Rotational Thromboelastometry in High-Risk Patients on Dual Antithrombotic Therapy After Percutaneous Coronary Intervention

Aims: Patients using antithrombotic drugs after percutaneous coronary intervention (PCI) are at risk for bleeding and recurrent ischemia. We aimed to explore routine and tissue plasminogen activated (tPA) ROTEM results in a post-PCI population on dual antithrombotic treatment.Methods and Results: In this prospective cohort, 440 patients treated with double antithrombotic therapy after recent PCI and with ≥3 risk factors for either ischemic or bleeding complications were included and compared with a control group (n = 95) consisting of perioperative patients not using antithrombotic medication. Laboratory assessment, including (tPA) ROTEM, was performed one month post-PCI and bleeding/ischemic complications were collected over a five-month follow-up. Patients were stratified by antithrombotic regimen consisting of a P2Y12 inhibitor with either aspirin (dual antiplatelet therapy; DAPT, n = 323), a vitamin K antagonist (VKA, n = 69) or a direct oral anticoagulant (DOAC, n = 48). All post-PCI patients had elevated ROTEM clot stiffness values, but only the DAPT group additionally presented with a decreased fibrinolytic potential as measured with tPA ROTEM. Patients receiving anticoagulants had prolonged clotting times (CT) when compared to the control and DAPT group; EXTEM and FIBTEM CT could best discriminate between patients (not) using anticoagulants (AUC > 0.97). Furthermore, EXTEM CT was significantly prolonged in DAPT patients with bleeding complications during follow-up (68 [62–70] vs. 62 [57–68], p = 0.030).Conclusion: ROTEM CT has high potential for identifying anticoagulants and tPA ROTEM could detect a diminished fibrinolytic potential in patients using DAPT. Furthermore, the ability of EXTEM CT to identify patients at risk for bleeding may be promising and warrants further research.

Real-World Use of Fostamatinib in Patients with Immune Thrombocytopenia and Thrombotic Risk

Patients with immune thrombocytopenia (ITP) are at increased risk for bleeding and are paradoxically at increased risk for thrombosis. Many patients with ITP have underlying cardiovascular (CV) disease and/or other thrombotic risk factors for which considerable attention to selecting a therapeutic agent to manage ITP is needed. Fostamatinib, a spleen tyrosine kinase inhibitor, may reduce the risk of thrombosis while not interfering with hemostasis. We present a case series of 5 patients with ITP who had significant CV histories; each had at least 2 thrombotic risk factors. After unsuccessful management of ITP with other treatments, fostamatinib was initiated, was observed to be tolerable, and provided a durable platelet response without associated thromboembolic events. Fostamatinib may be the treatment of choice for patients with ITP in whom use of prothrombotic treatments should be avoided and/or continued use of antiplatelet or anticoagulant medication is needed.

Validation of a Prognostic Score to Identify Hospitalized Patients with COVID-19 at Increased Risk for Bleeding

Introduction: Hospitalized patients with COVID-19 are at increased risk for venous thromboembolism (VTE), but also for bleeding. We previously derived a prognostic score including four variables (elevated D-dimer, elevated ferritin, critical illness, and therapeutic-dose anticoagulation) that identified those at increased risk for major bleeding. Methods: We aimed to validate the score in a subsequent cohort of hospitalized patients with COVID-19 receiving standard-, intermediate- or therapeutic doses of VTE prophylaxis. We evaluated its capacity to predict major bleeding, non-major bleeding, and bleeding-related death. Results: The cohort included 972 patients from 29 hospitals, of whom 280 (29%) received standard-; 412 (42%) intermediate-, 157 (16%) therapeutic doses of VTE prophylaxis and 123 (13%) other drugs. Median duration of prophylaxis was 14.7 ± 10.3 days. Major bleeding occurred in 65 patients (6.7%) and non-major bleeding in 67 (6.9%). Thirty patients with major bleeding (46%) died within the first 30 days after bleeding. The prognostic score identified 203 patients (21%) at very low risk, 285 (29%) at low risk, 263 (27%) intermediate-risk and 221 (23%) at high risk for bleeding. Major bleeding occurred in 1.0%, 2.1%, 8.7% and 15.4% of the patients, respectively. Non-major bleeding occurred in 0.5%, 3.5%, 9.5% and 14.2%, respectively. The c-statistics was: 0.74 (95% confidence intervals [CI]: 0.68–0.79) for major bleeding, 0.73 (95% CI: 0.67–0.78) for non-major bleeding and 0.82 (95% CI: 0.76–0.87) for bleeding-related death. Conclusions: In hospitalized patients with COVID-19, we validated that a prognostic score including 4 easily available items may identify those at increased risk for bleeding.

Gastrointestinal Endoscopy in Patients Receiving Antithrombotic Therapy

Gastrointestinal endoscopy is used as a diagnostic and therapeutic tool. Patients receiving antithrombotic agents are at higher risk for bleeding in this procedure. Regarding its thromboembolic versus bleeding risk, physicians should consider to adjust antithrombotic therapy in patients undergoing gastrointestinal endoscopy. Some important factors including the urgency of the procedure, bleeding risk from the procedure and antithrombotic itself, and the risk of thromboembolic events during endoscopy if antithrombotic is to be stopped need to be considered wisely. Based on recommendations of ASGE, ESGE, and BSG, endoscopic procedures were divided based on the level of emergency, namely elective and urgent. In elective endoscopy with high risk of bleeding and thromboembolism, antithrombotic therapy is given in the minimum duration required and then discontinued before the procedure. In elective endoscopy with low risk of bleeding and thromboembolism, antithrombotic can be continued as usual. In urgent endoscopy due to gastrointestinal bleeding, all antithrombotic should be discontinued. Antithrombotic can be restarted within 48 hours after the procedure if no bleeding is evident

Transradial Access for High-Risk Percutaneous Coronary Intervention: Implications of the Risk-Treatment Paradox

Background: Transradial percutaneous coronary intervention (PCI; TRI) reduces adverse outcomes when compared with transfemoral PCI (TFI). However, TRI is also used less in high-risk patients. It remains unknown how baseline patient risk influences access-site choice among PCI operators and whether the absolute benefit of TRI is greater among patients at high risk for bleeding, acute kidney injury (AKI), and death. Methods: We analyzed 28 005 PCIs performed in a 7-hospital system between July, 01, 2009 and April 30, 2018, to assess the choice of access-site (TRI versus TFI) as a function of baseline risk for bleeding, AKI, and death, and examined whether the association between TRI use (versus TFI) and in-hospital outcomes is influenced by baseline risk. Results: Among 28 005 PCIs, over a 9-year period, TRI increased over time, however, a risk-treatment paradox for TRI use was observed not only for bleeding risk, but also AKI, and mortality risks, where TRI use was lower in those at highest risk. Operator variability with TRI was large. The incidences of bleeding, AKI, and death were higher with TFI versus TRI. The absolute risk difference between TRI and TFI increased with increasing baseline risk. The number needed to treat to prevent one adverse event with TRI (versus TFI) in low-, moderate- and high-risk groups, respectively, was 259, 82, and 32 for bleeding; 194, 53, and 40 for AKI; and 957, 78, and 18 for death. Conclusions: This analysis of a large multicenter cohort of patients with PCI demonstrates a risk-treatment paradox for TRI use, not only for bleeding, but also for AKI and death. Despite this, a greater absolute risk difference favoring TRI was observed among patients with the highest baseline risk. Addressing the risk-treatment paradox by preferentially selecting TRI across the spectrum of risk, but especially high-risk cases, may be an important potential strategy for improving outcomes with PCI.

Incidence of bleeding in patients on different anticoagulants and antiplatelet therapies undergoing thoracentesis

IntroductionThoracentesis is one of the most commonly performed procedures in the inpatient setting. Although coagulation profile is usually evaluated prior to thoracentesis, bleeding is a rare complication, occurring in less than 1% of the cases. Several society guidelines recommend holding antiplatelet medications and anticoagulants prior to thoracentesis. Clinical practice guidelines also recommend correcting international normalised ratios of more than two and platelet counts <50 X10∧9/L.MethodsThis is a retrospective descriptive study that included 292 patients who underwent thoracentesis in the inpatient setting at Ascension St John Hospital in Detroit, Michigan, USA from 2016 to 2018. We identified patients who had uncorrected risk for bleeding and collected data about their demographics, comorbidities, use of antiplatelet or anticoagulants and procedural details including complications. We looked for any postprocedural bleeding events to study their relation to the already established bleeding risk.ResultsTwo hundred and ninety-two thoracenteses were performed, 95.5% (n=279) were performed by interventional radiology. Majority of patients were at risk of bleeding 83% (n=242). No bleeding events occurred. Medications that were not held prior to thoracentesis included: clopidogrel 11% (n=32), novel anticoagulants 8.2% (n=24) and unfractionated heparin 50% (n=146). Use of ultrasound guidance decreased the amount of haemoglobin decline from 1 to 2 g/L (p=0.029). Seventeen patients suffered pneumothorax, eight of which required intervention.DiscussionOur study suggests that performing thoracentesis without correction of underlying coagulopathy may be safe. This may prevent consequences of holding essential medications and reduce the amount of blood products administered to patients in need of thoracentesis.

MO657RANDOMIZED CONTROL TRIAL OF INTERMITTENT HEMODIALYSIS WITH REGIONAL CITRATE VS PRIMING HEPARIN WITH PREDILUTION IN PATIENTS AT RISK OF BLEEDING

Background and Aims Standard intermittent haemodialysis (SIHD) includes anticoagulation to avoid clotting of the dialysis system. In patients at high risk for bleeding, alternativ methods have been developed to avoid systemic anticoagulation. Regional citrate anticoagulation (RCA) is usually used with continuous renal replacement therapy and low blood flow but the Promotheus® device (Freseinus Medical care-Germany) allow RCA for liver support therapy with dialysis system 4008H® and blood flow over 200ml/min. The aim of this study was to compare the IHD with RCA (IHD-RCA) to SIHD without systemic anticoagulation in patients at high risk for bleeding. Method We conducted a randomized control trial study evaluating the superiority of IHD-RCA with Prometheus® device compared to SIHD with 5008H® dialysis monitor using priming heparin (5000UI unfractionated heparin) with predilution (25 ml/min) in a 4 hour IHD strategy in patients with high risk for bleeding. Randomization was stratified on vascular access. Sixty adult patients were randomly allocated to one IHD-RCA session or SIHD in a one ICU unit university center from 2019 to 2020. Bleeding risk was defined by nephrologist and inclusion need well-functioning fistula or double-lumen catheters with a protocol blood flow higher than 200 ml/min. The primary end point was the percentage of successful study period, defined as no premature interruption of a 4 hour hemodialysis session. Secondary end points included dialysis adequacy (KT/V), dialysis circuit bubble trap status and dialyzer membrane status by visual inspection. The study was declared in ClinicalTrial NCT03562754. Results Two patients from IHD-RCA were excluded of analysis because of early vascular access failure. Causes of bleeding risk were activ bleeding in 25(43%), recent surgery or organ biopsy in 31(53%) and Stroke in 2 sessions. 10(17%) patients were treated by IHD for AKI3 and other for chronic hemodialysis. 24(41%) patients have fistula, and the mean blood flow was significantly higher in SIDH group vs IHD-RCA (294 vs 263 ml/min, p&lt;0.001). All sessions were performed with FX800 dialyzer (Polysulfone, hollow-filter 1.8M2, FMC). No statistically significant difference was observed for primary end point between group with 96% (27/28) of success for IHD-RCA and 83% (23/28) for SIHD (p=0.09). For secondary end point, no statistically significant difference was observed for KT/V delivery between group (1.69 vs 1.61, p=0.27) but score was statistically significant different between groups for visual inspection of fiber bundles (p&lt;0.01) and dialysis circuit bubble traps aspect ( p&lt;0.01 ) with higher score for SIHD. Conclusion No statitically significant difference was observed between 2 groups for 4-hour heparin-free hemodialysis sessions but we observed lower session failure with IHD-RCA. We confirm efficacy of Prometheus device for IHD-RCA in this population. Moreover, we report a low risk of 4-hour heparin-free session failure with SIHD without systemic anticoagulation using double lumen access, priming heparin, high blood flow, predilution and Polysulfone High-flux dialyser in comparison with other studies.

Management of anticoagulated patients in dentoalveolar surgery: a retrospective study comparing bridging with heparin versus unpaused vitamin K antagonist medication

Background The aim of this study was to investigate the occurrence of postoperative bleeding following dentoalveolar surgery in patients with either continued vitamin K antagonist medication or perioperative bridging using heparin. Methods A retrospective study was performed analyzing patients who underwent tooth extraction between 2012 and 2017. Patients were retrospectively allocated into two comparative groups: un-paused vitamin K antagonist medication versus bridging using heparin. A healthy, non-anticoagulated cohort with equivalent surgery served as a control group. Main outcome measures were: the occurrence and frequency of postoperative bleeding, the number of removed teeth, the surgical technique of tooth removal (extraction/osteotomy/combined extraction and osteotomy) and the prothrombin time. Results In total, 475 patients were included in the study with 170 patients in the group of un-paused vitamin K antagonist medication VG, 135 patients in the Bridging group BG and 170 patients in the control group CG. Postoperative bleeding was significant: CG versus VG p = 0.004; CG versus BG p < 0.001, BG versus VG p < 0.001. A significant correlation of number of the extracted teeth in the BG (p = 0.014) and no significance in VG (p = 0.298) and CG (p = 0.210) and in the BG versus VG and CG with p < 0.001 in terms of surgical intervention extraction. No difference observed in terms of prothrombin time. Conclusions Bridging with heparin increases the risk for bleeding compared to un-paused vitamin K antagonist medication. The perioperative management of anticoagulated patients requires a well-coordinated interdisciplinary teamwork to minimize or at best avoid both: postoperative bleeding and thromboembolic incidences.

A 56-Year-Old Woman with Recurrent Strokes: A Clear Case with a Therapeutic Dilemma

A 56-year-old woman with a history of cerebral amyloid angiopathy (CAA) complicated by prior intracranial hemorrhage (ICH) was evaluated for an asymptomatic ischemic stroke discovered on screening brain MRI. On echocardiogram, she was found to have a mass on her mitral valve and strongly positive antiphospholipid antibodies. She was diagnosed with nonbacterial thrombotic (Libman-Sacks) endocarditis associated with the primary antiphospholipid syndrome (APS). The treatment decision was complicated by the history of CAA with ICH within the last year with very high risk for bleeding complications if on anticoagulation. A multidisciplinary decision was made to initiate a trial of warfarin for 3 months. She fared well and warfarin was continued. She has not had any further bleeding or ischemic events over the subsequent 1.5 years and remains on warfarin for her APS.

Management of anticoagulated patients in dentoalveolar surgery: a retrospective study comparing Bridging with heparin versus unpaused vitamin K antagonist medication.

Background: The aim of this study was to investigate the occurrence of postoperative bleeding following dentoalveolar surgery in patients with either continued vitamin K antagonist medication or perioperative bridging using heparin. Methods: A retrospective study was performed analyzing patients who underwent tooth extraction between 2012 and 2017. Patients were retrospectively allocated into two comparative groups: un-paused vitamin K antagonist medication versus bridging using heparin. A healthy, non-anticoagulated cohort with equivalent surgery served as a control group. Main outcome measures were: the occurrence and frequency of postoperative bleeding, the number of removed teeth, the surgical technique of tooth removal (extraction/ osteotomy/ combined extraction and osteotomy) and the prothrombin time. Results: In total, 475 patients were included in the study with 170 patients in the group of un-paused vitamin K antagonist medication VG, 135 patients in the Bridging group BG and 170 patients in the control group CG. Postoperative bleeding was significant: CG vs.VG p=0.004; CG vs. BG p<0.001, BG vs.VG p<0.001. A significant correlation of number of the extracted teeth in the BG (p=0.014) and no significance in VG (p=0.298) and CG (p=0.210) and in the BG vs. VG and CG with p<0.001 in terms of surgical intervention extraction. No difference observed in terms of prothrombin time. Conclusion: Bridging with heparin increases the risk for bleeding compared to un-paused vitamin K antagonist medication. The perioperative management of anticoagulated patients requires a well- coordinated interdisciplinary teamwork to minimize or at best avoid both: postoperative bleeding and thromboembolic incidences. Key words: