Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New synthetic direct and indirect factor Xa or factor IIa inhibitors are increasingly used for the prevention and treatment of thrombotic disorders, including patients suffering from antiphospholipid syndrome. In this study, the effects of the synthetic direct factor Xa inhibitor DX-9065a, the indirect synthetic heparinomimetic pentasaccharide, and the direct factor IIa inhibitor Argatroban were studied. These two widely used assays for the detection of lupus anticoagulant, namely the tissue thromboplastin inhibition (TTIT) and the dilute Russell viper venom tests (DRWT) proved useful. The drugs were added to a normal human plasma pool ranging in concentration from 0.04 to 10 microg/mL. Using the two tests named above, DX-9065a and Argatroban showed a dose-related prolongation of TTIT and DRWT in the concentration range from 0.04 to 5 micromol/mL, but the pentasaccharide only slightly prolonged the clotting times of these assays even at high concentrations. Argatroban had the more pronounced effect on both tests when compared with DX-9065a (p < 0.001). The most responsive assay for DX-9065a up to a concentration of 2.5 micromol/mL was the DRWT. For Argatroban both TTIT and DRWT were equally responsive. Patients whose plasma was tested for suspected lupus anticoagulant and who have been given DX-9065a or Argatroban may have false-positive results with the TTIT tests and DRWT. This effect should be considered during patient management. These results indicate that these assays could be used for the effective quantitation of the direct factor Xa or factor IIa inhibitors when suitable controls are used.
 ...
PMID:Differential effects of DX-9065a, argatroban, and synthetic pentasaccharide on tissue thromboplastin inhibition test and dilute Russell's viper venom test. 1465 41

Argatroban is a direct thrombin inhibitor approved for the treatment of heparin-induced thrombocytopenia (HIT) type II. Argatroban is predominantly metabolized in the liver. It is widely believed that no dosage adjustment is required in patients with renal insufficiency, making it a preferred agent in patients on renal replacement therapy (Reddy and Grossman, Ann Pharm 2005;39:1601-1605). The elimination half-life of argatroban is approximately 50 min. Lupus anticoagulants can cause baseline elevation of the PTT and hence it is difficult to monitor the effects of anticoagulants such as heparin, lepirudin, or argatroban in patients with antiphospholipid antibody syndrome. Heparin levels may be used as an alternative for heparin monitoring but plasma levels of argatroban are not commercially available. A chromogenic antifactor IIa assay could be useful for monitoring argatroban in the presence of a lupus anticoagulant, but it is not widely available at present. We report a patient with end-stage renal disease, maintained on peritoneal dialysis with HIT, who demonstrated a markedly prolonged half-life when treated with argatroban despite the discontinuation of therapy. This case also demonstrates the lack of guidelines for the monitoring of argatroban therapy in the presence of an underlying lupus anticoagulant.
 ...
PMID:Prolonged half-life of argatroban in patients with renal dysfunction and antiphospholipid antibody syndrome being treated for heparin-induced thrombocytopenia. 1791 40