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Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase, causes vasoconstriction, impairs cardiac function, and may predict cardiovascular risk. The prognostic value of plasma ADMA concentrations in acute vascular situations may be confounded by concomitant factors such as clot formation. In an effort to address the effect of hemostatic system activation, the authors have measured plasma concentrations of ADMA, its stereoisomer symmetrical dimethylarginine (SDMA), and L-arginine in 74 patients with suspected deep vein thrombosis (DVT). DVT was confirmed by sonography or venography in 39 subjects. There was no difference of L-arginine, ADMA, or SDMA (all P > 0.05) between subjects with or without DVT. ADMA correlated with SDMA, L-arginine, and plasma creatinine (all P < 0.05) but not with age, body mass index, D-dimer, thrombus extension, or history of symptoms. Venous thrombembolism does not influence circulating ADMA concentrations. The lack of association between ADMA and DVT argues against a contribution of endogenous NO synthase inhibition in hemostatic systemic activation. [Copyright &y& Elsevier]

Abstract: Background: Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies that recognize platelet factor 4/heparin (PF4/hep) complexes. The in vitro demonstration of PF4/hep antibodies using functional and immunological methods is essential for optimal management of patients suspected to have HIT. Since functional assays are technically challenging and limited to specialized laboratories, antigen-binding assays are commonly used in routine laboratories. Study Design: Blood samples from 448 consecutive patients in whom HIT was suspected were investigated using a latex agglutination test HemosIL® HIT-Ab(PF4-H) (HemosIL-Ab), two chemiluminescence tests HemosIL AcuStar HIT-Ab(PF4-H) (HemosIL AcuStar-Ab) and AcuStar HIT-IgG(PF4-H) (HemosIL AcuStar-IgG), an in-house PF4/hep IgG enzyme immunoassay (EIA) and the heparin induced platelet aggregation (HIPA) test. Results: Antibodies against PF4/hep were detectable in 44 out of 119 samples using HemosIL-Ab among which 20 samples were also reactive in the HIPA; and in 122, 64 and 108 out of 448 sera using HemosIL AcuStar-Ab, HemosIL AcuStar-IgG and in-house PF4/hep IgG-EIA, respectively, among which 52 sera were also reactive in the HIPA. All assays had high sensitivities of >95% for platelet activating antibodies; however, they differed in their specificities. The highest specificity and positive predictive value was observed by HemosIL AcuStar-IgG (96% and 78%, respectively). Conclusion: Automated immunoassays are useful in the laboratory investigations of HIT and present a potential improvement toward standardization of laboratory investigations of HIT. The high positive predictive capability may justify treating the patient with alternative anticoagulants without waiting for the results of a functional assay. [Copyright &y& Elsevier]