Protamine requirements in cardiac surgery: effect of changes in the heparin reference standard.

OBJECTIVE: UFH (unfractionated heparin) and protamine are integral to cardiac surgery, and inappropriate dosing can predispose to coagulopathy and hemorrhage. The FDA (Food and Drug Administration) recently has instituted changes to UFH formulation and it is not known if this has influenced its susceptibility to neutralization by protamine. Hence, the authors sought to compare 2 commercial preparations of UFH (old and new) with regard to their neutralization by protamine in patients undergoing cardiopulmonary bypass (CPB). DESIGN: Prospective, observational, cohort study. SETTING: Tertiary care university hospital and associated research laboratory PARTICIPANTS: Twenty adult patients undergoing elective cardiac surgery with CPB. INTERVENTIONS: Blood samples were drawn preinduction, prior to, and 5 and 30 minutes following protamine, and 0 and 2 hours after ICU admission. Protamine titration assays were conducted in vitro on samples drawn prior to and following protamine administration. Anti-IIa and anti-Xa activity were assayed in all samples. RESULTS: Anti-IIa and anti-Xa activity were detected ubiquitously at all time points following CPB, and there were no differences in susceptibility to protamine neutralization between the 2 groups. In vitro protamine titration studies revealed that anti-IIa was more resistant to protamine neutralization compared to anti-Xa activity. CONCLUSIONS: The 'old' and 'new' formulations of UFH evaluated in this study were similar in their susceptibility to protamine neutralization. Circulating UFH is detected as early as 5 minutes after protamine administration and anti-IIa is more resistant to protamine neutralization as compared to anti-Xa activity. Further studies are required to quantify the precise dose of protamine following CPB.

Exploring the Role of Rhodtestolin, A Cardio-Inhibitor from the Testes of Rhodnius prolixus, in Relation to the Structure and Function of Reproductive Organs in Insect Vectors of Chagas Disease.

Rhodtestolin is a cardio-inhibitor that was first discovered in testes extracts of the blood-feeding insect, Rhodnius prolixus. Its role in reproduction remains unconfirmed, but if delivered to the female during spermatophore formation, it may serve to calm the female and/or relax the vaginal muscles to facilitate delivery and storage of the spermatophore. We describe here the anatomy of reproductive organs in R. prolixus and show that rhodtestolin is present in a low-molecular weight fraction of testes extracts separated by gel filtration, as well as in spermatophores delivered to the female during spermatophore formation. We also report that a rhodtestolin-like factor is present in the testes of R. brethesi, Triatoma dimidiata, T. klugi and Nesotriatoma bruneri, other Reduviidae, which are vectors of Chagas disease. Male secretions in insects are known to modify female behavior after copulation, and the presence of rhodtestolin in several genera of Reduviidae suggests that it plays an important role in reproductive success. Determining this role could lead to developing additional population control strategies for these bugs.

Thrombelastographic method to quantify the contribution of factor XIII to coagulation kinetics.

Factor XIII (FXIII) plays a critical role in clot strength, and FXIII deficiency or excess is associated with hemorrhage or thrombosis, respectively. Our goal was to design a thrombelastography-based method to characterize the effects of FXIII on plasma clot strength. Normal human plasma was exposed to 0 or 200 mug/ml anti-FXIII antibodies for 20 min prior to celite activation and calcium addition. Other plasma had addition of fibrinogen (625 mg/dl)/FXIII (2 U/ml) or 30% dilution with hydroxyethyl starch before exposure to 0 or 200 mug/ml anti-FXIII antibodies. Thromboelastography was performed and data were collected until stable clot strength was observed. The exposure of normal plasma to anti-FXIII antibodies resulted in a significant (P < 0.05) decrease in clot strength (63%) compared with plasma without antibodies. Further samples exposed to anti-FXIII antibodies had clot strength no different from FXIII-deficient plasma. The FXIII-mediated clot strength varied between 44 and 50% in hypercoagulable and hypocoagulable plasma, respectively. In conclusion, the present investigation successfully demonstrated a novel method to detect the impact of FXIII activity in plasma samples. Further actuarial investigation will be required to determine the utility of this approach in the diagnosis and treatment of patients with either acquired FXIII deficiency or excess and concordant coagulopathy.

Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in pediatric patients with systemic lupus erythematosus.

Study objectives were to determine, in children with systemic lupus erythematosus (SLE), (1) the association of antiphosholipid antibody (APLA) subtypes with thrombotic events (TEs) and (2) the predictive value of persistent versus transient antibodies for TEs. This is a cohort study of 58 SLE children in whom lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), anti-beta2-glycoprotein-I (anti-beta2-GPI), and antiprothrombin (anti-PT) were assessed on at least 2 occasions (more than 3 months apart). Antibodies were classified as persistent (positive on at least 2 occasions) or transient (positive once). Outcomes were symptomatic TEs confirmed by objective radiographic tests identified retrospectively and prospectively. Seven of the 58 patients (12%) had 10 TEs; 5 patients had TEs during prospective follow-up. Persistent LAs showed the strongest association with TEs (P < .001). Persistent ACLAs (P = .003) and anti-beta2-GPI (P = .002) were significantly associated with TEs; anti-PT (P = .063) showed a trend. Persistent or transient LAs and anti-beta2-GPI showed similar strength of association, while ACLAs and anti-PT were no longer associated with TEs. Positivity for multiple APLA subtypes showed stronger associations with TEs than for individual APLA subtypes because of improved specificity. Lupus anticoagulant is the strongest predictor of the risk of TEs; other APLA subtypes provide no additional diagnostic value. Anticardiolipin antibodies and anti-PT require serial testing because only persistent antibodies are associated with TEs.