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Thrombophilia Thrombophilia A pediatric perspective Craig Dobson MD CPT

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Thrombophilia Thrombophilia A pediatric perspective Craig Dobson MD CPT Powered By Docstoc
					        Thrombophilia


A pediatric perspective.
                     Craig Dobson, MD
                     CPT, MC, USAR
                     NCC Pediatrics
                     Residency Program
              Definitions
 Unexpected tendency to form clots under
  inappropriate circumstances.
 Family history of vascular disease under
  age 50. Incl. MI, CVA or DVT.
                  Case
 9yo male at presents for eval for psych
  admission to CNMC for acute psychosis.
 Disorganized behavior, non-communicative
  except occasional screaming fits.
 Associated symptoms headache, high
  fevers, occasional watery stools.
 Head CT with contrast notes lateral venous
  sinus thrombosis. But why?
            Epidemiology
 Venous thrombosis lifetime prevalence 5-
  10% of total population.
 Highest incidence in neonatal and post-
  pubertal.
 Neonates 5/100k.
 Teens incidence 23/100k.
        Neonatal Presentation
 Typically in-utero or within first 48hrs of life.
 Catheter thrombosis.
    – Still requires evaluation.
   Renal vein thrombosis
    – Flank mass on exam
    – Thrombocytopenia, HTN, hematuria.
 Seizures from CVA or lesion on head U/S.
 Neonatal Purpura Fulminans
    – Homozygous Protein C or S def.
    Adolescent Presentation
 DVT
 CVA
 Asymptomatic, suspected through FHx.
 Important to screen to avoid sudden death
  early in adulthood.
Coagulation Cascade   (Robbins)
Anti-coagulation   (Subar)
Virchow’s Triad   (Robbins)
                  Work Up
   PT/PTT, Mixing studies if elev PTT.
   CBC
   ATIII, Protein C&S (total and free)
   Factor V Leiden
   Homocysteine level or MTHFR gene mutation
   Prothrombin G20210A gene mutation
   Anti-phospholipid Abs
   Lipoprotein a
          Etiology/Genetic
 Excessive factor VIII (11/100 whites)
 Factor V Leiden (8/100 whites)
 Prothrombin excess (2/100 whites)
 Antithrombin III def. (1/5000)
          Etiology/Genetic
 Sickle cell disease (1/400 blacks)
 Protein C deficiency (1/500)
 Protein S deficiency
 Rare conditions: Def in fibrinolysis,
  congenital HUS, pro-coagulant platelets.
            Etiology/Acquired
   Platelets and RBCs
    – Polycythemia/thrombocythemia
    – TTP, HUS
   Excess Thrombin
    – Factor V Leiden
    – Lupus anticoagulant/ anti-cardiolipin
    – Incr tissue factor (infection/trauma/malignancy)
             Etiology/Acquired
   Def thrombin regulation
    – ATIII deficiency (renal failure)
    – Hepatic synthetic dysfunction.
    – Auto-antibodies
    – DIC
   Medications
    – OCPs
    – Heparin
    – L-asp (really hepatic synth.)
          Etiologies/Acquired
   Homocysteinemia
    – Smoking
    – Sedentary lifestyle
    – Coffee
    – Diet (low folate, B6 or B12)
           Therapies/Heparin
 Mechanism: catalysis of AT.
 Neonates have lower AT levels.
 Monitoring: aPTT
 Problems
    – aPTT levels based on adult therapeutic studies.
    – Even in adults, therapeutic aPTT may not
      suggest clinically sufficient anti-coag.
           Therapies/Heparin
 Recommended dose 75U/kg loading.
 Maintenance drip dose varies:
    – Infants <1yr of age 28U/kg/hr
    – Children > 1yr 20U/kg/hr
   Side effects (besides bleeding):
    – Heparin induced thrombocytopenia
    – Osteoporosis
           Therapies/ LMWH
 Low Molecular Weight Heparin
 Less monitoring needed, more predictable
  blood levels, less osteoporosis.
 Increase dose needed for age <2mo (0.75mg
  Q12). >2mo (0.5mg)
 Monitor anti-factor Xa levels.
    – In children you need to monitor , unlike adults.
    – Peak is 2-6hrs after injection SQ.
Therapies/Oral-anticoagulants
 Increases vitamin-K dependent proteins (II,
  VII, IX, X) plus Proteins C & S.
 Newborns have reduced levels of vitamin-K
  dependent proteins. (Shot at birth helps.)
 Vitamin K added to formulas.
 Minimal in breastmilk.
         Therapies/Oral Anti-
             coagulants
 Monitor INR 2-3.
 Problem: requires stable diet. Impossible in
  2yr old.
 Some recommend INR 1.5-2.5.
 Large difference in required dose:
    – Infants 0.32mg/kg/d
    – Teens 0.09mg/kg/d
            Case Revised
 Etiology thought originally to be erosive
  mastoiditis due to fluid in mastoid near
  lateral venous sinus.
 Mastoidectomy performed, culture negative
  transudate.
 Further testing by GI, revealed pt with early
  presentation of Crohn’s disease.
                       References
   Manco-Johnson, M & Nuss, R. Advances in Pediatrics, Chp 12, Vol
    48. 2001.)
   Monagle, et al. Antithrombotic Therapy in Children. Chest. 119 (1),
    2001.
   Cotran: Robbins Pathologic Basis of Disease, 1999 (all images).
   Subar M - Clin Geriatr Med - 01-Feb-2001; 17(1): 57-70, vi
    Van Cott, E. Coagulation disorders and treatment strategies: laboratory
    evaluation of hypercoagulable states. Hematology/oncology Clinics of
    North Amer. V12 (6), 1998.

				
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