Introductory Chapter: Defining the True Global Impact of Embolic Phenomena

In the realm of medical practice, the word “embolism” has many implications to many people [1, 2], with most providers instinctively placing this word within a negative context [3–5]. Derived from the Greek word, ἐμβολισμός, this term most literally means “interposition” [6]. Yet regardless of how benign the etymology may be, the clinical context is quite the opposite—synonymous with much dreaded morbidity and mortality [1, 2, 7–10]. Whether the embolus consists of a blood clot [8], a fat globule [11], a bubble of gas [12], amniotic fluid [9, 10], or even an iatrogenic or traumatic foreign body [13, 14], the unfavorable connotations persist even if the patient has few or no associated symptoms and requires no intervention. The primary goal of this book is to provide the reader with an overview of the most common types of embolic phenomena encountered in clinical practice, including some of the key related diagnostic and therapeutic areas. The current collection of chapters includes important contributions in the areas of pulmonary embolism (PE), fat embolism (FE), embolic complications of nonmalignant cardiac tumors, acute arterial embolism (AAE) of the lower extremity, thrombophilia in pregnancy, bullet and shrapnel embolization (BSE), and coronary artery embolization (CAE), as well as a comprehensive chapter on venous interventions utilized in the management of thromboembolic disorders. Perhaps the best way to paint the picture of the tremendous impact of “embolism” globally is to present the human costs and the resources required to treat various types, manifestations, and complications of embolic diseases. Although challenging to gather, such information was compiled by our team for the purposes of this introductory chapter and summarized in Table 1 [12, 14–37]. Although far from comprehensive, we hope to provide the reader with valuable insight into the gravity of the collective problem.


Introduction
In the realm of medical practice, the word "embolism" has many implications to many people [1,2], with most providers instinctively placing this word within a negative context [3][4][5]. Derived from the Greek word, ἐμβολισμός, this term most literally means "interposition" [6]. Yet regardless of how benign the etymology may be, the clinical context is quite the opposite-synonymous with much dreaded morbidity and mortality [1,2,[7][8][9][10]. Whether the embolus consists of a blood clot [8], a fat globule [11], a bubble of gas [12], amniotic fluid [9,10], or even an iatrogenic or traumatic foreign body [13,14], the unfavorable connotations persist even if the patient has few or no associated symptoms and requires no intervention.
The primary goal of this book is to provide the reader with an overview of the most common types of embolic phenomena encountered in clinical practice, including some of the key related diagnostic and therapeutic areas. The current collection of chapters includes important contributions in the areas of pulmonary embolism (PE), fat embolism (FE), embolic complications of nonmalignant cardiac tumors, acute arterial embolism (AAE) of the lower extremity, thrombophilia in pregnancy, bullet and shrapnel embolization (BSE), and coronary artery embolization (CAE), as well as a comprehensive chapter on venous interventions utilized in the management of thromboembolic disorders.
Perhaps the best way to paint the picture of the tremendous impact of "embolism" globally is to present the human costs and the resources required to treat various types, manifestations, and complications of embolic diseases. Although challenging to gather, such information was compiled by our team for the purposes of this introductory chapter and summarized in Table 1 [12,. Although far from comprehensive, we hope to provide the reader with valuable insight into the gravity of the collective problem.

Pulmonary embolism
Initial clinical tests obtained when a patient exhibits symptoms of a PE are commonly electrocardiogram (EKG), arterial blood gas (ABG) analysis, and chest X-ray (CXR). However, none of these studies are sufficiently sensitive or specific for this diagnosis. Clinical scoring systems such as the Wells or PERC score have been established but in isolation are not able to diagnose PE [38]; rather, they provide clinically relevant risk stratification. Based on such risk stratification, it is recommended that a test of exclusion (e.g., one with a high negative predictive value) such as D-dimer be performed in the setting of low or intermediate clinical probability of a PE [39]. In the cases where a PE is highly suspected or likely, it is preferred to proceed directly to imaging such as a computed tomography pulmonary arteriography (CTPA). The ease of obtaining it, combined with the high predictive value (92-96%), has placed CTPA as the dominant imaging modality for suspected PE [40]. In patients unable to receive iodinated contrast, a ventilation-perfusion (V-Q ) scan or a contrast-enhanced magnetic resonance angiography (MRA) may represent a valid alternative. MRA has a sensitivity of 78% and specificity of 99%. This imaging study, however, relies on patient participation and compliance, and therefore a nontrivial proportion of studies will be inadequate to obtain sufficient level of diagnostic accuracy [40]. Once diagnosed, the treatment of PE involves systemic anticoagulation, with more invasive measures such as thrombolysis or embolectomy performed in patients with significant hemodynamic instability, respiratory decompensation, or acute right ventricular dysfunction [37].

Fat emboli
Fat embolism syndrome (FES) differs in that there is no reliably accurate diagnostic or imaging test. Rather, the diagnosis is primarily clinical [11]. Multiple scoring systems exist which utilize the findings of petechiae, respiratory symptoms, fever, tachycardia, and radiographic changes with these either being identified as "major" or "minor" in magnitude or assigned a value on a pre-determined scale [11,21,41]. The lack of an imaging confirmatory test, however, makes it difficult to evaluate the true diagnostic accuracy or sensitivity of these indices. Ultrasound and echocardiography have been used to detect circulating fat globules; however, several studies suggest that a much higher percentage of patients with long bone fractures have circulating fat globules than previously thought, and only a fraction of these patients develop symptoms or FES [21,42]. Computed tomography (CT) and magnetic resonance imaging (MRI) have been used, often with few abnormal findings reported. Treatment is mainly supportive and consists of intravenous fluids, respiratory support, and other forms of symptomatic management as appropriate. Medications such as steroids, heparin, alcohol, and dextran have not been proven beneficial [21].

Amniotic fluid embolism
Amniotic fluid embolism (AFE) is another condition that requires a high degree of clinical suspicion, as the diagnosis is based on a heterogeneous constellation of symptoms [9,10]. AFE should be suspected in any case of sudden maternal cardiovascular collapse with accompanying coagulopathy, hypotension, seizures, or distress, with no other clearly identifiable cause [43][44][45]. There are currently no truly reliable laboratory tests that are diagnostic of AFE [46]. Detection of formed amniotic fluid components (epidermal squamous cells, meconium, or lanugo hairs) in the maternal pulmonary blood flow is sufficient for histologic diagnosis of AFE [20]. Unfortunately, in many cases AFE goes unrecognized until these findings are

Air embolism
The most sensitive test for diagnosing an air embolism is the transesophageal echo (TEE), detecting as little as 0.02 ml/kg of air administered by bolus injection [12,37]. In fact, it has been deemed almost "too sensitive," in that it will detect air in circulation that is not associated with any symptoms. A precordial Doppler is also highly sensitive, detecting as little as 0.25 ml of air (0.05 ml/kg) [37]. It is highly operator dependent, however, as one must rely on the detection of a change in sound with air interrupting the blood flow within the cardiac chambers. Much less sensitive is the pulmonary artery catheter, with a detection threshold of 0.25 mL/ kg of air [47]. Additionally, it is of limited use therapeutically as its small caliber internal lumen is often insufficient to withdraw air from the chamber as a therapeutic maneuver (or at least quickly enough to be truly effective). In the operating room, the most practical diagnostic tool is a sudden fall in end-tidal CO 2 , albeit this is highly nonspecific. Other times, air emboli will go undiagnosed by any formal means and may well end up being "presumed" based on clinical symptomatology presenting in a scenario where an air embolus is possible ( Table 2).

Foreign body embolism
The method of detecting a foreign body embolus (FBE) is dependent on the resting intravascular location of the embolus, which may vary according to the etiology, object type, and route of introduction [13,14,52,53]. For cardiac emboli, transesophageal echocardiography (TEE) is commonly used and is beneficial in that it can also assess for any structural damage associated with such FBEs [54]. This imaging modality may be limited, however, especially in instances when the emboli are small, minimally echogenic, located in difficult-to-access locations, or obscured by acoustic shadowing. In these cases, computed tomography (CT) imaging may represent a helpful adjunct to determine location and operative or endovascular plan for removal. CT angiography is also useful for more peripherally located FBEs [52,53]. The decision on whether to remove the foreign body is also highly dependent on symptomatology and potential complications of the emboli, especially when considered in the context of any downstream anatomic structures as well as immediately surrounding tissues. In the current age, an endovascular approach is the most common, with open approaches often reserved for failure of endovascular retrieval. Rarely, an embolus may be left in place if it is unlikely to further migrate and the patient is asymptomatic, though this does leave the patient at potential risk for future complications that can occur remotely, even years later [13,14,55,56].

Conclusion
Perhaps the most valuable take-away message of this book is that diagnostic relativity-rather than absolutism-continues to prevail in the realm of "embolic diseases." Such is the state of modern medical decision-making in this important area of active clinical investigation and management. Table 2 summarizes the most common risk factors, organized by "embolism" type. Compiled from variety of sources, this information represents an good foundation for clinical discussions based on diagnostic probabilities.
In summary, this book represents a collection of contributions by a multidisciplinary team of clinicians and medical researchers. The editors' goal was to solicit the highest quality contributions from some of the top experts in their respective fields. We hope we were able to achieve this goal satisfactorily. Ultimately, the book's readers will be the best arbiters of its success, whether it is determined by the number of downloaded chapters or the cumulative number of citations attributable to this collection of chapters. To be able to contribute to the generation and dissemination of new knowledge in this important area of clinical investigation is a true privilege.
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