Association of hyperfibrinolysis with poor prognosis in refractory circulatory arrest: implications for extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Identifying candidates for extracorporeal cardiopulmonary resuscitation (eCPR) is challenging, and novel predictive markers are urgently needed. Hyperfibrinolysis is linked to tissue hypoxia and is associated with poor outcomes in out-of-hospital cardiac arrest (OHCA). Rotational thromboelastometry (ROTEM) can detect or rule out hyperfibrinolysis, and could, therefore, provide decision support for initiation of eCPR. We explored early detection of hyperfibrinolysis in patients with refractory OHCA referred for eCPR. METHODS: We analysed ROTEM results and resuscitation parameters of 57 adult patients with ongoing OHCA who presented to our ICU for eCPR evaluation. RESULTS: Hyperfibrinolysis, defined as maximum lysis ≥15%, was present in 36 patients (63%) and was associated with higher serum lactate, lower arterial blood pH, and increased low-flow intervals. Of 42 patients who achieved return of circulation, 28 had a poor 30-day outcome. The incidence of hyperfibrinolysis was higher in the poor outcome group compared with patients with good outcomes (75% [21 of 28] vs 7.1% [1 of 14]; P<0.001). The ratio of EXTEM A5 to lactate concentration showed good predictive value in detecting hyperfibrinolysis (AUC of 0.89 [95% confidence interval 0.8-1]). CONCLUSIONS: Hyperfibrinolysis was common in patients with refractory cardiac arrest, and was associated with poor prognosis. The combination of high lactate with early clot firmness values, such as EXTEM A5, appears promising for early detection of hyperfibrinolysis. This finding could facilitate decisions to perform eCPR, particularly for patients with prolonged low-flow duration but lacking hyperfibrinolysis.

Hyperfibrinolysis during the treatment of rhabdomyosarcoma.

Background: Coagulopathies are frequently observed in alveolar rhabdomyosarcoma (ARMS), with disseminated intravascular coagulation (DIC) being the most common presentation. However, hyperfibrinolysis represents a distinct but often overlapping and potentially life-threatening subset of coagulation disorders that requires specific diagnostic and management approaches. Key Clinical Question: How can clinicians identify hyperfibrinolysis and what are the implications for management? Clinical Approach: This case report describes a 25-year-old man with metastatic ARMS arising from the prostate who developed persistent gross hematuria one week after initiating chemotherapy. A comprehensive coagulation workup was performed, including assessment of platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, and fibrin degradation products. Management included repletion of fibrinogen and the use of anti-fibrinolytic agents. Conclusion: Recognizing hyperfibrinolysis in ARMS patients is crucial for appropriate management. Clinicians should maintain a high index of suspicion for hyperfibrinolysis in ARMS patients presenting with severe coagulation abnormalities, particularly those with prostatic involvement or undergoing chemotherapy. In cases of primary hyperfibrinolysis, antifibrinolytic agents may be considered, whereas they are generally contraindicated in DIC.

Case report: Chronic disseminated intravascular coagulopathy with concurrent paraneoplastic secondary hyperfibrinolysis in a dog with metastatic nasal adenocarcinoma.

In human medicine, hemostatic disorders such as thrombocytopenia, hyperfibrinolysis, and disseminated intravascular coagulopathy (DIC) have been associated with many cancers. Acute hemorrhage secondary to hyperfibrinolysis has been predominantly reported with prostatic adenocarcinoma in human patients. To the author's knowledge, severe bleeding due to paraneoplastic hyperfibrinolysis has not yet been reported in veterinary medicine. The case involves an 8-year-old neutered male Border Collie who was evaluated for progressive and recurrent epistaxis, having a history of 1 year of treatment for metastatic nasal adenocarcinoma. A progressive and severe coagulopathy thought to be related to the known cancer was diagnosed. Advanced coagulation testing was consistent with a chronic DIC and secondary hyperfibrinolysis. Throughout 1 week of hospitalization, the dog was treated with multiple blood products, vitamin K1, and anti-fibrinolytic medications. While the dog was initially discharged home, the dog re-presented the following day and was humanely euthanized due to a perceived poor quality of life. Post-mortem analysis revealed a histopathologic diagnosis of disseminated adenocarcinoma. In dogs with disseminated nasal adenocarcinoma that are experiencing severe bleeding, paraneoplastic secondary hyperfibrinolysis should be considered as a differential. Knowing this association could help guide treatment recommendations for optimal patient management.

Feline aortic thromboembolism with and without congestive heart failure did not exhibit hypercoagulability using a novel viscoelastic coagulation monitor.

OBJECTIVE: To demonstrate hypercoagulability with a benchtop viscoelastic monitor in cats with congestive heart failure (CHF) and/or aortic thromboembolism (ATE) compared to controls. METHODS: 97 cats were enrolled throughout this prospective observational cohort study from September 2022 through October 2023. Cats were grouped by diagnosis of CHF, ATE, ATE plus CHF, or controls. Enrollment required diagnosis of heart disease and no previous antithrombotic therapy. The results of viscoelastic testing with the benchtop viscoelastic coagulation monitor (VCM Vet [VCM]; Entegrion) were compared between groups using factorial analysis of variance. RESULTS: Cats with heart disease had significantly higher clot times when compared to controls (control: mean, 285.3 [SD, 172.6]; CHF: mean, 391.7 [SD, 106.8]; ATE: mean, 415.9 [SD, 109.2]; and ATE plus CHF: mean, 368.6 [SD, 232.6]). Heart disease cats were noted to have significantly lower 45-minute lysis index values (control: median, 100 [range, 93 to 100]; CHF: median, 99 [range, 89 to 100]; ATE: median, 98 [range, 88 to 100]; and ATE plus CHF: range, 98 [91 to 100]). Age was a covariate to this variable, and when applied to analysis, statistical significance was lost. No significant difference in any other variables were noted. CLINICAL RELEVANCE: The hypercoagulability of ATE and CHF cats was not detected by the VCM. Further research with other coagulation monitors is required in this population.

Presumptive spontaneous hemothorax associated to thymic involution in a dog with steroid responsive meningitis-arteritis (SRMA).

OBJECTIVE: To describe an unusual case of spontaneous hemothorax resulting from thymic involution in a dog with suspected acquired bleeding dyscrasia associated with steroid-responsive meningitis-arteritis (SRMA). CASE DESCRIPTION: A 6-month-old spayed female Golden Retriever was referred due to the sudden onset of lethargy, fever (pyrexia), loss of appetite (anorexia), and moderate neck pain. These symptoms emerged six days after an ovariohysterectomy performed by the primary veterinarian. Upon admission, the patient exhibited pale mucous membranes, tachycardia (180 bpm), bilateral muffled heart sounds and tachypnea. Abdominal and thoracic point-of-care ultrasound (POCUS) were performed and revealed bilateral pleural effusion. Due to the patient's unstable condition, emergent thoracocentesis and transfusion of packed red blood cells was required. The initial work-up performed included a complete blood cell count (CBC), biochemistry profile, venous blood gas and coagulation panel (PT, APTT, fibrinogen). Pleural effusion analysis was compatible with hemothorax. Bloodwork was unremarkable including the initial coagulation panel. Further coagulation test was performed including buccal mucosal bleeding time, viscoelastic-based clot detection tests (TEG) and Von Willebrand factor antigen measurement. TEG revealed marked hyperfibrinolysis. Angiostrongylus vasorum and 4DX snap test were performed and yielded a negative result. Thoracic CT scan revealed the presence of a soft tissue-attenuating mass in the ventral mediastinum, thymic involution, and enlargement of the sternal and mediastinal lymph nodes. Therapy with tranexamic acid and corticosteroids at anti-inflammatory doses was initiated. Marked clinical improvement was observed within 24 hours, and after three days of hospitalization the patient was discharged. One month later, the dog was referred again for acute pyrexia, hyporexia, and neck pain which progressed to non-ambulatory tetraparesis. Neurological examination was compatible with C6-T2 lesion. MRI and cerebrospinal fluid analysis were performed and revealed a final diagnosis of steroid-responsive meningitis-arteritis (SRMA) with associated intramedullary hemorrhage. Corticosteroids were started again, and the patient showed a dramatic improvement over the next 24 hours. Three weeks after the diagnosis, the dog returned to a clinically normal state. The treatment was gradually tapered over the following months, guided by regular neurological and clinical examinations and CRP measurements, without any relapses. NEW OR UNIQUE INFORMATION: To the best of the author's knowledge, this is the first documented case of a dog experiencing spontaneous hemothorax as a result of thymic hemorrhage/involution which, in the absence of other identifiable diseases, was attributed to a hyperfibrinolytic state induced by a severe inflammatory disease such as SRMA.

Comparison of results obtained using clot-fibrinolysis waveform analysis and global fibrinolysis capacity assay with rotational thromboelastography.

Global fibrinolysis assays detect the fibrinolysis time of clot dissolution using tissue-type plasminogen activator (tPA). Two such assays, clot-fibrinolysis waveform analysis (CFWA) and global fibrinolysis capacity (GFC) assay, were recently developed. These were compared with rotational thromboelastography (ROTEM). Healthy donor blood samples were divided into four groups based on tPA-spiked concentrations: 0, 100, 500, and 1000 ng/mL. CFWA and GFC fibrinolysis times, including 4.1 µg/mL and 100 ng/mL tPA in the assays, were determined, denoted as CFWA-Lys and GFC-Lys, respectively. Statistical differences were recognized between tPA concentrations of 0 and 500/1000 ng/mL for CFWA-Lys, and 0 and 100/500/1000 ng/mL for GFC-Lys. The correlation coefficients with lysis onset time (LOT) of extrinsic pathway evaluation and intrinsic pathway evaluation in ROTEM were statistically significant at 0.610 and 0.590 for CFWA-Lys, and 0.939 and 0.928 for GFC-Lys, respectively (p-values < 0.0001 for all correlations). Both assays showed significant correlations with ROTEM; however, the GFC assay proved to have better agreement with ROTEM compared with the CFWA assay. These assays have the potential to reflect a hyperfibrinolysis status with high tPA concentrations.

The effect of ε-aminocaproic acid on blood product requirement, outcome and thromboelastography parameters in severely thrombocytopenic dogs.

BACKGROUND: No treatment other than platelet administration is known to protect against spontaneous hemorrhage in thrombocytopenic dogs. OBJECTIVES: Primary: determine if treatment with ε-aminocaproic acid (EACA) decreases the requirement for blood transfusions and improves outcome in dogs with severe thrombocytopenia. Secondary: find evidence of hyperfibrinolysis and determine the effect EACA administration on rapid (rTEG) and tissue plasminogen activator-spiked (tPA-rTEG) thromboelastography parameters. ANIMALS: Twenty-seven dogs with severe thrombocytopenia were treated with EACA, and data from an additional 33 were obtained from the hospital database as historical control (HC) cohort. METHODS: Single arm clinical trial with HCs. The EACA group dogs received EACA (100 mg/kg IV followed by a constant-rate infusion [CRI] of 400 mg/kg/24 hours). Thromboelastography before and during EACA infusion, hospitalization days, number of transfusions, and mortality were compared. RESULTS: No difference was found in number of transfusions per dog (median, interquartile range; 1, 0-2.5 vs 0.9, 0-2; P = .5) and hospitalization days (4, 4-6 vs 4.5, 3.75-6; P = .83) between HC and EACA groups, respectively, and no difference in survival was identified by log-rank analysis (P = .15). Maximum amplitude on both rTEG and tPA-rTEG increased after EACA administration (rTEG baseline: 23.6, 9.6-38.9; post-EACA: 27.3, 19.8-43.2; P < .001; tPA-rTEG baseline: 23, 10.9-37.2; post-EACA: 24.7, 16.7-44.8; P < .002). CONCLUSIONS AND CLINICAL IMPORTANCE: Although EACA increased clot strength, there was no effect on outcome. Treatment with EACA at this dosage cannot be recommended as a routine treatment but may be considered for dogs with severe ongoing hemorrhage.

Levels of peripheral blood routine, biochemical and coagulation parameters in patients with hemorrhagic fever with renal syndrome and their relationship with prognosis: an observational cohort study.

BACKGROUND: Hantaan virus (HTNV), Seoul virus (SEOV) and Puumala virus (PUUV) are major serotypes of the Hantavirus, which can cause hemorrhagic fever with renal syndrome (HFRS). The pathophysiology of HFRS in humans is complex and the determinants associated with mortality, especially the coagulation and fibrinolysis disorders, are still not been fully elucidated. Severe patients usually manifest multiple complications except for acute kidney injury (AKI). The aim of this study was to observe the levels of peripheral blood routine, biochemical and coagulation parameters during the early stage, so as to find independent risk factors closely related to the prognosis, which may provide theoretical basis for targeted treatment and evaluation. METHODS: A total of 395 HFRS patients from December 2015 to December 2018 were retrospectively enrolled. According to prognosis, they were divided into a survival group (n = 368) and a death group (n = 27). The peripheral blood routine, biochemical and coagulation parameters were compared between the two groups on admission. The relationship between the parameters mentioned above and prognosis was analyzed, and the dynamic changes of the coagulation and fibrinolysis parameters during the first week after admission were further observed. RESULTS: In addition to AKI, liver injury was also common among the enrolled patients. Patients in the death group manifested higher levels of white blood cell counts (WBC) on admission. 27.30% (107/392) of the patients enrolled presented with disseminated intravascular coagulation (DIC) on admission and DIC is more common in the death group; The death patients manifested longer prothrombin time (PT) and activated partial thromboplastin time (APTT), higher D-dimer and fibrinogen degradation product (FDP), and lower levels of platelets (PLT) and fibrinogen (Fib) compared with those of the survival patients. The proportion of D-dimer and FDP abnormalities are higher than PT, APTT and Fib. Prolonged PT, low level of Fib and elevated total bilirubin (TBIL) on admission were considered as independent risk factors for prognosis (death). CONCLUSIONS: Detection of PT, Fib and TBIL on admission is necessary, which might be benefit to early predicting prognosis. It is also important to pay attention to the dynamic coagulation disorders and hyperfibrinolysis during the early stage in the severe HFRS patients.

Prospective evaluation of platelet function and fibrinolysis in 20 dogs with trauma.

OBJECTIVES: To determine platelet function and assess fibrinolysis in dogs following trauma using multiple electrical impedance aggregometry and a modified thromboelastographic (TEG) technique. To determine if the severity of trauma, as assessed by the Animal Trauma Triage (ATT) score and clinicopathological markers of shock, is associated with a greater degree of platelet dysfunction and fibrinolysis. SETTING: University teaching hospital. ANIMALS: Twenty client-owned dogs with trauma (occurring <24 h prior to admission and blood sampling) and ATT score of >4 were prospectively recruited. A control group of 10 healthy dogs was included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Platelet function was measured using multiple electrode platelet aggregometry (MEPA) utilizing arachidonic acid, ADP, and collagen agonists. Fibrinolysis was assessed in citrated whole blood with the addition of tissue plasminogen activator (tPA; 50 U/mL) using kaolin-activated TEG. Conventional statistical analysis was performed to compare coagulation parameters between the groups and assess linear correlations. Median (interquartile range) ATT score was 5 (5-7), and 65% (n = 13) of dogs suffered polytrauma. Mean (± SD) time from trauma to blood sampling was 9 hours (± 6). Median (interquartile range) shock index and plasma lactate concentration were 1.1 (0.7-2.0, n = 16) and 2.9 mmol/L (0.9-16.0, n = 18), respectively. Four dogs did not survive to discharge (20%). There were no differences between the trauma and control group coagulation variables. A moderate negative correlation between ATT score and area under the curve for ADP was found (P = 0.043, r2  = -0.496). CONCLUSIONS: Preliminary evaluation of platelet function measured by MEPA, and fibrinolysis measured by tPA-modified TEG, is not significantly different in this population of dogs with traumatic injury compared to healthy dogs.

Fibrinogen Fragment X Mediates Endothelial Barrier Disruption via Suppression of VE-Cadherin.

INTRODUCTION: Major traumatic injury is associated with early hemorrhage-related and late-stage deaths due to multiple organ failure (MOF). While improvements to hemostatic resuscitation have significantly reduced hemorrhage-related deaths, the incidence of MOF among trauma patients remains high. Dysregulation of vascular endothelial cell (EC) barrier function is a central mechanism in the development of MOF; however, the mechanistic triggers remain unknown. Accelerated fibrinolysis occurs in a majority of trauma patients, resulting in high circulating levels of fibrin(ogen) degradation products, such as fragment X. To date, the relationship between fragment X and EC dysregulation and barrier disruption is unknown. The goal of this study was to determine the effects of fragment X on EC barrier integrity and expression of paracellular junctional proteins that regulate barrier function. METHODS: Human lung microvascular endothelial cells (HLMVECs) were treated with increasing concentrations of fragment X (1, 10, and 100 µg/mL), and barrier function was monitored using the xCELLigence live-cell monitoring system. Quantitative PCR (qPCR) was performed to measure changes in EC expression of 84 genes. Immunofluorescent (IF) cytostaining was performed to validate qPCR findings. RESULTS: Fragment X treatment significantly increased endothelial permeability over time (P < 0.05). There was also a significant reduction in VE-cadherin mRNA expression in fragment X-treated HLMVECs compared to control (P = 0.01), which was confirmed by IF staining. CONCLUSIONS: Fragment X may induce EC hyperpermeability by reducing VE-cadherin expression. This suggests that a targeted approach to disrupting EC-fragment X interactions could mitigate EC barrier disruption, organ edema, and MOF associated with major trauma.

Viscoelastic Testing Methods.

Viscoelastic testing methods examine the real-time formation of a clot in a whole blood sample, and include thromboelastography (TEG), rotational thromboelastometry (ROTEM), and several other testing platforms. They allow for concurrent assessment of multiple aspects of clotting, including plasmatic coagulation factors, platelets, fibrinogen, and the fibrinolytic pathway. This testing is rapid and may be performed at the point-of-care, allowing for prompt identification of coagulopathies to guide focused and rational administration of blood products as well as the identification of anticoagulant effect. With recent industry progression towards user-friendly, cartridge-based, portable instruments, viscoelastic testing has emerged in the 21st century as a powerful tool to guide blood transfusions in the bleeding patient, and to identify and treat both bleeding and thrombotic conditions in many operative settings, including trauma surgery, liver transplant surgery, cardiac surgery, and obstetrics. In these settings, the use of transfusion algorithms guided by viscoelastic testing data has resulted in widespread improvements in patient blood management as well as modest improvements in select patient outcomes. To address the increasingly wide adoption of viscoelastic methods and the growing number of medical and laboratory personnel tasked with implementing, performing, and interpreting these methods, this chapter provides an overview of the history, physiology, and technology behind viscoelastic testing, as well as a practical review of its clinical utility and current evidence supporting its use. Also included is a review of testing limitations and the contextual role played by viscoelastic methods among all coagulation laboratory testing.

Sensitivity and specificity of thromboelastography for hyperfibrinolysis: Comparison of TEG 5000 and TEG 6S CK LY30 systems.

OBJECTIVES: The sensitivity and specificity of clot lysis at 30 minutes after maximum clot strength (LY30), as measured by thromboelastography (TEG), for clinically significant hyperfibrinolysis have not been compared across the 2 US Food and Drug Administration-approved instruments (the TEG 5000 and TEG 6s [Haemonetics]). METHODS: We performed a retrospective, single-center analysis of these 2 instruments using the kaolin (CK) reagent. RESULTS: Local verification studies showed that the TEG 5000 and TEG 6s CK LY30 upper limits of normal (ULNs) were distinct (5.0% and 3.2%, respectively). Retrospective analysis of patient data showed that abnormal LY30 was 6 times more prevalent with the TEG 6s than with the TEG 5000 instrument. LY30 was a significant predictor of mortality with both instruments (TEG 6s: receiver operating characteristic [ROC] area under the curve [AUC] = 0.836, P ≤ .0001; TEG 5000: ROC AUC = 0.779, P = .028). The optimal LY30 cut point was determined based on these mortality data for each instrument. The TEG 6s showed superior mortality prediction than the TEG 5000 at lower LY30 levels (≥10%), with likelihood ratios of 8.22 and 2.62 for the TEG 6s and TEG 5000, respectively. Patients with a TEG 6s CK LY30 of 10% or higher were significantly more likely to die, receive cryoprecipitate, receive transfusions, or receive massive transfusion than patients with a TEG 6s LY30 of 3.3% to 9.9% (all P < .01). Patients with a TEG 5000 LY30 of 17.1% or higher were significantly more likely to die or use cryoprecipitate (P < .05); transfusion and massive transfusion protocol were not significantly different. Whole blood spiking studies showed that 70 ng/mL tissue plasminogen activator (tPA) achieved an average LY30 of approximately 10% for both instruments. CONCLUSIONS: CK LY30 above the ULN is a sensitive but not specific cutoff for hyperfibrinolysis. At least moderately elevated CK LY30 carries more clinical portent on the TEG 6s instrument than on the TEG 5000. These TEG instruments are not sensitive to low concentrations of tPA.

A retrospective validation of ROTEM algorithms for detecting hyperfibrinolysis demonstrates poor agreement for prediction of in-hospital mortality and transfusion requirement in a general, non-cardiac, surgical population.

INTRODUCTION: Hyperfibrinolysis diagnosed on Rotational Thromboelastography (ROTEM) is associated with increased transfusion requirements and mortality in trauma. The diagnosis and significance of hyperfibrinolysis in a mixed, non-cardiac, general surgical population has not been investigated. We aimed to measure agreement between four ROTEM algorithms for diagnosing hyperfibrinolysis and transfusion requirements and mortality in general surgical patients. These algorithms mostly incorporate measures of early or late clot amplitude reduction on the Extrinsic Clotting Pathway Test with Tissue Factor (EXTEM) channel. METHOD: Four hospital administrative data sets were linked from 2019 to 2022. Adults >18 years were included if a ROTEM was performed during their surgery (intraoperative period) or within 24-h of the surgery completion (postoperative period). The four hyperfibrinolysis criteria were applied to the ROTEM data and assessed for their agreement, intraoperative and postoperative transfusion requirements and in-patient mortality. RESULTS: We linked 933 ROTEMs to 558 patient-procedures. One algorithm identified hyperfibrinolysis on only three patients so was excluded. Agreement between the remaining three was slight (Cohens Kappa 0.18 (p < 0.001)) with hyperfibrinolysis diagnosed between 22 and 69 % of the procedures. The association between hyperfibrinolysis diagnosis and intraoperative or postoperative transfusion requirement was inconsistent between the criteria. However, an algorithm put forward by Goerling et al. was more often associated with transfusion requirement and inpatient mortality. DISCUSSION: The poor agreement between criteria suggests that some ROTEM criteria may not transfer directly to general surgical patients. Future research should focus on optimising hyperfibrinolysis cut-off values to update algorithms for bleeding general surgical patients.

Coagulation profiles in patients with sepsis/septic shock identify mixed hypo-hypercoagulation patterns based on rotational thromboelastometry: A prospective observational study.

INTRODUCTION: Sepsis-induced hemostatic disturbances are common and are associated with poor outcomes. Additionally, conventional coagulation tests (CCTs) overdiagnose hypocoagulation and cannot detect hypercoagulation and hyperfibrinolysis. The aim of this study was to describe the coagulation profiles of patients with sepsis/septic shock using rotational thromboelastometry (ROTEM) and to compare coagulation states between sepsis and septic shock groups and between surviving and non-surviving groups. MATERIALS AND METHODS: This prospective, observational, single-center study was conducted in the intensive care unit (ICU) of the University Medical Center Ho Chi Minh City, from 6/2020-12/2021. Patients aged ≥18 years with sepsis or septic shock according to the Sepsis-3 criteria were included. ROTEM and CCTs were concurrently performed within the first 24 h of ICU admission. RESULTS: In total, 161 patients were enrolled. Based on ROTEM, 72.7 % of patients with sepsis/septic shock had coagulation disorders, including 25.5 % hypercoagulation, 54.7 % hypocoagulation, 13.6 % mixed hypo-hypercoagulation patterns, and 18.6 % hyperfibrinolysis. A common mixed disorder subtype was characterized by prolonged initial clotting time (CT) with subsequently increased clot firmness. Fibrinogen levels and maximum clot formation (MCF)-fibtem were strongly correlated (rho = 0.73, p < 0.05). Hypocoagulation was observed more in the septic shock group than in the sepsis group. Compared to survivors, non-survivors had more prolonged CT-extem. CONCLUSIONS: ROTEM could identify hypocoagulability, hypercoagulability, mixed hypo-hypercoagulability patterns, and hyperfibrinolysis in patients with sepsis/septic shock. Elevated MCF-fibtem and elevated fibrinogen levels were notably common and strongly correlated. The septic shock group had more hypocoagulation than the sepsis group. Lastly, non-survivors had more prolonged CT-extem than survivors.

Identification by whole genome sequencing of genes associated with delayed postoperative hemorrhage in Scottish deerhounds.

BACKGROUND: Delayed postoperative hemorrhage (DEPOH) is an important health concern for Scottish deerhounds. HYPOTHESIS/OBJECTIVES: Identify genes associated with DEPOH in Scottish deerhounds. ANIMALS: Two hundred sixty-nine privately owned Scottish deerhounds. METHODS: Retrospective case-control study. DEPOH cases and controls were identified through an owner health survey. Genome-wide association analysis was performed using whole genome sequences from 8 cases and 17 controls. All cases and controls were genotyped for selected variants. RESULTS: Of 269 dogs, 10 met inclusion and exclusion criteria for DEPOH, while 62 controls had undergone similar surgical procedures without DEPOH. Genome-wide association analysis identified a single locus on chromosome 9 spanning 40 genes. One of these genes (SERPINF2 encoding alpha-2 antiplasmin) was directly linked to the pathophysiology of DEPOH. The entire cohort was genotyped for a missense SERPINF2 variant (c.605 C>T; p.A202V). Compared to dogs with the reference C/C genotype, the likelihood of DEPOH was significantly higher for dogs with the T/T genotype (odds ratio [OR] = 1235; 95% confidence interval [CI] = 23-6752; P = 0.0005) and with the C/T genotype (OR = 28; 95% CI = 1.4-542; P = 0.03). CONCLUSIONS AND CLINICAL IMPORTANCE: SERPINF2 is associated with DEPOH in Scottish deerhounds. Genetic testing might be able to identify dogs that are susceptible to DEPOH.

Placenta Accreta Spectrum Prophylactic Therapy for Hyperfibrinolysis with Tranexamic Acid.

BACKGROUND: To report on prophylactic therapy for hyperfibrinolysis with tranexamic acid (TXA) during expectant management (EM) in the placenta accreta spectrum (PAS). METHODS: This is a monocentric retrospective study of women with PAS presenting at our hospital between 2005 and 2021. All data were retrospectively collected through the departmental database. RESULTS: 35 patients with PAS were included. EM was planned in 25 patients prior to delivery. Complete absorption of the retained placenta was seen in two patients (8%). Curettage was performed in 14 patients (56%). A hysterectomy (HE) was needed in seven (28%) patients; 18 patients (72%) underwent uterus-preserving treatment without severe complications. The mean duration of EM was 107 days. The mean day of onset of hyperfibrinolysis and beginning of TXA treatment was day 45. The mean nadir of fibrinogen level before TXA was 242.4 mg/dL, with a mean drop of 29.7% in fibrinogen level. CONCLUSIONS: Our data support EM as a safe treatment option in PAS. Hyperfibrinolysis can be a cause of hemorrhage during EM and can be treated with TXA. To our knowledge, this is the first cohort of patients with EM of PAS in whom coagulation monitoring and use of TXA have been shown to successfully treat hyperfibrinolysis.

Conventional and Pro-Inflammatory Pathways of Fibrinolytic Activation in Non-Traumatic Hyperfibrinolysis.

Hyperfibrinolysis (HF) frequently occurs after severe systemic hypoperfusion during major trauma and out-of-hospital cardiac arrest (OHCA). In trauma-induced HF, hypoperfusion, the activation of protein C (APC), and the release of tissue plasminogen activator (t-PA) have been identified as the driving elements of premature clot breakdown. The APC pathway also plays a role in inflammatory responses such as neutrophil extracellular trap formation (NETosis), which might contribute to lysis through cleavage of fibrin by neutrophil elastases. We investigated whether the APC and the plasminogen pathway were general drivers of HF, even in the absence of a traumatic incident. Additionally, we were interested in inflammatory activation such as the presence of NETs as potential contributing factors to HF. A total of 41 patients with OHCA were assigned to a HF and a non-HF group based on maximum lysis (ML) in thromboelastometry. Thrombin-antithrombin (TAT)-complex, soluble thrombomodulin (sTM), APC-PC inhibitor complex, t-PA, PAI-1, t-PA-PAI-1 complex, plasmin-antiplasmin (PAP), d-dimers, neutrophil elastase, histonylated DNA (hDNA) fragments, and interleukin-6 were assessed via immunoassays in the HF group vs. non-HF. APC-PC inhibitor complex is significantly higher in HF patients. Antigen levels of t-PA and PAI-1 do not differ between groups. However, t-PA activity is significantly higher and t-PA-PAI-1 complex significantly lower in the HF group. Consistent with these results, PAP and d-dimers are significantly elevated in HF. HDNA fragments and neutrophil elastase are not elevated in HF patients, but show a high level of correlation, suggesting NETosis occurs in OHCA as part of inflammatory activation and cellular decay. Just as in trauma, hypoperfusion, the activation of protein C, and the initiation of the plasminogen pathway of fibrinolysis manifest themselves in the HF of cardiac arrest. Despite features of NETosis being detectable in OHCA patients, early pro-inflammatory responses do not appear be associated with HF in cardiac arrest.

Disseminated Intravascular Coagulation With Excessive Fibrinolysis Following Diagnostic Prostatic Biopsy for Prostate Cancer.

The most common hematological disorder associated with prostate cancer is disseminated intravascular coagulation (DIC). In most cases, cancer patients with DIC have compensated fibrinolysis with a low incidence of bleeding. However, DIC with excessive fibrinolysis is a rare albeit life-threatening variant that can present with massive bleeding and is thought to occur due to the unique properties of neoplastic cells of prostate cancer that activate both procoagulant and anticoagulant pathways simultaneously. Depending on the shift of the intricate balance between the two forces, the net result can be either systemic micro- (DIC) or macro-thrombi, deep venous thrombosis (DVT) or pulmonary embolism, or a bleeding syndrome from excessive vicious activation of fibrinolysis. Here, we present a unique case of suspected prostate cancer who underwent a diagnostic prostatic biopsy. Subsequently, he developed massive hematuria requiring intensive care unit admission with multiple supportive blood products. Additionally, he was administered epsilon-aminocaproic acid with a prophylactic dose of heparin, with prompt resolution of bleeding. After stabilization, he was discharged with planned outpatient chemotherapy. However, he subsequently presented with lower extremity DVT within a week, which led to a stroke in the setting of a patent foramen ovale. This unique case report highlights how a change in the intricate balance of the coagulation cascade causes a polar shift in clinical presentation and complications.

Fibrinolysis in Dogs with Intracavitary Effusion: A Review.

Physiologic fibrinolysis is a localized process in which stable fibrin strands are broken down by plasmin in response to thrombosis. Plasmin activation can also take place separately from the coagulation process, resulting in pathologic fibrinolysis. When plasmin activation exceeds the neutralizing capacity of plasmin inhibitors, severe bleeding can potentially take place. Although the processes which regulate coagulation and fibrinolysis in the blood are well known, it is less clear as to what extent the same processes take place in the body cavities and whether they influence systemic hemostasis. The results of the studies herein cited demonstrate that coagulation followed by fibrinogenolytic/fibrinolytic activity takes place in all kinds of canine ascitic and pleural fluids. Moreover, systemic clotting abnormalities suggesting primary fibrinolysis/primary hyperfibrinolysis (i.e., elevated plasma fibrin/fibrinogen degradation products [FDPs] and normal D-dimer concentrations with fibrinogen concentrations ≤ 100 mg/dL or above this cut-off, respectively) occur in dogs with intracavitary effusion. Enhanced fibrinolytic activity in dogs with intracavitary effusion can also be detected using rotational thromboelastometry (ROTEM), although the degree of agreement between ROTEM and FDPs, D-dimer and fibrinogen concentrations is poor. Finally, contrary to the thrombotic events commonly documented in some humans and cats with cardiac diseases, bleeding tendencies due to primary fibrinolysis/primary hyperfibrinolysis have been documented in dogs with cardiogenic ascites.

A case of hemorrhagic shock due to intercostal artery injury that occurred during initial trauma care with multiple displaced rib fractures and traumatic head injury.

Rib fractures can cause injury to some organs. We herein report a case of hemorrhagic shock due to intercostal artery injury that occurred during initial trauma care (ITC) treated by resuscitative thoracotomy (RT) and transcatheter arterial embolization (TAE) with multiple displaced rib fractures (RFs) and traumatic head injury (THI). A man in his 50s who was injured in a traffic accident was transferred to our institution by helicopter for emergency medical treatment. He underwent left thoracic drainage on site. On admission, he was diagnosed with multiple RF, THI, pelvic fracture and right humerus fracture. His D-dimer and fibrin degradation products (FDP) level were extremely elevated. However, contrast enhance CT (CECT) revealed no extravasation. At 2 h after arrival, massive hemorrhaging from his thoracic tube suddenly occurred and his blood pressure decreased to approximately 40s mmHg. CECT performed after volume resuscitation and massive transfusion revealed extravasation from the intercostal artery. Because his blood pressure could not be maintained by massive transfusion, we performed RT and TAE followed by RT. He then received intensive care and several surgical procedures were performed, including craniotomy for removal of hematoma, rib fixation and humerus fixation. He was transferred to another hospital for rehabilitation on day 63, with a GCS of 15. Hemorrhagic shock due to intercostal artery injury may occur at any time from arrival in cases with displaced RF, especially when complicated by THI.