Coagulopathic Patients Research Articles

Correction of Trauma-induced Coagulopathy by Goal-directed Therapy: A Secondary Analysis of the ITACTIC Trial.

Trauma hemorrhage induces a coagulopathy with a high associated mortality rate. The Implementing Treatment Algorithms for the Correction of Trauma Induced Coagulopathy (ITACTIC) randomized trial tested two goal-directed treatment algorithms for coagulation management: one guided by conventional coagulation tests and one by viscoelastic hemostatic assays (viscoelastic). The lack of a difference in 28-day mortality led the authors to hypothesize that coagulopathic patients received insufficient treatment to correct coagulopathy. During ITACTIC, two sites were coenrolling patients into an ongoing prospective observational study, which included serial blood sampling at the same intervals as in ITACTIC. The subgroup in both studies had conventional and viscoelastic test results for each patient available for analysis. A goal-directed treatment was defined as one triggered by an ITACTIC algorithm. Coagulopathy was defined as rotational thromboelastometry EXTEM A5 less than 40 mm. The primary outcome was correction of coagulopathy by the 12th unit of erythrocyte transfusion during resuscitation. Full viscoelastic and conventional coagulation test results were available for 133 patients. Of these patients, 71% were coagulopathic on admission, and 16% developed a coagulopathy during resuscitation. ITACTIC viscoelastic hemostatic assay group patients were more likely to receive goal-directed treatment than the standard group (76% vs. 47%; odds ratio, 3.73; 95% CI, 1.64 to 8.49; P = 0.002). However, only 54% of patients received goal-directed treatment, and only 20% corrected their coagulopathy (vs. 0% with empiric treatment alone; not significant). Median time to first goal-directed treatment was 68 (53 to 88) min for viscoelastic and 110 (77 to 123) min for standard (P = 0.005). In ITACTIC, many bleeding trauma patients did not receive an indicated goal-directed treatment. Interventions arrived late during resuscitation and were only partially effective at correcting coagulopathy.

Coagulopathy in Penetrating Ballistic Cranial Trauma: A 7-Year Experience.

Penetrating ballistic cranial trauma (PBCT) carries significant mortality when compared with blunt trauma. The development of coagulopathy in PBCT is a strong predictor of mortality. The goal of the study was to describe the incidence and risk factors of coagulopathy in PBCT and to report the value of tranexamic acid administration in PBCT. We retrospectively analyzed 270 patients who presented with PBCT to a single, Level 1 trauma center between 2016 and 2023. A total of 47% (127/270) of patients with PBCT developed coagulopathy at presentation. Fifty-seven patients received tranexamic acid at presentation, which did not affect the development of coagulopathy. Coagulopathic patients were more likely to have more serious injury patterns (bihemispheric [adjusted odds ratio, aOR: 2.6 CI: 1.4-4.9, P = .004] or transventricular trajectories [aOR: 4.9 CI: 1.9-19.6, P = .03]). In addition, they presented with a larger base deficit (aOR: 0.9 CI: 1.002-1.2 per mEq/L, P = .006) which negatively correlated with the international normalized ratio (ρ: -0.46, P < .0001, Spearman correlation). Using thromboelastography helped to identify an additional 20% of patients who presented with normal coagulation on conventional testing. Coagulopathy is prevalent in approximately 50% of patients with PBCT and is persistent despite treatment in a substantial subset of patients. The addition of thromboelastography with its increased coagulopathy sensitivity can potentially guide treatment more efficiently than traditional coagulopathy laboratory tests and fibrinogen alone. Patients with a significant base deficit on arterial blood gas are at higher risk for coagulopathy.

Targeting GPVI with glenzocimab in COVID-19 patients: Results from a randomized clinical trial.

Glenzocimab is a novel antithrombotic agent which targets platelet glycoprotein VI (GPVI) and does not induce haemorrhage. SARS-CoV-2 triggers a prothrombotic state and lung injury whose mechanisms include coagulopathy, endothelial dysfunction, and inflammation with dysregulated platelets. GARDEN was a randomised double-blind, exploratory phase II study of glenzocimab in SARS-CoV-2 respiratory failure (NCT04659109). PCR+ adults in Brazil and France (7 centres) were randomized to standard-of-care (SOC) plus glenzocimab (1000 mg/dayx3 days) or placebo, followed for 40 days. Primary efficacy endpoint was clinical progression at Day 4. All analyses concerned the intention-to-treat population. Between December 2020 and August 2021, 61 patients received at least one dose (30 glenzocimab vs 32 placebo) and 58 completed the study (29 vs 29). Clinical progression of COVID-19 ARDS was not statistically different between glenzocimab and placebo arms (43.3% and 29.0%, respectively; p = 0.245). Decrease in the NEWS-2 category at D4 was statistically significant (p = 0.0290) in the glenzocimab arm vs placebo. No Serious Adverse Event (SAE) was deemed related to study drug; bleeding related events were reported in 6 patients (7 events) and 4 patients (4 events) in glenzocimab and placebo arms, respectively. Therapeutic GPVI inhibition assessment during COVID-19 was conducted in response to a Public Health emergency. Glenzocimab in coagulopathic patients under therapeutic heparin was neither associated with increased bleeding, nor SAE. Clinical impact of glenzocimab on COVID-19 ARDS was not demonstrated. A potential role for GPVI inhibition in other types of ARDS deserves further experimentation. Glenzocimab is currently studied in stroke (ACTISAVE: NCT05070260) and cardiovascular indications.

The Influence of Coagulopathy on Radiographic and Clinical Outcomes in Patients Undergoing Middle Meningeal Artery Embolization as Standalone Treatment for Non-acute Subdural Hematomas.

Middle meningeal artery embolization (MMAE) is emerging as a safe and effective standalone intervention for non-acute subdural hematomas (NASHs); however, the risk of hematoma recurrence after MMAE in coagulopathic patients is unclear. To characterize the impact of coagulopathy on treatment outcomes, we analyzed a multi-institutional database of patients who underwent standalone MMAE as treatment for NASH. We classified 537 patients who underwent MMAE as a standalone intervention between 2019 and 2023 by coagulopathy status. Coagulopathy was defined as use of anticoagulation/antiplatelet agents or pre-operative thrombocytopenia (platelets <100,000/μL). Demographics, pre-procedural characteristics, in-hospital course, and patient outcomes were collected. Thrombocytopenia, aspirin use, antiplatelet agent use, and anticoagulant use were assessed using univariate and multivariate analyses to identify any characteristics associated with the need for rescue surgical intervention, mortality, adverse events, and modified Rankin Scale score at 90-day follow-up. Propensity score-matched cohorts by coagulopathy status with matching covariates adjusting for risk factors implicated in surgical recurrence were evaluated by univariate and multivariate analyses. Minimal differences in pre-operative characteristics between patients with and those without coagulopathy were observed. On unmatched and matched analyses, patients with coagulopathy had higher rates of requiring subsequent surgery than those without (unmatched: 9.9% vs. 4.3%; matched: 12.6% vs. 4.6%; both p < 0.05). On matched multivariable analysis, patients with coagulopathy had an increased odds ratio (OR) of requiring surgical rescue (OR 3.95; 95% confidence interval [CI] 1.68-9.30; p < 0.01). Antiplatelet agent use (ticagrelor, prasugrel, or clopidogrel) was also predictive of surgical rescue (OR 4.38; 95% CI 1.51-12.72; p = 0.01), and patients with thrombocytopenia had significantly increased odds of in-hospital mortality (OR 5.16; 95% CI 2.38-11.20; p < 0.01). There were no differences in follow-up radiographic and other clinical outcomes in patients with and those without coagulopathy. Patients with coagulopathy undergoing standalone MMAE for treatment of NASH may have greater risk of requiring surgical rescue (particularly in patients using antiplatelet agents), and in-hospital mortality (in thrombocytopenic patients).

873 Code Brain Ultra-Early Clinical Pathway for Patient Identification and Management in Spontaneous Non-traumatic Intracranial Hemorrhage Single-Institution Study

INTRODUCTION: Spontaneous non-traumatic intracranial hemorrhage causes high morbidity and mortality. Clinical pathways for the management of acute ischemic stroke are well established but fall short in identifying intracranial hemorrhage, preventing early therapy. METHODS: Using Class 1 recommendations from the AHA/ASA Spontaneous Intracranial Hemorrhage Guidelines, our multi-disciplinary stroke team developed a hyper-acute clinical pathway. Once the hemorrhagic stroke patient was identified, protocolized measures were immediately initiated to lower systolic blood pressure to 140 mmHg, institute factor replacement therapies in coagulopathic patients and anti-platelet reversal when appropriate. Key performance indicators and quality metrics were established to compare post-intervention groups to the baseline cohort. RESULTS: Of 180 patients, 113 and 67 patients were treated pre- and post-protocol, respectively. From pre- to post-protocol, diagnosis of hemorrhagic stroke using the alert increased from 59% to 81%. Anti-hypertensive initiation within 60 minutes increased from 79.5% to 88.7%, with the average time from CT result decreasing from 32.7 to 21.7 minutes. Time to reversal agent decreased from 53 to 23 minutes for pro-coagulation agents and 106 to 55 minutes for DDAVP. Reversal agent initiation within 60 minutes of CT result increased from 66.6% to 100% for pro-coagulation agents and 28.5% to 84.6% for DDAVP. CONCLUSIONS: The initiation of this management protocol for hemorrhagic stroke resulted in a higher proportion of patients being rapidly identified and earlier initiation of anti-hypertensive and hemostatic therapies. These processes are the key to important interventions designed to reduce injury extension associated with intracranial hemorrhage, like “time to thrombolysis” measures for acute ischemic stroke.

Major vascular reconstructions in thoracic oncological surgery.

The replacement of the superior vena cava and thoracic outlet vessels for thoracic malignancies often becomes necessary for radical oncological surgery. The pulmonary artery can be directly infiltrated by the tumor or affected by metastatic hilar lymph nodes. In some cases, it must be resected and reconstructed to achieve oncological radicality and/or avoid pneumonectomy. This study reflects a single-surgeon, retrospective experience spanning 6years (2017-2023). We reviewed data from patients undergoing early anticoagulant therapy after superior vena cava or thoracic outlet vessels bypass and from patients undergoing early antiaggregation therapy following pulmonary artery reconstruction or resection. This series comprises 41 patients treated by a single surgeon. Fourteen patients underwent superior vena cava and thoracic outlet vessel procedures. Among these, eight patients received superior vena cava replacement (six for thymic malignancies and two for lung cancer), and six patients underwent jugular and subclavian artery/vein resection or replacement (all six had sarcomas). There was one death due to respiratory failure, not associated with bleeding or bypass closure. Additionally, there was one graft closure in a patient with severe coagulopathy and three instances of hemothorax (two patients had undiagnosed complex coagulopathies not evident in pre-operative routine blood tests). Following bleeding incidents, anticoagulation was initiated the next day in one case and based on hematological indications in the two coagulopathic patients. In the pulmonary artery series, 27 patients were involved: 20 underwent direct suture after tangential resection, and 7 received pericardial patch reconstruction. Only one case experienced bleeding necessitating redo-surgery. All these patients received early and chronic antiaggregation therapy after pulmonary artery reconstruction. We conclude that major thoracic oncological vascular surgery is safe and feasible with appropriate technical skills. However, achieving optimal results requires integration with correct early anticoagulant therapy or antiaggregation to maintain the patency of bypasses/grafts and prevent life-threatening risks associated with closure of the "new vessels."

Thromboelastography-Guided Correction of Coagulopathy Before Tunneled Central Venous Access in Critically Ill Patients With Liver Disease: A Propensity Score-Matched Study.

Optimal blood product transfusion strategies before tunneled central venous catheter (CVC) placement are required in critically ill coagulopathic patients with liver disease to reduce exposure to allogeneic blood products and mitigate bleeding and thrombotic complications. This study evaluated the safety and efficacy of a thromboelastography-guided transfusion strategy for the correction of coagulopathy in patients with liver disease compared with a conventional transfusion strategy (using international normalized ratio, platelet count, and fibrinogen) before tunneled CVC insertion. A retrospective propensity score-matched single-center cohort study was conducted at a quaternary care academic medical center involving 364 patients with liver disease (cirrhosis and acute liver failure) who underwent tunneled CVC insertion in the ICU. Patients were stratified into two groups based on whether they received blood product transfusions based on a thromboelastography-guided or conventional transfusion strategy. Primary outcomes that were evaluated included the volume, units and cost of blood products (fresh frozen plasma, cryoprecipitate, and platelets) when using a thromboelastography-guided or conventional approach to blood transfusions. Secondary outcomes included the frequency of procedure-related bleeding and thrombotic complications. The total number of units/volume/cost of fresh frozen plasma (12 U/3,000 mL/$684 vs. 32 U/7,500 mL/$1,824 [p = 0.019]), cryoprecipitate (60 U/1,500 mL/$3,240 vs. 250 U/6,250 mL/$13,500 [p < 0.001]), and platelets (5 U/1,500 mL/$2,610 vs. 13 units/3,900 mL/$6,786 [p = 0.046]) transfused were significantly lower in the thromboelastography-guided transfusion group than in the conventional transfusion group. No differences in the frequency of bleeding/thrombotic events were observed between the two groups. A thromboelastography-guided transfusion strategy for correction of coagulopathy in critically ill patients with liver disease before tunneled CVC insertion, compared with a conventional transfusion strategy, reduces unnecessary exposure to allogeneic blood products and associated costs without increasing the risk for peri-procedural bleeding and thrombotic complications.

Point-of-care, goal-directed management of bleeding in trauma patients.

The purpose of this review is to consider the clinical value of point-of-care (POC) testing in coagulopathic trauma patients with traumatic brain injury (TBI) and trauma-induced coagulopathy (TIC). Patients suffering from severe TBI or TIC are at risk of developing pronounced haemostatic disorders. Standard coagulation tests (SCTs) are insufficient to reflect the complexity of these coagulopathies. Recent evidence has shown that viscoelastic tests (VETs) identify haemostatic disorders more rapidly and in more detail than SCTs. Moreover, VET results can guide coagulation therapy, allowing individualised treatment, which decreases transfusion requirements. However, the impact of VET on mortality remains uncertain. In contrast to VETs, the clinical impact of POC platelet function testing is still unproven. POC SCTs are not able to characterise the complexity of trauma-associated coagulopathy. VETs provide a rapid estimation of underlying haemostatic disorders, thereby providing guidance for haemostatic therapy, which impacts allogenic blood transfusion requirements. The value of POC platelet function testing to identify platelet dysfunction and guide platelet transfusion is still uncertain.

Defining critical illness using immunological endotypes in patients with and without sepsis: a cohort study

BackgroundSepsis is a heterogenous syndrome with limited therapeutic options. Identifying immunological endotypes through gene expression patterns in septic patients may lead to targeted interventions. We investigated whether patients admitted to a surgical intensive care unit (ICU) with sepsis and with high risk of mortality express similar endotypes to non-septic, but still critically ill patients using two multiplex transcriptomic metrics obtained both on admission to a surgical ICU and at set intervals.MethodsWe analyzed transcriptomic data from 522 patients in two single-site, prospective, observational cohorts admitted to surgical ICUs over a 5-year period ending in July 2020. Using an FDA-cleared analytical platform (nCounter FLEX®, NanoString, Inc.), we assessed a previously validated 29-messenger RNA transcriptomic classifier for likelihood of 30-day mortality (IMX-SEV-3) and a 33-messenger RNA transcriptomic endotype classifier. Clinical outcomes included all-cause mortality, development of chronic critical illness, and secondary infections. Univariate and multivariate analyses were performed to assess for true effect and confounding.ResultsSepsis was associated with a significantly higher predicted and actual hospital mortality. At enrollment, the predominant endotype for both septic and non-septic patients was adaptive, though with significantly different distributions. Inflammopathic and coagulopathic septic patients, as well as inflammopathic non-septic patients, showed significantly higher frequencies of secondary infections compared to those with adaptive endotypes (p < 0.01). Endotypes changed during ICU hospitalization in 57.5% of patients. Patients who remained adaptive had overall better prognosis, while those who remained inflammopathic or coagulopathic had worse overall outcomes. For severity metrics, patients admitted with sepsis and a high predicted likelihood of mortality showed an inflammopathic (49.6%) endotype and had higher rates of cumulative adverse outcomes (67.4%). Patients at low mortality risk, whether septic or non-septic, almost uniformly presented with an adaptive endotype (100% and 93.4%, respectively).ConclusionCritically ill surgical patients express different and evolving immunological endotypes depending upon both their sepsis status and severity of their clinical course. Future studies will elucidate whether endotyping critically ill, septic patients can identify individuals for targeted therapeutic interventions to improve patient management and outcomes.

A prospective observational phase IV study on effectiveness of animal derived polyclonal antibody antivenoms against West African carpet viper (Echis romani) induced coagulopathy and mortality

Conventional polyclonal antibody antivenoms are the mainstay of snakebite therapy. They have not been proven to be efficacious in randomized placebo controlled clinical trials among severely envenomed patients. There is also paucity of evidence on effectiveness especially in routine use. The current study evaluated their effectiveness in post marketing use among those managed with and without antivenom as regards to reversal of venom induced coagulopathy defined using the 20 min Whole Blood Clotting Test [20WBCT] and in averting death. The effectiveness of antivenom was evaluated among 5467 patients predominantly envenomed by the West African carpet viper (Echis romani) at 3 hospitals in Nigeria from 2021 to 2022. Two antivenoms Echitab G (EG) and Echitab ICP Plus (EP) were able to restore normal clotting within 6 h of administration in 58.0% [95% Confidence Interval (95%CI)] (51.2–64.5%) and 91.7% (90.4–93.0%) of patients respectively. They were able to restore normal clotting within 24 h of administration in 96.9% (94.0–98.7%) and 99.0% (98.4–99.4%) of patients respectively. The Odds Ratio [OR (95%CI)] of dying among patients with positive 20WBCT who were treated with ≥1 vial of either EG or EP compared to those not treated was 0.06 (0.02–0.23) and 0.07 (0.03–0.15) respectively. This equated to antivenom protection against in-hospital mortality of 93–94% among patients with confirmed coagulopathy though the benefit appeared abrogated among those without coagulopathy. The untreated natural mortality was 15.94% (95%CI:8.24–26.74%) without antivenom therapy while the overall mortality was 84/5105 (1.65%; 95%CI:1.32–2.03%. The Number Needed to Treat (NNT) to avert a death was 7 patients among those with coagulopathy. Antivenoms were safe with mild early adverse reactions observed among 2.6% (95%CI:2.13–3.08%) of antivenom recipients. Polyclonal antibody antivenoms are effective and safe for treating coagulopathic envenomed patients in Nigeria.

An ultrafast water absorption composite cryogel containing Iron-doped bioactive glass with rapid hemostatic ability for non-compressible and coagulopathic bleeding

Traditional hemostatic materials have limited hemostatic effect on non-compressible wound, that is likely to develop into coagulopathy and leads to high mortality. As a powerful hemostatic material, in addition to having the function of forming solid physical barriers and effectively activating coagulation factors to rapidly control hemostasis, it should also has the ability to bypass the coagulation pathway to handle the bleeding of coagulopathic patients. In this work, we designed a QCOC composite cryogel by gelation of quaternized chitosan (QCS) and hydroxyethyl cellulose oxide (OHEC) at low temperature. Meanwhile, iron-doped bioactive glass (FeBG) as an active substance was introduced into the QCOC composite cryogel to promote erythrocyte aggregation by ion dissolution and activate intrinsic and extrinsic pathways. QCOC/FeBG composite cryogel had interconnected macroporous structure, ultrafast water absorption performance (reaching water absorption saturation in 4 s) and good shape memory properties (restoring to its original shape in 1 s). Additionally, the composite cryogel showed excellent antibacterial properties against S. aureus and E. coli as well as good cell biocompatibility. Furthermore, the QCOC/FeBG composite cryogel showed excellent hemostatic performance in the model of liver non-compressible hemorrhage with coagulation disorders, and the hemostasis time and blood loss were 60.87 ± 2.09 s and 366.38 ± 32.69 mg respectively, which were much lower than commercial gelatin sponge (196.62 ± 19.02 s and 1439.37 ± 165.27 mg). These results proved that QCOC/FeBG composite cryogel has excellent hemostatic properties, antibacterial properties, portability and usability, indicating a great potential as a timely hemostatic material in daily civil and military hemostasis.

Does the Use of Tranexamic Acid in Patients Who Have Preoperative Coagulopathy Undergoing Total Joint Arthroplasty Normalize Their Risk of Complications? A Matched Equivalence Analysis

BackgroundWhile patients who have a preoperative coagulopathy have an increased risk of perioperative blood loss, tranexamic acid (TXA) has been shown to decrease the risk of complications in this subset. However, a direct comparison of the use of TXA in coagulopathic and noncoagulopathic patients has not been performed. In addition to comparing differences in decreases in hemoglobin, transfusions, and complications, this study examined whether the use of TXA in coagulopathic patients normalized the risk of blood loss relative to matched noncoagulopathic patients. MethodsWe performed a retrospective review of 230 patients who had a preoperative coagulopathy and underwent primary total joint arthroplasty (127 hips, 103 knees) from 2012 to 2019 and received TXA. Coagulopathy was defined as international normalized ratio >1.2, partial thromboplastin time >35 seconds, or platelet count <150,000/mL (mL). A matched comparison group of 689 patients who did not have a coagulopathy and received TXA was identified. A 2 1-sided test (TOST) analysis was performed to test for equivalence. Assuming a clinically relevant difference of 1 g/dL in postoperative decrease in hemoglobin, the equivalence margin was set as ±1 g/dL between the groups. ResultsWhen comparing coagulopathic and noncoagulopathic patients, total hip arthroplasty (THA) patients had no differences in hemoglobin, but had an increased reported estimated blood loss (243 versus 207 mL, P = .040) as well as an increased percent of patients requiring blood transfusions (11.8 versus 5.32%, P = .022). Total knee arthroplasty (TKA) patients had no differences in hemoglobin, estimated blood loss, or percent of patients requiring transfusion. There were no differences in medical or surgical complications for both groups for THA and TKA patients. Equivalence testing for both groups revealed statistical significance that THA and TKA coagulopathic patients receiving TXA had an equivalent risk of blood loss compared to noncoagulopathic patients receiving TXA. ConclusionCoagulopathic patients receiving TXA and undergoing THA had an increased risk of receiving a transfusion; however, there were no differences in complications for both TKA and THA, as well as a normalized risk of blood loss when compared to noncoagulopathic patients. Level of evidenceIII.

Abstract Number ‐ 44: Middle Meningeal Artery Embolization: 294 Non‐Acute Subdural Hematomas with Outcomes and Risk Factors for Recurrence

Introduction Treatment of non‐acute subdural hematoma (NASDH) remains challenging due to recurrence ranging from 2–37%. Middle meningeal artery embolization (MMAe) has emerged as a minimally invasive procedure uniquely poised to improve outcomes in NASDH. The goal of this study is to evaluate the clinical and radiographic characteristics of patients undergoing MMAe for NASDH, and how outcomes for MMAe differ when utilized upfront, prophylactically, or as a salvage modality after surgical evacuation. Furthermore, we investigated how independent patient risk factors, such as oncologic history and anticoagulant/antiplatelet (ACAP) medication use, may impact MMAe and NASDH outcomes. Methods This prospective study followed patients undergoing MMAe for NASDH from 2016–2021. All patients were diagnosed with a NASDH on non‐contrast CT imaging and underwent MMAe by the lead neurosurgeon. The primary outcome was NASDH recurrence post‐MMAe requiring surgical evacuation, repeat MMAe, or both within the one‐year follow up period. Additional radiographic outcomes included reduction of hematoma width and midline shift at longest follow‐up. Subgroup analyses stratified outcomes by MMAe indication: upfront (previously untreated and nonoperative NASDH), prophylactic (MMAe 1–5 days after surgical evacuation), or salvage (individuals with radiographic and clinical NASDH recurrence). Outcomes among oncologic, coagulopathic, and ACAP patients were also assessed. The modified Rankin scale (mRS) quantified post‐MMAe clinical outcomes. Results A total of 236 NASDH patients underwent 294 MMAe. Of these, 115 (48.7%), 92 (39.0%), and 29 (12.3%) patients received upfront, prophylactic, and salvage MMAe, respectively. Upfront MMAe was performed more frequently than prophylactic and salvage for patients with co‐existing malignancy (29.6%, 12.0%, 20.7%; P &lt; 0.01) and coagulopathy (17.4%, 4.3%, 10.3%; P = 0.01). Prophylactic MMAe was more commonly performed for subacute SDH compared with upfront or salvage (15.2%, 2.6%, 0%; P &lt; 0.001); no differences in utilization were seen for chronic or acute on chronic SDH. Sixteen (5.4%) patients presented with hematoma recurrence after MMAe requiring repeat intervention, of which 5 (1.7%) received a craniotomy, 7 (2.4%) received repeat MMAe, and 4 (1.3%) underwent both MMAe and surgical evacuation. Risk of overall NASDH recurrence requiring re‐intervention did not differ among prophylactic, upfront, and salvage groups (6.5%, 7.0%, 6.9%; P &gt; 0.99). Clinical outcomes did not differ between MMAe indications at longest follow‐up. Within the prophylactic group, radiographic and clinical outcomes were similar between MMAe paired with twist‐drill craniostomy or with craniotomy. Subgroup analysis revealed MMAe also effectively decreased NASDH recurrence in ACAP, oncologic, and coagulopathic patients. However, patients with both an oncologic history and concurrent ACAP use less frequently achieved improved clinical status at follow‐up compared with those harboring ACAP/coagulopathic history alone, oncologic history alone, or neither (31.4%, 45.9%, 50.0%, 57.3%; P = 0.049). Conclusions MMAe is emerging as a viable treatment for curtailing recurrence and improving NASDH outcomes, with similar clinical outcomes when performed prophylactically, upfront, or as salvage treatment. NASDH patients presenting with an oncologic history and concurrent ACAP use may be less likely to achieve improved clinical status after MMAe.

Abstract 14633: A Case of Acute Coronary Syndrome With Incidental Acquired Factor VIII Deficiency With Inhibitor Present: How to Navigate Being Between a “Rock” and a Bleeding Disorder

Introduction: Acute coronary syndrome (ACS) occurring in the presence of a bleeding diathesis can make clinical decision-making difficult. We present a case of a non-ST elevation MI in the presence of an acquired factor VIII deficiency with an inhibitor present. Case: A 66-year-old male with a medical history significant for coronary artery disease and COPD presented with a 4-day history of persistent, profuse bleeding after attaining a laceration on his arm. Shortly after admission, he reported pressure-like chest pain relieved by sublingual nitroglycerin. His 5th generation troponin level was 61 ng/L on presentation and peaked at 600 ng/L 36 hours later. The EKG revealed ST depressions in leads V3 and V4 and T-wave flattening in leads V5 and V6. Transthoracic echocardiography revealed preserved ejection fraction but could not exclude wall motion abnormalities due to poor windows. Hematology was consulted due to uncontrolled bleeding, and the patient was diagnosed with acquired factor VIII deficiency with an inhibitor present. Low-dose heparin infusion was initiated. He was taken for a diagnostic left heart catheterization, which revealed left main with moderate obstruction, left anterior descending (LAD) with 70% proximal stenosis, and a small diagonal branch with 90% stenosis. The patient had been previously offered evaluation for coronary artery bypass graft(CABG) surgery but declined. CABG work up was ultimately deferred in favor of percutaneous coronary intervention based on literature review extrapolated from hemophiliac patients. The patient’s hematologic care is ongoing with recombinant antihemophilic factor, porcine sequence, prednisone, cyclophosphamide, and rituximab administration. Discussion: Choosing the type of coronary revascularization in coagulopathic patients poses a significant challenge. To avoid complications, a multidisciplinary approach to short- and long-term anticoagulation management is necessary. In this case we decided to use existing data that is based on hemophilia patients in the past with myocardial infarction where dual antiplatelet therapy is limited to 1 month with factor 8 activity maintained above 30%. Then transition to aspirin alone for maintenance with factor 8 levels maintained above 10%.

Sodium Phytate-Incorporated Gelatin-Silicate Nanoplatelet Composites for Enhanced Cohesion and Hemostatic Function of Shear-Thinning Biomaterials.

Shear-thinning biomaterials (STBs) based on gelatin-silicate nanoplatelets (SNs) are emerging as an alternative to conventional coiling and clipping techniques in the treatment of vascular anomalies. Improvements in the cohesion of STB hydrogels pave the way toward their translational application in minimally invasive therapies such as endovascular embolization repair. In the present study, sodium phytate (Phyt) additives are used to tune the electrostatic network of SNs-gelatin STBs, thereby promoting their mechanical integrity and facilitating injectability through standard catheters. We show that an optimized amount of Phyt enhances storage modulus by approximately one order of magnitude and reduces injection force by ≈58% without compromising biocompatibility and hydrogel wet stability. The Phyt additives are found to decrease the immune responses induced by SNs. In vitro embolization experiments suggest a significantly lower rate of failure in Phyt-incorporated STBs than in control groups. Furthermore, the addition of Phyt leads to accelerated blood coagulation (reduces clotting time by ≈45% compared to controls) due to the contributions of negatively charged phosphate groups, which aid in the prolonged durability of STB in coagulopathic patients. Therefore, the proposed approach is an effective method for the design of robust and injectable STBs for minimally invasive treatment of vascular malformations.

Protein-based polymer liquid embolics for cerebral aneurysms

Cerebral aneurysms (CA), an abnormal bulge in the arteries that supply blood to the brain, are prone to rupture and can cause hemorrhagic stroke. Physicians can treat CA by blocking blood flow to the aneurysmal sac via clipping of the aneurysm neck via open procedure, or endovascular occlusion of the aneurysm with embolic materials to promote thrombus formation to prevent further inflow of blood into the aneurysm. Endovascular treatment options for CA still have significant limitations in terms of safety, usability in coagulopathic patients, and risks of device migration. Bioactive embolic therapies, consisting of non-toxic bioresorbable materials that encourage the growth of neointima across the aneurysm neck, are needed to improve the healing of CA. In this work, the bioinspired silk-elastinlike protein-based polymer (SELP 815K), was used to embolize aneurysms in a rabbit elastase model. SELP 815K effectively embolized the model aneurysms in vivo, achieving >90% occlusion, using commercial microcatheters. No device-associated adverse effects were observed in any of the animals, and SELP 815K showed no cytotoxicity. SELP embolization did not show any deleterious effects to local tissues, and features consistent with reendothelialization of the aneurysm neck were noted in histological examination one-month post-embolization. SELP 815K shows promise as an embolic treatment for unruptured CA. Statement of significanceUnruptured cerebral aneurysms are present in approximately 3% of the population, with a fatality rate of up to 65% upon rupture. In this work a silk-elastinlike protein polymer (SELP) is explored as a liquid embolic for occlusion of cerebral aneurysms. This embolic exists as a liquid at room temperature before rapidly forming a gel at physiological temperature. This shape filling property was used to successfully occlude cerebral aneurysms in rabbits, with stable occlusion persisting for over thirty days. SELP occlusions show evidence for reendothelialization of the aneurysm sac and provide an opportunity for delivery of bioactive agents to further improve treatments.

Comparison of Bacterial Risk in Cryo AHF and Pathogen Reduced Cryoprecipitated Fibrinogen Complex.

Until November 2020, cryoprecipitated antihaemophilic factor (cryo AHF) was the only United States Food and Drug Administration (FDA)-approved fibrinogen source to treat acquired bleeding. The post-thaw shelf life of cryo AHF is limited, in part, by infectious disease risk. Concerns over product wastage demand that cryo AHF is thawed as needed, with thawing times delaying the treatment of coagulopathic patients. In November 2020, the FDA approved Pathogen Reduced Cryoprecipitated Fibrinogen Complex for the treatment and control of bleeding, including massive hemorrhage, associated with fibrinogen deficiency. Pathogen Reduced Cryoprecipitated Fibrinogen Complex (also known as INTERCEPT® Fibrinogen Complex, IFC) has a five-day post-thaw room-temperature shelf life. Unlike cryo AHF, manufacturing of IFC includes broad spectrum pathogen reduction (Amotosalen + UVA), enabling this extended post-thaw shelf life. In this study, we investigated the risk of bacterial contamination persisting through the cryoprecipitation manufacturing process of cryo AHF and IFC. Experiments were performed which included spiking plasma with bacteria prior to cryoprecipitation, and bacterial survival was analyzed at each step of the manufacturing process. The results show that while bacteria survive cryo AHF manufacturing, IFC remains sterile through to the end of shelf life and beyond. IFC, with a five-day post-thaw shelf life, allows the product to be sustainably thawed in advance, facilitating immediate access to concentrated fibrinogen and other key clotting factors for the treatment of bleeding patients.

Endothelial biomarkers of thrombosis in critically ill patients with acquired coagulopathy: a prospective cohort study.

Background: It remains largely unknown whether endothelial biomarkers can be used to predict thromboembolism in critically ill patients with an acquired coagulopathy. Materials & methods: The ability of syndecan-1, P-selectin and microRNA expressions to predict thromboembolism were assessedin 40 critically ill coagulopathic patients. Results: The area under the receiver operating characteristic curves for syndecan-1, P-selectin and the four differentially expressed microRNAs - determined by real-time qPCR analysis - to predict thromboembolism (n=10, 25%) were 0.71 (95% CI: 0.52-0.89), 0.73 (95% CI: 0.52-0.95) and >0.80, respectively. Syndecan-1 and P-selectin concentrations were also significantly correlated with one another (R=0.41, p=0.008). Conclusion: Endothelial function biomarkers, including endothelial microRNA expressions, were associated with subsequent thromboembolism in critically ill patients who had a deranged coagulation profile.

Management of antithrombotic treatment and bleeding disorders in patients requiring venous access devices: A systematic review and a GAVeCeLT consensus statement.

Insertion of venous access devices (VAD) is usually considered a procedure with low risk of bleeding. Nonetheless, insertion of some devices is invasive enough to be associated with bleeding, especially in patients with previous coagulopathy or in treatment with antithrombotic drugs for cardiovascular disease. The current practices of platelet/plasma transfusion in coagulopathic patients and of temporary suspension of the antithrombotic treatment before VAD insertion are based on local policies and are often inadequately supported by evidence, since many of the clinical studies on this topic are not recent and are not of high quality. Furthermore, the protocols of antithrombotic treatment have changed during the last decade, after the introduction of new oral anticoagulant drugs. Though some guidelines address some of these issues in relation with specific procedures (port insertion, etc.), no evidence-based document covering all the aspects of this clinical problem is currently available. Thus, the Italian Group of Venous Access Devices (GAVeCeLT) has decided to develop a consensus on the management of antithrombotic treatment and bleeding disorders in patients requiring VADs. After a systematic review of the available evidence, the panel of the consensus (which included vascular access specialists, surgeons, intensivists, anesthetists, cardiologists, vascular medicine experts, nephrologists, infective disease specialists, and thrombotic disease specialists) has structured the final recommendations as detailed answers to three sets of questions: (1) which is an appropriate classification of VAD-related procedures based on the specific bleeding risk? (2) Which is the appropriate management of the patient with bleeding disorders candidate to VAD insertion/removal? (3) Which is the appropriate management of the patient on antithrombotic treatment candidate to VAD insertion/removal? Only statements reaching a complete agreement were included in the final recommendations, and all recommendations were offered in a clear and synthetic list, so to be easily translated into clinical practice.

Routine Repeat Imaging Is Unnecessary for Coagulopathic Patients Sustaining Head Trauma

In trauma patients using warfarin, current guidelines recommend computed tomography of the brain (CTH), 24-hour observation, and repeat CTH to monitor for stability. Despite growing evidence of uncommon delayed hemorrhage, this remains standard practice even in mild traumatic brain injury without intracranial hemorrhage (ICH). Our study sought to determine the incidence and outcomes of delayed ICH (DICH) in trauma patients on supra-therapeutic warfarin without initial ICH. A retrospective, single institutional study was performed of all adult trauma patients (>18years old) who presented on prehospital warfarin with an international normalized ratio (INR) >3 and initial CTH that did not demonstrate ICH. Each of these patients underwent subsequent CTH within 24hours and any DICH was identified. Those who demonstrated DICH were further examined to identify potential risk factors and outcomes such as need for further imaging or surgical intervention. Analyses were performed using Fisher's exact tests and Student's t-tests. 225 patients were identified from January 2015 to April 2021 that met inclusion criteria. Of those identified, only 3 (1.33%) were found to develop any DICH on routine repeat CTH. Identified characteristics did not reach statistical significance due to the low number of DICH. None of the patients with DICH went on to require intervention. In patients with identified traumatic injury on supra-therapeutic warfarin, an initial CTH without identified ICH alone is an adequate survey. DICH in these patients is uncommon and routine reimaging within 24hours is unlikely to change clinical management in patients with intact neurologic status.