What Is Venous Thromboembolism in Children?
Venous thromboembolism is a condition that includes both deep venous thrombosis and pulmonary embolism. Although the condition is rare in healthy children, it can pose a significant risk in children with underlying medical conditions or hospitalized children. Venous thromboembolism is being diagnosed more frequently from increased awareness and invasive technology that can detect underlying medical conditions.
What Is the Incidence and Pathophysiology of Venous Thromboembolism in Children?
Pathophysiology of venous thromboembolism depends on changes in blood flow, endothelial injury, or hypercoagulability of blood. Disruption between the balance of procoagulant, anticoagulant, and fibrinolytic causes thrombosis formation.
Venous thromboembolism is rare and accounts for one case in every lakh population. The incidence of venous thromboembolism peaks during the neonatal and adolescent stages. CVAD (central venous abscess device) use, which gives premature and severely ill infants life-sustaining medication, is blamed for the peak during the neonatal stage. Adolescents developing venous thromboembolism indicate the development of adult risk factors for the condition.
What Are the Causes of Developing Venous Thromboembolism in Children?
Multiple factors cause venous thromboembolism in 90 percent of children, the most predominant being genetic and acquired. Genetic factors responsible for increased thrombosis risk are inherited thrombophilia. Common inherited thrombophilic defects are protein S and C deficiency and anti-thrombin deficiency. Therefore, all neonates, children, and adolescents suspected of venous thromboembolism must undergo testing.
Venous thromboembolism is often classified as provoked and unprovoked. Provoked venous thromboembolism is caused by an acquired risk factor. Transient causes include surgery, CVAD, infection, and estrogen therapy. Persistent causes include active cancer, inflammatory bowel disease (inflammation in the digestive tract), and congenital heart disease. Any acquired risk factors do not cause unprovoked venous thromboembolism. Both transient and persistent causes occur in children. However, less than 10 percent of children develop unprovoked venous thromboembolism.
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Neonates or Infants: Children below one year account for many venous thromboembolism cases. Most cases develop in premature babies or infants with congenital heart disease. Since this age group has developed homeostasis, their response to anticoagulation therapy, bleeding, site of thrombosis, and optimal drug dosage could vary. The changes to the infant’s homeostasis occur during the first six months of the child’s life.
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CVAD-Associated Venous Thromboembolism: It is the most common risk factor for venous thromboembolism in more than 90 percent of neonates and 50 percent of children. CVAD predominantly causes thrombosis due to endothelial injury from their placement, venous stasis due to disruption in venous flow, and underlying factors inducing hypercoagulability (tendency to develop blood clots). Even in CVAD, the catheters inserted peripherally have a higher risk for venous thromboembolism than tunneled catheters. The obstruction from the clot could be at the CVAD tip, or there might be a partial or complete vein occlusion. Treatment includes leaving the device in place if functional or clinically necessary. However, the CVAD is withdrawn if it is non-functional or no longer needed.
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Adolescents: Adolescents are more likely to develop unprovoked venous thromboembolism. The characteristics and treatment guidelines for venous thromboembolism in adolescents are similar to those of adults. The common risk factors for developing venous thromboembolism are inherited thrombophilia, thoracic outlet obstruction (nerves and blood vessels in thoracic outlet are compressed), May-Thurner syndrome (syndrome affecting pelvic vein), or defects in the inferior vena cava. Other risk factors are malignancy, obesity, hormonal contraception, rheumatic or inflammatory diseases, and immobility. However, the risk of recurrence for venous thromboembolism is higher in adolescents.
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Other Factors: Infections or bacterial toxins can cause uncontrolled inflammation that induces changes in endothelium, epithelium, and immune system and cause multiple organ failure. As a result, it causes alteration in bleeding and coagulation.
What Is the Presentation of Venous Thromboembolism in Children?
Pediatric venous thromboembolism is highly heterogeneous and exhibits differences in presentation based on age, thrombosis location, and underlying medical condition. Among children, venous thromboembolism can develop in various locations, including upper and lower deep veins, abdominal veins, right atrium, pulmonary arteries, and cerebral sinuses.
How Is Venous Thromboembolism Treated in Children?
There is limited data about treatment in pediatric trials. Therefore, treatment decisions are based on adult clinical studies and expert consensus. The treatment mainly focuses on observation, anticoagulation, or thrombectomy. Anticoagulants like low-molecular-weight Heparin and Warfarin help treat venous thromboembolism in children. The primary treatment goal with anticoagulants is to prevent clot formation, embolism, and recurrence. It is not given to patients with a risk of bleeding. However, the limitations of this treatment method are subcutaneous injection and frequent monitoring. Clinical trials are ongoing for oral anticoagulant use in pediatric patients with venous thromboembolism.
Generally, unprovoked venous thromboembolism requires anticoagulation therapy for a minimum of three months. The duration can extend to 6 to 12 months based on underlying disease. CVAD-associated venous thromboembolism is treated for only six weeks. When a rapid clot resolution is needed, thrombolytic agents are used. A frequently used thrombolytic agent in children is Alteplase. However, the major limitation of this treatment is severe bleeding in neonates.
What Care Is a Must in Children Receiving Anticoagulant Therapy?
To prevent injury, caregivers should talk to their children about appropriate activities. Toddlers must use safe helmets to protect their scalps or face from bruising. To reduce the impact of falls, older kids are recommended to always maintain one foot on the ground. Collision and contact sports are restricted while the child is on anticoagulation therapy.
What Are the Complications Due to Venous Thromboembolism in Children?
Proper diagnosis, treatment, and optimal prophylactic strategies for venous thromboembolism are essential to avoid long-term complications. Some of the complications are:
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Pulmonary embolism.
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Paradoxial emboli and stroke.
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Organ dysfunction.
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Infection.
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Post-thrombotic syndrome.
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Loss of venous abscess.
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Pain.
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Death.
The common complication of venous thromboembolism is bleeding. Protamine successfully reverses bleeding caused by low molecular weight or unfractionated heparin. Warfarin's side effects are reversed with vitamin K.
What Is the Prognosis for Venous Thrombosis in Children?
A 2.2 percent mortality rate was reported among children with venous thromboembolism. Therefore, venous thromboembolism in the pediatric population is a severe condition due to significant complications such as pulmonary embolism, cerebrovascular events, and post-thrombotic syndrome.
Conclusion
Recently, venous thromboembolism in children is increasingly being diagnosed. Most cases are caused due to an underlying medical disorder. Treatment for venous thromboembolism for the pediatric population is anticoagulant and thrombolytic therapy.
