Alex Wallace

Deep vein thrombosis: pathogenesis, diagnosis, and medical management

Deep vein thrombosis (DVT) is a major preventable cause of morbidity and mortality worldwide. Venous thromboembolism (VTE), which includes DVT and pulmonary embolism (PE), affects an estimated 1 per 1,000 people and contributes to 60,000-100,000 deaths annually. Normal blood physiology hinges on a delicate balance between pro- and anti-coagulant factors. Virchows Triad distills the multitude of risk factors for DVT into three basic elements favoring thrombus formation: venous stasis, vascular injury, and hypercoagulability. Clinical, biochemical, and radiological tests are used to increase the sensitivity and specificity for diagnosing DVT. Anticoagulation therapy is essential for the treatment of DVT. With few exceptions, the standard therapy for DVT has been vitamin K-antagonists (VKAs) such as warfarin with heparin or fractionated heparin bridging. More recently, a number of large-scale clinical trials have validated the use of direct oral anticoagulants (DOACs) in place of warfarin in select cases. In this review, we summarize the pathogenesis, diagnosis, and medical management of DVT, with particular emphasis on anticoagulation therapy and the role of DOACs in the current treatment algorithm.

Animal models of venous thrombosis

Venous thrombosis (VT) is a prevalent clinical condition with significant adverse sequela or mortality. Anticoagulation and pharmacologic or pharmacomechanical thrombolytic therapies are the mainstays of VT treatment. An understanding of thrombosis biology will allow for more effective VT-tailored diagnosis and therapy. In vivo models of thrombosis provide indispensable tools to study the pathogenesis of thrombus formation and to evaluate novel therapeutic or preventive adjuncts for VT management or prevention. In this article, we review the most prominent in vivo models of VT created in rodents and swine species and outline how each model can serve as a useful tool to promote our understanding of VT pathogenesis and to examine novel therapies.

Pathogenesis of Thromboembolism and Endovascular Management

Venous thromboembolism (VTE), a disease that includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with high mortality, morbidity, and costs. It can result in long-term complications that include postthrombotic syndrome (PTS) adding to its morbidity. VTE affects 1/1000 patients, costs

Using Naïve Bayesian Analysis to Determine Imaging Characteristics of KRAS Mutations in Metastatic Colon Cancer

13.5 billion annually to treat, and claims 100,000 lives annually in the US. The current standard of care for VTE is anticoagulation, though thrombolysis may be performed in patients with PE and threatened limb. This review discusses pathogenesis and medical treatment of VTE and then focuses on endovascular treatment modalities. Mechanical- and catheter-directed thrombolysis (CDT) is discussed, as well as patient selection criteria, and complications. The first prospective study (CaVenT) comparing CDT with anticoagulation alone in acute DVT, despite study shortcomings, corroborates the existing literature indicating improved outcomes with CDT. The potential of the ongoing prospective, multicenter, randomized ATTRACT trial is also highlighted.

Statins as a preventative therapy for venous thromboembolism

Genotype, particularly Ras status, greatly affects prognosis and treatment of liver metastasis in colon cancer patients. This pilot aimed to apply word frequency analysis and a naive Bayes classifier on radiology reports to extract distinguishing imaging descriptors of wild-type colon cancer patients and those with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. In this institutional-review-board-approved study, we compiled a SNaPshot mutation analysis dataset from 457 colon adenocarcinoma patients. From this cohort of patients, we analyzed radiology reports of 299 patients (> 32,000 reports) who either were wild-type (147 patients) or had a KRAS (152 patients) mutation. Our algorithm determined word frequency within the wild-type and mutant radiology reports and used a naive Bayes classifier to determine the probability of a given word belonging to either group. The classifier determined that words with a greater than 50% chance of being in the KRAS mutation group and which had the highest absolute probability difference compared to the wild-type group included: “several”, “innumerable”, “confluent”, and “numerous” (p < 0.01). In contrast, words with a greater than 50% chance of being in the wild type group and with the highest absolute probability difference included: “few”, “discrete”, and “[no] recurrent” (p = 0.03). Words used in radiology reports, which have direct implications on disease course, tumor burden, and therapy, appear with differing frequency in patients with KRAS mutations versus wild-type colon adenocarcinoma. Moreover, likely characteristic imaging traits of mutant tumors make probabilistic word analysis useful in identifying unique characteristics and disease course, with applications ranging from radiology and pathology reports to clinical notes.

Elastography techniques in the evaluation of deep vein thrombosis

The anti-inflammatory effects of statins have likely not been used to their fullest extent, particularly in reducing venous thromboembolic events. Current therapy for thrombotic events hinges on anticoagulation via heparin, warfarin or new oral anticoagulants. Interventional procedures with thrombectomy may also play a critical role. Unfortunately, thrombotic events can occur and recur despite meticulous anticoagulation therapy. Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism (PE), two complicated and prevalent diseases that can cause chronic disease states such as post-thrombotic syndrome (PTS). In 2009 the JUPITER trial demonstrated that rosuvastatin may be effective when dealing with vascular inflammation by providing an anti-inflammatory effect. Multiple subsequent studies have looked at this association with some promising findings. The mechanism of action for statins is not entirely understood but there has been a variety of proposals and subsequent testing of inflammatory biomarkers. Additional prospective trials are needed to confirm the possible benefit of VTE reduction through an anti-inflammatory effect, but if this can be shown then statins may become a safe adjunctive therapy for VTE prevention.

Anti-fouling strategies for central venous catheters

Deep venous thrombosis (DVT) is a significant medical problem with an incidence of 1 in 1,000 adults and greatly reduces quality of life through post-thrombotic syndrome. Treatment choice for DVT can be influenced by the age of the clot. While new endovascular catheter techniques treat venous clots to potentially prevent post-thrombotic syndrome, they require improved imaging techniques to accurately determine clot age. This review investigates experimental and clinical evidence of elastography techniques for aging DVT. Strain elastography and shear wave elastography are the most common techniques to age thrombus. These elastography techniques can distinguish between acute and chronic clots by characterizing tissue stiffness. When clot age cannot be determined with ultrasound duplex analysis, elastography may offer a helpful adjunct. However, further investigation is required to validate accuracy and reproducibility for clinical implementation of this novel technique.

Outcomes and clinical management of isolated below-knee DVT

Central venous catheters (CVCs) are ubiquitous in the healthcare industry and carry two common complications, catheter related infections and occlusion, particularly by thrombus. Catheter-related bloodstream infections (CRBSI) are an important cause of nosocomial infections that increase patient morbidity, mortality, and hospital cost. Innovative design strategies for intravenous catheters can help reduce these preventable infections. Antimicrobial coatings can play a major role in preventing disease. These coatings can be divided into two major categories: drug eluting and non-drug eluting. Much of these catheter designs are targeted at preventing the formation of microbial biofilms that make treatment of CRBSI nearly impossible without removal of the intravenous device. Exciting developments in catheter impregnation with antibiotics as well as nanoscale surface design promise innovative changes in the way that physicians manage intravenous catheters. Occlusion of a catheter renders the catheter unusable and is often treated by tissue plasminogen activator administration or replacement of the line. Prevention of this complication requires a thorough understanding of the mechanisms of platelet aggregation, signaling and cross-linking. This article will look at the advances in biomaterial design specifically drug eluting, non-drug eluting, lubricious coatings and micropatterning as well as some of the characteristics of each as they relate to CVCs.