venous thromboembolism in pediatrics
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Venous Thromboembolism in Pediatrics. Shalu 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) - PowerPoint PPT PresentationTRANSCRIPT
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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