Heparin monitoring therapy with

Heparin-induced thrombocytopenia (HIT) is a very serious adverse effect associated with UFH use. Platelet counts should be monitored every 2 to 3 days dining the course of UFH therapy.5 HIT should be suspected if the platelet count drops by more than 50% from baseline or to below 120,000. In patients with contraindications to anticoagulation therapy, UFH should not be administered (Table 7-7). 

Heparin may be given intravenously or subcutaneously, and there is no universally accepted dose. Full-dose heparin therapy in adults is a bolus of 5000 units, followed by a continuous infusion of 1000 units/hour. Since the aPTT is already elevated in individuals with DIC, monitoring full-dose heparin therapy may be difficult, and D-dimer and fibrinogen levels maybe better markers of activity. Subcutaneous heparin at a dose of 80 to 100 units/kg every 4 to 6 hours and low-molecular-weight heparins are other, less studied options.25... 

Contraindications to heparin therapy include hypersensitivity to the drug, active bleeding, hemophilia, severe liver disease with elevated prothrombin time (PT), severe thrombocytopenia, malignant hypertension, and inability to meticulously supervise and monitor treatment. 

Mild thrombocytopenia - Mild thrombocytopenia may remain stable or reverse even if heparin is continued. However, closely monitor thrombocytopenia of any degree. If a count falls below 100,000/mm or if recurrent thrombosis develops, discontinue heparin. If continued heparin therapy is essential, administration of heparin from a different organ source can be reinstituted with caution. 

White clot syndrome - Rarely, patients may develop new thrombus formation in association with thrombocytopenia resulting from irreversible aggregation of platelets induced by heparin, the so-called white clot syndrome. The process may lead to severe thromboembolic complications. Monitor platelet counts before and during therapy. If significant thrombocytopenia occurs, immediately... 

The recommendation for UFH is based on documented efficacy in many older mid-sized trials. Meta-analyses showed a clear reduction in Ml and death, but at the cost of an increase in major bleeding rates (35,36). The advantages of LMWH over unfractionated heparin include a better bioavailability, a stronger and longer anti-Xa activity, less platelet activation, and no need for monitoring. A major drawback of standard heparin therapy is the potential risk of heparin-induced thrombocytopenia, which is considerably reduced with LMWH (37). 

Antithrombin inhibits the activity of factors Ka, Xa, Xlla, and thrombin (Ila). It also inhibits thrombin-induced activation offactors V and VIII. UFH prevents the growth and propagation of a formed thrombus and allows the patient s own thrombolytic system to degrade the clot. Contrainchcations to heparin therapy include hypersensitivity to the drug, active bleeding, hemophilia, severe hver chsease with elevated prothrombin time (PT), severe thrombocytopenia, malignant hypertension, and inability to meticulously supervise and monitor treatment. 

Type I heparin-induced thrombocytopenia is common and is characterized by a mild transient thrombocytopenia (with platelet counts that usually do not fall below 50 X 10 /1) the thrombocytopenia occurs on the first few days of heparin administration (usually 1-5 days) and requires careful monitoring but not usually withdrawal of heparin. Type I thrombocytopenia is generally harmless and very probably results from direct heparin-induced platelet aggregation. Thrombocjdopenia is most common when large doses of heparin are used, or in some particular circumstances, such as after thrombolytic therapy (35) or in the early orthopedic postoperative period (36) it can abate in spite of continued therapy. Tjrpe I thrombocytopenia is a non-immune reaction, probably due to a direct activating effect of heparin on platelets. 

Platelet counts should be carefully monitored for any decline. If thrombocytopenia develops, the time course and severity should help differentiate which type of HIT exists. If HIT I is suspected, heparin may be continued with caution. If HIT II is suspected, heparin therapy should be discontinued and an alternate form of anticoagulation therapy begun. If a low platelet count is encountered with a thrombotic complication, heparin should be discontinued immediately. Thrombolytic therapy or embolectomy may be necessary. Lepirudin (recombinant hirudin) is... 

Mini-dose or subcutaneous heparin was reported on briefly in previous reviews.13 14 In 1975-76 more clinical evaluations have been reported.89-71 These smaller doses with lower and more sustained effect are efficacious i n vivo for use before surgery and other thrombotic conditions to prevent venous thrombosis and pulmonary embolism. This new form of dosing was advanced by the development of new understanding of mechanism and development of new methods for measuring activity. Such therapy eliminates the necessity of laboratory monitoring and the danger of bleeding. 

Heparin therapy may be monitored by its increases in clotting time in the APTT, although this method for measuring heparin is difficult to standardize. Heparin is more specifically assayed by its effect on factor Xa inactivation by antithrombin. Such factor Xa-based heparin assays usually employ purified factor Xa as a reagent and factor X-deficient substrate plasma as the source of antithrombin. The prolongation of the clotting time that results from the heparin in the patient s plasma is compared with pooled normal plasma that is known to be free of heparin. Many variations of this heparin assay are available. Heparin assays can use thrombin rather than factor Xa, however, the low-molecular-weight heparins are not reliably measured in thrombin-based assays. 

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. 

Only a handful of smdies have formally evaluated the cost-effectiveness of VTE prevention strategies. The acquisition costs of graduated compression stockings, heparin, and warfarin are considerably less than those of the LMWHs, DTls, and fondaparinux. However, the acquisition cost for drug therapy is relatively small when compared with the overall cost of care. Economic analyses must take into account the efficacy of the strategy, treatment complications, and monitoring costs. 

Rosenbloom D, Ginsberg JS. Arguments against monitoring levels of anti-factor Xa in conjunction with low-molecular-weight heparin therapy. Can J Hosp Pharm 2002 55 15-19. 

ADMINISTRATION AND MONITORING FuU-dose heparin therapy usually is administered by continuous intravenous infusion. Treatment of venous thromboembolism is initiated with a bolus injection of 5000 units, followed by 1200-1600 units/h delivered by an infusion pump. Therapy routinely is monitored by the aPTT the target is an elevation to 1.8-2.5 times the normal value. The risk of recurrence of thromboembolism is greater in patients who do not achieve a therapeutic level of anticoagulation within the first 24 hours. Initially, the aPTT should be measured and the infusion rate adjusted every 6 hours dose adjustments may be aided by use of a nomogram. Once a steady dosage schedule has been established, daily monitoring is sufficient. 

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