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International Journal of Molecular... Feb 2024Hemochromatosis represents clinically one of the most important genetic storage diseases of the liver caused by iron overload, which is to be differentiated from hepatic... (Review)
Review
Hemochromatosis represents clinically one of the most important genetic storage diseases of the liver caused by iron overload, which is to be differentiated from hepatic iron overload due to excessive iron release from erythrocytes in patients with genetic hemolytic disorders. This disorder is under recent mechanistic discussion regarding ferroptosis, reactive oxygen species (ROS), the gut microbiome, and alcohol abuse as a risk factor, which are all topics of this review article. Triggered by released intracellular free iron from ferritin via the autophagic process of ferritinophagy, ferroptosis is involved in hemochromatosis as a specific form of iron-dependent regulated cell death. This develops in the course of mitochondrial injury associated with additional iron accumulation, followed by excessive production of ROS and lipid peroxidation. A low fecal iron content during therapeutic iron depletion reduces colonic inflammation and oxidative stress. In clinical terms, iron is an essential trace element required for human health. Humans cannot synthesize iron and must take it up from iron-containing foods and beverages. Under physiological conditions, healthy individuals allow for iron homeostasis by restricting the extent of intestinal iron depending on realistic demand, avoiding uptake of iron in excess. For this condition, the human body has no chance to adequately compensate through removal. In patients with hemochromatosis, the molecular finetuning of intestinal iron uptake is set off due to mutations in the high-FE () genes that lead to a lack of hepcidin or resistance on the part of ferroportin to hepcidin binding. This is the major mechanism for the increased iron stores in the body. Hepcidin is a liver-derived peptide, which impairs the release of iron from enterocytes and macrophages by interacting with ferroportin. As a result, iron accumulates in various organs including the liver, which is severely injured and causes the clinically important hemochromatosis. This diagnosis is difficult to establish due to uncharacteristic features. Among these are asthenia, joint pain, arthritis, chondrocalcinosis, diabetes mellitus, hypopituitarism, hypogonadotropic hypogonadism, and cardiopathy. Diagnosis is initially suspected by increased serum levels of ferritin, a non-specific parameter also elevated in inflammatory diseases that must be excluded to be on the safer diagnostic side. Diagnosis is facilitated if ferritin is combined with elevated fasting transferrin saturation, genetic testing, and family screening. Various diagnostic attempts were published as algorithms. However, none of these were based on evidence or quantitative results derived from scored key features as opposed to other known complex diseases. Among these are autoimmune hepatitis (AIH) or drug-induced liver injury (DILI). For both diseases, the scored diagnostic algorithms are used in line with artificial intelligence (AI) principles to ascertain the diagnosis. The first-line therapy of hemochromatosis involves regular and life-long phlebotomy to remove iron from the blood, which improves the prognosis and may prevent the development of end-stage liver disease such as cirrhosis and hepatocellular carcinoma. Liver transplantation is rarely performed, confined to acute liver failure. In conclusion, ferroptosis, ROS, the gut microbiome, and concomitant alcohol abuse play a major contributing role in the development and clinical course of genetic hemochromatosis, which requires early diagnosis and therapy initiation through phlebotomy as a first-line treatment.
Topics: Humans; Hemochromatosis; Hepcidins; Reactive Oxygen Species; Alcoholism; Ferroptosis; Artificial Intelligence; Gastrointestinal Microbiome; Confounding Factors, Epidemiologic; Histocompatibility Antigens Class I; Hemochromatosis Protein; Membrane Proteins; Iron; Iron Overload; Ferritins; Ethanol; Liver Neoplasms
PubMed: 38473913
DOI: 10.3390/ijms25052668 -
Journal of the American Veterinary... May 2024This case report describes a cat with severe erythrocytosis (Hct, 80%), which after initial treatment with hydroxyurea has gone into remission for over 3 years.
OBJECTIVE
This case report describes a cat with severe erythrocytosis (Hct, 80%), which after initial treatment with hydroxyurea has gone into remission for over 3 years.
ANIMAL
A 1-year-old neutered male American Maine Coon crossbred cat.
CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES
A 1-year-old neutered male American Maine Coon crossbred domestic cat was presented with acute neurologic signs, systolic heart murmur, and extreme erythrocytosis (Hct, 80%; normal interval, 30% to 48%). There were no clinical signs of dehydration, and several diagnostic tests for absolute erythrocytosis did not identify an underlying cause. A presumptive diagnosis of primary erythrocytosis (polycythemia vera [P vera], a myeloproliferative disease) was made.
TREATMENT AND OUTCOME
Repeated phlebotomies were declined by the owner, and thus the cat was treated with oral hydroxyurea. The neurologic signs, heart murmur, and erythrocytosis resolved within 2 months (Hct, 41%). Treatment with hydroxyurea was continued for 2 years and then discontinued. The Hct remained in the normal range (between 37% and 44%) during a 3-year observation period.
CLINICAL RELEVANCE
This case illustrates the challenges of determining a precise cause of erythrocytosis. The extreme erythrocytosis reverted after treatment with hydroxyurea and did not recur even after drug withdrawal, suggesting an undefined singular or multifactorial cause of the erythrocytosis rather than a primary absolute erythrocytosis, such as P vera. The reversibility of this cat's erythrocytosis suggested that in select cases the discontinuation of treatment is warranted.
PubMed: 38452480
DOI: 10.2460/javma.23.11.0659 -
Journal of Special Operations Medicine... Mar 2024Fast and reliable blood collection is critical to emergency walking blood banks (WBB) because mortality significantly declines when blood is quickly administered to a...
BACKGROUND
Fast and reliable blood collection is critical to emergency walking blood banks (WBB) because mortality significantly declines when blood is quickly administered to a warfighter with hemorrhagic shock. Phlebotomy for WBB is accomplished via either the "straight stick" (SS) or "ruggedized lock" (RL) method. SS comprises a 16-gauge phlebotomy needle connected to a blood collection bag via tubing. The RL device collects blood through the same apparatus, but has a capped, intravenous (IV) catheter between the needle and the donor's arm. This is the first study to compare these two methods in battlefield-relevant metrics.
METHODS
Military first responders and licensed medical providers (N=86) were trained in SS and RL as part of fresh whole blood training exercises. Outcomes included venipuncture success rates, time to IV access, blood collection times, total time, and user preferences, using a within-subjects crossover design. Data were analyzed using ANOVA and nonparametric statistics at p<0.05.
RESULTS
SS outperformed RL in first venipuncture success rates (76% vs. 64%, p=0.07), IV access times (448 [standard error of the mean; SE 23] vs. 558 [SE 31] s, p<0.01), and blood collection bag fill times (573 [SE 48] vs. 703 [SE 44] s, p<0.05), resulting in an approximate 3.5-minute faster time overall. Survey data were mixed, with users perceiving SS as simpler and faster, but RL as more reliable and secure.
CONCLUSION
SS is optimal when timely collection is imperative, while RL may be preferable when device stability or replacing the collection bag is a consideration.
PubMed: 38446068
DOI: 10.55460/N87K-W6BZ -
Patient Preference and Adherence 2024Typical barriers to venous blood collection for wellness testing include discomfort, time spent, and collection site accessibility. This study assessed individuals'...
PURPOSE
Typical barriers to venous blood collection for wellness testing include discomfort, time spent, and collection site accessibility. This study assessed individuals' experience, satisfaction, and preference associated with a FDA-cleared blood-collection device, the BD MiniDraw™ Capillary Blood Collection System (BD MiniDraw), in retail locations.
PATIENTS AND METHODS
A total of 113 individuals (≥18 years) with venous blood collection experience were enrolled; 107 completed the study. A pre-collection survey gathered information on demographics and past experiences with healthcare and venous blood collection settings. BD MiniDraw collection was conducted at three retail sites (two pharmacies and one grocery store) by trained healthcare workers using the Babson BetterWay blood testing service model. A follow up survey was performed two weeks later to determine experience with, and preference for, BD MiniDraw in terms of staff professionalism, blood collection location, blood collection time, and staff trustworthiness.
RESULTS
Among the 107 participants, 74 (69%) were female and 33 (31%) were male; the mean age was 49 years (range=18-71 years). Sixty-six (62%) participants viewed their prior venipuncture experience as "somewhat" or "very" positive. Following capillary collection, 96 (90%) participants expressed a "somewhat" or "very" positive experience with BD MiniDraw at a retail location. In particular, "very satisfied" responses were given for location (87/107; 81%) and collection time (78/1407; 73%). In a subset of respondents (n=89), those reasons (location and time savings) were most frequent for likelihood of future use. Ninety-nine participants (92%) rated the retail blood collection team as "very" or "extremely" trustworthy. Overall, 90 participants (84%) "strongly preferred" (56/107; 52%), "somewhat preferred" (14/107; 13%), or had "no preference" (20/107; 19%) for BD MiniDraw, compared to traditional venous blood collection.
CONCLUSION
Most participants conveyed a preference for BD MiniDraw, primarily based on the blood collection retail location, perceived time savings, and professionalism and trustworthiness of the staff.
PubMed: 38444755
DOI: 10.2147/PPA.S437969 -
Clinical Chemistry and Laboratory... Jul 2024The pre-analytical stability of various biochemical analytes requires careful consideration, as it can lead to the release of erroneous laboratory results. There is...
OBJECTIVES
The pre-analytical stability of various biochemical analytes requires careful consideration, as it can lead to the release of erroneous laboratory results. There is currently significant variability in the literature regarding the pre-analytical stability of various analytes. The aim of this study was to determine the pre-analytical stability of 65 analytes in whole blood, serum and plasma using a standardized approach.
METHODS
Blood samples were collected from 30 healthy volunteers (10 volunteers per analyte) into five vacutainers; either SST, Li-heparin, K-EDTA, or Na-fluoride/K-oxalate. Several conditions were tested, including delayed centrifugation with storage of whole blood at room temperature (RT) for 8 h, delayed centrifugation with storage of whole blood at RT or 4 °C for 24 h, and immediate centrifugation with storage of plasma or serum at RT for 24 h. Percent deviation (% PD) from baseline was calculated for each analyte and compared to the maximum permissible instability (MPI) derived from intra- and inter-individual biological variation.
RESULTS
The majority of the analytes evaluated remained stable across all vacutainer types, temperatures, and timepoints tested. Glucose, potassium, and aspartate aminotransferase, among others, were significantly impacted by delayed centrifugation, having been found to be unstable in whole blood specimens stored at room temperature for 8 h.
CONCLUSIONS
The data presented provides insight into the pre-analytical variables that impact the stability of routine biochemical analytes. This study may help to reduce the frequency of erroneous laboratory results released due to exceeded stability and reduce unnecessary repeat phlebotomy for analytes that remain stable despite delayed processing.
Topics: Humans; Blood Specimen Collection; Plasma; Serum; Blood Chemical Analysis; Adult; Male; Temperature; Female; Healthy Volunteers; Centrifugation
PubMed: 38443327
DOI: 10.1515/cclm-2023-1192 -
Cureus Jan 2024Traumatic hemorrhagic shock is a common yet life-threatening occurrence across the United States and is typically managed with blood transfusions as the standard of...
Traumatic hemorrhagic shock is a common yet life-threatening occurrence across the United States and is typically managed with blood transfusions as the standard of care. However, providers caring for a Jehovah's Witness patient who refuses transfusions due to religious reasons face unique ethical challenges in upholding evidence-based shock resuscitation protocols while respecting the patient's autonomy and faith-based stance that strictly prohibits blood products. We present a complex clinical case of a 46-year-old Jehovah's Witness who developed severe hemorrhagic shock, partial amputation, and critical anemia after a traumatic 40-mile-per-hour motorcycle collision resulting in comminuted fractures and arterial disruption. Despite receiving emergent blood transfusions initially, further transfusions were declined once his identity as a practicing Jehovah's Witness was disclosed. His hemoglobin plunged to dangerously low levels of 4.6 g/dL before stabilizing to 5.3 g/dL with pharmaceutical alternatives including intravenous iron, high-dose erythropoietin, and phlebotomy minimization. Respecting patient convictions while delivering effective evidence-based shock management created significant ethical conflicts given the proven efficacy of blood transfusions. However, this complex case demonstrates that through meticulous medical and surgical care coordinated by a multi-disciplinary team applying customized non-transfusion techniques, traumatic hemorrhagic shock and life-threatening anemia can still achieve favorable outcomes without relying on transfusions when respecting faith-based refusal of blood products.
PubMed: 38435957
DOI: 10.7759/cureus.53301 -
Laboratory Medicine Mar 2024Rainbow blood draws for add-on testing in the emergency department (ED) are a common practice at our institution. We sought to determine the prevalence of this practice...
BACKGROUND
Rainbow blood draws for add-on testing in the emergency department (ED) are a common practice at our institution. We sought to determine the prevalence of this practice among reference laboratory clients and characterize the impact of pandemic-driven supply shortages.
METHODS
This cross-sectional study surveyed 354 client laboratories to understand specimen collection practices in specific clinical environments and how these practices may have been affected by supply chain shortages. Data analysis by descriptive statistics was performed in Qualtrics.
RESULTS
A total of 138 laboratories took the survey (39% response rate) with 57% indicating that their ED performed rainbow draws. Of these, 16% have a formal policy regarding rainbow draws, and 76% of respondents indicated that their institution was required to modify practices due to pandemic-driven supply shortages. A total of 19% indicated they routinely collect multiple urine aliquots for add-on testing.
CONCLUSION
Rainbow draws and collection of urine aliquots in the ED for add-on testing are relatively common practices, with few institutions maintaining formal policies regarding the practice. Pandemic-driven supply chain shortages affected a majority of respondent laboratories and local cost-benefit analysis regarding extra specimen collection is recommended to limit waste of laboratory resources.
PubMed: 38431798
DOI: 10.1093/labmed/lmae011 -
Journal of the American Association For... May 2024Many experiments require the collection of serial blood samples from mice. However, the size of mice limits the volume of blood that can be safely collected as a...
Many experiments require the collection of serial blood samples from mice. However, the size of mice limits the volume of blood that can be safely collected as a survival procedure. In IACUC protocols, investigators may report the amount of blood they collect from mice as a number of drops. Many institutions, including ours, use an anecdotal conversion factor (1drop of mouse blood = 25μL) to ensure that blood-collection volumes are compliant with institutional guidelines. To our knowledge, previous work has not experimentally determined the volume of a drop of mouse blood. In this 10-wk crossover experiment, 2 phlebotomists bled 30 C57BL/6J mice from 3 sites (facial, saphenous, and tail) using one or 2 different needle gauge sizes per site. Male and female mice were weighed weekly and divided among 5 groups (n = 6): left and right tail vein, left and right saphenous vein, and facial vein. A single blood drop from each site was weighed, and the volume of each drop was calculated using the average blood density determined from 8 mice terminally bled at the end of the study. Venipuncture site and side significantly influenced blood-drop weight and thus calculated volume. Facial vein puncture produced the largest drop volume (mean: 21.7μL), followed by the saphenous vein (mean: 9.97μL) and tail vein (mean: 4.96μL). Collection from the facial vein was associated with more hemorrhage and morbidity. Left-sided venipuncture was associated with slightly larger-volume blood drops, though the effect size of side was small. The results of this study may be useful in more accurately estimating blood loss via conversion of drops to volume. Our data indicate that blood collection from saphenous and tail veins minimizes blood loss relative to facial vein puncture and may optimize both serial collection of small-volume blood samples and animal welfare.
Topics: Animals; Mice, Inbred C57BL; Phlebotomy; Female; Male; Mice; Tail; Face; Cross-Over Studies
PubMed: 38428941
DOI: 10.30802/AALAS-JAALAS-23-000083 -
Journal of Neonatal-perinatal Medicine 2024Guidelines on when to screen for neonatal hyperbilirubinemia apply to infants born at 35 weeks or later of gestation. It is unknown whether infants born earlier would...
BACKGROUND
Guidelines on when to screen for neonatal hyperbilirubinemia apply to infants born at 35 weeks or later of gestation. It is unknown whether infants born earlier would benefit from similar guidelines. Our objective was to examine hyperbilirubinemia screening and phototherapy prescription among early preterm infants during the first 6 days of life.
METHODS
We reviewed the charts of 193 infants born prior to 35 weeks of gestation who were admitted to a tertiary care NICU in Southeastern Ontario in 2018-2019. Information on total serum bilirubin (TSB) measurements over each 12-hour interval during the first six days of life and the treatment decision (no treatment, initiate, continue, or stop phototherapy) was extracted. We also examined what proportion of infants were prescribed phototherapy during each 12-hour interval.
RESULTS
Of 1006 TSB measurements performed over the first 6 days of life, 605 were done to determine whether phototherapy should be initiated. Treatment was prescribed in 275 instances (45%). A higher proportion of infants born prior to 28 weeks of gestation required phototherapy in the first 12 hours of life (37%) compared to those born at 28-32 weeks (20%) and 33-34 weeks (5.7%).
CONCLUSIONS
Our results suggest that TSB measurements are often poorly timed to detect treatment need in infants born prior to 35 weeks of gestation. This unnecessarily increases the risk of complications from phlebotomy and is an ineffective use of health care resources. There is a need to develop guidelines to optimize hyperbilirubinemia screening among early preterm infants.
Topics: Humans; Infant, Newborn; Phototherapy; Hyperbilirubinemia, Neonatal; Neonatal Screening; Female; Gestational Age; Infant, Premature; Male; Ontario; Retrospective Studies; Bilirubin; Practice Guidelines as Topic
PubMed: 38427505
DOI: 10.3233/NPM-230128