Corrigendum for: Early Uterine Transplant Graft Loss Due to Thrombosis: Single-Center Experience With Causes, Prevention, Diagnosis, and Treatment.

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Management of Extracorporeal Membrane Oxygenation Anticoagulation in the Perioperative Period: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To derive systematic review-informed, modified Delphi consensus regarding the management of children on extracorporeal membrane oxygenation (ECMO) undergoing invasive procedures or interventions developed by the Pediatric Anticoagulation on ECMO CollaborativE (PEACE) Consensus Conference. DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. STUDY SELECTION: ECMO anticoagulation and hemostasis management in the perioperative period and during procedures. DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. Seventeen references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. DATA SYNTHESIS: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. Four good practice statements, 7 recommendations, and 18 consensus statements are presented. CONCLUSIONS: Although agreement among experts was strong, important future research is required in this population for evidence-informed recommendations.

Management of Bleeding and Thrombotic Complications During Pediatric Extracorporeal Membrane Oxygenation: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To derive systematic-review informed, modified Delphi consensus regarding the management of bleeding and thrombotic complications during pediatric extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE Consensus Conference. DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. STUDY SELECTION: The management of bleeding and thrombotic complications of ECMO. DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Twelve references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. DATA SYNTHESIS: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. Two good practice statements, 5 weak recommendations, and 18 consensus statements are presented. CONCLUSIONS: Although bleeding and thrombotic complications during pediatric ECMO remain common, limited definitive data exist to support an evidence-based approach to treating these complications. Research is needed to improve hemostatic management of children supported with ECMO.

Antiplatelet effects of hydroxychloroquine in patients with systemic lupus erythematosus evaluated by the total thrombus-formation analysis system (T-TAS).

OBJECTIVES: Hydroxychloroquine (HCQ) has been shown to reduce thrombotic events in patients with SLE. However, the antiplatelet effects of HCQ are only supported by the platelet aggregation assay, which is a non-physiological test. The total thrombus-formation analysis system (T-TAS) is a microchip-based flow chamber system that mimics physiological conditions and allows for the quantitative analysis of thrombogenicity. The present study investigated the antiplatelet effects of HCQ using T-TAS. METHODS: This was a single-centre cross-sectional study on 57 patients with SLE. We measured the area under the pressure curve for 10 min (PL-AUC10) and the time to 10 kPa (T10) in patients with SLE using T-TAS and examined their relationships with the use of HCQ. PL-AUC10 and platelet aggregation were also measured at several HCQ concentrations using blood samples from healthy donors. RESULTS: PL-AUC10 was significantly lower in the HCQ/real body weight (RBW) ≥5 mg/kg group than in the <5 mg/kg group, while T10 was similar, indicating that HCQ inhibited overall thrombus formation rather than the initiation of thrombus formation. The antiplatelet effects of HCQ were initially detected at HCQ/RBW of approximately 4 mg/kg and reached a plateau at around 5.5 mg/kg. The administration of HCQ/RBW >4.6 mg/kg clearly exerted antiplatelet effects. Additionally, HCQ inhibited thrombus formation in T-TAS and the platelet aggregation response to epinephrine in a dose-dependent manner. CONCLUSIONS: We demonstrated the antiplatelet effects of HCQ under conditions simulating the physiological environment by using T-TAS and identified the range of doses at which HCQ exerted antiplatelet effects.

Antiplatelet and Antithrombotic Properties of Compound L-36, a 6H-1,3,4-Thiadiazine Derivative.

Compound L-36, a new derivative of 6H-1,3,4-thiadiazine, was studied in in vitro and in vivo experiments. This compound exhibits high antiplatelet and antithrombogenic activity. In in vitro experiments, compound L-36 by its antiplatelet activity (by IC50) was superior to acetylsalicylic acid by 9.4 times. In in vivo experiments, compound L-36 by its ED50 value was close to the comparison drug. On the model of pulmonary artery thrombosis, compound L-36 ensured better survival of experimental animals than acetylsalicylic acid. Morphological studies showed that compound L-36 effectively attenuated the thrombosis processes in the pulmonary tissue induced by intravenous injection of a thrombogenic mixture (epinephrine and collagen).

Preventing adverse events during paediatric cancer treatment: protocol for a multi-site hybrid randomised controlled trial of catheter lock solutions (the CLOCK trial).

INTRODUCTION: Central venous access devices (CVADs) are commonly used for the treatment of paediatric cancer patients. Catheter locking is a routine intervention that prevents CVAD-associated adverse events, such as infection, occlusion and thrombosis. While laboratory and clinical data are promising, tetra-EDTA (T-EDTA) has yet to be rigorously evaluated or introduced in cancer care as a catheter lock. METHODS AND ANALYSIS: This is a protocol for a two-arm, superiority type 1 hybrid effectiveness-implementation randomised controlled trial conducted at seven hospitals across Australia and New Zealand. Randomisation will be in a 3:2 ratio between the saline (heparinised saline and normal saline) and T-EDTA groups, with randomly varied blocks of size 10 or 20 and stratification by (1) healthcare facility; (2) CVAD type and (3) duration of dwell since insertion. Within the saline group, there will be a random allocation between normal and heparin saline. Participants can be re-recruited and randomised on insertion of a new CVAD. Primary outcome for effectiveness will be a composite of CVAD-associated bloodstream infections (CABSI), CVAD-associated thrombosis or CVAD occlusion during CVAD dwell or at removal. Secondary outcomes will include CABSI, CVAD-associated-thrombosis, CVAD failure, incidental asymptomatic CVAD-associated-thrombosis, other adverse events, health-related quality of life, healthcare costs and mortality. To achieve 90% power (alpha=0.05) for the primary outcome, data from 720 recruitments are required. A mixed-methods approach will be employed to explore implementation contexts from the perspective of clinicians and healthcare purchasers. ETHICS AND DISSEMINATION: Ethics approval has been provided by Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC) (HREC/22/QCHQ/81744) and the University of Queensland HREC (2022/HE000196) with subsequent governance approval at all sites. Informed consent is required from the substitute decision-maker or legal guardian prior to participation. In addition, consent may also be obtained from mature minors, depending on the legislative requirements of the study site. The primary trial and substudies will be written by the investigators and published in peer-reviewed journals. The findings will also be disseminated through local health and clinical trial networks by investigators and presented at conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000499785.

Stent coating containing a charged silane coupling agent that regulates protein adsorption to confer antithrombotic and cell-adhesion properties.

The evolution of endovascular therapies, particularly in the field of intracranial aneurysm treatment, has been truly remarkable and is characterized by the development of various stents. However, ischemic complications related to thrombosis or downstream emboli pose a challenge for the broader clinical application of such stents. Despite advancements in surface modification technologies, an ideal coating that fulfills all the desired requirements, including anti-thrombogenicity and swift endothelialization, has not been available. To address these issues, we investigated a new coating comprising 3-aminopropyltriethoxysilane (APTES) with both anti-thrombogenic and cell-adhesion properties. We assessed the anti-thrombogenic property of the coating using an in vitro blood loop model by evaluating the platelet count and the level of the thrombin-antithrombin (TAT) complex, and investigating thrombus formation on the surface using scanning electron microscopy (SEM). We then assessed endothelial cell adhesion on the metal surfaces. In vitro blood tests revealed that, compared to a bare stent, the coating significantly inhibited platelet reduction and thrombus formation; more human serum albumin spontaneously adhered to the coated surface to block thrombogenic activation in the blood. Cell adhesion tests also indicated a significant increase in the number of cells adhering to the APTES-coated surfaces compared to the numbers adhering to either the bare stent or the stent coated with an anti-fouling phospholipid polymer. Finally, we performed an in vivo safety test by implanting coated stents into the internal thoracic arteries and ascending pharyngeal arteries of minipigs, and subsequently assessing the health status and vessel patency of the arteries by angiography over the course of 1 week. We found that there were no adverse effects on the pigs and the vascular lumens of their vessels were well maintained in the group with APTES-coated stents. Therefore, our new coating exhibited both high anti-thrombogenicity and cell-adhesion properties, which fulfill the requirements of an implantable stent.

Early Online.

BACKGROUND: Long-haul flights have been associated with a two- to four-fold increased risk of aviation-related thrombosis (ART). Several studies have investigated the extent to which hypoxic hypobaric exposure, dehydration and prolonged immobilisation during air travel induce changes in haemostasis. OBJECTIVE: To investigate the role of high altitude as a risk factor for ART. METHODS: Healthy volunteers aged ≥18 years (N=40), without risk factors for venous thromboembolism, were exposed to an exacerbated altitude of 18 000 feet (5 486 m) for 1 hour. During the flight, the oxygen (O2) levels of the participants, who received supplemental O2, were measured by pulse oximetry and maintained at >92%. Venous blood and urine samples were collected prior to departure and immediately after flying in an unpressurised twin-engine airplane. D-dimer levels, thromboelastography (TEG) parameters, von Willebrand factor (VWF) activity and urine osmolality were measured. RESULTS: The participants were 19 men and 21 women, with a mean (standard deviation) age of 46 (14) years. A significant difference in D-dimer levels, VWF activity, urine osmolality and TEG parameters (reaction (R) time, kinetic (K) time and maximum amplitude (MA)) before and after the 1-hour flight was observed (p<0.001). Urine osmolality correlated positively with VWF activity levels (r=0.469; p<0.002). CONCLUSION: Air travel at high altitude induced a hypercoagulable state in healthy volunteers. Future research should focus on whether thromboprophylaxis can significantly obviate the activation of coagulation in response to high altitude.

A Randomized, Controlled Trial of Continuous Heparin Infusion to Prevent Asymptomatic Catheter-related Thrombosis at Discharge in Infants After Cardiac Surgery: The CHIP-CRT Trial.

OBJECTIVES: There are conflicting results in preventing catheter-related thrombosis (CRT). Continuing infusion of unfractionated heparin (UFH) was a potential option for CRT. This study was to determine the effect of continuous UFH infusion on asymptomatic CRT at discharge in infants after cardiac surgery. STUDY DESIGN: This study was a randomized, placebo-controlled, clinical trial at a single center. All infants with central venous catheters after cardiac surgery, below 3 months of age, were eligible. Stratified by CRT, infants were randomly assigned to the UFH group or the normal saline group. UFH was initiated at a speed of 10 to 15 units/kg/h for infants with CRT and 2 to 3 units/kg/h without CRT. The primary outcome was to determine the rate of CRT at discharge. The secondary outcomes included thrombosis 6 months after surgery, adverse events of UFH, and post-thrombotic symptoms. RESULTS: Due to slow recruitment during the COVID-19 pandemic, this trial was prematurely stopped. Only 35 infants were randomly assigned to the UFH or control groups. There was no statistically significant difference in CRT rate at discharge ( P =0.429) and 6 months after surgery ( P =1.000) between groups. All CRTs except one disappeared at discharge. No thrombosis or post-thrombotic symptom was reported at follow-up evaluation. There was no difference between groups in duration of thrombus ( P =0.088), D dimer ( P =0.412), catheter in situ days ( P =0.281), and post-thrombotic syndrome ( P =1.000), except for activated partial thromboplastin time ( P =0.001). CONCLUSIONS: With the early stop of this trial and limited data, it is difficult to draw a definitive conclusion about the efficacy of UFH on CRT. Meanwhile, considering the data from 6 months follow-up, in this population, asymptomatic CRT might resolve with no intervention.

[Heparin-Induced Thrombocytopenia].

The extensive use of therapeutic doses of heparin to prevent thrombosis in critically ill patients with COVID-19 during the pandemic has led to an increased incidence of bleeding and heparin-induced thrombocytopenia (HIT). In addition, the introduction of the AstraZeneca and Johnson&Johnson vaccines against COVID-19 into clinical practice was associated with the development of a rare but very severe, adverse thrombotic complication, vaccine-induced immune thrombotic thrombocytopenia (VITT). Thrombotic complications of VITT turned out to be similar to HIT both clinically and pathophysiologically. HIT is a potentially fatal immune-mediated adverse drug response that results in emergence of antibodies that activate platelets in the presence of heparin. HIT is characterized by a high incidence of venous and arterial thromboses, often with fatal outcomes. Currently, there are clearly defined international guidelines for the diagnosis, treatment and prevention of HIT. In case of thrombotic complications, non-heparin anticoagulants should be used.

Perioperative anticoagulation in free microvascular flaps - a comparison of different prophylactic regimes in oncologic reconstructive surgery.

OBJECTIVE: Free tissue transfer has an established place in oncologic head and neck surgery. However, the necessity and specific regimen of perioperative thromboprophylaxis remain controversial. Here, the risk of postoperative hemorrhage contrasts with vascular pedicle thrombosis and graft loss. This work compares three different heparin protocols (A-C) with regard to postoperative complications. PATIENTS AND METHODS: A retrospective analysis of our free flap transplants between 2004 and 2023 was conducted. Inclusion criteria were thromboprophylaxis with (A) 500 IU/h unfractionated heparin (UFH), (B) low-molecular-weight heparin (LMWH) once daily, and (C) LMWH once daily with additional immediate preoperative administration. Primary endpoints were the incidence of postoperative bleeding and hematoma and the appearance of flap thrombosis. RESULTS: We evaluated 355 cases, 87 in group A, 179 in group B, and in group C 89 patients. Overall, postoperative bleeding occurred in 8.7% of patients, and 83% underwent hemostasis under intubation anesthesia, with no significant difference between groups (p = 0.784). Hematoma formation requiring revision was found in 3.7% of patients (p = 0.660). We identified postoperative hematoma as a significant influencing factor for venous pedicle thrombosis (OR 3.602; p = 0.001). Venous and arterial flap thrombosis in the graft vessel showed no difference between the groups (p = 0.745 and p = 0.128). CONCLUSIONS: The three anticoagulation regimens appear to be equivalent therapy for the prevention of thrombosis without significant differences in postoperative bleeding. The use of LMWH with additional preoperative administration can, therefore, be administered in free flap reconstruction.

Platelet-targeted thromboprophylaxis with a human serum albumin fusion drug: Preventing thrombosis and reducing cardiac ischemia/reperfusion injurywithout bleeding complications.

Background: Myocardial infarction (MI) as a consequence of atherosclerosis-associated acute thrombosis is a leading cause of death and disability globally. Antiplatelet and anticoagulant drugs are standard therapies in preventing and treating MI. However, all clinically used drugs are associated with bleeding complications, which ultimately limits their use in patients with a high risk of bleeding. We have developed a new recombinant drug, targ-HSA-TAP, that combines targeting and specific inhibition of activated platelets as well as anticoagulation. This drug is designed and tested for a prolonged circulating half-life, enabling unique thromboprophylaxis without bleeding complications. Methods: Targ-HSA-TAP combines a single-chain antibody (scFv) that targets activated glycoprotein IIb/IIIa on activated platelets, human serum albumin (HSA) for prolonged circulation, and tick anticoagulant peptide (TAP) for coagulation FX inhibition. A non-binding scFv is employed as a non-targeting control (non-targ-HSA-TAP). Its efficacy was investigated in vivo using murine models of acute thrombosis and cardiac ischemia-reperfusion (I/R) injury. Results: Our experiments confirmed the targeting specificity of targ-HSA-TAP to activated platelets and demonstrated effective prevention of platelet aggregation and thrombus formation, as well as FXa inhibition in vitro. Thromboprophylactic administration of targ-HSA-TAP subcutaneously in mice prevented occlusion of the carotid artery after ferric chloride injury as compared to non-targ-HSA-TAP and PBS-control treated mice. By comparing the therapeutic outcomes between targ-TAP and targ-HSA-TAP, we demonstrate the significant improvements brought by the HSA fusion in extending the drug's half-life and enhancing its therapeutic window for up to 16 h post-administration. Importantly, tail bleeding time was not prolonged with targ-HSA-TAP in contrast to the clinically used anticoagulant enoxaparin. Furthermore, in a murine model of cardiac I/R injury, mice administered targ-HSA-TAP 10 h before injury demonstrated preserved cardiac function, with significantly higher ejection fraction and fractional shortening, as compared to the non-targ-HSA-TAP and PBS control groups. Advanced strain analysis revealed reduced myocardial deformation and histology confirmed a reduced infarct size in targ-HSA-TAP treated mice compared to control groups. Conclusion: The inclusion of HSA represents a significant advancement in the design of targeted therapeutic agents for thromboprophylaxis. Our activated platelet-targeted targ-HSA-TAP is a highly effective antithrombotic drug with both anticoagulant and antiplatelet effects while retaining normal hemostasis. The long half-life of targ-HSA-TAP provides the unique opportunity to use this antithrombotic drug for more effective, long-lasting and safer anti-thrombotic prophylaxis. In cases where MI occurs, this prophylactic strategy reduces thrombus burden and effectively reduces cardiac I/R injury.

Underlying Mechanisms of Thrombosis Associated with Cancer and Anticancer Therapies.

OPINION STATEMENT: Cancer-associated thrombosis (CAT) has been identified as the second most prevalent cause of death after cancer itself. Moreover, the risk of thrombotic events in cancer patients increases due to anticancer drugs, such as tyrosine kinase inhibitors (TKIs). Venous thromboembolism (VTE) as well as arterial thromboembolic (ATE) events are present in CAT. Although VTE occurs more frequently, ATE events are very significant and in some cases are more dangerous than VTE. Guidelines for preventing thrombosis refer mainly VTE as well as the contribution of ATE events. Several factors are involved in thrombosis related to cancer, but the whole pathomechanism of thrombosis is not clear and may differ between patients. The activation of the coagulation system and the interaction of cancer cells with other cells including platelets, endothelial cells, monocytes, and neutrophils are promoted by a hypercoagulable state caused by cancer. We present an update on the pathomechanisms of CAT and the effect of anticancer drugs, mainly targeted therapies with a focus on TKIs. Considering the risk of bleeding associated with anticoagulation in each cancer patient, the anticoagulation strategy may involve the use of FXIa inhibitors, direct oral anticoagulants, and low-molecular-weight heparin. Further research would be valuable in developing strategies for reducing CAT.

Anti-Xa-guided Anticoagulation With Unfractionated Heparin and Thrombosis During Extracorporeal Membrane Oxygenation Support: A Systematic Review and Meta-analysis.

OBJECTIVE: The initiation of extracorporeal membrane oxygenation (ECMO) triggers complex coagulation processes necessitating systemic anticoagulation. Therefore, anticoagulation monitoring is crucial to avoid adverse events such as thrombosis and hemorrhage. The main aim of this work was to analyze the association between anti-Xa levels and thrombosis occurrence during ECMO support. DESIGN: Systematic literature review and meta-analysis (Scopus and PubMed, up to July 29, 2023). SETTING: All retrospective and prospective studies. PARTICIPANTS: Patients receiving ECMO support. INTERVENTION: Anticoagulation monitoring during ECMO support. MEASUREMENTS AND MAIN RESULTS: A total of 16 articles with 1,968 patients were included in the review and 7 studies in the meta-analysis (n = 374). Patients with thrombosis had significantly lower mean anti-Xa values (standardized mean difference -0.36, 95% confidence interval [CI] -0.62 to -0.11, p < 0.01). Furthermore, a positive correlation was observed between unfractionated heparin infusion and anti-Xa levels (pooled estimate of correlation coefficients 0.31, 95% CI 0.19 to 0.43, p < 0.001). The most common adverse events were major bleeding (42%) and any kind of hemorrhage (36%), followed by thromboembolic events (30%) and circuit or oxygenator membrane thrombosis (19%). More than half of the patients did not survive to discharge (52%). CONCLUSIONS: This work revealed significantly lower levels of anti-Xa in patients experiencing thromboembolic events and a positive correlation between anti-Xa and unfractionated heparin infusion. Considering the contemplative limitations of conventional monitoring tools, further research on the role of anti-Xa is warranted. New trials should be encouraged to confirm these findings and determine the most suitable monitoring strategy for patients receiving ECMO support.

An ISHLT consensus statement on strategies to prevent and manage hemocompatibility related adverse events in patients with a durable, continuous-flow ventricular assist device.

Life expectancy of patients with a durable, continuous-flow left ventricular assist device (CF-LVAD) continues to increase. Despite significant improvements in the delivery of care for patients with these devices, hemocompatability-related adverse events (HRAEs) are still a concern and contribute to significant morbility and mortality when they occur. As such, dissemination of current best evidence and practices is of critical importance. This ISHLT Consensus Statement is a summative assessment of the current literature on prevention and management of HRAEs through optimal management of oral anticoagulant and antiplatelet medications, parenteral anticoagulant medications, management of patients at high risk for HRAEs and those experiencing thrombotic or bleeding events, and device management outside of antithrombotic medications. This document is intended to assist clinicians caring for patients with a CF-LVAD provide the best care possible with respect to prevention and management of these events.

Structure and pharmacokinetics/pharmacodynamics of the anticoagulant tetradecasaccharide oHG-14 as an intrinsic tenase inhibitor.

The intrinsic tenase complex (iXase) is an attractive antithrombotic target to treat or prevent pathological thrombosis with negligible bleeding risk. Fucosylated glycosaminoglycan (FG) is a promising anticoagulant by inhibiting iXase. A depolymerized FG (dHG-5) as an anticoagulant has been approved for clinical trials. Given that dHG-5 is a multi-component drug candidate consisting of a homologous series of oligosaccharides, it is difficult to predict a clear pharmacokinetics. Here, as a major oligosaccharide component, the tetradecasaccharide (oHG-14) was purified from dHG-5 and its structure was defined as L-Fuc3S4S-α(1,3)-L-Δ4,5GlcA-α(1,3)-{D-GalNAc4S6S-ß(1,4)-[L-Fuc3S4S-α(1,]3)-D-GlcA-ß(1,3)-}3-D-GalNAc4S6S-ß(1,4)-[L-Fuc3S4S-α(1,]3)-D-GlcA-ol. oHG-14 showed potent iXase inhibitory activity in vitro and antithrombotic effect in vivo comparable to dHG-5. After single subcutaneous administration of oHG-14 at 8, 14.4 and 32.4 mg/kg to rats, the absolute bioavailability was 71.6 %-80.9 % determined by the validated bioanalytical methods. The maximum concentration (Cmax) was 3.73, 8.07, and 11.95 µg/mL, respectively, and the time reaching Cmax (Tmax) was about 1 h. oHG-14 was mainly excreted by kidney as the parent compound with the elimination kinetics of first-order linear model. Anticoagulant activity of oHG-14 was positively correlated with its concentration in rat plasma. The pharmacokinetics/pharmacodynamics (PK/PD) of oHG-14 is similar to that of dHG-5. This study could provide supportive data for the clinical trial of dHG-5 and further development of pure oligosaccharide as an antithrombotic drug candidate.

Antithrombotic therapy for durable left ventricular assist devices: protocol for a living systematic review with indirect comparison/network meta-analysis.

BACKGROUND: Left ventricular assist devices (LVADs) have emerged as a successful treatment option for patients with end-stage heart failure. Compared with the best medical therapy, LVADs improve survival and enhance functional capacity and quality of life. However, two major complications compromise this patient population's outcomes: thrombosis and bleeding. Despite technological innovations and better hemocompatibility, these devices alter the rheology, triggering the coagulation cascade and, therefore, require antithrombotic therapy. Anticoagulation and antiplatelet therapies represent the current standard of care. Still, inconsistency in the literature exists, especially whether antiplatelet therapy is required, whether direct oral anticoagulants can replace vitamin K antagonists and even whether phosphodiesterase type 5 inhibitors with their antithrombotic effects could be added to the regimen of anticoagulation. METHODS AND ANALYSIS: We will perform a living systematic review with network meta-analysis and indirect comparison between current antithrombotic therapies, which have and have not been directly compared within clinical trials and observational studies. We will systematically search the following electronic sources: Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica Database (EMBASE). We will exclusively examine studies published in English from 2016 to the present. Studies conducted before 2016 will be omitted since our primary focus is evaluating continuous flow devices. Two independent reviewers will assess the articles by title, abstract and full text; any disagreement will be resolved through discussion, and a third reviewer will be involved if necessary. The Cochrane Risk of Bias tool will be used to assess the risk of bias. We will then conduct a pairwise meta-analysis; if the assumption of transitivity is satisfied, we will proceed with network meta-analysis using Bayesian methodology. ETHICS AND DISSEMINATION: Formal ethical approval is not required as no primary data are collected. This systematic review and network meta-analysis will delineate the risks of stroke, thromboembolic events, pump thrombosis, gastrointestinal bleeding and mortality in patients equipped with LVADs who are subjected to various antithrombotic regimens. The findings will be disseminated via a peer-reviewed publication and presented at conference meetings. This will enhance clinical practice and guide future research on anticoagulation strategies within this distinct patient cohort. PROSPERO REGISTRATION NUMBER: CRD42023465288.