Heparin Resistance (Last Updated - 3/14/2005)
-consider in pts. w/ normal therapeutic plasma levels of heparin w/ normal aPTT's
-assoc. conditions:
1) Massive Pulmonary Embolus (PE):
-induces heparin clearance
2) Hyper-Factor VIII-emia:
-pts. have elevated Factor VIII levels @ baseline
-so pts. not actually resistant to heparin --> they just have very short aPTT's @ baseline
3) Acquired Anti-Thrombin Deficiency:
-pts. have only ~25% of normal anti-thrombin levels (vs. 40%-60% in Inherited Anti-Thrombin Deficiency)
-pts. may require increased IV Heparin dosing to achieve usual aPTT increases
-seen with:
1) Hepatic Cirrhosis
2) Nephrotic Syndrome
3) DIC
4) Inherited Anit-Thrombin Deficiency:
-pts. have only ~40%-60% of normal anti-thrombin levels (vs. 25% in Acquired Anti-Thrombin Deficiency)
-most pts. respond normally to IV Hep dosing
-Mechanism --> competitive inhibition of heparin (or heparan sulfate) / anti-thrombin binding by:
A) Histidine-rich glycoprotein
B) Vitronectin
C) Platelet Factor 4 (PF4)
-pro-coagulant
-promotes localized clot formation @ the site of vessel injury
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References:
Goodman & Gilman's: The Pharmacologic Basis Of Therapeutics - 10th Edition - 2001. Chapter 55.