Management of patients with heparin-associated thrombocytopenia and thrombosis requiring cardiac surgery

Heparin-associated thrombocytopenia and thrombosis (HATT) is a serious complication of heparin therapy that results in intravascular platelet aggregation with arterial or venous thrombosis. Platelet aggregation to heparin in vitro is used to confirm the diagnosis. Cessation of heparin therapy with avoidance of reexposure to heparin is an important principle in the management of HATT. However, certain patients with HATT may require reexposure to heparin for emergency cardiac operations requiring cardiopulmonary bypass while still demonstrating positive in vitro platelet aggregation with heparin. The present report describes the management of 2 such patients. In each patient aspirin was shown to inhibit platelet aggregation to heparin in vitro; therefore, aspirin and dipyridamole were administered to each patient before heparin reexposure and continued throughout the perioperative period. Cardiopulmonary bypass with full heparinization was achieved without thrombotic or hemorrhagic complications in both patients. Despite the presence of a heparin-dependent platelet-aggregating factor in the plasma of these 2 patients, inhibition of platelet aggregation with aspirin and dipyridamole allowed uneventful reexposure to heparin.     

Suppression of both antimony-susceptible and antimony-resistant Leishmania donovani by a bis(benzyl)polyamine analog.

It was recently demonstrated that a bis(benzyl)polyamine analog (MDL 27695; N,N'-bis(3-[(phenylmethyl)amino]propyl)-1,7-diaminoheptane) possessed potent antimalarial activity in vitro and in vivo (A. J. Bitonti, J. A. Dumont, T. L. Bush, M. L. Edwards, D. M. Stemerick, P. P. McCann, and A. Sjoerdsma, Proc. Natl. Acad. Sci. USA 86:651-655, 1989). We now report that MDL 27695 also has potent antileishmanial activity, eliminating 77 to 100% of Leishmania donovani amastigotes from mouse peritoneal macrophages in vitro at 1 microM. Administration of 15 mg of MDL 27695 per kg three times per day for 5 days to L. donovani-infected mice suppressed parasite burdens in liver, spleen, and bone marrow by 83 to 96, 90, and 87%, respectively, and by 99.9% in livers of mice given the same dose two times per day for 10 days. Liver parasites were suppressed 74% in L. donovani-infected hamsters treated three times per day for 4 days with 5 mg of MDL 27695 per kg. The 50% effective doses for MDL 27695 were 2.5 mg/kg in mice and about 1 mg/kg in hamsters. In hamsters, MDL 27695 was equally effective against both antimony-susceptible and antimony-resistant L. donovani, suggesting a different mechanism of action for the two types of drugs. Coadministration of N1,N4-bis(butadienyl)-butanediamine (MDL 72527) to mice to inhibit host polyamine oxidase, and hence the formation of oxidative metabolites of MDL 27695, did not affect the antileishmanial activity of MDL 27695. Thus, the mechanism of action of MDL 27695 does not appear to be related to its oxidation to toxic metabolites but may involve interference with DNA and RNA syntheses as found previously in Plasmodium falciparum (Bitonti et al., Proc. Natl. Acad. Sci. USA 86:651-655, 1989).     

A new protocol for the treatment of stage I cutaneous malignant melanoma; interim results of the first 806 patients treated

A protocol is described which has been used in a prospective study of 806 patients with stage I malignant melanoma. Excisional biopsies are performed as soon as possible and Breslow thickness and Clark's levels determined. Patients are allocated to low, medium and high risk groups and definitive excision is carried out with a clearance of 2, 20 and 50 mm respectively. Preliminary results are reported on the 806 patients treated over 7 years in three plastic surgery units. No local recurrences have occurred so far in the low and medium risk groups, which suggests that the protocol is safe.     

Successful treatment of nonpurging bulimia nervosa with desipramine: a double-blind, placebo-controlled study

Twenty-three women with nonpurging bulimia underwent a 12-week, double-blind, placebo-controlled trial of desipramine hydrochloride. Repeated standardized rating scales, mood assessments, and self-reports of dietary habits were used to measure changes in binge frequency and cognitive processes associated with food intake. The women who received desipramine reduced their frequency of binge eating by 63%, but women receiving placebo increased their frequency of binge eating by 16%. Twelve weeks after initiating treatment, 60% of the treatment group but only 15% of the placebo group abstained from binge eating. The women who received desipramine showed significantly more dietary restraint and reported significantly less hunger, suggesting that desipramine acts to suppress appetite. These preliminary findings suggest that the therapeutic effects of desipramine established in the treatment of purging bulimia nervosa extend to patients with nonpurging bulimia.     

Adrenergic function in patients with panic anxiety

Increased beta-adrenergic receptor sensitivity could account for many aspects of panic disorder. We tested this hypothesis by comparing 14 patients with six normal control subjects. The controls and eight patients had 14 blood samples taken, and heart rate and BP measured, during a four-hour protocol that included supine rest, a posture and isometric exercise stimulus, and a series of up to seven logarithmically increasing bolus intravenous doses of isoproterenol hydrochloride. The other six patients were studied only at rest. Patients had markedly elevated resting heart rate, substantially elevated levels of plasma epinephrine, cortisol, and growth hormone, mildly elevated plasma norepinephrine levels, and decreased heart rate responses to isoproterenol. These results suggest that beta-adrenergic receptor response is not increased, and may be decreased, in patients with panic disorder. Receptor down-regulation could result from the increased adrenergic function that these patients demonstrate, even in the absence of panic attacks.     

Monitoring heparin therapy with thromboelastography and activated partial thromboplastin time

Blood coagulability in patients undergoing anticoagulant therapy has been studied using the Thromboelastograph® and activated partial thromboplastin time. Currently used tests, such as activated partial thromboplastin time (APTT) and whole blood clotting time, lack sensitivity and do not correlate well with clinically significant bleeding and clotting events. The Thromboelastograph® is an instrument that allows continuous measurement of overall coagulation and fibrinolysis. Sixty patients on heparin therapy were monitored with thromboelastography and activated partial thromboplastin time. Continuous heparin infusion or intermittent administration was used. The Thromboelastograph® was found to be a more sensitive device for detection of response to heparin than APTT. Early response to heparin was reflected in the reaction time, k time, and maximum amplitude of the thromboelastogram. A more precise administration of heparin was made possible, resulting in use of less heparin and a more stable patient response. A more individualized approach to the patient's therapy was achieved by monitoring with the Thromboelastograph, and the best results were obtained with continuous infusion rather than intermittent administration of heparin.