Treatment Of Bleeding In Patients Research Articles

Endoscopy in the diagnosis and treatment of gastroduodenal bleedings in patients with pancreatitis

The OBJECTIVE was to study the possibilities of endoscopy in the diagnosis and treatment of bleedings in patients with pancreatitis.METHODS AND MATERIALS. Based on the analysis of 135 patients with pancreatitis complicated by gastroduodenal bleeding, we determined the location and possibilities of endoscopic hemostasis. The article analyzes 2 groups of patients. The first group (64 patients with acute pancreatitis and gastroduodenal bleeding). The second group (71 patients with chronic pancreatitis complicated by gastroduodenal bleeding). The article shows features of endoscopic examination of patients with pancreatitis complicated by gastroduodenal bleeding.RESULTS. The leading method of stopping bleeding in these groups of patients is endoscopic hemostasis.CONCLUSION. The choice of endoscopic hemostasis method depends on the cause and nature of the bleeding. The developed technique of endoscopic hemostasis has reduced the mortality rate from gastroduodenal bleeding in patients with pancreatitis to 3 %.

Real-world long-term safety and effectiveness of turoctocog alfa in the treatment of haemophilia A in Japan: results from a multicentre, non-interventional, post-marketing study

ABSTRACT Objectives To assess the safety and effectiveness of turoctocog alfa in previously treated patients (PTPs) and previously untreated patients (PUPs) with haemophilia A in a real-world setting in Japan. Methods This multicentre, non-interventional, post-marketing study recruited patients with haemophilia A who initiated treatment with turoctocog alfa from 18 sites (08/2014-12/2018). The primary endpoint was adverse events (AEs) during the 2-year study period. Results The safety and effectiveness analysis set included 39 patients. In total, 13 (33.3%) patients reported ≥1 AE; incidence rate was 60.4 events/100 patient-years of exposure (PYE). Treatment was withdrawn in two cases: pruritus in a PTP and factor VIII inhibitor development in a PUP. Inhibitor development occurred in 2.6% of all patients, with an incidence rate of 3.8 events/100 PYE. The rate of inhibitor development was 0%, 25% and 20% in PTPs, PUPs and PUPs with severe type, respectively. The haemostatic success rate was 91.4% for 383 bleeding episodes and 85.7% for 14 surgeries. The negative binomial annualised bleeding rate for the prophylaxis regimen was 6.19 episodes/year (95% CI, 3.69–10.38). The mean (SD) total consumption of turoctocog alfa (n = 34; excluding FVIII inhibitors) was 5,382.6 (7,180.1) IU/kg/year/patient; consumption was 4,133.1 (1,452.4) IU/kg/year/patient for prophylaxis. Discussion The effectiveness and safety profiles were comparable to those observed in other turoctocog alfa trials; effectiveness analysis and consumption were not affected by treatment regimens. Conclusion Long-term use of turoctocog alfa therapy in clinical practice posed no newly identified safety issues and was effective for prophylaxis and treatment of bleeds in patients with haemophilia A in Japan.

Comparison of coagulation parameters associated with fibrinogen concentrate and cryoprecipitate for treatment of bleeding in patients undergoing cytoreductive surgery for pseudomyxoma peritonei: Subanalysis from a randomized, controlled phase 2 study.

The FORMA-05 study compared the efficacy and safety of human fibrinogen concentrate (HFC) versus cryoprecipitate for hemostasis in bleeding patients undergoing cytoreductive surgery for pseudomyxoma peritonei (PMP). This subanalysis explores coagulation parameters in the FORMA-05 patients, with a focus on the seven patients who developed thromboembolic events (TEEs). FORMA-05 was a prospective, randomized, controlled phase 2 study in which patients with predicted blood loss ≥2 L received HFC (4 g) or cryoprecipitate (two pools of five units), repeated as needed. Plasma fibrinogen, platelet count, factor (F) XIII, FVIII, von Willebrand Factor (VWF) antigen and ristocetin cofactor activity levels, EXTEM A20, FIBTEM A20, and endogenous thrombin potential (ETP) were measured perioperatively. Fibrinogen, platelet count, EXTEM and FIBTEM A20, FXIII, FVIII, VWF levels, and ETP were maintained throughout surgery in both the HFC group (N = 21) and the cryoprecipitate group (N = 23). Seven TEEs were observed in the cryoprecipitate group. The two patients developing deep vein thromboses (DVT) appeared to have a procoagulant status preoperatively, with distinctively higher fibrinogen level, FIBTEM A20, and platelet levels, all of which persisted perioperatively. The five patients developing pulmonary embolism (PE) had slightly higher VWF levels preoperatively, with a disproportionate increase intraoperatively (postcryoprecipitate administration) and postoperatively. Patients treated with HFC versus cryoprecipitate showed broad overlaps in coagulation parameters. Patients with PE experienced a disproportionate VWF rise following cryoprecipitate administration, whereas patients developing DVT displayed a procoagulant status before and following surgery. Preoperative testing may allow these patients to be identified.

Eftrenonacog Alfa: A Review in Haemophilia B.

Eftrenonacog alfa (Alprolix®) is an extended half-life recombinant factor IX (rFIX)-Fc fusion protein (hereafter referred to as rFIXFc). Administered as an intravenous bolus, it is approved for prophylactic use and the treatment of bleeding in patients with haemophilia B in various countries worldwide, including those of the EU, as well as the USA. In multinational, phase III trials, rFIXFc was effective for the prophylaxis, perioperative management or on-demand treatment of bleeding in male patients with severe haemophilia B regardless of age and irrespective of whether or not they had been previously treated with FIX replacement products. Prophylactic efficacy was maintained over the longer term (up to 5years) in previously treated patients. rFIXFc effectiveness in the real-world setting is supported by results of prospective studies, as well as the outcomes of several retrospective trials. rFIXFc was well tolerated in clinical trials in previously treated and untreated children, adolescents and/or adults with severe haemophilia B. Thus, rFIXFc continues to represent a useful treatment option among the haemophilia B patient population.

EE476 Cost-Effectiveness of Emicizumab Prophylaxis in Patients with Hemophilia a without Inhibitors

Emicizumab is a novel monoclonal antibody approved for the prevention and treatment of bleeds in patients with hemophilia A with or without inhibitors. The development of inhibitors, which are neutralizing antibodies to clotting factor replacement therapy, is a major treatment-related complication in hemophilia management. In patients with inhibitors, bleed prophylaxis using emicizumab has been shown to be cost-effective compared to prophylaxis using bypassing agents – with supporting evidence for its reimbursement in this population in Canada.

Perioperative Management of Subdural Hemorrhage (SDH) Trepanation Decompression with Hemophilia A

<p>Hemophilia is a serious inherited blood disease, transmitted by women, that affects mainly men and lasts for a lifetime. Hemophilia A is the most common form. If any of the factors necessary for blood clotting are absent or insufficient, the clotting mechanism is disturbed, causing insatiable bleeding. The most common cause of death in hemophilia patients is cerebral hemorrhage due to head trauma. In cases of intracranial hemorrhage, surgery should be performed immediately to obtain a better prognosis. A 17-year-old man diagnosed with a 2x4 loss of consciousness due to intracranial subdural hemorrhage (SDH) in the left frontotemporoparietal region and cerebral edema on day 4 accompanied by subfalcine herniation to the right with hemophilia A, planned trepanation decompression for SDH evacuation. The patient received 4000 units of factor VIII injection before surgery. Bleeding during surgery was 1100cc and he received a transfusion of 1940cc blood products until hemodynamically stable. In the postoperative phase, he was admitted to the ICU for 8 days, extubation was performed after the condition improved. In patient with hemophilia, evacuation of bleeding should be performed immediately, but there is a high risk of rebleeding. A recombinant factor VIII substitute should be administered immediately for the treatment of acute bleeding in patients with severe haemophilia A. Anesthetic maintenance should include reducing the risk of hypertension and tachycardia to minimize bleeding.</p>

Clinical experience of treatment of hemorrhage in patients, suffering complications of chronic pancreatitis

Clinical experience of treatment of hemorrhage in patients, suffering complications of chronic pancreatitis

Eptacog Beta for Bleeding Treatment and Prevention in Congenital Hemophilia A and B With Inhibitors: A Review of Clinical Data and Implications for Clinical Practice.

To review the pharmacology, dosing and administration, safety, clinical efficacy, and role of eptacog beta in the treatment of congenital hemophilia with inhibitors. A literature search of PubMed (1966 to August 2021) was conducted using the keywords eptacog beta, recombinant FVII, and hemophilia. All relevant published articles and prescribing information on eptacog beta for the treatment of congenital hemophilia with inhibitors were reviewed. Eptacog beta is a novel recombinant activated factor VII (rVIIa) product that demonstrated efficacy in controlling bleeding and associated pain in patients with hemophilia A or B with inhibitors. Eptacog beta has limited Food and Drug Administration-approved and off-label indications compared with other bypassing agents (BPAs; activated prothrombin complex concentrates [aPCC; eptacog alfa]). Eptacog beta costs less than eptacog alfa, but still more than aPCCs. This review provides insight into the role of eptacog beta for treatment of congenital hemophilia with inhibitors and reviews important health system formulary considerations for available BPAs. Eptacog beta is more cost-effective than eptacog alfa and, as such, may become the preferred rVIIa formulary product. However, eptacog alfa availability remains necessary for the treatment of disorders where eptacog beta has limited data. aPCC should remain the first-line BPA for the treatment of bleeding in patients with inhibitors with no contraindications to use because of its equivocal efficacy and safety and in light of the magnitude of cost savings associated with this strategy.

Treatment of bleeding in patients with liver disease

Patients with cirrhosis frequently have complex alterations in their hemostatic system. Although routine diagnostic tests of hemostasis in cirrhosis (platelet count, prothrombin time, fibrinogen level) are suggestive of a bleeding tendency, it is now widely accepted that these tests do not reflect hemostatic competence in this population. Rather, patients with cirrhosis appear to have a rebalanced hemostatic system with hypercoagulable elements. Therefore, routine correction of hemostasis laboratory values, for example by fresh frozen plasma or platelet concentrates, with the aim to avoid spontaneous or procedure‐related bleeding is not indicated as is outlined in recent clinical guidance documents. However, little guidance on how to manage patients with cirrhosis that are actively bleeding is available. Here we present three common bleeding scenarios, variceal bleeding, post‐procedural bleeding and bleeding in a critically ill cirrhosis patient, with specific management suggestions. As patients with cirrhosis generally have adequate hemostatic competence and as bleeding complications may be unrelated to hemostatic failure, prohemostatic therapy is not the first line of management in bleeding patients with cirrhosis, even in the presence of markedly abnormal platelet counts and/or prothrombin times. We provide a rationale for the restrictive approach to prohemostatic therapy in bleeding patients with cirrhosis.

Individually Tailored By-Passing Therapy for the Management of Breakthrough Bleeds in Hemophilia Patients with Inhibitors Receiving Prophylaxis with Emicizumab

Background: Emicizumab is a recombinant, humanized, bispecific, monoclonal antibody that bridges activated factor IX and factor X to restore the function of deficient factor VIII, which is needed for effective hemostasis. Treatment of bleeding in patients with hemophilia A and inhibitors involves by-passing agents such as recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (APCC). These molecules are also used for the management of breakthrough bleeds in patients on prophylaxis with emicizumab. There may be risks in combining two procoagulant drugs. In addition, there is no validated laboratory assay to evaluate the combined effect of emicizumab with a by-passing agent. We have previously reported that thrombin generation assay (TGA) may represent a surrogate marker for monitoring by-passing therapies.Methods: After obtaining informed consent of two patients with severe hemophilia A and high titer of inhibitors included in phase 3 HAVEN 1 trial evaluating emicizumab prophylaxis, TGA was performed to determine in vitro individual response of patients to 5 different dosages of APCC (15 -25 - 45 - 75 - 100 U/kg) and rFVIIa (45 - 90 - 150 -200 - 270 µg/kg), while on emicizumab prophylaxis. Thrombin generation was measured according to the recent recommendations published by the ISTH FVIII/FIX subcommittee.Results: A dose dependent increase of thrombin generation was observed with both by-passing agents, rFVIIa and APCC, in platelet rich- and platelet poor-plasma. However, very low dosages of APCC i.e. 15 to 25 U/kg were sufficient to fully normalize thrombin generation in our two patients.One patient experienced an acute spontaneous arterial bleeding while on prophylaxis regimen with emicizumab 1.5 mg/kg weekly. He had presented a dissection of an aberrant renal artery supplying the inferior pole of the left kidney responsible for a perirenal hematoma of 16x10x7 cm. The patient was suffering from arterial dysplasia, he also had high blood pressure and dyslipidemia. As the individual response of the patient to by passing agents was determined before the bleeding event, he could benefit from personally tailored by-passing therapy with APCC. He had a single “high dose” of 24 U/kg followed by 15 U/kg every 12 hours during 2 weeks and then 15 U/kg every 24 hours during one additional week, for a total treatment duration of 3 weeks. Thrombin generation capacity was 2039 nM.min with APCC 24 U/kg and 1488 nM.min with APCC 15 U/kg. Normal thrombin generation capacity is 1487±372 nM.min (mean±2SD) as determined in 100 healthy volunteers (2). The patient safely recovered with no thrombotic complication during the 3 weeks of APCC treatment. No low molecular weight heparin prophylaxis was prescribed during the treatment with APCC. HAVEN 1 study reported 9% of thrombotic complications in patients who had received multiple infusions of APCC. The coagulation capacity of patients receiving combined emicizumab and by-passing therapy may be very different. This case illustrates that global haemostasis assays may help physician to determine the individual profile of patients with by-passing agents and emicizumab and to tailor their by-passing therapy when treating breakthrough bleeding.Conclusion: The use of an objective laboratory criterion, such as thrombin generation capacity, may be helpful to guide by-passing therapy in patients receiving emicizumab prophylaxis. In vitro spiking experiments, easy to perform, may represent valuable information for the choice of dosages that may effectively achieve haemostasis and not represent a high risk of thrombosis. Thus, individually tailored by-passing therapy may help to limit adverse events that may occur when emicizumab is used in combination with other procoagulant molecules. DisclosuresDargaud:Stago: Honoraria; CSL Behring: Honoraria, Research Funding; BMS: Honoraria, Research Funding; LFB: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Baxalta/Shire: Honoraria, Research Funding; Alnylam: Research Funding; Octapharma: Honoraria, Research Funding; Bayer: Honoraria, Research Funding. Negrier:LFB: Honoraria, Speakers Bureau; Baxalta: Honoraria, Speakers Bureau; Bayer: Honoraria, Research Funding, Speakers Bureau; Baxter: Research Funding; Pfizer: Honoraria, Research Funding, Speakers Bureau; Biogen/SOBI: Honoraria, Research Funding, Speakers Bureau; Octapharma: Honoraria, Research Funding, Speakers Bureau; Novo Nordisk: Honoraria, Research Funding, Speakers Bureau; Inspiration: Research Funding; CSL Behring: Honoraria, Research Funding, Speakers Bureau; Alnylam: Research Funding.

Challenges and Advances in Managing Thrombocytopenic Cancer Patients.

Cancer patients have varying incidence, depth and duration of thrombocytopenia. The mainstay of managing severe chemotherapy-induced thrombocytopenia (CIT) in cancer is the use of platelet transfusions. While prophylactic platelet transfusions reduce the bleeding rate, multiple unmet needs remain, such as high residual rates of bleeding, and anticancer treatment dose reductions/delays. Accordingly, the following promising results in other settings, antifibrinolytic drugs have been evaluated for prevention and treatment of bleeding in patients with hematological malignancies and solid tumors. In addition, Thrombopoeitin receptor agonists have been studied for two major implications in cancer: treatment of severe thrombocytopenia associated with myelodysplastic syndrome and acute myeloid leukemia; primary and secondary prevention of CIT in solid tumors in order to maintain dose density and intensity of anti-cancer treatment. Furthermore, thrombocytopenic cancer patients are often prescribed antithrombotic medication for indications arising prior or post cancer diagnosis. Balancing the bleeding and thrombotic risks in such patients represents a unique clinical challenge. This review focuses upon non-transfusion-based approaches to managing thrombocytopenia and the associated bleeding risk in cancer, and also addresses the management of antithrombotic therapy in thrombocytopenic cancer patients.

Результати застосування анти-VEGF-терапії в лікуванні гемофтальму після вітректомії у хворих з проліферативною діабетичною ретинопатією

Post-vitrectomy vitreous hemorrhage in patients with proliferative diabetic retinopathy (PDR) occurs in up to 75% of cases, and this highlights the need to search for new treatment options. The aim. To analyze the results of anti-VEGF therapy in the treatment of post-vitrectomy vitreous hemorrhage in patients with PDR. Materials and methods. Seventy-eight patients (78 eyes) were examined. Twenty patients (20 eyes) of the control group underwent outpatient fluid gas exchange (OFGE) with 20% gas-air mixture of perfluoropropane for the treatment of post-vitrectomy vitreous hemorrhage. The first main group included 28 patients in whom OFGE with the same mixture was supplemented by the injection of Lucentis at a dose of 0.5 mg into the vitreous cavity. The second main group included 30 patients who achieved Eylea at a dose of 2 mg in addition to the OFGE. Results. Within 2 months, no significant difference between groups in achieving vitreous transparency or in vitreous hemorrhage recurrence rate was found. After 6 months, the frequency of vitreous hemorrhage recurrence in the control group was significantly higher (χ2 = 4.27; p = 0.039) than that in the Lucentis group (9 eyes [45%] vs. 3 eyes [10.7%]). When using Eylea in the same period, the recurrence rate was 6.7% (2 eyes) which is significantly lower than 45% (9 eyes) in the control group (χ2 = 4.59; p = 0.032). Conclusions. The effectiveness of treatment of post-vitrectomy vitreous hemorrhage by OFGE with 20% gas-air mixture of perfluoropropane within 6 months of observation is 85.5%. The use of Lucentis increases the effectiveness to 92.8% with a recurrence rate of 10.7%, and the use of Eylea to 96.6% with a recurrence rate of 6.7%. There are no significant differences between the use of Lucentis and Eylea. Keywords: proliferative diabetic retinopathy, post-vitrectomy vitreous hemorrhage, outpatient fluid gas exchange, Lucentis, Eylea.

Pre-endoscopic intravenous proton pump inhibitors therapy for upper gastrointestinal bleeding: A prospective, multicentre study

Background/AimThe indiscriminate use of high-dose, proton pump inhibitor (PPI) infusion in non-variceal upper gastrointestinal bleeding (UGIB) patients to reduce the rate of peptic ulcers with high-risk stigmata (HRS) has been questioned. We evaluated the prevalence of HRS on peptic ulcer and non-ulcer lesions in patients receiving or not receiving pre-endoscopic PPI therapy. MethodsData of consecutive UGIB patients observed in 50 Italian centres were analysed. The prevalence of both HRS on peptic ulcers and active bleeding on non-ulcer lesions between patients treated or not treated with PPI were compared. Multivariate analysis was performed. ResultsA total of 1,792 (69.8%) out of 2,566 patients received PPI therapy. Prevalence of HRS on ulcers was 51.8% and 53.4% (P = 0.58) in treated and not treated patients, respectively, and the rate of endoscopic therapy did not differ between groups. Prevalence of non-ulcer bleeding lesions was higher in patients treated than in those not treated with PPI (18.7% vs 10.6%; P = 0.023). At multivariate analysis, PPI therapy (OR: 1.16, 95% CI = 0.82–1.64; P = 0.4) was not an independent factor affecting HRS prevalence, which was inversely correlated with timing to endoscopy (OR: 0.85, 95% CI = 0.76–0.95; P = 0.005). ConclusionsOur data failed to detect a significant role of pre-endoscopic PPI therapy in decreasing prevalence of HRS and need for endoscopic treatment in bleeding patients with either peptic ulcer or non-ulcer lesions.

Effects of Tranexamic Acid Prophylaxis on Bleeding Outcomes in Hematologic Malignancy: The a-TREAT Trial

Background: Despite optimal prophylactic platelet (plt) transfusion therapy for severe thrombocytopenia in patients undergoing treatment for hematologic malignancy, WHO Grade 2 or greater bleeding continues to occur at rates of 43% to 70%. Although antifibrinolytic therapy has been shown to reduce bleeding and transfusion needs in patients with inherited bleeding disorders and in multiple surgical settings, evidence in therapy-induced thrombocytopenia in hematologic malignancy is lacking. The American Trial Using Tranexamic Acid (TXA) in Thrombocytopenia (A-TREAT) evaluated the effects of prophylactic TXA as an adjunct to routine transfusion therapy on bleeding and transfusion requirements in a multicenter, double blind placebo controlled randomized clinical trial in patients undergoing treatment for hematologic malignancy. Methods: Adult patients at 3 US academic medical centers with hematologic malignancy undergoing chemotherapy or hematopoietic stem cell transplantation (HSCT) anticipated to have hypoproliferative thrombocytopenia were enrolled between June 15, 2016 and February 4, 2020. Randomization was stratified by site and therapeutic group: Chemotherapy, Allogeneic transplant, or Autologous transplant. Patients received study drug intravenously (1,000mg TXA or saline) or orally (1300mg TXA or placebo) every 8 hours beginning when the plt count was ≤30,000/µL and continued until platelet count recovery >30,000/ul or if a diagnosis of thrombosis was made. Patients were transfused prophylactically for counts of ≤10,000/µL or if indicated in the judgement of the treating physician. Daily assessments for bleeding were made by trained research staff (inpatients) or by self-assessment in a patient diary (outpatients), and by patient interview and chart review. The primary endpoint was the proportion of patients with bleeding of WHO grade 2 or above over 30 days after activation of study drug. A score test based on logistic regression was used, adjusted for study site and therapeutic group and adjusted for sequential monitoring. Multiple imputations were used to account for missing data. Secondary endpoints were number of transfusions and number of days alive without WHO grade 2+ bleeding during the first 30 days post activation of study drug. Results: 3,788 patients were screened and 360 patients consented. 330 patients were activated and evaluable; 327 received at least one dose of study drug. The adjusted odds ratio of grade 2+ bleeding was 0.86 (95% CI: 0.52, 1.38; p-value=0.74). The difference in mean number of transfusions was 0.1 (95% CI: -1.9, 2.0; p-value=0.94), while the average difference in days alive without grade 2+ bleeding was 0.1 (95% CI: -1.4, 1.5; p-value=0.94). No differences in exploratory outcomes were observed. The mean difference in transfusions per thrombocytopenic day was -0.02 (95% CI: -0.09, 0.04; p-value=0.51). The mean difference in RBC transfusions per thrombocytopenic day was 0.03 (95% CI: -0.05, 0.11; p-value=0.43). The average number of days with thrombocytopenia or bleeding was similar across treatment arms (9.2 [SD=6.7] TXA vs. 9.1 [6.2] placebo). The hazard ratio of time to grade 2+ bleeding or death was 0.96 (95% CI: 0.43, 2.16; p-value=0.92). The mean difference in highest grade of bleeding was -0.1 (95% CI: -0.2, 0.1; p-value=0.42). There were no deaths due to bleeding. VOD was observed in 3/164 TXA subjects (1.8%) and 2/163 (1.2%) placebo subjects. An increase in the incidence of central venous line occlusions and the use of tissue plasminogen activator was noted in the TXA arm. (11.0% vs. 19.5% and 25.8% vs. 42.1% for placebo and TXA groups, respectively). Recurrent line occlusion led to permanent discontinuation of drug in 4.9% of TXA and 1.8% of placebo subjects. No increase in any other non-catheter thrombotic events was noted. No patient died from a thrombotic event in 120 days following activation of study drug. Conclusions: Prophylactic TXA has no effect on the incidence of WHO Grade 2+ bleeding when given in addition to routine plt transfusions to severely thrombocytopenic patients undergoing therapy for hematologic malignancy. An increased incidence of line occlusion in the TXA arm was observed but no increase in other types of thrombotic events was detected. Disclosures Gernsheimer: Rigel Corporation: Consultancy, Research Funding; Principia: Research Funding; Sanofi: Consultancy; Vertex: Consultancy; Dova Pharmaceuticals: Consultancy; Cellphire: Consultancy; Novartis: Consultancy; Amgen Corporation: Consultancy, Honoraria. Triulzi:Cerus Corp: Research Funding; Fresenius Kabi: Consultancy. Key:Uniqure: Consultancy; Takeda: Research Funding; Novo Nordisk: Other: Chair of Grants Committee; Grifols: Research Funding. OffLabel Disclosure: Tranexamic Acid is an antifibrinolytic agent approved for treatment of bleeding in patients with hemophilia to reduce the risk of hemorrhage during and following tooth extraction. The oral form is indicated for the treatment of cyclic heavy menstrual bleeding.

Management of portal hypertension severe complications.

Portal hypertension is a clinical syndrome characterized by an increase in the portal pressure gradient, defined as the gradient between the portal vein at the site downstream of the site of obstruction and the inferior vena cava. The most frequent cause of portal hypertension is cirrhosis. In patients with cirrhosis, portal hypertension is the main driver of cirrhosis progression and development of hepatic decompensation (ascites, variceal hemorrhage and hepatic encephalopathy), which defines the transition from compensated to decompensated stage. In decompensated patients, treatments aim at lowering the risk of death by preventing further decompensation and/or development of acute-on-chronic liver failure. Decompensated patients often pose a complex challenge which typically requires a multidisciplinary approach. The aims of the present review were to discuss the current knowledge regarding interventional treatments for patients with portal hypertension complications as well as to highlight useful information to aid hepatologists in their clinical practice. Specifically, we discussed the indications and contraindications of transjugular intra-hepatic portosystemic shunt and for the treatment of gastro-esophageal variceal hemorrhage in patients with decompensated cirrhosis (first section); we reviewed the use of interventional treatments in patients with hepatic vein obstruction (Budd-Chiari Syndrome) and in those with portal vein thrombosis (second section); and we briefly comment on the most frequent applications of selective splenic embolization in patients with and without underlying cirrhosis (third section).

New approach to the risk variables for administration of fibrinogen in patients with postpartum hemorrhage by using cluster analysis

To analyze all the variables in women who received fibrinogen for postpartum hemorrhage (PPH) usinghierarchicalcluster analysis, to provide greater insight into the risk variables involved in these women. This retrospective study of women with at least 500mL of bleeding at birth or during the postpartum period and treated with fibrinogen was conducted at the Department of Obstetrics and Gynecology, Atatürk University School of Medicine from January 2013 to January 2018. Data on the women were obtained from medical records and various risk variables were recorded and analyzed using hierarchical cluster analysis. A total of 114 women with PPH were included in the study. Based on a dendrogram, three main clusters of similar quality variables were created: 1) gravida, parity, age, cervical/vaginal hematoma, laparotomy, hypogastric artery ligation, uterine artery embolization, uterine artery ligation, uterine atony, distance from outer center, lowest hemoglobin, preoperative platelets, endometritis, preoperative white blood cells; 2) lowest fibrinogen, highest fibrinogen, type of birth, placenta invasion anomaly, Bakri balloon tamponade, postpartum hysterectomy, preoperative activated partial thromboplastin time (APTT), preoperative international normalized ratio (INR), placental abruption, in-utero ex fetus; 3) postoperative APTT, postoperative INR, maternal mortality, erythrocyte transfusion, plasma transfusion, hospital stay time, disseminated intravascular coagulation/HELLP syndrome, highest hemoglobin, blood group, postoperative platelets, platelet transfusion, pre-eclampsia/eclampsia, fibrinogen extract. According to the cluster analysis, we should keep fibrinogen extract in the foreground especially in the treatment of hemorrhage in patients with variable conditions. As a result, we can determine whether fibrinogen extract, which has a high economic cost, should be kept at each center. We can also direct which patient will be referred in accordance with the referral steps.

Stability of Turoctocog Alfa, a Recombinant Factor VIII Product, during Continuous Infusion In Vitro.

Objective Turoctocog alfa is a recombinant factor VIII (rFVIII) for the prevention and treatment of bleeding in patients with hemophilia A, including those undergoing surgery and invasive medical procedures. This in vitro study evaluated the physical and chemical stability of turoctocog alfa during continuous infusion (CI) over 24 hours at 30°C. Materials and Methods The study was performed at 30°C ( ± 2°C). A CI system with pump speed set at either 0.6 or 1.5 mL/h was used to evaluate the stability of three turoctocog alfa strengths (500, 1,000, and 3,000 IU), equating to doses of 1.1 to 16.1 IU/h per kilogram of body weight. The following parameters were evaluated at selected time points between 0 and 24 hours: appearance of solution, clarity, pH, potency, purity, content, total high molecular weight proteins (HMWPs), and oxidized rFVIII. Results The mean potency of turoctocog alfa was maintained within the predefined acceptance criteria during CI for both pump speeds with all three strengths at 6, 12, or 24 hours (500 IU: ≥484 IU/vial; 1,000 IU: ≥1,014 IU/vial; and 3,000 IU: ≥3,029 IU/vial). Furthermore, the appearance of solution, clarity, pH, purity, content of turoctocog alfa, total HMWP, and oxidized forms were also within the predefined limits, and comparable to the reference samples (time = 0 hours) for the pump speeds and product strengths assessed. Conclusion Physical and chemical stability of turoctocog alfa was maintained during CI over 24 hours. There was only minor degradation or changes in any of the parameters tested. Potency was within the prespecified acceptance limits throughout 24 hours of infusion. These findings confirm the suitability of turoctocog alfa for CI.

Metabolomics and Proteomics Reveal the Variation of Substances in Apheresis Platelets during Storage and Their Effects on Cancer Cell Proliferation

Introduction: Apheresis platelets (APs) are clinically and crucially important in the prevention and treatment of bleeding in patients with thrombocytopenia or cancer. However, few researchers have addressed the variation of supernatant metabolites and exosome proteins in APs during storage and their effects on cancer cell proliferation. Objective: This study was designed to explore the change rules of the metabolites and exosomal proteins of APs during storage and their effects on cancer cell proliferation. Methods: Metabolomics and proteomics were separately applied to analyze the variation of AP supernatant metabolites and exosomal proteins between freshly prepared day-0 and day-5 terminal-stored APs. Cell counting kit (CCK)-8 assay was performed to detect the effects of AP supernatants and exosomes on the proliferation of cancer cells. Results: We found that the supernatant metabolites and exosomal proteins in APs were significantly different on day 0 and day 5, and that many differential metabolites and exosomal proteins were associated with cancer characteristics. Furthermore, the day-5 AP supernatants had a greater inhibition of the proliferation of K562, HepG2, and HCT116 cancer cells, but the day-5 AP exosomes had no significant effect on the proliferation of these cancer cells. Conclusion: The variant terminal-stored AP supernatants may inhibit the proliferation of cancer cells but the variant terminal AP exosomes have no effect on cancer cell proliferation.

Clinical and immunological features of platelet transfusion refractoriness in young patients with de novo acute myeloid leukemia.

Platelet transfusion is important in the prevention and treatment of bleeding in patients with acute myeloid leukemia (AML) after receiving intensive chemotherapy. However, platelet transfusion refractoriness (PTR) is an intractable clinical issue occurred in these patients. And its clinical and immunological features remain largely unknown. The potential causes and clinical features of PTR were retrospectively analyzed in 560 patients who were diagnosed as de novo AML in Tongji Hospital from June 2012 through June 2018. A high‐throughput antibody screening for the detection of human leukocyte antigen (HLA) and its serotypes was performed in 133 newly diagnosed AML patients. PTR occurred in 11.8% of the de novo AML patients. The median age for patients with PTR was 46 years (range, 15‐70). It frequently manifested in female patients and in patients with splenomegaly, M4 subtype, c‐Kit gene mutation, and rearrangements of RUNX1‐RUNX1T1 or CBFB‐MYH11, commonly referred to as core binding factor AML (CBF‐AML). Notably, CBF‐AML was independently associated with the occurrence of PTR. PTR predominantly developed in patients who had CBF‐AML (P < .001) and in patients who further had better minimal residual disease (MRD) reduction (≥3‐log) before the second consolidation chemotherapy (P = .007). HLA‐I antibodies were detected in the serum of 9.0% of AML patients and markedly enriched in patients with PTR (P < .001) and in patients with CBF‐AML (P = .018). HLA‐B was the most frequently identified serum epitope in PTR patients. Patients with CBF‐AML had higher tendency to develop HLA‐I antibodies and PTR, which depicted novel features of PTR in AML and might provide insights into its efficient managements.

Transcatheter Arterial Embolization in the Treatment of Abdominal Bleeding in Patients Being Treated with Open Abdomen Due to Duodenal Fistula.

This study aimed to investigate the transcatheter arterial embolization (TAE) in treatment of abdominal bleeding in patients being treated with open abdomen due to duodenal fistula. This was a retrospective study performed at our center. From January 2005 to November 2010, all patients with abdominal bleeding were treated with surgical hemostasis (SH) and included in SH group. From January 2012 to December 2018, all patients with a bleeding were treated with TAE and included in the TAE group. Clinical data were reviewed and compared between the two groups. The effect of TAE in the management of abdominal bleeding was evaluated. A total of 131 patients were enrolled, and there were 64 in the SH group and 67 in the TAE group. The success rate of hemostasis was higher in the TAE group (89.55% vs. 73.44%, adjusted OR = 4.065, 95% CI 1.336-12.336, P = 0.013). Moreover, the recognition rate of hemorrhagic vessels in the TAE group was higher (91.04 vs. 51.56; P < 0.001). The re-bleeding occurred in 20 patients, 7(11.67%) in the TAE group and 13(27.66%) in the SH group. The re-bleeding rate in SH group was higher (adjusted HR = 2.564, 95% CI 1.023-6.428, P = 0.045) CONCLUSIONS: TAE is an effective method in treatment of abdominal bleeding in patients being treated with open abdomen due to duodenal fistula.