Heparin-induced thrombocytopenia (HIT) is caused by heparin-dependent, platelet-activating
IgG antibodies that increase thrombin generation in vivo, producing a prothrombotic
phenotype. In addition to platelet activation, there is in vitro evidence that activation
of endothelium and monocytes occurs, perhaps directly by HIT antibodies, but more
likely through activated platelet (or microparticle)-endothelial-leukocyte interactions.
Patients with cardiac disease receiving heparin present important diagnostic and therapeutic
issues when unexpected thrombocytopenia arises. Concomitant vascular disease burden
and intravascular catheter use further increase risk of HIT-associated arterial thrombosis
in this patient population. Whether arterial thrombosis simply reflects the “hypercoagulability
state” of HIT interacting with diseased or injured arteries, or whether arterial “white
clots” reflect additional prothrombotic effects of HIT via endothelial and monocyte
activation, remains uncertain. Patients with HIT can also develop deep-vein thrombosis,
which can progress to limb loss if coumarin (warfarin) leads to severe protein C depletion
(coumarin-induced venous limb gangrene). Therapy for patients strongly suspected to
have HIT should focus on inhibiting thrombin (or its generation) pharmacologically.
Two direct thrombin inhibitors (lepirudin, argatroban) are approved for treating HIT.
When using these agents, coumarin anticoagulation should be delayed pending substantial
resolution of thrombocytopenia, before cautiously introducing overlapping coumarin
therapy.
KEYWORDS
Heparin-induced thrombocytopenia - thrombin generation - platelet activation - endothelium
- monocyte
REFERENCES
twarken@mcmaster.ca
