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Stroke Jan 2020Background and Purpose- Patients with active malignancy are at risk for intracerebral hemorrhage (ICH). We aimed to characterize perihematomal edema (PHE) and hematoma...
Background and Purpose- Patients with active malignancy are at risk for intracerebral hemorrhage (ICH). We aimed to characterize perihematomal edema (PHE) and hematoma volumes after spontaneous nontraumatic ICH in patients with cancer without central nervous system involvement. Methods- Patients with active malignancy who developed ICH were retrospectively identified through automated searches of institutional databases. Control patients were identified with ICH and without active cancer. Demographic and cancer-specific data were obtained by chart review. Hematoma and PHE volumes were determined using semiautomated methodology. Univariate and multivariate linear regression models were created to assess which variables were associated with hematoma and PHE expansion. Results- Patients with cancer (N=80) and controls (N=136) had similar demographics (all >0.20), although hypertension was more prevalent among controls (=0.004). Most patients with cancer had received recent chemotherapy (n=45, 56%) and had recurrence of malignancy (n=43, 54%). Patients with cancer were thrombocytopenic (median platelet count 90 000 [interquartile range, 17 500-211 500]), and most had undergone blood product transfusion (n=41, 51%), predominantly platelets (n=38, 48%). Thirty-day mortality was 36% (n=29). Patients with cancer had significantly increased PHE volumes (23.67 versus 8.61 mL; =1.88×10) and PHE-to-ICH volume ratios (2.26 versus 0.99; =2.20×10). In multivariate analyses, variables associated with PHE growth among patients with cancer were ICH volume (β=1.29 [95% CI, 1.58-1.30] =1.30×10) and platelet transfusion (β=15.67 [95% CI, 3.61-27.74] =0.014). Variables associated with 30-day mortality were ICH volume (odds ratio, 1.06 [95% CI, 1.03-1.10] =6.76×10), PHE volume (odds ratio, 1.07 [95% CI, 1.04-1.09] =7.40×10), PHE growth (odds ratio, 1.05 [95% CI, 1.01-1.10] =0.01), and platelet transfusion (odds ratio, 1.48 [95% CI, 1.22-1.79] =0.0001). Conclusions- Patients with active cancer who develop ICH have increased PHE volumes. PHE growth was independent of thrombocytopenia but associated with blood product transfusion. Thirty-day mortality was associated with PHE and ICH volumes and blood product transfusion.
Topics: Aged; Brain Edema; Cerebral Hemorrhage; Edema; Female; Hematoma; Humans; Male; Middle Aged; Neoplasms; Retrospective Studies; Severity of Illness Index
PubMed: 31744426
DOI: 10.1161/STROKEAHA.119.027085 -
Cell Death & Disease Feb 2023During intracerebral hemorrhage (ICH), hematoma formation at the site of blood vessel damage results in local mechanical injury. Subsequently, erythrocytes lyse to...
During intracerebral hemorrhage (ICH), hematoma formation at the site of blood vessel damage results in local mechanical injury. Subsequently, erythrocytes lyse to release hemoglobin and heme, which act as neurotoxins and induce inflammation and secondary brain injury, resulting in severe neurological deficits. Accelerating hematoma resorption and mitigating hematoma-induced brain edema by modulating immune cells has potential as a novel therapeutic strategy for functional recovery after ICH. Here, we show that intracerebroventricular administration of recombinant human cerebral dopamine neurotrophic factor (rhCDNF) accelerates hemorrhagic lesion resolution, reduces peri-focal edema, and improves neurological outcomes in an animal model of collagenase-induced ICH. We demonstrate that CDNF acts on microglia/macrophages in the hemorrhagic striatum by promoting scavenger receptor expression, enhancing erythrophagocytosis and increasing anti-inflammatory mediators while suppressing the production of pro-inflammatory cytokines. Administration of rhCDNF results in upregulation of the Nrf2-HO-1 pathway, but alleviation of oxidative stress and unfolded protein responses in the perihematomal area. Finally, we demonstrate that intravenous delivery of rhCDNF has beneficial effects in an animal model of ICH and that systemic application promotes scavenging by the brain's myeloid cells for the treatment of ICH.
Topics: Animals; Humans; Cerebral Hemorrhage; Brain Injuries; Inflammation; Hematoma; Immunity, Innate; Disease Models, Animal; Brain Edema; Nerve Growth Factors
PubMed: 36792604
DOI: 10.1038/s41419-022-05520-2 -
GeroScience Jun 2022Chronic subdural hematoma (CSH) affects mostly elderly subjects. Previously, pathophysiological concepts suggested that CSH is secondary to degradation of subdural... (Review)
Review
Chronic subdural hematoma (CSH) affects mostly elderly subjects. Previously, pathophysiological concepts suggested that CSH is secondary to degradation of subdural collections of blood and its products exerting merely a mass effect on the underlying brain. During the last decades, however, new insights into the pathogenetic mechanisms urge us to reconsider such a simplistic view. Here, we critically review novel pathophysiological, imaging, interventional, and medical treatment aspects and establish an integrative concept of the pathogenesis of CSH stressing the role of age as key factor. Trauma is considered a trigger event that unleashes a cascade of immunological and angiogenic age-dependent responses. These are associated with hypervascularization of the outer hematoma membrane, rebleeding, and exsudation which are crucial determinants for further development and propagation of CSH. Neurosurgical evacuation of the hematoma has long been thought the only viable treatment option, and it is still the method of choice in the majority of cases. Only more recently, embolization of the middle meningeal artery has been introduced as an alternative to surgery, and pharmacological treatment options are being investigated. Persons with advanced age trauma and other trigger events encounter a repair system with characteristics of senescence. This repair system implies a dysfunctional secretory phenotype of senescent cells and results in an insufficient repair process including chronic inflammation and fibrosis. Increased knowledge about the pathomechanisms of CSH will inform future studies and open new perspectives for its treatment and possibly also for its prevention.
Topics: Aged; Hematoma, Subdural, Chronic; Humans
PubMed: 35461468
DOI: 10.1007/s11357-022-00570-y -
Oxidative Medicine and Cellular... 2022Acute intracerebral hemorrhage (ICH) is a devastating type of stroke worldwide. Neuronal destruction involved in the brain damage process caused by ICH includes a... (Review)
Review
Acute intracerebral hemorrhage (ICH) is a devastating type of stroke worldwide. Neuronal destruction involved in the brain damage process caused by ICH includes a primary injury formed by the mass effect of the hematoma and a secondary injury induced by the degradation products of a blood clot. Additionally, factors in the coagulation cascade and complement activation process also contribute to secondary brain injury by promoting the disruption of the blood-brain barrier and neuronal cell degeneration by enhancing the inflammatory response, oxidative stress, etc. Although treatment options for direct damage are limited, various strategies have been proposed to treat secondary injury post-ICH. Perihematomal edema (PHE) is a potential surrogate marker for secondary injury and may contribute to poor outcomes after ICH. Therefore, it is essential to investigate the underlying pathological mechanism, evolution, and potential therapeutic strategies to treat PHE. Here, we review the pathophysiology and imaging characteristics of PHE at different stages after acute ICH. As illustrated in preclinical and clinical studies, we discussed the merits and limitations of varying PHE quantification protocols, including absolute PHE volume, relative PHE volume, and extension distance calculated with images and other techniques. Importantly, this review summarizes the factors that affect PHE by focusing on traditional variables, the cerebral venous drainage system, and the brain lymphatic drainage system. Finally, to facilitate translational research, we analyze why the relationship between PHE and the functional outcome of ICH is currently controversial. We also emphasize promising therapeutic approaches that modulate multiple targets to alleviate PHE and promote neurologic recovery after acute ICH.
Topics: Biomarkers; Brain Edema; Cerebral Hemorrhage; Edema; Hematoma; Humans
PubMed: 36164392
DOI: 10.1155/2022/3948921 -
Clinical and Laboratory Haematology 1990The whole blood reference specimens are carefully selected in order to minimize errors in either reference methods or the assay method that might be produced by... (Review)
Review
The whole blood reference specimens are carefully selected in order to minimize errors in either reference methods or the assay method that might be produced by interferants in the specimens. Fundamental to the process of assigning values to calibrators and controls is the rule that fresh whole blood from normal donors be used as the transfer medium between reference measurement methods and the automated blood cell counter that will be used to assay the stabilized whole blood product. Increasing recognition is being given to the need to adopt K2EDTA salts as global standards for reference specimen anticoagulant. The reference methods used by Coulter closely follow the methods recommended by the Cytometry Panel of the International Committee for Standardization in Haematology and by the National Committee for Clinical Laboratory Standards. Methods used for the statistical control of value assignment are appropriate for commercial rather than institutional use. Simplification of methods is possible because of high levels of test replication and the homogeneous nature of stabilized blood products.
Topics: Automation; Calibration; Hematology; Humans; Quality Control; Reference Standards; Reproducibility of Results
PubMed: 2282762
DOI: No ID Found -
Skeletal Radiology Jan 2000Hematomas in the extremities can present clinically as a soft tissue mass. Hematomas can usually be distinguished from neoplasia on MR by the signal patterns of... (Review)
Review
Hematomas in the extremities can present clinically as a soft tissue mass. Hematomas can usually be distinguished from neoplasia on MR by the signal patterns of hemoglobin breakdown products, which are dependent on the chemical bonding and oxidation state of hemoglobin iron. Beginning with a discussion of relevant atomic electronic structure, this review will examine how oxyhemoglobin, deoxyhemoglobin, methemoglobin, and hemosiderin, the principal iron compounds occurring in the various stages of a hematoma, affect its appearance on MRI.
Topics: Diagnosis, Differential; Hematoma; Hemoglobins; Hemosiderin; Humans; Magnetic Resonance Imaging; Musculoskeletal Diseases
PubMed: 10663582
DOI: 10.1007/s002560050001 -
Blood Jul 1996
Topics: Hematology; Humans; Practice Guidelines as Topic; Purpura, Thrombocytopenic, Idiopathic; Societies, Medical
PubMed: 8704163
DOI: No ID Found -
Journal of Clinical Pathology Mar 2022Peripheral blood smear (PBS) review by a pathologist is a necessary and invaluable diagnostic tool. However, innovative highly sophisticated haematology analysers that...
Peripheral blood smear (PBS) review by a pathologist is a necessary and invaluable diagnostic tool. However, innovative highly sophisticated haematology analysers that flag peripheral blood abnormalities have decreased the need for a PBS review. Ordering practices including PBS reviews lumped as part of an 'order set' or with complete blood count (CBC) constituted most PBS requests at our institution. A retrospective review of all PBS review orders from 1 April 2016 to 31 January 2017 was performed to investigate the ordering practices at our institution. A total of 2864 PBS were ordered during the above study period. In many cases, the PBS report did not add any significant clinical information beyond that acquired by the CBC and differential count. These findings inspired policy changes within our institution for pathologist PBS reviews. Within the electronic order system, all PBS orders for inpatients were linked to a pop-up window with criteria for peripheral smear review and instructions on the approval policy. Outpatient orders required clinicians to request pathology approval. This implementation reduced total number of PBS orders by 42.5% with no adverse effect on patient management. Empowering pathologists and clinicians with guidelines on PBS review orders is a beneficial educational exercise of resource utilisation. Discussion with physicians regarding clinical indications reduces non-contributory PBS reviews, provides guidance to appropriate testing, and aptly allocates pathologist and laboratory staff time and resources.
Topics: Blood Cell Count; Cost-Benefit Analysis; Hematology; Humans; Leukocytes, Mononuclear; Pathologists; Retrospective Studies
PubMed: 34782422
DOI: 10.1136/jclinpath-2021-207905 -
Transfusion Medicine Reviews Oct 2016Although congenital bleeding disorders can manifest in the newborn period, the most common causes of bleeding and thrombosis in neonates are acquired conditions. Factor... (Review)
Review
Although congenital bleeding disorders can manifest in the newborn period, the most common causes of bleeding and thrombosis in neonates are acquired conditions. Factor concentrates are used for specific diagnoses (hemophilia with inhibitors, specific factor deficiency, von Willebrand disease) and approved indications, and increasingly for off-label indications (bleeding in surgery cardiopulmonary bypass, extracorporeal membrane oxygenation). We will review the approved indications for factor products in the neonate and discuss the evidence and rationale for off-label use of factor products in management of bleeding and thrombosis in the neonate.
Topics: Anticoagulants; Blood Coagulation; Factor VIII; Factor VIIa; Hematology; Hemophilia A; Hemorrhage; Humans; Infant, Newborn; Infant, Premature; Recombinant Proteins; Thrombosis; von Willebrand Diseases
PubMed: 27576087
DOI: 10.1016/j.tmrv.2016.07.002 -
Journal of Thrombosis and Haemostasis :... Dec 2017
Topics: Health Care Costs; Health Promotion; Health Services Accessibility; Healthcare Disparities; Hematology; Humans; Research Design; Research Support as Topic; Thrombosis
PubMed: 29150887
DOI: 10.1111/jth.13889