Thrombophilia - Pediatric - Lecture Slides, Slides of Pediatrics

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Thrombophilia

A pediatric perspective.

Definitions

 Unexpected tendency to form clots under inappropriate circumstances.

 Family history of vascular disease under age 50. Incl. MI, CVA or DVT.

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.

Coagulation Cascade (Robbins)

Anti-coagulation (Subar)

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/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.)

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/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