Heparin-bound protein, effects

Heparin is prescribed on a unit (lU) rather than milligram basis. Tlie dose must be determined on an individual basis. Heparin is not absorbed after oral administration and therefore must be given parenterally. Intravenous administration results in an almost immediate anticoagulant effect. There is an approximate 2-hour delay in onset of drug action after subcutaneous administration. Intramuscular injection of heparin is to be avoided because of unpredictable absorption rates, local bleeding, and irritation. Heparin is not bound to plasma proteins or secreted into breast mUk, and it does not cross the placenta. 

Fondaparinux is a chemically synthesized pentasaccharide that mimics the antithrombin-binding site of heparin and LMWH. Its molecular size (1728Da) is too small to bind to thrombin molecules while it is bound to antithrombin, Therefore, it is a pure anti-Xa inhibitor. It binds very little to platelets, proteins, or endothelium and is excreted in the urine, It does not form a complex with PF4 or other positively charged molecules. It is not neutralizable by protamine sulfate, Recent clinical trials have resulted in FDA approval for prophylaxis of deep vein thrombosis in orthopedic surgery, It has been shown to be effective and safe for the treatment of pulmonary embolism (20,21) and ACS (non-ST-elevation Ml) (OASIS 5—Michelangelo Trial) (17). 

Absorption/distribution Must be gi en IV or SC (ncrt absorbed PO) IV bolus results in immediate anticoagulant effects peak plasma levels of heparin are achieved in 2 to 4 h fbliow ing SC use once absorbed, heparin is distributed in plasma and is extensively and nonspecifically protein bound. Bioavailability of SC injection is about 90%. The onset of anticoagulant effect is approximately 4h. Rapidly and completely absorbed. Highly bound to plasma proteins, primarily albumin. 

Heparin is highly plasma protein-bound. Because of the negative charge associated with the molecule, it binds to any positively charged protein, including tissue proteins and cyto-skeletal/membrane proteins. This results in a somewhat unpredictable anticoagulant effect between patients, as the amount and types of available binding proteins varies with the patient and state of health. 

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