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Cerebral venous sinus thrombosis (CVST) is a serious and potentially life-threatening condition, whose diagnosis is often missed or delayed due to often non-specific presentations. However, if diagnosed and managed appropriately prognosis is generally favourable. This Element covers the common presentations and epidemiology of CVST, progressing through the approach to investigation and management of this condition in the acute, sub-acute and more chronic timeframes.
n-3 PUFA delivered by fish oil supplements alter the number and functions of circulating extracellular vesicles (EV), but consumption of oily fish does not reproduce this effect. In order to assess the effects of fish oil supplements and oily fish, at a level achievable in the diet, on EV numbers, composition and procoagulant activity in healthy human volunteers, forty-two healthy subjects were assigned to one of three treatment groups: (i) fish oil supplements plus white fish meals, (ii) control supplements plus oily fish meals or (iii) control supplements plus white fish meals for 12 weeks in a randomised, double-blind, placebo-controlled, parallel trial; circulating EV were enumerated and their procoagulant activity assessed using thrombin generation and fibrinolysis assays. Our results showed that fish oil supplements decreased circulating EV numbers and reduced EV-stimulated thrombin generation, but the consumption of oily fish at half the dose of EPA had no effect on either EV number or thrombogenic capacity. Consumption of both oily fish and fish oil supplements increased the EPA and DHA contents of EV, and the proportion of EPA in circulating EV was strongly associated with EV-stimulated thrombin generation. This study revealed that the additional 1 g/d EPA delivered in the fish oil supplements is required to decrease the numbers and thrombogenic capacity of EV, since oily fish at a level achievable in the diet had no effect. Increasing EPA intake beyond current guidelines for oily fish consumption may therefore be required for cardiovascular benefits relating to EV.
A randomised parallel intervention study was conducted with male patients diagnosed with CHD. Participants were assigned to three groups: Group A abstained from alcohol (n 20), Group B consumed red wine (n 21) and Group C (n 16) consumed an alcoholic beverage without wine micro-constituents. Biological samples were collected at baseline, 4 and 8 weeks. Enzyme activities of acetyl-CoA:lyso-platelet-activating factor (PAF) acetyltransferase, cytidine 5’-diphospho (CDP)-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-cholinephosphotransferase), PAF-acetylhydrolase in leukocyte homogenates, serum lipoprotein-associated phospholipase-A2 and plasma markers of thrombosis were measured. PAF-, ADP- and collagen-induced platelet aggregation was measured in human platelet-rich plasma. Red wine consumption led to a 15·3 % reduction in LysoPAF-acetyltransferase activity at 4 weeks (P= 0·008) compared with baseline and Group A (P= 0·01). PAF-cholinephosphotransferase activity was reduced by 11·1 % at 8 weeks (P= 0·04) compared with baseline and by 24·9 % compared with Group C (P= 0·02). PAF-acetylhydrolase activity was reduced by 36·2 % at 8 weeks compared with baseline (P= 0·001) and compared with Group A (P< 0·000) and Group C (P= 0·009). Fibrinogen levels in Group B reduced by 6–9 % at 4 (P= 0·04) and 8 weeks (P= 0·01) compared with baseline while D-dimer in Group C increased by 16·1 % at 8 weeks (P= 0·005) compared with baseline. Platelet aggregation against PAF and collagen was reduced in Group B (82·6 and 35·4 %, respectively), and in Group C (158·4 and 37·1 %, respectively) compared with baseline and Group A (P< 0·05). In conclusion, moderate wine consumption improved the activity of PAF-metabolism enzymes regardless of ethanol and reduced platelet aggregation, probably through mechanisms different from those of ethanol.
We report on a 7-month-old boy (4.2 kg/60 cm) with severe immunodeficiency disorder and bacterial septicaemia who was referred for an infected atrial thrombus secondary to a jugular central line. The echocardiogram showed a teardrop-shaped thrombus with a wide base adherent to the interatrial wall and a flimsy tail moving freely in the right atrium. Chest CT scan showed multiple lesions in both lungs consistent with infected micro-thrombi. The thrombus increased in size despite 2 weeks of antibiotics and anticoagulation. We applied the Indigo® Lightning® 7 aspiration system from Penumbra® (Alameda, USA) and removed percutaneously the thrombus under transoesophageal ultrasound and biplane fluoroscopic guidance. At 6 weeks of follow-up, the patient is alive, under enoxaparin with no procedure-related complication.
Many paediatric studies report that patients must be established on aspirin therapy for a minimum of 5 days to achieve adequate response. This is not always practical especially in critical settings. Prospective identification of patients that are unresponsive to aspirin sooner could potentially prevent thrombotic events.
Aims:
The aim of this study was to investigate prospectively if the first dose of aspirin is effective in decreasing platelet aggregation, and thromboxane formation and if this can be measured after 2 hours in paediatric cardiology patients. A secondary aim was to identify a cut-off for a novel marker of aspirin responsiveness the maximum amplitude with arachidonic acid, which could potentially dramatically reduce the blood volume required. Third, we aimed to prospectively identify potentially non-responsive patients by spiking a sample of their blood ex vivo with aspirin.
Results:
The majority (92.3%) of patients were responsive, when measured 2 hours post first dose of aspirin. Non-response or inadequate response (7.7%) can also be identified at 2 hours after taking the first dose of aspirin. Additionally, we have shown a novel way to reduce blood sample volume requirements by measurement of the maximum amplitude with arachidonic acid as a marker of response, particularly for monitoring.
Conclusions:
These findings of rapid efficacy in the majority of patients offer assurance in a sound, practical way to attending clinicians, patients, and families.
Hematological disorders are a heterogeneous group that may be inherited or acquired. During pregnancy the condition may improve, stabilize, or deteriorate due to normal physiological changes. Major risks in women are hemorrhage or thrombosis; inherited conditions may affect fetus as well. A multidisciplinary team is required to manage the pregnancy, delivery, and postpartum. This chapter reviews and summarizes the literature on maternal and fetal outcomes with a focus on anesthetic considerations and publications.
Cerebrovascular accident (CVA) or stroke is an interruption of blood supply due to thrombosis or embolization.
Thrombosis is caused by an in situ clot at a site of atherosclerotic plaque. Embolization is caused by an intravascular embolus. Sources include atrial fibrillation, ventricular aneurysm, hypokinetic ventricle, myocardial infarction, prosthetic valve, infective endocarditis and proximal friable atherosclerotic plaques.
Lying in after giving birth has a long tradition but carries a risk of thrombosis. Blood clots form in leg veins and may embolise to the lungs, causing death. Early CEMD Reports did not recognise the benefits of early ambulation but divided thromboembolism deaths into three groups – during pregnancy, after vaginal delivery and after caesarean section. The Reports identified risk factors including age, obesity and caesarean section, and found that warning symptoms were being ignored. Shorter hospital stay reduced the number of deaths after vaginal birth. Caesarean section rates rose and an Enquiry into Perioperative Deaths (modelled on the CEMD) revealed the risk factors for post-operative thromboembolism. An 1995 an RCOG report advised on preventive measures including anticoagulants, previously avoided lest they cause bleeding. A sharp fall in deaths after caesarean section followed in 1997-9. By then thromboembolism was the leading Direct cause of maternal death and the benefits of guidelines had become clear. In 2004 the RCOG published a guideline on thromboprophylaxis in pregnancy and in 2006-8 thomboembolism fell to third place among causes of Direct death.
Thrombosis is a common disorder with a relevant burden of morbidity and mortality worldwide, particularly among elderly patients. Growing evidence demonstrated a direct role of oxidative stress in thrombosis, with various cell types contributing to this process. Among them, erythrocytes produce high quantities of intracellular reactive oxygen species (ROS) by NADPH oxidase activation and haemoglobin autoxidation. Concomitantly, extracellular ROS released by other cells in the blood flow can be uptaken and accumulate within erythrocytes. This oxidative milieu can alter erythrocyte membrane structure, leading to an impaired erythrocyte function, and promoting erythrocytes lysis, binding to endothelial cells, activation of platelet and of coagulation factors, phosphatidylserine exposure and release of microvesicles. Moreover, these abnormal erythrocytes are able to adhere to the vessel wall, contributing to thrombin generation within the thrombus. This process results in accelerated haemolysis and in a hypercoagulable state, in which structurally impaired erythrocytes contribute to increase thrombus size, to reduce its permeability and susceptibility to lysis. However, the wide plethora of mechanisms by which oxidised erythrocytes contribute to thrombosis is not completely elucidated. This review discusses the main biochemical aspects linking erythrocytes, oxidative stress and thrombosis, addressing their potential implication for clinical and therapeutic management.
The incidence of prosthetic valve implantation is increasing in the paediatric population. Prosthetic valve thrombosis leading to obstruction could potentially be a life-threatening complication. There is a debate regarding optimal management of this complication, and there is limited use of thrombolytic therapy in childhood in the setting of valve thrombosis.
Objective:
We aim to share our experience of successfully using fibrinolytic therapy in terms of alteplase for paediatric prosthetic mitral valve thrombosis and to propose a management algorithm.
Methods:
This retrospective analysis of the database was conducted at our hospital including patients who underwent thrombolysis (alteplase) for prosthetic mitral valve thrombosis from June, 2011 to June, 2021. A total of 10 patients with 20 attempts of alteplase infusion were found in our record.
Results:
Alteplase was successful in 19 attempts to relieve valve thrombosis. The safe and effective dose of alteplase was between 0.1 and 0.3 mg/kg/hour. There were no associated major bleeding complications and alteplase was administered either by central or peripheral line.
Conclusion:
Thrombolysis by alteplase infusion was found to be successful in relief of prosthetic mitral valve thrombosis in paediatric population without major bleeding complications.
Infradiaphragmatic partial anomalous pulmonary venous connection is occasionally diagnosed in adulthood. Management of infradiaphragmatic PAPVC depends on anatomy and clinical presentation.
Methods:
Over a 10-year period, we observed seven adult patients (median age 29 years) with partial anomalous pulmonary venous connection. We classified our patients in two groups. Group I: isolated partial anomalous pulmonary venous connection from one pulmonary lobe to the inferior vena cava, three patients. Group II: partial anomalous pulmonary venous connection of the entire right lung to IVC, four patients.
Results:
The mean term follow-up was 5.4 years. Patients in Group I have been managed conservatively, as they were asymptomatic, without a significant shunt. Patients in Group II were surgically corrected using long right intra-atrial baffles. After 6 months of follow-up, the first two cases were diagnosed with complete tunnel thrombosis and loss of right lung function. Oral anticoagulation failed to recanalize the tunnel. Considering this serious complication, the other two patients were empirically and preventively treated with anticoagulation after surgery, with good outcome on long-term follow-up.
Conclusions:
Conservative management should be considered for asymptomatic patients, without a significant shunt. Surgical treatment of infradiaphragmatic partial anomalous pulmonary venous connection of the entire right lung in inferior vena cava is challenging. Slow blood flow inside the long intra-atrial baffles inclines to thrombosis and occlusion, as we observed in two cases. Therefore, oral anticoagulation should be considered for long baffles with slow blood flow.
A 6-year-old boy, born with hypoplastic left heart syndrome, underwent total cavopulmonary connection and later presented in a significantly deteriorated condition. A CT scan revealed multiple thrombi in the extracardiac conduit, although the patient was maintained on an effective anticoagulant therapy. Further examination revealed anamnestic antibodies suggesting that the patient had gone through a clinically inapparent COVID-19 infection, which we conclude most likely contributed to his hypercoagulable state and led to the formation of significant thrombi impairing the patient’s haemodynamics. The patient underwent a surgical thrombectomy; there were no post-operative thrombotic complications.
Paediatric otogenic cerebral venous sinus thrombosis is a rare, heterogeneous and life-threatening condition, with possible otological, neurological and ophthalmological sequelae. Its course and outcomes can be widely variable. The publications available often consider individual aspects of paediatric otogenic cerebral venous sinus thrombosis management. The condition itself and the nature of the currently available guidance can lead to uncertainties when holistically managing patients with paediatric otogenic cerebral venous sinus thrombosis.
Objectives
Clear recommendations for the comprehensive assessment and management of paediatric otogenic cerebral venous sinus thrombosis are presented, along with the literature review upon which they are based. Its clinical and radiological assessment are discussed.
Conclusion
A multidisciplinary approach to assessment and management is recommended, inclusive of infectious diseases, ENT surgery, neurology, ophthalmology and haematology. On balance, anticoagulation is recommended for three months. Follow-up imaging is not recommended in the absence of clinical concern. Follow up by ENT surgery, neurology and ophthalmology departments is recommended.
Acute stent thrombosis may complicate neonatal arterial duct stenting for reduced pulmonary blood flow. Thrombolytic agents recanalise the clot but may cause bleeding around the vascular sheaths and other sites. Since early thrombus is platelet mediated, intravenous platelet glycoprotein inhibitor like eptifibatide is likely to be effective, but rarely utilised in neonates. Ductal stent thrombosis treated with eptifibatide is reported.
Patients with cyanotic heart disease are at an increased risk of developing thrombosis. Aspirin has been the mainstay of prophylactic anticoagulation for shunt-dependent patients with several reports of prevalent aspirin resistance, especially in neonates. We investigate the incidence of aspirin resistance and its relationship to thrombotic events and mortality in a cohort of infants with shunt-dependent physiology.
Methods:
Aspirin resistance was assessed using the VerifyNow™ test on infants with single-ventricle physiology following shunt-dependent palliation operations. In-hospital thrombotic events and mortality data were collected. Statistical analysis was performed to evaluate the effect of aspirin resistance on in-hospital thrombotic events and mortality risk.
Results:
Forty-nine patients were included with 41 of these patients being neonates. Six patients (12%) were aspirin resistant. A birth weight < 2500 grams was a significant factor associated with aspirin resistance (p = 0.04). Following a dose increase or additional dose administration, all patients with initial aspirin resistance had a normal aspirin response. There was no statistically significant difference between aspirin resistance and non-resistance groups with respect to thrombotic events. However, a statistically significant incidence of in-hospital mortality in the presence of thrombotic events was observed amongst aspirin-resistant patients (p = 0.04) in this study.
Conclusion:
Low birth weight was associated with a higher incidence of aspirin resistance. Inadequate initial dosing appears to be the primary reason for aspirin resistance. The presence of both thrombotic events and aspirin resistance was associated with significantly higher in-hospital mortality indicating that these patients warrant closer monitoring.
Aspirin (acetylsalicylic acid, ASA) is inexpensive and is established in preventing cardiovascular disease (CVD) and colorectal adenomas. Omega-3 (n3) polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have also shown benefit in preventing CVD. The combination could be an effective preventative measure in patients with such diseases. ASA and n3 PUFA reduced the risk of CVD in ASA-resistant or diabetic patients. EPA- and DHA-deficient patients also benefited the most from n3 PUFA supplementation. Synergistic effects between ASA and EPA and DHA are ‘V-shaped’ such that optimal ASA efficacy is dependent on EPA and DHA concentrations in blood. In colorectal adenomas, ASA (300 mg/d) and EPA reduced adenoma burden in a location- and subtype-specific manner. Low doses of ASA (75–100 mg/d) were used in CVD prevention; however, ultra-low doses (30 mg/d) can also reduce thrombosis. EPA-to-DHA ratio is also important with regard to efficacy. DHA is more effective in reducing blood pressure and modulating systemic inflammation; however, high-dose EPA can lower CVD events in high-risk individuals. Although current literature has yet to examine ASA and DHA in preventing CVD, such combination warrants further investigation. To increase adherence to ASA and n3 PUFA supplementation, combination dosage form may be required to improve outcomes.
Bleeding in the perioperative period of congenital heart surgery with cardiopulmonary bypass is associated with increased morbidity and mortality both from the direct effects of haemorrhage as well as the therapies deployed to restore haemostasis. Perioperative bleeding is complex and multifactorial with both patient and procedural contributions. Moreover, neonates and infants are especially at risk. The objective of this review is to summarise the evidence regarding bleeding management in paediatric surgical patients and identify strategies that might facilitate appropriate bleeding management while minimising the risk of thrombosis. We will address the use of standard and point-of-care tests, and the role of contemporary coagulation factors and other novel drugs.
Symptomatic presentation of ductal arteriosus aneurysm is usually a consequence of associated complications, including thromboembolism, infection, and compression of adjacent structures. In this case report, we present a thrombosed ductal aneurysm that developed antenatally with further postnatal progression of the thrombus and complete occlusion of the left pulmonary artery. Urgent surgical thrombectomy was successful and the post-operative course was uneventful.