Intentional overdose with tinzaparin: management dilemmas.

BACKGROUND: Low-molecular-weight heparin (LMWH) is increasingly being prescribed for prophylaxis and treatment of thromboembolic diseases. Despite the fact that its therapeutic use is considered to be safe, it can be complicated by major hemorrhage and, in contrast to unfractionated heparin, it can only partially be neutralized by protamine. Recent reports of LMWH overdose illustrate the need for a consensus on its management. OBJECTIVES: To describe a case of self-poisoning with a very large dose of tinzaparin and discuss management options in patients with LMWH overdose. CASE REPORT: A 69-year-old woman was brought to the Emergency Department 2 h after injecting herself with 280,000 IU of tinzaparin subcutaneously in an attempt to commit suicide. Despite an unrecordable activated partial thromboplastin time (APTT > 180 s) and prolonged prothrombin time, there was no evidence of active bleeding. She was given an intravenous infusion of 100 mg protamine sulfate and was admitted to the intensive care unit, where further infusions of protamine were administered. Normalization of the APTT occurred 40-50 h post admission, reflecting normal tinzaparin clearance rather than neutralization by protamine. No hemorrhagic complications occurred during her hospitalization except for prolonged bleeding from venipuncture sites. CONCLUSION: In this case of massive tinzaparin overdose, conventional doses of protamine failed to rapidly normalize the deranged coagulation parameters. The favorable clinical outcome suggests that, regardless of the LMWH amount injected, no active treatment is needed in the absence of hemorrhage. This is in accordance with the limited published data concerning cases of overdose with other LMWHs.

Comparative study of candidate housekeeping genes for quantification of target gene messenger RNA expression by real-time PCR in patients with inflammatory bowel disease.

BACKGROUND: Mucosal expression of immunological mediators is modified in inflammatory bowel disease (IBD). Quantification of target gene messenger RNA (mRNA) transcripts depends on the normalization to a housekeeping or reference gene. Stability of housekeeping gene expression is critical for the accurate measurement of transcripts of the target gene. No studies have addressed the optimization of reference gene performance for mRNA studies in healthy intestinal mucosa and during mucosal inflammation. METHODS: RNA was extracted from endoscopically obtained intestinal biopsies from healthy control subjects and patients with active IBD or non-IBD inflammatory diseases. Comparative analysis of 10 candidate housekeeping genes for quantitative real-time PCR was carried out according to predefined criteria, including use of the Web-based RefFinder platform. RESULTS: We demonstrate that intestinal inflammation may significantly affect the stability of mucosal expression of housekeeping genes. Commonly used controls, such as glyceraldehyde-3-phosphate dehydrogenase, ß-actin, or ß2-microglobulin displayed high variability within the control group and/or between the healthy and inflamed mucosae. In contrast, we have identified novel genes with optimal stability, which may be used as appropriate housekeeping controls. The ribosomal proteins encoding genes (RPLPO and RPS9) were the most stable because their expression was not affected by interindividual differences, the presence of inflammation, or intestinal location. Normalization ofthe mRNA expression of mucosal tumor necrosis factor-α was highly dependent on the specific reference gene and varied significantly when normalized to genes with high or low stability. CONCLUSIONS: Validation for optimal performance of the housekeeping gene is required for target mRNA quantification in healthy intestine and IBD-associated lesions. Suboptimal reference gene expression may explain conflicting results from published studies on IBD gene expression.