Hemostatic Therapy Research Articles

Thromboelastometry-Guided Therapy of Fulminant Coagulopathy during C-Section and Amniotic Fluid Embolism

This article describes the emergency case of a mid-thirty-year-old pregnant woman who suffered the rare obstetric complication of an amniotic fluid embolism, resulting in fulminant Disseminated Intravascular Coagulopathy (DIC) and shock. DIC was diagnosed with Thromboelastometry (TEM) and therapy was consequently guided by TEM. Thromboelastometry is a viscoelastic hemostatic assay that enables assessment of different aspects of whole blood clot formation under shear stress. This technique is increasingly used in anesthesia and critical care to guide hemostatic therapy. This report underlines the importance of TEM-monitoring of hemostatic complications such as DIC.

Acquired Hemophilia A In Adults: A Multicenter Study from Turkey.

Acquired hemophilia A (AHA) is a rare disease caused by autoantibodies inhibiting factor VIII (FVIII) activity. Although the conditionis usually idiopathic, there may be other underlying diseases. Treatment consists of two steps: treatment of acute bleeding and immunosuppression. In this multicenter study, we aimed to demonstrate the clinical characteristics, management details, and survival of AHA patients in Turkey. Data was collected from eleven centers in Turkey. aPTT, FVIII, FVIII inhibitor, and hemoglobin (HB) levels, mixing test results, and demographics at diagnosis, treatment information, adverse events, bleeding episodes during follow-up, relapses, and outcome were analyzed. Twenty-nine patients were analyzed (58.6% female). No underlying disorder could be detected in 14 patients. The most prevalent etiologies were pregnancy, malignancy and infections. The median FVIII activity and FVIII inhibitor titer at diagnosis were 0.7% (0.0-29.4%) and 32.6 BU (0.6-135.6 BU) respectively. Bleeding was severe in 44.8% of patients. The HB value was significantly lower in patients with severe bleeding. Most of the patients (n = 25, 86.2%) had only one bleeding episode without relapse, three patients (10.3%) had two bleeding episodes, and one patient had more than three bleedings. 21 (75%) patients received hemostatic therapy. The use of recombinant FVIIa was slightly higher than activated prothrombin complex concentrate (15 versus 10 patients). Immunosuppressive treatment was initiated in 26 (93%) patients. Regimens containing steroid, cyclophosphamide, and rituximab in different combinations were the most preferred. The median follow-up period was 13 months (2-156 months). Median overall survival was 154.97 months. Four and six-year survival were 90.9 ± 0.8% and 77.9 ± 14.1% respectively. This is a unique study that investigated the demographic characteristics, treatment approaches, and patient survival of AHA in Turkey.

Cerebral venous sinus thrombosis caused by traumatic brain injury complicating thyroid storm: a case report and discussion

IntroductionCerebral venous sinus thrombosis (CVST) is an uncommon cerebrovascular disease with diverse predisposing factors. We report a case of CVST caused by a thyroid storm induced by traumatic brain injury.Case presentationA 29-year-old male patient with a history of Graves’ disease with hyperthyroidism presented to our hospital with head trauma of cerebral contusion and laceration in both frontal lobes confirmed by admission CT scan. He received mannitol to lower intracranial pressure, haemostatic therapy, and antiepileptic treatment. Eight days later, he presented with signs of thyroid storms, such as tachycardia, hyperthermia, sweating and irritation, and his thyroid function tests revealed high levels of TPO-Ab, TR-Ab, TG-Ab, FT3 and FT4. Then, he entered a deep coma. His brain CT showed a thrombosis of multiple venous sinuses, along with the opening of peripheral collateral vessels, congestive infarction with haemorrhage and brain swelling. He regained consciousness after treatment with antithyroid drugs, anticoagulants, respiratory support and a regimen of sedation/analgesia. After a half-year follow-up, most of the patient’s blocked cerebral venous sinuses had been recanalized, but there were still some sequelae, such as an impaired fine motor performance of the right hand and verbal expression defects.ConclusionsCVST can be induced by thyroid storms, and trauma-related thyroid storms can develop on the basis of hyperthyroidism. The purpose of this case report is to raise clinicians’ awareness and improve their ability to diagnose CVST early in patients with traumatic brain injury complicating thyroid storms to improve the neurological prognosis among similar patients.

Treatment tactics for a patient with acquired hemophilia: continuous infusion of recombinant activated coagulation factor VII and the inhibitor eradication

Introduction. Acquired hemophilia is a rare autoimmune disease caused by an inhibitor to clotting factor VIII (FVIII). It complicates the course of many diseases, in particular autoimmune diseases, and in women is often associated with pregnancy.Aim — to present a case of successful treatment of a patient with acquired hemophilia using long-term continuous infusion of rFVIIa and inhibitor eradication as a result of immunosuppressive therapy.Main findings. A clinical observation of severe hemorrhagic syndrome in a patient with acquired hemophilia associated with pregnancy is presented. Uterine bleeding in the patient after spontaneous delivery, refractory to standard hemorrhagic syndrome treatment, required multiple surgical interventions. Laboratory tests showed prolongation of APTT, CT in the INTEM rotational thromboelastometry test, a decrease in plasma FVIII activity and presence of inhibitor to FVIII. Vacuum-assisted closure was applied to treat infected laparotomy wound. Therapy for acquired hemophilia consisted of hemostatic therapy and the inhibitor eradication. Hemostatic therapy included a continuous infusion of rFVIIa at a rate of 30 μg/kg/h with a gradual decrease up to 9.6 μg/kg/h, as well as its fractional administration before every surgery at a dosage of 80 μg/kg. The effectiveness of the therapy was assessed by the dynamics of CT in the INTEM test and the shortening of the APTT. The inhibitor eradication was achieved by prednisolone therapy, combined immunosuppression with rituximab and azathioprine, followed by its replacement with cyclophosphamide. As a result, the hemorrhage was stopped, reference plasma activity of FVIII and eradication of the inhibitor were reached.

Evaluation of Blood Coagulation by Optical Vortex Tracking.

Blood coagulation is a complicated dynamic process that maintains the blood’s fluid state and prevents uncontrollable bleeding. The real-time monitoring of coagulation dynamics is critical for blood transfusion guidance, emergency management of trauma-induced coagulopathy, perioperative bleeding, and targeted hemostatic therapy. Here, we utilize optical vortex dynamics to detect the blood coagulation dynamic process in a rapid and non-contact manner. To characterize the temporal changes in viscoelastic properties of blood during coagulation, we track the stochastic motion of optical vortices in the time-varying speckles reflected from 100 blood samples with varied coagulation profiles. The mean square displacement (MSD) of the vortices increases nonlinearly with time lag during blood coagulation reminiscent of the particles in viscoelastic fluids. The MSD curves with coagulation time are similar to the tracings of thromboelastography (TEG) during the blood coagulation. The retrieved coagulation parameters, such as reaction time and activated clotting time measured using the optical vortex method, exhibit a close correlation to those parameters acquired from TEG. These results demonstrate the feasibility of the optical vortex method for monitoring blood coagulation at the point of care. Our method is also applicable to measuring the viscoelasticity of complex fluids and turbid soft matters.

Tactics of therapy for acute gastrointestinal bleeding

The number of patients with non-varicose acute gastrointestinal bleeding who needanticoagulants has increased in the last decade. The choice of method and amount of safetherapy in case of acute gastrointestinal bleeding is complicated. A reasonable optimalbalance of therapy between hypo- and hypercoagulant components was determined on thebasis of an objective assessment of risk factors for re-bleeding and thromboemboliccomplications. A council of surgeons, resuscitators and cardiologists decided on therationality of anticoagulant therapy and its scope. With a low risk of recurrent bleeding and ahigh risk of thromboembolic complications, hemostatic therapy (tranexamic acid,ethamsylate) was combined with the introduction of low molecular weight heparin(bemiparin) in prophylactic doses. An important parameter for the appointment ofconservative therapy were thromboelastography. The data obtained indicate the safety ofhemostatic and thromboprophylactic therapy (the level of re-bleeding did not differ from thelevel of bleeding without the use of low molecular weight heparins, according to theliterature). Stroke was observed in only 1 patient. The complexity, multifactorial and diversityof clinical conditions of patients with acute gastrointestinal bleeding indicates the need forfurther study of the treatment problem.

Effects of low and high factor X concentrations on thrombin generation in vitro

IntroductionPlasma factor X (FX) levels may affect the therapeutic effects of bypass hemostatic therapy among patients with hemophilia with inhibitors. This study aimed to reproduce low and high FX level conditions in vitro and analyze changes in coagulation capacity. Materials and methodsTo achieve low FX concentrations, FX-deficient plasma was preincubated with anti-factor VIII (FVIII) or anti-factor IX (FIX) antibody. Following this, it was incubated with activated factor VII (FVIIa) or FVIIa/FX mixture in the presence of FX (0.13–0.64 IU/mL). To achieve high FX concentrations, FVIII- or FIX-deficient plasma was preincubated with anti-FVIII or anti-FIX antibody. Next, FX (4–20 IU/mL) was added in the presence of FVIIa (140 IU/mL). Under both conditions, changes in coagulation capacity were assessed by evaluating thrombin generation (TG) and activated partial thromboplastin time (aPTT). ResultsFX at low concentrations induced concentration-dependent changes in TG. In the presence of FX (0.13 IU/mL), adding FVIIa inadequately restored TG. Further, TG in the plasma was normalized after adding FVIIa/FX (62.5/2 IU/mL), and the FVIIa/FX-added group had a stable TG and aPTT, regardless of FX concentrations (0.13–0.64 IU/mL). The FVIIa-added group exhibited a FX concentration-dependent increase in TG and a decrease in aPTT. Furthermore, TG increased with FX concentrations under high FX concentrations (up to 10 IU/mL). ConclusionsSimultaneous FX supplementation in addition to FVIIa may be effective in promoting hemostasis under low plasma FX levels. Moreover, the risk of overcoagulation might be low even under high plasma FX levels.

Glucose-responsive biomimetic nanoreactor in bacterial cellulose hydrogel for antibacterial and hemostatic therapies

Anti-infections therapy accompanied with effective hemorrhage control is highly urgent in clinics. Herein, a biomimetic nanoreactor encapsulated self-healing hydrogel with glucose-responsive catalytic activity was constructed for synergetic antibacterial defense and hemostasis. A metal-organic frameworks (MOF)-based nanocatalyst loaded with glucose oxidase (GOx) was fabricated and encapsulated in the bacterial cellulose (BC) reinforced hydrogel, while the sustained release of GOx could catalyze the decomposition of glucose for triggering the MOF-mediated catalytic activity to in situ generate OH for bacteria killing. Importantly, this nanozyme-based hydrogel exhibited excellent hemostatic property owing to the enhanced absorption capacity, which provides the essential glucose from blood for triggering the glucose-responsive antibacterial activity simultaneously. Antibacterial tests revealed that the hydrogel exhibited significant antibacterial efficacy and biofilm inhibition ability in the presence of normal blood level of glucose. Such design of biocatalytic hydrogel for synergistic hemostatic and antibacterial application brings new insight for nanozyme-based biomedical therapies.

Longitudinal profiling of anti-factor VIII antibodies in Japanese patients with congenital hemophilia A during factor VIII replacement and immune-tolerance induction therapy.

When patients with hemophilia A develop factor VIII (FVIII) inhibitors, FVIII replacement therapy becomes ineffective. Although immune-tolerance induction (ITI) therapy has been used to eradicate inhibitors, treatment is unsuccessful in approximately 30% of cases. However, the mechanism behind treatment failure remains unclarified. We retrospectively examined the longitudinal profiles of immunoglobulin G (IgG) subclasses and/or the inhibitory activities of FVIII in plasma samples from 14 Japanese patients with congenital hemophilia A during hemostatic, FVIII replacement, and/or ITI therapies. In five patients, an increase in IgG4 was observed simultaneously with a decrease in IgG1 when the patient had a history of relatively high FVIII inhibitor titers, reflecting an apparent change in humoral immunity. In addition, we examined the reactivity and specificity of the patients' anti-FVIII IgG1 and IgG4 to FVIII domains by immunoblotting. Under our experimental conditions, plasma from three patients with historically higher inhibitor titers appeared to have high titers of antibodies against the A2-a2 domain, which did not necessarily correlate with ITI failure. These observations may improve scientific understanding of the immune response to infused FVIII in patients with hemophilia A.

Acquired haemophilia A: Italian Consensus Recommendations on diagnosis, general management and treatment of bleeding.

Acquired haemophilia A (AHA) is a rare bleeding disorder due to autoantibodies to coagulation factor VIII that may be secondary to autoimmune diseases, cancer, drugs, pregnancy, infections, or be idiopathic. Recurrent bleeding, often severe, mostly in muscles and soft tissues, and isolated prolonged activated partial thromboplastin time (aPTT), in the absence of personal and family history of bleeding, are typical features that should raise the suspicion of AHA. Poor awareness of the disease results in diagnostic delays and inappropriate treatment. The Italian Association of Haemophilia Centres (AICE) developed consensus recommendations in cooperation with the Italian Society on Thrombosis and Haemostasis (SISET). The document was shared with scientific societies of specialist physicians, laboratory professionals and pharmacists to spread knowledge about AHA and promote appropriate diagnosis/treatment. Ready availability of the aPTT mixing test is crucial, although diagnostic confirmation and optimal management require prompt referral of patients to specialised centres with rapidly available diagnostic and therapeutic facilities. If immediate referral is unfeasible, treatment must be undertaken early, under guidance of specialised centres or based on shared protocols. Recommendations about diagnosis, general management and, in bleeding patients, haemostatic therapy using bypassing agents or replacement treatment, including the recently available recombinant porcine factor VIII, are provided, considering the different clinical settings and laboratory facilities. This consensus document aims to improve the overall healthcare pathways for AHA, harmonise the management and therapeutic approaches to newly diagnosed patients and reduce the still relevant complications and mortality in this setting.

Implementation of Viscoelastic Hemostatic Assay-guided Therapy to Evaluate and Manage Trauma-related Bleeding: A Pilot Study from a Level 1 Trauma Center in Bangkok, Thailand

Objective: To evaluate the effectiveness of viscoelastic hemostatic assay (VHA)-guided therapy for assessing and managing trauma-related bleeding using a multidisciplinary team approach at a level 1 trauma center.Materials and Methods: This retrospective pilot study included trauma-related hemorrhagic patients who underwent rotational thromboelastometry (ROTEM) during September 2019-May 2020. ROTEM trace results were compared with those of conventional coagulation tests (CCT).Results: Thirteen patients (median age: 29.1 years; male: 76.92%) were included. The median (range) days of ventilator support, ICU length of stay, and hospital length of stay was 4 [0-65], 5 [1-65], and 6 [1-83], respectively. ROTEM-guided therapy was applied 26 times, and was repeated in 7 cases. Of those, four cases were repeated to correct coagulopathy. The median time-to-confirmed hemostasis for ROTEM was substantially shorter than for CCT (92 minutes [70-110] vs. 287 minutes [204-354], respectively). The coagulation results from 26 ROTEM tests were also compared between those requiring and not requiring a massive transfusion protocol (MTP). MTP with ROTEM-guided therapy was activated in 6/13 cases. Following the resuscitation endpoints in traumatic shock, four of those had their median serum lactate levels decreased from 10.9 d/L (2.1-16.8) to 3.9 d/L (1.7-17.7). ROTEM traces detected cases with low fibrinogen that only required cryoprecipitate transfusion, and red blood cell and fresh frozen plasma use was less in ROTEM than in conventional MTP.Conclusion: VHA-guided therapy was shown to effectively facilitate goal-directed hemostatic resuscitation and efficient blood product use during resuscitation, definitive treatment, and postoperative intensive care.

Abnormal uterine bleeding. Hemostatic therapy: hematologist point of view

Abnormal uterine bleeding (AUB) is a common pathology at the confluence of different specialties, mainly occurring in women of reproductive age. There are two main groups of AUB causes: the structural pathology of the female reproductive system and the functional changes, which include the pathology of the hemostatic system, among other things. Regardless of the severity of manifestations, for the efficacy of the treatment, it is important to establish the certain cause of AUB and to choose the precision therapeutic strategy. However, there are universal therapeutic approaches to provide the hemostatic effect, regardless of the etiology of the process. Fibrinolysis inhibitors, in particular, tranexamic acid, are the basis of this approach.

Cerebral Hemorrhage: Pathophysiology, Treatment, and Future Directions.

Intracerebral hemorrhage (ICH) is a devastating form of stroke with high morbidity and mortality. This review article focuses on the epidemiology, cause, mechanisms of injury, current treatment strategies, and future research directions of ICH. Incidence of hemorrhagic stroke has increased worldwide over the past 40 years, with shifts in the cause over time as hypertension management has improved and anticoagulant use has increased. Preclinical and clinical trials have elucidated the underlying ICH cause and mechanisms of injury from ICH including the complex interaction between edema, inflammation, iron-induced injury, and oxidative stress. Several trials have investigated optimal medical and surgical management of ICH without clear improvement in survival and functional outcomes. Ongoing research into novel approaches for ICH management provide hope for reducing the devastating effect of this disease in the future. Areas of promise in ICH therapy include prognostic biomarkers and primary prevention based on disease pathobiology, ultra-early hemostatic therapy, minimally invasive surgery, and perihematomal protection against inflammatory brain injury.

A rare case of an anaphylactic reaction to plasma and recombinant blood coagulation factor VIII in a child with severe hemophilia A

A rare case of anaphylactic shock after administration of 4 th generation recombinant blood coagulation factor VIII is presented. Anaphylactic shock is a life-threatening complication for a patient with hemophilia A. Temporarily refrain from re-administration of factor VIII, a skin test confirming drug choice, and a patient desensitization procedure provide the clinician with a chance to continue hemostatic replacement therapy for a patient with hemophilia A. The main purpose of this case report is to determine the algorithm of actions to overcome the consequences of anaphylactic shock and continue the prophylactic administration of coagulation factor VIII concentrate to prevent bleeding in a child with a rare random combination of an anaphylactic reaction and congenital coagulation disorders.

Hemorrhage Enlargement Is More Frequent in the First 2 Hours: A Prehospital Mobile Stroke Unit Study.

Hematoma enlargement (HE) after intracerebral hemorrhage (ICH) is a therapeutic target for improving outcomes. Hemostatic therapies to prevent HE may be more effective the earlier they are attempted. An understanding of HE in first 1 to 2 hours specifically in the prehospital setting would help guide future treatment interventions in this time frame and setting. Patients with spontaneous ICH within 4 hours of symptom onset were prospectively evaluated between May 2014 and April 2020 as a prespecified substudy within a multicenter trial of prehospital mobile stroke unit versus standard management. Baseline computed tomography scans obtained <1, 1 to 2, and 2 to 4 hours postsymptom onset on the mobile stroke unit in the prehospital setting were compared with computed tomography scans repeated 1 hour later and at 24 hours in the hospital. HE was defined as >6 mL if baseline ICH volume was <20 mL and 33% increase if baseline volume >20 mL. The association between time from symptom onset to baseline computed tomography (hours) and HE was investigated using Wilcoxon rank-sum test when time was treated as a continuous variable and using Fisher exact test when time was categorized. Kruskal-Wallis and Wilcoxon rank-sum tests evaluated differences in baseline volumes and HE. Univariable and multivariable logistic regression analyses were conducted to identify factors associated with HE and variable selection was performed using cross-validated L1-regularized (Lasso regression). This study adhered to STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology) for cohort studies. One hundred thirty-nine patients were included. There was no difference between baseline ICH volumes obtained <1 hour (n=43) versus 1 to 2 hour (n=51) versus >2 hours (n=45) from symptom onset (median [interquartile range], 13 mL [6-24] versus 14 mL [6-30] versus 12 mL [4-19]; P=0.65). However, within the same 3 time epochs, initial hematoma growth (volume/time from onset) was greater with earlier baseline scanning (median [interquartile range], 17 mL/hour [9-35] versus 9 mL/hour [5-23]) versus 4 mL/hour [2-7]; P<0.001). Forty-nine patients had repeat scans 1 hour after baseline imaging (median, 2.3 hours [interquartile range. 1.9-3.1] after symptom onset). Eight patients (16%) had HE during that 1-hour interval; all of these occurred in patients with baseline imaging within 2 hours of onset (5/18=28% with baseline imaging within 1 hour, 3/18=17% within 1-2 hour, 0/13=0% >2 hours; P=0.02). HE did not occur between the scans repeated at 1 hour and 24 hours. No association between baseline variables and HE was detected in multivariable analyses. HE in the next hour occurs in 28% of ICH patients with baseline imaging within the first hour after symptom onset, and in 17% of those with baseline imaging between 1 and 2 hours. These patients would be a target for ultraearly hemostatic intervention.

Treatment of patients with rare bleeding disorders in the Netherlands: Real‐life data from the RBiN study

BackgroundPatients with rare inherited bleeding disorders (RBDs) exhibit hemorrhagic symptoms, varying in type and severity, often requiring only on‐demand treatment. Prolonged bleeding after invasive procedures is common. Adequate peri‐procedural therapy may reduce this bleeding risk. ObjectiveTo describe general treatment plans of RBD patients and evaluate the use of peri‐procedural hemostatic therapy. MethodsIn the Rare Bleeding Disorders in the Netherlands (RBiN) study, RBD patients from all six Dutch Hemophilia Treatment Centers were included. General treatment plans were extracted from patient files. Patients with a dental or surgical procedure in their history were interviewed about use of peri‐procedural treatment and bleeding complications. ResultsTwo‐hundred sixty‐three patients with a rare coagulation factor deficiency or fibrinolytic disorder were included. Eighty‐four percent had a documented general treatment plan. General treatment plans of patients with the same RBD were heterogeneous, particularly in factor XI deficiency.Overall, 308 dental and 408 surgical procedures were reported. Bleeding occurred in 50% of dental and 53% of surgical procedures performed without hemostatic treatment and in 28% of dental and 19% of surgical procedures performed with hemostatic treatment. Not only patients with severe RBDs, but also patients with mild deficiencies, experienced increased bleeding without proper hemostatic treatment. ConclusionLarge heterogeneity in general treatment plans of RBD patients was found. Bleeding after invasive procedures was reported frequently, both before and after RBD diagnosis, irrespective of factor activity levels and particularly when peri‐procedural treatment was omitted. Improved guidelines should include uniform recommendations for most appropriate hemostatic products per RBD and emphasize the relevance of individual bleeding history.

Colonoscopy Versus Catheter Angiography for Lower Gastrointestinal Bleeding After Localization on CT Angiography.

The aim of this study was to compare catheter angiography (CA) and colonoscopy outcomes after successful CT angiographic (CTA) localization for patients with overt lower gastrointestinal bleeding (LGIB). Seventy-one consecutive patients from two institutions between 2010 and 2020 had both contrast extravasation on CTA imaging in the lower gastrointestinal tract and subsequent CA or colonoscopy. The primary outcome was confirmation of active bleeding during CA or colonoscopy (defined as confirmation yield). The secondary outcomes were to determine therapeutic yield (hemostatic therapy), time to procedure, rebleeding rate, and adverse outcome rates (defined as surgery, acute kidney injury, initiation of dialysis, and overall mortality). Univariate analyses and multivariable analyses with P < .05 were used to determine statistical significance. Forty-four patients underwent CA and 27 underwent colonoscopy. CA had higher overall confirmation yield (55% vs 26%, P= .026), whereas therapeutic yields were similar (70% vs 56%, P= .214). Time to procedure was 5.1 ± 3.4 hours for CA and 15.5 ± 13.6 hours for colonoscopy (P < .001). On multivariable analysis, shorter time to procedure was the only statistically significant predictor of confirmation yield (P= .037) and therapeutic yield (P= .013), whereas procedure, hemoglobin, transfusions, and hemodynamic instability were not. Adverse events and rebleeding were not statistically different between patients who underwent CA and colonoscopy (P > .05). Shorter time to procedure was the only statistically significant predictor of confirmation and therapeutic yield after CTA localization of LGIB. Because CA can be performed sooner than colonoscopy without increased rates of adverse outcomes or rebleeding, CA may be a reasonable first-line treatment option in patients with CTA localization of LGIB.

Disseminated talaromycosis complicated by recurrent gastrointestinal bleeding and hemorrhagic shock: a case report

BackgroundGastrointestinal involvement is not uncommon in patients with disseminated talaromycosis, but successful management of massive gastrointestinal bleeding and hemorrhagic shock secondary to talaromycosis is rarely reported. Clinical management strategies for these patients have not been well documented.Case presentationHere, we reported a case of disseminated talaromycosis with recurrent gastrointestinal bleeding and hemorrhagic shock who was successfully alleviated solely with medical treatment.ConclusionsEarly diagnosis and treatment for Talaromyces marneffei, intravenous fluid resuscitation, hemostatic therapy and blood transfusion are all essential for talaromycosis complicated with gastrointestinal bleeding and hemorrhagic shock. It is also necessary to warn about the possibility of bleeding induced or aggravated by endoscopic biopsy trauma.

Long-term outcomes of hemostatic therapy for variceal bleeding and the challenge pending in the post-direct-acting antivirals era.

This study evaluated the longterm outcomes of mainly endoscopic hemostatic therapy for gastrointestinal variceal bleeding and of the transition of hemostatic therapy. Among 1,163 patients treated for gastrointestinal varices between April 2006 and June 2020, a total of 125 patients who underwent emergency hemostatic therapy were enrolled. Survival rates and secondary evaluation points were analyzed. Additionally, patients were classified into two groups: the previous and latter term. Patients' background, therapeutic method, and treatment results were compared between the groups. 94.4% had cirrhosis. The average Child-Pugh score was 8.90. Successful primary hemostasis rate was 98.4%, and 5.6% died within 2 weeks, all with a Child-Pugh score ≥9. The respective 1- and 5-year survival rates for Child-Pugh grade A/B were 81.3% and 55.4%, while those for Child-Pugh grade C were 58.1% and 17.8%. Child-Pugh grade C or hepatocellular carcinoma was significantly associated with poor prognosis. In total, 21.6% experienced variceal re-bleeding; 62.9% of these cases were triggered by continued alcohol consumption. There was no significant difference in survival between patients with and without variceal re-bleeding and in post-treatment survival between the previous and latter terms. In the latter term, the number of cases caused by continued alcohol consumption significantly increased. Multidisciplinary treatment and continuation of proper management after hemostatic therapy for variceal bleeding are crucial. Continued alcohol consumption leads to variceal bleeding and re-bleeding; its proper management, including alcohol abstinence, is one of the major challenges left in the post-directacting antivirals era.

Pregnancy with Post Inferior Vena Cava Balloon Angioplasty with Uterine Arterio-Venous Malformation

Venous thromboembolism (VTE) complicates one in 1000 pregnancies. The standard therapy in venous thromboembolism are anticoagulants, heparin, or warfarin. Uterine artery malformation is rare but can result in life-threatening bleeding which needs immediate intervention. A 33-year-old female, G2A1 at 36 weeks period of gestation, with h/o inferior vena cava (IVC) thrombus and uterine arterio-venous (AV) malformation, which was treated with uterine artery embolisation and Inferior vena cava (IVC) balloon angioplasty 3 years back, was successfully managed during her antenatal, intrapartum and postpartum period with anticoagulants at therapeutic doses. Both mother and baby were discharged in stable condition. The balance between prevention of thrombus formation and bleeding complication with the use of anticoagulants is critical in such patients. Successful management of both VTE and bleeding uterine artery malformation needs intensive monitoring and requires both anticoagulant and haemostatic therapy under close supervision of multidisciplinary team.