The anticoagulant effect of protamine sulfate is attenuated in the presence of platelets or elevated factor VIII concentrations.

BACKGROUND: Protamine sulfate is the antidote for heparin, but in excess it exerts weak anticoagulation. METHODS: We evaluated the effects of increasing protamine concentrations (0 to 24 microg/mL) on prothrombin time and diluted Russell's viper venom time measurements on thrombin generation in platelet-poor and platelet-rich plasma after activation by tissue factor or actin, and on thromboelastometry in platelet-poor plasma and whole blood from 6 healthy volunteers. The reversibility of excess protamine (24 microg/mL) by recombinant factor VIIa or factor VIII/von Willebrand factor concentrate was also tested. RESULTS: Protamine prolonged prothrombin time and Russell's viper venom time, concentration dependently. Protamine also increased lag time and decreased peak of thrombin generation in platelet-poor plasma after tissue factor and actin activation. In platelet-rich plasma with platelets at 50 to 200 x 10(3)/microL, protamine (24 microg/mL) prolonged the lag time, but had no effect on peak thrombin generation. The addition of factor VIII/von Willebrand factor (1.5-3.0 U/mL) to platelet-poor plasma with protamine (24 microg/mL) decreased lag time and increased peak thrombin generation with actin activation. A therapeutic concentration of recombinant factor VIIa (60 nM) only affected the lag time of thrombin generation triggered with actin. In agreement, protamine increased coagulation time evaluated by thromboelastometry significantly more in platelet-poor plasma than in whole blood. CONCLUSIONS: We demonstrated that protamine affects the propagation of thrombin generation, which is partially reversed by platelets or increased factor VIII/von Willebrand factor concentrations. The present data suggest that excess protamine might potentially increase bleeding in the case of severe thrombocytopenia or low factor VIII.

Novel oral anticoagulants: implications in the perioperative setting.

Patients undergoing surgery receive anticoagulation for perioperative thromboprophylaxis or ischemic cardiovascular disease. Because anticoagulants may also potentiate bleeding, clinicians need to understand the implications of anticoagulation in perioperative and postoperative patient management. Many newer anticoagulants that are now available or are in clinical development do not require routine coagulation monitoring, have more predictable dose responses, and have fewer interactions with other drugs and food. The most advanced oral anticoagulants in clinical development are the direct factor Xa inhibitors rivaroxaban and apixaban, and the direct thrombin inhibitor dabigatran etexilate. These agents have been evaluated in the postoperative setting in patients undergoing total hip- or knee-replacement surgery with promising results, and it remains to be seen whether these results will translate into other surgical settings. The impact of the new agents will be influenced by the balance between efficacy and safety, improved convenience, and potential cost-effectiveness benefits.

Anesthetic concerns for patients with coagulopathy.

PURPOSE OF REVIEW: Patients often receive preoperative therapies that interfere with hemostasis, and can present for surgery with underlying hemostatic disorders because of pre-existing preoperative anticoagulation or antiplatelet therapy. Perioperative bleeding can occur following surgery due to multiple causes; however, the addition of pharmacologic agents creates an acquired defect that complicates the surgical injury and may result in increased blood loss. An understanding of the potential impact of anticoagulation therapies on hemostasis is critical in managing these patients. Further, newer agents are evolving in clinical practice that clinicians should be aware of. RECENT FINDINGS: The anticoagulants and antiplatelet agents that patients are receiving preoperatively apart from unfractionated heparin include low-molecular-weight heparins (LMWHs); a pentasaccharide (fondaparinux); oral anticoagulants: vitamin K antagonists (warfarin), new oral Xa inhibitors (rivaroxaban, apixiban), or the oral direct thrombin inhibitor (DTI) dabigatran; platelet inhibitors: thienopyridines (clopidogrel, ticlopidine, prasugrel) or IIb/IIIa receptor antagonists (tirofiban, abciximab, eptifibatide); or DTIs (r-hirudin, bivalirudin, argatroban). SUMMARY: There are multiple pharmacologic therapies that surgical patients may be exposed to preoperatively, although there are currently few available methods to antagonize their effects. Often therapeutic prohemostatic pharmacologic approaches are used to treat or prevent bleeding, in addition to transfusional therapies.

Magnetic resonance imaging abnormalities in cat-scratch disease encephalopathy.

A 23-year-old woman who presented with a branch retinal artery occlusion followed by encephalopathy showed, by brain magnetic resonance imaging, a nonenhancing lesion in the right parietal gray matter with normal diffusion-weighted imaging. Of 64 reported cases of cat-scratch encephalopathy with documented neuroimaging findings, only 12 (18.8%) have had abnormal imaging findings. The abnormalities have included cerebral white matter lesions, basal ganglia and thalamic lesions, and multifocal lesions in immunocompromised patients, but no gray matter lesions similar to those in this patient. The variety of neuroimaging findings supports multiple pathophysiologic mechanisms of central nervous system involvement in this disorder.