Venous Thromboembolism in Pediatrics
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Transcript of Venous Thromboembolism in Pediatrics
Venous Thromboembolism in PediatricsShalu Narang, M.D.
Pediatric Hematology Newark Beth Israel Medical Center
Objectives
• Epidemiology and pathophysiology of pediatric thrombotic disorders
• Signs, symptoms and diagnosis of deep venous thrombosis (DVT)
• Acquired vs. inherited thrombophilia• Diagnostic screening tests for thrombotic
disorders• Role of anticoagulation in children with
thrombotic disorders• Long-term sequelae of thrombosis
Epidemiology
DVT=63%CSVT=18%Isol PE=5%RVT=6%IAS=10%
DVT is the Most Common Blood Clot in Children (n=84)
Goldenberg et al. NEJM 2004;351:1081-8.
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Highest incidence of DVT in neonates and adolescents
Pathophysiology
Pathophysiology
• Virchow’s Triad • Endothelial Injury– Indwelling catheters
• Abnormal Blood Flow– Immobilization– Dehydration– Inflammation– Nephrosis– Cancer therapy– Hyperviscosity
• Hypercoagulability
Conceptual Model of Hemostasis
Reprinted with permission from Sidney Harris.
Coagulation Cascade
Pathophysiology
Hemostasis
Coagulation Fibrinolysis
Pathophysiology
HemostasisCoagulation
↓Thrombosis
Fibrinolysis
Signs, Symptoms and Diagnosis
Signs & Symptoms
• DVT:– Poorly Functioning
Catheters– Edematous extremity– Plethoric extremity– Warm extremity– Painful extremity
• PE:– Cough, SOB, Hemoptysis– Tachycardia
Risk Factors
• Indwelling catheters• Thrombophilia• Malignancy• Chemotherapy• Prosthetic cardiac valves• Diabetes mellitus• Sickle cell anemia• Infection• Surgery
Thrombophilia
Thrombophilia
• Inherited: – Protein C deficiency– Protein S deficiency– Antithrombin deficiency– Factor V leiden – Prothrombin gene mutation– Elevated Lipoprotein a, homocysteine
• Acuired: – Antiphospholipid Syndrome– Nephrotic syndrome
Revel-Vilk. J Thromb Haemost 1 (2003), 915-921
Prevalence of inherited thrombophilia in children with DVT
Prevalence Test Affected/tested
Study Population
Factor V Leiden 8/171 4.7 % 4 %
Prothrombin G20210A 4/171 2.3 % 2 %
Protein S deficiency 2/171 1.2 % 0.3 %
Protein C deficiency 1/171 0.6 % 0.3 %
Antithrombin deficiency 0/171 0.0 % 0.02 %
Lipoprotein (a) >30mg/dl 8/107 7.5 % 7 %
Revel-Vilk. J Thromb Haemost 1 (2003), 915-921
Length of therapy remains the same regardless of thrombophilia
First episode of DVT Length of anticoagulation
Transient risk factor 3 months
Idiopathic TE 6-12 months
Thrombophilia 6-12 months
7th ACCP evidence based guidelines
Why Screen?
Nowak-Gottl et al. Blood 2001;97:858-862.
Single Defect: OR 4.6, p<.0001Combined Defect: OR 24.0, p<.0001
Laboratory Studies
• DIC Screen:– CBC, PT, aPTT, Thrombin Time, Fibrinogen, D-dimer
• Protein C Activity• Protein S Activity• Antithrombin III Activity• Lupus Anticoagulant• Anticardiolipin antibody• Prothrombin gene mutation• Factor V leiden
Healthy Children w/ Family History of DVT or
Thrombophilia
• Screening is rarely indicated:– Risk assessment limited by heterogeneity of
genotype and phenotype– No guidelines for management– Potential risk of anticoagulation outweighs benefit– May inhibit ability to obtain life/disability insurance– Ethical concerns: autonomy, assent, consent– Appropriate age for screening unknown– Unnecessary anxiety
Courtesy: Bryce A. Kerlin, M.D.
Anticoagulation Therapy
Therapeutic Goals
• Prevent thrombus propagation and/or embolization
• Restore blood flow (rapidly, when necessary)
• Minimize long-term sequelae
Anticoagulants
• Heparin– Un-fractionated vs. low
molecular weight– IV or SQ– Monitoring with PTT or
anti-Factor Xa – Reversible with
protamine
• Warfarin– Vitamin K antagonist– Only oral anticoagulant– Monitor with PT– Reversible with vitamin
K– Very long T½
Risk Stratification*
(for persistence or recurrence)• Low Risk
– Thrombus post surgery, trauma, CVL– Resolves within 6 weeks
• Standard Risk– FVIII <150U/dL– D-dimer <500ng/mL– < 3 thrombophilic factors– Non-occlusive thrombus
• High Risk– FVIII >150u/dL– D-dimer >500ng/mL– >3 thrombophilic factors– Occlusive thrombus
Manco-Johnson, Blood 2006*Studies in progress
Anticoagulant Duration
• Ongoing Studies: no guidelines!– Low/Standard Risk:
• 6 wks (Thrombus Resolution and no thrombophilia) • 3 months (Residual Thrombus or thrombophilia)
– High Risk:• Early thrombolysis AND• 6 months vs.12 months
Multi-institutional studies in progress.
Long-term Sequelae
• Post-thrombotic Syndrome (PTS)– Pain, swelling, visible
collateral vain formation, skin abnormalities
– 10-60% children• Recurrent TE
– Life-Threatening Embolic Disease
– 7-8% children
Summary
• Pediatric thrombosis is most common in infants and adolescents
• DVT is most common form of VTE• The upper extremity circulation is most
commonly affected• Diagnosis should be confirmed with:
– D-dimer– Venous Doppler Ultrasonography– CT Angiogram
Summary
• Initial treatment should be standard or low molecular weight heparinization
• Short courses may be completed with heparin, longer courses may benefit from transition to Warfarin
• Duration of anticoagulant therapy is individualized based on underlying co-morbidities
• Patients should be followed closely for recurrent disease and/or post-phlebitic syndrome
Summary
• All thrombosis patients should be screened for treatable molecular thrombophilias
• Some patients may benefit from additional screening
• Asymptomatic patients and family members not at increased risk for thrombosis should not routinely be screened
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