LMWHs heparins

Hypersensitivity to LMWHs, heparin, or pork products hypersensitivity to sulfites or benzyl alcohol (multidose vials) history of heparin-induced thrombocytopenia (tinzaparin) active major bleeding thrombocytopenia associated with positive in... 

When anti-factor Xa activity is used to monitor LMWH therapy, the sample should be drawn approximately 4 hours after the subcutaneous injection, during the peak period of anti-factor Xa activity. A calibrated LMWH heparin should be used to establish the standard curve for the assay. The therapeutic range for anti-factor Xa activity is not well defined and to date has not been correlated clearly with efficacy or the risk of bleeding. Eor the treatment of VTE, an acceptable target range is 0.5 to 1.0 unit/mL. Specific algorithms for dosing adjustments based on anti-factor Xa activity are not available at the present time. 

Danaparoid (Orgaran mean MW, 6,000 Da) is a mixture of nonheparin glycosaminoglycans derived from pig gut (dermatan sulfate, heparan sulfate, chondroitin sulfate). Die anti-Xa/anti-IIa ratio (22 1) is even greater than seen with LMWH. Die anti-IIa effect may be mediated in part by dermatan sulfate, which catalyzes thrombin inhibition by heparin cofactor II. 

Heparin inhibits the formation of fibrin clots, inhibits the conversion of fibrinogen to fibrin, and inactivates several of the factors necessary for the clotting of blood. Heparin cannot be taken orally because it is inactivated by gastric acid in the stomach therefore, it must be given by injection. Heparin has no effect on clots that have already formed and aids only in preventing the formation of new blood clots (thrombi). The LMWHs act to inhibit clotting reactions by binding to antithrombin HI, which inhibits the synthesis of factor Xa and the formation of thrombin. 

The LMWHs cause fewer adverse reactions tiian heparin. Bleeding related to die LMWHs is possible but has generally been low. See die Summary Drug Table Anticoagulants for additional adverse reactions associated widi die LMWHs. 

The LMWHs are contraindicated in patients witii a hypersensitivity to the drug, heparin, or pork products and inpatients with active bleeding or thrombocytopenia... 

Blood coagulation tests are usually ordered before and during heparin tiierapy, and die dose of heparin is adjusted to die test results. Optimal results of therapy are obtained when the APTT is 1.5 to 2.5 times the control value The LMWHs do not require close monitoring of blood coagulation tests. 

Monitoring and Managing Adverse Drug Reactions Bleeding at virtually any site can occur during tiierapy with any heparin preparation, even the LMWHs. The nurse monitors the patient s vital signs every 2 to 4 hours or as ordered by the primary health care provider. 

The multiple effects of UFH on the coagulation cascade may increase its potential to cause hemorrhage." Anticoagulants with more specific sites of action may confer a better safety profile. Two such anticoagulants are low-molecular-weight heparin (LMWH) and heparinoids. 

LMWHs are formed by various methods of fractionation or depolymerization of polymeric heparin (Table 7.1). Although they are enzymatically derived from UFH, they have a different site of achon and can be administered subcutaneously. LMWHs exert their anhcoagulant effect by inhibiting factor Xa and augmenting tissue-factor-pathway inhibitor, but minimally affect thrombin or factor Ila (Figs. 7.1 and 7.2)." Thus, the PTT, a measure of antithrombin (anh-factor Ila) achvity, is not used to measure the achvity of LMWHs. 

FIGURE 7.2 LMWH inhibits factor Xa and minimally affects factor Ha thus, activated partial thromboplastin time is not used to measure its anticoagulant activity. (Reprinted from the American Family Physician published by the American Academy of Family Physicians, February 15th, 1999, in an article entitled Low-molecular-weight heparin in outpatient treatment of DVT. )... 

The Heparin in Acute Embolic Stroke Trial (HAEST) was a multicenter, randomized trial of the effect of LMWH (dalteparin 100 lU/kg sc twice daily) or aspirin (160 mg once daily) for the acute treatment of 449 patients with ischemic stroke and atrial fibrillation (AF). The primary outcome was the rate of recurrent stroke within 14 days. No difference in rates of early recurrence (8.5% dalteparin treated vs. 7.5% aspirin treated) or good 3-month functional outcome was found. The frequency of early slCH was 2.7% on dalteparin versus 1.8% on aspirin. 

Trials of Unfractionated Heparin Compared to LMWH and Heparinoids... 

The most extensively studied drugs for the prevention of VTE are unfractionated heparin (UFH), the low-molecular-weight heparins (LMWHs dalteparin, enoxaparin, and tinza-parin), fondaparinux, and warfarin.2 The LMWHs and fondaparinux provide superior protection against VTE when... 

FIGURE 7-5. Treatment approach for patients with VTE. INR, International Normalized Ratio IV, intravenous LMWH, low-molecular-weight heparin PO, oral SC, subcutaneous UFH, unfractionated heparin VTE, venous thromboembolism. (Adapted from Nutescu EA. Emerging options in the treatment of venous thromboembolism. Am J Health Syst Pharm 2004 61 (Suppl 7) S16, with permission.)... 

Mechanism of action of unfractionated heparin, low-molecular-weight heparin (LMWH), and fondaparinux. (Reproduced from Haines ST, Zeolla M, Witt DM. Venous thromboembolism. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy ... 

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