Frontiers in Clinical Drug Research

Hematology: Volume 5

Atta-ur-Rahman

• Publisher: Bentham Science Publishers
• Year: 2022
• Print ISBN: 9789815039559
• eBook ISBN: 9789815039535
• Topic: Ciencias físicas
• Subtopic: Química clínica

Frontiers in Clinical Drug Research – Hematology is a book series that brings updated reviews to readers interested in learning about advances in the development of pharmaceutical agents for the treatment of hematological disorders. The scope of the book series covers a range of topics including the medicinal chemistry, pharmacology, molecular biology and biochemistry of natural and synthetic drugs employed in the treatment of anemias, coagulopathies, vascular diseases and hematological malignancies. Reviews in this series also include research on specific antibody targets, therapeutic methods, genetic hemoglobinopathies and pre-clinical / clinical findings on novel pharmaceutical agents. Frontiers in Clinical Drug Research – Hematology is a valuable resource for pharmaceutical scientists and postgraduate students seeking updated and critically important information for developing clinical trials and devising research plans in the field of hematology, oncology and vascular pharmacology. The fifth volume of this series features 7 reviews with a focus on thalassemia treatment and preeclampsia among other topics. - Recent advances in the diagnosis and management of pulmonary embolism - An evidence-based approach to treatment with iron chelators in transfusion- dependent thalassemia patients: present trends and future scenario - Current and future treatments of iron overload in thalassemia patients - Preeclampsia: biological and clinical aspects - Haematological modulations by fixed dose combination (FDC) of tramadol hydrochloride/paracetamol (THP) - Possible use of eculizumab in critically ill patients infected with covid-19 role of complement c5, neutrophils, and nets in the induction DIC, sepsis, and MOF hematological markers - Emerging diagnostic and therapeutic targets in preeclampsia

Recent Advances in the Diagnosis and Management of Pulmonary Embolism

Kulothungan Gunasekaran^{*, 1, 2}, Mandeep Singh Rahi, MD¹

¹ Division of Pulmonary Critical Care, Yale-New Haven Health Bridgeport Hospital, Bridgeport, 06610, USA

² Division of Pulmonary Critical Care, Yuma Regional Medical Center, Yuma, AZ, 85364, USA

Abstract

Acute pulmonary embolism (PE) is a form of venous thromboembolism (VTE) and has varied clinical manifestations with significant morbidity and mortality. The general population's overall incidence is on the rise due to the increasing availability of D-dimer and computed tomographic pulmonary angiography. The incidence is higher in males than females (58 versus 48 per 100,000, respectively), increasing with age. In the United States, PE accounts for approximately 100,000 deaths annually. Specific populations, including patients with malignancy, pregnant females, hospitalized medical and surgical patients, or patients with total joint replacement, or arthroplasty, are at a higher risk for PE. Patients presenting with hemodynamic compromise due to PE need to be treated with intravenous thrombolytic therapy unless contraindicated, followed by anticoagulation. For over six decades, traditional anticoagulants like unfractionated heparin (UFH) are used for short-term anticoagulation. For patients who require long-term anticoagulation, low molecular weight heparin (LMWH) like enoxaparin and a vitamin K antagonist like warfarin are used to achieve therapeutic anticoagulation. Options for anticoagulation have been expanding steadily over the last decade with the introduction of the first direct oral anticoagulant (DOAC). Since their introduction, DOACs have changed the landscape of anticoagulation. This narrative review aims to summarize for clinicians managing pulmonary embolism (PE) the main recent advances in patient care, including risk stratification, current data regarding the use of thrombolytic treatment, and direct oral anticoagulants.

Keywords: Anticoagulation, Catheter-Directed Therapy, Pulmonary Embolism, Thrombolysis.

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^* Corresponding author Kulothungan Gunasekaran: Yuma Regional Medical Center, Yuma, AZ, USA 85364;
Tel: [phone]; E-mail: [email protected]

INTRODUCTION

Hemostasis is achieved by a fine balance between coagulation and fibrinolytic factors in the blood. Imbalance due to certain inherited and acquired risk factors can predispose one to bleed or thrombose. Venous thromboembolism is one such condition with significant health and economic impact around the globe. Venous thromboembolism (VTE) encompasses deep venous thrombosis (DVT) and pulmonary embolism (PE). Virchow’s triad, which includes blood stasis, hypercoagulability, and endothelial damage or dysfunction, underlies the thrombus formation. Inherited risk factors which contribute to this triad include hereditary thrombophilia like factor V Leiden mutation, antithrombin III deficiency, or deficiencies in fibrinolytic factors like protein C and protein S. Acquired risk factors that contribute to this triad include critical illness like bacterial sepsis or acute pancreatitis, immobility, orthopedic surgery, and systemic inflammatory states like coronavirus disease 2019 predispose patients to thrombus formation. Hematologic conditions, such as paroxysmal nocturnal hemoglobinuria, heparin-induced thrombocytopenia, and myeloproliferative disorders are associated with thrombosis. Malignancy is another important risk factor that can cause thrombosis by a complex interplay of endothelial damage, activation of clotting factors by cancer itself, and chemotherapeutic agents. Pulmonary embolism carries significant mortality and long-term morbidity among survivors.

Blood clots can travel to the pulmonary circulation from deeper veins in the lower extremities, pelvis, or upper extremities. Thrombosis can occur intrinsically in the pulmonary circulation as well as in conditions like sickle cell disease. Clinical manifestations range from an asymptomatic state or mild shortness of breath to hemodynamic collapse and cardiac arrest, depending on the location and burden of thrombosis in the pulmonary circulation. Prompt recognition, diagnosis, and institution of anticoagulation are the key to survival. Scoring systems and algorithmic approaches should also be followed. Patients with significant hemodynamic instability or cardiac arrest are managed with systemic thrombolysis followed by systemic anticoagulation and close monitoring in the intensive care setting. These usually require respiratory and hemodynamic support with invasive mechanical ventilation and vasopressors, respectively. In others, systemic anticoagulation should generally suffice. Given the significant risk of bleeding with thrombolytic therapy, catheter-directed therapies have been introduced, reducing the bleeding risk. Anticoagulation treatments come with a risk of bleeding, and shared decision-making discussing risks and benefits is necessary before long-term treatment is started. The duration of anticoagulation depends on the risk of recurrent PE and the presence of reversible, persistent, or non-identifiable risk factors. The long-term complication of pulmonary embolism is chronic thromboembolic pulmonary hypertension (CTEPH), challenging to treat. Therefore, close follow-up and early referral to a CTEPH center are necessary.

Epidemiology

The exact incidence of disease will change with changing demographics, location, and the particular population being studied. A systematic review showed the significant burden of VTE across Western Europe, North America, Australia, and Argentina. The annual incidence ranged from 0.75 to 2.69 per 1,000 individuals in the population. A higher incidence of 2 to 7 per 1,000 individuals was observed in a population aged 70 years or above [1]. There are about 250,000 cases annually among United States whites [2]. Population-based studies have been conflicting in terms of incidence according to sex. Population-based research has reported a slightly higher incidence in men than women (130 versus 110 per 100,000) with a male:female sex ratio of 1.2:1 [3]. Higher incidence in males is supported by another population-based study with male to female incidence of 134 versus 115 per 100,000 [4]. On the other hand, a Norwegian population-based study demonstrated a slightly higher incidence in women than men. In the same study, the incidence of VTE was 1.43 per 1,000 person-years, DVT was 0.93 per 1,000 person-years, and PE was 0.50 per 1,000 person-years [5]. A prospective Swedish study found similar incidence in men and women [6].

A retrospective study using the Nationwide Inpatient Sample (NIS) assessed the impact of computed tomography pulmonary angiogram (CTPA) on PE incidence and mortality....

Table of contents

• Welcome
• Table of Content
• Title
• BENTHAM SCIENCE PUBLISHERS LTD.
• PREFACE
• List of Contributors
• Recent Advances in the Diagnosis and Management of Pulmonary Embolism
• An Evidence-Based Approach to Treatment with Iron Chelators in Transfusion- Dependent Thalassemia Patients : Present Trends and Future Scenario
• Current and Future Treatments of Iron Overload in Thalassemia Patients
• Preeclampsia: Biological and Clinical Aspects
• Haematological Modulations by Fixed Dose Combination (FDC) of Tramadol Hydrochloride/Paracetamol (THP)
• Possible Use of Eculizumab in Critically Ill Patients Infected with Covid-19 Role of Complement C5, Neutrophils, and NETs in the Induction DIC, Sepsis, and MOF
• Hematological Markers: Emerging Diagnostic and Therapeutic Targets in Preeclampsia