Occasionally a patient receiving heparin therapy may appear resistant to therapy. This may be present as a failure of monitoring tests to change, higher than expected doses, or onset of new thrombotic events. Review of the clinical history and laboratory test findings may be able to identify the cause.

The most important cause of apparent resistance to heparin therapy is antithrombin III deficiency. Replacement of antithrombin III in a deficient patient may restore heparin efficacy.


Other possible causes for apparent resistance to heparin therapy:

(1) elevated levels of low-density lipoproteins (LDL)

(2) elevated levels of lysozyme (muramidase)

(3) elevated levels of platelet factor 4

(4) elevated levels of beta-thromboglobulin

(5) heparin cofactor II deficiency

(6) intravenous nitroglycerin

(7) possibly acidosis

(8) drug interfering with activity (according to the PDR, this may include digitalis, nicotine, tetracycline or some antihistamines)


Differential diagnosis:

(1) inadequate dosing

(2) thrombosis associated with heparin-induced thrombocytopenia

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