TOXICOLOGY■ Fresh frozen plasma
■ 10–15mg/kg will restore factor levels to ≥30% of normal.
■ Prothrombin complex concentrate and recombinant factor VIIa
■ Allow for factor replacement and immediate complete reversal of anti-
coagulation
COMPLICATIONS
■ Intravenous Vitamin K 1 therapy can rarely cause anaphylaxis.
■ Warfarin-induced skin necrosis:
■ Occurs 3–8 days after initiating warfarin therapy in patients with pro-
tein C deficiency (transient hypercoagulable state)
■ Thrombosis of cutaneous vessels
■ Prevented by coadministration of heparin during initiation of warfarin
therapy
■ Treated with discontinuation of warfarin and initiation of heparin therapy
Heparin
MECHANISM/TOXICITY
■ Binds antithrombin III →heparin-antithrombin III complex →inhibits
multiple steps (IXa, Xa, XIa, XIIaand thrombin) in intrinsic and extrinsic
pathways.
■ Low-molecular-weight heparins (LMWH) are obtained from heparin, but
have a longer half-life, greater bioavailability, and greater activity against
factor Xa.
SYMPTOMS/EXAM
■ Bleeding may be spontaneous or related to trauma.
DIFFERENTIAL
■ Warfarin, other “warfain-like” anticoagulants, ingestion of brodifacoum
(rat poison)
DIAGNOSIS
■ Usually clear from patient’s history and exam
■ Elevation of PT/INR and aPTT
TREATMENT
■ Stop heparin.
■ Protamine sulfate:
■ Indicated for severe bleeding complications only (risk of serious ana-
phylaxis with administration)
■ Reverses the effect of heparin and partially inactivates LMWH
■ Dose is calculated from the dose of heparin given.
■ Onset of action is 30–60 seconds with a duration lasting 2 hours.
COMPLICATIONS
■ Heparin-induced thrombocytopenia (HIT): May occur 5–8 days after ini-
tiating therapy or as late as 3 weeks after stopping therapy. Antibodies cause
significant drop in platelets (>50%) and skin changes at injection sites. Sys-
temic venous and arterial thromboticeventscan cause a wide variety of
end organ damage. This is more common with heparin versus LMWH.
Prothrombin complex
concentrates and recombinant
factor VIIa are used when
immediate and complete
reversal of warfarin
anticoagulation is desired.Heparin-induced
thrombocytopenia is
associated with systemic
venous and arterial
thromboticevents.