**4. Unfractionated standard heparin**

#### **4.1 Mechanism of action**

Unfractionated standard heparin enhances the rate by which antithrombin III neutralizes the activity of several coagulation factors including factor Xa and thrombin [17].

Average half-life when administered intravenously is 60 minutes in adults. Its half-life is dose dependent (higher dose has more duration in the circulation). It has a shorter half-life than normal in patients with thrombotic disease and a longer half-life than normal in cirrhosis or uremia patients.

Contraindications of unfractionated standard heparin include recent bleeding in the central nervous system, bleeding from an inaccessible site, malignant hypertension, bacterial endocarditis, and recent surgery.

Partial thromboplastin time (PTT) may not reflect the correct degree of anticoagulation, therefore specific heparin level should be determined (heparin level is 0.35–0.70 U/ml by anti-factor Xa assay or 0.2–0.4 U/ml by protamine sulfate assay).

Protamine sulfate can neutralize heparin immediately. Because of the rapid clearance rate of heparin, stopping the infusion is adequate treatment for most patients (1 mg of protamine sulfate can neutralize 90–110 units of heparin). In addition, heparin has rapid metabolic decay and therefore it needs only one-half of a total dose of protamine.

#### **4.2 Enoxaparin**

Enoxaparin is an effective and convenient alternative to standard heparin therapy [17]. Adult patients rarely need to have their heparin level monitored, but in pediatric patients there is more diversity of response. Monitoring is critical to ensure that a therapeutic level is achieved.

PTT cannot be used to monitor heparin levels; a specific assay should be used. Once therapeutic range is achieved, routine monitoring is not required or is required infrequently.

When enoxaparin is used for prophylaxis against thrombosis, the dose is 0.5 mg/ kg/12 hr subcutaneously.

#### **4.3 Warfarin**

Warfarin is an oral anticoagulant drug that acts to reduce the functional level of vitamin K-dependent factors II, IIV, IX, and X as well as proteins S and C [17]. Warfarin will reduce the level of following factors gradually depending on the half life, factor VII is firstly as the shortest its half life, followed by factor IX and X and lastly factor II, it usually needed 4-5 days to decrease all these factors. PT is a clotting test used to monitor warfarin therapy.

The most adverse effect is hemorrhage, which is related to dose or metabolism and is treated by discontinuation of the drug along with administration of vitamin K (vitamin K given is equal to the daily warfarin dose) either orally, subcutaneously, or intravenously (not intramuscularly). The parenteral route has a much longer half-life and may overshoot the correction. Sometimes, warfarin is associated with life-threatening bleeding. When severe hemorrhage develops, 15 ml/kg of fresh frozen plasma should be given in addition to vitamin K.
