Life-threatening Bleeding Complications Research Articles

Platelet-sparing properties of aprotinin: A scoping review on mechanisms and clinical effects.

Cardiac surgery involving cardiopulmonary bypass (CPB) is associated with the risk of acquired coagulopathy, including dysregulated fibrinolysis, which can result in life-threatening bleeding complications. Aprotinin, an antifibrinolytic agent, has been recommended for the prevention of these complications. Its effectiveness has been attributed to its ability to nonspecifically inhibit various serine proteases involved in the coagulation and fibrinolysis cascade. Additionally, aprotinin may protect platelets from CPB-induced dysfunction through a platelet-sparing effect, further enhancing its efficacy. The biochemical pathways underlying aprotinin's platelet-sparing effect remain unclear. Furthermore, it is uncertain to what extent this effect contributes to reducing blood loss and need for transfusion. A scoping review. MEDLINE, Embase and Cochrane were searched from inception until 21 December 2023. Studies in which a platelet-sparing effect of aprotinin was investigated. These included systematic reviews; experimental, and observational studies describing healthy humans, patients, or animals undergoing any type of surgery; studies in which donated blood was used for in-vitro studies. Sixty-four studies were deemed eligible, the majority of which observed a platelet-sparing effect, attributing it to the inhibition of platelet aggregation (via protection of glycoprotein (GP) IIb/IIIa receptors), platelet adhesion (by protection of GP Ib receptors), both aggregation and adhesion receptors, proteolysis of protease-activated receptor 1 receptors, platelet activation (by inhibition of plasmin) and platelet activation (by inhibition of thrombin). A dose-dependency of the platelet-sparing effect was investigated in both in-vitro studies and randomised controlled trials, yielding mixed results. No studies have explored the relative contribution of aprotinin's platelet-sparing effect and its antifibrinolytic effect in reducing blood loss and need for transfusion. This review elucidated current knowledge on how aprotinin influences platelets and exerts its platelet-sparing effect, while highlighting gaps in the existing literature.

A safety comparison of heparin and argatroban anticoagulation in veno-venous extracorporeal membrane oxygenation with a focus on bleeding.

Anticoagulation during extracorporeal membrane oxygenation (ECMO) might still lead to severe bleeding complications. Heparin is the most frequently used anticoagulant, but novel drugs could be promising. Argatroban is a new alternative to heparin. To date, no robust studies have confirmed the clear superiority of argatroban (AG) over heparin, although it has some advantages and may be safer. An observational study was conducted in all adult veno-venous ECMO patients with COVID-19-associated acute respiratory distress syndrome admitted to the University Hospital Ostrava (n = 63). They were anticoagulated with heparin in the first period and with AG in the second period, targeting the same activated partial thromboplastin time (aPTT; 45-60 s). Bleeding complications requiring transfusion and life-threatening bleeding events were evaluated. The primary objective was to compare heparin and AG in terms of bleeding, transfusion requirements and mortality-related bleeding. The total time on ECMO per patient was 16 days with an in-hospital mortality of 55.6%. The red blood cell consumption in the AG group (median 2.7 transfusions/week) was significantly lower than in the heparin group (median 4.2 transfusions/week, p = 0.011). Life-threatening bleeding complications were higher in the heparin group compared to the AG group (35.7% vs. 10.2%, p = 0.035), and mortality-related bleeding complications were also higher in the heparin group (21.4% vs. 2.0%, p = 0.032). Argatroban is an interesting alternative to heparin with less bleeding, less need for red blood cell transfusions and improved safety of ECMO with less mortality-related bleeding.

Comparative incidence and risk factors for gastrointestinal bleeding following percutaneous coronary intervention for coronary artery disease: Insights from the Keio Cardiovascular Registry in Japan

In patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), antiplatelet medication usage is crucial for preventing thrombotic events. However, it requires careful monitoring, especially because of the risk of life-threatening bleeding complications. In hemorrhagic complications, assessment of patient background and risk of gastrointestinal bleeding (GIB) remain limited for GIB that develops during long-term observation after hospital discharge. This study aimed to examine the incidence of GIB and patient characteristics in CAD post-PCI. All CAD patients undergoing PCI for urgent, emergent, or elective indications were enrolled in the Keio Interhospital Cardiovascular Studies (JCD-KiCS)-PCI registry (January 2009 and December 2017) and followed up to 2years after PCI discharge. From the JCD-KiCS PCI registry, 8864 patients (median [interquartile range [IQR]] age: non-GIB: 69.0 y [16 y], upper GIB (UGI): 72.0 y [15.5 y], lower GIB (LGI): 73.0 y [IQR: 13 y]) were categorized based on the occurrence of hospitalization-requiring GIB. Patient characteristics and detailed information regarding these GIB events, including the location (upper vs lower GI) and bleeding severity, were analyzed. Overall, 36 patients experienced UGI, while 85 patients experienced LGI. The rates of dual antiplatelet therapy (DAPT) and triple therapy were significantly different among the non-GIB (n=8734), UGI (n=36) and LGI (n=85) groups (DAPT [aspirin+P2Y12 (clopidogrel/prasugrel/ticlopidine)]: 64 [76.2%] in the LGI group vs 24 [68.6%] in the UGI group vs 7330 [84.6%] in the non-GIB group; triple therapy [aspirin+P2Y12 (clopidogrel/prasugrel/ticlopidine)]+oral anticoagulant (OAC) (warfarin/direct oral anticoagulant [DOAC]): 17 [20.2%] in the LGI group vs 8 [22.9%] in the UGI group vs 836 [9.6%] in the non-GIB group; p<0.001). In the LGI and UGI groups, aspirin and warfarin were used in 2 (2.4%) and 2 (5.7%) patients, respectively, but not in combination with DOAC. The 2-year post-PCI hospitalization incidence for GIB was 1.4% (LGI, 1.0%; UGI, 0.4%). The most common causes were colonic diverticular hemorrhage (43.5%) for LGI and duodenal ulcer (21.9%) for UGI. No significant differences were found in the cumulative 2-year post-PCI risks between the LGI and UGI groups (log-rank p=0.97). Most GIB events were Bleeding Academic Research Consortium 2-equivalent (hemoglobin decrease <3g/dL). Notably, the use of OACs at PCI discharge, bleeding complications within 72h, and preprocedural anemia were significantly correlated with an increased GIB risk. The real-world incidence of LGI is two times higher than that of UGI in CAD patients undergoing PCI, and most events are mild. OAC use at PCI discharge is the strongest potential risk factor for GIB development.

Transcarotid versus transfemoral transcatheter aortic valve replacement: A systematic review and meta-analysis

In the 2021 Transcatheter Valve Therapy (TVT) registry, 8.9% of patients underwent TAVR via access sites other than the femoral artery. Transthoracic approaches may be contraindicated in some patients and may be associated with poorer outcomes. Therefore other alternative access routes are increasingly being performed. We conducted a systematic review of the literature on transcarotid transcatheter aortic valve replacement (TC-TAVR) and meta-analysis comparing outcomes of TC-TAVR and other access routes. We comprehensively searched for controlled randomized and non-randomized studies from 4 online databases. We presented data using risk ratios (95% confidence intervals) and measured heterogeneity using Higgins' I2. Sixteen observational studies on transcarotid TAVR were included in the analysis; 4 studies compared TC-TAVR vs TF-TAVR. The mean age and STS score for patients undergoing TC-TAVR were 80years and 7.6 respectively. For TF-TAVR patients, mean age and STS score were 81.2years and 6.5 respectively. There was no difference between patients undergoing TC-TAVR and TF-TAVR in the following 30-day outcomes: MACE [8.4% vs 6.7%; OR 1.32 (95% CI 0.71-2.46 p=0.38) I2=0%], mortality [5.6% vs 4.0%; OR 0.42 (95% CI 0.60-3.37, P=0.42) I2=0%] and stroke [0.7% vs 2.3%; OR 0.49 (95% CI 0.09-2.56, P=0.40) I2=0%]. There was no difference in 30-day major vascular complications [0.7% vs 3%; OR 0.55 (95% CI 0.06-5.29, P=0.61) I2=39%], major bleeding [0.7% vs 3.8%; OR 0.39 (95% CI 0.09-1.67, P=0.21) I2=0%], and moderate or severe aortic valve regurgitation [8.6% vs 9.9%; OR 0.89 (95% CI 0.48-1.65, P=0.72) I2=0%]. There are no significant differences in mortality, stroke MACE and major or life-threatening bleeding or vascular complications when TC-TAVR is compared to TF-TAVR approaches.

Management of ear, nose and throat emergencies

Emergency situations involving the ears, nose, and throat (ENT) area can pose considerable challenges for clinicians and often require an interdisciplinary approach due to the involvement of different organ systems. To avoid damage to highly relevant sensory and perception organs and life-threatening bleeding or respiratory complications, strategies that are as quick and targeted as possible are necessary. This article aims to provide an overview of ENT emergency management strategies. The entire spectrum from simple conservative to highly complex surgical measures plays arole here, both diagnostically and therapeutically. Aspects such as bleeding, respiratory problems, inflammation, hearing disorders, vertigo, facial palsy and injuries to the head and neck area are discussed. In addition, important topics such as preventive measures and possible complications are also addressed to ensure optimal patient care.

Abstract B030: Intracerebral and intraventricular hemorrhage due to severe thrombocytopenia: A rare case of Evans syndrome

Abstract Introduction: Evans syndrome (ES) is a rare autoimmune disorder characterized by the development of autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and/or immune neutropenia (AIN) without an identifiable cause. It is believed to involve immune system dysregulation, leading to the destruction of red blood cells, platelets, and neutrophils. Case Presentation: A 68-year-old male with a history of coronary artery disease, hypertension, diabetes, and atrial fibrillation presented with abdominal pain and diarrhea. Laboratory tests revealed a platelet count of 3k, suggesting ITP. Initial treatment with dexamethasone and platelet transfusion provided limited improvement. A bone marrow biopsy showed mildly hypercellular bone marrow with trilineage hematopoiesis. However, the patient's condition rapidly deteriorated, and he returned to the emergency department with severe symptoms, including headache, gum bleeding, and lower extremity petechiae. A CT scan revealed a large intraparenchymal hematoma with intraventricular hemorrhage, highlighting the risk of life-threatening bleeding in ES patients. Discussion: The patient was managed with platelet transfusions, high-dose steroids, and intravenous immunoglobulin (IVIG), which provided temporary relief but failed to maintain stable platelet levels. Further investigations revealed a positive antinuclear antibody (ANA), suggesting an underlying rheumatological condition and confirming the diagnosis of secondary ES. This finding necessitated the exploration of treatment options. Of interest is Romiplostim (Promacta), a thrombopoietin receptor agonist, which has shown promise in increasing platelet counts and reducing bleeding episodes in refractory ITP. Considering the positive ANA and the suspected rheumatological etiology, Romiplostim may serve as a viable long-term treatment option to stabilize platelet levels and mitigate bleeding risks in this case. Conclusion: This case highlights the complexity of Evans syndrome and emphasizes the need to promptly recognize and manage life-threatening bleeding complications, particularly in older patients. The presence of a positive ANA suggests an underlying rheumatological condition, necessitating comprehensive evaluation, and tailored therapeutic approaches. Although further research is needed to understand the pathogenesis and optimal management strategies for ES, Romiplostim holds promise as a potential treatment for patients with secondary ES who are unresponsive to conventional therapies. Citation Format: Kiersten R. Patterson, Aliya M. Khan, Raj Patel. Intracerebral and intraventricular hemorrhage due to severe thrombocytopenia: A rare case of Evans syndrome [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B030.

Safety and efficacy of protamine administration for prevention of bleeding complications in patients with recent PCI undergoing TAVR

Abstract Background Despite major advances, TAVR is still associated with vascular and bleeding complications, that have an impact on mortality. Recent studies have shown that heparin antagonization using protamine resulted in lower bleeding rates in patients undergoing TAVR as compared to those without heparin reversal. However, there are only limited data on the safety of protamine regarding thromboembolic complications including in-stent thrombosis in TAVR patients who have had a recent PCI. Accordingly, daily practice varies between Centers. Purpose The aim of this multicentre study was to evaluate the safety and efficacy of protamine administration in patients who have had a recent PCI undergoing subsequent TAVR. Methods Our study included 1838 patients undergoing TAVI between 2017 and 2020. Of the patients included, 173 (9.4%) had a recent PCI (≤30 days), 319 (17.4%) had an intermediately (≥30 days) and 303 (16.5%) a previously performed PCI (≥6 months). Standardized vascular access management included the use of preclosure devices and PTA or implantation of a stent-graft, if necessary. The primary endpoint was a composite of one-year mortality and myocardial infarction at 30 days. Secondary endpoints included 30-day mortality and VARC-3-defined complications. Results The overall study population had a mean age of 81.1±6.2 years. Among patients with recent PCI, 134 (77.5%) patients received protamine for heparin reversal during the TAVR procedure. In the group of patients with intermediately and previously performed PCI 258 (80.9%) and 249 (82.2%) patients received protamine, respectively. In the recent PCI group, the occurrence of the primary endpoint was comparable between patients with protamine administration (24.6%) as compared to patients without heparin reversal (30.8%, p=0.53, Figure 1). Similarly, among patients with intermediately as well as previously performed PCI, the rates of the primary endpoint were comparable irrespective of protamine administration (20.1 vs 16.4%, p=0.59; 17.3 vs 27.7%, p=0.08, respectively, Figure 2). Moreover, among all three groups, the incidence of myocardial infarction at 30 days after TAVR was low and comparable between patients with and without heparin reversal (p&amp;gt;0.50). Overall, protamine administration was associated with decreased life-threatening bleeding (3.2 vs 9.4%, p&amp;lt;0.01) and major vascular complications (4.4 vs 7.9%, p=.02). Regarding safety endpoints, no overall differences were observed in the incidence of stroke between patients with and without protamine administration (1.5 vs 2.9%, p=0.13). Conclusion Protamine administration during the TAVR procedure did not increase the rate of myocardial infarction or one-year mortality in patients who have had a recently or intermediately performed PCI. Overall, heparin reversal using protamine resulted in significantly lower rates of life-threatening bleeding and major vascular complications, without increasing the incidence of stroke.Figure 1Figure 2

Neurological Complications Associated with Hereditary Bleeding Disorders.

Hereditary bleeding disorders may have a wide variety of clinical presentations ranging from mild mucosal and joint bleeding to severe central nervous system (CNS) bleeding, of which intracranial hemorrhage (ICH) is the most dreaded complication. In this review, we will discuss the pathophysiology of specific hereditary bleeding disorders, namely, hemophilia A, hemophilia B, and von Willebrand disease (vWD); their clinical manifestations with a particular emphasis on neurological complications; a brief overview of management strategies pertaining to neurological complications; and a review of literature guiding treatment strategies. ICH is the most significant cause of morbidity and mortality in patients with hemophilia. Adequate control of bleeding with the administration of specific factors or blood products, identification of risk factors for bleeding, and maintaining optimal coagulant activity are essential for appropriately managing CNS bleeding complications in these patients. The administration of specific recombinant factors is tailored to a patient's pharmacokinetics and steady-state levels. During acute bleeding episodes, initial factor activity should be maintained between 80 and 100%. Availability of monoclonal antibody Emicizumab has revolutionized prophylactic therapies in patients with hemophilia. Management of ICH in patients with vWD involves using plasma-derived factor concentrates, recombinant von Willebrand factor, and supportive antifibrinolytic agents individualized to the type and severity of vWD. Hemophilia and vWD are the most common hereditary bleeding disorders that can predispose patients to life-threatening CNS complications-intracranial bleeds, intraspinal bleeding, and peripheral nerve syndromes. Early care coordination with a hematologist can help develop an effective prophylactic regimen to avoid life-threatening bleeding complications in these patients. Further research is needed to evaluate using emicizumab as an on-demand treatment option for acute bleeding episodes in patients with hemophilia.

Transcatheter Aortic Valve Implantation Using the Transcervical Vascular Access (from a 7-Year Experience from a Swiss Tertiary Center)

The gold-standard transfemoral (TF) access for transcatheter aortic valve implantation (TAVI) is not suitable in 10% to 15% of patients, and alternative accesses are needed. Studies have suggested that the transcervical (TC) access might yield outcomes comparable to the TF access. In our center, TC-TAVI is the first-line alternative to TF-TAVI. We herein present our 7-year experience regarding the use of the TC access in TAVI. We included all consecutive patients referred for TC-TAVI between January 1, 2016 and December 31, 2022. Data regarding the patients' characteristics,perioperative and 30-day outcomes were prospectively collected. Patients were separated into 2 temporal groups (group 1: January 1, 2016 to June 30, 2019; group 2: July 1, 2019 to December 31, 2022) to assess the changes of their characteristics and outcomes over time. A total of 95 patients were included, with more belonging to group 2 (n=56 vs n=39 in group 1). Patients in group 2 were significantly younger (81.0 [interquartile range 77.0 to 87.0] vs 89.0 [interquartile range 83.0 to 92.0] years, p <0.001) and had a higher prevalence of hypertension (87.5% vs 66.7%, p=0.028) and chronic pulmonary disease (35.7% vs 15.4%, p=0.029). There was no significant difference regarding other co-morbidities or surgical scores. All-cause mortality and the risk of stroke at 30days were low and similar (group 2 vs group 1, 3.6% vs 2.5%, p=0.787 and 1.8% vs 0%, p=0.397, respectively), as were the risks of permanent pacemaker implantation, postoperative acute kidney injury, cardiac tamponade, life-threatening bleeding, and major vascular complications. In conclusion, the use of the TC access increased over time. The rates of adverse events did not change, despite patients from mid-2019 onward having slightly more co-morbidities.

Dental considerations in patients on antiplatelet and anticoagulant drugs – Clearing the fog: A case series

The use of antiplatelet and anticoagulant drugs is increasing day by day. Hence, recently dentists are coming across a greater number of patients on such medications. Dentists should have in-depth knowledge about the indications, bleeding complications, postoperative instructions, and antidotes of these drugs on oral health and therapy. The dental surgeon should also be aware of the consequences of withdrawal or continuation of these drugs on life-threatening thromboembolic events or bleeding complications. The present observational study included 1240 cardiac patients who were on antithrombotic therapy. Out of which 78 patients underwent various dental procedures involving probable bleeding complications, 11 patients met with bleeding complications, and 2 patients of which reported spontaneous bleeding. This case series reports bleeding complications associated with dental procedures (either procedure-related or spontaneous oral bleeding) in patients with drug-induced coagulopathies (patients either on antiplatelet or anticoagulant or on both). A description of the medical conditions of these patients along with a regimen of antithrombotic therapy is discussed. Management of bleeding complications is also described. These case series recommend continuing antiplatelet or anticoagulant therapy during dental procedures to prevent the risk of life-threatening conditions owing to thromboembolic complications. Simultaneously, the necessary armamentarium to deal with bleeding complications should be readily available.

Abstract 12642: Protamine Administration in Patients Undergoing Percutaneous Left Atrial Appendage Occlusion

Introduction: Intravenous protamine sulfate is widely used to reverse anticoagulation after structural heart interventions. Protamine is currently designated as in shortage by the US FDA, and its use has potential adverse events such as anaphylaxis, thrombosis, and stroke. There is limited data on the safety and efficacy of heparin reversal with protamine after left atrial appendage occlusion (LAAO). Hypothesis: We hypothesize that patients who received protamine for heparin reversal after percutaneous LAAO have no changes in bleeding complication rates versus patients who did not receive protamine. Methods: This retrospective study included 242 atrial fibrillation patients with a high risk of stroke and bleeding who received percutaneous LAAO between January 2020 and November 2021. The primary outcome assessed was life-threatening, disabling, or major bleeding within 48 hours following the procedure. Secondary outcomes included major adverse cardiac events (MACE) within 48 hours, minor bleeding events, MACE, device-related thrombosis or pericardial effusion within 45 days, and RBC transfusions. Patients with peri-procedure complications including pericardial effusion and/or thrombosis were excluded. Baseline characteristics were compared between both cohorts. Results: No significant difference in the primary outcome was observed between patients who received protamine compared to those who did not (5.8% vs 4.9%, p-value 0.57). There was significantly more minor bleeding in patients who did not receive protamine (0.6% vs 4.9%, p-value 0.05). MACE within 48h following the procedure, MACE, device-related thrombosis or pericardial effusion within 45 days, and RBC transfusions were comparable between the two cohorts, as described in table 2. Conclusions: Protamine administration for heparin reversal did not affect rates of life-threatening, disabling, or major bleeding complications in patients who underwent percutaneous LAAO.

Advancing anticoagulation stewardship: A call to action for stewardship from the US-based anticoagulation forum

Anticoagulation Stewardship is urgently needed to improve anticoagulation management and bend the current, negative trajectory on anticoagulation-related harm. This manuscript catalogs the origins and the progression of the Anticoagulation Stewardship model and serves as a call to action for healthcare providers and organizations committed to improving the quality and safety of anticoagulation management. Tens of millions of patients around the world currently require anticoagulant therapy to prevent or treat thrombotic events. Concerningly, there is a growing body of evidence confirming that increasing volume and complexity of anticoagulant use is significantly impacting the therapeutic landscape, posing major challenges to safe prescribing and management of these high-risk, yet essential therapies, and leading to increased patient harm including life-threatening bleeding and thrombotic complications across the continuum of care. In response, anticoagulation stewardship programs, modeled after highly successful antimicrobial stewardship efforts, are gaining increased traction to counteract this growing health concern. The current health care system is inadequate to protect patients from avoidable harms and to maximize the benefits of therapy. Apart from anticoagulation stewardship, there does not currently exist another cross-setting, multidisciplinary model for achieving maximum quality and safety for patients. If we are to collectively meet the challenge that stands before us, we must commit ourselves (as individuals and organizations) to leveraging the available resources to advance the anticoagulation stewardship model while also contributing to the burden of evidence and the effective articulation of the stewardship message. • Millions of people around the world require essential anticoagulant therapies for prevention or treatment of thromboembolic disease and this is anticipated to double in the next two to three decades due to an aging population, increasing rates of obesity and increasing hospitalizations. • Unfortunately, anticoagulants are a leading cause of medication-related adverse events in the Unites States and across the globe due to inappropriate prescribing and management. • Changing the negative trajectory of anticoagulant-related ADEs requires comprehensive, resolute and sustainable efforts in the form of anticoagulation stewardship. • The US-based Anticoagulation Forum has issued a call to action and is leading the charge for change through key efforts such as development of core elements for anticoagulation stewardship, program implementation guidance, advanced training opportunities and advocacy for national-level mandates requiring anticoagulation stewardship programs in all care settings.

Spontaneous rectus sheath hematoma associated with apixaban in an elderly gentleman with chronic obstructive airway disease – a case report

BackgroundRectus sheath hematoma (RSH) is a relatively uncommon cause of acute abdominal pain and can be mistaken as other surgical causes of acute abdomen. A diagnosis requires high index of suspicion especially in susceptible patients, for example, in patients on anticoagulation. While anticoagulation is the commonest risk factor for RSH, direct-acting oral anticoagulants have only been very recently implicated as a potential cause with fewer than ten cases reported in the literature.Case presentation.An 82-year-old Chinese man with chronic obstructive airway disease, ischemic heart disease, heart failure and atrial fibrillation on apixaban presenting with acute onset of lower abdominal pain. Physical examination showed peritoneal signs with tenderness and guarding over the lower quadrants with hypotension. Computed tomography (CT) of the abdomen confirmed a large rectus sheath hematoma (RSH) without active extravasation. He was given fluid resuscitation and was managed successfully with supportive treatment and cessation of apixaban. A follow-up CT two months later showed resolving hematoma and aspirin was resumed primarily for ischemic heart disease. The patient tolerated anti-platelet therapy without recurrence of RSH. The risk factors, treatment options, prognosis and issue related to anticoagulation resumption after an episode of RSH are discussed. Reported cases of RSH associated with direct-acting oral anticoagulants are reviewed.ConclusionsDirect-acting oral anticoagulant-associated rectus sheath hematoma is rare. With increasing use of direct-acting oral anticoagulants in multiple clinical settings, clinicians should remain vigilant of this potentially life-threatening bleeding complication when a patient presents with acute abdominal pain. Conservative treatment with cessation of anti-coagulant and supportive transfusion remains the mainstay of treatment.

Life-threatening retroperitoneal bleeding in coronavirus disease 2019 patient while on full dose anticoagulation: A case report

Introduction: Thromboembolism is one of the common complications in patients presenting with coronavirus disease 2019. Studies on coronavirus disease 2019 patients recommend the use of anticoagulation to prevent thrombotic complications in these patients and have shown to decrease mortality. However, spontaneous retroperitoneal bleeding is one of the life-threatening complications of therapeutic anticoagulation. Case Report: This case report is about an 82-year-old male who was admitted for coronavirus disease 2019 pneumonia, started on therapeutic dose anticoagulation on presentation, and developed life-threatening retroperitoneal bleeding. He was managed with conservative treatment because of the advanced age of the patient, high risk of deterioration, and guarded prognosis. Conclusion: Although anticoagulation protects against the thrombotic complications of coronavirus-19 infection, it has life-threatening bleeding complications. The use of anticoagulation in these patients should be practiced with caution while monitoring for bleeding complications. There needs to be more clinical studies and trials to assess the risk-benefit ratio of anticoagulation in coronavirus disease 2019 patients.

The use of self-assembling peptides (PuraStat) for hemostasis in cervical endocrine surgery. A real-life case series of 353 patients.

IntroductionCervical endocrine surgery is frequent and carries the risk of rare but potentially life-threatening bleeding complications. Energy-based devices for stopping bleeding are not always usable in contact with nerves or parathyroid glands. Topical hemostatic agents may be an additional resource. PuraStat™, made of the self-assembling peptide RADA16, forms a new category of topical hemostatic agents.ObjectiveTo assess the performance and safety of PuraStat to achieve hemostasis in cervical endocrine surgery.MethodsA retrospective chart review over four years was performed on 353 patients undergoing thyroidectomy and/or parathyroidectomy by a single senior surgeon, using PuraStat at the end of surgery in contact with recurrent nerves and parathyroid glands.Results353 patients (79.06% female, mean age 54 years) underwent surgery with six weeks follow-up visit. Three patients had revision surgery for hematoma within the first 4 h (0.84%), which is within the low ranges reported in the literature. There was no delayed bleeding after 24 h, and dysphonia was observed in 15 patients, more severe for 2 patients (one unilateral and one bilateral palsy), and transient for the other 13 patients suggesting no product-related damage to the recurrent nerves. Hypocalcemia with clinical signs were reported in 8 cases. There were no unexpected adverse events.ConclusionThis is the first report of the use of PuraStat in patients undergoing cervical endocrine surgery, showing high performance and safety in achieving hemostasis and in preventing delayed bleeding without damage to the recurrent nerves. Further randomized controlled studies are needed to confirm the results.

Pharmacological and interventional management of pulmonary embolism: where do we stand?

As the third most common cardiovascular disease, pulmonary embolism (PE) has an uptrending incidence and mortality, resulting in significant healthcare expenditure. Risk stratification of acute PE guides management. Although anticoagulation remains the cornerstone management, systemic fibrinolysis and targeted therapeutic approaches, catheter-directed thrombolysis and catheter-based embolectomy are available for high-risk patients. Life-threatening bleeding complications associated with systemic fibrinolysis have restricted its widespread implementation. Catheter-based techniques for intermediate high-risk categories were devised to reduce bleeding complications and improve outcomes. Catheter-directed thrombolysis helps minimize bleeding by way of direct drug delivery. Catheter-based embolectomy mechanically retrieves thrombi without using fibrinolytics. This focused review of medical and interventional management of acute PE provides a highlight of ongoing trials expected to add value to current practice.

Influence of using recommended radiological criteria on MDCT-angiography diagnosis of single isolated subsegmental pulmonary embolism

We assessed the rate of false-positive diagnoses of MDCT-pulmonary angiography (MDCT-A) in patients with single isolated subsegmental pulmonary embolism (SISSPE). All patients who underwent MDCT-A between 2006 and 2017 for ruling out acute pulmonary embolism (PE) and received an initial diagnosis of SISSPE were included. The MDCT-A of these patients were reviewed retrospectively by four experienced thoracic radiologists, who applied radiological criteria recommended by the American College of Chest Physicians Antithrombotic Guidelines (ACCP 2016) for the diagnosis of SISSPE. Data extracted from medical records were history of venous thromboembolism (VTE), alternative diagnoses, other diagnostic studies for VTE, anticoagulation, bleeding complications, and VTE over the following 3months. Of 3839 patients undergoing MDCT-A, PE was found in 1021 (26.6%) and SISSPE in 59 (1.5% overall and 5.8% of all patients with PE). An alternative diagnosis to PE was made on the basis of CT in 33 (55.9%) patients. Forty-one (69.5%) patients received anticoagulants, and major life-threatening bleeding complications occurred in 2, with one death. Recurrent PE was not documented in any patient with SISSPE. In the retrospective assessment of the 59 cases of SISSPE, 21 were negative for PE, with a false-positive rate of 35.6% (21/59); so the percentage of SISSPE cases after the revision was 3.7% of all patients with PE; 11 of these 21 patients received anticoagulation. Radiologists should be aware of the high rate of false-positives when making the diagnosis of SISSPE on MDCT-A without using strict diagnostic criteria. Misdiagnosis exposes patients to unnecessary anticoagulation. • Radiologist should be aware of the high rate of false-positive diagnoses of single isolated subsegmental pulmonary embolism (SISSPE) in MDCT-pulmonary angiography (MDCT-A) performed for ruling out pulmonary embolism. • Misdiagnosis of SISSPE in MDCT-A can be reduced by using strict diagnostic radiological criteria recommended by the American College of Chest Physicians Antithrombotic Guidelines. • Unnecessary anticoagulation therapy with potential severe bleeding complications may result from misdiagnosis of SISSPE.

Deep Learning in Prediction of Late Major Bleeding After Transcatheter Aortic Valve Replacement.

PurposeLate major bleeding is one of the main complications after transcatheter aortic valve replacement (TAVR). We aimed to develop a risk prediction model based on deep learning to predict major or life-threatening bleeding complications (MLBCs) after TAVR.Patients and MethodsThis was a retrospective study including TAVR patients from West China Hospital of Sichuan University Transcatheter Aortic Valve Replacement Registry (ChiCTR2000033419) between April 17, 2012 and May 27, 2020. A deep learning-based model named BLeNet was developed with 56 features covering baseline, procedural, and post-procedural characteristics. The model was validated with the bootstrap method and evaluated using Harrell’s concordance index (c-index), receiver operating characteristics (ROC) curve, calibration curve, and Kaplan–Meier estimate. Captum interpretation library was applied to identify feature importance. The BLeNet model was compared with the traditional Cox proportional hazard (Cox-PH) model and the random survival forest model in the metrics mentioned above.ResultsThe BLeNet model outperformed the Cox-PH and random survival forest models significantly in discrimination [optimism-corrected c-index of BLeNet vs Cox-PH vs random survival forest: 0.81 (95% CI: 0.79–0.92) vs 0.72 (95% CI: 0.63–0.77) vs 0.70 (95% CI: 0.61–0.74)] and calibration (integrated calibration index of BLeNet vs Cox-PH vs random survival forest: 0.007 vs 0.015 vs 0.019). In Kaplan–Meier analysis, BLeNet model had great performance in stratifying high- and low-bleeding risk patients (p < 0.0001).ConclusionDeep learning is a feasible way to build prediction models concerning TAVR prognosis. A dedicated bleeding risk prediction model was developed for TAVR patients to facilitate well-informed clinical decisions.

Could a Haematoma Be Due to an Acquired Phenomenon?

Acquired hemophilia, as opposed to congenital hemophilia, develops in individuals with no previous history of bleeding disorder with almost similar numbers of males and females affected. It is predominantly a disease of the elderly. It is an autoimmune disorder and occurs when the immune system produces antibodies that mistakenly attack healthy tissue, specifically the clotting factors, in particular clotting factor VIII. As a result, affected individuals develop abnormal uncontrolled bleeding into the muscles, soft tissues, and the skin and it can occur spontaneously during surgery, or following trauma, and potentially cause life-threatening bleeding complications in severe cases. The affected individuals may remain undiagnosed or be misdiagnosed, making it difficult to determine the actual frequency of the disorder in the general population. The clinical presentation should suspect it with confirmation by an abnormal coagulation test. Typical laboratory results with a recent onset of abnormal bleeding and an isolated prolongation of the activated partial thromboplastin time (APTT), especially in the elderly and peri- and post-partum women, should raise eyebrows. We present two cases following different symptomatology and emphasize the clinical challenges for junior medical doctors who receive patients on the front end. We hope to emphasize understanding simple coagulation blood results followed by a meaningful discussion with the hematology team towards appropriate and timely management of the bleeding diathesis. We hope this case series report will help junior medical doctors manage patients appropriately and consult with their hematology colleagues.

A Phase II Study to Investigate the Efficacy and Safety of Eltrombopag in Combination with Dexamethasone As First-Line Treatment in Adults Patients with Newly Diagnosed Primary ITP (XPAG-ITP)

A Phase II Study to Investigate the Efficacy and Safety of Eltrombopag in Combination with Dexamethasone As First-Line Treatment in Adults Patients with Newly Diagnosed Primary ITP (XPAG-ITP)