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To develop an evidence-based protocol for the management of iliofemoral deep vein thrombosis (IDVT) in childhood.
A search of the literature was undertaken. All publications pertaining to IDVT in childhood were analysed and then categorised according to their level of evidence. Recommendations were then made on the basis of this.
The commonest pres...
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Context 1
... Since 3 years of age, he was noted to have some autistic features and thus continues to attend a special needs school. On examin- ation he was well with no features of systemic disease. Since, admission his right leg had become swollen (mid- thigh circumference 2.5 cm greater than left) with evidence of superficial venous hypertension (Fig. 1). It was also noted that the right testicle was absent. Examination of the hip and knee was normal. A diagnosis of proximal deep vein thrombosis was suspected and confirmed by compression duplex ...
Context 2
... estimated incidence of symptomatic venous thromboembolic disease (VTE) in children is 5.3/10,000 (0.05%) hospital admissions versus 2.5–5% for adults. 1–10 The occurrence of VTE in childhood has a bimodal distribution. The first peak is in the neonatal period (0–28 days) and is thought possibly to be due to the lower concentrations of antithrombin, heparin cofactor II and protein C along with a reduced fibrinolytic capacity, thus resulting in a prothrombotic state. The incidence then decreases significantly after the first year of life, with the second peak during puberty and on into adolescence, associated with reduced fibrinolytic activity. 11 VTE, does occur at all ages (as demonstrated in Section 2), has many well- recognised risk factors and others that are rarely considered. In this paper, we consider the evidence behind those risk factors that should be sought, the investigations best employed and treatment options in the management of iliofemoral deep vein thrombosis (IDVT) in the paediatric patient. A 7-year-old schoolboy presented with a 4-day history of right-sided hip and groin pain associated with a limp on that side. There was no prodromal illness of note. He had been born by normal vaginal delivery at 42 weeks and had no history of admission to Special Care Baby Unit or central venous catheterisation. Since 3 years of age, he was noted to have some autistic features and thus continues to attend a special needs school. On examin- ation he was well with no features of systemic disease. Since, admission his right leg had become swollen (mid- thigh circumference 2.5 cm greater than left) with evidence of superficial venous hypertension (Fig. 1). It was also noted that the right testicle was absent. Examination of the hip and knee was normal. A diagnosis of proximal deep vein thrombosis was suspected and confirmed by compression duplex scan. A thrombophilia screen was sent before commencing the patient on subcutaneous low molecular weight heparin (LMWH) for 2 weeks, prior to commencing warfarin. He was found to be heterozygous for factor V Leiden mutation. Compression therapy with grade I compression stockings was commenced and multi-slice CT scanning of the abdomen and pelvis was performed. This scan demonstrated an absent infra-renal inferior vena cava with the pelvic and lower limb veins draining through grossly dilated spinal and lumbar veins (Fig. 2). There was no abnormality of the solid abdominal organs. Anticoagulation with warfarin shall continue indefinitely. An electronic search of the literature was undertaken using search terms of ‘thrombosis’, ‘paediatric’, ‘pediatric’, ‘childhood’, ‘venous’, ‘diagnosis’, ‘therapy’, and ‘management’. All publications pertaining to the management of IDVT in childhood were analysed and then categorised according to their level of evidence. Recommendations were then made on the basis of this. The majority of VTE within the first year of life is associated with central venous access devices. 8–10,12,13 The femoral vein is rarely used for central venous access in the neonate (the majority of catheters were inserted via an umbilical vein or the upper venous system) so IDVT is rarely seen in this population. However, there have been reports of spontaneous thromboses in the visceral veins of neonates, but these have been linked to factors such as sepsis, dehy- dration, perinatal hypoxia, or maternal diabetes. 14 While an age greater than 1 year seems to be protective via such postulated mechanisms as a reduced capacity to produce thrombin, 15,16 increased capacity of alpha-2 macroglobulin to inhibit thrombin, 17 and enhanced antithrombotic potential of the vessel wall, 18,19 there are increasing numbers of children older than this developing VTE as secondary complications to other underlying disorders. Approxi- mately 95% of episodes of VTE in childhood have an underlying, serious condition as an aetiological factor causing the thrombosis. These conditions include malignancy, trauma, surgery, congenital heart disease and other malformations of the vascular system, renal disease and autoimmune diseases such as systemic lupus erythematosus (SLE). 8,20–22 The important acquired and congenital risk factors associated with VTE are shown in Tables 1 and 2, respectively. The role of congenital prothrombotic states in the aetiology of VTE remains controversial. There is good evidence that the defects affecting the physiological anticoagulant system (i.e. factor V Leiden mutation, factor II variant G20210A, and deficiencies in proteins C and S, and antithrombin) can play a causal role in thrombotic events. 23,24 Metabolic diseases such as hyperhomocysteinaemia due to the homozygous methylenetetrahydrofolate reductase (MTHFR) polymorphism C677T, homozygous homocystinuria, and increased concentrations of lipoprotein (a) have been shown to increase the risk of both arterial and venous thromboembolism. 23–28 VTE in children (and adults) is a multifactorial condition. There is now level II evidence that multiple haemostatic prothrombotic defects or the association of these risk factors with environmental or clinical situations greatly increases the risk of VTE. 29,30 The relative risk of recurrent episodes of VTE is also significant and increases with the number of inherited gene defects. It has been shown that there is a 4.6-fold increased risk of recurrent VTE in children with a first spontaneous thrombosis and a single prothrombotic defect, and a documented 24-fold increased risk in those with multiple defects. 27 Central venous catheters (CVC) are placed for short- term use. They are used mostly in intensive care settings for fluid management, haemodialysis, and drug administration or for long-term supportive care for children requiring total parenteral nutrition (TPN) or chemotherapy for malignant disease. CVC-related VTE does carry a significant morbidity, including pulmonary embolus (PE) 31,32 and post-thrombotic syndrome (PTS). 33 CVC-related VTE has been divided into three types; clots at the tips of the CVC that impair the withdrawal of blood or infusion, fibrin sleeves that are not adherent to the vessel wall but occlude the catheter, and CVC-related VTE that is adherent to the vessel wall, can cause complete or partial occlusion and is, therefore, the most clinically significant. 34 While in most circumstances such catheters are placed in the jugular or subclavian vein, in the older child that is critically ill, or a younger child with a chronic condition where alternative access sites have been exhausted, the femoral vein can provide central venous access. Femoral CVC-related VTE is, therefore, ...
Citations
... However, the efficiency and tolerance of LMWH and Warfarin have been evaluated in children. 7,8 Based on currently available best evidences, 9 the first line of treatment includes Heparin (UFH or LMWH) to prevent extension and oral anticoagulation to prevent recurrence. 4 ...
We describe a rare case of deep vein thrombosis (DVT) in children, highlight the importance of early diagnosis of rare disease with potential complications. In a 5 year old boy presented with persistent leg pain without any obvious cause. Detailed investigation led to diagnosis of DVT. As there are common differential diagnoses for leg pain in children, pediatricians usually have a low index of suspicious of DVT in children. This case highlight that paediatricians must consider DVT in their differential diagnosis when children present with leg pain.
... 2,3 Approximately 90% of venous thromboembolism episodes in childhood have an underlying condition. 4 Although IBD is associated with various venous thromboses, association of iliac vein thrombosis and inflammatory bowel disease is rare. We present a 9.5 year-old child with Crohn's disease and internal iliac vein thrombosis. ...
Thromboembolic events are one of the important extraintestinal manifestations of inflammatory bowel diseases that are associated with considerable morbidity and mortality. Iliac vein thrombosis is rarely reported in inflammatory bowel diseases. A 9.5 year-old girl was presented with joint pain, nausea, vomiting and weight loss. She was diagnosed with Crohn's disease and right internal iliac vein thrombosis. With the implementation of immunosuppressive and anticoagulant therapies clinical picture has improved and thrombosis has resolved. Timely diagnosis and early treatment of extraintestinal complications of inflammatory bowel diseases might be lifesaving.
... 25,26 One group has recently tried to rationalize these data, and provide an evidence-based management plan for deep vein thrombosis (DVT) in children. 27 Guidelines on treatment and prophylaxis of VTE in childhood are available but are rarely based on randomized controlled trials or registries of sufficient size. 28 As the risks of DVT are much lower than in the adult population, indications for primary prophylaxis in the paediatric population are fewer. ...
Antiphospholipid syndrome (APS) is defined by the persistent presence of moderate to high serum levels of antiphospholipid antibodies (aPL) in association with recurrent thrombotic events, pregnancy loss or both. APS may occur as a primary disorder or secondary to an underlying autoimmune disease. Half of all paediatric cases are of the secondary type, and approximately 80% of these have systemic lupus erythematosus as the underlying disease. Acute anticoagulant therapy is recommended for first episode of deep vein thrombosis, and thrombolytic therapy is recommended only for life- or limb-threatening thrombosis. We experienced a 13-year-old girl who was diagnosed as having primary APS with triple positivity for aPL, i.e. plasma lupus anticoagulant, anticardiolipin antibodies and anti-β2 glycoprotein I antibodies. She did not respond to initial treatment with anticoagulant therapy including unfractionated heparin and warfarin, and dyspnoea and chest pain were getting worse. Contrast computed tomography on day 12 revealed exacerbation of thromboembolism (TE). Owing to deterioration in patient condition, urokinase was added immediately after the placement of an inferior vena cava filter. After initiating thrombolytic therapy, her oxygenation and symptoms showed gradual improvement. In conclusion, it is obvious that refractory APS patients with triple-positive are at a high risk of recurrent thrombotic event and a first thrombotic event; the treatment of TE in the acute phase should be guided by careful risk-assessment based on the patient’s aPL profile.
Authors present risk factors of venous thromboembolism in children, diagnostics and treatment in deep venous thrombosis and management of complications of antithrombotic therapy.
Thromboembolism is one of the serious complications of pediatric idiopathic nephrotic syndrome (NS). We report the case of a 4-year-old boy suffering from steroid-resistant NS complicated with posterior reversible encephalopathy syndrome (PRES), acute kidney injury and multiple vein thrombosis. Although his symptoms with PRES subsequently improved by antihypertensive therapy, his renal dysfunction persisted requiring peritoneal dialysis. And then, intestinal thromboembolism caused sepsis and intestinal necrosis as a result. Despite thrombolytic and antibiotic therapy, his condition with sepsis and massive diarrhea caused by intestinal necrosis didn’t improve. Since his electroencephalogram suggested poor neurologic prognosis, we discontinued active treatments with fully informed consent of his parents and he died 93 days after onset. Adequate anticoagulation to prevent thromboembolism should be considered in treatment of the severe NS in children.
Authors present risk factors of venous thromboembolism in children, diagnostics and treatment in deep venous thrombosis and management of complications of antithrombotic therapy
Neonates and children differ from adults in physiology, pharmacologic responses to drugs, epidemiology, and long-term consequences of thrombosis. This guideline addresses optimal strategies for the management of thrombosis in neonates and children.
The methods of this guideline follow those described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
We suggest that where possible, pediatric hematologists with experience in thromboembolism manage pediatric patients with thromboembolism (Grade 2C). When this is not possible, we suggest a combination of a neonatologist/pediatrician and adult hematologist supported by consultation with an experienced pediatric hematologist (Grade 2C). We suggest that therapeutic unfractionated heparin in children is titrated to achieve a target anti-Xa range of 0.35 to 0.7 units/mL or an activated partial thromboplastin time range that correlates to this anti-Xa range or to a protamine titration range of 0.2 to 0.4 units/mL (Grade 2C). For neonates and children receiving either daily or bid therapeutic low-molecular-weight heparin, we suggest that the drug be monitored to a target range of 0.5 to 1.0 units/mL in a sample taken 4 to 6 h after subcutaneous injection or, alternatively, 0.5 to 0.8 units/mL in a sample taken 2 to 6 h after subcutaneous injection (Grade 2C).
The evidence supporting most recommendations for antithrombotic therapy in neonates and children remains weak. Studies addressing appropriate drug target ranges and monitoring requirements are urgently required in addition to site- and clinical situation-specific thrombosis management strategies.
Late complications of thrombosis of the deep veins in the region between the popliteal vein termination and the confluence of the common iliac veins and inferior vena cava (suprapopliteal deep-vein thrombosis) are common and often unrecognized by those responsible for the initial management. Pharmacomechanical-assisted clearance of the thrombus at the time of first presentation provides the best opportunity for complete recovery with preservation of normal venous valve function and avoidance of recurrent deep-vein thrombosis and postthrombotic syndrome. Recent interventional radiology methods provide for rapid and complete thrombolysis even in some patients in whom thrombolysis was previously considered contraindicated. This review describes the methods, safety, and efficacy of acute interventional treatment of suprapopliteal deep-vein thrombosis.
