Diagnostics in venous thromboembolism: from origin to future prospects.

Venous thromboembolism (VTE) is a prevalent and life-threatening condition that requires an accurate and timely diagnosis. The current diagnostic approach to this condition, entailing an efficient integration of clinical judgment, diagnostic imaging, and laboratory testing, is the result of decades of scientific and medical research. This article aims to present and discuss the major breakthroughs that have occurred in the diagnostic imaging of both deep vein thrombosis and pulmonary embolism, along with the various biological markers that have emerged from the laboratory bench and which have only marginally migrated to the bedside. Despite decades of research, the current diagnostic armamentarium for an efficient diagnosis of VTE remains suboptimal, and some wiggle room remains for the development of more efficient diagnostic tools, which may include thrombus-targeted molecular imaging, infrared thermal imaging, thrombin generation, and proteomics.

Venothromboembolic signs and medical eponyms: Part II.

Eponyms were established to serve the purpose of honoring individuals who have made important observations and discoveries. The use of eponyms remains controversial, and important questions have been raised regarding their appropriateness. Although there have been instances where eponyms were abandoned, the remainder are largely embedded within the established literature making their disappearance unlikely. Physicians used a variety of techniques to describe signs of medical eponyms as a method for diagnosing deep venous thrombosis (DVT), pulmonary embolism (PE) or venothromboembolism (VTE). These methods (observation, palpation, pressure, or maneuvers), were detected during the physical examination and using bedside sphygmomanometer or radiographic imaging. Reviewed are both common and less frequently encountered VTE eponyms identified during the physical examination and radiologic imaging. Most of these signs have not been further studied and, therefore, there is a lack of information regarding their accuracy and reliability in clinical practice.

Venothromboembolic signs and medical eponyms: Part I.

Eponyms are honorific terms ascribed to individuals who discovered a sign, test, syndrome, technique, or instrument. Despite some contentions, eponyms continue to be widely ingrained and incorporated into the medical literature and contemporary language. Physical signs are considered unreliable methods alone for detecting deep venous thrombosis (DVT). The accuracy of the majority of these signs is unknown. For those signs that have been studied, there are a number of methodological limitations hindering the ability to draw meaningful conclusions about their accuracy and validity in clinical practice. Nevertheless, some findings when present and used in conjunction with other key signs, symptoms, and aspects of the patients history may be useful in further supporting the clinical suspicion and likelihood of DVT and/or pulmonary embolism (PE) or venothromboembolism (VTE). These signs also provide the means to better recognize the relationship between clinical findings and VTE. The acquisition of historical knowledge about these signs is important as it further enhances our understanding and appreciation of the diagnostic acumen that physicians were required to employ and to diagnose VTE prior to the advent of advanced imaging methods. Described in this paper is a brief overview of thrombosis as enumerated by Rudolf Virchow, and eponymous signs described in the late eighteenth and nineteenth centuries.

Virchow and his triad: a question of attribution.

Virchow's triad describes three factors that contribute to the development of venous thrombosis: hypercoagulability, stasis and endothelial injury. Yet, extensive review of the historical literature casts doubt on the existence of a triad described by Virchow in the form it is currently quoted throughout contemporary medical literature. Certainly his work involved extensive study of venous thrombosis and pulmonary embolism, with these two terms being coined by Virchow, but a triad of factors relating to the development of venous thrombosis is elusive. Interestingly, Virchow only began to be routinely credited with this triad one hundred years after publication of his work on venous thrombosis. This acknowledgement coincided with the accumulation of experimental evidence for the role these factors play in thrombogenesis. Controversial as the origins of Virchow's triad might be, it is apt given his substantial contribution to our knowledge of venous thromboembolism, and the fact that the triad continues to be clinically relevant today that a triad pertaining to Virchow should remain.

Anticoagulation in Pulmonary Embolism: Update in the Age of Direct Oral Anticoagulants.

The emergence of direct oral anticoagulants (DOACs) represents a major advancement and paradigm shift in the treatment of venous thromboembolism. Currently, dabigatran, rivaroxaban, apixiban, and edoxoban are approved and used routinely for the prevention and treatment of patients with venous thromboembolism. Because each of the DOACs has different doses and dosing regimens, clinicians need to become familiar with their use. This article focuses on the practical considerations of how and when to use the DOACs. It also aims to explore follow-up monitoring, use in special populations, reversal agents, periprocedural management, and how to handle bleeding complications with the DOACs.

Risk factors and prophylaxis for deep venous thrombosis in neurosurgery.

Acceptance is increasing for pharmacological prophylaxis against deep vein thrombosis (DVT) and pulmonary embolism (PE) for most types of surgery, but its use remains controversial in neurosurgical patients because of the threat of catastrophic hemorrhage. Consequently, mechanical measures such as sequential calf compression and graduated compression stockings are currently the preferred prophylaxis for neurosurgical patients. However, some patients remain at high risk despite these measures and may require prophylaxis with low molecular weight heparins or unfractionated heparin. In neurosurgical patients, known risk factors for DVT or PE include advanced age, malignancy, limb weakness, prolonged surgery, and cranial as opposed to spinal surgery. Using comprehensive neurosurgery databases, the authors identify more specific neurosurgical diagnoses and procedures as risk factors for DVT and PE, and show increases in the frequency of DVT and PE for the wider neurosurgery population and for glioma patients over time. DVT prophylaxis is compared in public and private hospital settings. This chapter contributes to the changing picture of DVT and PE in neurosurgical patients over the last two decades.

[Pulmonary embolism: the past and . . . the future]. / Embolia polmonare: il passato e ... il futuro.

The history of pulmonary embolism cannot be reconstructed reliably beyond the last two centuries, starting with the Napoleon's times by the works of Laennec. We owe the first pathological and clinical descriptions to European scientists, especially French, German and Italian. Interestingly, some ideas regarding pathophysiology and even hemodynamics can be found in papers published as early as the end of the 19th century. Of note, the strong relationship between venous thrombosis and pulmonary embolism, suspected already in the middle of the 19th century, resulted later in a new clinical entity named venous thromboembolic disease. Only just before the second world war "modern" diagnostic tests entered into the clinical arena. Beginning with electrocardiography and X-ray techniques including pulmonary angiography, the progress in the field of imaging continued with lung scan, echocardiography, computed tomography, and finally still largely unexplored ultra-fast magnetic resonance imaging techniques: despite this technological development the correct diagnosis of pulmonary embolism in daily practice remains an important challenge. This is due to the lack of a single test which would combine high diagnostic power, round-the-clock availability and reasonably low cost. Though thrombotic origin of pulmonary embolism was well documented for almost two centuries, anticoagulation as a treatment for venous thromboembolism dates back much less than a century and thrombolysis was initiated only 30 years ago. What is even worse, those 30 years were not enough for us to identify clear-cut criteria in the selection between thrombolysis and anticoagulation in individual patients. Not to speak about the problem regarding optimal duration of secondary prophylaxis after a thromboembolic episode. Still how long shall we be debating about the same problems at the bed of our patients with venous thromboembolism? Or maybe the near future will bring completely new answers to our old questions? What type of case report related to pulmonary embolism will have the chance to be accepted for publication in the Italian Heart Journal in the year ... 2050? Future will show? But only if we help it....

Armand Trousseau--some of his contributions to neurology.

Trousseau made a remarkably large number of original clinical contributions to medicine and neurology. Best known are Trousseau's syndrome, the combination of venous thrombosis with visceral carcinoma; tache cérébrale, the red streak seen on scratching the skin in acute meningitis; and Trousseau's sign, the cardinal physical sign in tetany. His pioneering work in tracheostomy in diphtheria, haemochromatosis, Parkinson's disease, aphasia and chorea are but a few of his outstanding clinical studies. Based on his famously comprehensive text, Clinique Médicale de l'Hôtel Dieu, this paper highlights a few of his discoveries. The name of Armand Trousseau must stand alongside those of Charcot, Oppenheim, Jackson and Gowers in the annals of neurology.

[Use the entire "analysis package" when investigating patients with venous thrombosis! Don't forget the relatives...]. / Använd hela "analyspaketet" vid utredning av trombospatienten! Och glöm inte släktingarna....

During the last few years several genetic markers have been discovered that contribute to an increased risk of venous thrombosis. Patients who have several genetic markers are at a considerably higher risk of being affected than patients with only one marker. Recommendations are made as to which patients should be investigated, with appropriate laboratory analyses, when an increased risk of venous thrombosis is suspected. Most of the analyses can be done even if the patient is undergoing warfarin treatment.

Did Rubens' Delilah have Mondor's disease?

BACKGROUND: Rubens was a master of European Baroque painting and a practitioner of realism. A female model for his paintings of Samson and Delilah and the Three Graces has apparent right-sided breast abnormalities. METHOD AND RESULTS: Examination of the images shows persistent changes. The clinical scenario suggests Mondor's disease, possibly related to rheumatoid arthritis or chronic infection. DISCUSSION: Visible breast changes such as distortion, skin retraction and nipple deviation warrant concern and require investigation.

The history and historical treatments of deep vein thrombosis.

Deep vein thrombosis (DVT) is a common disease. However, unlike that of varicose veins, which have been depicted since antiquity in art and literature, its description was more recent in the history of medicine. The first well-documented case of DVT was reported during the Middle Ages: in 1271, Raoul developed a unilateral edema in the ankle, which then extended to the leg. The number of reported DVT cases steadily increased thereafter, particularly in pregnant and postpartum women. During the first half of the 20th century, well before the discovery of anticoagulants, many therapeutic approaches were used, and arose from the pathologic hypotheses that prevailed at their time. Despite the development of anticoagulants, and the fact that they were thought to dramatically decrease DVT mortality, numerous complementary treatments have also been developed during the last 50 years: they include vena cava clips and surgical thrombectomy, and are intended to decrease mortality or to prevent late complications. Most of these treatments have now been abandoned, or even forgotten. In this review, we recall also the discovery and the use of vitamin K antagonists and heparin, which have constituted the mainstay of treatment for decades. We also bring some perspective to historical aspects of this disease and its treatment, notably regarding elastic compression and early mobilization, but also abandoned and complementary treatments. In these times of change regarding DVT treatment, mainly marked by the arrival of new oral anticoagulants, efforts of physicians through the ages to treat this common disease provide a beautiful example of the history of knowledge.

Phlebitis, pulmonary emboli and presidential politics: Richard M. Nixon's complicated deep vein thrombosis.

In September of 1974, Richard Nixon resigned the Presidency of the United States during an impeachment investigation concerning the Watergate Affair. One month after his resignation, the former President had an exacerbation of his chronic deep vein thrombosis. He also received a Presidential pardon from Gerald Ford on the same day that his recurrent deep vein thrombosis was diagnosed. The political, legal, and medical events that unfolded in the fall of 1974 are the substance of this report. Presidents often receive medical care that stretches the ordinary as a result of their position and the importance of their actions. The events surrounding Richard Nixon's care for deep vein thrombosis and its complications were not unusual for Presidential health care but were closely intertwined with the legal proceedings during the prosecution of the Watergate defendants.

Mondor's disease: what's new since 1939?

Mondor's disease (MD) is a rare and self-limited benign disease first described in 1939. Originally its clinical presentation was a superficial vein thrombosis (SVT) without contiguous skin inflammation of the chest wall veins. Over time its definition has evolved and now also includes subcutaneous thrombosis of the dorsal vein of the penis but also retractile scarring of the fascia after breast surgery without concomitant SVT. In all cases clinical examination constitutes the first step of diagnostic management. It is followed by an ultrasound exploration (US) to search for a thrombus. In about half of all cases the disease is considered as idiopathic and cancer is rare. Whatever the location considered, the follow-up is usually uneventful with low rates of recurrence and of subsequent cancer. Treatment is debated and ranges from therapeutic abstention to anticoagulants or even surgery. It is likely that the new locations and mechanisms (without thrombosis) of the MD have lead to the constitution of a heterogeneous entity precluding from a consensual mode of care.

Topical vs. intravenous administration of tranexamic acid in knee arthroplasty and prevalence of deep venous thrombosis: a randomized clinical trial / Uso tópico versus intravenoso de ácido tranexâmico na artroplastia de joelho e prevalência de trombose venosa profunda: estudo clínico randomizado

BACKGROUND: Tranexamic acid (TXA) is widely used in orthopedic surgery to reduce perioperative bleeding. Since TXA inhibits fibrinolysis, there is concern that it may increase the risk of thromboembolic events. OBJECTIVES: To verify the prevalence of deep venous thrombosis (DVT) in patients receiving TXA during total knee arthroplasty and to compare topical with intravenous administration of the drug. METHODS: All patients admitted for total knee arthroplasty due to primary arthrosis between June and November of 2014 were recruited consecutively. Thirty patients were randomized to a "topical group&" (1.5 g TXA diluted in 50ml saline sprayed over the area operated, before tourniquet release), 30 to an intravenous; (20mg/kg TXA in 100 ml of saline, given at the same time as anesthesia), and 30 to a control group (100 ml of saline, given at the same time as anesthesia). All patients had duplex ultrasound scans of the legs on the 15th postoperative day. RESULTS: Deep venous thrombosis events occurred in five of the 90 patients operated (one out of 30 in the topical group [3.3%], four out of 30 in the control group [13.3%], and zero in the intravenous group). All were confirmed by duplex ultrasound scans and all were asymptomatic. Prevalence rates of DVT were similar between groups (p = 0.112 for control vs. intravenous; p = 0.353 for control vs. topical; and p =1.000 for intravenous vs. topical, according to two-sided exact tests). CONCLUSIONS: Both topical and intravenous administration of TXA are safe with regard to occurrence of DVT, since the number of DVT cases in patients given TXA was not different to the number in those given placebo.

CONTEXTO: O ácido tranexâmico é amplamente utilizado em cirurgia ortopédica para reduzir a hemorragia perioperatória. Como o ácido tranexâmico inibe a fibrinólise, há uma preocupação de que ele possa aumentar o risco de eventos tromboembólicos. OBJETIVOS: Verificar se o uso do ácido tranexâmico é seguro em relação à prevalência de trombose venosa profunda em pacientes submetidos a artroplastia total do joelho, e comparar as administrações tópica e intravenosa desse medicamento. MÉTODOS: Todos os pacientes consecutivamente admitidos para artroplastia total do joelho devido a artrose primária entre junho e novembro de 2014 foram recrutados. Os pacientes foram randomizados em um "grupo tópico" (1,5 g de ácido tranexâmico diluído em 50 ml de solução salina cobrindo toda a área operada antes de liberar o torniquete), um "grupo intravenoso" (20 mg/kg de ácido tranexâmico em 100 ml de solução salina no momento da anestesia) e um "grupo controle" (100 ml de solução salina com a anestesia). No 15º dia de pós-operatório, todos os pacientes foram submetidos a ultrassonografia vascular com Doppler de membros inferiores, independentemente de sintomas. RESULTADOS: Dos 90 pacientes operados, apenas cinco apresentaram trombose venosa profunda (um no grupo tópico e quatro no grupo controle). CONCLUSÕES: Tanto a administração tópica quanto a intravenosa de ácido tranexâmico são seguras em termos de ocorrência de trombose venosa profunda, pois o número de casos de trombose venosa profunda foi semelhante quando comparamos os pacientes que receberam ácido tranexâmico e os que receberam placebo. Novos estudos, com amostras maiores, são necessários para confirmar esse achado.