Table 195 O Screening Laboratory Tests for Hypercoagulable State

• Activated protein C resistance

• Functional assays for antithrombin, protein C, and protein S

• Prothrombin G20210A by polymerase chain reaction

• APTT, DRVVT, mixing studies, and confirmatory test for lupus anticoagulant

• Enzyme-linked immunosorbent assays for anticardi-olipin antibody

• Factor VIII activity

Anticoagulant Drugs

Anticoagulant drugs are used for the prevention and treatment of thromboembolic disorders. Short-term anticoagulant drugs such as heparin are administered by intravenous infusion or subcutaneous injection. Long-term anticoagulant drugs such as Coumadin are orally administered.

Heparin

Heparin is present in human tissue as naturally occurring highly sulfated glycosaminoglycan. Commercially unfractionated heparin (UFH) is isolated from bovine lung or porcine intestine. It contains a mixture of polysaccharide chains with a molecular weight of 4000 to 30,000 daltons.1 Heparin sulfate is a heparin-like substance made by the vascular endothelium. The anticoagulant activity of heparin is enhanced by binding to AT. Heparin-AT complex inactivates thrombin and factor Xa (see Fig. 19.2).

The half-life of heparin is dose dependent. Heparin is cleared from the circulation by the reticu-loendothelial system and metabolized by the liver.1 Heparin is given in a weight-adjusted dosage with an initial bolus (high dose) followed by continuous infusion (lower dose).

Heparin dosage is monitored by aPTT value to range from 1.5 to 2.5 times the mean of the laboratory normal ranges. This level of aPTT is equivalent to heparin levels of 0.3 to 0.7 U/mL that can be measured by factor Xa activity assay.1,8

The adverse effects of heparin include bleeding, HIT, and heparin resistance. Heparin resistance may occur as a result of nonspecific binding of heparin to plasma proteins, platelets, and endothelial cells or as a result of AT deficiency

Low-Molecular-Weight Heparin

Low-molecular-weight heparin (LMWH) is derived from the UFH via enzymatic digestion to produce smaller and low-molecular-weight glycosaminoglycan molecules. The mean weight of LMWH is about 5000 daltons.1 LMWH has a higher half-life and has low affinity to bind to plasma proteins and endothelial cells.1,9 The half-life of the drug is not dose dependent. LMWH is administered subcutaneously, once or twice daily based on the body's weight, and does not require monitoring.1 LMWH has a higher inhibitory effect on factor Xa than on factor IIa.9 LMWH is cleared by the kidney. The adverse reaction of LMWH includes bleeding, HIT, or sensitivity to LMWH. The LMWH drugs available in the United States, which are approved

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