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Cancers May 2022Alectinib is a standard initial treatment for patients with advanced anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC). The current study...
Alectinib is a standard initial treatment for patients with advanced anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC). The current study analyzed a prospective cohort of 24 consecutive alectinib-treated patients and controls in order to comprehensively characterize longitudinal erythrocyte changes under treatment with ALK inhibitors. Upon starting alectinib, all examined patients developed reticulocytosis and abnormal erythrocyte morphology with anisocytosis and a predominance of acanthocytes (64% of red blood cells on average, range 36−100%) in the peripheral blood smear within approximately 2 weeks. Changes were accompanied by a gradual reduction in Eosin-5-maleimide (EMA) binding, which became pathologic (<80% of cells) within 1−2 months in all cases, mimicking an abortive form of hereditary spherocytosis. The latter could be ruled out in 3/3 of analyzed cases by normal sequencing results for the ANK1, EPB42, SLC4A1, SPTA1, or SBTB genes. The direct Coombs test was also negative in 11/11 tested cases. Besides, anemia, increased LDH, and increased bilirubin were noted in a fraction of patients only, ranging between 42 and 68%. Furthermore, haptoglobin decreases were infrequent, occurring in approximately 1/3 of cases only, and mild, with an average value of 0.93 g/L within the normal range of 0.3−2 g/dL, suggesting that hemolysis occurred predominantly in the extravascular compartment, likely due to splenic trapping of the deformed erythrocytes. These changes showed no association with progression-free survival under alectinib or molecular features, i.e., ALK fusion variant or TP53 status of the disease, and resolved upon a switch to an alternative ALK inhibitor. Thus, alectinib induces mild, reversible erythrocyte changes in practically all treated patients, whose most sensitive signs are aberrant red cell morphology in the peripheral smear, a pathologic EMA test, and reactive reticulocytosis. Frank hemolytic anemia is rare, but mild subclinical hemolysis is very frequent and poses differential-diagnostic problems. Alectinib can be continued under the regular control of hemolysis parameters, but the risk of long-term complications, such as cholelithiasis due to increased serum bilirubin in most patients, remains unclear at present.
PubMed: 35681698
DOI: 10.3390/cancers14112720 -
Cells Oct 2022The GATA1 transcription factor is essential for normal erythropoiesis and megakaryocytic differentiation. Germline GATA1 pathogenic variants in the N-terminal zinc...
The GATA1 transcription factor is essential for normal erythropoiesis and megakaryocytic differentiation. Germline GATA1 pathogenic variants in the N-terminal zinc finger (N-ZF) are typically associated with X-linked thrombocytopenia, platelet dysfunction, and dyserythropoietic anemia. A few variants in the C-terminal ZF (C-ZF) domain are described with normal platelet count but altered platelet function as the main characteristic. Independently performed molecular genetic analysis identified a hemizygous variant (c.865C>T, p.H289Y) in the C-ZF region of GATA1 in a German patient and in a Spanish patient. We characterized the bleeding and platelet phenotype of these patients and compared these findings with the parameters of two German siblings carrying the likely pathogenic variant p.D218N in the GATA1 N-ZF domain. The main difference was profound thrombocytopenia in the brothers carrying the p.D218N variant compared to a normal platelet count in patients carrying the p.H289Y variant; only the Spanish patient occasionally developed mild thrombocytopenia. A functional platelet defect affecting αIIbβ3 integrin activation and α-granule secretion was present in all patients. Additionally, mild anemia, anisocytosis, and poikilocytosis were observed in the patients with the C-ZF variant. Our data support the concept that GATA1 variants located in the different ZF regions can lead to clinically diverse manifestations.
Topics: Humans; Male; GATA1 Transcription Factor; Integrins; Phenotype; Thrombocytopenia; Zinc Fingers; Genetic Diseases, X-Linked; Genetic Variation; Anemia, Dyserythropoietic, Congenital; Blood Platelets
PubMed: 36291092
DOI: 10.3390/cells11203223 -
Retrospective and Prospective Investigations about "Quatrefoil" Erythrocytes in Canine Blood Smears.Veterinary Medicine International 2014The presence of unusual two RBCs patterns (so-called "quatrefoil RBCs," qRBCs) on canine blood smears at Optical Microscope (OM) was seen during routine evaluation of...
The presence of unusual two RBCs patterns (so-called "quatrefoil RBCs," qRBCs) on canine blood smears at Optical Microscope (OM) was seen during routine evaluation of CBCs. Two consecutive retrospective investigations were arranged including about 7,000 CBCs and clinical records and laboratory data from dogs showing qRBCs. Few samples with qRBCs were prepared for Scanning Electron Microscope (SEM). qRBCs were found in 6.89% (139 of 2016) and 8.47% (133 of 1569) of dogs and in 3.89% (154 of 3,958) and 4.47% (138 of 3,081) of CBCs (some dogs were tested more than once). Statistical analysis was significant for age groups (Chi squared, P < 0.0001), decreased total leukocyte and neutrophil counts (ANOVA, P < 0.0001), RBCs anisocytosis, polychromasia, and Howell-Jolly bodies (ANOVA, P < 0.018, <0.005, and <0.003, respectively). qRBCs were distributed in the area of feathered edge and at the smear side of body-feathered edge area in blood films. SEM ruled out the possibility of an optical illusion or an accidental overlap. qRBCs are associated with ageing of dogs, total leukocyte and neutrophil counts, and RBC anisocytosis, polychromasia, and Howell-Jolly bodies. Few hypotheses were discussed to explain the origin and meaning of this RBC arrangement.
PubMed: 24511413
DOI: 10.1155/2014/409573 -
Animals : An Open Access Journal From... Jun 2021Apocrine gland anal sac adenocarcinoma (AGASACA) is locally aggressive and highly metastatic to regional lymph nodes. The aim of this study was to evaluate the...
Apocrine gland anal sac adenocarcinoma (AGASACA) is locally aggressive and highly metastatic to regional lymph nodes. The aim of this study was to evaluate the prognostic significance of Ki67 in surgically excised AGASACA. Prognostic impact of size, regional lymph nodes metastasis, hypercalcemia, histologic pattern, mitotic count, necrosis, inflammatory and lympho-vascular invasion, anisokaryosis and anisocytosis was also evaluated. Thirty-five dogs were included, twenty-four of which also had metastatic lymph nodes. When the entire population was evaluated, only metastatic disease spread to regional lymph nodes, and necrosis and inflammatory infiltration were correlated to prognosis. When only dogs with metastatic disease were evaluated, size, solid histologic pattern, presence of lymphatic and vascular invasion showed influence on prognosis. Ki67 index was not associated with survival time and disease free interval in any case. The results of this study showed that lymph nodes metastasis at diagnosis reduced disease free interval. Moreover, tumor size greater than 5.25 cm, presence of lymphatic and vascular invasion and a solid histologic pattern were associated with a shorter survival time in dogs with metastasis to regional lymph nodes. Ki67 expression was not significantly associated with prognosis, therefore it could not be considered as a prognostic factor in this tumor type, while the role of hypercalcemia remained unclear.
PubMed: 34199347
DOI: 10.3390/ani11061649 -
Journal of Clinical Medicine Dec 2023Diabetes and obesity have been recognized as confirmed risk factors for the occurrence of liver fibrosis. Despite the long-standing acknowledgment of "diabesity", the...
Diabetes and obesity have been recognized as confirmed risk factors for the occurrence of liver fibrosis. Despite the long-standing acknowledgment of "diabesity", the simultaneous existence of diabetes and obesity, scholarly literature has shown limited attention to this topic. The aim of this pilot study was to assess the prevalence of liver fibrosis among individuals with diabetes (specifically those who are obese) in order to identify the key factors associated with hepatofibrosis and determine the most important associations and differences between patients with and without liver fibrosis. The research included a total of 164 participants (48.17% had comorbid obesity). Liver elastography (Fibroscan) was performed on these individuals in addition to laboratory tests. Liver fibrosis was found in 34.76% of type 2 diabetes patients; male gender almost doubled the risk of hepatofibrosis (RR 1.81) and diabesity nearly tripled this risk (RR 2.81; however, in degree III of obesity, the risk was elevated to 3.65 times higher). Anisocytosis, thrombocytopenia, or elevated liver enzymes raised the incidence of liver fibrosis by 1.78 to 2.47 times. In these individuals, liver stiffness was negatively correlated with MCV, platelet count, and albumin concentration; GGTP activity and HbA1c percentage were positively correlated. The regression analysis results suggest that the concentration of albumin and the activity of GGTP are likely to have a substantial influence on the future management of liver fibrosis in patients with diabesity. The findings of this study can serve as the basis for subsequent investigations and actions focused on identifying potential therapeutic and diagnostic avenues.
PubMed: 38137829
DOI: 10.3390/jcm12247760 -
Comparative Medicine Dec 2016In the present study, we described the phenotype, histologic morphology, and molecular etiology of a mouse model of unstable hemoglobin Santa Ana. Hematologic evaluation...
In the present study, we described the phenotype, histologic morphology, and molecular etiology of a mouse model of unstable hemoglobin Santa Ana. Hematologic evaluation of anemic mice (Anem/+) discovered after N-ethyl-N-nitrosourea mutagenesis revealed moderate anemia with intense reticulocytosis and polychromasia, followed by anisocytosis, macrocytosis, hypochromia, and intraerythrocytic inclusion and Heinz bodies. The mice also demonstrated hemoglobinuria, bilirubinemia, and erythrocytic populations with differing resistance to osmotic lysis. Splenomegaly (particularly in older mutant mice) and jaundice were apparent at necropsy. Histopathologic examination revealed dramatically increased hematopoiesis and hemosiderosis in hematopoietic organs and intracellular iron deposition in tubular renal cells. These data are characteristic of a congenital hemolytic regenerative anemia, similar to human anemias due to unstable hemoglobin. Genetic mapping assigned the affected gene to mouse chromosome 7, approximately 50 cM from the Hbb locus. The sequence of the mutant Hbb gene exhibited a T→C transversion at nucleotide 179 in Hbb-b1, leading to the substitution of proline for leucine at amino acid residue 88 and thus homologous to the genetic defect underlying Santa Ana anemia in humans.
Topics: Anemia, Hemolytic, Congenital; Animals; Chromosome Mapping; Disease Models, Animal; Ethylnitrosourea; Female; Genotype; Hemoglobins, Abnormal; Humans; Male; Mice; Mice, Inbred BALB C; Mutation
PubMed: 28304246
DOI: No ID Found -
Journal of Cytology 2016Small round cell tumors (SRCTs) are a group of tumors composed of small, round, and uniform cells with high nuclear/cytoplasmic (N/C) ratios. The appearance of SRCT...
BACKGROUND
Small round cell tumors (SRCTs) are a group of tumors composed of small, round, and uniform cells with high nuclear/cytoplasmic (N/C) ratios. The appearance of SRCT neoplastic cells in the effusion fluid is very rare. We reported the cytomorphological findings of SRCTs in effusion cytology, and performed statistical and mathematical analyses for a purpose to distinguish SRCTs.
MATERIALS AND METHODS
We analyzed the cytologic findings of effusion samples from 40 SRCT cases and measured the lengths of the nuclei, cytoplasms, and the cell cluster areas. The SRCT cases included 14 Ewing sarcoma (EWS)/primitive neuroectodermal tumor cases, 5 synovial sarcoma cases, 6 rhabdomyosarcoma cases, 9 small cell lung carcinoma (SCLC) cases, and 6 diffuse large B-cell lymphoma (DLBL) cases.
RESULTS
Morphologically, there were no significant differences in the nuclear and cytoplasmic lengths in cases of EWS, synovial sarcoma, and rhabdomyosarcoma. The cytoplasmic lengths in cases of SCLC and DLBL were smaller than those of EWS, synovial sarcoma, and rhabdomyosarcoma. The nuclear density of the cluster in SCLC was higher than that in other SRCTs, and cases of DLBL showed a lack of anisokaryosis and anisocytosis.
CONCLUSION
We believe that it might be possible to diagnose DLBL and SCLC from cytologic analysis of effusion samples but it is very difficult to use this method to distinguish EWS, synovial sarcoma, and rhabdomyosarcoma. Statistical and mathematical analyses indicated that nuclear density and dispersion of nuclear and cytoplasmic sizes are useful adjuncts to conventional cytologic diagnostic criteria, which are acquired from experience.
PubMed: 27279684
DOI: 10.4103/0970-9371.182529 -
Anesthesia and Analgesia Jun 2015Prolonged administration of nitrous oxide causes an increase in plasma homocysteine in children via vitamin B12 inactivation. However, it is unclear whether nitrous...
BACKGROUND
Prolonged administration of nitrous oxide causes an increase in plasma homocysteine in children via vitamin B12 inactivation. However, it is unclear whether nitrous oxide doses used in clinical practice cause adverse hematological effects in pediatric patients.
METHODS
This retrospective study included 54 pediatric patients undergoing elective spinal surgery: 41 received nitrous oxide throughout anesthesia (maintenance group), 9 received nitrous oxide for induction and/or emergence (induction/emergence group), and 4 did not receive nitrous oxide (nitrous oxide-free group). Complete blood counts obtained before and up to 4 days after surgery were assessed for anemia, macrocytosis/microcytosis, anisocytosis, hyperchromatosis/hypochromatosis, thrombocytopenia, and leukopenia. The change (Δ) from preoperative to the highest postoperative value was calculated for mean corpuscular volume (MCV) and red cell distribution width (RDW).
RESULTS
No pancytopenia was present in any patient after surgery. All patients had postoperative anemia, and none had macrocytosis. Postoperative MCV (mean [99% confidence interval]) peaked at 86 fL (85-88 fL), 85 fL (81-89 fL), and 88 fL (80-96 fL) and postoperative RDW at 13.2% (12.8-13.5%), 13.3% (12.7-13.8%), and 13.0% (11.4-14.6%) for the maintenance group, the induction/emergence group, and the nitrous oxide-free group. Two patients in the maintenance group (5%) developed anisocytosis (RDW >14.6%), but none in the induction/emergence group or in the nitrous oxide-free group (P = 0.43). Both ΔMCV (P = 0.52) and ΔRDW (P = 0.16) were similar across all groups.
CONCLUSIONS
Nitrous oxide exposure for up to 8 hours is not associated with megaloblastic anemia in pediatric patients undergoing major spinal surgery.
Topics: Administration, Inhalation; Adolescent; Age Factors; Anemia; Anesthetics, Inhalation; Blood Cells; Child; Child, Preschool; Drug Administration Schedule; Elective Surgical Procedures; Female; Humans; Leukopenia; Male; Nitrous Oxide; Pancytopenia; Retrospective Studies; Risk Assessment; Risk Factors; Spine; Thrombocytopenia; Time Factors; Treatment Outcome
PubMed: 25658315
DOI: 10.1213/ANE.0000000000000642 -
Journal of Hematology Dec 2018The study shows the effect of hyperglycemia on RBCs in terms of morphological changes and their chromic status in women with gestational diabetes mellitus (GDM).
BACKGROUND
The study shows the effect of hyperglycemia on RBCs in terms of morphological changes and their chromic status in women with gestational diabetes mellitus (GDM).
METHODS
A total of 100 pregnant women were enrolled from Maternity and Children Hospital, Qassim, Saudi Arabia including 40 women with confirmed GDM (group-1), 30 women with either type 1 or type 2 diabetes (group-2) and 30 women with normal pregnancy without GDM or pre-gestational diabetes (control group-3). Demographic, anthropometric, medical and biochemical data were obtained from the study subjects. Complete blood count (CBC) and peripheral smears were performed from routine blood samples. Red blood cells (RBCs) morphological analysis was carried out by a hematologist and deviations in size, shape, and staining properties of the RBCs were recorded.
RESULTS
The groups were similar in demographic characteristics (P > 0.05). RBCs showed normocytic and normochromic features in 83.3% patients of group-3 as compared to 57.5% in group-1, 30% in group-2, respectively. Microcytic hypochromic cells and anisocytosis were mostly encountered in group-2 in 53.3% and 93.3% patients respectively (P = 0.000). Forty percent of RBCs in goup-1 showed microcytic and hypochromic characteristics as compared to group-3 (P = 0.015). Additionally, 42.5% group-1 patients had anisocytosis as compared to group-3 (P = 0.003). Poikilocytosis, target cells and macrocytes were mostly observed in group-2.
CONCLUSIONS
Persistent hyperglycemia changes shape, size and hemoglobin contents of RBCs which are associated with the hyperglycemic status and exposure time.
PubMed: 32300429
DOI: 10.14740/jh449w -
Cardiology Journal 2020Acute kidney injury (AKI) is one of the serious postoperative complications in patients undergoing heart valve surgery. The aim of the present study was to identify...
BACKGROUND
Acute kidney injury (AKI) is one of the serious postoperative complications in patients undergoing heart valve surgery. The aim of the present study was to identify selected biomarkers to predict AKI requiring renal replacement.
METHODS
A prospective study was conducted on a group of 751 patients undergoing heart valve surgery. The data on risk factors, preoperative complete blood count, course of operations and postoperative period was assessed. The primary endpoint at the 30-day follow-up was postoperative AKI requiring renal replacement therapy. The secondary end-point was death from all causes in patients with postoperative AKI requiring renal replacement.
RESULTS
The primary endpoint occurred in 46 patients. At multivariate analysis: age, red cell distribution width (RDW) and C-reactive protein remained independent predictors of the primary endpoint. Hemoglobin and RDW were associated with an increased risk of death.
CONCLUSIONS
Elevated RDW is associated with a higher risk of postoperative AKI and death in patients with AKI.
Topics: Cardiac Surgical Procedures; Heart Valves; Humans; Postoperative Complications; Postoperative Period; Prospective Studies; Renal Replacement Therapy; Risk Factors
PubMed: 30799549
DOI: 10.5603/CJ.a2019.0020