CONDITION
MECHANISM
SETTING
CLUE · TEST
Factor V Leiden
inherited, most common
Mutant factor V (Arg506Gln) can't be cut by activated protein C.
Autosomal dominant; White populations; venous clots, worse with OCPs and pregnancy
APC-resistance assay, genetic test
Prothrombin G20210A
inherited
Mutation in the 3′ UTR → ↑ prothrombin levels.
Autosomal dominant; second most common
Venous thrombosis
Antithrombin deficiency
inherited or acquired
Less inactivation of thrombin and Xa.
Inherited (AD) or lost in nephrotic syndrome, used in DIC, ↓ in liver disease
Heparin resistance — PTT barely rises
Protein C or S deficiency
inherited
Va and VIIIa not inactivated.
Autosomal dominant; homozygous protein C → neonatal purpura fulminans
Warfarin skin necrosis on starting warfarin — bridge with heparin
Hyperhomocysteinemia
inherited or acquired
Homocysteine damages endothelium.
↓ folate, B12, B6; cystathionine β-synthase deficiency (homocystinuria)
Arterial + venous clots; tall, lens dislocated downward, intellectual disability
Antiphospholipid syndrome
acquired
Antibodies to phospholipid-binding proteins activate endothelium and platelets.
Primary or with SLE; recurrent pregnancy loss
Arterial + venous clots; ↑ PTT not corrected by mixing
Heparin-induced thrombocytopenia
acquired
IgG to heparin–PF4 activates platelets.
5–10 days into heparin
Platelets ↓ > 50% + thrombosis → argatroban
Other acquired states
hypercoagulable
More factors, more platelets, or activated cells.
Pregnancy, estrogen/OCPs, malignancy, nephrotic syndrome, smoking, obesity, PNH, myeloproliferative neoplasms
Unusual sites (Budd-Chiari, portal vein) → PNH, JAK2 neoplasm