Internal Medicine

0521779407-20 CUNY1086/Karliner 0 521 77940 7 June 4, 2007 21:22

Thrombophilia 1423

Protein S Deficiency

■Unknown frequency in general population

■Found in 1–2% of patients with venous thrombosis

■Homozygotes develop neonatal purpura fulminans, cerebral vein

thrombosis.

■Heterozygotes have 10-fold increased relative risk for venous throm-

bosis.

Antithrombin Deficiency

■Frequency: 0.02% of general population

■Found in 1% of patients with venous thrombosis

■Homozygous state is lethal in utero.

■Heterozygotes have 25-fold increased relative risk for venous throm-

bosis.

■Pregnancy leads to thrombosis in as many as 60% of patients.

■AT concentrates are available for patients with acquired or congenital

AT deficiency.

Lupus Anticoagulant (LA)

■Criteria for diagnosis:

➣Prolonged aPTT that fails to correct after 1:1 plasma mix

➣Prolongation of at least 1 phospholipid-dependent clotting assay

➣Correction after addition of exogenous phospholipid

■Frequency is 0–2% of general population.

■Found in 5–15% of patients with venous thrombosis

■Estimated relative risk for thrombosis is about 10-fold.

Hyperhomocysteinemia

■Elevated levels of hymocysteine can arise from congenital mutations

in either Cystathionine beta-syntethase or methyl tetrahydrofolate

reductase, but are more commonly acquired.

■Secondary causes of elevated homocysteine levels:

➣renal insufficiency

➣hypothyroidism

➣smoking

➣deficiencies of either folate or B12

➣drugs (theophylline, methotrexate, phenytoin)

➣increase age

■Hyperhomocysteinemia can be found in∼10% of patients with

venous thromboembolism.

■Elevated homocysteine levels increase risk of venous clots by 2- to

4-fold.