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Venous Thromboembolism in Pediatrics

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)

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Venous Thromboembolism in Pediatrics

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  1. Venous Thromboembolism in Pediatrics Shalu Narang, M.D. Pediatric Hematology Newark Beth Israel Medical Center

  2. 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

  3. Epidemiology

  4. DVT is the Most Common Blood Clot in Children(n=84) Goldenberg et al. NEJM 2004;351:1081-8.

  5. Highest incidence of DVT in neonates and adolescents

  6. Pathophysiology

  7. Virchow’s Triad Endothelial Injury Indwelling catheters Abnormal Blood Flow Immobilization Dehydration Inflammation Nephrosis Cancer therapy Hyperviscosity Hypercoagulability Pathophysiology

  8. Conceptual Model of Hemostasis Reprinted with permission from Sidney Harris.

  9. Coagulation Cascade

  10. Pathophysiology Hemostasis Fibrinolysis Coagulation

  11. Hemostasis Pathophysiology Fibrinolysis Coagulation ↓ Thrombosis

  12. Signs, Symptoms and Diagnosis

  13. Signs & Symptoms • DVT: • Poorly Functioning Catheters • Edematous extremity • Plethoric extremity • Warm extremity • Painful extremity • PE: • Cough, SOB, Hemoptysis • Tachycardia

  14. Risk Factors • Indwelling catheters • Thrombophilia • Malignancy • Chemotherapy • Prosthetic cardiac valves • Diabetes mellitus • Sickle cell anemia • Infection • Surgery

  15. Thrombophilia

  16. 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

  17. Prevalence of inherited thrombophilia in children with DVT Revel-Vilk. J Thromb Haemost 1 (2003), 915-921 Revel-Vilk. J Thromb Haemost 1 (2003), 915-921

  18. Length of therapy remains the same regardless of thrombophilia 7th ACCP evidence based guidelines

  19. Why Screen? Single Defect: OR 4.6, p<.0001 Combined Defect: OR 24.0, p<.0001 Nowak-Gottl et al. Blood 2001;97:858-862.

  20. 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

  21. 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.

  22. Anticoagulation Therapy

  23. Therapeutic Goals • Prevent thrombus propagation and/or embolization • Restore blood flow (rapidly, when necessary) • Minimize long-term sequelae

  24. 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 Anticoagulants

  25. 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

  26. 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.

  27. 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

  28. 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

  29. 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

  30. 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

  31. Thanks!

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