Cangrelor and Heparin for Pulmonary Thromboendarterectomy in Heparin-Induced Thrombocytopenia.

Perioperative anticoagulation management for patients with heparin-induced thrombocytopenia requiring cardiopulmonary bypass and deep hypothermic circulatory arrest presents a clinical challenge. Alternative anticoagulants have been used but can cause significant postoperative bleeding. We report the successful use of cangrelor and heparin in a 30-year-old patient with severe heparin-induced thrombocytopenia undergoing urgent pulmonary thromboendarterectomy.

Nucleophilic reactivity of thiolate, hydroxide and phenolate ions towards a model O-arylated diazeniumdiolate prodrug in aqueous and cationic surfactant media.

The kinetics of aromatic nucleophilic substitution of the nitric oxide generating diazeniumdiolate ion, DEA/NO, by thiols, (L-glutathione, L-cysteine, DL-homocysteine, 1-propanethiol, 2-mercaptoethanol and sodium thioglycolate) from the prodrug, DNP-DEA/NO, has been examined in aqueous solution and in solutions of cationic DOTAP vesicles. Second-order rate constants in buffered aqueous solutions (k(RS(-) ) = 3.48 - 30.9 M(-1)s(-1); 30 °C) gave a linear Brønsted plot (ß(nuc) = 0.414 ± 0.068) consistent with rate-limiting S(N)Ar nucleophilic attack by thiolate ions. Cationic DOTAP vesicles catalyze the thiolysis reactions with rate enhancements between 11 and 486-fold in Tris-HCl buffered solutions at pH 7.4. The maximum rate increase was obtained with thioglycolate ion. Thiolysis data are compared to data for nucleophilic displacement by phenolate (k(PhO(-) ) = 0.114 M(-1)s(-1)) and hydroxide (k(OH(-) ) = 1.82 × 10(-2) M(-1)s(-1), 37 °C) ions. The base hydrolysis reaction is accelerated by CTAB micelles and DODAC vesicles with vesicles being ca 3-fold more effective as catalysts. Analysis of the data using pseudophase ion-exchange formalism implies that the rate enhancement of the thiolysis and base hydrolysis reactions is due primarily to reactant concentration in the surfactant pseudophase.