OBJECTIVE To report our experience of reduced-dose argatroban in a patient with suspected heparin-induced thrombocytopenia (HIT) and Child-Pugh class C liver disease and review the relevant literature to summarize current recommendations on argatroban use in patients with severe liver disease. CASE SUMMARY A 58-year-old male with Child-Pugh class C liver disease (Model for End-Stage Liver Disease [MELD] score = 31, total bilirubin 4.5 mg/dL) and hemodialysis-dependent renal failure was hospitalized with acute deep vein thrombosis (DVT). Three days after heparin initiation for DVT, he developed thrombocytopenia. Given his heparin exposure (both for treatment of DVT and ongoing hemodialysis), HIT was suspected and all heparinoids were immediately discontinued. Argatroban was initiated for the treatment of HIT while laboratory testing for HIT antibodies and the serotonin release assay were completed. Because of the patient’s advanced liver disease, the starting dose of argatroban was reduced to 0.2 µg/kg/min, with frequent monitoring of the activated partial thromboplastin time (aPTT) (goal 60–85 seconds). Despite this dose reduction, the aPTT was supratherapeutic. Following further dose reductions, a final argatroban maintenance dose of 0.05 µg/kg/min was necessary for the attainment of goal aPTTs. DISCUSSION Reducing the starting dose of argatroban to 0.5 µg/kg/min is recommended in patients with liver disease. Nevertheless, this recommended dose is largely based on data from patients with more moderate liver disease (eg, Child-Pugh class A or B), and dosing in more advanced liver disease remains largely unexplored. Patients with more advanced liver disease may require additional dose reductions to avoid supratherapeutic concentrations of anticoagulation agents and to minimize bleeding risk. CONCLUSIONS This report illustrates the importance of careful selection of argatroban dosing and appropriate aPTT monitoring in patients with severe liver disease. Excessive anticoagulation may precipitate major bleeding complications, placing patients with this complicated disease at undue risk.

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Potential anti-inflammatory and anticarcinogenic effects of aspirin (ASA) may be suitable for melanoma chemoprevention, but defining biomarkers in relevant target tissues is prerequisite to performing randomized controlled chemoprevention trials. We conducted open-label studies with ASA in 53 human subjects with melanocytic nevi at increased risk for melanoma. In a pilot study, 12 subjects received a single dose (325 mg) of ASA; metabolites salicylate, salicylurate, and gentisic acid were detected in plasma after 4–8 h, and prostaglandin E2 (PGE2) was suppressed in both plasma and nevi for up to 24 h. Subsequently, 41 subjects received either 325 or 81 mg ASA (nonrandomized) daily for one week. ASA metabolites were consistently detected in plasma and nevi, and PGE2 levels were significantly reduced in both plasma and nevi. Subchronic ASA dosing did not affect 5” adenosine monophosphate-activated protein kinase (AMPK) activation in nevi or leukocyte subsets in peripheral blood, although metabolomic and cytokine profiling of plasma revealed significant decreases in various (non-ASA-derived) metabolites and inflammatory cytokines. In summary, short courses of daily ASA reduce plasma and nevus PGE2 and some metabolites and cytokines in plasma of human subjects at increased risk for melanoma. PGE2 may be a useful biomarker in blood and nevi for prospective melanoma chemoprevention studies with ASA.