Hypercoaguable states

• Factor V Leiden Mutation (most common inheritable cause) or Resistance to Activated Protein C
• Antithrombin III Deficiency
• Protein C & Protein S Deficiency
• Prothrombin 20210A Mutation
• Hyperhomocystinemia
• Abnormal Plasminogen
• Lipoprotein (a)
• Lupus Anticoagulant / antiphospholipid antibodies
• Plasminogen deficiency/ abnormalities
• MTHFR mutation
• Increased Factor VIII, increased Fibrinogen, decreased Factor XII

MOST COMMON OVERALL:

• Acquired Nephroticsyndrome, central lines, CHD, chemo (L-ASP), trauma, OCP….and many others
• Neonates at risk more because of the higher incidence of central catheters

Diagnosis

• Gold standard to detect DVT: venogram
• Also: Doppler U/S (not that great, esp for upper venous system), Spiral CT (for PE), MRI
• Any child with a thrombosis should be evaluated for an etiology

Lab testing for hypercoaguable states

• Coagulation proteins may be falsely low during the acute event, or during a state of sepsis, maliganancy, etc.
• Therefore it is best to wait on diagnostic lab testing until 3-6 months after event (at least 1 month)
• Consider evaluating family members
• APC (activated protein C) Ratio (less than 2.0 is abnormal)
• genetic test for Factor V Leiden
• Prothrombin 20210A mutation
• Protein C & S activity (functional assays)
• ATIII Activity (functional assay)
• Antiphospholipid antibodies
• Fibrinogen functional assays and Thrombin clotting time
• Consider:
  • plasma homocysteine
  • Lipoprotein (a)

Treatment

• Acutely: LMWH
• if severe: tPA or recombinant urokinase
• Then change to oral warfarin or continue LMWH for 3-6 months, and prn high risk situations (long term tx varies)
• If recurrent/ severe, may need life-long tx
• if one time event assoc with catheter, no long term tx
• Warfarin : follow INR (goal 2-3)
• LMWH: follow anti-Factor Xa level
• Monitor for signs of skin necrosis, growth retardation, hemorrhage, osteoporosis, PE, other thromboembolic events
• Screen family members

CHLA Board review 2005

American Academy of Pediatrics. PREP The Curriculum Pediatric Review and Education Program, 1997-present
2.BehrmanRE,KliegmanRM, Jenson HB. Nelsons Textbook of Pediatrics. 16thedition. WB Saunders Company, Philadelphia, 2000
3.JourneycakeJM, Buchanan GR. “Coagulation Disorders” Pediatrics in Review, Vol. 24, No.3, March 2003
4.Nathan DG,OrkinSH, Ginsburg D, Look AT. Nathan andOski’sHematology of Infancy and Childhood. 6thedition. WB Saunders Company, Philadelphia, 2003