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Hematology Reports May 2024Viral infections, including those caused by COVID-19, can produce striking morphologic changes in peripheral blood. Distinguishing between reactive changes and abnormal...
Viral infections, including those caused by COVID-19, can produce striking morphologic changes in peripheral blood. Distinguishing between reactive changes and abnormal morphology of monocytes remains particularly difficult, with low consensus rates reported amongst hematopathologists. Here, we report a patient who developed transient monocytosis of 11.06 × 10/L with 32% promonocytes and 1% blasts during hospitalization that was secondary to severe COVID-19 infection. Three days later, the clinical status of the patient improved and the WBC had decreased to 8.47 × 10/L with 2.2 × 10/L monocytes. Flow cytometry studies did not reveal immunophenotypic findings specific for an overt malignant population. At no time during admission did the patient develop cytopenia(s), and she was discharged upon clinical improvement. However, the peripheral blood sample containing promonocytes was sent for molecular testing with an extended next-generation sequencing myeloid panel and was positive for pathogenic Type A and R882H mutations. Subsequently, despite an essentially normal complete blood count, the patient underwent a bone marrow assessment that showed acute myeloid leukemia with 77% promonocytes. This case emphasizes the critical importance of a full work up to exclude acute leukemia when classical promonocyte morphology is encountered in the peripheral blood. Promonocytes are not a part of the reactive changes associated with COVID-19 and remain specific to myeloid neoplasia.
PubMed: 38921181
DOI: 10.3390/hematolrep16020033 -
Bone Marrow Transplantation Jun 2024
PubMed: 38909123
DOI: 10.1038/s41409-024-02333-z -
Translational Psychiatry Jun 2024Depression is a prevalent and incapacitating condition with a significant impact on global morbidity and mortality. Although the immune system's role in its pathogenesis...
Depression is a prevalent and incapacitating condition with a significant impact on global morbidity and mortality. Although the immune system's role in its pathogenesis is increasingly recognized, there is a lack of comprehensive understanding regarding the involvement of innate and adaptive immune cells. To address this gap, we conducted a multicenter case-control study involving 121 participants matched for sex and age. These participants had either an active (or current) major depressive episode (MDE) (39 cases) or a remitted MDE (40 cases), including individuals with major depressive disorder or bipolar disorder. We compared these 79 patients to 42 healthy controls (HC), analyzing their immunological profiles. In blood samples, we determined the complete cell count and the monocyte subtypes and lymphocyte T-cell populations using flow cytometry. Additionally, we measured a panel of cytokines, chemokines, and neurotrophic factors in the plasma. Compared with HC, people endorsing a current MDE showed monocytosis (p = 0.001), increased high-sensitivity C-reactive protein (p = 0.002), and erythrocyte sedimentation rate (p = 0.003), and an altered proportion of specific monocyte subsets. CD4 lymphocytes presented increased median percentages of activation markers CD69 (p = 0.007) and exhaustion markers PD1 (p = 0.013) and LAG3 (p = 0.014), as well as a higher frequency of CD4CD25FOXP3 regulatory T cells (p = 0.003). Additionally, patients showed increased plasma levels of sTREM2 (p = 0.0089). These changes are more likely state markers, indicating the presence of an ongoing inflammatory response during an active MDE. The Random Forest model achieved remarkable classification accuracies of 83.8% for MDE vs. HC and 70% for differentiating active and remitted MDE. Interestingly, the cluster analysis identified three distinct immunological profiles among MDE patients. Cluster 1 has the highest number of leukocytes, mainly given by the increment in lymphocyte count and the lowest proinflammatory cytokine levels. Cluster 3 displayed the most robust inflammatory pattern, with high levels of TNFα, CX3CL1, IL-12p70, IL-17A, IL-23, and IL-33, associated with the highest level of IL-10, as well as β-NGF and the lowest level for BDNF. This profile is also associated with the highest absolute number and percentage of circulating monocytes and the lowest absolute number and percentage of circulating lymphocytes, denoting an active inflammatory process. Cluster 2 has some cardinal signs of more acute inflammation, such as elevated levels of CCL2 and increased levels of proinflammatory cytokines such as IL-1β, IFNγ, and CXCL8. Similarly, the absolute number of monocytes is closer to a HC value, as well as the percentage of lymphocytes, suggesting a possible initiation of the inflammatory process. The study provides new insights into the immune system's role in MDE, paving the ground for replication prospective studies targeting the development of diagnostic and prognostic tools and new therapeutic targets.
Topics: Humans; Female; Male; Case-Control Studies; Depressive Disorder, Major; Adult; Immunophenotyping; Middle Aged; Cytokines; Monocytes; Bipolar Disorder; Inflammation; Antigens, CD; Flow Cytometry
PubMed: 38866753
DOI: 10.1038/s41398-024-02902-2 -
Heart, Lung & Circulation Jun 2024Aortic stenosis has recently been characterised as having an inflammatory aetiology, beyond the traditional degenerative model. Recruitment of monocytes has been...
BACKGROUND
Aortic stenosis has recently been characterised as having an inflammatory aetiology, beyond the traditional degenerative model. Recruitment of monocytes has been associated with inflammation contributing to progression of calcific aortic-valve disease. Prior research has demonstrated that pre-procedure inflammatory biomarkers do not consistently discriminate poorer outcomes in those with aortic stenosis. It remains, however, unclear if postprocedure inflammatory biomarkers, which are influenced by intraprocedural pro-inflammatory insults, can predict major adverse cardiovascular events (MACE) post transcatheter aortic valve implantation (TAVI).
METHOD
All patients with postprocedure monocyte levels undergoing transcatheter aortic valve implantation at The Alfred Hospital, Melbourne, Australia (2008-2019) were included. The highest monocyte count from postprocedure days 1 to 3 was used. Patients were divided into "high" or "low" postprocedure monocyte count groups using the Youden Index. The incidence of 30-day MACE a composite of stroke, acute myocardial infarction, and death) was then compared.
RESULTS
In total, 472 patients were included (54% men, median age 84 years). Fourteen (14) patients (3%) suffered a 30-day MACE. Those with high postprocedure monocyte count were more likely to: be hypertensive (p=0.049); have a higher Society of Thoracic Surgeons risk score (p=0.032); and, undergo non-transfemoral access (p=0.018). A high (≥0.975) postprocedure monocyte count was significantly associated with 30-day MACE (odds ratio [OR] 1.16 for each 0.1 increase in monocyte, p=0.025). This association remained present on multivariable analysis adjusted for age, sex, Society of Thoracic Surgeons risk score, and self-expanding valve prosthesis type (OR 1.17, p=0.028).
CONCLUSIONS
The association between postprocedure monocytosis and 30-day MACE suggests that minimising peri-procedural inflammatory insults may improve outcomes. This inexpensive and readily available biomarker may also aid in tailored risk stratification for patients.
PubMed: 38845242
DOI: 10.1016/j.hlc.2024.03.013 -
BioRxiv : the Preprint Server For... Jun 2024PTPN11 encodes for a tyrosine phosphatase implicated in the pathogenesis of hematologic malignancies such as Juvenile Myelomonocytic Leukemia (JMML), Acute Myeloid...
UNLABELLED
PTPN11 encodes for a tyrosine phosphatase implicated in the pathogenesis of hematologic malignancies such as Juvenile Myelomonocytic Leukemia (JMML), Acute Myeloid Leukemia (AML), and Acute Lymphoblastic Leukemia (ALL). Since activating mutations of PTPN11 increase proliferative signaling and cell survival through the RAS/MAPK proliferative pathway there is significant interest in using MEK inhibitors for clinical benefit. Yet, single agent clinical activity has been minimal. Previously, we showed that PTPN11 is further activated by upstream tyrosine kinases TNK2/SRC, and that PTPN11-mutant JMML and AML cells are sensitive to TNK2 inhibition using dasatinib. In order to validate these findings, we adopted a genetically engineered mouse model of PTPN11 driven leukemia using the mouse strain 129S/Sv- /Mmucd crossed with B6.129P2- /J. The F1 progeny expressing Ptpn11 within hematopoietic cells destined along the granulocyte-monocyte progenitor lineage developed a fatal myeloproliferative disorder characterized by neutrophilia and monocytosis, and infiltration of myeloid cells into the liver and spleen. Cohorts of Ptpn11 expressing animals treated with combination of dasatinib and trametinib for an extended period of time was well tolerated and had a significant effect in mitigating disease parameters compared to single agents. Finally, a primary patient-derived xenograft model using a myeloid leukemia with PTPN11 F71L also displayed improved disease response to combination. Collectively, these studies point to combined therapies targeting MEK and TNK2/SRC as a promising therapeutic potential for PTPN11-mutant leukemias.
KEY POINTS
Combining MEK and TNK2/SRC inhibitors has therapeutic potential in PTPN11 mutant JMML and AML.
PubMed: 38798550
DOI: 10.1101/2024.05.16.594555 -
Veterinary Clinical Pathology Jun 2024A 13-year-old male domestic short-hair cat presented for evaluation of labored breathing, hyporexia, and lethargy. Pertinent initial diagnostics yielded leukocytosis,...
A 13-year-old male domestic short-hair cat presented for evaluation of labored breathing, hyporexia, and lethargy. Pertinent initial diagnostics yielded leukocytosis, characterized by neutrophilia and monocytosis. Numerous small, round, magenta granules were observed within all neutrophils in Wright-Giemsa-stained blood films on the day of presentation and the day thereafter. No other neutrophil morphologic abnormalities were present, making cytoplasmic toxicity highly unlikely. Hyperadrenocorticism was diagnosed based on the lack of suppression in a low-dose dexamethasone suppression test, and without other diagnostics, the cat was discharged on trilostane therapy. Neutrophil granules did not stain with Alcian blue pH 1.0, periodic acid-Schiff (PAS), PAS and Alcian blue pH 2.5, and toluidine blue. Electron microscopy identified no differences in the morphology of the secretory granules or other neutrophil features. Metabolic screening tests of the cat's urine did not identify a genetic metabolic disorder. However, serum α- and β -hexosaminidase (HexA and HexB) activities were 4.3% and 0% of normal controls, respectively, which is supportive of GM2-gangliosidosis, that is, Sandhoff disorder. However, the historical, clinical, and electron microscopy findings did not provide evidence to confirm this genetic defect. To the author's knowledge, this is the first case of magenta-staining granules within neutrophils in a breed other than a Birman, Siamese, or Himalayan.
Topics: Animals; Cats; Male; Neutrophils; Cat Diseases; Cytoplasmic Granules
PubMed: 38797715
DOI: 10.1111/vcp.13356 -
Journal of Fungi (Basel, Switzerland) Apr 2024Blood count is crucial for assessing bone marrow's cell production and differentiation during infections, gaging disease severity, and monitoring therapeutic responses....
Blood count is crucial for assessing bone marrow's cell production and differentiation during infections, gaging disease severity, and monitoring therapeutic responses. The profile of blood count in chronic forms of paracoccidioidomycosis (PCM) has been insufficiently explored. To better understand the changes in hematological cells in different stages of the PCM chronic form, we evaluated the blood count, including immature blood cells in automated equipment, before and during the treatment follow-up of 62 chronic PCM patients. Predominantly male (96.8%) with an average age of 54.3 (standard deviation SD 6.9) years, participants exhibited pre-treatment conditions such as anemia (45.2%), monocytosis (38.7%), and leukocytosis (17.7%), which became less frequent after clinical cure. Anemia was more prevalent in severe cases. Notably, hemoglobin and reticulocyte hemoglobin content increased, while leukocytes, monocytes, neutrophils, immature granulocytes, and platelets decreased. Chronic PCM induced manageable hematological abnormalities, mainly in the red blood series. Monocytosis, indicating monocytes' role in PCM's immune response, was frequent. Post-treatment, especially after achieving clinical cure, significant improvements were observed in various hematological indices, including immature granulocytes and reticulocyte hemoglobin content, underscoring the impact of infection on these parameters.
PubMed: 38786672
DOI: 10.3390/jof10050317 -
Cytometry. Part B, Clinical Cytometry May 2024Peripheral blood lymphocyte phenotyping panels typically include CD45 for discrimination of the lymphocyte population, and fluorophore-conjugated monoclonal antibodies...
Peripheral blood lymphocyte phenotyping panels typically include CD45 for discrimination of the lymphocyte population, and fluorophore-conjugated monoclonal antibodies to identify T, B, and Natural Killer (NK) cells. While CD45 combined with side scatter is generally sufficient to clearly distinguish lymphocytes from monocytes in the majority of peripheral blood samples, it is challenging to accurately gate lymphocytes in samples from patients with monocytosis or significant lymphopenia, or from very young infants. Addition of a monocyte marker to lymphocyte phenotyping panels for monocyte exclusion has previously been evaluated for improved discrimination of lymphocytes, albeit largely in healthy donor adult samples. Here we evaluate the effect of the addition of CD14 to a standard lymphocyte phenotyping panel on total lymphocyte, T, B, and NK cell percentages in a predominantly pediatric population of patients under evaluation chiefly for immunodeficiency, immune-depletion, or immune reconstitution. Addition of CD14 to the standard lymphocyte phenotyping improved discrimination of lymphocytes from monocytes, resulted in decreased NK cell percentages, likely because CD16+ and/or CD56+ monocytes were included in the CD56+CD16+ NK cell gate with conventional gating, and although less significant, resulted in an increased percentage of B cells, since relatively larger B cells were likely gated out by more restrictive light scatter gating used with the conventional gating approach. The change in NK and B cell percentages were more pronounced in samples from patients below a year of age, and in patients who were relatively lymphopenic. These data suggest that addition of CD14 to conventional lymphocyte phenotyping panels that utilize CD45 versus side scatter gating results in significant improvement in the accuracy of lymphocyte gating, and accurate quantification of NK and B cells particularly in samples from infants and lymphopenic individuals.
PubMed: 38757910
DOI: 10.1002/cyto.b.22180 -
Saudi Medical Journal May 2024To investigate the prevalence of hematologic findings and the relationship between hemogram parameters and brucellosis stages in patients.
OBJECTIVES
To investigate the prevalence of hematologic findings and the relationship between hemogram parameters and brucellosis stages in patients.
METHODS
This multi-center study included patients older than 16 years of age who were followed up with a diagnosis of brucellosis. Patients' results, including white blood cell, hemoglobin, neutrophil, lymphocyte, monocyte, mean platelet volume, platelet and eosinophil counts were analyzed at the initial diagnosis.
RESULTS
In this study 51.3% of the patients diagnosed with brucellosis were male. The age median was 45 years for female and 41 years for male. A total of 55.1% of the patients had acute brucellosis, 28.2% had subacute, 7.4% had chronic and 9% had relapse. The most common hematologic findings in brucellosis patients were anemia (25.9%), monocytosis (15.9%), eosinopenia (10.3%), and leukocytosis (7.1%). Pancytopenia occurred in 0.8% of patients and was more prominent in the acute phase. The acute brucellosis group had lower white blood cell, hemoglobin, neutrophil, eosinophil, and platelet counts and mean platelet volume, and higher monocyte counts compared to subacute and chronic subgroups.
CONCLUSION
It was noteworthy that in addition to anemia and monocytosis, eosinopenia was third most prominent laboratory findings in the study. Pancytopenia and thrombocytopenia rates were low.
Topics: Humans; Brucellosis; Male; Female; Adult; Middle Aged; Turkey; Young Adult; Thrombocytopenia; Adolescent; Aged; Anemia; Blood Cell Count
PubMed: 38734423
DOI: 10.15537/smj.2024.45.5.20230847 -
Clinical Nephrology. Case Studies 2024A 19-year-old woman with a history of asthma presented with acute confusion following a near-drowning event 2 weeks prior to admission. She was found to have severe...
A 19-year-old woman with a history of asthma presented with acute confusion following a near-drowning event 2 weeks prior to admission. She was found to have severe thrombocytopenia and microangiopathic hemolytic anemia (MAHA). The treatment for thrombotic thrombocytopenic purpura (TTP) was started on the day of admission due to high clinical suspicion. Subsequent workup confirmed a diagnosis of TTP with no clear etiology except the near-drowning incident. TTP following a near-drowning event has never been reported in the literature. Furthermore, she developed refractory TTP that required reinitiation of therapeutic plasma exchange and rituximab. After discharge, the patient had been doing well over a year of follow-up without remission.
PubMed: 38716112
DOI: 10.5414/CNCS111301