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Anesthesiology May 2023Inherited and acquired coagulopathy are frequently associated with major bleeding in severe trauma, cardiac surgery with cardiopulmonary bypass, and postpartum...
Inherited and acquired coagulopathy are frequently associated with major bleeding in severe trauma, cardiac surgery with cardiopulmonary bypass, and postpartum hemorrhage. Perioperative management is multifactorial and includes preoperative optimization and discontinuation of anticoagulants and antiplatelet therapy in elective procedures. Prophylactic or therapeutic use of antifibrinolytic agents is strongly recommended in guidelines and has been shown to reduce bleeding and need for allogeneic blood administration. In the context of bleeding induced by anticoagulants and/or antiplatelet therapy, reversal strategies should be considered when available. Targeted goal-directed therapy using viscoelastic point-of-care monitoring is increasingly used to guide the administration of coagulation factors and allogenic blood products. In addition, damage control surgery, which includes tamponade of large wound areas, leaving surgical fields open, and other temporary maneuvers, should be considered when bleeding is refractory to hemostatic measures.
Topics: Female; Humans; Anticoagulants; Blood Coagulation Disorders; Hemorrhage; Hemostatics; Platelet Aggregation Inhibitors; Postpartum Period
PubMed: 36862401
DOI: 10.1097/ALN.0000000000004520 -
Seminars in Thrombosis and Hemostasis Feb 2020Adequate plasma levels of fibrinogen are essential for clot formation, and in severe bleeding, fibrinogen reaches a critically low plasma concentration earlier than... (Review)
Review
Adequate plasma levels of fibrinogen are essential for clot formation, and in severe bleeding, fibrinogen reaches a critically low plasma concentration earlier than other coagulation factors. Although the critical minimum concentration of fibrinogen to maintain hemostasis is a matter of debate, many patients with coagulopathic bleeding require fibrinogen supplementation. Among the treatment options for fibrinogen supplementation, fibrinogen concentrate may be viewed by some as preferable to fresh frozen plasma or cryoprecipitate. The authors review major studies that have assessed fibrinogen treatment in trauma, cardiac surgery, end-stage liver disease, postpartum hemorrhage, and pediatric patients. Some but not all randomized controlled trials have shown that fibrinogen concentrate can be beneficial in these settings. The use of fibrinogen as part of coagulation factor concentrate based therapy guided by point-of-care viscoelastic coagulation monitoring (ROTEM [rotational thromboelastometry] or TEG [thromboelastography]) appears promising. In addition to reducing patients' exposure to allogeneic blood products, this strategy may reduce the risk of complications such as transfusion-associated circulatory overload, transfusion-related acute lung injury, and thromboembolic adverse events. Randomized controlled trials are challenging to perform in patients with critical bleeding, and more evidence is needed in this setting. However, current scientific rationale and clinical data support fibrinogen repletion in patients with ongoing bleeding and confirmed fibrinogen deficiency.
Topics: Blood Component Transfusion; Fibrinogen; Hemorrhage; Humans; Plasma; Point-of-Care Systems; Randomized Controlled Trials as Topic; Risk Factors; Thrombelastography; Transfusion-Related Acute Lung Injury
PubMed: 31574543
DOI: 10.1055/s-0039-1696946 -
Journal of Cancer Research and Clinical... Aug 2023Artificial intelligence (AI) is influencing our society on many levels and has broad implications for the future practice of hematology and oncology. However, for many... (Review)
Review
BACKGROUND
Artificial intelligence (AI) is influencing our society on many levels and has broad implications for the future practice of hematology and oncology. However, for many medical professionals and researchers, it often remains unclear what AI can and cannot do, and what are promising areas for a sensible application of AI in hematology and oncology. Finally, the limits and perils of using AI in oncology are not obvious to many healthcare professionals.
METHODS
In this article, we provide an expert-based consensus statement by the joint Working Group on "Artificial Intelligence in Hematology and Oncology" by the German Society of Hematology and Oncology (DGHO), the German Association for Medical Informatics, Biometry and Epidemiology (GMDS), and the Special Interest Group Digital Health of the German Informatics Society (GI). We provide a conceptual framework for AI in hematology and oncology.
RESULTS
First, we propose a technological definition, which we deliberately set in a narrow frame to mainly include the technical developments of the last ten years. Second, we present a taxonomy of clinically relevant AI systems, structured according to the type of clinical data they are used to analyze. Third, we show an overview of potential applications, including clinical, research, and educational environments with a focus on hematology and oncology.
CONCLUSION
Thus, this article provides a point of reference for hematologists and oncologists, and at the same time sets forth a framework for the further development and clinical deployment of AI in hematology and oncology in the future.
Topics: Humans; Artificial Intelligence; Medical Oncology; Hematology; Forecasting
PubMed: 36920563
DOI: 10.1007/s00432-023-04667-5 -
Military Medical Research Mar 2020Hemorrhage is the leading cause of preventable death in combat trauma and the secondary cause of death in civilian trauma. A significant number of deaths due to... (Review)
Review
Hemorrhage is the leading cause of preventable death in combat trauma and the secondary cause of death in civilian trauma. A significant number of deaths due to hemorrhage occur before and in the first hour after hospital arrival. A literature search was performed through PubMed, Scopus, and Institute of Scientific Information databases for English language articles using terms relating to hemostatic agents, prehospital, battlefield or combat dressings, and prehospital hemostatic resuscitation, followed by cross-reference searching. Abstracts were screened to determine relevance and whether appropriate further review of the original articles was warranted. Based on these findings, this paper provides a review of a variety of hemostatic agents ranging from clinically approved products for human use to newly developed concepts with great potential for use in prehospital settings. These hemostatic agents can be administered either systemically or locally to stop bleeding through different mechanisms of action. Comparisons of current hemostatic products and further directions for prehospital hemorrhage control are also discussed.
Topics: Blood Coagulation Factors; Blood Platelets; Emergency Medical Services; Hemorrhage; Hemostasis; Hemostatics; Humans; Plasma; Polymers; Resuscitation; Tranexamic Acid
PubMed: 32209132
DOI: 10.1186/s40779-020-00241-z -
The Australasian Journal of Dermatology Aug 2020Facial aesthetic treatment with injectable neuromodulators and hyaluronic acid fillers is well established, with favourable safety profiles and consistent outcomes. As... (Review)
Review
Facial aesthetic treatment with injectable neuromodulators and hyaluronic acid fillers is well established, with favourable safety profiles and consistent outcomes. As with any medical treatment, adverse events and complications may occur. Adverse events associated with these products are typically transient and mild to moderate in severity. Serious adverse events, such as infection and intravascular occlusion, are rare. Proper patient selection, consent and counselling, preparation and impeccable injection technique are important risk reduction strategies. Both clinicians and patients must be alert to the signs and symptoms of complications so that appropriate treatment can be started promptly. In this article, the authors review the current literature and provide their consensus recommendations for minimising adverse outcomes when treating patients with botulinum toxin or hyaluronic acid fillers.
Topics: Botulinum Toxins, Type A; Consensus; Contusions; Cosmetic Techniques; Dermal Fillers; Directive Counseling; Edema; Erythema; Face; Hematoma; Humans; Hyaluronic Acid; Injection Site Reaction; Injections; Neuromuscular Agents; Pain; Patient Education as Topic; Patient Selection
PubMed: 32201935
DOI: 10.1111/ajd.13273 -
The Lancet. Haematology Apr 2022Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red... (Randomized Controlled Trial)
Randomized Controlled Trial
Resuscitation with blood products in patients with trauma-related haemorrhagic shock receiving prehospital care (RePHILL): a multicentre, open-label, randomised, controlled, phase 3 trial.
BACKGROUND
Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red blood cells (PRBC) and lyophilised plasma (LyoPlas) was superior to use of 0·9% sodium chloride for improving tissue perfusion and reducing mortality in trauma-related haemorrhagic shock.
METHODS
Resuscitation with pre-hospital blood products (RePHILL) is a multicentre, allocation concealed, open-label, parallel group, randomised, controlled, phase 3 trial done in four civilian prehospital critical care services in the UK. Adults (age ≥16 years) with trauma-related haemorrhagic shock and hypotension (defined as systolic blood pressure <90 mm Hg or absence of palpable radial pulse) were assessed for eligibility by prehospital critial care teams. Eligible participants were randomly assigned to receive either up to two units each of PRBC and LyoPlas or up to 1 L of 0·9% sodium chloride administered through the intravenous or intraosseous route. Sealed treatment packs which were identical in external appearance, containing PRBC-LyoPlas or 0·9% sodium chloride were prepared by blood banks and issued to participating sites according to a randomisation schedule prepared by the co-ordinating centre (1:1 ratio, stratified by site). The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. This study is completed and registered with ISRCTN.com, ISRCTN62326938.
FINDINGS
From Nov 29, 2016 to Jan 2, 2021, prehospital critical care teams randomly assigned 432 participants to PRBC-LyoPlas (n=209) or to 0·9% sodium chloride (n=223). Trial recruitment was stopped before it achieved the intended sample size of 490 participants due to disruption caused by the COVID-19 pandemic. The median follow-up was 9 days (IQR 1 to 34) for participants in the PRBC-LyoPlas group and 7 days (0 to 31) for people in the 0·9% sodium chloride group. Participants were mostly white (62%) and male (82%), had a median age of 38 years (IQR 26 to 58), and were mostly involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, IQR 25 to 50). Before randomisation, participants had received on average 430 mL crystalloid fluids and tranexamic acid (90%). The composite primary outcome occurred in 128 (64%) of 199 participants randomly assigned to PRBC-LyoPlas and 136 (65%) of 210 randomly assigned to 0·9% sodium chloride (adjusted risk difference -0·025% [95% CI -9·0 to 9·0], p=0·996). The rates of transfusion-related complications in the first 24 h after ED arrival were similar across treatment groups (PRBC-LyoPlas 11 [7%] of 148 compared with 0·9% sodium chloride nine [7%] of 137, adjusted relative risk 1·05 [95% CI 0·46-2·42]). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in 0·9% sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the 0·9% sodium chloride group (abnormal liver function test). There were no treatment-related deaths.
INTERPRETATION
The trial did not show that prehospital PRBC-LyoPlas resuscitation was superior to 0·9% sodium chloride for adult patients with trauma related haemorrhagic shock. Further research is required to identify the characteristics of patients who might benefit from prehospital transfusion and to identify the optimal outcomes for transfusion trials in major trauma. The decision to commit to routine prehospital transfusion will require careful consideration by all stakeholders.
FUNDING
National Institute for Health Research Efficacy and Mechanism Evaluation.
Topics: Adolescent; Adult; Blood Transfusion; COVID-19; Emergency Medical Services; Humans; Male; Middle Aged; Pandemics; Shock, Hemorrhagic; Treatment Outcome
PubMed: 35271808
DOI: 10.1016/S2352-3026(22)00040-0 -
BMJ Sexual & Reproductive Health Jan 2024Heavy menstrual bleeding affects up to one third of menstruating individuals and has a negative impact on quality of life. The diagnosis of heavy menstrual bleeding is...
BACKGROUND
Heavy menstrual bleeding affects up to one third of menstruating individuals and has a negative impact on quality of life. The diagnosis of heavy menstrual bleeding is based primarily on history taking, which is highly dependent on traditional disposable menstrual products such as pads and tampons. Only tampons undergo industry-regulated testing for absorption capacity. As use of alternative menstrual products is increasing, there is a need to understand how the capacity of these products compare to that of standard products.
METHODS
A variety of commercially available menstrual products (tampons, pads, menstrual cups and discs, and period underwear) were tested in the laboratory to determine their maximal capacity to absorb or fill using expired human packed red blood cells. The volume of blood necessary for saturation or filling of the product was recorded.
RESULTS
Of the 21 individual menstrual hygiene products tested, a menstrual disc (Ziggy, Jiangsu, China) held the most blood of any product (80 mL). The perineal ice-activated cold pack and period underwear held the least (<3 mL each). Of the product categories tested, on average, menstrual discs had the greatest capacity (61 mL) and period underwear held the least (2 mL). Tampons, pads (heavy/ultra), and menstrual cups held similar amounts of blood (approximately 20-50 mL).
CONCLUSION
This study found considerable variability in red blood cell volume capacity of menstrual products. This emphasises the importance of asking individuals about the type of menstrual products they use and how they use them. Further understanding of capacity of newer menstrual products can help clinicians better quantify menstrual blood loss, identify individuals who may benefit from additional evaluation, and monitor treatment.
Topics: Female; Humans; Menorrhagia; Menstrual Hygiene Products; Hygiene; Quality of Life; Menstruation; Erythrocytes
PubMed: 37550075
DOI: 10.1136/bmjsrh-2023-201895 -
JAMA Surgery Nov 2019Current therapies for traumatic blood loss focus on hemorrhage control and blood volume replacement. Severe hemorrhagic shock, however, is associated with a state of... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Low-Dose Supplementation of Arginine Vasopressin on Need for Blood Product Transfusions in Patients With Trauma and Hemorrhagic Shock: A Randomized Clinical Trial.
IMPORTANCE
Current therapies for traumatic blood loss focus on hemorrhage control and blood volume replacement. Severe hemorrhagic shock, however, is associated with a state of arginine vasopressin (AVP) deficiency, and supplementation of this hormone may decrease the need for blood products in resuscitation.
OBJECTIVE
To determine whether low-dose supplementation of AVP in patients with trauma (hereinafter referred to as trauma patients) and with hemorrhagic shock decreases their need for transfused blood products during resuscitation.
DESIGN, SETTING, AND PARTICIPANTS
This randomized, double-blind placebo-controlled clinical trial included adult trauma patients (aged 18-65 years) who received at least 6 U of any blood product within 12 hours of injury at a single urban level 1 trauma center from May 1, 2013, through May 31, 2017. Exclusion criteria consisted of prehospital cardiopulmonary resuscitation, emergency department thoracotomy, corticosteroid use, chronic renal insufficiency, coronary artery disease, traumatic brain injury requiring any neurosurgical intervention, pregnancy, prisoner status, or AVP administration before enrollment. Data were analyzed from May 1, 2013, through May 31, 2017, using intention to treat and per protocol.
INTERVENTIONS
After administration of an AVP bolus (4 U) or placebo, participants received AVP (≤0.04 U/min) or placebo for 48 hours to maintain a mean arterial blood pressure of at least 65 mm Hg.
MAIN OUTCOMES
The primary outcome was total volume of blood product transfused. Secondary end points included total volume of crystalloid transfused, vasopressor requirements, secondary complications, and 30-day mortality.
RESULTS
One hundred patients underwent randomization (49 to the AVP group and 51 to the placebo group). Patients were primarily young (median age, 27 years [interquartile range {IQR}, 22-25 years]) and male (n = 93) with penetrating trauma (n = 79). Cohort characteristics before randomization were well balanced. At 48 hours, patients who received AVP required significantly less blood products (median, 1.4 [IQR, 0.5-2.6] vs 2.9 [IQR, 1.1-4.8] L; P = .01) but did not differ in requirements for crystalloids (median, 9.9 [IQR, 7.9-13.0] vs 11.0 [8.9-15.0] L; P = .22) or vasopressors (median, 400 [IQR, 0-5900] vs 1400 [IQR, 200-7600] equivalent units; P = .22). Although the groups had similar rates of mortality (6 of 49 [12%] vs 6 of 51 [12%]; P = .94) and total complications (24 of 44 [55%] vs 30 of 47 [64%]; P = .37), the AVP group had less deep venous thrombosis (5 of 44 [11%] vs 16 of 47 [34%]; P = .02).
CONCLUSIONS AND RELEVANCE
Low-dose AVP during the resuscitation of trauma patients in hemorrhagic shock decreases blood product requirements. Additional research is necessary to determine whether including AVP improves morbidity or mortality.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT01611935.
Topics: Adolescent; Adult; Aged; Arginine Vasopressin; Blood Component Transfusion; Clinical Protocols; Double-Blind Method; Female; Hemostatics; Humans; Male; Middle Aged; Shock, Hemorrhagic; Trauma Centers; Wounds and Injuries; Young Adult
PubMed: 31461138
DOI: 10.1001/jamasurg.2019.2884 -
Critical Care (London, England) Jul 2023Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this... (Review)
Review
BACKGROUND
Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this first systematic review, we aimed to identify all MT definitions used in randomised controlled trials (RCTs) to date to inform the development of consensus definitions for MT.
METHODS
We systematically searched the following databases for RCTs from inception until 11 August 2022: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Cumulative Index to Nursing and Allied Health Literature, and Transfusion Evidence Library. Ongoing trials were sought from CENTRAL, ClinicalTrials.gov, and World Health Organisation International Clinical Trials Registry Platform. To be eligible for inclusion, studies had to fulfil all the following three criteria: (1) be an RCT; (2) include an adult patient population with major bleeding who had received, or were anticipated to receive, an MT in any clinical setting; and (3) specify a definition for MT as an inclusion criterion or outcome measure.
RESULTS
Of the 8,458 distinct references identified, 30 trials were included for analysis (19 published, 11 ongoing). Trauma was the most common clinical setting in published trials, while for ongoing trials, it was obstetrics. A total of 15 different definitions of MT were identified across published and ongoing trials, varying greatly in cut-offs for volume transfused and time period. Almost all definitions specified the number of red blood cells (RBCs) within a set time period, with none including plasma, platelets or other haemostatic agents that are part of contemporary transfusion resuscitation. For completed trials, the most commonly used definition was transfusion of ≥ 10 RBC units in 24 h (9/19, all in trauma), while for ongoing trials it was 3-5 RBC units (n = 7), with the timing for transfusion being poorly defined, or in some trials not provided at all (n = 5).
CONCLUSIONS
Transfusion of ≥ 10 RBC units within 24 h was the most commonly used definition in published RCTs, while lower RBC volumes are being used in ongoing RCTs. Any consensus definitions should reflect the need to incorporate different blood components/products for MT and agree on whether a 'one-size-fits-all' approach should be used across different clinical settings.
Topics: Adult; Humans; Hemorrhage; Hemostatics; Blood Transfusion; Blood Platelets; Erythrocyte Transfusion
PubMed: 37407998
DOI: 10.1186/s13054-023-04537-z -
Critical Care (London, England) Jun 2022Andexanet alfa is approved (FDA "accelerated approval"; EMA "conditional approval") as the first specific reversal agent for factor Xa (FXa) inhibitor-associated...
Andexanet alfa versus four-factor prothrombin complex concentrate for the reversal of apixaban- or rivaroxaban-associated intracranial hemorrhage: a propensity score-overlap weighted analysis.
BACKGROUND
Andexanet alfa is approved (FDA "accelerated approval"; EMA "conditional approval") as the first specific reversal agent for factor Xa (FXa) inhibitor-associated uncontrolled or life-threatening bleeding. Four-factor prothrombin complex concentrates (4F-PCC) are commonly used as an off-label, non-specific, factor replacement approach to manage FXa inhibitor-associated life-threatening bleeding. We evaluated the effectiveness and safety of andexanet alfa versus 4F-PCC for management of apixaban- or rivaroxaban-associated intracranial hemorrhage (ICH).
METHODS
This two-cohort comparison study included andexanet alfa patients enrolled at US hospitals from 4/2015 to 3/2020 in the prospective, single-arm ANNEXA-4 study and a synthetic control arm of 4F-PCC patients admitted within a US healthcare system from 12/2016 to 8/2020. Adults with radiographically confirmed ICH who took their last dose of apixaban or rivaroxaban < 24 h prior to the bleed were included. Patients with a Glasgow Coma Scale (GCS) score < 7, hematoma volume > 60 mL, or planned surgery within 12 h were excluded. Outcomes were hemostatic effectiveness from index to repeat scan, mortality within 30 days, and thrombotic events within five days. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using propensity score-overlap weighted logistic regression.
RESULTS
The study included 107 andexanet alfa (96.6% low dose) and 95 4F-PCC patients (79.3% receiving a 25 unit/kg dose). After propensity score-overlap weighting, mean age was 79 years, GCS was 14, time from initial scan to reversal initiation was 2.3 h, and time from reversal to repeat scan was 12.2 h in both arms. Atrial fibrillation was present in 86% of patients. Most ICHs were single compartment (78%), trauma-related (61%), and involved the intracerebral and/or intraventricular space(s) (53%). ICH size was ≥ 10 mL in volume (intracerebral and/or ventricular) or ≥ 10 mm in thickness (subdural or subarachnoid) in 22% of patients and infratentorial in 15%. Andexanet alfa was associated with greater odds of achieving hemostatic effectiveness (85.8% vs. 68.1%; OR 2.73; 95% CI 1.16-6.42) and decreased odds of mortality (7.9% vs. 19.6%; OR 0.36; 95% CI 0.13-0.98) versus 4F-PCC. Two thrombotic events occurred with andexanet alfa and none with 4F-PCC.
CONCLUSIONS
In this indirect comparison of patients with an apixaban- or rivaroxaban-associated ICH, andexanet alfa was associated with better hemostatic effectiveness and improved survival compared to 4F-PCC. Trial registration NCT02329327; registration date: December 31, 2014.
Topics: Adult; Aged; Anticoagulants; Blood Coagulation Factors; Factor Xa; Factor Xa Inhibitors; Hemorrhage; Hemostatics; Humans; Intracranial Hemorrhages; Propensity Score; Prospective Studies; Pyrazoles; Pyridones; Recombinant Proteins; Retrospective Studies; Rivaroxaban; Thrombosis
PubMed: 35710578
DOI: 10.1186/s13054-022-04043-8