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ThrombophiliaThrombophilia
A pediatric perspective.Craig Dobson, MD
CPT, MC, USAR
NCC Pediatrics Residency Program
DefinitionsDefinitions
Unexpected tendency to form clots under inappropriate circumstances.
Family history of vascular disease under age 50. Incl. MI, CVA or DVT.
CaseCase
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?
EpidemiologyEpidemiology
Venous thrombosis lifetime prevalence 5-10% of total population.
Highest incidence in neonatal and post-pubertal.
Neonates 5/100k.Teens incidence 23/100k.
Neonatal PresentationNeonatal 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 PresentationAdolescent Presentation
DVTCVAAsymptomatic, suspected through FHx.Important to screen to avoid sudden death
early in adulthood.
Work UpWork 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/GeneticEtiology/Genetic
Excessive factor VIII (11/100 whites)Factor V Leiden (8/100 whites)Prothrombin excess (2/100 whites)Antithrombin III def. (1/5000)
Etiology/GeneticEtiology/Genetic
Sickle cell disease (1/400 blacks)Protein C deficiency (1/500)Protein S deficiencyRare conditions: Def in fibrinolysis,
congenital HUS, pro-coagulant platelets.
Etiology/AcquiredEtiology/Acquired
Platelets and RBCs– Polycythemia/thrombocythemia– TTP, HUS
Excess Thrombin– Factor V Leiden– Lupus anticoagulant/ anti-cardiolipin– Incr tissue factor (infection/trauma/malignancy)
Etiology/AcquiredEtiology/Acquired
Def thrombin regulation– ATIII deficiency (renal failure)– Hepatic synthetic dysfunction.– Auto-antibodies– DIC
Medications– OCPs– Heparin– L-asp (really hepatic synth.)
Etiologies/AcquiredEtiologies/Acquired
Homocysteinemia– Smoking– Sedentary lifestyle– Coffee– Diet (low folate, B6 or B12)
Therapies/HeparinTherapies/Heparin
Mechanism: catalysis of AT.Neonates have lower AT levels.Monitoring: aPTTProblems
– aPTT levels based on adult therapeutic studies.– Even in adults, therapeutic aPTT may not
suggest clinically sufficient anti-coag.
Therapies/HeparinTherapies/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/ LMWHTherapies/ LMWH
Low Molecular Weight HeparinLess 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-anticoagulantsTherapies/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-Therapies/Oral Anti-coagulantscoagulants
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 RevisedCase 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.
ReferencesReferences
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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