Hyperfibrinolytic State Research Articles

Personalized delayed anticoagulation therapy alleviates postoperative bleeding in total knee arthroplasty (TKA) patients.

Ecchymosis is one of the most common complications following total knee arthroplasty (TKA), which is closely related to postoperative bleeding. However, it is still controversial whether anticoagulation treatment should be continued for postoperative ecchymosis patients. We suppose that personalized delayed anticoagulation therapy could be beneficial for decreasing postoperative bleeding. A total of 201 TKA patients were retrospectively included in this study, among whom ecchymosis patients received drug anticoagulation treatment 1-2 days later than usual, while nonecchymosis patients received regular drug anticoagulation treatment. The perioperative blood loss, coagulation state, fibrinolytic state and complications were collected and analyzed. Eighty-nine patients (44.3%) developed ecchymosis within 3 days after TKA. There were no differences in baseline characteristics between the two groups. In the ecchymosis group, higher K values and lower calculated coagulation index values were observed in thromboelastography, along with greater total blood loss and a more significant decrease in haemoglobin levels on postoperative Day 1 (POD1) compared to the nonecchymosis group. Additionally, the ecchymosis patients exhibited higher levels of fibrinogen degradation products and D-dimer (D-D) on POD1, with no differences noted on POD3, indicating that patients with ecchymosis are in a relatively hypocoagulable and hyperfibrinolytic state compared to those without ecchymosis. Therefore, the delayed anticoagulation treatment proved beneficial for correcting these postoperative conditions. No statistically significant differences were found between the two groups in postoperative complications, demonstrating that delayed anticoagulation treatment is safe. Patients with ecchymosis exhibited a relatively hypocoagulable and hyperfibrinolytic state with a stronger tendency for postoperative bleeding. Delayed anticoagulation in ecchymosis patients could effectively prevent further exacerbation of postoperative bleeding by avoiding sustained hypocoagulable and hyperfibrinolysis states. Personalized delayed anticoagulation therapy could be beneficial for managing postoperative ecchymosis for TKA patients. Level IV.

Methods, precision, and analytical sensitivity of a novel low-plasma-volume assay of fibrinolytic capacity utilizing the euglobulin fraction.

Fibrinolysis is a critical aspect of the hemostatic system, with assessment of fibrinolytic potential being critical to predict bleeding and clotting risk. We describe the method for a novel low-plasma-volume assay of fibrinolytic capacity utilizing the euglobulin fraction (the "modified mini-euglobulin clot lysis assay [ECLA]"), its analytic sensitivity to alterations in key fibrinolytic substrates/regulators, and its initial applications in acute and convalescent disease cohorts. The modified mini-ECLA requires 50 μL of plasma, a maximal read time of 3 h (with most results available within 60 min), and is entirely performed in a 96-well microplate. Assay measurements were obtained in a variety of commercial control and deficient plasmas representing clinically relevant hypo- and hyperfibrinolytic states, and in three distinct adolescent cohorts with acute or convalescent illness: critically ill, following endotracheal intubation; acute COVID-19-related illness; and ambulatory, 3 months following a venous thromboembolic event. In 100% and 75% deficient plasmas, hypofibrinolysis for plasminogen-deficient, fibrinolysis for alpha-2-antiplasmin-deficient, and hyperfibrinolysis for plasminogen activator inhibitor-1-deficient plasmas were observed. The modified mini-ECLA Clot Lysis Time Ratio ("CLTR") demonstrated moderate-strength correlations with the Clot Formation and Lysis (CloFAL) assay, is analytically sensitive to altered fibrinolytic states in vitro, and correlates with clinical outcomes in preliminarily-studied patient populations.

Evaluation of the Prognostic Role of D-dimer in Egyptian Hepatocellular Carcinoma Patients Undergoing Locoregional Treatment

Abstract Background The blood coagulation function is often abnormal in HCC patients due to hypercoagulatory state, hyperfibrinolytic state, and increased plasma D-dimer. HCC patients treated with locoregional treatment may show changes of D-dimer levels. Several studies explored the validity of D-dimer levels during locoregional treatment in HCC but definitive data are still lacking. Aim of the Work Determination of the efficacy of D-dimer profile as a prognostic marker regarding tumor features, and post interventional response in HCC subjects undergoing TACE or RFA. Patients and Methods The clinical data of 50HCC patients who underwent TACE or RFA in our hospital from October 2021 to June 2022 were collected, including the CBC, CRP Alfa-fetoproteins and plasma d-dimer level 1 week before TACE or RFA(D0), D-dimer level 1 month (D1) and 4 months(D2) after TACE or RFA. Contrast enhanced CT was performed within 1 week before locoregional treatment and was repeated 1month and 4 months after locoregional treatment to assess for treatment efficacy according to the mRECIST criteria based on change in tumor size as measured by CT scan. One month after TACE or RFA, these patients were divided into four groups according to the mRecist criteria: complete response, partial response, stationary disease and progressive disease. D0, D1 and D2 were compared between the 4 groups and the relation between D-dimer level and the efficacy of locoregional treatment was assessed. Results In patients with negative D-dimer before locoregional treatment (D0), there was no significant difference between D0 and D1 (P > 0.05), while patients with elevated pretreatment D-dimer levels (D0), D1 was significantly higher than D0 (P < 0.05) and the D1 is higher than that in patients with negative Do. Progressive rise of D-dimer levels 4months post locoregional treatment (D2) in HCC was associated with tumor progression suggesting aggressive tumor biology and poor outcome(P = 0.02). Conclusion The changes in plasma D-dimer level can be used as a potential prognostic biomarker in predicting the efficacy of locoregional treatment in HCC patients and thus, elevated D-dimer levels pre and post locoregional treatment may serve as predictors of adverse tumor profile and poor outcome.

Utility of Global Hemostatic Assays in Patients with Bleeding Disorders of Unknown Cause.

Bleeding disorder of unknown cause (BDUC) is a diagnosis of exclusion after exhaustive evaluation of plasmatic coagulation and platelet function. This review explores the utility of global hemostatic assays as confirmatory tests and in elucidating the pathophysiology of BDUC. Unlike traditional hemostatic tests that focus on coagulation factors, global assays are conducted both in plasma and also whole blood. These assays provide a more comprehensive understanding of the cell-based model of coagulation, aid in the identification of plasmatic factor abnormalities that may reduce hemostatic capacity, and allow for the assessment of impaired platelet-endothelial interactions under shear stress, as well as hyperfibrinolytic states. While clinical tests such as skin bleeding time and global assays such as PFA-100 exhibit limited diagnostic capacity, the role of viscoelastic testing in identifying hemostatic dysfunction in patients with BDUC remains unclear. Thrombin generation assays have shown variable results in BDUC patients; some studies demonstrate differences compared with healthy controls or reference values, whereas others question its clinical utility. Fibrinolysis assessment in vitro remains challenging, with studies employing euglobulin clot lysis time, plasma clot lysis time, and fluorogenic plasmin generation yielding inconclusive or conflicting results. Notably, recent studies suggest that microfluidic analysis unveils shear-dependent platelet function defects in BDUC patients, undetected by conventional platelet function assays. Overall, global assays might be helpful for exploring underlying hemostatic impairments, when conventional hemostatic laboratory tests yield no results. However, due to limited data and/or discrepant results, further research is needed to evaluate the utility of global assays as screening tools.

Plasma from patients with vaccine-induced immune thrombotic thrombocytopenia displays increased fibrinolytic potential and enhances tissue-type plasminogen activator but not urokinase-mediated plasminogen activation

BackgroundVaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus vector-based COVID-19 vaccines. VITT is associated with markedly raised levels of D-dimer; yet, how VITT modulates the fibrinolytic system is unknown. ObjectivesWe aimed to compare changes in fibrinolytic activity in plasma from patients with VITT, patients diagnosed with venous thromboembolism (VTE) after vaccination but without VITT (VTE–no VITT), and healthy vaccinated controls. MethodsPlasma levels of plasmin-antiplasmin (PAP) complexes, plasminogen, and alpha-2-antiplasmin (α2AP) from 10 patients with VITT, 10 patients with VTE–no VITT, and 14 healthy vaccinated controls were evaluated by enzyme-linked immunosorbent assay and/or Western blotting. Fibrinolytic capacity was evaluated by quantitating PAP levels at baseline and after ex vivo plasma stimulation with 50-nM tissue-type plasminogen activator (tPA) or urokinase for 5 minutes. ResultsBaseline PAP complex levels in control and VTE–no VITT individuals were similar but were ∼7-fold higher in plasma from patients with VITT (P < .0001). VITT samples also revealed consumption of α2AP and fibrinogenolysis consistent with a hyperfibrinolytic state. Of interest, VITT plasma produced significantly higher PAP levels after ex vivo treatment with tPA, but not urokinase, compared to the other groups, indicative of increased fibrinolytic potential. This was not due to D-dimer as addition of D-dimer to VTE–no VITT plasma failed to potentiate tPA-induced PAP levels. ConclusionA marked hyperfibrinolytic state occurs in patients with VITT, evidenced by marked elevations in PAP, α2AP consumption, and fibrinogenolysis. An unidentified plasma cofactor that selectively potentiates tPA-mediated plasminogen activation also appears to exist in the plasma of patients with VITT.

OC 37.5 Vaccine-Induced Immune Thrombotic Thrombocytopenia Produces a Marked Hyperfibrinolytic State and Generates a Plasma Cofactor that Potentiates tPA-Mediated Plasminogen Activation

OC 37.5 Vaccine-Induced Immune Thrombotic Thrombocytopenia Produces a Marked Hyperfibrinolytic State and Generates a Plasma Cofactor that Potentiates tPA-Mediated Plasminogen Activation

The Hematological Effects of Extracorporeal Membrane Oxygenator Exchange.

Membrane oxygenator failure during venovenous (V-V) extracorporeal membrane oxygenation (ECMO) can lead to life-threatening hypoxia, high replacement costs, and may be associated with a hyperfibrinolytic state and bleeding. The current understanding of the underlying mechanisms that drive this is limited. The primary aim of this study therefore is to investigate the hematological changes that occur before and after membrane oxygenator and circuit exchanges (ECMO circuit exchange) in patients with severe respiratory failure managed on V-V ECMO. We analyzed 100 consecutive V-V ECMO patients using linear mixed-effects modeling to evaluate hematological markers in the 72 hours before and 72 hours after ECMO circuit exchange. A total of 44 ECMO circuit exchanges occurred in 31 of 100 patients. The greatest change from baseline to peak were seen in plasma-free hemoglobin (42-fold increase p < 0.01) and the D-dimer:fibrinogen ratio (1.6-fold increase p = 0.03). Bilirubin, carboxyhemoglobin, D-dimer, fibrinogen, and platelets also showed statistically significant changes ( p < 0.01), whereas lactate dehydrogenase did not ( p = 0.93). Progressively deranged hematological markers normalize more than 72 hours after ECMO circuit exchange, with an associated reduction in membrane oxygenator resistance. This supports the biologic plausibility that ECMO circuit exchange may prevent further complications such as hyperfibrinolysis, membrane failure, and clinical bleeding.

Thrombotic Mechanism Involving Platelet Activation, Hypercoagulability and Hypofibrinolysis in Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19) has spread, with thrombotic complications being increasingly frequently reported. Although thrombosis is frequently complicated in septic patients, there are some differences in the thrombosis noted with COVID-19 and that noted with bacterial infections. The incidence (6-26%) of thrombosis varied among reports in patients with COVID-19; the incidences of venous thromboembolism and acute arterial thrombosis were 4.8-21.0% and 0.7-3.7%, respectively. Although disseminated intravascular coagulation (DIC) is frequently associated with bacterial infections, a few cases of DIC have been reported in association with COVID-19. Fibrin-related markers, such as D-dimer levels, are extremely high in bacterial infections, whereas soluble C-type lectin-like receptor 2 (sCLEC-2) levels are high in COVID-19, suggesting that hypercoagulable and hyperfibrinolytic states are predominant in bacterial infections, whereas hypercoagulable and hypofibrinolytic states with platelet activation are predominant in COVID-19. Marked platelet activation, hypercoagulability and hypofibrinolytic states may cause thrombosis in patients with COVID-19.

Features of Coagulo-Fibrinolytic Derangement Due to Bleeding in Nonacclimatized Rabbits Acutely Exposed to High Altitude.

Zhong, Xin, Wenqiong Du, Zhaowen Zong, Renqing Jiang, Yijun Jia, Zhao Ye, and Haoyang Yang. Features of coagulo-fibrinolytic derangement due to bleeding in nonacclimatized rabbits acutely exposed to high altitude. High Alt Med Biol. 24:68-75, 2023. Background: The present study aimed to observe the time course of coagulo-fibrinolytic derangement due to bleeding in rabbits acutely exposed to high altitude (HA). Materials and Methods: Forty-eight rabbits were randomly divided into four groups and were subjected to minor bleeding at low altitude, major bleeding at low altitude, minor bleeding after acute exposure to HA, and major bleeding after acute exposure to HA. To produce minor and major bleeding, 10% and 30% of the total blood volume was removed, respectively. At designated time points, samples were taken for laboratory examination. Results: While minor bleeding at low altitude led to minor coagulo-fibrinolytic derangements, it led to complicated derangements at HA, which presented as an early hypercoagulable state and transition to hypocoagulable and hyperfibrinolytic states with lower clot firmness. Major bleeding at HA resulted in greater derangements of the R time, K values, the D-dimer concentration, the alpha angle, maximum amplitude, and the concentration of fibrinogen than were observed at low altitude. Conclusions: The extent of coagulo-fibrinolytic derangements due to bleeding in rabbits after acute exposure to HA was more severe and complicated than that at low altitude. Therefore, proper resuscitation should be applied based on these changes.

Laboratory evaluation of a new integrative assay to phenotype plasma fibrinolytic system

BackgroundThere is currently no universal and standardized test available to phenotype plasma fibrinolytic system.AimsOur main aims were to evaluate the performances of the ‘global fibrinolysis capacity’ assay (GFC) performed with the Lysis Timer® instrument, and to study the influence of some preanalytical conditions.MethodEuglobulin clot lysis time (ECLT) and GFC were performed under several preanalytical conditions.ResultsGFC showed satisfactory intra- and inter-run precision. Frozen controls and reagents showed stability over the studied period.There was no statistically significant difference between GFC assessed in plasma samples processed at 4 °C or at 20 °C. GFC assessed with frozen-thawed plasma samples was prolonged when compared to fresh samples (p = 0.014). The centrifugation scheme had no influence on PAI-1 activity levels, GFC and ECLT.Reference interval for GFC ranges from 29.3 (C I90% = 26.9–31.9) to 49.5 (90% CI = 45.9–52.2) minutes.In addition, a preliminary study in 40 healthy volunteers and 43 adult patients referred for investigation of a bleeding disorder was conducted to compare GFC and ECLT assays in their ability to classify samples with shortened or prolonged clot lysis times. Disagreements between ECLT and GFC were observed for 23 samples (out of 83), most of them minor.ConclusionGFC is suitable and convenient for a broad clinical use and can be performed with frozen-thawed plasma samples.Unlike ECLT, GFC is designed to take into account the balance between inhibitors and activators of the fibrinolytic system and could detect both hypo- and hyperfibrinolytic states. Whether it is as suitable as or even better than ECLT to detect a bleeding tendency due to a hyperactive fibrinolytic system deserves to be properly investigated.

Menorrhagia as main presentation sign of severe hypothyroidism in a pediatric patient: a case report

BackgroundThe relative high frequency of menstrual irregularities in the first two–three years after menarche may lead to the risk of underestimation of associated pathological conditions, which are always to be accurately researched with careful examination and anamnesis. The association between menstrual irregularities and hypothyroidism is described in literature but the available data are scarce and mainly based on adult case series. It is described that low plasma levels of thyroid hormone can shift the hemostatic system towards a hypocoagulable and hyperfibrinolytic state and seem to lead to an increased bleeding risk.Case presentationThis case report describes the case of a thirteen years old girl who presented to our Emergency Department complaining of menorrhagia for the last fifteen days, leading to severe anemia. The objective examination revealed clinical signs of hypothyroidism and a severe short stature, lower than mid-parental height, with stunting of growth and a significant bone age delay. Blood exams and thyroid ultrasound were consistent with the diagnosis of severe hypothyroidism in autoimmune thyroiditis with acquired von Willebrand syndrome, growth hormone deficiency. Magnetic resonance showed pituitary functional hyperplasia.The substitutive therapy with levothyroxine led to the resolution of heavy bleeding after five days and following normalization of coagulative parameters and pituitary hyperplasia.ConclusionsHypothyroidism usually presents with unspecific symptoms, with consequent risk of diagnostic delay. It can influence the coagulation system and it seems to be associated to increased risk of menstrual irregularities.We underline the importance of a regular follow up of the pubertal development, including height measurements, thyroid palpation and menstrual anamnesis to intercept red flags findings for hypothyroidism.

Coagulation Abnormalities in Renal Pathology of Chronic Kidney Disease: The Interplay between Blood Cells and Soluble Factors.

Coagulation abnormalities in renal pathology are associated with a high thrombotic and hemorrhagic risk. This study aims to investigate the hemostatic abnormalities that are related to the interaction between soluble coagulation factors and blood cells, and the effects of hemodialysis (HD) on it, in end stage renal disease (ESRD) patients. Thirty-two ESRD patients under HD treatment and fifteen healthy controls were included in the study. Whole blood samples from the healthy and ESRD subjects were collected before and after the HD session. Evaluation of coagulation included primary and secondary hemostasis screening tests, proteins of coagulation, fibrinolytic and inhibitory system, and ADAMTS-13 activity. Phosphatidylserine (PS) exposure and intracellular reactive oxygen species (iROS) levels were also examined in red blood cells and platelets, in addition to the platelet activation marker CD62P. Platelet function analysis showed pathological values in ESRD patients despite the increased levels of activation markers (PS, CD62P, iROS). Activities of most coagulation, fibrinolytic, and inhibitory system proteins were within the normal range, but HD triggered an increase in half of them. Additionally, the increased baseline levels of ADAMTS-13 inhibitor were further augmented by the dialysis session. Finally, pathological levels of PS and iROS were measured in red blood cells in close correlation with variations in several coagulation factors and platelet characteristics. This study provides evidence for a complex coagulation phenotype in ESRD. Signs of increased bleeding risk coexisted with prothrombotic features of soluble factors and blood cells in a general hyperfibrinolytic state. Hemodialysis seems to augment the prothrombotic potential, while the persisted platelet dysfunction might counteract the increased predisposition to thrombotic events post-dialysis. The interaction of red blood cells with platelets, the thrombus, the endothelium, the soluble components of the coagulation pathways, and the contribution of extracellular vesicles on hemostasis as well as the identification of the unknown origin ADAMTS-13 inhibitor deserve further investigation in uremia.

Bleeding Disorders in Primary Fibrinolysis.

Fibrinolysis is a complex enzymatic process aimed at dissolving blood clots to prevent vascular occlusions. The fibrinolytic system is composed of a number of cofactors that, by regulating fibrin degradation, maintain the hemostatic balance. A dysregulation of fibrinolysis is associated with various pathological processes that result, depending on the type of abnormality, in prothrombotic or hemorrhagic states. This narrative review is focused on the congenital and acquired disorders of primary fibrinolysis in both adults and children characterized by a hyperfibrinolytic state with a bleeding phenotype.

Vascular mechanisms and manifestations of COVID-19

Vascular mechanisms and manifestations of COVID-19

Fibrinolysis in Traumatic Brain Injury: Diagnosis, Management, and Clinical Considerations.

Posttraumatic coagulopathy involves disruption of both the coagulation and fibrinolytic pathways secondary to tissue damage, hypotension, and inflammatory upregulation. This phenomenon contributes to delayed complications after traumatic brain injury (TBI), including intracranial hemorrhage progression and systemic disseminated intravascular coagulopathy. Development of an early hyperfibrinolytic state may result in uncontrolled bleeding and is associated with increased mortality in patients with TBI. Although fibrinolytic assays are not routinely performed in the assessment of posttraumatic coagulopathy, circulating biomarkers such as D-dimer and fibrin degradation products have demonstrated potential utility in outcome prediction. Unfortunately, the relatively delayed nature of these tests limits their clinical utility. In contrast, viscoelastic tests are able to provide a rapid global assessment of coagulopathy, although their ability to reliably identify disruptions in the fibrinolytic cascade remains unclear. Limited evidence supports the use of hypertonic saline, cryoprecipitate, and plasma to correct fibrinolytic disruption; however, some studies suggest more harm than benefit. Recently, early use of tranexamic acid in patients with TBI and confirmed hyperfibrinolysis has been proposed as a strategy to further improve clinical outcomes. Moving forward, further delineation of TBI phenotypes and the clinical implications of fibrinolysis based on phenotypic variation is needed. In this review, we summarize the clinical aspects of fibrinolysis in TBI, including diagnosis, treatment, and clinical correlates, with identification of targeted areas for future research efforts.

Pathological coagulation parameters in as many as 54 patients with autoimmune acquired factor XIII deficiency due to anti-factor XIII autoantibodies.

Autoimmune factor XIII (FXIII) deficiency (AiF13D) due to anti-FXIII autoantibodies is an extremely rare, life-threatening bleeding disorder that mostly occurs in the elderly. The number of patients diagnosed with AiF13D has been increasing in Japan, probably because of the nationwide survey on AiF13D supported by the Japanese Ministry of Health, Labour and Welfare. To explore the pathologic characteristics of coagulation parameters in AiF13D. AiF13D-suspected cases were consulted, and underwent unified/integrated coagulation screening and were definitively diagnosed as AiF13D separately. AiF13D patients had lower FXIII antigen levels than non-AiF13D patients, but their values overlapped. Among a series of 22-item screening tests and their resulting parameters, the 'FXIII inhibitory potential' yielded by a 1:1 mixing test of the patient's and healthy control's plasma and its 'residual FXIII activity' in 54 AiF13D cases were most distinguishable from 139 non-AiF13D cases, followed by FXIII activity per se and FXIII-specific activity. While the cross-linked α2 -plasmin inhibitor level reduced, the levels of D-dimer, fibrin/fibrinogen degradation products and plasmin-plasmin inhibitor complex increased, probably because the patients' haematoma nonspecifically induced secondary fibrinolysis in both AiF13D and non-AiF13D patients. AiF13D appears to induce a hypocoagulopathy combined with a hyper-fibrinolytic state secondary to severe FXIII deficiency caused by anti-FXIII autoantibodies, and the consequent bleeding further modifies its pathological conditions. In addition, the 1:1 mixing test of FXIII activity was confirmed to be a reliable screening method for AiF13D, especially when its derivative parameter, such as the 'FXIII inhibitory potential' or 'FXIII inhibitory potential ratio', is employed.

Fibrinolysis in Patients with Liver Disease.

Patients with liver disease acquire complex changes in their hemostatic system. Historically, these patients were considered to have a bleeding tendency related, in part, to a hyperfibrinolytic state. However, studies using more modern fibrinolysis tests have questioned the presence of a hyperfibrinolytic state in patients with liver disease and its association with bleeding risk. It may be that the sickest patients with liver disease do have fibrinolytic abnormalities. However, the debate on the fibrinolytic state of patients with (decompensated) cirrhosis or critically ill liver disease is complicated by the fact that hypo- and hyperfibrinolysis have been poorly defined. This could, in part, be explained by the lack of reliable tests that assess a patient's fibrinolytic status. Moreover, large clinical studies on the relationship between bleeding and fibrinolysis in patients with liver disease are scarce. Here, we provide an overview of the current knowledge on fibrinolysis in various types of liver diseases and possible implications as a target for therapeutic strategies in liver disease. As antifibrinolytic therapy has been shown to be safe and effective during liver transplantation, it could potentially be of use in patients with (either laboratory-established or suspected) hyperfibrinolysis-related bleeding.

Application of Viscoelastic testing to the field of Otolaryngology Head and Neck Surgery: A Scoping Review

Background: &#x0D; In Otolaryngology Head and Neck Surgery (OHNS), hematologic management requires attention to the intricate nature of hemostatic competence. Elderly patients can experience drug induced coagulopathies. Strategies are needed in order to minimize hemorrhagic and thromboembolic risk and maximize positive outcomes. Viscoelastic tests (VETs) such as Thromboelastography (TEG) and Rotational Thromboelastometry (ROTEM) have been used to guide blood component therapy. The purpose of this scoping review is to understand the utilization of VETs in OHNS. &#x0D; &#x0D; Methods: &#x0D; &#x0D; This scoping review included studies that discussed the utilization of VETs in the field of OHNS. The inclusion criteria was studies that discussed the application of VETs in Flap/Plastic Reconstruction, Facial Trauma/Resuscitation, Tonsillectomy, Obstructive Sleep Apnea (OSA), Epistaxis, Sinus Surgery, and HNC Resection. Studies that focused on general medical VET use were not included. &#x0D; &#x0D; Results: &#x0D; &#x0D; Fourteen articles met the study inclusion criteria from an initial pool of 45 articles. Seven articles discussed the use of VETs in free flap/reconstructive surgery, five articles explored use in HNC, two articles discussed use in facial trauma and resuscitation, one article mentioned use in OSA, and one article examined use in epistaxis. &#x0D; &#x0D; Conclusion and potential impact: &#x0D; &#x0D; Of the fourteen articles included, two articles found no clinically significant association between TEG parameters and flap loss or complications. Five studies found that TEG or ROTEM helpful in predicting coagulation clotting, a prothrombotic state, or a hyperfibrinolytic state in free flap and HNC patients. For facial trauma and HNC cancer patients two different studies found ROTEM helpful in guiding blood component resuscitation. Using the TEG, one study demonstrated a hypercoagulable state in OSA patients. This review encourages wider use of VETs in OHNS in order to monitor hemostasis and improve surgical outcomes. Further research is necessary to better understand how VETs can tailor hematologic management of OHNS patients.

Acute Kidney Injury in Decompensated Cirrhosis Is Associated With Both Hypo‐coagulable and Hyper‐coagulable Features

Recent evidence suggests that acute kidney injury (AKI) is the main predictor of postparacentesis bleeding in patients with cirrhosis. To assess the factors responsible for bleeding tendency in AKI, we performed a prospective study comparing all three aspects of hemostasis (platelets, coagulation, and fibrinolysis) in patients with decompensated cirrhosis with and without AKI. Primary hemostasis assessment included platelet aggregation and secretion (platelet function markers) and von Willebrand factor. Secondary hemostasis assessment included pro-coagulant (factor VIII and factor XIII) and anti-coagulant (protein C, protein S, and antithrombin) factors and thrombin generation. Tertiary hemostasis assessment included fibrinolytic factors and plasmin-antiplasmin complex. Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Severity of cirrhosis and platelet count were comparable between groups. Median serum creatinine was 1.8 mg/dL and 0.8mg/dL in patients with and without AKI, respectively. At baseline, patients with cirrhosis and AKI had lower platelet aggregation and secretion, indicative of impaired platelet function (increased bleeding tendency), without differences in von Willebrand factor. Regarding coagulation factors, factor VIII was higher, whereas protein C, protein S, and antithrombin were all lower, which, together with increased thrombin generation, indicate hypercoagulability. In contrast, factor XIII was lower in AKI (increased bleeding tendency). Finally, while both hypofibrinolytic and hyperfibrinolytic changes were present in AKI, a higher plasmin-antiplasmin complex indicated a hyperfibrinolytic state. After AKI resolution (n=23 of 40), platelet function and coagulation improved to levels observed in patients with cirrhosis patients without AKI; however, fibrinolysis remained hyperactivated. In patients with decompensated cirrhosis, AKI is associated with both hypocoagulable and hypercoagulable features that can potentially increase the risk of both bleeding and thrombosis.

Bleeding and Bleeding Risk in COVID-19.

Coronavirus disease 2019 (COVID-19) is a new, emerging medical challenge worldwide, with those affected showing a variety of clinical presentations, ranging from asymptomatic or mild conditions to critical illness. Patients affected by the causative virus—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—usually experience cough, fever, dyspnea, myalgia, less frequently gastrointestinal (GI) manifestations and, rarely, neurological complications. Coagulopathy is common among those afflicted and appears to be one of the most significant adverse prognostic signs.[1] [2] Coagulopathy results from concomitant activation of coagulation and fibrinolytic systems, most likely due to a severe proinflammatory state (i.e., the so-called cytokine storm) and/or by viral sepsis that sometimes leads to consumption of coagulation factors and decreased platelet count, resulting in thrombohemorrhagic events.[3] In this process, plasmin breaks down fibrin present in plasma and the bronchoalveolar lavage fluid, as well as potentially other organs, and leading to excess D-dimer/fibrin(ogen) degradation product (FDP) formation. This may also lead to reduction in platelet count and increased risk for hemorrhage.[4] In a systematic review of 6,892 patients and meta-analysis of 3,496 patients, platelets were low in 22.9% and D-dimer was high in 34.8%; D-dimer was associated with a severe clinical course with an odds ratio (OR) of 4.03, and low platelets with an OR of 1.78.[5] Disseminated intravascular coagulation (DIC) in COVID-19 is accompanied by a significant decrease of fibrinogen, and a marked increase of FDP and D-dimer, which are characteristics of DIC with hyperfibrinolysis, whereas the DIC caused by infection is accompanied by plasminogen activator inhibitor-1 release and suppression of fibrinolysis. Administration of antiproteases may prove beneficial.[6] Elevated D-dimer, and FDP, often mildly prolonged prothrombin time and mildly decreased platelet counts were also reported as common findings by Tang et al, more common and more profound in severely affected patients.[2] Fibrinogen levels are sometimes lowered, but may instead be elevated, while activated partial thromboplastin time is sometimes prolonged, but may instead be shortened, with these potentially suggestive of acute phase events.[2] [6] Although hypercoagulability and thrombotic events are common in COVID-19, bleeding may occur at any time during the course of disease. Several factors make patients with COVID-19 prone to bleeding, including thrombocytopenia, hyperfibrinolytic state, consumption of coagulation factors, and thromboprophylaxis administration of anticoagulants. A proposed cytokine storm, prolonged tissue hypoxia, and direct invasion of affected tissues are other possible causes.[2] [7] [8] Although thrombosis is relatively well studied in COVID-19, bleeding and bleeding risk appear to be the forgotten side of this story, most probably due to the less-fatal consequences; however, hemorrhagic diatheses represents a significant morbidity and potential cause of death in COVID-19 in at least in a subset of patients.[7] [8]