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Hematology/Oncology

Links

• local: Anticoagulation
• Thrombocytopenia, pediatric (Pedes in Rev, Feb 1999)
• NCI/PDG Antiemetics

DVT and Coagulation Disorders

Activated Protein C (APC) Resistance

• gene defect present in about 5% of Euros, may account for 64% of DVT
• APC normally inhibits clot formation by inhibiting Factor VIII and, together with protein S inhibiting Factor V
• most APC resistance due to a mutation in factor V so that it binds less well (factor V Leiden or FVL). FVL is autosomal-dominant
• DVT risk 5-10 times normal with FVL-het, 50-100 times normal with FVL-homoz
• acquired APC resistance from OCP (60% increase prevalence), HRT (80% increased prevalence) and pregnancy (arguably people with APC should not take OCP or HRT)
• testing for APC requires a special assay, PT, PTT and TT are normal

Genetics

Breast Cancer

• BRCA1: breast cancer in women. 60%+ risk for female carrier, also 20-60% risk of ovarian.
• BRCA2: breast cancer in men and women, 60%+ risk for female, 10% risk for male. Ovarian 10%.

Hemochromatosis

• natural history very unclear, ?non-specific symptoms early (fatigure, joint pains, impotence), later pen-endocrine ("bronze diabetes")?
• autosomal recessive. Northern europeans heterozygous: 1/10 - 1/100 homozygous: 1/200
• consider screen all > 20 yo
• serum iron & transferrin saturation (sat > 60%)
• Am J Gast 1997 $

VonWillebrand’s

History

platelet defect like bleeding (slow persistent oozing), esp. post-tonsillectomy, wisdom tooth extraction, menorrhagia, worse with ASA or NSAIDs, epistaxis as child

Diagnosis

1. Any sign abnormality on two sets 2 months apart:
   • Factor VIII clotting activity
   • ristocetin cofactor (VWF activity)
   • VWF Ag level
2. AB blood norms are higher than O
3. OCP and estrogens increase VWF, give FN result