Perioperative consultative hematology: can you clear my patient for a procedure?

Periprocedural management of antithrombotics is a common but challenging clinical scenario that renders patients vulnerable to potential adverse events such as bleeding and thrombosis. Over the past decade, periprocedural antithrombotic approaches have changed considerably with the advent of direct oral anticoagulants (DOACs), as well as a paradigm shift away from bridging in many warfarin patients. Successfully navigating this high-risk period relies on a number of individualized patient assessments conducted within a framework of standardized, systematic approaches. It also requires a thorough understanding of antithrombotic pharmacokinetics, multidisciplinary coordination of care, and comprehensive patient education and empowerment. In this article, we provide clinicians with a practical, stepwise approach to periprocedural management of antithrombotic agents through case-based examples of relevant clinical scenarios.

Efficacy and Safety of Peroral Endoscopic Myotomy for Esophageal Achalasia and Achalasia-Related Diseases in Patients Aged 75 Years and Over

Peroral endoscopic myotomy (POEM) has become a popular treatment for esophageal achalasia and other esophageal motility disorders. However, its efficacy and safety in elderly patients are unclear. To clarify that, we reviewed the medical records of patients who underwent POEM in our hospital. A total of 11 patients who underwent POEM for esophageal achalasia (n = 10) and jackhammer esophagus (n = 1) were included. Procedural success, defined as the completion of an esophageal and gastric myotomy, was 100%. Clinical success, defined as an Eckardt score of 3 or less, without the use of additional treatments at 2 months, was 100%. The median Eckardt score significantly decreased after the POEM (baseline vs. 2 months after POEM; 7 (2-8) vs. 0 (0-1), p < 0.01). In the second and third years, the cumulative treatment effect maintenance rate was 88.9%. All patients taking antithrombotic agents had safe operations with the temporary discontinuation of these agents. There were four adverse events (two pneumoperitoneum, one mucosal injury, and one pneumonia), all of which improved with fasting or antibiotics. In conclusion, POEM is an effective and safe treatment for esophageal achalasia and achalasia-related diseases in patients aged 75 years and over.

Early, Subacute Coronary Stent Thrombosis: A Complication of COVID-19 Infection

Soon after it was discovered in Wuhan, China, in December 2019, coronavirus disease 2019 (COVID-19) blow-out very fast and became a pandemic. The usual presentation is respiratory tract infection, but cardiovascular system involvement is sometimes fatal and also a serious personal and health care burden. We report a case of a 57-year-old man who was admitted with anterior wall acute myocardial infarction secondary to early coronary stent thrombosis and associated with COVID-19 infection. He was managed with primary coronary angioplasty and discharged home. Procoagulant and hypercoagulability status associated with severe acute respiratory syndrome coronavirus 2 infection is the most likely culprit. Choosing aggressive antithrombotic agents after coronary angioplasty to prevent stent thrombosis during the COVID-19 pandemic may be the answer but could be challenging.

Data-driven methodology for discovery and response to pulmonary symptomology in hypertension through statistical learning and data mining: Application to COVID-19 related pharmacovigilance

Background: Potential therapy and confounding factors including typical co‐administered medications, patient's disease states, disease prevalence, patient demographics, medical histories, and reasons for prescribing a drug often are incomplete, conflicting, missing, or uncharacterized in spontaneous adverse drug event (ADE) reporting systems. These missing or incomplete features can affect and limit the application of quantitative methods in pharmacovigilance for meta-analyses of data during randomized clinical trials.Methods: Data from patients with hypertension were retrieved and integrated from the FDA Adverse Event Reporting System. 134 antihypertensive drugs out of 1151 drugs were filtered and then evaluated using the Empirical Bayes Geometric Mean (EBGM) of the posterior distribution to build ADE-drug profiles with an emphasis on the pulmonary ADEs (pADE). Afterward, the Graphical Least Absolute Shrinkage and Selection Operator (GLASSO) captured drug associations based on pADEs by correcting hidden factors and confounder misclassification. Selected drugs were then compared using the Friedman test in drug classes and clusters obtained from GLASSO.Results: Following multiple filtering stages to exclude insignificant and noise-driven reports, we found that drugs from antihypertensives agents, urologicals, and antithrombotic agents (macitentan, bosentan, epoprostenol, selexipag, sildenafil, tadalafil, and beraprost) form a similar class with a significantly higher incidence of pADEs. Macitentan and bosentan were associates with 64% and 56% of pADEs, respectively. Because these two medications are prescribed in diseases affecting pulmonary function and may be likely to emerge among the highest reported pADEs, in fact, they serve to validate the methods utilized here. Conversely, doxazosin and rilmenidine were found to have the least pADEs in selected drugs from hypertension patients. Nifedipine and candesartan were also found by signal detection methods to form a drug cluster, shown by several studies an effective combination of these drugs on lowering blood pressure and appeared an improved side effect profile in comparison with single-agent monotherapy.Conclusions: We consider pADE profiles in multiple long-standing groups of therapeutics including antihypertensive agents, antithrombotic agents, beta-blocking agents, calcium channel blockers, or agents acting on the renin-angiotensin system, in patients with hypertension associated with high-risk for COVID-19. We found that several individual drugs have significant differences between their drug classes and compared to other drug classes. For instance, macitentan and bosentan from endothelin receptor antagonists show major concern while doxazosin and rilmenidine exhibited the least pADEs compared to the outcomes of other drugs. Using techniques in this study, we assessed and confirmed the hypothesis that drugs from the same drug class could have very different pADE profiles affecting outcomes in acute respiratory illness.Funding: GJW and MJD accepted funding from BioNexus KC for funding on this project, but BioNexus KC had no direct role in this article.

Perioperative Safety of Gastrectomy for Patients Receiving Antithrombotic Treatment

Background: With the aging population, more patients are expected to receive antithrombotic treatment. Although many studies have investigated the perioperative management of antithrombotic therapy, few have targeted gastrectomy. Hence, the safety of gastrectomy for patients receiving antithrombotic agents remains unclear. This retrospective cohort study sought to compare outcomes between patients who did and did not receive antithrombotic agents.Methods: This single-center retrospective cohort study included 548 patients who underwent gastrectomy for primary gastric adenocarcinoma from January 2011 to December 2019. Patients were subsequently classified into two groups according to whether they received antithrombotic therapy (n = 121) or not (n = 427), after which surgical outcomes were compared. Propensity score analysis was performed based on age, sex, body mass index, open versus laparoscopic surgery, and total versus distal gastrectomy. After propensity score matching, 121 patients were included in each group.Results: Among the entire cohort, receiving antithrombotic therapy group was significantly older than those who did not (age ≥ 75 years, 48% vs. 33%; p ≤ 0.0001). Those receiving antithrombotic therapy had significantly higher postoperative complication rates than those who did not (33.1% vs. 23.9%; p = 0.046). After matching, no significant difference in the postoperative complication rate was observed between both groups.Conclusion: Despite having a high risk for postoperative complications, patients receiving antithrombotic therapy can safely undergo gastric resection.

Impact of LMWH and Specific Factor Xa Inhibitors, Apixaban and Fondaparinux, on Cancer Cell Biology and Procoagulant Properties of Cancer Microenvironment

Background Cancer patients with venous thromboembolism (VTE) or at risk of VTE are treated with antithrombotic agents. Cancer cells express procoagulant properties and induce hypercoagulability in the microenvironment, that could impact the efficiency of the antithrombotic agents. Aims In the present study, we investigated the interaction between antithrombotic agents with pancreatic cancer cells, as well as with their microenvironment. The impact of apixaban, fondaparinux, enoxaparin and tinzaparin on the procoagulant properties of pancreatic cancer cells BXPC3 was examinated. Reciprocally, we also investigated the impact of BXPC3 on the potency of these antithrombotic agents. Methods BXPC3 cells (400 cells/μl) were exposed for 48 hours to apixaban (2 µg/ml), fondaparinux (2 µg/ml), enoxaparin, tinzaparin (2 anti-Xa IU/ml) or NaCL (control). Then, conditioned media (CM) and BXPC3 cells were harvested, separated and put in contact with normal platelet-poor plasma (PPP). Subsequently, thrombin generation (TG) was assessed using Thrombogram-Thrombinoscope® assay (Diagnostica Stago). Cells' viability was also assessed with the MTT assay. Gene expression for Tissue Factor (TF), Vascular Endothelial Growth Factor (VEGF), Thrombospondin 1 (THSB1) was assessed with RT-qPCR at the cells exposed or not to the antithrombotic agents. Expression of TF protein and activity of cancer cells was assessed using ELISA method. Residual anti-Xa activity in CM was measured using specific amidolytic assays for each antithrombotic agent. Results Apixaban, fondaparinux, enoxaparin, and tinzaparin significantly reduced cell viability by 25%, 12%, 14%, and 11% respectively. In the control experiment non treated BXPC3 cells enhanced TG. Pre-treatment of BXPC3 with the antithrombotic agents did not significantly modify their capacity to trigger and enhance TG. Among the studied agents only apixaban resulted in significant decrease of TF mRNA expression. However, protein expression of TF was not significantly modified by any of the antithrombotic agents. VEGF's mRNA expression was significantly decreased by fondaparinux and enoxaparin. THBS1's mRNA expression was significantly increased by apixaban. The concentrations of the anti-Xa activity of fondaparinux, enoxaparin and tinzaparin in the CM obtained at 48h after exposure of cells were reduced by 27%, 48% and 26% respectively as compared to those initially added in the culture medium. In contrast, the concentration of apixaban in the CM did not significantly change. The CM obtained by cells exposed to apixaban, fondaparinux, enoxaparin and tinzaparin inhibited TG by 70%, 30%, 40% and 90% respectively. Conclusion. Antithrombotic agents reduced the viability of BXPC3 cells. Among the studied agents, apixaban had the most pronounced effect on cells' viability. The antithrombotic agents had a potential downregulating effect on the proangiogenetic properties of BXPC3 via the decrease of VEGF gene expression (fondaparinux and enoxaparin) and enhancement of THBS1 gene expression (apixaban). Nevertheless, preincubation of BXPC3 with the antithrombotic agents did not alter the expression of TF protein and their effect on thrombin generation. Moreover, BXPCE exerted a "degradation" effect on LMWH and fondaparinux. Apixaban appeared to escape from this effect of the cancer cells. A significant inhibitory effect on thrombin generation was exerted by the residual concentrations of the antithrombotic agents in the microenvironment of cancer cells. The ensemble of these data highlight for the first time that the presence of antithrombotic agents in cancer cell microenvironment alters the biology of cancer cells and offer a constant antithrombotic effect in the microenvironment. Disclosures No relevant conflicts of interest to declare.

Abstract 1122‐000129: Management of Traumatic Carotid‐Cavernous Fistulas in the Acute Setting of Penetrating Brain Injury

Introduction : Traumatic carotid‐cavernous fistulas (tCCFs) represent abnormal vascular shunt between the carotid artery, in its cavernous segment, and the cavernous sinus, after direct or indirect trauma. Literature on tCCF associated with gunshot wounds (GSW) is scarce and is unique due to potential risk of exsanguination or bleeding into the brain proper. Furthermore, the management of tCCF in the GSW population is particularly relevant as gunshot patients represent a unique challenge be it due to the presence of concomitant cranio‐cervical vascular injury, other organ involvement, or contraindications for anticoagulation and /or antithrombotic use. Methods : Case presentation Case A Patient is a 23 y/o female with GSW to the right side of the head with multiple skull base fractures and right temporal lobe penetrating injury with retained bullet fragment, traumatic subarachnoid hemorrhage in the basal cisterns, diffuse cerebral edema, and a 5mm right to left midline shift. Patient also has a high‐flow right tCCF with significant arterialization of cortical veins. Patient underwent venous coiling of the cavernous sinus with flow diverter stents in the arterial wall of the cavernous segment of the carotid artery. The patient remained in the hospital fifty‐one days and suffered multiple neurological complications, including cerebral vasospasm, development of a pseudoaneurysm in the right anterior choroidal artery that was embolized, and hydrocephalus, requiring ventriculo‐peritoneal shunting (VPS). Patient had a GOSE 2 at the discharge to a long‐term acute care facility. Results : Case B Patient is a 30 y/o male with GSW to the left side of the head with left hemispheric subdural hematoma, left temporal lobe injury, and diffuse traumatic subarachnoid hemorrhage. The injury also resulted in a temporal bone fracture, lateral to the carotid canal, and extensive left facial fractures. Patient also has a high‐flow left tCCF that was also treated successfully with cavernous sinus coiling with flow diverter stenting of the carotid artery at the site of the fistula after initiating antithrombotic agents. Post the tCCF repair the patient developed a CSF leak that necessitated an extensive surgical repair that would not have been possible while on antithrombotic agents. At this point, the patient underwent balloon test occlusion (BTO) and sacrifice of the carotid artery at the site of the fistula. Patient was discharged to acute rehab facility with a GOSE of 5. Conclusions : Traumatic CCF may occur in patient with gunshot wounds to the head, representing an extreme of penetrating mechanisms associated with this type of injury. Current penetrating brain injury guidelines are outdated and provide no consensus on management of this condition. Embolization of the fistula, flow diversion via stenting of the fistula site and finally vessel sacrifice are viable options depending on the size of the fistula, flow grade, collateral flow, phase on injury, and concomitant injury that may dictate permissibility of antithrombotic therapy.

Cerebral Infarction Caused by Direct Cardiac Tumor Emboli Mixed with Thrombus

Cerebral infarction in cancer patients is often caused by thrombosis due to hypercoagulability, and in some cases, caused by direct tumor embolism. We report the case of cerebral infarction due to direct tumor embolism mixed with thrombus. Biopsy of blood clots obtained during thrombectomy is important for diagnosis. If there is a high risk of thrombosis among cancer patients with cerebral infarction, the use of appropriate antithrombotic agents along with maintaining a certain level of platelets should be considered.