Professional Documents
Culture Documents
I II III IV V
OSO 3 -
COO -
CH2OSO3 H2CO R’
O O O O O
COO-
O OH O
O *OSO -
3 O OH
O OH O
Lysine
Sites
Heparin
ATIII Factor Xa
Lysine
Sites
5 <13
VIIIa Platelet
aPC = sites of Aggregation
FACTOR Xa Heparin/ATIII
Inhibition
Fibrinogen
Prothrombin Thrombin
Va
aPC XIIIa
PC / Thrombomodulin
Heparin-Induced Thrombocytopenia -
TWO FORMS:
–Mild reduction in platelet count, 2-15 days
after initiation of full-dose heparin therapy
–Platelet count usually remains above
100,000/µl. Bleeding risk is minimal
Heparin-Adverse Effects (continued)
Heparin-Induced Thrombocytopenia-and
Thrombosis
–Severe reduction in platelet count, 7-14 days after
initiation of therapy with full-dose or low-dose
heparin
–May be associated with thrombotic
complications, including arterial thrombosis with
platelet-fibrin clots that may cause MI or stroke
–Presence of antiplatelet IgG in patients with
severe form ?
–May be less common with heparin from pork.
Heparin - Laboratory Monitoring
aPTT / TCT
–Therapy is routinely monitored by means of the
aPTT (at UofM it is the TCT)
–A clotting time of 1.5 to 2.0 times the normal
mean aPTT value (50 - 70 seconds) is therapeutic
–Initially the aPTT should be measured and the
infusion rate adjusted every 4 hours.
–Once a steady state is achieved, daily monitoring
is sufficient.
Resistance to Heparin
• Some patients may not show a
prolongation of the aPTT unless very
high doses of heparin are used
• Presence of an increased concentration of
FACTOR VIII will give rise to a very
short control aPTT - they may not be
truly resistant to heparin
Heparin-Resistance to Heparin
(continued)
• Accelerated clearance of heparin may exist - as in
the case of massive pulmonary embolism
• Inherited AT III deficiency have 40 - 60 % of the
normal plasma concentration of AT III. They
respond normally to heparin
• Acquired AT III deficiency as with hepatic
cirrhosis, nephrotic syndrome or disseminated
intravascular coagulation; large doses of heparin
may not prolong the aPTT
Heparin - Managing Over-
Anticoagulation
• Anticoagulant effect of heparin disappears
within hours after discontinuation of the drug.
• Mild bleeding due to heparin can be
controlled without administration of an
antagonist.
• Antagonists are used if bleeding is life-
threatening.
Heparin - Managing of Over-
Anticoagulation
Enoxaparin (Lovenox™)
Dalteparin (Fragmin™)
–contain a lower proportion of the critical
pentasaccharide sequence than the parent
compound.
–they increase the action of ATIII on factor Xa,
but not its action on thrombin.
Low Molecular-Weight Heparins
• The LMWHs are not inactivated by platelet
factor 4, therefore activity extends to factor Xa
bound to platelet membranes.
• In clinical doses, no affect on platelet reactivity,
PT or aPTT.
• Currently approved for prevention of deep vein
thrombosis:
• After hip or knee surgery or abdominal surgery.
• Unstable angina (NQWMI).
Low Molecular Weight Heparins
• Do not require routine monitoring of INR, PT, or
aPTT.
• One fixed dose administered subcutaneously.
– 30 mg every 12 hours.
• Must not be administered IM and is not intended
for IV administration.
• Use with caution in patients with a history of
heparin-induced thrombocytopenia.
• Reversed by protamine, 1 mg for each mg of
LMWH.