Management Of Thrombotic Complications Research Articles

Approach to Contemporary Risk Assessment, Prevention and Management of Thrombotic Complications in Multiple Myeloma.

Multiple myeloma (MM) is associated with an increased risk of thrombotic complications, which remains substantial despite the implementation of thromboprophylaxis. The procoagulant state that characterizes the disease is multifactorial, and a greater understanding of the underlying pathophysiology is required to inform appropriate thrombosis prevention. Currently, there is a shift towards using direct oral anticoagulants (DOACs) in this setting; head-to-head comparisons in the context of controlled clinical trials between class agents are still missing. MM-specific VTE risk assessment scores have been developed to optimize management and minimize the associated mortality/morbidity. Their clinical utility remains to be evaluated. The value of adding biomarkers to clinical scores to optimize their performance and increase their discriminatory power is also under assessment.

Management of Thrombotic Complications in COVID-19: An Update.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2), is now a global pandemic. This virus primarily affects the respiratory tract and causes lung injury characterized by acute respiratory distress syndrome. Although the pathophysiology of COVID-19 is not yet clear, the most widely accepted mechanism is systemic inflammation. A clinically significant effect of the inflammation is coagulopathy. As a result of this effect, patients are found to have a high risk of venous thromboembolism. Studies have reported a high incidence of thrombotic complications in critically ill patients with COVID-19. In this review, we discuss the most updated evidence on the pathophysiology, diagnosis, and treatment of the coagulopathy of COVID-19. Prophylactic anticoagulation is recommended for all in-patients with COVID-19. Those with a higher risk of developing thromboembolic events or who have already developed venous thromboembolism should be treated with therapeutic anticoagulation. We also discuss post-discharge prophylaxis for high-risk patients and some newly proposed treatments for the hypercoagulability that could improve the outcomes of the affected patients.

Risk of Venous Thromboembolism in Acute Leukemias: A Meta-Analysis

Background: Venous thromboembolism (VTE) is an important cause of morbidity and mortality in cancer patients (pts). The risk of VTE, however, differs according to cancer type. Pts with hematologic malignancies are at an increased risk of VTE events, either due to the underlying disease biology or related to treatment. This risk exists even in acute leukemia (AL), which is characterized by profound thrombocytopenia and coagulopathies that present treatment challenges. Advances in anti-leukemic therapies and improved supportive care over the last several decades may have impacted the extent to which an average patient is at risk for VTE We performed a meta-analysis of published literature on VTE rates in AL pts and evaluated trends in VTE incidence in relation to the reported study time period.Methods: This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, EMBASE, Medline, Scopus and Cochran databases to identify relevant studies published between January 1980 and June 2018. All studies including randomized controlled, retrospective or observational studies in AL pts which investigated VTE as an endpoint were included. Abstracts, posters, review articles, and case reports were excluded. Articles were excluded if they did not provide disease-level data. The search terms included “venous thromboembolism”, “deep venous thrombosis”, “pulmonary embolism”, and “leukemia”. Furthermore, citations were supplemented by cross checking the reference lists of eligible studies and relevant reviews to identify additional published data. We collected study period, study design, study publication date, AL subtype, total patients, and rates of VTE. When reported, we collected information on VTE prophylaxis and presence of central lines. Meta-analysis of VTE rates was performed using an established Bayesian logistic random effects model. The model assumes that the log odds of VTE is exchangeable across studies with Gaussian distribution and random hierarchical mean and standard deviation. For both analyses, the hierarchical mean assumed a Gaussian prior with mean 0 and variance = 200. The inter-study standard deviation was assumed uniform (0,10). Given treatment and patient heterogeneity among distinct subtypes of AL, analyses were undertaken separately for each AL subtype. Results for individual studies and the combined inter-study mean VTE rate are described by the resultant posterior medians and 95% highest posterior density (HPD) intervals.Results: From the initial search, 2527 articles were identified. Among these, 938 were duplicate publications, 1408 did not meet content inclusion criteria, 150 were review articles or case reports, 2 studies lacked disease level data, thus, leaving 31 studies for analysis. A total of 29 studies focused on ALL, 11 on AML, 11 on APL, and some studies included multiple disease populations. The inter-study mean incidence of VTE for ALL was 8.67% (95% HPD 6.01%-11.58%), fig 1a, for AML was 7.25% (95% HPD 4.12%-11.09%), fig 1b, and for APL was 12.94% (95% HPD 7.04%-20.67%), fig 1c. .. Our graphical analysis indicates an increase in risk of VTE with time for ALL (fig 2a), AML (fig 2b), and APL (fig 2c).Conclusion: In the present meta-analysis, we determined that the overall incidence of VTE in AL pts ranged from 7-13%. Among AL subtypes, APL pts had the highest rate of VTE. We observed an increased risk of VTE over time. We postulate this is multifactorial and may be related to an increase in case findings from increased screening, aging sedentary population, and increased use of prothombotic agents. Notable strengths of this study include the largest review of association of VTE with AL and evolving risk of VTE with time. These findings need to be considered in light of several limitations - lack of comparator group limiting ability to generate pooled relative risks for VTE, heterogeneity in study populations and reporting and scare data on VTE prophylaxis. Further data are required to determine the mechanism for the increase in risk. Given the VTE risk and its known impact on morbidity, mortality and associated health care costs, prospective studies are warranted in AL pts to facilitate establishment of guidelines for prophylaxis and management of thrombotic complications. DisclosuresCarraway:Amgen: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Speakers Bureau; FibroGen: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Speakers Bureau; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Speakers Bureau. Advani:Amgen: Research Funding; Novartis: Consultancy; Glycomimetics: Consultancy; Pfizer: Honoraria, Research Funding. Nazha:MEI: Consultancy. Gerds:Apexx Oncology: Consultancy; Celgene: Consultancy; CTI Biopharma: Consultancy; Incyte: Consultancy. Sekeres:Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

Epidemiology of venous thrombosis in children with cancer

There has been an extensive body of research focusing on the epidemiology of thrombosis in adult cancer populations; however, there is significantly less knowledge about thrombosis in paediatric cancer populations. Thrombosis is diagnosed with increasing frequency in children being treated for cancer, and there is an urgent need to increase our understanding of the epidemiology of thrombosis in this population. Currently, there are no guidelines for identification of high-risk groups, prophylaxis or management of thrombotic complications in paediatric cancer patients. We reviewed the available literature regarding the epidemiology, mechanisms, risk factors, prophylaxis and outcomes of thrombosis in children with cancer and identified areas that require further research. The reported incidence of symptomatic venous thromboembolism (VTE) in children with cancer ranges between 2.1% and 16%, while the incidence of asymptomatic events is approximately 40%. Approximately 30% of VTE in this population is associated with central venous lines (CVL). The most common location of VTE is upper and lower extremity deep venous thrombosis (43 to 50% of events, respectively), while 50% of events in ALL patients occur in the central nervous system. Key characteristics that increase the risk of thrombosis include the type of cancer, age of the patient, the presence of a CVL, presence of pulmonary/intra thoracic disease, as well as the type of chemotherapy. Outcomes for paediatric cancer patients with VTE include post-thrombotic syndrome, pulmonary embolism, recurrent thromboembolism, destruction of upper venous system and death. Prospective studies aimed at enabling risk stratification of patients are required to facilitate development of paediatric specific recommendations related to thromboprophylaxis in this population.

Management of Thrombotic Complications in Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most common type of cancer diagnosed in children, and has been reported as the most common malignancy associated with thromboembolism in the pediatric age group. Treatment with Escherichia coli asparaginase, concomitant steroids, presence of central venous lines, and thrombophilic abnormalities are established risk factors for thromboembolism. The incidence varies with age, co-morbidities and chemotherapy regimens but the risk is highest during the induction and intensification phases. Treatment is necessary in majority of children to prevent serious sequelae. Mortality from thromboembolic events in any location is 2 to 4 % and the risk of recurrence is 7 to 10 %, further enhanced in the setting of malignancy. Randomized trials of venous thromboembolism (VTE) management in pediatric patients with ALL are lacking due to the low overall incidence, resulting in considerable variation in practice. The objective of this article is to review current knowledge on the treatment and prevention of thrombosis associated with pediatric ALL.

Case of the Season: Lemierre Syndrome

To review the thrombotic complications of head and neck infections, including Lemierre's syndrome, and their management.A retrospective review of pediatric patients presenting to McMaster Children's Hospital from 2009 to 2013 was undertaken. The literature was reviewed for evidence regarding the use of anticoagulation therapy in this population.Eleven cases (6 males, 5 females) were identified. The median age was 10.9 (range 14 months–17 years). The most frequent head and neck infection causing a thrombotic complication was mastoiditis (n = 6). All had thrombi identified on imaging, with the most common location being the sigmoid sinus (n = 6) followed by the internal jugular vein (n = 5). All 11 patients were anti-coagulated with low molecular weight heparin (LMWH) within a median of 2 days of diagnosis (average duration 105.8 days). Ten patients (90.9%) had thrombus improvement or resolution within a median of 3.4 months (range 1.0–13.9). Adverse sequelae from the thrombi were MCA infarct (n = 1), septic pulmonary emboli (n = 4), cranial nerve palsies (n = 3) and Horner's syndrome (n = 2). There were no adverse effects from anti-coagulation therapy. Review of the literature revealed anticoagulant use in 63.7% of pediatric cases reported since 2002.Anticoagulation remains controversial in the management of thrombotic complications from head and neck infections. Based on this case series, certain recommendations can be made regarding the benefits of anticoagulation, which appear to outweigh the risks. Further research is required to establish evidence for consensus in the antithrombotic management of thrombotic sequelae of head and neck infections.

High-risk Retrieval of Adherent and Chronically Implanted IVC Filters: Techniques for Removal and Management of Thrombotic Complications

To evaluate the safety and efficacy of aggressive techniques for retrieving adherent and chronically implanted inferior vena cava (IVC) filters. A single-center retrospective review was performed on all patients who underwent attempted filter retrieval from October 2007 through October 2008. Patients were included in the study if they had an adherent filter, refractory to standard retrieval techniques, and underwent high-risk retrieval after procedural risks were deemed lower than risks of long-term filter implantation. Fourteen patients were diagnosed with an adherent filter, 13 (93%) of whom were candidates for high-risk retrieval. These patients included seven men and six women (mean age, 40 years; age range, 18-71 years). Nine of the 13 patients (69%) were referred from an outside hospital. Filter retrieval was performed for the following indications: to avoid the risk of long-term thrombotic complications in a young patient (n= 6), to treat symptomatic filter-related IVC stenosis (n= 5), to treat symptomatic filter penetration (n= 1), and to avoid the need for lifelong anticoagulation (n= 1). There were eight Günther-Tulip filters (mean dwell time, 356 days; range 53-1,181 days), two Optease filters (mean dwell time, 62 days; range, 52-72 days), one G2 filter (dwell time, 420 days), and two Recovery filters (mean dwell time, 1,630 days; range, 1,429-1,830 days). Three IVC occlusions necessitated recanalization to facilitate retrieval. High-risk retrieval with use of various techniques with aggressive force was successful in all 13 patients (100%). Partial caval thrombosis occurred in the first four patients (31%) but did not occur after procedural modifications were implemented. There were no complications at clinical follow-up (mean, 221 days; range, 84-452 days). Alternative techniques can be used to retrieve adherent IVC filters implanted for up to 3-5 years. Although caval thrombosis was an observed complication, protocol modifications appeared to reduce this risk.

Endovascular repair of infrarenal abdominal aortic aneurysm associated with a horseshoe kidney and graft thrombosis in early follow-up

Endovascular aneurysm repair (EVAR) is a well-established alternative to open surgery. The presented case underwent endovascular therapy of an abdominal aortic aneurysm (AAA) with the anatomical prerequisite of a horseshoe kidney. We describe the technique used, including the embolization of aortic side branches, to avoid endoleaks, and the management of thrombotic complications during follow-up.

IgA Anticardiolipin in Patients with Gastroenteric Tumor

Recently the presence of antiphospholipid antibodies in patients with cancer has been demonstrated, suggesting an involvement of autoimmune response in neoplastic conditions. The presence of antiphospholipid antibodies in tumor disease is highly correlated with the risk of developing thrombotic complications, which represents a significant cause of morbidity and mortality in cancer patients. Interestingly, it has been highlighted that high levels of IgM and IgG anticardiolipin antibodies are more often produced in patients with gastroenteric tumor than in patients with either ovarian or breast tumor. Thus far, there are no data looking into the role or measurements of IgA in patients with solid cancer. Our preliminary results, in this study, demonstrate that testing only for IgG and IgM anticardiolipin antibodies may increase the incidence of false positive because 44% who were IgA positive and IgG and IgM negative had high titres of CA19.9 and CEA. We suggest that taking into account the role of IgA could substantially improve the detection of antiphospholipids antibodies in subjects with solid cancer, and this detection may allow us for better prevention and management of thrombotic complications in these patients.

Low molecular weight heparins in cancer patients: to treat thromboembolic events, the tumor, or both?

The interrelationship between cancer and thrombosis is well known. Recent data help physicians to optimize the management of thrombotic complications occurring in cancer patients. However, many issues are still uncertain. First, although the development of venous thromboembolism (VTE) in a patient with known cancer is the most common presentation, concerns remain about the optimal duration and dosages of anticoagulants. Questions also arise concerning the need to implement heparin prophylaxis in the course of chemotherapy. Secondly, in some patients, thrombosis precedes the diagnosis of malignancy. In this case, the question is whether or not to screen patients for an occult cancer. Thirdly, very recent studies have shown the hemostatic system plays a key role at different stages of tumor growth. Anticoagulants, especially low molecular weight heparin (LMWH), appear therefore to be an attractive strategy not only for managing the risk for thrombosis but, possibly, to improve patient outcome and survival. However, the use of these compounds in settings other than VTE is questionable. Finally, most of the data come from studies evaluating patients with different types of cancer at different stages, thus making results difficult to evaluate. Additional research is required to clarify the biological mechanisms involved and to answer still unresolved clinical questions. In this review, the evidence for the use of LMWHs in cancer patients will be presented and remaining doubts discussed.

Combined Surgical and Endovascular Removal of Thrombus Entirely Occluding a Bifurcated Aortic Stent-Graft

Purpose: To explore a method combining interventional, endovascular, and conventional surgical techniques for treating a completely occluded bifurcated stent-graft after endovascular aortic aneurysm repair. Methods and Results: A 60-year-old patient underwent endovascular repair of an abdominal aortic aneurysm (AAA) with a Talent bifurcated stent-graft. Five months later, after chronic thrombotic occlusion of the right iliac limb, he presented with acute occlusion of the entire stent-graft. Local intra-arterial infiltration thrombolysis successfully reconstituted flow through the main aortic segment and left iliac limb. With a combination of conventional surgical and intraoperative endovascular procedures, thrombectomy and recanalization of the right iliac limb was completed by stenting a severe stenosis of the proximal iliac limb. Conclusions: A combination of techniques may be essential for successful management of thrombotic complications after endovascular AAA repair.

Prevention and management of thrombotic complications during coronary interventions: Combination therapy with antithrombins, antiplatelets, and/or thrombolytics: risks and benefits

Acute occlusions after percutaneous transluminal coronary intervention occur in about 5% of cases. The incidence of these serious adverse events may be reduced by the identification of risk factors, appropriate indication for the intervention, and by medical therapy with antiplatelets and antithrombins. The medical management of complications during percutaneous transluminal interventions also may include thrombolytics. Aspirin has been shown to significantly reduce the incidence of procedure-related coronary occlusion and ischaemic events. Available data suggest pre-treatment with 250-500 mg followed by 100-300 mg aspirin after the intervention. Ticlopidine seems to be equally effective; however, because of its side effects it should be used only in cases of a contra-indication to aspirin. The second indispensable therapeutic concept in the prevention of acute thrombotic events during PTCA is thrombin inhibition. The level of anticoagulation achieved by heparin seems to be critically important. Therefore the recommendation for heparin dosing is a bolus of 10,000 U followed by an intravenous infusion over 24 h of either 1000 U.h-1 or an infusion adjusted to keep the aPTT above 3 times control, but lower doses of shorter duration may be equally effective in uncomplicated cases. Prolonged pre-treatment with heparin may be useful if the pre-intervention angiogram is suggestive of intracoronary thrombus. Thrombolysis as an adjunct to PTCA did not reduce the rate of periprocedural coronary occlusions, but pre-treatment with thrombolysis may be useful in patients with recanalization of occluded vein grafts or in patients with large amounts of thrombotic material. In acute coronary occlusion, thrombolysis has rarely been used as a sole rescue therapy and results have not been encouraging, although a thrombotic process often is involved. Thrombolysis as an adjunct to rescue angioplasty showed no better clinical outcome than prolonged balloon inflation or stenting. Because of serious bleeding complications, thrombolysis should only be considered as a treatment option if thrombosis is unequivocally the major cause of the acute occlusion.