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.