Evaluation of the International Society on Thrombosis and Haemostasis definition of major bleeding in Arizona rattlesnake bites.

INTRODUCTION: In 2023, a group of experts proposed that a definition of major bleeding in pharmaceutically anticoagulated patients be used in all snakebite trials. This includes bleeding that results in death, is life-threatening, causes chronic sequelae, or consumes major healthcare resources, including bleeding into a major area or hemoglobin concentration decrease ≥20 g/L. We hypothesized that a decline in hemoglobin concentration ≥20 g/L is common but rarely clinically significant in our population of Arizona rattlesnake bite patients. METHODS: Poison center records of rattlesnake bites in humans from 2018 through 2022 were retrospectively reviewed and assessed for major bleeding by the above criteria. RESULTS: Four hundred and eighty-one patients met the inclusion criteria, of whom 265 (55.1%) had a hemoglobin concentration decrease ≥20 g/L. No patients died, and there was no evidence of bleeding into a critical organ. Three patients (1.1%) received blood transfusions. A decrease in hemoglobin concentration ≥20 g/L was 100% sensitive for identifying the major bleeding-associated outcomes; however, specificity was only 45.2%. Measures of healthcare utilization and chronic sequelae were somewhat higher in patients with a decrease in hemoglobin concentration ≥20 g/L. DISCUSSION: Laboratory manifestations of hemotoxicity were common in this population, but hemorrhage was rare. While over half of patients met the major bleeding criterion of a decline in hemoglobin concentration ≥20 g/L, only 1.1% had bleeding that was potentially life-threatening as measured by receipt of a red blood cell transfusion. None died or had bleeding into a critical area. While nonspecific for major bleeding, a drop in hemoglobin concentration correlated with worse envenomation severity: these patients received more vials of antivenom, had a higher medical bill, a longer hospital stay, and were less likely to report full recovery at 90 days. CONCLUSIONS: A decrease in hemoglobin concentration ≥20 g/L should not be used as evidence of major bleeding for Arizona rattlesnake envenomation studies, but it may have a role as an indirect marker of envenomation severity.

Evaluation of variants in the ENTPD1 and ENTPD2 genes in athletic horses with exercise-induced pulmonary haemorrhage.

BACKGROUND: Exercise-induced pulmonary haemorrhage (EIPH) in athletic horses is characterized by the presence of blood from the lungs in the tracheobronchial tree after intense exercise. Despite the high prevalence of EIPH in horses, the primary aetiology remains unknown. Variants in the genes encoding CD39 and CD39L1 (ENTPD1 and ENTPD2, respectively) were previously reported as potential genetic causes involved in EIPH pathogenesis. However, the role of these variants in haemostatic functions is unknown. RESULTS: To investigate the association between EIPH and missense variants in the ENTPD1 (rs1152296272, rs68621348, and rs68621347) and ENTPD2 genes (rs782872967), 76 Thoroughbred horses diagnosed with EIPH and 56 without clinical signs of EIPH (control group) by trachea-bronchial endoscopy were genotyped. The rs1152296272 and rs68621347 variants were linked, which explained why the same results were found in all horses. Approximately 96% and 95% of the EIPH and control horses, respectively, carried at least one nonreference allele for these variants. In contrast, 100% of the control horses and 96% of the EIPH horses were homozygous for the reference allele for the rs68621348 variant. In the EIPH group, 1.5% of the horses were homozygotes and 24% were heterozygous for the nonreference allele of the rs782872967 variant. In the control group, the nonreference allele of this variant was observed only in heterozygotes (16%). There were no significant differences between groups for any of the variants. CONCLUSIONS: The variants previously described in the genes encoding the CD39 and CD39L1 enzymes were highly present in the studied population. However, no association was found between the occurrence of EIPH and the presence of these variants in Thoroughbred horses in this study.

Revisiting the full blood count: Circulating blood cells and their role in coagulation.

There has been an expansion in our understanding of the multifaceted roles of circulating blood cells in regulating haemostasis and contributing to thrombosis. Notably, there is greater recognition of the interplay between coagulation with inflammation and innate immune activation and the contribution of leucocytes. The full blood count (FBC) is a time-honoured test in medicine; however, its components are often viewed in isolation and without consideration of their haemostatic and thrombotic potential. Here, we review how the individual components of the FBC, that is, haemoglobin, platelets and leucocytes, engage with the haemostatic system and focus on both their quantitative and qualitative attributes. We also explore how this information can be harnessed into better management of people with multiple long-term conditions because of their higher risk of adverse clinical events.

A call for subspecialty training programmes in women's thrombosis and haemostasis.

Multidisciplinary collaboration to create formal education/training programmes in women's thrombosis and haemostasis will ideally lead to improved knowledge and health equity and potentially improve patient outcomes.

A comparative study on the haemostatic changes in kidney failure patients: Pre- and post- haemodialysis and haemodiafiltration.

BACKGROUND: Individuals with kidney failure have a compromised haemostatic system making them susceptible to both thrombosis and bleeding. OBJECTIVES: Assessment of primary haemostasis in patients treated with either haemodialysis (HD) or haemodiafiltration (HDF) was performed through the measurement of several coagulation-based tests, both pre- and post-dialysis. PATIENTS/METHODS: 41 renal failure patients and 40 controls were recruited. Platelet aggregometry, Factor XIII (FXIII), Fibrinogen, Von Willebrand Factor (VWF) and Soluble P-Selectin (sP-Sel) levels were measured. RESULTS: Maximum platelet aggregation was diminished in renal patients irrespective of aspirin intake. Post-dialysis, platelet function was exacerbated. Pre-dialysis FXIII levels were similar to the healthy cohort and became elevated post-dialysis. This elevation could not be explained by the relative decrease of water by dialysis. Fibrinogen levels were already elevated pre-dialysis and further increased post-dialysis. This elevation was associated with the relative decrease of water by dialysis. VWF levels in males were similar to the healthy cohort and became elevated post-dialysis. This elevation was associated with dialysis-related water loss. VWF antigen and activity in female patients were already elevated pre-dialysis and further increased post-dialysis with the exception of VWF activity in HDF treated female patients. sP-Sel levels were lower than those of the healthy cohort and became similar to the healthy cohort post-dialysis. This elevation could not be explained by the relative decrease of water by dialysis. CONCLUSIONS: Whilst platelet aggregometry was diminished, we noted elevated clotting factors such as fibrinogen, FXIII and VWF with no significant differences between HD and HDF-treated patients.

Comparison of two haemostasis techniques on procedural duration, postoperative pain and gastrointestinal function in pet rabbits undergoing ovariohysterectomy.

Ovariohysterectomy is a common surgical procedure in pet rabbits and one of its potential complications is postoperative gastrointestinal stasis, possibly exacerbated by prolonged surgery time. The objective of this prospective clinical study was to compare two techniques for surgical haemostasis with respect to procedural duration, postoperative pain, and return of gastrointestinal function, in 22 female rabbits undergoing ovariohysterectomy. Rabbits were assigned to one of two groups: conventional vessel ligation (CVL) and haemostasis with a vessel sealing device (VSD). The outcome variables for comparison between the two groups, recorded at 60-, 120-, 180-, and 360-minutes post anaesthesia, were duration of anaesthesia and surgery, postoperative Rabbit Grimace Scale scores, and measured food intake and faecal output. The vessel sealing device caused no appreciable blood loss. The duration of both surgery and anaesthesia was shorter in group VSD (20 ± 4 and 31 ± 6 minutes, respectively) than in group CVL (43 ± 9 and 54 ± 9 minutes, respectively) (p < 0.001). There were no differences between groups in time elapsed from the end of anaesthesia to both first food intake and first defecation. In both groups, the score of the Rabbit Grimace Scale decreased over time with statistically significant differences between 60 minutes and all the subsequent time points (p < 0.001). Vessel sealing devices may be recommended over conventional haemostasis for rabbit ovariohysterectomy to decrease the duration of surgery and anaesthesia, with potential beneficial effects on sustainability and practice workflow.

Haemostatic spray in the management of acute nonvariceal upper gastrointestinal bleeding in children: A single-centre experience in Singapore.

Introduction/Objectives: Haemostatic spray (HS; Hemospray) is a powder agent for endoscopic haemostasis in patients with acute upper gastrointestinal bleeding (UGIB). It has been shown to be effective and easy to administer. However, published data on efficacy and safety in children remain scarce. Our aim was to describe our experience with the use of HS in the management of UGIB. Patients and Methods: A retrospective review was conducted of patients aged 0-18 receiving HS for endoscopic haemostasis from January 2017 to December 2021. Information was obtained on demographics, clinical presentation and comorbidities. Outcomes were successful initial haemostasis and rates of re-bleeding. Results: A total of 25 applications of HS occurred in 23 patients. The median patient age was 8 years (range: 4 months to 16 years). HS was used in 17/25 (68%) applications as monotherapy. Other treatments employed were clip application and adrenaline injection. One hundred per cent initial haemostasis was achieved with three (13.0%) patients who experienced re-bleeding. All patients tolerated HS applications with no adverse events. Conclusions: Our finding supports the use of HS in the management of UGIB in children. HS, either as monotherapy or in combination with other conventional therapy, could potentially be the treatment of choice in children with UGIB with its excellent feasibility and good safety profile.

Spring coil displacement after interventional embolization of severe pelvic fracture: a case report.

Haemorrhagic shock, which arises as a complication of pelvic fracture subsequent to severe trauma, represents a perilous state. The utilization of interventional endovascular haemostasis assumes a pivotal role in the management of patients with vascular injury following pelvic fracture. This article reports the treatment of a patient with pelvic fracture caused by a serious work-related vehicle accident. Despite the implementation of timely blood and fluid transfusion to combat shock, the application of aortic balloon obstruction, and interventional iliac artery embolization for haemostasis, the patient's condition failed to display any discernible improvement. Repeat angiography further revealed a displacement of the interventional embolization material, and the patient subsequently died of multiple organ failure. The occurrence of spring coil displacement is infrequent, but the consequences thereof are considered grave, necessitating meticulous discernment in the selection of haemostatic materials for this type of patient. The diagnostic and therapeutic processes encompassing the particular case described here were analysed and are discussed with the objective of augmenting the efficacy and success rate of treatment modalities for patients in similar circumstances.

Intravenous lipid emulsion interference in coagulation testing: an ex vivo analysis.

INTRODUCTION: Intravenous lipid emulsion is used in the rescue treatment of certain poisonings. A complication is interference with laboratory analyses. The aim of this study was to determine the impact of intravenous lipid emulsion on routine laboratory analysis of coagulation parameters ex vivo and determine if any of the analytical techniques remain reliable. METHODS: Samples were obtained from 19 healthy volunteers and divided in triplicate. One sample served as a control, and the other two were diluted to simulate the treatment of an average adult with Intralipid® 20 per cent Fresenius Kabi 100 mL (dilution-1) or 500 mL (dilution-2). Coagulation tests performed were prothrombin time, activated prothrombin time, D-dimer concentration and fibrinogen. Coagulation testing was performed by three techniques. Test-1 was performed on a Sysmex CN6000 analyzer. Test-2 was performed with a manual mechanical endpoint method using the semi-automated Stago KC4 Delta. Test-3 involved high-speed centrifugation before repeat testing on the Sysmex CN6000 analyzer. RESULTS: For test-1, only nine (47 per cent) samples in dilution-1 could be analyzed for coagulation tests, and no coagulation tests could be analyzed for dilution-2 because of lipaemia. For test-2 and test-3, all samples could be analyzed, and all results of both testing methods fell within the limits of the laboratory reference range. DISCUSSION: Difficulties in laboratory analysis of patients having received intravenous lipid emulsion are due to multiple factors. Most automated coagulation analyzers use optical measurements, which can be unreliable in the presence of a high intravenous lipid concentration. By altering the lipaemia in the testing solution using high-speed centrifugation or by using manual mechanical endpoint detection, we were able to obtain reliable results. These findings are limited by the use of an ex vivo method and healthy volunteers. CONCLUSIONS: This ex vivo model confirms that Intralipid® interferes with routine coagulation studies. It is important that clinicians are aware and inform their laboratories of its administration.

Immuno-Haematologic Aspects of Dengue Infection: Biologic Insights and Clinical Implications.

Dengue infection is caused by the dengue virus (DENV) and is transmitted to humans by infected female Aedes aegypti and Aedes albopictus mosquitoes. There are nearly 100 million new dengue cases yearly in more than 120 countries, with a five-fold increase in incidence over the past four decades. While many patients experience a mild illness, a subset suffer from severe disease, which can be fatal. Dysregulated immune responses are central to the pathogenesis of dengue, and haematologic manifestations are a prominent feature of severe disease. While thrombocytopaenia and coagulopathy are major causes of bleeding in severe dengue, leucocyte abnormalities are emerging as important markers of prognosis. In this review, we provide our perspective on the clinical aspects and pathophysiology of haematologic manifestations in dengue. We also discuss the key gaps in our current practice and areas to be addressed by future research.

Rapid haemostasis to achieve dressing longevity: evaluation trial results using StatSeal catheter exit site protection.

Peripherally inserted central catheters (PICCs) are vital in delivering intravenous therapy. Despite their advantages, PICCs can lead to complications such as catheter exit site bleeding, which can cause patient distress and increase infection risk. This study evaluated the efficacy of StatSeal, a topical haemostatic device, in managing PICC exit site bleeding. StatSeal uses a hydrophilic polymer and potassium ferrate to form a seal, reducing access site bleeding and minimising dressing changes. For this study, Patients were recruited at Frimley Health NHS Foundation Trust; the trial involved 177 patients with StatSeal, and shows that 99% did not require additional dressing changes within the standard 7-day period. The findings demonstrate StatSeal's effectiveness in improving patient outcomes by reducing exit site bleeding and associated complications, enhancing the efficiency of vascular access maintenance and potentially lowering associated healthcare costs. The trial emphasises the importance of innovative solutions such as StatSeal to advance PICC care and improve patient experience.

Moving towards Normalization of haemostasis and health equity: Evolving treatment goals for haemophilia A.

BACKGROUND: Treatment options for people with haemophilia are evolving at a rapid pace and a range of prophylactic treatment options using various technologies are currently available, each with their own distinct safety and efficacy profile. TREATMENT GOALS: The access to replacement therapy and prophylaxis has driven a dramatic reduction in mortality and resultant increase in life expectancy. Beyond this, the abolition of bleeds and preservation of joint health represent the expected, but rarely attained, goals of haemophilia treatment and care. These outcomes also do not address the complexity of health-related quality of life impacted by haemophilia and its treatment. CONCLUSION: Capitalizing on the major potential of therapeutic innovations, 'Normalization' of haemostasis, as a concept, should include the aspiration of enabling individuals to live as normal a life as possible, free from haemophilia-imposed limitations. To achieve this-being supported by the data reviewed in this manuscript-the concept of haemostatic and life Normalization needs to be explored and debated within the wider multidisciplinary teams and haemophilia community.

Rotational thromboelastometry predicts future bleeding events in patients with cirrhosis.

BACKGROUND AND AIMS: Patients with cirrhosis of the liver are in a delicate state of rebalanced haemostasis and are at risk of developing both bleeding and thrombotic complications. Conventional haemostatic tests are unable to predict bleeding and thrombosis in these patients. We aimed to explore the role of Rotational Thromboelastometry (ROTEM) in predicting bleeding and thrombotic events in patients with cirrhosis. METHODS: We conducted a prospective cohort study of patients with cirrhosis at two metropolitan hospitals. All patients underwent ROTEM analysis and were then followed to record any bleeding and thrombotic events. Univariate and multivariate logistic regression analyses were performed to explore associations with bleeding and thrombotic events. RESULTS: Nineteen of the 162 patients recruited experienced a bleeding event within one year of ROTEM analysis. On univariate analysis, maximum clot firmness (MCF) using both EXTEM and INTEM tests was significantly reduced in patients who had a bleeding event, compared to those who did not (50 mm vs. 57 mm, p < 0.01 and 48 mm vs. 54 mm, p < 0.01, respectively). In addition, on univariate analysis, clotting time (CT) in the INTEM test was prolonged in the bleeding group (214 s vs. 198 s, p = 0.01). On multivariate analysis, only MCFEX was a significant predictor of bleeding events. In contrast, there was no association found between ROTEM parameters and development of thrombosis within a one-year period. CONCLUSIONS: ROTEM may provide a useful tool in predicting future bleeding events in patients with cirrhosis. Larger studies are required to further validate this finding and explore its application in clinical practice.

Quantification of the contribution of individual coagulation factors to haemostasis using a microchip flow chamber system and reconstituted blood from deficient plasma.

BACKGROUND AND OBJECTIVES: Quantifying the contribution of individual coagulation factors to haemostasis may aid our understanding of the haemostatic function in patients with rare coagulation deficiencies (RCDs) and the exploration of suitable treatments. MATERIALS AND METHODS: Reconstituted blood prepared from specific coagulation factor-deficient plasma (factor [F]II; prothrombin, FV, FVII, FVIII, FIX, FX, FXI or FXII) and red blood cell/platelet products were used to simulate the whole blood of patients with RCD. We prepared in vitro treatment models for patients with prothrombin deficiency using coagulation factor agents and fresh frozen plasma. Haemostatic function was measured using a microchip flow chamber system at 600 s-1. RESULTS: The haemostatic function was low, especially in blood samples reconstituted with prothrombin- and FX-deficient plasma. In a plasma transfusion model of prothrombin deficiency, haemostatic function recovered after 10% replacement with normal plasma and reached a plateau at ≧60% replacement. A treatment model of prothrombin deficiency with prothrombin complex concentrates revealed dose-dependent therapeutic effects in the range of 0-50 IU/kg. CONCLUSION: Microchip flow chamber system-based quantification of haemostatic function using reconstituted blood could predict haemostasis and therapeutic effects of treatments in patients with prothrombin deficiency.

The use of Arista AH as a local haemostatic agent in distal splenopancreatectomy: report of two cases.

Bleeding is still one of the most feared intraoperative and postoperative complications that can lead to an increase in morbidity, mortality, length of hospital stay and costs. Nowadays, in addition to accurate surgical techniques, several local haemostatic agents are available and can be used in case of oozing bleeding. Herein, we report our experience with a ready-to-use polysaccharide powder in two patients undergoing distal splenopancreatectomy. Bleeding control was achieved in both cases. No patient showed postoperative bleeding, and no other complications were reported.

In vitro analysis of tantalum-containing mesoporous bioactive glass fibres for haemostasis.

Haemorrhage is the leading cause of battlefield deaths and second most common cause for civilian mortality worldwide. Biomaterials-based haemostatic agents are used to aid in bleeding stoppage; mesoporous bioactive glasses (MBGs) are candidates for haemostasis. Previously made Tantalum-containing MBG (Ta-MBG) powders' compositions were fabricated as electrospun fibres for haemostatic applications in the present study. The fibres were fabricated to address the challenges associated with the powder form: difficult to compress without gauze, getting washed away in profuse bleeding, generating dust in the surgical environment, and forming thick callus-difficult to remove for surgeons and painful for patients. Ta-MBGs were based on (80-x)SiO2-15CaO-5P2O5-xTa2O5 mol% compositions with x = 0 (0Ta), 0.5 (0.5Ta), 1 (1Ta), and 5 (5Ta) mol%. The present study details the fibres' in vitro analyses, elucidating their cytotoxic effects, and haemostatic capabilities and relating these observations to fibre chemistry and previously fabricated powders of the same glasses. As expected, when Ta addition is increased at the expense of silica, a new FTIR peak (non-bridging oxygen-silicon, Si-NBO) develops and Si-O-Si peaks become wider. Compared to 0Ta and 1Ta fibres, 0.5Ta show Si-O peaks with reduced intensity. The fibres had a weaker intensity of Si-NBO peaks and release fewer ions than powders. A reduced ion profile provides fibres with a stable matrix for clot formation. The ion release profile for 1Ta and 5Ta fibres was significantly lower than 0Ta and 0.5Ta fibres. Ta-MBGs were not found to be cytotoxic to primary rat fibroblasts using a methyl thiazolyl tetrazolium (MTT) assay. Furthermore, a modified activated partial thromboplastin time assay analysing the fibrin absorbance showed that the absorption increases from physiological clotting < 0Ta < 0.5Ta < 5Ta < commercial haemostat, Surgical SNoWTM, Ethicon, USA < 1Ta. Higher absorption signifies a stronger clot. It is concluded that Ta-MBG fibres can provide stable matrix for clot formation and 1Ta can potentially enhance clotting best among other Ta-MBGs.

Laser-Assisted Lingual Frenectomy: A Case Report.

A lingual frenectomy is a surgical procedure aimed at addressing "tongue-tie" or ankyloglossia, where a strip of tissue restricting tongue movement is removed. Typically, this strip extends from the bottom of the mouth to the underside of the tongue. The procedure, often performed using a diode laser, offers several advantages including simplicity and safety for patients. It can significantly improve speech articulation and eating for individuals with ankyloglossia. This case report highlights the successful treatment of a female patient experiencing speech difficulties with diode laser therapy for tongue-tie.

Ultra-Hydrophobic Gauze Driving Super-Haemostasis.

Controlling bleeding by applying pressing cotton gauze is the most facile treatment in prehospital emergencies. However, the wettable nature of cotton fibers leads to unnecessary blood loss due to excessive blood absorption, inseparable adhesion-induced pain, and pliable to infection. Here, a kind of ultra-hydrophobic haemostatic anti-adhesive gauze whose surface is loaded with polydimethylsiloxane (PDMS) and hydrophobic-modified cellulose nanocrystals (CNCs), achieving a water contact angle of ≈160° is developed. It is demonstrated that the mechanism by which hydrophobic CNCs promote blood clotting is associated with their ability to activate coagulation factors, contributing to fibrin formation, and promoting platelet activation. The blood-restricting effect results from the low surface energy layer formed by PDMS and then the alkyl chains of hydrophobic CNCs are combined. The produced ultra-hydrophobic gauze resists blood flow and diffusion, decreases blood loss, is effortlessly peelable, and minimizes pathogen adhesion. Compared to the commercial cotton gauze, this gauze achieved effective haemostasis and antiadhesion by reducing blood loss by more than 90%, shortening haemostasis time by more than 75%, lowering peeling force by more than 90% and minifying bacterium attachment by more than 95%. This work presents promising applications in terms of prehospital first aid.

Limited value of testing for factor XIII and α2-antiplasmin deficiency in patients with a bleeding disorder of unknown cause.

INTRODUCTION: In patients with an increased bleeding tendency, extensive diagnostic blood testing is often performed. When results of tier 1 assays of primary haemostasis are normal, protocols recommend additional testing to rule out rare disorders including coagulation factor XIII (FXIII) and α2-antiplasmin (α2AP) deficiency. AIM: To evaluate the added diagnostic value of FXIII and α2AP levels in patients with a bleeding disorder of unknown cause (BDUC). METHODS: A retrospective monocentre cohort study between August 2011 and August 2023 was conducted. In all patients with bleeding tendencies and normal diagnostic tests for von Willebrand disease and platelet function, FXIII and α2AP were measured. RESULTS: We included 158 consecutive patients; mean ISTH-BAT scores were 8.2 (SD ± 3.7) in children, 6.2 (SD ± 2.1) in men and 10.6 (SD ± 3.3) in women. Median age was 37 (range 5-79) years, 88.6% of patients were female. Patients displayed median FXIII activity of 111% (IQR = 97-131) and median α2AP activity of 112% (IQR = 103-119). Three (1.9%) patients had FXIII levels < 50%, respectively 43%, 45% and 46%. Corresponding ISTH-BAT scores were 7, 12 and 14. No α2AP levels < 60% was observed. No significant association was found between FXIII levels and ISTH-BAT scores. CONCLUSION: In our cohort of BDUC patients, no clinical relevant FXIII deficiencies were detected; absolute values were well above the 30% cutoff considered adequate for normal haemostasis. No α2AP deficiencies were detected. These data suggest that in BDUC patients, measuring FXIII or AP activity is of limited value.