Heparin therapy, monitoring

T8. Triplett, D. A., Heparin biochemistry, therapy and laboratory monitoring. Ther. Drug Monit. I, 173-197 (1979). 

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. 

A number of laboratory tests are available to measure the phases of hemostasis described above. The tests include platelet count, bleeding time, activated partial thromboplastin time (aPTT or PTT), prothrombin time (PT), thrombin time (TT), concentration of fibrinogen, fibrin clot stabifity, and measurement of fibrin degradation products. The platelet count quantitates the number of platelets, and the bleeding time is an overall test of platelet function. aPTT is a measure of the intrinsic pathway and PT of the extrinsic pathway. PT is used to measure the effectiveness of oral anticoagulants such as warfarin, and aPTT is used to monitor heparin therapy. The reader is referred to a textbook of hematology for a discussion of these tests. 

Unfractionated heparin should not be used during thrombolytic therapy. Neither the aPTT nor any other anticoagulation parameter should be monitored during the thrombolytic infusion... 

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... 

The CTAD additive mixture has found application in the monitoring of heparin therapy by either the chromogenic substrate assay or the APTT and in the measurement of platelet markers such as P-selectin (CD62) by flow cytometry (108, 109). 

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... 

Baseline platelet count, prothrombin time, aPTT during INF closely monitor platelet count and aPTT (heparin therapy)... 

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). 

Pharmacokinetics Streptokinase therapy is instituted within 4 hours of a myocardial infarction and is infused for 1 hour. Its ti/2 is less than a half-hour. Thromboplastin time is monitored and maintained at two to five times control value. On discontinuation of treatment, either heparin or oral anticoagulants may be administered. 

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. 

In view of the severity of the Type II syndrome, it has been recommended that heparin therapy be monitored by twice-weekly platelet counts (56). 

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