Risk Factors, Prophylaxis, and Treatment of Venous Thromboembolism in Congenital Heart Disease Patients.
ABSTRACT: Congenital heart disease (CHD) is a common condition in the pediatric population, affecting up to 1% of all live births (i.e., around 40,000 newborns/year in the United States). Although CHD does have a wide range of severity, by the age of 5 years approximately 80% of patients will require at least one surgical intervention to achieve a complete/palliative cardiac repair. Today, in light of their much-improved surgical survival, the care of these patients focuses on morbidity prevention and/or treatment. One such morbidity has been the increased frequency of thrombotic occlusions [e.g., cardioembolic arterial ischemic strokes; arterial, cardiac, and/or newly created shunt thrombosis; venous thromboembolism (VTE)]. Patients with CHD are at high risk of developing thrombosis due to the disruption of blood flow, CHD-related coagulopathy, inflammation, and/or platelet activation secondary to extracorporeal circulation support required during open-heart surgery or as a bridge to recovery, which can increase thrombus formation. In this article, we will discuss how the coagulation system is altered in patients with CHD in regard to the patient's anatomy, procedures they undergo to correct their congenital heart defect, and other risk factors that may increase their thrombotic risk, focusing on VTE. We will also discuss the most recently published reports pertaining to guidelines on prophylaxis and treatment of VTE in this population. Finally, we will briefly address the long-term VTE outcomes for patients with CHD.
Project description:Antiphospholipid syndrome (APS), is an acquired autoimmune disorder characterised by thrombosis, pregnancy morbidity, and the presence of antiphospholipid antibodies (aPL). Although venous thromboembolism is the most common manifestation, thrombotic events in APS may also occur in virtually any vascular bed, with cerebral circulation being the arterial territory most commonly affected. As APS is a heterogeneous condition, its management should be tailored with a patient-centred approach based on individual risk assessment, which includes the aPL profile, concomitant auto-immune diseases, and traditional cardiovascular risk factors. Although literature data are conflicting regarding primary prophylaxis, there is some evidence indicating that antiplatelet agents may reduce the risk of a first thrombotic event in individuals with a high-risk profile. In patients with thrombotic APS, current evidence-based guidelines recommend lifelong vitamin K antagonists (VKAs), preferably warfarin. The optimal intensity of anticoagulation following arterial thrombosis remains controversial. Arterial thrombosis should be treated either with high-intensity warfarin at a target INR > 3.0, or low-dose aspirin (LDA) combined with moderate-intensity warfarin (INR 2.0-3.0). It is recommended to avoid direct oral anticoagulants (DOACs) in patients with high-risk APS, mainly those with triple-positive PL and previous arterial events. They would only be used exceptionally in selected patients with low-risk venous thromboembolism (VTE). In low-risk VTE patients currently treated with a DOAC due to warfarin intolerance or a previous unstable International Normalized Ratio on warfarin, the decision of continuing DOACs would be taken in carefully selected patients. In women with obstetric APS, the combination therapy with LDA plus heparin remains the conventional strategy.
Project description:AbstractBackgroundVeno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a well-recognized form of haemodynamic support for patients with refractory cardiogenic shock, who are unable to be weaned off cardiopulmonary bypass. Thrombosis or bleeding from cannula sites or surgical wounds are the leading cause of morbidity and mortality in these patients, and presents a delicate balance of anticoagulation during management of patients undergoing circulatory support.Case summaryIn this case series, we discuss three cases of patients undergoing mitral valve replacements or repair with thrombosis of their new bio-prosthesis in the immediate post-operative setting. All three patients were supported with VA-ECMO post-operatively, and thrombosis occurred despite anticoagulation.DiscussionDuring extracorporeal membrane oxygenation, the reduced flow throughout the heart increases the risk of intra-cardiac thrombosis. This is of particular importance in the context of mitral valve replacements and repairs, where the bio-prosthesis is an additional risk factor for thrombosis. Our cases demonstrate the morbidity and mortality of such complications, with the likely aetiology being low transvalvular flow in a newly inserted valve combined with the pro-thrombotic state created by the VA-ECMO circuit.
Project description:•Increased incidence of venous thrombosis has been demonstrated in SARS-CoV2 infected patients but no data are available for arterial thrombosis.•We observed very severe arterial thrombotic complications in COVID-19 patients with cardiovascular history despite the use of antiplatelet or anticoagulant therapy, including five irreversible lower limb ischemia and two thoracic aortic free floating thrombi.•Three patients were in intensive care unit (ICU) and two of them also presented VTE, one deep vein thrombosis and one segmental PE.•Further studies are needed to evaluate the necessity of therapeutic anticoagulation in COVID-19 patients with peripheral arterial occlusive disease or thrombophilia.
Project description:Venous thromboembolism (VTE) is common in patients with cancer and is an important contributor to morbidity and mortality in these patients. Early thromboprophylaxis initiated only in those cancer patients at highest risk for VTE would be optimal. Risk stratification scores incorporating tumor location, laboratory values and patient characteristics have attempted to identify those patients most likely to benefit from thromboprophylaxis but even well-validated scores are not able to reliably distinguish the highest-risk patients. Recognizing that tumor genetics affect the biology and behavior of malignancies, recent studies have explored the impact of specific molecular aberrations on the rate of VTE in cancer patients. The presence of certain molecular aberrations in a variety of different cancers, including lung, colon, brain and hematologic tumors, have been associated with an increased risk of VTE and arterial thrombotic events. This review examines the findings of these studies and discusses the implications of these findings on decisions relating to thromboprophylaxis use in the clinical setting. Ultimately, the integration of tumor molecular genomic information into clinical VTE risk stratification scores in cancer patients may prove to be a major advancement in the prevention of cancer-associated thrombosis.
Project description:Antiphospholipid syndrome (APS) is associated with arterial and venous thrombosis. The unfavorable fibrin clot phenotype, including formation of dense and poorly lysable clots, has been reported both in thrombotic APS and venous thromboembolism (VTE). The presence and amount of different proteins within a plasma clot, not only associated with the coagulation system, may influence clot properties. To our knowledge, there is a lack of data on plasma fibrin-clot bound proteins in patients with thrombotic APS or VTE. The aim of our study was to perform a quantitative proteomic analysis of fibrin clots prepared from citrated plasma from subjects with thrombotic APS and prior VTE, along with fibrin clot permeability (Ks) and clot lysis time (CLT) assessed ex vivo. We investigated 23 consecutive patients with APS, 18 with a history of first-ever VTE, and 20 age and sex matched healthy subjects. A multiple enzyme digestion filter aided sample preparation and a multienzyme digestion (MED) FASP method combined with LC-MS/MS analysis performed on a Proxeon Easy-nLC System coupled to the Q Exactive HF mass spectrometer were used. The proteomic analysis revealed that clot composition regarding 117 proteins in APS patients and 48 proteins in VTE patients was changed as compared to healthy controls, while 72 clot-bounded proteins differed between APS and VTE subjects. In healthy controls, Ks was associated with fibrinogen alpha and gamma chains (r=0.46 and r=0.46, both p<0.05, respectively) or apolipoprotein B-100 (r=-0.53, p<0.05), while CLT correlated with annexin A2 (r=-0.58, p<0.05), apolipoportein(a) (r=0.47, p<0.05), or platelet glycoprotein 4 (r=0.59, p<0.05). In VTE patients correlations of Ks with complement C1q and histone H2B, as factors closely linked with thrombosis, were observed (r=-0.52 and r=-0.47, both p<0.05, respectively). In patients with thrombotic APS all above-mentioned associations were not found. This study is the first to show that different proteins are able to influence the clot formation, structure, and properties. Since, prothrombotic conditions abolished associations observed in healthy subjects fibrin clots, differences in protein clot components might explain the links between prothrombotic fibrin clot phenotype and thromboembolic events.
Project description:Venous thromboembolism (VTE; deep vein thrombosis and/or pulmonary embolism) is a well-established cause of morbidity and mortality in the medical and surgical patient populations. Clinical research in the prevention and treatment of VTE has been a dynamic field of study, with investigations into various treatment modalities ranging from mechanical prophylaxis to the direct oral anticoagulants. Aspirin has long been an inexpensive cornerstone of arterial vascular disease therapy, but its role in the primary or secondary prophylaxis of VTE has been debated. Risk-benefit tradeoffs between aspirin and anticoagulants have changed, in part due to advances in surgical technique and postoperative care, and in part due to the development of safe, easy-to-use oral anticoagulants. We review the proposed mechanisms in which aspirin may act on venous thrombosis, the evidence for aspirin use in the primary and secondary prophylaxis of VTE, and the risk of bleeding with aspirin as compared with anticoagulation.
Project description:BACKGROUND:Congenital heart disease accounts for almost a third of all major congenital anomalies. Congenital heart defects have a significant impact on morbidity, mortality and health costs for children and adults. Research regarding the risk of pre-surgical mortality is scarce. OBJECTIVES:Our goal is to generate a predictive model calculator adapted to the regional reality focused on individual mortality prediction among patients with congenital heart disease undergoing cardiac surgery. METHODS:Two thousand two hundred forty CHD consecutive patients' data from InCor's heart surgery program was used to develop and validate the preoperative risk-of-death prediction model of congenital patients undergoing heart surgery. There were six artificial intelligence models most cited in medical references used in this study: Multilayer Perceptron (MLP), Random Forest (RF), Extra Trees (ET), Stochastic Gradient Boosting (SGB), Ada Boost Classification (ABC) and Bag Decision Trees (BDT). RESULTS:The top performing areas under the curve were achieved using Random Forest (0.902). Most influential predictors included previous admission to ICU, diagnostic group, patient's height, hypoplastic left heart syndrome, body mass, arterial oxygen saturation, and pulmonary atresia. These combined predictor variables represent 67.8% of importance for the risk of mortality in the Random Forest algorithm. CONCLUSIONS:The representativeness of "hospital death" is greater in patients up to 66 cm in height and body mass index below 13.0 for InCor's patients. The proportion of "hospital death" declines with the increased arterial oxygen saturation index. Patients with prior hospitalization before surgery had higher "hospital death" rates than who did not required such intervention. The diagnoses groups having the higher fatal outcomes probability are aligned with the international literature. A web application is presented where researchers and providers can calculate predicted mortality based on the CgntSCORE on any web browser or smartphone.
Project description:Antiphospholipid syndrome (APS) is an acquired autoimmune condition characterized by thrombotic events, pregnancy morbidity, and laboratory evidence of antiphospholipid antibodies (aPL). Management of these patients includes the prevention of a first thrombotic episode in at-risk patients (primary prevention) and preventing recurrent thrombotic complications in patients with a history of thrombosis (secondary prevention). Assessment of thrombotic risk in these patients, balanced against estimated bleeding risks associated with antithrombotic therapy could assist clinicians in determining whether antithrombotic therapy is warranted. Thrombotic risk can be assessed by evaluating a patient's aPL profile and additional thrombotic risk factors. Although antithrombotic options for secondary prevention of venous thromboembolism (VTE) have been evaluated in clinical trials, studies in primary prevention of asymptomatic aPL-positive patients are needed. Primary prevention with aspirin may be considered in asymptomatic patients who have a high-risk aPL profile, particularly if additional risk factors are present. Secondary prevention with long-term anticoagulation is recommended based on estimated risks of VTE recurrence, although routine evaluation of thrombotic risk can assist in determining whether ongoing anticoagulation is warranted. Studies that stratify thrombotic risk in aPL-positive patients, and patients with APS evaluating antithrombotic and non-antithrombotic therapies will be useful in optimizing the management of these patients.
Project description:Newly diagnosed multiple myeloma (NDMM) patients treated with immunomodulatory drugs are at high risk of venous thromboembolism (VTE), but data are lacking from large prospective cohorts. We present thrombosis outcome data from Myeloma IX (n = 1936) and Myeloma XI (n = 4358) phase 3 randomized controlled trials for NDMM that treated transplant-eligible and transplant-ineligible patients before and after publication of thrombosis prevention guidelines. In Myeloma IX, transplant-eligible patients randomly assigned to cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) induction had higher risk of VTE compared with patients treated with cyclophosphamide, thalidomide, and dexamethasone (CTD) (22.5% [n = 121 of 538] vs 16.1% [n = 89 of 554]; adjusted hazard ratio [aHR],1.46; 95% confidence interval [95% CI], 1.11-1.93). For transplant-ineligible patients, those randomly assigned to attenuated CTD (CTDa) induction had a higher risk of VTE compared with those treated with melphalan and prednisolone (MP) (16.0% [n = 68 of 425] vs 4.1% [n = 17 of 419]; aHR, 4.25; 95% CI, 2.50-7.20). In Myeloma XI, there was no difference in risk of VTE (12.2% [n = 124 of 1014] vs 13.2% [n = 133 of 1008]; aHR, 0.92; 95% CI, 0.72-1.18) or arterial thrombosis (1.2% [n = 12 of 1014] vs 1.5% [n = 15 of 1008]; aHR, 0.80; 95% CI, 0.37-1.70) between transplant-eligible pathways for patients treated with cyclophosphamide, lenalidomide, and dexamethasone (CRD) or CTD. For transplant-ineligible patients, there was no difference in VTEs between attenuated CRD (CRDa) and CTDa (10.4% [n = 95 of 916] vs 10.7% [n = 97 of 910]; aHR, 0.97; 95% CI, 0.73-1.29). However, arterial risk was higher with CRDa than with CTDa (3.1% [n = 28 of 916] vs 1.6% [n = 15 of 910]; aHR, 1.91; 95% CI, 1.02-3.57). Thrombotic events occurred almost entirely within 6 months of treatment initiation. Thrombosis was not associated with inferior progression-free survival (PFS) or overall survival (OS), apart from inferior OS for patients with arterial events (aHR, 1.53; 95% CI, 1.12-2.08) in Myeloma XI. The Myeloma XI trial protocol incorporated International Myeloma Working Group (IMWG) thrombosis prevention recommendations and compared with Myeloma IX, more patients received thromboprophylaxis (80.5% vs 22.3%) with lower rates of VTE for identical regimens (CTD, 13.2% vs 16.1%; CTDa, 10.7% vs 16.0%). However, thrombosis remained frequent in spite of IMWG-guided thromboprophylaxis, suggesting that new approaches are needed.
Project description:<h4>Background</h4>As adults with congenital heart disease (ACHD) are getting older, acquired comorbidities play an important role in morbidity and mortality. Data regarding their prevalence in ACHD that are representative on a population level are not available.<h4>Methods</h4>The German National Register for Congenital Heart Defects was screened for ACHD. Underlying congenital heart disease (CHD), patient demographics, previous interventional/surgical interventions, and comorbidities were retrieved. Patients <40 years of age were compared to those ?40 years.<h4>Results</h4>A total of 4673 patients (mean age 33.6 ± 10.7 years, female 47.7%) was included. At least one comorbidity was present in 2882 patients (61.7%) altogether, and in 56.8% of patients below vs. 77.7% of patients over 40 years of age (<i>p</i> < 0.001). Number of comorbidities was higher in patients ?40 years (2.1 ± 2.1) than in patients <40 years (1.2 ± 1.5, <i>p</i> < 0.001). On multivariable regression analysis, age and CHD complexity were significantly associated with the presence and number of comorbidities.<h4>Conclusions</h4>At least one acquired comorbidity is present in approximately two-thirds of ACHD. Age and complexity of the CHD are significantly associated with the presence of comorbidities. These findings highlight the importance of addressing comorbidities in ACHD care to achieve optimal long-term outcomes.