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American Family Physician Nov 2000Leukocytosis, a common laboratory finding, is most often due to relatively benign conditions (infections or inflammatory processes). Much less common but more serious... (Review)
Review
Leukocytosis, a common laboratory finding, is most often due to relatively benign conditions (infections or inflammatory processes). Much less common but more serious causes include primary bone marrow disorders. The normal reaction of bone marrow to infection or inflammation leads to an increase in the number of white blood cells, predominantly polymorphonuclear leukocytes and less mature cell forms (the "left shift"). Physical stress (e.g., from seizures, anesthesia or overexertion) and emotional stress can also elevate white blood cell counts. Medications commonly associated with leukocytosis include corticosteroids, lithium and beta agonists. Increased eosinophil or basophil counts, resulting from a variety of infections, allergic reactions and other causes, can lead to leukocytosis in some patients. Primary bone marrow disorders should be suspected in patients who present with extremely elevated white blood cell counts or concurrent abnormalities in red blood cell or platelet counts. Weight loss, bleeding or bruising, liver, spleen or lymph node enlargement, and immunosuppression also increase suspicion for a marrow disorder. The most common bone marrow disorders can be grouped into acute leukemias, chronic leukemias and myeloproliferative disorders. Patients with an acute leukemia are more likely to be ill at presentation, whereas those with a chronic leukemia are often diagnosed incidentally because of abnormal blood cell counts. White blood cell counts above 100,000 per mm3 (100 x 10(9) per L) represent a medical emergency because of the risk of brain infarction and hemorrhage.
Topics: Bone Marrow Diseases; Humans; Hypersensitivity; Infections; Inflammation; Leukocyte Count; Leukocytosis; Stress, Psychological
PubMed: 11087187
DOI: No ID Found -
Blood Advances Jun 2022Bone marrow specimens are the core of the diagnostic workup of patients with cytopenia. To explore whether next-generation sequencing (NGS) could be used to rule out...
Bone marrow specimens are the core of the diagnostic workup of patients with cytopenia. To explore whether next-generation sequencing (NGS) could be used to rule out malignancy without bone marrow specimens, we incorporated NGS in a model to predict presence of disease in the bone marrow of patients with unexplained cytopenia. We analyzed the occurrence of mutations in 508 patients with cytopenia, referred for primary workup of a suspected hematologic malignancy from 2015 to 2020. We divided patients into a discovery (n = 340) and validation (n = 168) cohort. Targeted sequencing, bone marrow biopsy, and complete blood count were performed in all patients. Mutations were identified in 267 (53%) and abnormal bone marrow morphology in 188 (37%) patients. Patients with isolated neutropenia had the lowest frequency of both mutations (21%) and abnormal bone marrow morphology (5%). The median number of mutations per patient was 2 in patients with abnormal bone marrow morphology compared with 0 in patients with a nondiagnostic bone marrow morphology (P < .001). In a multivariable logistic regression, mutations in TET2, SF3B1, U2AF1, TP53, and RUNX1 were significantly associated with abnormal bone marrow morphology. In the validation cohort, a model combining mutational status and clinical data identified 34 patients (20%) without abnormal bone marrow morphology with a sensitivity of 100% (95% confidence interval: 93%-100%). Overall, we show that NGS combined with clinical data can predict the presence of abnormal bone marrow morphology in patients with unexplained cytopenia and thus can be used to assess the need of a bone marrow biopsy.
Topics: Anemia; Bone Marrow; Bone Marrow Diseases; High-Throughput Nucleotide Sequencing; Humans; Mutation; Myelodysplastic Syndromes
PubMed: 35427424
DOI: 10.1182/bloodadvances.2021006649 -
Osteoporosis International : a Journal... Jan 2018In fibrous dysplasia/McCune-Albright syndrome (FD/MAS), bone and bone marrow are, to varying degrees, replaced by fibro-osseous tissue typically devoid of hematopoietic...
In fibrous dysplasia/McCune-Albright syndrome (FD/MAS), bone and bone marrow are, to varying degrees, replaced by fibro-osseous tissue typically devoid of hematopoietic marrow. Despite the extensive marrow replacement in severely affected patients, bone marrow failure is not commonly associated with FD/MAS. We present a 14-year-old girl with FD/MAS, who developed pancytopenia and extramedullary hematopoiesis (EMH) with no identified cause, in the setting of iatrogenic thyrotoxicosis and hyperparathyroidism. Pancytopenia, requiring monthly blood transfusions, persisted despite multiple strategies to correct these endocrinopathies. Due to worsening painful splenomegaly, likely as a result of sequestration, splenectomy was performed. Following splenectomy, pancytopenia resolved and patient has since been transfusion-independent. We report the first detailed case of bone marrow failure and EMH in FD/MAS. The etiology of marrow failure is likely multifactorial and related to the loss of marrow reserve due to extensive polyostotic FD, exacerbated by iatrogenic thyrotoxicosis and hyperparathyroidism. Mini Abstract: A patient with fibrous dysplasia developed bone marrow failure and extramedullary hematopoiesis. The etiology likely involved loss of hematopoetic marrow space and uncontrolled endocrinopathies. Splenectomy was therapeutic.
Topics: Adolescent; Anemia, Aplastic; Biopsy; Bone Marrow; Bone Marrow Diseases; Bone Marrow Failure Disorders; Female; Fibrous Dysplasia, Polyostotic; Hematopoiesis, Extramedullary; Hemoglobinuria, Paroxysmal; Humans; Liver; Pancytopenia; Radiography; Splenectomy
PubMed: 29071359
DOI: 10.1007/s00198-017-4217-7 -
Biology of Blood and Marrow... Jan 2010Diamond Blackfan anemia (DBA) is a congenital bone marrow (BM) failure syndrome that typically results in macrocytic anemia within the first year of life. DBA is also... (Review)
Review
Diamond Blackfan anemia (DBA) is a congenital bone marrow (BM) failure syndrome that typically results in macrocytic anemia within the first year of life. DBA is also associated with birth defects, increased incidence of cancer, and other cytopenias. Shwachman-Diamond syndrome (SDS) is a multisystem disease characterized by exocrine pancreatic dysfunction, impaired hematopoiesis, and leukemia predisposition. Other clinical features include skeletal, immunologic, hepatic, and cardiac disorders. Treatment for these BM failure syndromes, including stem cell transplantation (SCT), will be discussed in this review.
Topics: Anemia, Diamond-Blackfan; Animals; Bone Marrow Diseases; Genetic Diseases, Inborn; Hematopoietic Stem Cell Transplantation; Humans; Ribosomes
PubMed: 19770060
DOI: 10.1016/j.bbmt.2009.09.012 -
Blood Advances Jan 2022Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure syndrome with leukemia predisposition. An understanding of the hematologic complications of SDS with...
Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure syndrome with leukemia predisposition. An understanding of the hematologic complications of SDS with age could guide clinical management, but data are limited for this rare disease. We conducted a cohort study of 153 subjects from 143 families with confirmed biallelic SBDS mutations enrolled on the North American Shwachman Diamond Registry or Bone Marrow Failure Registry. The SBDS c.258 + 2T>C variant was present in all but 1 patient. To evaluate the association between blood counts and age, 2146 blood counts were analyzed for 119 subjects. Absolute neutrophil counts were positively associated with age (P < .0001). Hemoglobin was also positively associated with age up to 18 years (P < .0001), but the association was negative thereafter (P = .0079). Platelet counts and marrow cellularity were negatively associated with age (P < .0001). Marrow cellularity did not correlate with blood counts. Severe marrow failure necessitating transplant developed in 8 subjects at a median age of 1.7 years (range, 0.4-39.5), with 7 of 8 requiring transplant prior to age 8 years. Twenty-six subjects (17%) developed a myeloid malignancy (16 myelodysplasia and 10 acute myeloid leukemia) at a median age of 12.3 years (range, 0.5-45.0) and 28.4 years (range, 14.4-47.3), respectively. A lymphoid malignancy developed in 1 patient at the age of 16.9 years. Hematologic complications were the major cause of mortality (17/20 deaths; 85%). These data inform surveillance of hematologic complications in SDS.
Topics: Adolescent; Adult; Bone Marrow Diseases; Child; Child, Preschool; Cohort Studies; Exocrine Pancreatic Insufficiency; Hematologic Diseases; Humans; Infant; Middle Aged; Shwachman-Diamond Syndrome; Young Adult
PubMed: 34758064
DOI: 10.1182/bloodadvances.2021005539 -
Stem Cells (Dayton, Ohio) Feb 2017Bone marrow failure syndromes (BMFS) are a group of disorders with complex pathophysiology characterized by a common phenotype of peripheral cytopenia and/or hypoplastic... (Review)
Review
Bone marrow failure syndromes (BMFS) are a group of disorders with complex pathophysiology characterized by a common phenotype of peripheral cytopenia and/or hypoplastic bone marrow. Understanding genetic factors contributing to the pathophysiology of BMFS has enabled the identification of causative genes and development of diagnostic tests. To date more than 40 mutations in genes involved in maintenance of genomic stability, DNA repair, ribosome and telomere biology have been identified. In addition, pathophysiological studies have provided insights into several biological pathways leading to the characterization of genotype/phenotype correlations as well as the development of diagnostic approaches and management strategies. Recent developments in bone marrow transplant techniques and the choice of conditioning regimens have helped improve transplant outcomes. However, current morbidity and mortality remain unacceptable underlining the need for further research in this area. Studies in mice have largely been unable to mimic disease phenotype in humans due to difficulties in fully replicating the human mutations and the differences between mouse and human cells with regard to telomere length regulation, processing of reactive oxygen species and lifespan. Recent advances in induced pluripotency have provided novel insights into disease pathogenesis and have generated excellent platforms for identifying signaling pathways and functional mapping of haplo-insufficient genes involved in large-scale chromosomal deletions-associated disorders. In this review, we have summarized the current state of knowledge in the field of BMFS with specific focus on modeling the inherited forms and how to best utilize these models for the development of targeted therapies. Stem Cells 2017;35:284-298.
Topics: Anemia, Aplastic; Animals; Bone Marrow; Bone Marrow Diseases; Bone Marrow Failure Disorders; Disease Models, Animal; Hemoglobinuria, Paroxysmal; Humans; Models, Biological
PubMed: 27870251
DOI: 10.1002/stem.2543 -
Disease Markers 2022To investigate the feasibility and correlation of sacroiliac joint (SIJ) fat fraction (FF) and R2 as markers of bone metabolism in patients with ankylosing spondylitis...
OBJECTIVE
To investigate the feasibility and correlation of sacroiliac joint (SIJ) fat fraction (FF) and R2 as markers of bone metabolism in patients with ankylosing spondylitis (AS).
METHODS
75 AS patients were classified into an early active group (EA), late active group (LA), and inactive group (IA). Additionally, 54 matched healthy individuals were selected to be part of the normal control group (NC). All participants underwent chemical shift encoded based MRI (IDEAL-IQ) and routine clinical SIJ MRI at 3.0 T. FF and R2 were measured in subchondral bone, bone marrow edema (BME), and fat metaplasia (FM). Out of the participants, 39 with BME lesions (15 from EA, 16 from LA, 8 from IA) and 39 with FM lesions (9 from EA, 17 from LA, 13 from IA) were included. Differences in FF, R2 value for subchondral bone of all participants and for BME, FM lesions were evaluated. Subsequently, different stages of BME and FM in patient groups were compared, and the relationship between FF and R2 was analyzed.
RESULTS
A significant difference in FF was demonstrated among the BME, FM and the normal bone marrow ( < 0.001), meanwhile, the difference of R2 value in FM was significantly lower (p = 0.034, 0.012) than that of BME and that of normal bone marrow. At lever of different lesions, only the FF for BME was significantly different among 3 patient groups ( = 0.001), while there was no significantly different FF for FM among 3 patient groups. Unlike in BME lesions, the FF in FM lesions had a negative correlation with R2 ( < 0.001, = -0.488).
CONCLUSION
FF and R2 measurements help to quantitatively analyze the bone marrow fat composition and bony trabecular microstructure changes in AS, providing a noninvasive and accurate assessment basis for AS bone metabolism abnormalities.
Topics: Humans; Spondylitis, Ankylosing; Sacroiliac Joint; Bone Marrow Diseases; Magnetic Resonance Imaging; Edema
PubMed: 36277974
DOI: 10.1155/2022/1846667 -
Journal of Orthopaedic Surgery and... Nov 2023Knee injuries are prevalent, and early diagnosis is crucial for guiding clinical therapy. MRI is the diagnostic gold standard for bone marrow edema (BME) in patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Knee injuries are prevalent, and early diagnosis is crucial for guiding clinical therapy. MRI is the diagnostic gold standard for bone marrow edema (BME) in patients with acute knee injuries, yet there are still limitations. Dual-energy CT, a possible viable replacement, is being explored (DECT).
METHODS
We systematically retrieved studies from EMBASE, Scopus, PUBMED, and the Cochrane Library and collected gray literatures. In accordance with the PRISMA-DTA standards, a systematic review was conducted between the study's initiation and July 31, 2021, utilizing an MRI reference standard and at least 10 adult patients with acute knee injuries to evaluate the diagnostic effectiveness of DECT for diagnosing BME. Two reviewers collected the study's details independently. For the meta-analysis, a bivariate mixed-effects regression model was utilized, and subgroup analysis was employed to determine the sources of variability.
RESULTS
The research included nine studies that examined 290 individuals between the ages of 23 and 53 with acute knee injuries who had DECT and MRI. Overall, the sensitivity, specificity, and AUC of the BME were 85% (95% confidence interval [CI]: 77-90%), 96% (95% CI: 93-97%), and 0.97 (95% CI: 0.95-0.98), respectively. To account for the assumed diversity of research, there were no statistically significant differences between the comparison groups in terms of specificity and sensitivity.
CONCLUSION
DECT is a viable alternative to MRI for individuals with acute knee injuries when MRI is inappropriate or unavailable.
Topics: Adult; Humans; Young Adult; Middle Aged; Bone Marrow; Sensitivity and Specificity; Tomography, X-Ray Computed; Bone Marrow Diseases; Knee Injuries; Edema; Magnetic Resonance Imaging
PubMed: 37919746
DOI: 10.1186/s13018-023-04151-3 -
The Canadian Veterinary Journal = La... Oct 2009Exogenous estrogens used for therapeutic purposes or endogenous estrogen sources such as functional Sertoli cell or ovarian granulosa cell tumors may cause bone marrow... (Review)
Review
Exogenous estrogens used for therapeutic purposes or endogenous estrogen sources such as functional Sertoli cell or ovarian granulosa cell tumors may cause bone marrow toxicity in dogs. The condition is characterized by hematologic abnormalities including thrombocytopenia, anemia, and leukocytosis or leukopenia. Despite intensive therapy with blood or platelet-rich transfusions, broad-spectrum antibiotics, steroids, and bone marrow stimulants, prognosis is unfavorable. Due to the the risk of stimulating the development of uterine diseases and the potential for inducing aplastic anemia, estrogen use in dogs is best avoided where possible. This paper describes the causes of estrogen-induced myelotoxicity, the clinical presentation of the patients, the diagnosis, and the treatment options in the dog.
Topics: Anemia; Animals; Blood Transfusion; Bone Marrow; Bone Marrow Diseases; Dog Diseases; Dogs; Estrogens; Hemostasis; Leukocytosis; Leukopenia; Prognosis; Thrombocytopenia
PubMed: 20046604
DOI: No ID Found -
Blood Reviews May 2010The inherited marrow failure syndromes are a diverse set of genetic disorders characterized by hematopoietic aplasia and cancer predisposition. The clinical phenotypes... (Review)
Review
The inherited marrow failure syndromes are a diverse set of genetic disorders characterized by hematopoietic aplasia and cancer predisposition. The clinical phenotypes are highly variable and much broader than previously recognized. The medical management of the inherited marrow failure syndromes differs from that of acquired aplastic anemia or malignancies arising in the general population. Diagnostic workup, molecular pathogenesis, and clinical treatment are reviewed.
Topics: Bone Marrow Diseases; Genetic Diseases, Inborn; Humans; Syndrome
PubMed: 20417588
DOI: 10.1016/j.blre.2010.03.002