Leukemia risk and rate of radiation dose accumulation. Part 2: Comparative analysis of leukocytic indices and dynamics of peripheral blood values in relation to external gamma-exposure dose

The results of a retrospective analysis of leukocytic indices and dynamics of peripheral blood values in relation to external gamma-exposure dose among the personnel of the first atomic production facility in Russia were presented. The study was performed on the basis of the database “Leukemia in the cohort of workers of the Mayak Production Association employed in 1948-1958”. The database contains hematological, clinical and dosimetry information on the two groups of workers: the study group includes individuals with leukemia as the cause of death (n=84); control group includes personnel without hematological cancer pathology (n=300). The control group was composed by selecting 3-4 internal control cases for each leukemia case taking into account gender, age of the start of the exposure and the same accumulated absorbed dose of gamma-exposure to red bone marrow. Based on 19592 analysis of peripheral blood we had described hematopoiesis shifts along cell lines, performed correlation analysis of interrelation between hemogram values and radiation dose, analyzed particular characteristics of blast cells’ appearance in peripheral blood flow in the period prior to leukemias. Comparative analysis of various leukocytic indices was performed among Mayak PA personnel for the first time. The diverse nature of the response of bone marrow hematopoiesis was noted; more pronounced hematological shifts were indicated regarding more intensive production exposure. A number of hematopoietic features were detected among people exposed to production radiation: 1) cytopenia in relation to minimum accumulated doses of radiation exposure in both studied groups; 2) more pronounced lability of hemograms in relation to increased accumulation dose of external gamma-exposure and period of radiation exposure among individuals who had developed leukemia in future in comparison to controls; 3) correlation between peripheral blood cells and accumulated doses of external gamma-exposure was characterized by the highest values of coefficients among individuals with future leukemias; 4) myeloblasts were most often registered among all the blast cells; proerythroblasts were characterized by the shortest average period from the start of the exposure and to the moment of their appearance in the peripheral blood flow (178 days in the study group); polychromatophile erythroblasts in peripheral blood were registered only among the workers with future leukemia; 5) when comparing leukocytic indices in proportion to the categories of accumulated doses of external gamma-exposure, a pronounced variability in the ratio of blood cells was observed among exposed individuals who were subsequently diagnosed with leukemia, especially in the range of 2.0-2.5 Gy. Thus, a comprehensive analysis of hematological parameters, including the assessment of leukocytic indices, is more informative than studying a standard hemogram. Particular features of the dynamics of the cellular composition of peripheral blood can be used as indicators of pathological hematopoiesis in exposed workers prior to clinical manifestation of leukemia.

Download Full-text

Effects of the Airway Obstruction on the Skin Microcirculation in Patients with Bronchial Asthma

Annals of the Russian academy of medical sciences ◽

10.15690/vramn661 ◽

2016 ◽

Vol 71 (3) ◽

Cited By ~ 2

Author(s):

Irina V. Tikhonova ◽

N. I. Kosyakova ◽

A. V. Tankanag ◽

N. K. Chemeris

Keyword(s):

Blood Flow ◽

Airway Obstruction ◽

Bronchial Asthma ◽

Skin Blood Flow ◽

Peripheral Blood ◽

Atopic Asthma ◽

Control Group ◽

Bronchial Obstruction ◽

Peripheral Blood Flow ◽

Flow Parameters

Background: Pulmonary hemodynamic disorders depend on the inflammatory phases and severity of the obstructive syndrome. However, the effect of asthma bronchial obstruction on the state of peripheral hemodynamics remains insufficiently known. Aims: To study the effects of airway obstruction on skin blood flow parameters and its regulatory systems in patients with persistent atopic bronchial asthma in the remission state.Materials and methods: A comparative study of the skin peripheral blood flow in patients with bronchial asthma with severe airway obstruction (1st group) and without obstruction (2nd group) was conducted. 20 patients with confirmed diagnosis of atopic asthma of 50–74 years old participated in the study. All patients received basic therapy in a constant dosing of high doses of inhaled glucocorticosteroids/long-acting beta-2-agonists. The control group included 20 healthy volunteers without evidence of bronchial obstruction. The study lasted for 3 months. The forced expiratory volume in 1 s (FEV1) was used to evaluate the bronchial obstruction by spirometry technique. Skin blood perfusion changes were recorded by laser Doppler flowmetry at rest and in response to short-term local ischemia. Registered peripheral blood flow signals were examined using the amplitude temporal filtering in five frequency intervals to identify the functional features of the peripheral blood flow regulation systems. Results: Consistent two-fold decrease of the oscillation amplitudes was found in the neurogenic interval at rest (p=0.031), as well as in the myogenic (p=0.043; p=0.031) and endothelial intervals (p=0.037; p≤0.001) both at rest and during the postocclusive reactive hyperemia respectively in the 1st group of patients with bronchial obstruction (FEV1 80%) compared with the control group. No significant changes were revealed for skin blood flow parameters in the 2nd patient group (without obstruction, FEV1 80%) in comparison to control subjects.Conclusions: The presence of bronchial obstruction has a significant impact on the changes of the amplitudes of skin blood flow oscillations in patients with bronchial asthma in the myogenic, neurogenic and endothelial intervals.

Download Full-text

Temperature Biofeedback Training to Improve Peripheral Blood Flow in the Upper Extremities of Diabetic Patients

Canadian Journal of Occupational Therapy ◽

10.1177/000841748405100501 ◽

1984 ◽

Vol 51 (5) ◽

pp. 219-224 ◽

Cited By ~ 1

Author(s):

Elizabeth Dean

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Diastolic Blood Pressure ◽

Peripheral Blood ◽

Diabetic Group ◽

Biofeedback Training ◽

Control Group ◽

Diabetic Patients ◽

Peripheral Blood Flow ◽

Temperature Biofeedback

Ten control and ten diabetic subjects were first given a baseline session of no temperature biofeedback, and then were exposed to four 40-minute temperature biofeedback sessions over consecutive days. As the result of feedback training, peripheral skin temperatures increased on the training (right) hands of both groups, and this occurred to a greater extent in the diabetic group. Concomitant temperature increases occurred also in the left hands of both groups. Neither group produced any significant changes in heart rate, respiration rate, or systolic blood pressure with the exception of a significant decrease in diastolic blood pressure for the diabetic group. No difference in diastolic blood pressure was observed, however, when the diabetics were compared with the control group. The results would suggest further evaluation of temperature biofeedback training is warranted in a diabetic population as a potential means of increasing peripheral blood flow in the extremities.

Download Full-text

Parvovirus B19 and Aplastic Anemia: Case Control Study: Preliminary Report from the ITESM Hematology Study Group.

Blood ◽

10.1182/blood.v106.11.3765.3765 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3765-3765

Author(s):

Jose R. Borbolla Escoboza ◽

Marcos E. Garza-Madrid ◽

Luis Villela ◽

Manuel A. Lopez-Hernandez ◽

Jorge Vela-Ojeda

Keyword(s):

Bone Marrow ◽

Aplastic Anemia ◽

Peripheral Blood ◽

Blood Cells ◽

Parvovirus B19 ◽

Bone Marrow Failure ◽

Control Group ◽

Number Of Patients ◽

Two Samples ◽

Sense Primer

Abstract Aplastic anemia (AA) is a classic bone marrow failure syndrome simply defined as peripheral blood pancytopenia and a hypocelular bone marrow, yet the diagnosis must be made by excluding other causes of bone marrow failure. The incidence rate of AA reported by the International Aplastic Anemia and Agranulocytosis Study (IAAAS) in the 1980s was 2 cases per 1 million people. This disease is known to be caused by exposure to radiation, chemotherapy and some viral agents, yet most of the cases are idiopathic. Epstein Barr virus and non-A, non-B or non-C Hepatitis virus have classically been related to the development of some AA cases. Recently there have been some reports of AA following Parvovirus B19 (PvB19) infection. This virus, the only parvoviridae virus capable of infecting humans, attacks erythrocyte precursors attaching to the P antigen in their surface and requiring Beta1 integrin for viral entry. Although PvB19 seems to infect only erytroid precursors, it is widely recognized that the infection with this virus can cause not only anemia, but neutropenia and thrombocytopenia as well, producing aplastic crisis of varying intensity. A correlation has recently been found between PvB19 DNA in peripheral blood and AA in children. We pretend to corroborate this observation and include adult patients in order to improve our understanding of the relationship between PvB19 and AA. So far we have taken peripheral blood samples from 9 AA patients and 9 controls paired by age, sex and community; we plan to include 100 AA patients and their controls from several hospitals around Mexico. DNA was extracted using the PUREGENE DNA extraction kit (Gentra, Minneapolis MN). Nested PCR was performed using the sense primer (P1) 5-AATACACTGTGGTTTTATGGGCCG-3, antisense (P2) 5-CCATTGCTGGTTATAACCACAGGT-3 for the first round and the sense primer (P3) 5-AATGAAAACTTTCCATTTAATGATGTAG-3 and antisense primer (P4) 5-CTAAAATGGCTTTTGCAGCTTCTAC-3for the second round. A DNA sample from a patient with active infectious mononucleosis with positive IgG and IgM against PvB19 in serum was used as positive control. Two samples from the AA group (22%) and 1 from the control group (11%) have turned positive for PvB19 DNA. The reported incidence for the presence of this virusDNA in the peripheral blood of the population is 3%. We expect that, as the number of patients grows, the percentage of positive samples in the control group will decrease, while the percentage of positive samples in the AA group will rise or be sustained. Our partial results point towards a possible relationship between AA and the presence of PvB19 DNA in the peripheral blood cells. It is possible that this virus is one of many factors capable of precipitating the development of AA by limiting the bone marrows capacity to produce blood cells. We are in the process of gathering more samples to prove if a relationship really exists and, if so, future studies will likely shed light upon the mechanism by which PvB19 contributes to the development of AA and other marrow failure syndromes.

Download Full-text

Effects of red blood cells with reduced deformability on cerebral blood flow and vascular water transport: measurements in rats using time-resolved pulsed arterial spin labelling at 9.4 T

European Radiology Experimental ◽

10.1186/s41747-021-00243-z ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Adnan Bibic ◽

Tea Sordia ◽

Erik Henningsson ◽

Linda Knutsson ◽

Freddy Ståhlberg ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Red Blood Cells ◽

Blood Cells ◽

Repeated Measures ◽

Arterial Spin Labelling ◽

Control Group ◽

Study Group ◽

Percentage Points ◽

Spin Labelling

Abstract Background Our aim was to introduce damaged red blood cells (RBCs) as a tool for haemodynamic provocation in rats, hypothesised to cause decreased cerebral blood flow (CBF) and prolonged water capillary transfer time (CTT), and to investigate whether expected changes in CBF could be observed and if haemodynamic alterations were reflected by the CTT metric. Methods Damaged RBCs exhibiting a mildly reduced deformability were injected to cause aggregation of RBCs. Arterial spin labelling (ASL) magnetic resonance imaging experiments were performed at 9.4 T. Six datasets (baseline plus five datasets after injection) were acquired for each animal in a study group and a control group (13 and 10 female adult Wistar rats, respectively). For each dataset, ASL images at ten different inversion times were acquired. The CTT model was adapted to the use of a measured arterial input function, implying the use of a realistic labelling profile. Repeated measures ANOVA was used (alpha error = 0.05). Results After injection, significant differences between the study group and control group were observed for relative CBF in white matter (up to 20 percentage points) and putamen (up to 18–20 percentage points) and for relative CTT in putamen (up to 35–40 percentage points). Conclusions Haemodynamic changes caused by injection of damaged RBCs were observed by ASL-based CBF and CTT measurements. Damaged RBCs can be used as a tool for test and validation of perfusion imaging modalities. CTT model fitting was challenging to stabilise at experimental signal-to-noise ratio levels, and the number of free parameters was minimised.

Download Full-text

Assessment of the Peripheral Blood Flow of Lower Limbs in Patients with Diabetes Mellitus with the Use of Digital Photoplethysmography

Acta Medica Martiniana ◽

10.1515/acm-2015-0008 ◽

2015 ◽

Vol 15 (2) ◽

pp. 21-29 ◽

Cited By ~ 1

Author(s):

G. Hubena ◽

O. Osina ◽

Busikova Prindesova ◽

T. Vasicko

Keyword(s):

Blood Flow ◽

Peripheral Blood ◽

Structural Changes ◽

Lower Limbs ◽

Control Group ◽

Diabetic Patients ◽

Peripheral Blood Flow ◽

Peak Time ◽

Pulse Peak ◽

The Mean

Abstract Introduction: The microcirculation of the lower limbs (LL) of diabetics is influenced by hyperglycemia and several factors (hypertension, obesity, dyslipidemia) leading to the functional and later the structural changes, manifesting as dysregulation of the peripheral blood flow. Materials and Methods: The study included 39 patients with type 2 diabetes, and the same number of the control group. The digital photoplethysmography (PPG) was used for assessment of the peripheral circulation with reflectance mode, sensing from the 1st and 2nd toe of the LL after acclimatisation of the patient in the supine position. The subjects were also asked to refrain from smoking, to avoid drinks containing caffeine and using of medicaments with vasodilatator function at least 2 hours before examination. Results: The pulse amplitudes and the peak times of the PPG curves were significantly higher in diabetic group than in the control group. The mean pulse amplitudes in diabetics were in the range of 0.69 % 0.86 %, the pulse peak time in the range of 140 - 154 ms. The mean pulse amplitudes in the control group were in the range of 0.37 0.54 %, the mean pulse peak time were in the range of 120 - 133 ms. The PPG findings of the LL were symmetrical (non-significant t-test). We have not found a correlation between the PPG records and duration, compensation of diabetes, age, glycemia, blood pressure, dyslipidemia, smoking and obesity. Conclusion: This simple-to-use technique shows the increased total skin microcirculation in diabetic patients. Microvascular shunting of blood presenting in peripheral nerves and in the skin of diabetic feet are responsible for reduced hyperemia response to any inflammatory process with the increased susceptibility for inquiring the diabetic foot infection.

Download Full-text

Flow cytometric detection of receptors for interleukin-6 on bone marrow and peripheral blood cells of humans and rhesus monkeys

Blood ◽

10.1182/blood.v81.8.2036.bloodjournal8182036 ◽

1993 ◽

Vol 81 (8) ◽

pp. 2036-2043

Author(s):

AW Wognum ◽

FC van Gils ◽

G Wagemaker

Keyword(s):

Bone Marrow ◽

T Lymphocytes ◽

Rhesus Monkey ◽

Interleukin 6 ◽

Peripheral Blood ◽

Blood Cells ◽

Rhesus Monkeys ◽

Cell Types ◽

Cd8 T Lymphocytes ◽

Blast Cells

The expression of receptors for interleukin-6 (IL-6) on human and rhesus monkey peripheral blood and bone marrow (BM) cells was examined by multiparameter flow cytometry after staining with biologically active, biotin-labeled human IL-6 and phycoerythrin-conjugated streptavidin. Consistent with the multiple biologic effects of IL-6 in stimulating immune functions and hematopoiesis, IL-6 receptors were detectable on a wide variety of cell types. In peripheral blood, IL-6 receptors were detectable on monocytes, granulocytes, and on CD4+ T lymphocytes but not on resting, CD19+ B lymphocytes and CD56+ natural killer (NK) cells. CD8+ T lymphocytes also expressed IL-6 receptors but at lower levels than CD4+ cells. The IL-6 receptors on granulocytes were only detectable after staining with high concentrations of biotin- IL-6, suggesting that most IL-6 receptors on these cells represent low- affinity sites. In contrast, IL-6 receptors on both CD4+ and CD8+ T lymphocytes were detectable at biotin-IL-6 concentrations as low as 10 pmol/L, indicating that these cells bind IL-6 with high affinity. IL-6 receptor expression patterns on rhesus monkey and human blood cells were very similar except that receptor levels on granulocytes were lower in humans than in rhesus monkeys. Similar differences in expression levels were observed for IL-6 receptors that were detectable on most granulocyte precursors in the mononuclear fraction of rhesus monkey and human bone marrow. In addition to these relatively mature cell types, IL-6 receptors were detectable on a large fraction of human and rhesus monkey BM blast cells that express the CD34 antigen. The presence of IL-6 receptors on CD34+ BM blast cells, which are the precursor cells of most, if not all, BM-derived blood cells, is consistent with the ability of IL-6, in conjunction with other cytokines, to stimulate immature hemopoietic cells in vitro and to promote blood cell production when administered in vivo.

Download Full-text

Pro- and Antiapoptotic Proteins Expression on Bone Marrow and Peripheral Blood CD34+Cells in Acute Leukemia (AL) Patients

Blood ◽

10.1182/blood.v118.21.4996.4996 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4996-4996

Author(s):

Elena E. Khodunova ◽

Elena N Parovichnikova ◽

Irina V. Galtzeva ◽

Sergey M. Kulikov ◽

Valeri G Savchenko

Keyword(s):

Bone Marrow ◽

Peripheral Blood ◽

Conflicts Of Interest ◽

Expression Level ◽

Leukemia Cells ◽

Control Group ◽

Healthy Donors ◽

Cd34 Cells ◽

Significant Difference ◽

Blast Cells

Abstract Abstract 4996 It was shown that drug resistance, poor-risk cytogenetics and poor prognosis in AL is associated with high level of Bcl-2 expression and low Bax/Bcl-2 ratio (<0,3). Fas-antigen (CD95) as a protein triggering the extrinsic apoptotic pathway is differently expressed on hematopoietic precursors. More immature CD34+/CD38- AML blast cells have lower expression of Fas/Fas-L and lower Fas-induced apoptosis than CD34+/CD38+cells. CD34+/CD38− leukemia precursors also have a reduced sensitivity to daunorubicin in vitro and increased expression of multidrug resistance genes (mrp/lrp). CD34+ leukemia cells have not yet been properly characterized regarding the expression of angiotensin converting enzyme (ACE) which regulatory influence on hematopoiesis is now beeing extensively investigated. ACE expression on blast cells is high, but it's still unknown how CD34+ACE+ leukemia cells behave after chemotherapy. Recent publications indicate that CD34+ACE+ hematopoietic precursors transplanted into NOD/SCID mice contribute 10-fold higher numbers of multilineage blood cells than their CD34+ACE- counterparts. We have studied the dynamics of Bcl-2, Bax, CD95 and ACE expression on CD34+ cells in peripheral blood (PB) and bone marrow (BM) in AL pts during treatment. PB and BM samples were collected before and on +36 day after chemotherapy. The antigens were detected by flow cytometry using monoclonal antibodies. We calculated 10 000 cells in each sample. 19 pts were included in the study: 10 - AML and 9 - ALL. The control group comprised 8 healthy donors. At time of diagnosis there were 40±5,7% of CD34+ cells in BM and 26±4,9% - in PB. There was no significant difference between AML and ALL. CD34+ cells in BM and PB of healthy donors constituted 1,6% and 0,27%, respectively. After induction therapy (+36 day) CD34+ cells decreased in BM to 6,1%±3,3 (p=0,0001), in PB to 3,7%± 2,7 (p=0,0008) in all pts. The data on antigens expression on CD34+ cells of BM and PB are presented in table 1 CD34+/Bcl-2+ CD34+/Bax+ CD34+/CD95+ CD34+/ACE+ BM PB BM PB BM PB BM PB AML pts n=10 0 day 38±11,6* 41±14 24,4±7,9 29,2±7,6* 16,4±8,5 23,2±7,8 21,7±9,5 20,8±8,7* 36 day 13,5±3,4** 23,7±5** 46,2±11,5 50,3±11 19,9±5,5 36,4±10 34±6,6 35±9,2** ALL pts n=9 0 day 36±11 33,7±12 46,2±9,4 37,4±3,7* 3,4±1,1* 7,1±2,5* 41±10,9 33,2±9,7* 36 day 18,4±5,8 26±8,9 38±11,8 40,5±10 26,2±9,1** 40,9±9,2** 34±10 62,8±10** Donors n=8 11,7±1,6 26,1±5,9 22,8±4 67,8±6,7 13,4±3,2 47,7±11,6 28±5,3 68,2±10,2 * − p<0.05 compare with donors ** − p<0.05 compare with day 0 CD34/Bcl-2 expression in BM in AML pts is significantly higher (p=0,04) at the diagnosis comparing with donors. CD34/Bcl-2 expression in PB in AML pts and in BM and PB in ALL pts is higher too, but not significantly. This expression level decreased substantially in BM and PB in AML pts on +36 day comparing with day 0 (p<0,05). We did not found significant changes in ALL pts. CD34/Bax expression in PB is significantly lower (p=0,003) both in AML and ALL pts in comparison with donors. In AML, not in ALL, chemotherapy caused augmentation of Bax expression in CD34+ BM and PB cells on +36 day. BM and PB CD34+ cells in donors had different expression characteristics of Bcl-2 and Bax, demonstrating much higher level of pro- and antiapoptotic markers in PB cells. On the contrast CD34+ leukemia cells in BM and PB had similar characteristics regarding CD34/Bcl-2 and CD34/Bax expression. This fact demonstrates the heterogeneity of donor CD34+cells in BM and PB and points that leukemia CD34+cells in BM and PB are rather similar. CD95 expression on CD34+ BM and PB before treatment is significantly lower (p=0,01, p=0,008) in ALL pts in comparison with donors, and this expression level increased after chemotherapy (p<0,05). CD34/CD95 expression in AML pts is similar with donors, and we didn't find changes after treatment. CD34/ACE coexpression in BM cells of leukemia pts and donors did not differ much at any time of evaluation. But CD34/ACE expression in PB cells of AML and ALL pts was much lower (p<0,05) than in donors and substantially increased on the day 36. So, our data demonstrate that Bcl-2, Bax, CD95 and ACE expression on CD34+ cells in AL pts and donors significantly differs. The chemotherapy provokes critical changes in CD34/CD95 expression in BM and PB in ALL pts, CD34/Bcl-2 expression in AML pts and ÑÂ34/ACE expression in PB in all AL pts. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Reductive regulation of BECN1 gene in adult Egyptian patients with do novo AML

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-020-00087-z ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Manal Fawzy Ghozlan ◽

Botheina Ahmed Thabet Farweez ◽

Nesma Ahmed Safwat ◽

Noha Bassiouny Hassan ◽

Walaa Ali Elsalakawy

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

Peripheral Blood ◽

De Novo ◽

Quantitative Polymerase Chain Reaction ◽

Control Group ◽

Significant Difference ◽

Egyptian Patients ◽

Blast Cells ◽

De Novo Aml

Abstract Background Acute myeloid leukaemia (AML) is a clonal haematopoietic disease characterized by the proliferation of immature blast cells in the bone marrow and peripheral blood. Autophagy is an inherent cellular route by which waste macromolecules are engulfed within autophagosomes prior to their fusion with cytoplasmic lysosomes for degradation. The BECN1 gene encodes the Beclin-1 protein, which regulates autophagy. Few reports have investigated BECN1 gene expression and its value in AML patients. Results This randomized case-control study included 50 newly diagnosed AML patients, in addition to 20 subjects as a control group. BECN1 gene expression was assessed using real-time quantitative polymerase chain reaction (qRT-PCR). The median level of BECN1 gene expression in AML patients was 0.41 (IQR 0.29–1.03) in comparison to 1.12 (IQR 0.93–1.26) in the control group (P = 0.000). Seventy-two percent of AML patients showed reduced BECN1 gene expression, which was highly significantly associated with intermediate and adverse cytogenetic risk. Reduced BECN1 gene expression was associated with older age, higher total leukocyte counts, the presence of peripheral blood blast cells, a higher percentage of bone marrow blast cells, and higher expression of CD34 and CD117. FLT3-ITD mutation was detected in 14 patients (38.9%), all of whom showed reduced BECN1 gene expression (P = 0.006). BECN1 gene expression was also reduced in non-responder AML patients, with a highly statistically significant difference (P = 0.002). Conclusion A reduction in BECN1 gene expression might indicate a poor prognosis in adult Egyptian patients with de novo AML. Decreased BECN1 gene expression is associated with a higher risk of resistance to treatment. Targeting autophagy pathways may help in the treatment of AML patients.

Download Full-text

Two Rare Cases of Severe Autoimmune Dyserythropoiesis without Any Underlying Haematological Malignancy or Autoimmune Disease

Blood ◽

10.1182/blood-2020-142281 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 2-3

Author(s):

James A Paterson ◽

Angela Hwang ◽

Stephen Wong ◽

William Sewell ◽

Joanne E. Joseph ◽

...

Keyword(s):

Bone Marrow ◽

Flow Cytometry ◽

Blood Flow ◽

Autoimmune Disease ◽

Peripheral Blood ◽

Inflammatory Markers ◽

Reticulocyte Count ◽

Haematological Malignancy ◽

Peripheral Blood Flow ◽

Clinical Exam

Background: Autoimmune dyserythropoiesis is a rare disorder with only 4 adult cases and 3 paediatric cases reported in the literature. These suggest an underlying cause of haematological malignancy i.e. CLL or autoimmune disorder e.g. SLE1. Two proposed mechanisms of the pathophysiology include erythroblastic synartesis, or a Fas deficiency in autoimmune conditions2. There is no standard of care, however most cases respond to immunosuppression and/or treatment of the underlying condition. This is a report of 2 rare cases of severe autoimmune dyserythropoiesis without any underlying haematological or autoimmune conditions that have both responded to immunosuppression. Methods: Investigations included a haemolytic screen (LDH, bilirubin, haptoglobin, reticulocyte count and DAT), iron, B12 and folate studies, viral screening (EBV, CMV, HBV, HCV, HIV and parvovirus serologies and parvovirus PCR), autoimmune screen (ENA, ANA, RF, anti CCP, dsDNA, ANCA, C3/4), malignancy screen (EPG/IEPG and serum light chains, peripheral blood flow cytometry and imaging including CT CAP and/or PET scans). Bone marrow aspirate and trephine were performed with cytogenetics and molecular testing for myeloid mutations using NGS panels. Results: Case 1 is a 56-year-old female who initially presented in 2006 with fevers, weight loss, night sweats and an unexplained anaemia with a haemoglobin of 67g/L and MCV of 109 fl. WCC was 6.3 x10^9/L and platelet count 495 x 10^9/L. Clinical exam revealed no signs of haematological malignancy or autoimmune disease. Reticulocyte count was low at 7x10^9/L. ESR was significantly elevated at 130 mm/hr. Bone marrow biopsy was hypercellular with increased early erythroid precursors and some erythroid islands that resembled erythroblastic synartesis. Moderate dyserythropoiesis with numerous binucleate forms was also noted. The rest of her investigations were normal. She responded briskly to low dose prednisone (25mg daily) with resolution of her anaemia, reticulocytopaenia and inflammatory markers. She was transitioned onto azathioprine in 2011 as a steroid sparing agent which was ceased in 2018 due to a diagnosis of localised breast cancer. She remained in remission off immunosuppression for 18 months. Her relapse clinical findings and investigations were identical to her initial presentation. Her NGS testing at this time was negative for myeloid genetic mutations. She again responded briskly to prednisolone. Case 2 is a 65-year-old female referred for a 4th opinion in May 2019 regarding transfusion dependent anaemia. Clinical exam revealed no signs of malignancy nor autoimmune disease. Haemoglobin averaged 60g/L with a low reticulocyte count at 11x10^9/L and elevated MCV of 117fL. Ferritin was elevated secondary to multiple prior transfusions at 1190 ug/L. ESR and CRP were elevated with an ANA titre of 1:80 (homogenous). Bone marrow was hypercellular with some minor dysplastic features and increased immature forms. Peripheral blood flow cytometry revealed a small monoclonal B cell population (0.1% of lymphocytes) that was not detected on bone marrow biopsy. The rest of her investigations were normal. She declined a trial of steroid therapy She was commenced on weekly IV rituximab 375mg/m2 for 3 weeks but was unable to tolerate mild infusion reactions and had no response. She was then treated with intravenous immunoglobulin as well as iron chelation therapy and her anaemia, reticulocytopaenia and inflammatory markers quickly resolved. Discussion: These are two rare cases of severe autoimmune dyserythropoiesis with reticulocytopaenia with no autoimmune haemolysis and no underlying autoimmune or malignant disease. Due to the rarity of this disease, there are no clear guidelines on how to manage these patients and more evidence/research is required. Both cases responded well to immunosuppressive treatment in a relapsing/remitting fashion that further reinforces the autoimmune nature of this disease.One patient did not respond to rituximab despite a small monoclonal B lymphocyte population unlike the only other case treated with rituximab reported where this was successful. References: 1. Croisille L, Tchernia G, Casadevall N. Autoimmune disorders of erythropoiesis. Current Opinion in Haematology; 2001. p. 68-73 2. Cramer E, Garcia I, Masse J, Zini J, Lambin P, Oksenhendler E, et al. Erythroblastic Synartesis: An Auto-immune Dyserythropoiesis. Blood; 1994. p. 3683-93. Figure Disclosures Joseph: Bayer Australia:Membership on an entity's Board of Directors or advisory committees;Novo Nordisk:Other: non financial support;Aspen Australia:Other: personal fees .Hamad:Novartis:Honoraria;Abbvie:Honoraria.

Download Full-text

Peripheral blood flow in patients with graves’ disease depending on level of thyroid status compensation

Kazan medical journal ◽

10.17816/kmj1794 ◽

2013 ◽

Vol 94 (6) ◽

pp. 804-807 ◽

Cited By ~ 1

Author(s):

I S Kulabukhova ◽

L N Eliseeva

Keyword(s):

Blood Flow ◽

Peripheral Blood ◽

Vascular Tone ◽

Control Group ◽

Graves Disease ◽

Peripheral Blood Flow ◽

Average Dose ◽

Thyroid Status ◽

Total Recovery ◽

Doppler Flowmetry

Aim. To study the features of peripheral blood flow using laser Doppler flowmetry in patients with Graves’ disease depending on level of thyroid status compensation. Methods. 45 patients with Graves’ disease were divided into three groups 15 patients each depending on level of thyroid status compensation. The first group included patients with compensated hyperthyroidism, the second - with subcompensated hyperthyroidism, the third - with decompensated hyperthyroidism. All patients received combined thyrotropic (thiamazole 15-30 mg, average dose 22.4±1.7 mg) and cardio- and vasotropic therapy (metoprolol 50-100 mg, average dose 72.1±3.3 mg, and fozinopril 10-20 mg, average dose 17.8±2.4 mg), doses were individually adjusted. Results were compared with the control group (15 healthy patients). The peripheral blood flow was evaluated using LAKK-01 («LAZMA», Russia) device. Results. The comparison of control group and patients with Graves’ disease depending on level of thyroid status compensation demonstrated substantial differences. Doppler flowmetry registered increased blood flow, square deviation, variation coefficient in patients with diffuse thyrotoxic goitre, reflecting increase of tissue blood perfusion and reduced vascular tone. The analysis of the frequency histogram showed that the increase of average blood flow amplitude in case of hyperthyroidism was initiated by increase in amplitudes of all flaxmotions characterizing metabolic processes in capillaries. The relevant correlation between registered variables of blood flow and level of thyroid status compensation was registered. The most marked changes were revealed in patients with subcompensated and decompensated hyperthyroidism. In patients with compensated hyperthyroidism, the blood flow was altered the least compared to control group. Increased impact of active blood flow modulation mechanisms due to neurogenic activity and vascular tone was revealed. At the same time, endothelial activity was decreased. Predominance of sympathetic stimuli and compensatory mechanisms intensifying were discovered. Conclusion. The changes of peripheral blood flow in patients with Graves’ disease were typical for congestive-hyperemic type of microcirculation. Intensity of blood flow alterations is defined by thyroid status compensation. However, even the complete clinical and laboratory compensation doesn’t result in total recovery of capillary blood flow compared to healthy people.

Download Full-text