scholarly journals Management of Major Bleeding Caused By Rivaroxaban and the Use of Desmopressin

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5099-5099
Author(s):  
Ahmad Jajeh
Keyword(s):  
Major Bleeding ◽  
Large Scale ◽  
Conflicts Of Interest ◽  
Factor Xa ◽  
Fresh Frozen Plasma ◽  
Thrombin Time ◽  
Gi Bleeding ◽  
Complex Product ◽  
Packed Red Blood Cells ◽  
Treatment And Prevention

Abstract Rivaroxaban is a new anticoagulant that is substituted for Coumadin on a large scale in the treatment and prevention of Deep Vein Thrombosis DVT and Pulmonary Embolism PE. It is an oral agent that inhibits Factor Xa. The most attractive attribute of this new anticogulant is the lack of monitoring PT/INR. However, out of many cases put on Rivaroxaban a few reports of major and threatening bleed that could be fatal. Particularly, the the GI bleeding. Unfortunately, no set standard antidote or management is available when such catastrophic bleeds happen. This abstract present our experience with three major bleeding cases that presented with massive GI bleeding. Two are associated with peptic ulcer upon Upper GI endoscopy. Two males and one female age 60, 71 (males) and 71 (female). The first two patients were treated with Prothrombin complex product. The female patient presented with sever anemia of 4 grams of Hb with hematemesis and bright red blood per rectum. The Prothrombin complex product was not readly available . She was given multipe doses of Fresh Frozen Plasma FFP and multiple units of packed red blood cells. She was also given a product Profilnine which contains Factor II, IX and VII. Patient's coagulation profile of PTT, PT and Thrombin time were corrected. However, she continue to have bright blood per NG suction. Upon receiving D-DAVP Desmopressin 0.3 micrograms per Kg she stopped bleeding and EGD was done later with sclerosing treatment of gastric ulcer and ligation. Patient was given later a small dose of Prothrombine complex when was available since the last dose of Rivaroxaban was given less than 13 hours from her presentation to the hospital. All of the mentioned patients had prolongation of PT/INR/PTT at presentation. Thrombin time was monitored in all of them. All patients had survived the magor GI bleeding. D-DAVP were given to all of them. In conclusion D-DAVP Desmopressin should be considered as an adjuvant drug in patient presentong with major GI bleeding secondary to Rivaroxaban. Disclosures No relevant conflicts of interest to declare.

Hemostasis with Erythropoietin in Massive, Uncontrollable, Diffuse GI Bleeding.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4082-4082
Author(s):  
Veronica C. Zaharia ◽  
Daniel R. Zaharia
Keyword(s):  
Small Intestine ◽  
Protein S ◽  
Large Cell ◽  
Cell Interaction ◽  
Fresh Frozen Plasma ◽  
Gi Bleeding ◽  
Mesenteric Lymph Nodes ◽  
Packed Red Blood Cells ◽  
Hemostatic Factor ◽  
Uremic Patients

Abstract Purpose: Erythropoietin currently used as a hemopoietic agent, has remarkable hemostatic activity which can be lifesaving in diffuse, uncontrollable bleeding processes. Following is an example case report: Case presentation: 47 y/o male was admitted with massive GI bleeding and a Hemoglobin (Hg) of 6.7 mg/dl requiring transfusion of 26U Packed Red Blood Cells {PRBC) and 9U of Fresh Frozen Plasma (FFP). The work up revealed a large cell lymphoma infiltrating the mesenteric lymph nodes, the retroperitoneum and the spleen. The small intestine was diffusely infiltrated and bleeding. A portion of the small intestine was resected in an attempt to stop the bleeding; still, the bleeding continued and the Hg could not be raised above 7.8. Erythropoietin 20,000U was administered subcutaneously on day 9 to help correct the anemia. An additional 40,000U were administered on day 14 and 21. Three days after the 2nd dose of Erythropoietin the bowel movement did not appear grossly bloody, the Hg stabilized, and chemotherapy could be administered. After discharge with a follow up of 10 months his Hg stabilized at 12–12.5 mg/dl without any bleeding or transfusion. Discussion: Erythropoietin has been shown to shorten the bleeding time in chronic renal failure patients on hemodialysis by improving the platelet/subendotelial cell interaction and by raising the platelet count. An enhanced platelet aggregation in response to Ristocetin was noted in Erythropoietin treated uremic patients. This effect was correlated with a rise in platelet Serotonin. Erythropoietin also has been found to have a procoagulant effect in uremic patients by decreasing the protein C, protein S, antithrombin III level. These observations offer an explanation for the clinically observed hemostatic effect of Erythropoietin. Conclusion: This and other cases have shown that Erythropoietin is a potent hemostatic factor in anemic patients with diffuse uncontrollable bleeding processes, where large amounts of transfused PRBC can barely keep up with the losses and hemostatic procedures can either not be done or failed. As more experience accumulates Erythropoietin may start a second life as a hemostatic factor. Figure Figure

Idarucizumab, a Specific Antidote for Dabigatran, Cross-Reacts with Melagatran and May Also Interact with Other Benzamidine-Containing Compounds

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3836-3836
Author(s):  
Jawed Fareed ◽  
Larissa Reikensmeyer ◽  
Amanda Walborn ◽  
Debra Hoppensteadt ◽  
Jeanine M. Walenga ◽  
...  
Keyword(s):  
Whole Blood ◽  
Conflicts Of Interest ◽  
Dabigatran Etexilate ◽  
Factor Xa ◽  
Cross Reactivity ◽  
Thrombin Time ◽  
Fab Fragment ◽  
Strong Concentration ◽  
Procoagulant Effect ◽  
Us Fda

Abstract Introduction: Dabigatran etexilate is a pro-drug which is used to prevent embolic stroke in patients with atrial fibrillation. This oral anticoagulant is also approved for other indications in Europe. As with all anticoagulants, there is a potential for serious hemorrhage with dabigatran usage which may require antidotes to control bleeding. Idarucizumab is an anti-dabigatran Fab fragment (Boehringer-Ingelheim) that binds to the benzamidine group on dabigatran and inhibits its anti-thrombin activity. Idarucizumab has recently been approved by the US FDA for the control of bleeding associated with dabigatran. Materials and Methods: Such antithrombin agents as argatroban, melagatran, hirudin, and bivalirudin, human antithrombin, thrombomodulin, heparin cofactor II, and heparin-AT complex were commercially obtained. Anti-factor Xa agents (rivaroxaban, apixaban and DX-9065a were also obtained from various sources To test the specificity of the inhibitory effects of idarucizumab, each of these agents were supplemented to whole blood and citrated plasma at concentrations ranging from 0.1 to 100 µg/mL. Idarucizumab was added to each mixture at a concentration of 1 mg/mL and anticoagulant activities were assessed using PT, aPTT, thrombin time and chromogenic anti-IIa/Xa and flurometric thrombin generation assays. Results: Idarucizumab itself did not produce any anticoagulant effects on whole blood or plasma clotting profile. However it showed a slight procoagulant effect in the whole blood and plasma based assays. It produced a strong concentration dependant inhibition of both dabigatran and melagatran. The antibody showed strong specificity for the inhibition of dabigatran amd melagatran and did not affect the anticoagulant and other effects of the other synthetic and natural thrombin and FXa inhibitors. The prolongation of the PT, APTT and thrombin time by melagatran was completely inhibited by idarucizumab. Idarucizumab more effectively inhibited the prolongation of thrombin time by dabigatran than the prolongation induced by melagatran. Discussion: The cross-reactivity of idarucizumab with melagatran may result from the presence of a common benzamidine pharmacophore which is present in both of these anticoagulant agents. Since the benzamidine pharmacophore is present in a number of serine protease inhibitors as well as drugs such as pentamidine, propamidine and dibromopropamidine. These observations suggest that simultaneous administration of idarucizumab may compromise the pharmacodynamics profile of benzamidine derived drugs such as the anti-malarials, anti-psychotic, anti-fungal and other compounds. Thus there is a need for a systemic screening of idarucizumab for its potential interactions with drugs containing benzamidine based therapeutic agents. Disclosures No relevant conflicts of interest to declare.

Lyso-Sulfatide Binds Factor Xa and Potently Inhibits Thrombin Generation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1130-1130
Author(s):  
Subramanian Yegneswaran ◽  
Yajnavalka Banerjee ◽  
Jose A. Fernandez ◽  
Hiroshi Deguchi ◽  
John H. Griffin
Keyword(s):  
Free Amino ◽  
Conflicts Of Interest ◽  
Factor Xa ◽  
Coagulation System ◽  
Amino Group ◽  
Thrombin Time ◽  
Binding Studies ◽  
Binding Interaction ◽  
Dependent Inhibition ◽  
Gla Domain

Abstract Abstract 1130 Although phospholipids are well-recognized for their effects on coagulation reactions, little is generally known about the effects of sphingolipids on clotting pathways. Negatively-charged sulfatides can potently initiate the intrinsic pathway of coagulation system by binding and autoactivating factor (f) XII. Sphingosine potently inhibits the ability of factor Xa (fXa) to generate thrombin (fIIa) in the prothrombinase complex (II-ase) (fXa/fVa/phospholipids) by interacting directly with fXa's Gla domain. Here we report that lyso-sulfatide (lyso-SF) (sulfogalactosyl sphingosine), a lipid of minor abundance in plasma that is primarily in HDL particles, exhibits potent anticoagulant activity. Lyso-SF dose-dependently prolonged clotting in fXa-1-stage but not thrombin-time clotting assays. Lyso-SF inhibited II-ase activity by > 90 % in purified reaction mixtures (fXa/fVa/II) in the presence of 6 or 30 μM phospholipids (PL). However, lyso-SF did not inhibit fIIa generation by fXa/fVa in the absence of PL, suggesting the absolute requirement of PL for lyso-SF-dependent inhibition of fIIa generation. Lyso-SF inhibited fIIa generation by fXa/PL in the absence of fVa. Additionally, lyso-SF inhibited fIIa generation by Gla-domainless (gd)-fXa in the presence but not in the absence of fVa and PL. Lyso-SF-dependent inhibition of fIIa generation was also observed for fXa/fVa/PL when gd-II was used as the substrate instead of II. However, no inhibition by lyso-SF was observed when using gd-fXa/PL and gd-II/PL in the presence or absence of fVa. Lyso-SF had no effect on fXa or fIIa amidolytic activity. These data plus other studies suggested that ≥ two components of the II-ase complex needed to be PL-bound for potent inhibition of fIIa generation by lyso-SF. PL surfaces bind and assemble each the II-ase protein components; however, PL's and lyso-SF may also alter the conformations of fXa, fVa and II. To gain mechanistic insights for lyso-SF inhibition of II-ase activity, Surface Plasmon Resonance (SPR) and fluorescence spectroscopy were used to define molecular interactions. Remarkably, SPR binding studies showed that lyso-SF binds to immobilized fXa (KD = 83 μM) and gd-fXa (KD = 36 μM). Controls using SPR showed no binding of lyso-SF to immobilized fVIIa or fIXa whereas SPR confirmed the ability of fXa, fVIIa and fIXa to bind PL's. Fluorescence binding assays confirmed SPR data showing that lyso-SF bound to and altered the dansyl fluorescence of dansyl-GluGlyArg-labeled fXa (DEGR-fXa) both in the presence (KD = 50 μM) and absence (KD = 75 μM) of PL and that this binding required calcium ions. Thus, lyso-SF binds fXa outside the Gla domain. Fluorescence monitoring of fVa binding to DEGR-fXa in the presence of PL showed that lyso-SF inhibited this binding interaction. To characterize structure-activity relationships for lyso-SF inhibition of II-ase, different analogs of lyso-SF were tested for their ability to inhibit fIIa generation by gd-fXa/fVa/PL. Psychosine (galactosyl sphingosine), glucosyl sphingosine and lyso-sphingomyelin each inhibited fIIa generation showing that the sulfate ester moiety and the sugar group in lyso-SF were not essential for the anticoagulant effects of lyso-SF. However, acetylation of the free amino group in lyso-SF ablated its inhibition of fIIa generation showing that the free amino group on carbon 2 is essential for the inhibitory activity of lyso-SF. In conclusion, these findings show that lyso-SF and several of its analogs are potent anticoagulant lipids and that the mechanism for inhibition of fXa by lyso-SF may involve its binding to fXa at sites outside fXa's Gla domain. This suggests that certain sphingolipids may exert allosteric downregulation of fXa activity without inhibiting the enzyme's active site or the binding of the Gla domain to PL surfaces. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Fibrinogen Replacement Underutilization in ECMO

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-5
Author(s):  
Lisa N Boggio ◽  
Mindy L. Simpson
Keyword(s):  
Life Support ◽  
Conflicts Of Interest ◽  
Extracorporeal Life Support ◽  
Laboratory Data ◽  
Coagulation Factors ◽  
Fresh Frozen Plasma ◽  
Critically Ill Children ◽  
Packed Red Blood Cells ◽  
Therapeutic Anticoagulation ◽  
Thrombotic Complications

Background: Extracorporeal membrane oxygenation (ECMO) is a salvage therapy for critically ill children and adults. Hematologic complications, such as hemorrhage and thrombosis, are the major complications in ECMO. The contact of blood with the tubing of the circuit, lines, blood pump, and oxygenator all contribute to the process. Most patients require anticoagulation while on ECMO. According to the international summary of Extracorporeal Life Support Organization (ELSO) registry in 2017, patients on ECMO consist of 69% neonate and pediatric patients (Neo 44.8%, Peds 24.1%, Adult 31.1%). Contributors to the risk of bleeding include excessive heparin use for systemic anticoagulation, consumption of coagulation factors, low fibrinogen levels, thrombocytopenia, platelet dysfunction, and hyperfibrinolysis, among others. This gives the appearance of a consumptive coagulopathy, the hallmark of which is hypofibrinogenemia. Fibrinogen replacement is most efficiently done with cryoprecipitate (cryo) or fibrinogen concentrate, while fresh frozen plasma (FFP) has a low and variable fibrinogen content. Cryo and FFP may contribute to volume expansion and have other prothrombotic factors which could contribute to thrombotic complications. We performed a retrospective analysis of pediatric and adult patients who presented for ECMO to evaluate management of low fibrinogen and bleeding and thrombotic complications. Methods: Data was reviewed for 11 adult and 12 pediatric consecutive patients who received ECMO prior to June 1st, 2019. Time on ECMO (hours), type of ECMO, indication, presence of bleeding or thrombotic complications during ECMO, and use of therapeutic anticoagulation was collected. Laboratory data included platelet counts, hemoglobin, fibrinogen activity, antithrombin activity, prothrombin time, and partial thromboplastin time. Transfusion data was also collected for amount of packed red blood cells (PRBC), platelets, FFP, and cryo transfused. Data were analyzed to evaluate when fibrinogen was low and if cryo was given. According to our institutional guideline, the fibrinogen activity goal is >100 mg/dL and >200 mg/dL if bleeding. Bleeding and/or clotting complications were also noted. Data: There were 24 runs of ECMO evaluated (11 adults, 12 children), including VA and VV, lasting from 65-1343 hours. One child had 2 runs of ECMO. The majority were VA (13/24; 54%) with 33% (8/24) VV and 13% (3/24) combined VA/VV (all occurred in children). Therapeutic anticoagulation was given in 17/24 (71%) overall, but 92% (12/13) of pediatric cases. Bleeding and/or clotting complicated 17 (71%) runs. Overall, bleeding occurred in 13 (54%) runs and thrombosis in 12 (50%). Of these events, 8 (33%) runs had both bleeding and thrombosis. Bleeding occurred in 8/11 (73%) adults and 5/12 (42%) children. Bleeding and/or thrombus occurred more often with longer ECMO runs, but affected all runs longer than 250 hours (12/24, 50%). While on ECMO, the fibrinogen activity was below 100 mg/dL at some point in 11/24 (46%) of runs. Of those 11, only 6 (55%) received cryo in response to the fibrinogen activity. Cryo was more likely to be given if both a low fibrinogen and bleeding were present. Even with bleeding episodes and fibrinogen activities <200 mg/dL, cryo was not given in the majority of cases (70% adults, 40% children), but FFP was given preferentially. Conclusions: Almost half (45%) of the patients evaluated had low fibrinogen levels at some point while on ECMO. Despite cryoprecipitate being standard replacement at our institution for low fibrinogen, only 55% of those patients received cryo in response to the low level. Therefore, 21% (5/24) of all cases were not specifically treated for their low fibrinogen value. Bleeding and/or thrombotic complications are common with ECMO. Further study to determine if fibrinogen replacement or lack thereof contributes to these complications and guide management of fibrinogen deficiency in ECMO patients is warranted. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals USP Standardized Mixtures of Bovine, Ovine and Porcine Heparin Exhibit Comparable Biologic Effects to Referenced Single Sourced Heparins and May be Interchangeable,

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1067-1067
Author(s):  
Guy Olson ◽  
Walter Jeske ◽  
Omer Iqbal ◽  
Ambar Farooqui ◽  
Fakiha Siddiqui ◽  
...  
Keyword(s):  
Supply Chain ◽  
Conflicts Of Interest ◽  
Factor Xa ◽  
African Swine Fever ◽  
Single Species ◽  
Protamine Sulfate ◽  
Thrombin Time ◽  
Plasma Clot ◽  
Porcine Tissue ◽  
Biologic Effects

Abstract Introduction: Unfractionated heparin (UFH) is the first line anticoagulant for the management of medical indications. UFH complexes with antithrombin to produce strong inhibition of thrombin and factor Xa. The UFHs are standardized using USP compliant amidolytic anti-Xa and IIa methods in defined conditions. Clinically used UFH is solely sourced from porcine mucosal tissue. Because of the shortage of porcine tissue and the African Swine Fever, the supply chain of this anticoagulant is compromised. Thus, there is a need for resourcing of this anticoagulant. Bovine and ovine mucosal sources represent alternate material for production of UFH. Previous studies have shown that bovine and ovine UFH exhibit anticoagulant effects which can be standardized by using the USP method. Additionally, the standardized heparins from various sources can be blended and their potency can be adjusted to exhibit comparable effects as the single sourced UFH. The purpose of this study is to evaluate the pharmacologic profile of the blended heparin and compare these activities to that of the single sourced porcine, ovine and bovine heparins. Methods: Two groups of heparins were evaluated in this study, porcine, ovine, bovine, and the blended heparin in gravimetric measurements (ug/ml) and these same four in potency adjusted measurements (U/ml). The pharmacologic profiles of the heparins in this study were investigated via global anticoagulant assays and anti-protease assays performed in plasma. Clot based assays such as the activated partial thromboplastin time (aPTT) and thrombin time (TT) were used to study the anticoagulant effects of the single source and blended heparins. The amidolytic anti-Xa and IIa assays were used to assess the inhibitory effects of these heparins on these proteases. USP compliant anti-Xa and IIa assays were used to determine potencies of the various heparins. Protamine sulfate (PS) neutralization studies were performed to evaluate the reversal of anticoagulant effects in each of the heparins. Results: The aPTT assay showed that at final concentrations of 5 ug/ml and 2.5 ug/ml porcine heparin significantly (p < .01) prolonged the aPTT compared to ovine, bovine, and blended heparins. When studied with potency adjusted heparins, all heparins demonstrated comparable aPTT values at all concentrations (U/ml). The TT assay showed that porcine and ovine heparins prolonged the TT at 1.25 ug/ml compared to bovine and blended heparins. When studied with potency adjusted heparins, all heparins demonstrated comparable TT values at all concentrations (U/ml). The anti-Xa assay showed that at all final concentrations between 10 ug/ml and 0.625 ug/ml porcine, ovine, and blended heparins produced significantly (p <.001) stronger Xa inhibition than bovine heparin. When studied with potency adjusted heparins, all heparins demonstrated comparable anti-Xa inhibition at all concentrations (U/ml). The anti-IIa assay showed that at final concentrations 2.5 ug/ml, 1.25 ug/ml, and 0.625 ug/ml porcine and ovine heparins produced significantly (p < .05) stronger IIa inhibition than bovine heparin. When studied with potency adjusted heparins, all heparins demonstrated comparable anti-IIa inhibition at all concentrations (U/ml). The USP compliant anti-Xa assay with gravimetric heparins showed potencies of 201, 201, 150, and 184 U for porcine, ovine, bovine, and blended heparins respectively. The USP compliant anti-Xa assay with potency adjusted heparins showed comparable potencies for all four heparins. The USP compliant anti-IIa assay with gravimetric heparins showed potencies of 204, 196, 127, and 167 U for porcine, ovine, bovine, and blended heparins respectively. The USP compliant anti-IIa assay with potency adjusted heparins showed comparable potencies for all four heparins. The protamine sulfate neutralization studies demonstrated complete neutralization at all concentrations for all of the potency adjusted heparins in the aPTT, TT, anti-Xa, and anti-IIa assays. Conclusion: These studies support the hypothesis that a blended heparin product from bovine, ovine, and porcine tissue, when standardized in USP unit-equivalent proportions, exhibits a comparable anticoagulant profile to the single species heparins. These findings suggest that there is a potential for development of blended heparin to stabilize supply chain of this important anticoagulant and warrant clinical validation. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Increasing Doses of Anticoagulation Are Associated with Improved Survival in Hospitalized COVID-19 Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-22
Author(s):  
Filip Ionescu ◽  
Girish B Nair ◽  
Ioana Petrescu ◽  
Anish S Konde ◽  
Markie Sue Zimmer ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Conflicts Of Interest ◽  
Hazard Ratio ◽  
Red Blood Cell Transfusion ◽  
Packed Red Blood Cells ◽  
Risk Of Death ◽  
Hazards Model ◽  
Higher Doses

Background: Hypercoagulability may contribute to COVID-19 pathogenicity. Evidence comparing clinical outcomes among patients with COVID-19 receiving therapeutic compared to prophylactic dose anticoagulation is limited. We evaluated whether therapeutic anticoagulation (tAC) is associated with improved survival compared to prophylactic (pAC) and no anticoagulation (AC) in hospitalized COVID-19 patients. Methods: This was a retrospective, multi-center cohort study of consecutive COVID-19 patients admitted between March 13th, 2020 and May 5th, 2020 to eight hospitals within a large academic system in Southeast Michigan, USA. Participants were assigned to three groups based on whether they received no AC, pAC throughout most of their hospitalization, or at least 3 days of tAC. Major bleeding was defined as transfusion of five or more units of packed red blood cells within 48 hours regardless of hemoglobin level, hemoglobin < 7g/dL and any red blood cell transfusion or a diagnosis code for major bleeding during the hospitalization or radiological evidence of intracranial hemorrhage Results: A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n=642) were treated in the intensive care unit (ICU). 60.9% received pAC (n=2121), 28.7% received at least 3 days of tAC (n=998), and 10.4% (n=361) did not receive AC. Propensity score (PS) weighted Kaplan-Meier plot demonstrated a statistical difference in the 25-day survival probability in the tAC group compared to the pAC group (57.5% vs 50.7%, Figure). In a PS weighted multivariate proportional hazards model adjusting for age, body mass index and ICU status, AC was associated with a reduced risk of death at both prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22-0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05-0.23]) compared to no AC. Major bleeding occurred more frequently among tAC patients (81 [8.1%]) compared to those who received no AC (20 [5.5%]) or pAC (46 [2.2%]). Conclusions : Higher doses of AC are associated with lower mortality in hospitalized COVID-19 patients. The lowest hazard ratio was observed in ICU patients, but risk was also significantly lower in non-ICU hospitalized patients. Bleeding occurred more frequently with higher doses of anticoagulation. Ongoing randomized trials are warranted to prospectively evaluate efficacy and risk of tAC in patients with COVID-19. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Outcome of Conservative Therapy in COVID-19 Patients Presenting with Gastrointestinal Bleeding

2020 ◽  
Author(s):  
Shalimar ◽  
Manas Vaishnav ◽  
Anshuman Elhence ◽  
Ramesh Kumar ◽  
Srikant Mohta ◽  
...  
Keyword(s):  
Management Strategies ◽  
Fresh Frozen Plasma ◽  
Response To Treatment ◽  
Gi Bleeding ◽  
Hypoxemic Respiratory Failure ◽  
Acute Hypoxemic Respiratory Failure ◽  
Packed Red Blood Cells ◽  
Initial Control ◽  
Fresh Frozen

Background/Objective: There is a paucity of data on the management of gastrointestinal (GI) bleeding in patients with COVID-19 amid concerns about the risk of transmission during endoscopic procedures. We aimed to study the outcomes of conservative treatment for GI bleeding in patients with COVID-19. Methods: In this retrospective analysis, 24 of 1342 (1.8%) patients with COVID-19, presenting with GI bleeding from 22 April to 22 July 2020, were included. Results: The mean age of patients was 45.8 (12.7) years; 17 (70.8%) were males; upper GI (UGI) bleeding: lower GI (LGI) 23:1. Twenty-two (91.6%) patients had evidence of cirrhosis- 21 presented with UGI bleeding while one had bleeding from hemorrhoids. Two patients without cirrhosis were presumed to have non-variceal bleeding. The medical therapy for UGI bleeding included vasoconstrictors- somatostatin in 17 (73.9%) and terlipressin in 4 (17.4%) patients. All patients with UGI bleeding received proton pump inhibitors and antibiotics. Packed red blood cells (PRBCs), fresh frozen plasma and platelets were transfused in 14 (60.9%), 3 (13.0%) and 3 (13.0%), respectively. The median PRBCs transfused was 1 (0-3) unit(s). The initial control of UGI bleeding was achieved in all 23 patients and none required an emergency endoscopy. At 5-day follow-up, none rebled or died. Two patients later rebled, one had intermittent bleed due to gastric antral vascular ectasia, while another had rebleed 19 days after discharge. Three (12.5%) cirrhosis patients succumbed to acute hypoxemic respiratory failure during hospital stay. Conclusion: Conservative management strategies including pharmacotherapy, restrictive transfusion strategy, and close hemodynamic monitoring can successfully manage GI bleeding in COVID-19 patients and reduce need for urgent endoscopy. The decision for proceeding with endoscopy should be taken by a multidisciplinary team after consideration of the patient's condition, response to treatment, resources and the risks involved, on a case to case basis.

The Venous Antithrombotic Profile of Naroparcil in the Rabbit

1994 ◽  
Vol 72 (06) ◽  
pp. 874-879 ◽  
Author(s):  
Jean Millet ◽  
Jocelyne Theveniaux ◽  
Neil L Brown
Keyword(s):  
Oral Administration ◽  
Bleeding Time ◽  
Dermatan Sulfate ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Thrombin Time ◽  
Heparin Cofactor Ii ◽  
Antithrombotic Activity ◽  
Thrombin Inhibition ◽  
Maximal Reduction

SummaryThe venous antithrombotic profile of naroparcil or (4-[4-cyanoben-zoyl]-phenyl)-1.5-dithio-β-D-xylopyranoside was investigated in the rabbit following single i. v. and oral administration. Naroparcil attenuated thrombus development in a Wessler stasis model of venous thrombosis (jugular vein) employing bovine factor Xa as a thrombogenic stimulus giving ED50 values of 21.9 mg/kg and 36.0 mg/kg after respectively i. v. and oral administration. Venous antithrombotic activity was maximal 2-3 h after i. v. administration and 4-8 h after oral administration. Four hours after the oral administration of maximal antithrombotic (Wessler model, factor Xa) doses (100 and 400 mg/kg), naroparcil had no significant effect on bleeding time. In platelet poor plasma obtained from animals treated 4 h previously with various doses (25 to 400 mg/kg) of naroparcil, there was no detectable anti-factor Xa nor antithrombin activity. Similarly, naroparcil had no effect on APTT nor on thrombin time. A sensitized thrombin time (to about 35 s) was modestly but significantly increased following oral administration of the compound at 400 mg/kg. However, thrombin generation by the intrinsic pathway was reduced in a dose-related manner, maximal reduction being 65% at 400 mg/kg. The same doses of naroparcil enhanced the formation of thrombin/heparin cofactor II complexes at the expense of thrombin/antithrombin III complexes in plasma incubated with (125I)-human a-thrombin and induced the appearance of dermatan sulfate-like material in the plasma of treated rabbits, as measured by a heparin cofactor II-mediated thrombin inhibition assay. The results suggest that naroparcil could have a safe venous antithrombotic profile following oral administration (antithrombotic effect compared to bleeding risk). It is probable that part of the mechanism of action of the β-D-xyloside, naroparcil, is due to the induction of chondroitin sulfate-like glycosaminoglycan biosynthesis, this material being detectable in the plasma.

The Measurement of Heparin

1973 ◽  
Vol 30 (03) ◽  
pp. 471-479 ◽  
Author(s):  
K. W. E Denson ◽  
John Bonnar
Keyword(s):  
Degradation Products ◽  
Factor Xa ◽  
Assay Method ◽  
Thrombin Time ◽  
Fibrinogen Degradation Products ◽  
Low Levels

SummaryA method for the measurement of heparin utilising the potentiating effect of heparin on the action of anti-factor Xa is described. The effect on the assay of platelet contamination of plasma, the presence of fibrinogen degradation products and low levels of anti-factor Xa have been studied. The assay method has been compared with the calcium thrombin time method and a group of obstetrical patients have been studied using both methods.

Chrono-Pharmacological Study of Once Daily Curative Dose of a Low Molecular Weight Heparin (200IU antiXa/kg of Dalteparin) in Ten Healthy Volunteers

1995 ◽  
Vol 74 (02) ◽  
pp. 660-666 ◽  
Author(s):  
P Mismetti ◽  
J Reynaud ◽  
B Tardy-Poncet ◽  
S Laporte-Simitsidis ◽  
M Scully ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Healthy Volunteers ◽  
Low Molecular Weight Heparin ◽  
Pharmacological Study ◽  
Area Under The Curve ◽  
Factor Xa ◽  
Similar Efficacy ◽  
Low Molecular Weight ◽  
Thrombin Time ◽  
Once Daily

SummaryLow molecular weight heparin (LMWH) is currently prescribed for the treatment of deep vein thrombosis at the dose of 100 IU antiXa/kg twice daily or at a dose of 175 IU antiXa/kg once daily with a similar efficacy. We decided to study the chrono-pharmacology of curative dose of LMWH once daily administrated according to the one previously described with unfractionated heparin (UFH).Ten healthy volunteers participated in an open three-period crossover study according to three 24 h cycles, separated by a wash-out interval lasting 7 days: one control cycle without injection, two cycles with subcutaneous injection of 200 IU antiXa/kg of Dalteparin (Fragmin®) at 8 a.m. or at 8 p.m. Parameters of heparin activity were analysed as maximal values and area under the curve.Activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT) and tissue factor pathway inhibitor (TFPI) were higher after 8 p.m. injection than after 8 a.m. injection (p <0.05) while no chrono-pharmacological variation of anti factor Xa (AXa) activity was observed. Thus the biological anticoagulant effect of 200 IU antiXa/kg of Dalteparin seems to be higher after an evening injection than after a morning injection.A chrono-therapeutic approach with LMWH, as prescribed once daily, deserves further investigation since our results suggest that a preferential injection time may optimise the clinical efficacy of these LMWH.

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