Chronic Thromboembolic Pulmonary Hypertension.

This JAMA Insights discusses the symptoms, diagnosis, and treatment of chronic thromboembolic pulmonary hypertension.

[Thromboembolism - A common cause of stroke]. / Thromboembolien ­ Eine häufige Ursache des Schlaganfalls.

In the field of neurology, thromboembolic events are responsible for approximately 40% of ischemic strokes 1. The embolisms are differentiated according to their origin: One group includes emboli that occur in the heart, e.g. due to atrial fibrillation (cardioembolic stroke). Another group includes emboli, which are caused by arteriosclerotic plaques, e.g. in the area of the carotid bifurcation in the large vessels supplying the brain. After the acute therapy of the ischemic stroke, further diagnostics are essential to determine the exact cause of the ischemic stroke. Targeted therapy to prevent further strokes can only be initiated if the cause is known (secondary prevention). In the following - in addition to the current diagnostics and therapy of thromboembolic strokes - new guideline recommendations and COVID-19 will be discussed.

[Thromboembolic diseases from a cardiological point of view]. / Thromboembolische Erkrankungen aus kardiologischer Sicht.

Thromboembolic disease is associated with a high mortality. It can be divided into two groups: embolism from a venous and embolism from an arterial side. This article gives an overview on thromboembolic disease (with a focus on pulmonary embolism and ischemic stroke) from a cardiologist's perspective.The therapeutic options for acute pulmonary embolism range from anticoagulation to fibrinolysis to interventional recanalization and surgery. The deciding factor for choice of therapy is the risk of early death. Besides clinical parameters, laboratory markers like cardiac troponin and right ventricular function on echocardiography or CTPA (computed tomography pulmonary angiography) are used to determine the early mortality risk. In hemodynamically instable patients, immediate thrombolysis is required, whereas patients with intermediate and low risk can be treated with anticoagulation. Interventional recanalization is currently being studied in patients at risk for development of CTEPH (chronic thromboembolic pulmonary hypertension) or an intermediate risk of early mortality.In ischemic stroke, early interdisciplinary workup involving a cardiologist is paramount. Post stroke screening should include monitoring for arrythmias (especially atrial fibrillation) and transthoracic echocardiography as well as sonography of extra- and intracranial arteries. If no embolic source can be detected (embolic stroke of undetermined source), transesophageal echo can be helpful to detect intracardiac shunts like patent foramen ovale (PFO) or intracardiac tumors. Post stroke care includes secondary prevention measures like risk factor modification and lipid lowering therapy as well as anticoagulation. In high risk for paradoxical embolization, interventional PFO closure can be performed. Interventional closure of the left atrial appendage (LAA) can be discussed in patients with both high thromboembolic and bleeding risk.

Tailored antiplatelet therapy in stent assisted coiling for unruptured aneurysms: a nationwide registry study.

BACKGROUND: Antiplatelet therapy, where regimens are tailored based on platelet function testing, has been introduced into neurointerventional surgery. This nationwide registry study evaluated the effect and safety of tailored antiplatelet therapy in stent assisted coiling for unruptured aneurysms compared with conventional therapy using a standard regimen. METHODS: This study enrolled 1686 patients in 44 participating centers who received stent assisted coiling for unruptured aneurysms between January 1, 2019 and December 31, 2019. The standard regimen (aspirin and clopidogrel) was used for all patients in the conventional group (924, 19 centers). The regimen was selected based on platelet function testing (standard regimen for clopidogrel responders; adding cilostazol or replacing clopidogrel with other thienopyridines (ticlopidine, prasugrel, or ticagrelor) for clopidogrel non-responders) in the tailored group (762, 25 centers). The primary outcome was thromboembolic events. Secondary outcomes were bleeding and poor outcomes (increase in modified Rankin Scale score). Outcomes within 30 days after coiling were compared using logistic regression analysis. RESULTS: The thromboembolic event rate was lower in the tailored group than in the conventional group (30/762 (3.9%) vs 63/924 (6.8%), adjusted OR 0.560, 95% CI 0.359 to 0.875, P=0.001). The bleeding event rate was not different between the study groups (62/762 (8.1%) vs 73/924 (7.9%), adjusted OR 0.790, 95% CI 0.469 to 1.331, P=0.376). Poor outcomes were less frequent in the tailored group (12/762 (1.6%) vs 34 (3.7%), adjusted OR 0.252, 95% CI 0.112 to 0.568, P=0.001). CONCLUSION: Tailored antiplatelet therapy in stent assisted coiling for unruptured aneurysms reduced thromboembolic events and poor outcomes without increasing bleeding.

The Combination of Vacuum-Assisted Thromboaspiration and Covered Stent Graft for Acute Limb Ischemia due to Thromboembolic Complications of Popliteal Aneurysm.

BACKGROUND: We present a standardized protocol of endovascular revascularization for patients with acute limb ischemia due to popliteal artery aneurysm (PAA) thromboembolic complication, based on the combination of vacuum-assisted thromboaspiration to improve tibiopedal outflow and covered stent graft to exclude the PAA. METHODS: All patients with a diagnosis of PAA complicated by thromboembolic events undergoing total endovascular rescue were prospectively enrolled in a dedicated database from November 2018 to November 2021. To assess vessel patency, the TIPI (Thromboaspiration In Peripheral Ischemia) classification was used. The primary end point was the primary technical success (at least one tibial vessel with a TIPI flow of 2 or 3). The 30-day overall mortality and amputation rates were considered as secondary end points. Patients' overall survival, limb salvage, freedom from reocclusion and reinterventions were reported as secondary late outcomes using Kaplan-Meier method. RESULTS: Seventeen male patients were enrolled with a mean age of 75.7 ± 9 years. Rutherford grading score was IIa in 52.9% (9/17) and IIb in 47.1% (8/17). PAA mean diameter was 37.4 ± 11.2 mm. All patients had tibial arteries involvement, and in 9 cases (52.9%) there was also the occlusion of the PAA. Mechanical thrombectomy with Indigo/Penumbra thromboaspiration system was used in all patients. PAAs were excluded using one or more VIABAHN covered endografts (range 1-3 pieces). Technical success was achieved in 94.1%. Fasciotomy was performed in 1 case (5.9%). Mortality and amputation rates at 30-day follow-up were respectively 0% and 5.9%. Survival rates at 6, 12, and 24 months were respectively 94.1%, 86.3%, and 67.9%. Secondary patency was achieved in all cases (100%). Freedom from reintervention was 80.4%, 65.8%, and 54.8% at 6-, 12-, and 24-month follow-up. Limb salvage was 88.2% at 6-, 12-, and 24-month follow-up, respectively. CONCLUSIONS: Although preliminary, our experience of total endovascular rescue for complicated PAA with thromboembolic events highlighted promising rates of limb salvage at 30 days after intervention. The total endovascular approach seems able to maximize tibiopedal outflow offering an interesting strategy in limb salvage.

Safety and Efficacy of the Off-Label Use of Pipeline Embolization Device Based on the 2018 Food and Drug Administration-Approved Indications for Intracranial Aneurysms: A Single-Center Retrospective Cohort Study.

BACKGROUND: The pipeline embolization device (PED; ev3/Covidien) has proven safe and effective for treating selected intracranial aneurysms. This device's versatility and popularity have driven increased interest in expanding the latest 2018 Food and Drug Administration-approved indications. OBJECTIVE: To compare "off-label" and "on-label" PED treatment. METHODS: Retrospective analysis of aneurysms treated with PED at a single center from 2013 to 2019. Comparisons were made based on the 2018 Food and Drug Administration-approved indications. RESULTS: A total of 492 treated aneurysms were included (65.2% on-label and 34.8% off-label). Aneurysm complete and near-complete occlusion rate was nonsignificantly lower in the off-label group (80.9% vs 85.7%; P = .19). Off-label treatment had higher rate of poor functional outcomes (modified Rankin Scale [mRS] >2: 10.3% vs 3.5%; P = .002). Although pretreatment mRS was already higher in the off-label group (5.3% vs 0.3%; P < .001) and there were no differences in mRS worsening during follow-up (5.5% vs 2.9%; P = .15). We also found a trend to a higher rate of intracranial hemorrhagic complications in the off-label group (4.7% vs 1.6%; P = .05), but there were no differences in hemorrhages requiring surgical intervention (1.8% vs 1.3%; P = .65). There were no differences in retreatment, thromboembolic complications, and mortality rates. CONCLUSION: Off-label PED treatment may be considered for select aneurysms, which are challenging to treat with other techniques. These cases have similar complete and near-complete occlusion rates compared with on-label cases. There are, however, higher risks of poor functional outcomes despite similar rates of thromboembolic and hemorrhagic complications. This is partly explained by the significantly higher pretreatment mRS score in the off-label group.

Consenso multidisciplinar para el manejo de la tromboembolia de pulmón / Multidisciplinary Consensus for the Management of Pulmonary Thromboembolism

El objetivo del presente documento es actualizar el consenso previo publicado en 2013, en relación con 12 áreas controvertidas en el manejo de la tromboembolia de pulmón (TEP). Para cada área se realizó una exhaustiva revisión bibliográfica y una propuesta de recomendación, sometida a un proceso de debate interno en dos teleconferencias sucesivas. En relación con el diagnóstico, recomendamos no utilizar la escala Pulmonary Embolism Rule Out Criteria (PERC) de forma aislada para descartar la TEP y, cuando haya indicación de dímero D, recomendamos emplear un punto de corte ajustado a la edad. Sugerimos utilizar la angiotomografía computerizada de tórax como prueba de imagen para el diagnóstico de la mayoría de los pacientes con sospecha de la enfermedad. Se recomienda utilizar anticoagulantes de acción directa (en vez de antagonistas de la vitamina K) para el tratamiento de la mayoría de los pacientes con TEP, y se sugiere utilizar anticoagulación para la mayoría de los pacientes con TEP subsegmentaria. Se recomienda no colocar un filtro de vena cava inferior en la mayoría de los pacientes. Si se indica tratamiento de reperfusión, el panel recomienda utilizar fibrinolisis sistémica a dosis completas. La duración de la anticoagulación está condicionada principalmente por la presencia (o ausencia) y el tipo de factor de riesgo para enfermedad tromboembólica venosa, y recomendamos no realizar estudios de trombofilia para decidir la duración de la anticoagulación a la mayoría de los pacientes con TEP. Finalmente, sugerimos no realizar cribado extendido de cáncer oculto en pacientes con TEP. (AU)

We have updated recommendations on 12 controversial topics that were published in the 2013 National Consensus on the diagnosis, risk stratification and treatment of patients with pulmonary embolism (PE). A comprehensive review of the literature was performed for each topic, and each recommendation was evaluated in two teleconferences. For diagnosis, we recommend against using the Pulmonary Embolism Rule Out Criteria (PERC) rule as the only test to rule out PE, and we recommend using a D-dimer cutoff adjusted to age to rule out PE. We suggest using computed tomography pulmonary angiogram as the imaging test of choice for the majority of patients with suspected PE. We recommend using direct oral anticoagulants (over vitamin K antagonists) for the vast majority of patients with acute PE, and we suggest using anticoagulation for patients with isolated subsegmental PE. We recommend against inserting an inferior cava filter for the majority of patients with PE, and we recommend using full-dose systemic thrombolytic therapy for PE patients requiring reperfusion. The decision to stop anticoagulants at 3 months or to treat indefinitely mainly depends on the presence (or absence) and type of risk factor for venous thromboembolism, and we recommend against thrombophilia testing to decide duration of anticoagulation. Finally, we suggest against extensive screening for occult cancer in patients with PE. (AU)

[Translated article] Multidisciplinary consensus for the management of pulmonary thromboembolism / Consenso multidisciplinar para el manejo de la tromboembolia de pulmón

We have updated recommendations on 12 controversial topics that were published in the 2013 National Consensus on the diagnosis, risk stratification and treatment of patients with pulmonary embolism (PE). A comprehensive review of the literature was performed for each topic, and each recommendation was evaluated in two teleconferences. For diagnosis, we recommend against using the Pulmonary Embolism Rule Out Criteria (PERC) rule as the only test to rule out PE, and we recommend using a d-dimer cutoff adjusted to age to rule out PE. We suggest using computed tomography pulmonary angiogram as the imaging test of choice for the majority of patients with suspected PE. We recommend using direct oral anticoagulants (over vitamin K antagonists) for the vast majority of patients with acute PE, and we suggest using anticoagulation for patients with isolated subsegmental PE. We recommend against inserting an inferior cava filter for the majority of patients with PE, and we recommend using full-dose systemic thrombolytic therapy for PE patients requiring reperfusion. The decision to stop anticoagulants at 3 months or to treat indefinitely mainly depends on the presence (or absence) and type of risk factor for venous thromboembolism, and we recommend against thrombophilia testing to decide duration of anticoagulation. Finally, we suggest against extensive screening for occult cancer in patients with PE. (AU)

El objetivo del presente documento es actualizar el consenso previo publicado en 2013, en relación con 12 áreas controvertidas en el manejo de la tromboembolia de pulmón (TEP). Para cada área se realizó una exhaustiva revisión bibliográfica y una propuesta de recomendación, sometida a un proceso de debate interno en dos teleconferencias sucesivas. En relación con el diagnóstico, recomendamos no utilizar la escala Pulmonary Embolism Rule Out Criteria (PERC) de forma aislada para descartar la TEP y, cuando haya indicación de dímero D, recomendamos emplear un punto de corte ajustado a la edad. Sugerimos utilizar la angiotomografía computerizada de tórax como prueba de imagen para el diagnóstico de la mayoría de los pacientes con sospecha de la enfermedad. Se recomienda utilizar anticoagulantes de acción directa (en vez de antagonistas de la vitamina K) para el tratamiento de la mayoría de los pacientes con TEP, y se sugiere utilizar anticoagulación para la mayoría de los pacientes con TEP subsegmentaria. Se recomienda no colocar un filtro de vena cava inferior en la mayoría de los pacientes. Si se indica tratamiento de reperfusión, el panel recomienda utilizar fibrinolisis sistémica a dosis completas. La duración de la anticoagulación está condicionada principalmente por la presencia (o ausencia) y el tipo de factor de riesgo para enfermedad tromboembólica venosa, y recomendamos no realizar estudios de trombofilia para decidir la duración de la anticoagulación a la mayoría de los pacientes con TEP. Finalmente, sugerimos no realizar cribado extendido de cáncer oculto en pacientes con TEP.

Coil Embolization of Unruptured Cerebral Aneurysms Using Stents in Small Arteries Less Than 2 mm in Diameter.

BACKGROUND: Data regarding the safety and effectiveness of stent placement in small vessels (<2 mm in diameter) for treating wide-necked cerebral aneurysms are limited. OBJECTIVE: To report our experience regarding coil embolization of unruptured cerebral aneurysms using stents (specifically the Neuroform Atlas) in small arteries <2 mm in diameter. METHODS: Patients with unruptured cerebral aneurysms treated with stent-assisted coil embolization between March 2017 and March 2021 in our hospital were included. RESULTS: Of the 137 cerebral aneurysms included in this study, 49 required stent placement and 48 were treated using the Neuroform Atlas in the small vessels measuring <2 mm in diameter (small vessel group [SVG]). In the SVG, 43 aneurysms (87.8%) demonstrated complete occlusion. Regarding complications, 2 (4.1%) patients had in-stent thrombosis during procedures and 5 (10.2%) experienced symptomatic thromboembolic complications, but only 2 (4.1%) had worsening of the modified Rankin scale ≥1 at 90 days after embolization. Patients with middle cerebral artery aneurysms had a higher risk of thrombotic events (5/18 patients, 27.8%), such as symptomatic thromboembolic complications or intraprocedural in-stent thrombus than those with other aneurysms (1/31 patients, 3.2%), in the SVG (P = .0167). CONCLUSION: Stent-assisted coil embolization for unruptured cerebral aneurysms using stents, especially the Neuroform Atlas, in small arteries <2 mm in diameter is effective and feasible, but careful perioperative attention should be given to thrombotic events during the embolization of middle cerebral artery aneurysms.

Presentation, Diagnosis and Management of Innominate Artery Thromboembolism.

PURPOSE: Acute thromboembolic disease of the innominate artery (IA) poses a unique set of therapeutic challenges, owing to its contribution to both the cerebral and upper extremity circulation, and risks of distal embolization via the carotid and subclavian arteries, respectively. Herein, we present a 74-year-old female who presents with acute IA thrombus treated successfully with right axillary and common carotid exposure and aspiration catheter-directed mechanical thrombectomy (CDT). Furthermore, an emerging use of CDT and its application in acute thromboembolism are outlined. CASE REPORT: A 74-year-old female with history of right lung transplant for pulmonary fibrosis with severe pulmonary hypertension, and stage IIIA left lung adenocarcinoma status post left lower lobectomy undergoing adjuvant chemotherapy presented with acute IA thrombus and right-sided stroke. She was treated successfully with right axillary and common carotid exposure and aspiration CDT. Computed tomography angiography performed 1 month postoperatively confirmed patent IA with no evidence of residual or recurrent thrombus. CONCLUSION: There are currently no standard guidelines on the management of acute IA thromboembolism, with mostly individual cases reported in the literature describing this rare entity. Nevertheless, this unique clinical entity mandates expeditious diagnostic and therapeutic approaches in order to avoid permanent neurologic deficits from distal embolization. Our case demonstrates that aspiration CDT may be an effective treatment modality for patients with acute IA thrombus.

Late-onset hematological complications post COVID-19: An emerging medical problem for the hematologist.

Coronavirus disease 19 (COVID-19) is considered a multisystemic disease. Several studies have reported persistent symptoms or late-onset complications after acute COVID-19, including post-COVID-19 hematological disorders. COVID-19-induced coagulopathy, an immunothrombotic state, has been linked to thromboembolic and hemorrhagic events. Late-onset thrombocytopenia related to immune system dysregulation has also been reported as a rare manifestation post COVID-19. Close monitoring of laboratory dynamics is considered essential to identify timely abnormal values that need further investigation, providing supportive care whenever indicated. The role of hematologists is essential in terms of the multidisciplinary approach of long COVID-19. This review summarizes all the available evidence on post-acute COVID-19 hematological complications.

Balloon-Assisted Endovascular Thrombectomy for Tibial Thromboembolism.

We present a novel approach to endovascular thrombectomy using the Penumbra Indigo® Aspiration System with balloon assistance for a thromboembolic occlusion to the tibioperoneal trunk and tibial arteries causing acute limb ischemia. This technique allows for effective suction thrombectomy of distal vessels into a shorter, large-diameter aspiration catheter, thereby overcoming the limitations of the longer but smaller aspiration catheters.

Mesenchymal Stem Cells in the Treatment of COVID-19, a Promising Future.

Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have a potent self-renewal capacity and can differentiate into multiple cell types. They also affect the ambient tissue by the paracrine secretion of numerous factors in vivo, including the induction of other stem cells' differentiation. In vitro, the culture media supernatant is named secretome and contains soluble molecules and extracellular vesicles that retain potent biological function in tissue regeneration. MSCs are considered safe for human treatment; their use does not involve ethical issues, as embryonic stem cells do not require genetic manipulation as induced pluripotent stem cells, and after intravenous injection, they are mainly found in the lugs. Therefore, these cells are currently being tested in various preclinical and clinical trials for several diseases, including COVID-19. Several affected COVID-19 patients develop induced acute respiratory distress syndrome (ARDS) associated with an uncontrolled inflammatory response. This condition causes extensive damage to the lungs and may leave serious post-COVID-19 sequelae. As the disease may cause systemic alterations, such as thromboembolism and compromised renal and cardiac function, the intravenous injection of MSCs may be a therapeutic alternative against multiple pathological manifestations. In this work, we reviewed the literature about MSCs biology, focusing on their function in pulmonary regeneration and their use in COVID-19 treatment.

Nuts and bolts of COVID-19 associated coagulopathy: the essentials for management and treatment.

INTRODUCTION: COVID-19-associated coagulopathy (CAC) is a well-recognized hematologic complication among patients with severe COVID-19 disease, where macro- and micro-thrombosis can lead to multiorgan injury and failure. Major societal guidelines that have published on the management of CAC are based on consensus of expert opinion, with the current evidence available. As a result of limited studies, there are many clinical scenarios that are yet to be addressed, with expert opinion varying on a number of important clinical issues regarding CAC management. METHODS: In this review, we utilize current societal guidelines to provide a framework for practitioners in managing their patients with CAC. We have also provided three clinical scenarios that implement important principles of anticoagulation in patients with COVID-19. CONCLUSION: Overall, decisions should be made on acase by cases basis and based on the providers understanding of each patient's medical history, clinical course and perceived risk.

[Vascular emergencies in pregnant patients : Peripartum hemorrhage, thromboembolic events and hypertensive diseases in pregnancy]. / Vaskuläre Notfälle bei der schwangeren Patientin : Peripartale Hämorrhagie, thrombembolische Ereignisse und hypertensive Schwangerschaftserkrankungen.

In developed countries, peripartum hemorrhage, thromboembolic events and hypertensive pregnancy disorders are the most frequent complications in pregnancy. They pose a significant challenge for the interdisciplinary team of gynecology and anesthesiology. Untreated, these pregnancy-related complications result in a fulminant course. Close consultation between the specialist departments and knowledge of the area of responsibility are essential. In the case of acute bleeding the anesthesiologist is responsible for maintaining adequate circulatory conditions and management of hemostasis. Thromboembolic events require immediate anticoagulation and focused diagnostics. Thereby, both the fetal and the maternal risks must be weighed up. The hypertensive diseases in pregnancy have a very high risk of complications. In addition to symptomatic treatment in the intensive care unit, the optimal time of delivery must be determined by an interdisciplinary consensus. This is the only causal treatment option possible.

Extensive Thromboembolism in a Young Male with Asymptomatic COVID-19 Infection and Heterozygous Factor V Leiden Mutation.

In this case report we present a previously healthy 21-year-old male with extensive thromboembolism in the setting of asymptomatic COVID-19 infection and heterozygous factor V Leiden mutation with no additional thrombophilic risk factors.

Atrial fibrillation-related acute myocardial infarction and acute mesenteric ischemia.

Atrial fibrillation-related synchronous thromboembolism of the mesenteric and coronary arteries is a rare event. This case report is about an 82-year-old male patient who presented to the emergency department with epigastric pain and who was diagnosed with ST-elevated myocardial infarction accompanied with acute mesenteric ischemia. To our knowledge, this is the first report of angiographic evidence of synchronous thrombus in both the arteries.