris Lam, Danielle Vanasse, Yueh-wei Shen, Jeremy J. Rose, John Rossi, Allen Xue, Adrian Bot, Nathalie Scholler, Lekha Mikkilineni, Mark Roschewski, Robert Dean, Raul Cachau, Philippe Youkharibache, Rashmika Patel, Brenna Hansen, David F. Stroncek, Steven A. Rosenberg, Ronald E. Gress & James N. Kochenderfer
Nature Medicine (2020) (Web Link)

[5] Aljarad, Z., Nasser, M., Ghazal, A., Alkhaled, M., Obeed, B., Shaghaleh, M. and Alhussein, M. W. (2017) “A Rare Case Report of Duodenal Marginal Zone B-cell Lymphoma Related to Immunoproliferative Small Intestinal Disease and Associated Lymphoma (IPSID)”, Journal of Advances in Medicine and Medical Research, 20(8), (Web Link)