scholarly journals Affimer proteins as a tool to modulate fibrinolysis, stabilize the blood clot, and reduce bleeding complications

Blood ◽  
2019 ◽  
Vol 133 (11) ◽  
pp. 1233-1244 ◽  
Author(s):  
Katherine J. Kearney ◽  
Nikoletta Pechlivani ◽  
Rhodri King ◽  
Christian Tiede ◽  
Fladia Phoenix ◽  
...  
Keyword(s):  
Blood Clot ◽  
Bleeding Risk ◽  
Bleeding Complications ◽  
Clot Lysis ◽  
Binding Studies ◽  
Excessive Bleeding ◽  
Interaction Sites ◽  
Fibrin Networks ◽  
High Bleeding Risk ◽  
Clot Structure

Abstract Bleeding complications secondary to surgery, trauma, or coagulation disorders are important causes of morbidity and mortality. Although fibrin sealants are considered to minimize blood loss, this is not widely adopted because of its high cost and/or risk for infection. We present a novel methodology employing nonantibody fibrinogen-binding proteins, termed Affimers, to stabilize fibrin networks with the potential to control excessive bleeding. Two fibrinogen-specific Affimer proteins, F5 and G2, were identified and characterized for their effects on clot structure/fibrinolysis, using turbidimetric and permeation analyses and confocal and electron microscopy. Binding studies and molecular modeling identified interaction sites, whereas plasmin generation assays determined effects on plasminogen activation. In human plasma, F5 and G2 prolonged clot lysis time from 9.8 ± 1.1 minutes in the absence of Affimers to 172.6 ± 7.4 and more than 180 minutes (P < .0001), respectively, and from 7.6 ± 0.2 to 28.7 ± 5.8 (P < .05) and 149.3 ± 9.7 (P < .0001) minutes in clots made from purified fibrinogen. Prolongation in fibrinolysis was consistent across plasma samples from healthy control patients and individuals at high bleeding risk. F5 and G2 had a differential effect on clot structure and G2 profoundly altered fibrin fiber arrangement, whereas F5 maintained physiological clot structure. Affimer F5 reduced fibrin-dependent plasmin generation and was predicted to bind fibrinogen D fragment close to tissue plasminogen activator (tPA; residues γ312-324) and plasminogen (α148-160) binding sites, thus interfering with tPA–plasminogen interaction and representing 1 potential mechanism for modulation of fibrinolysis. Our Affimer proteins provide a novel methodology for stabilizing fibrin networks with potential future clinical implications to reduce bleeding risk.

scholarly journals Antithrombotic therapy according to baseline bleeding risk in patients with atrial fibrillation undergoing percutaneous coronary intervention: applying the PRECISE-DAPT score in RE-DUAL PCI

2020 ◽  
Author(s):  
Francesco Costa ◽  
Marco Valgimigli ◽  
Philippe Gabriel Steg ◽  
Deepak L Bhatt ◽  
Stefan H Hohnloser ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Antithrombotic Therapy ◽  
Bleeding Risk ◽  
Coronary Intervention ◽  
Bleeding Complications ◽  
Event Analysis ◽  
Increased Risk ◽  
Safety Endpoint ◽  
High Bleeding Risk ◽  
The Impact

Abstract Aims Patients with atrial fibrillation undergoing coronary intervention are at higher bleeding risk due to the concomitant need for oral anticoagulation and antiplatelet therapy. The RE-DUAL PCI trial demonstrated better safety with dual antithrombotic therapy (DAT: dabigatran 110 or 150 mg b.i.d., clopidogrel or ticagrelor) compared to triple antithrombotic therapy (TAT: warfarin, clopidogrel or ticagrelor, and aspirin). We explored the impact of baseline bleeding risk based on the PRECISE-DAPT score for decision-making regarding DAT vs. TAT. Methods and results A score ≥25 points qualified high bleeding risk (HBR). Comparisons were made for the primary safety endpoint International Society of Thrombosis and Haemostasis major or clinically relevant non-major bleeding, and the composite efficacy endpoint of death, thrombo-embolic events, or unplanned revascularization, analysed by time-to-event analysis. PRECISE-DAPT was available in 2336/2725 patients, and 37.9% were HBR. Compared to TAT, DAT with dabigatran 110 mg reduced bleeding risk both in non-HBR [hazard ratio (HR) 0.42, 95% confidence interval (CI) 0.31–0.57] and HBR (HR 0.70, 95% CI 0.52–0.94), with a greater magnitude of benefit among non-HBR (Pint = 0.02). Dual antithrombotic therapy with dabigatran 150 mg vs. TAT reduced bleeding in non-HBR (HR 0.60, 95% CI 0.45–0.80), with a trend toward less benefit in HBR patients (HR 0.92, 95% CI 0.63–1.34; Pint = 0.08). The risk of ischaemic events was similar on DAT with dabigatran (both 110 and 150 mg) vs. TAT in non-HBR and HBR patients (Pint = 0.45 and Pint = 0.56, respectively). Conclusions PRECISE-DAPT score appeared useful to identify AF patients undergoing PCI at further increased risk of bleeding complications and may help clinicians identifying the antithrombotic regimen intensity with the best benefit–risk ratio in an individual patient.

scholarly journals Long-term outcomes in high-bleeding risk patients undergoing PCI for acute coronary syndromes: results from a large single-center pci registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Nicolas ◽  
D Cao ◽  
B Claessen ◽  
S Sartori ◽  
R Chandiramani ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Acute Coronary Syndromes ◽  
Bleeding Risk ◽  
Bleeding Complications ◽  
Major Adverse Cardiovascular Events ◽  
Bleeding Events ◽  
Increased Risk ◽  
Risk Patients ◽  
Coronary Syndromes ◽  
High Bleeding Risk

Abstract Introduction Current clinical guidelines recommend prolonged dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndromes (ACS). However, an extended DAPT duration in high-bleeding risk (HBR) patients amplifies the risk of post procedural complications. Hence, clinicians often face the dilemma of prolonging DAPT duration to prevent recurrent ischaemic events at the expense of increasing the incidence of bleeding in high-risk patients. The actual incidence of ischaemic and bleeding events in this particular population is not well elucidated. Purpose To evaluate one-year ischemic and bleeding outcomes following PCI for ACS in a real-world HBR population as defined by the Academic Research Consortium (ARC) consensus document. Methods We included all patients who presented with ACS to a high-volume single PCI centre from 2012 to 2017 and underwent PCI with 2nd generation drug-eluting stent implantation. Patients were classified as HBR if they met ≥1 major or ≥2 minor criteria according to the recent ARC-HBR consensus. The outcomes of interest were major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction (MI), and target lesion revascularization (TLR), and major bleeding events, including both peri-procedural and post-discharge bleeding. All outcomes were assessed at 1-year follow-up. The Kaplan-Meier method was used for time-to-event analyses. Results Out of 6,097 ACS patients included in this analysis, 2,717 (44.6%) fulfilled the ARC-HBR definition. Compared to non-HBR group, HBR patients were more frequently female, older, more likely to have cardiovascular risk factors (e.g., diabetes, hypertension, and hyperlipidemia) and complex coronary artery disease (e.g., multi-vessel disease, bifurcation lesions, and calcification). The 1-year incidence of MACE was significantly higher in HBR patients (16.3% vs. 8.1%, HR 2.16, 95% CI [1.81–2.59], p<0.001) (Figure 1A). This finding was driven by higher rates of all-cause death and MI (Figure 1B). The 1-year incidence of major bleeding was also significantly higher in HBR patients compared to non-HBR (11.1% vs. 3.1%, HR: 3.92, 95% CI 3.10–4.95; p<0.001). Conclusions HBR patients undergoing PCI for ACS are not only subject to bleeding complications but are also at an increased risk for ischemic events and all-cause mortality. Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals Fibrin(ogen) as a Therapeutic Target: Opportunities and Challenges

2021 ◽  
Vol 22 (13) ◽  
pp. 6916
Author(s):  
Thembaninkosi G. Gaule ◽  
Ramzi A. Ajjan
Keyword(s):  
Therapeutic Target ◽  
Bleeding Risk ◽  
Clot Formation ◽  
Bleeding Events ◽  
Potential Therapeutic Target ◽  
Fibrin Networks ◽  
Blood Clots ◽  
Increasing Risk ◽  
Fibrinolytic Proteins ◽  
Clot Structure

Fibrinogen is one of the key molecular players in haemostasis. Thrombin-mediated release of fibrinopeptides from fibrinogen converts this soluble protein into a network of fibrin fibres that form a building block for blood clots. Thrombin-activated factor XIII further crosslinks the fibrin fibres and incorporates antifibrinolytic proteins into the network, thus stabilising the clot. The conversion of fibrinogen to fibrin also exposes binding sites for fibrinolytic proteins to limit clot formation and avoid unwanted extension of the fibrin fibres. Altered clot structure and/or incorporation of antifibrinolytic proteins into fibrin networks disturbs the delicate equilibrium between clot formation and lysis, resulting in either unstable clots (predisposing to bleeding events) or persistent clots that are resistant to lysis (increasing risk of thrombosis). In this review, we discuss the factors responsible for alterations in fibrin(ogen) that can modulate clot stability, in turn predisposing to abnormal haemostasis. We also explore the mechanistic pathways that may allow the use of fibrinogen as a potential therapeutic target to treat vascular thrombosis or bleeding disorders. Better understanding of fibrinogen function will help to devise future effective and safe therapies to modulate thrombosis and bleeding risk, while maintaining the fine balance between clot formation and lysis.

scholarly journals Factor XIII Deficiency in Patients with Acute Leukemia: One out of Three Is Presenting with Deficiency

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1528-1528 ◽  
Author(s):  
Elisabetta Vagge ◽  
Christian Dornes ◽  
Maisun Abu Samra ◽  
Wolfgang Blau ◽  
Mathias J Rummel ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Intracranial Hemorrhage ◽  
Factor Xiii ◽  
Bleeding Risk ◽  
Bleeding Complications ◽  
Invasive Procedures ◽  
Risk Of Bleeding ◽  
Median Level ◽  
High Bleeding Risk ◽  
Fxiii Deficiency

Abstract Introduction: Factor XIII (FXIII) is a coagulation factor, playing an important role in the coagulation process by keeping the hemostatic clot and allowing tissue repair. The incidence of FXIII deficiency in acute leukemia is not well characterized. FXIII deficiency is known to have a high bleeding risk and cannot be detected by lab evaluation of aPTT and/or INR levels. In combination with thrombocytopenia in patients (pts) presenting with acute leukemia, FXIII deficiency increases bleeding risk (for example in invasive procedures or for intracranial hemorrhage). In 2013 a study was conducted in 9 pediatric pts (6 acute leukemias, 1 burkitt, and 2 solid tumors) in whom FXIII deficiency was found. These pts had bleeding complications that were resolved by FXIII concentrate substitution (Wiegering. V. et al. Haematologica, June, 10, 2013).Patients affected from AML and ALL could easily be screened at diagnosis regarding FXIII level. In the setting of newly diagnosed acute leukemia pts in whom thrombocytopenia is frequently occurring, a preemptive substitution of FXIII could be considered in order to reduce the risk of bleeding complications. Methods: In this retrospective analysis (Jan. 2009 to June 2014) we identified a total of 103 ptspresentingwithnewly diagnosed acute leukemia in whom we assessed FXIII level. In 95 pts FXIII level was available at initial diagnosis of acute leukemia and during treatment. Substitution of FXIII concentrate have been used in case of factor’s deficiency below 70% (normal range 70%-130%). Results: Patients presented withAML (64 primary AML and 20 secondary AML), or ALL (10), or 1 AUL. Median age was 67 years (range: 25-95). Thirty-four pts (35.8%) were younger than 60 years, 61 pts (64.2 %) were older than 60 years. FXIII deficiency was found in 35/95 pts (36.8%) with a median level of 49% (range: 21%-68%). Of those 35 pts with FXIII deficiency 33 had AML (1 AML M0, 9 AML M1, 2 AML M1/2, 5 AML M2, 6 AML M4, 5 AML M5). All pts (5/95) with AML M3 showed a deficiency with a median level of 28%. A level below 70% could be found in 7 out of 13 FLT3-ITD positive pts (53.8%) and in 7 out of 24 NPM1 positive pts (29.2 %). Median FXIII level was 34% for FLT3-ITD positive pts, respectively 30% for NPM1. FXIII substitution in deficient pts was well tolerated and effective. No patient showed intracranial hemorrhage. In addition, invasive procedures like bone marrow biopsy and central line insertion were possible without clinically relevant bleeding complications. In responding pts achieving remission following chemotherapy, a trend towards higher concentration of factor XIII during treatment was observed. Conclusions: Patients affected by AML or ALL are presenting usually with thrombocytopenia and have a high bleeding risk. In case of FXIII deficiency, risk of bleeding is increased potentially leading to a higher leukemia-related morbidity and mortality. Detection of FXIII deficiency is an established method and routinely available. Substitution of FXIII decreases the risk of bleeding and can reduce leukemia associated morbidity and mortality. In our study FXIII deficiency occurred in more than a third of our pts, including all AML M3 patients. We found a trend for more FXIII deficiency in FLT3-ITD high risk group patients. We suggest screening at diagnosis and during treatment of all acute leukemia pts and FXIII substitution in case of deficiency. To evaluate further the role of FXIII assessment and substitution in case of FXIII deficiency in acute leukemia, a prospective trial should be considered. Disclosures No relevant conflicts of interest to declare.

The Interactions of Fibrin and Endothelial Cells within a Fibrin Clot

1997 ◽  
Vol 3 (S2) ◽  
pp. 233-234
Author(s):  
W. G. Jerome ◽  
R.R. Hantgan ◽  
S. Handt
Keyword(s):  
Endothelial Cells ◽  
Blood Clot ◽  
Direct Interaction ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Heart Attacks ◽  
Microscopic Studies ◽  
Life Threatening ◽  
Inhibitory Molecules ◽  
Clot Structure

A life threatening blood clot is the major cause of heart attacks. Thrombolytic therapy attempts to restore blood flow by activating the body's own fibrinolytic system at the site of the occlusive thrombus. However, for unknown reasons, therapy is unsuccessful in greater than 20% of patients. We have previously shown that the endothelial cells lining the wall of the vessel can play a substantial role in inhibiting clot lysis. This is due chiefly to the secretion of inhibitory molecules by endothelial cells. However, endothelial cells also have receptors for fibrin and little is known about how the direct interaction of fibrin with cells may influence lysis. To investigate this we have undertaken a series of microscopic studies to analyse the influence of endothelial cells on clot structure. We report here that endothelial cells can organize clot fibers into tight assemblies. We also show that, at least in culture, fibrin can act in concert with antithrombotic molecules to dramatically affect endothelial structure

The Use of a Surgical Patch Coated With Human Coagulation Factors in Surgical Routine: A Multicenter Postauthorization Surveillance

2006 ◽  
Vol 12 (4) ◽  
pp. 445-450 ◽  
Author(s):  
Sylvia Haas
Keyword(s):  
Vascular System ◽  
Clinical Importance ◽  
Cost Savings ◽  
Bleeding Risk ◽  
Coagulation Factors ◽  
Bleeding Complications ◽  
Lower Probability ◽  
Blood Component ◽  
Excessive Bleeding ◽  
Surgical Interventions

Local hemostyptic agents are of great value to significantly reduce bleeding complications and various devices have become available for clinical use. The aim of this multicenter postauthorization surveillance was to study the surgeons’ expectations regarding efficacy and safety of the surgical patch coated with human coagulation factors (TachoSil) under routine clinical conditions. A total of 408 patients had been included in this trial and the patients had to have an expected increased bleeding risk either due to patient related hemorrhagic risk factors or operations associated with an expected increase of bleeding complications. The main types of surgical interventions were operations on the liver (26%), vascular system (16%), gastrointestinal tract (10%), heart (8%), kidney (7%), thorax (7%), spleen (4%), and pancreas (4%). Other operations (18%) were reported in the fields of neurosurgery, urology, gynecology, dermatology, and on the thyroid gland. Based on subjective assessments the results have shown that TachoSil has met the surgeons’ expectations to be efficacious and safe as a hemostatic treatment in a broad variety of surgical interventions. The observed benefits far exceed the frequencies of complications and many of the observed benefits easily translate into cost savings. In almost 50% of the cases the surgeons thought that the use of the topical hemostat TachoSil may have led to savings in blood component therapy. The savings of intra- and postoperative transfusions may lead to less frequent transfusion-related adverse effects and the lower probability of postoperative complications is of clinical importance. In particular, it is worth mentioning that based on the surgeons’ assessment, the use of TachoSil may have helped to save the organ in 17% of the cases. Thus, these clinically relevant benefits may offer opportunities for improvements of hemostasis in patients at risk for bleeding complications and may facilitate the management of excessive bleeding.

A Unique Recombinant Plasmin Molecule Lacking Kringles 2-5 Possesses Equivalent Hemostatic Safety as Full-Length Human Plasmin.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2028-2028
Author(s):  
Victor J. Marder ◽  
Valery Novokhatny ◽  
Steve Manyak ◽  
Theresa Gruber ◽  
Jennifer Hunt ◽  
...  
Keyword(s):  
Animal Model ◽  
Factor Viii ◽  
Blood Clot ◽  
Plasma Concentrations ◽  
Full Length ◽  
Bleeding Complications ◽  
Clot Lysis ◽  
Serine Protease Domain ◽  
Pre Treatment

Abstract Background: All thrombolytic agents in current clinical use are plasminogen activators (PA). While effective, PA have a downside because of unavoidable and potentially lifethreatening bleeding complications in vulnerable patients. We previously demonstrated a striking margin of hemostatic safety for the “direct-acting” thrombolytic enzyme, plasmin. Now, a novel recombinant derivative of plasmin has been synthesized which lacks kringles 2-5, consisting only of kringle 1 linked to the serine protease domain. Methods: We evaluated escalating dosages of recombinant D (K2-K5) plasmin in a randomized and blinded manner in comparison with molar equivalent dosages of full-length plasmin in an animal model of fibrinolytic hemorrhage. Hemostatic safety was measured by primary bleeding time (PBT) and plasma concentrations of a-2 antiplasmin, factor VIII and fibrinogen. Results: A dose-related nadir in a-2 antiplasmin, factor VIII and fibrinogen followed administration of 4, 6, 8 and 10 mg/kg of D (K2-K5) plasmin, with residual fibrinogen of 65%, 40%, 30% and 0% of initial pre-treatment concentrations. Hemostasis was undisturbed with 4 mg/kg of D (K2-K5) plasmin (mean PBT 2.2 +/- 0.7 min), minimally so at the 6 or 8 mg/kg dosages (5 +/- 2.9 and 4.4 +/- 2.2 min). Hemostasis was markedly abnormal at the purposefully toxic 10 mg/kg dose (12.8 +/- 18.8 min), in association with complete depletion of plasma fibrinogen. Comparison of agents at 10 mg/kg showed no difference, but at 4 mg/kg (2-4-fold more than needed for efficacy), D (K2-K5) plasmin showed slightly less prolongation of PBT (2.2 +/- 0.7 vs 3.3 +/- 2.1 min). Both agents were equally potent for in vitro whole blood clot lysis, indicating that the safety advantage of D (K2-K5) plasmin was not due to decreased fibrinolytic activity. Conclusions: Recombinant D (K2-K5) plasmin has equivalent hemostatic safety as full-length plasmin in an animal model of fibrinolytic hemorrhage and warrants evaluation in clinical thrombotic disease.

Heparin-Free Hemodialysis with Prophylactic Change of Dialyser and Blood Lines

1988 ◽  
Vol 11 (4) ◽  
pp. 255-258 ◽  
Author(s):  
L. Preuschof ◽  
F. Keller ◽  
J. Seemann ◽  
G. Offermann
Keyword(s):  
Blood Flow ◽  
Bleeding Risk ◽  
Practical Method ◽  
Bleeding Complications ◽  
Major Surgery ◽  
Severe Bleeding ◽  
Total System ◽  
Bleeding Disorders ◽  
Clotting Time ◽  
High Bleeding Risk

Heparinization during hemodialysis may cause severe bleeding complications in patients with high bleeding risk. Heparin-free hemodialyses (n=208) were performed in 46 unselected patients with high bleeding risk after kidney transplantation (n=25), after major surgery (n=10), and with bleeding disorders (n=11). Dialyser and blood lines were primed without heparin. In addition to the established measures (high blood flow, intermittent rinsing), system clotting was prevented by prophylactically changing the dialyser and blood lines in 107 of 208 dialyses (52 percent). Total system clotting with blood loss ranging from 100 to 250 ml occurred in six cases (3 percent). Mean hemodialysis time (± SD) was 4.1 hours (± 0.4), rising volume of the extracorporeal system 1.4 liters/hour (± 0.6), blood flow 244 ml/min (± 38), clotting time 12 min (+ 4), and weight loss 2.5 kg (± 1.5). Mean hemodialysis creatinine clearance was 110 ml/min (± 34) and BUN clearance 138 ml/min (± 48). Heparin-free hemodialysis with prophylactic change of system is thus a safe and practical method of treatment for patients at high bleeding risk, but it is less effective, more expensive and the patient requires closer care.

Effect of Tranexamic Acid on Coagulation and Fibrin Clot Properties in Children Undergoing Craniofacial Surgery

2020 ◽  
Vol 120 (03) ◽  
pp. 392-399 ◽  
Author(s):  
Christian Fenger-Eriksen ◽  
Alexander D'Amore Lindholm ◽  
Lisbeth Krogh ◽  
Tobias Hell ◽  
Martin Berger ◽  
...  
Keyword(s):  
Data Analysis ◽  
Blood Loss ◽  
Tranexamic Acid ◽  
Thrombin Generation ◽  
Blood Clot ◽  
Fibrin Clot ◽  
Clot Formation ◽  
Clot Lysis ◽  
Clot Strength ◽  
Clot Structure

Abstract Objective Craniosynostosis surgery in small children is very often associated with a high blood loss. Tranexamic acid (TXA) reduces blood loss during this procedure, although the potential underlying coagulopathy in these children is not known in detail. Objective was to determine the nature of any coagulopathy found during and after craniosynostosis surgery and to characterize the effect of TXA on fibrin clot formation, clot strength, and fibrinolysis. Materials and Methods Thirty children received either TXA (bolus dose of 10 mg/kg followed by 8 hours continuous infusion of 3 mg/kg/h) or placebo. Dynamic whole blood clot formation assessed by thromboelastometry, platelet count, dynamic thrombin generation/thrombin-antithrombin, clot lysis assay, and fibrinogen/factor XIII (FXIII) levels were measured. Additionally, clot structure was investigated by real-time live confocal microscopy and topical data analysis. Results Increased ability of thrombin generation was observed together with a tendency toward shortened activated partial thromboplastin time and clotting time. Postoperative maximum clot firmness was higher among children receiving TXA. FXIII decreased significantly during surgery in both groups.Resistance toward tissue plasminogen activator-induced fibrinolysis was higher in children that received TXA, as evidenced by topical data analysis and by a significant longer lysis time. Fibrinogen levels were higher in the TXA group at 24 hours. Conclusion A significant coagulopathy mainly characterized by changes in clot stability and not parameters of thrombin generation was reported. Tranexamic acid improved clot strength and reduced fibrinolysis, thereby avoiding reduction in fibrinogen levels.

scholarly journals Periprocedural Interruption of Anticoagulation in Patients with Cancer-Associated VTE: An Analysis of Thrombotic and Bleeding Outcomes

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1235-1235
Author(s):  
Joseph R. Shaw ◽  
James Douketis ◽  
Gregoire Le Gal ◽  
Marc Carrier
Keyword(s):  
Major Bleeding ◽  
Patient Population ◽  
Research Funding ◽  
Bleeding Risk ◽  
Advisory Board ◽  
Bleeding Complications ◽  
Invasive Procedures ◽  
Patients With Cancer ◽  
High Bleeding Risk ◽  
Active Cancer

Abstract Background: Approximately 10-20% of patients with venous thromboembolic events (VTE) have underlying malignancy. VTE is considered the second leading cause of death in patients with cancer, and patients with cancer-associated VTE are at higher risk of anticoagulant-related bleeding. Although patients with cancer often undergo diagnostic or therapeutic invasive procedures, there is a paucity of data on adverse outcomes following the periprocedural interruption of anticoagulation in this patient population. Methods: We did a single-center, retrospective chart review of consecutive patients with cancer-associated VTE who had periprocedural interruption of anticoagulation for invasive procedures between November 2015 and March 2018. Perioperative interruption of warfarin/low-molecular-weight heparin was done as per CHEST guidelines (Douketis et al. Chest 141(2 Suppl). Heparin bridging anticoagulation was used only for patients with recent (< 3 months) VTE. Perioperative interruption of direct oral anticoagulants (DOACs) was done as per Thrombosis Canada guidelines, with anticoagulation held for 3 half-lives prior to low bleeding risk procedures and 5 half-lives for high bleeding risk procedures. Active cancer was defined as per the HOKUSAI VTE CANCER trial (Raskob et al. NEJM 378(7)). Primary outcomes were 30-day post-operative rates of VTE and major bleeding. Secondary outcomes were 30-day post-operative rates of clinically relevant non-major bleeding (CRNMB) and mortality. Major bleeding and CRNMB were defined according to ISTH definitions. Data are reported on a per-interruption basis. Herein, we present an interim analysis of results. Results: To date, 82 perioperative interruptions are included, of whom 69.5% were receiving a DOAC. Mean age of the cohort was 65.8 years, 62.2% were male, 92.6% had active cancer and 41.5% had metastatic cancer. Thrombocytopenia (platelet count < 100 x 106/L) was present in 12.2% of interruptions. Procedures were stratified as high bleeding risk in 65.9% of cases. The 30-day rates of thromboembolism and major bleeding were both 3.70 % (95% confidence interval [CI] 1.25 to 10.2%), as was the 30-day rate of CRNMB. There were no deaths during the 30-day follow-up period. Conclusions: The periprocedural interruption of anticoagulation in patients with cancer-associated VTE appears to be associated with high rates of post-operative thrombotic and bleeding complications. Prospective studies are required to better quantify the risks of periprocedural anticoagulation interruption in this patient population. Disclosures Shaw: Portola Pharmaceuticals: Research Funding. Douketis:BMS: Other: Advisory Board; Janssen: Consultancy; Bayer: Other: Advisory Board; Pfizer: Other: Advisory Board; Daiichi-Sankyo: Other: Advisory Board; Portola: Other: Advisory Board; Astra-Zeneca: Other: Advisory Board; Sanofi: Consultancy, Other: Advisory Board; Biotie: Other: Advisory Board; Boehringer-Ingelheim: Consultancy, Other: Advisory Board, Research Funding; The Medicines Company: Other: Advisory Board. Carrier:Pfizer: Honoraria; Bayer: Honoraria; BMS: Honoraria, Research Funding; Leo Pharma: Research Funding.

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