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Jerrold H Levy

Publications and source records attributed to Jerrold H Levy.

At least 37 records · Page 2Linked to original sources
PubMed2005

Activated recombinant factor VII in cardiac surgery.

PURPOSE OF REVIEW: Severe bleeding after cardiac surgery is a potential problem that poses major risks and challenges. Severe bleeding after cardiac surgery still occurs despite many pharmacological approaches to decrease bleeding and reduce transfusion requirements. Activated recombinant factor VII may be a therapy that is potentially useful in the management of refractory bleeding after cardiac surgery and in other postoperative bleeding states. RECENT FINDINGS: Several small, uncontrolled case series have suggested that activated recombinant factor VII may be useful in the management of some patients with intractable bleeding after cardiopulmonary bypass in both pediatric and adult populations. Blood loss or transfusion requirements have been reported to be substantially reduced in some patients who receive activated recombinant factor VII perioperatively. However, these reports have not established the optimal dosing or ideal timing of the administration of activated recombinant factor VII, or determined the frequency of serious adverse events related to its use. SUMMARY: Current reports summarized in this review suggest that activated recombinant factor VII may be a promising agent in the management of uncontrolled bleeding after cardiopulmonary bypass, but additional randomized, placebo-controlled trials are needed to support this use.

Journal Article↗
PubMed2005

Effects of antithrombin and heparin cofactor II levels on anticoagulation with Intimatan.

Heparin is the current mainstay drug for anticoagulation during cardiac surgery, but it requires normal levels of antithrombin (AT) for optimal anticoagulation. Heparin anticoagulation may be less effective in cardiac surgical patients because of decreased AT levels due to the prolonged heparin therapy. Therefore, other anticoagulants that would work well in AT deficient patients may be more desirable. One such agent currently being evaluated is Intimatan, which catalyzes heparin cofactor II (HCII) dependent inhibition of thrombin. In the current in vitro study we examined the effects of Intimatan (20 microg/ml), heparin (0.25 U/ml), or both drugs in combination on thrombin generation in plasma with decreasing levels of AT, HCII or both cofactors, using a novel method based on the continuous measurement of thrombin generation. For the study, we collected blood samples from healthy volunteers, isolated platelet poor plasma by centrifugation and mixed it with AT, HCII, or AT-HCII deficient plasma samples to achieve different levels of AT, HCII and AT-HCII. Thrombin generation was inhibited equally well with heparin or Intimatan when the level of their respective cofactors was within the normal range. With decreasing levels of AT or HCII, heparin and Intimatan became less effective in thrombin inhibition, respectively. With the absence of both cofactors, neither agent alone or in combination had any effect on thrombin generation. We conclude that Intimatan may be an effective adjunct to heparin therapy under low AT conditions.

Anticoagulants↗
PubMed2005

The effects of platelet count on clot retraction and tissue plasminogen activator-induced fibrinolysis on thrombelastography.

Clot retraction and fibrinolysis may present as a decrease in amplitude on thrombelastography (TEG). The former represents normal or hyperactive platelet function, and the latter represents a fibrinolytic state. It is important to distinguish clot retraction from fibrinolysis because the treatment of each condition is different. To distinguish between these phenomena, we performed TEG with platelet-poor plasma (PPP) and platelet-rich plasma (PRP) with an increasing platelet count (range, 50-1200 x 10(9)/L) with or without abciximab. Maximum amplitude (MA) and the percentage decrease of amplitude at 30 and 60 min after MA were examined for each sample. Blood samples to which tissue plasminogen activator (tPA) was added served as positive controls for fibrinolysis. Morphological changes of clots and D-dimer levels were also examined. With higher platelet counts, the percentage decrease of amplitude after MA increased significantly at 30 and 60 min, but not in the abciximab samples. Morphological changes of clots have shown clot retraction in PRP, but not in PPP or PRP pretreated with abciximab. D-dimer levels increased only in samples to which tPA was added, but not in native PPP or PRP samples. In conclusion, we have shown that the decrease in amplitude at 30 and 60 min can be due to platelet-mediated clot retraction and can be attenuated by sample pretreatment with abciximab, which interrupts platelet-fibrin(ogen) binding.

Abciximab↗
PubMed2005

Evaluation and management of bleeding during cardiac surgery.

Patients undergoing cardiac surgery with and potentially without cardiopulmonary bypass (CPB) are at risk for excessive microvascular bleeding. This bleeding often leads to transfusion of allogeneic blood and blood components as well as reexploration. Excessive bleeding after cardiac surgery occurs because of alterations in the hemostatic system pertaining to dilutional thrombocytopenia, excessive hemostatic activation, and exposure to long-acting antiplatelet or antithrombotic agents. Pharmacologic interventions have been extensively reported as means to attenuate the alterations in the hemostatic system during CPB in an attempt to reduce excessive bleeding, transfusion, and reexploration. Prophylactic administration of agents with antifibrinolytic and antiinflammatory properties can decrease blood loss and transfusion. Aprotinin is the most extensively studied and effective blood conservation agent and has the most potent antifibrinolytic and antiinflammatory effects. Other agents, including the lysine analogues with isolated antifibrinolytic properties, may be effective in low-risk patients. The ability to reduce blood product transfusions and to decrease operative times and reexploration rates favorably affects patient outcomes, availability of blood products, and overall health care costs.

Antifibrinolytic Agents↗
PubMed2005

Management of systemic and pulmonary hypertension.

The major therapeutic approach to systemic and pulmonary hypertension and vasospasm in cardiac surgery patients involves the use of parenteral agents that reverse systemic vasoconstriction and produce vasodilation. Potential pharmacologic approaches include 1) alpha1-adrenergic receptor blockers, ganglionic blockers, and calcium channel blockers; 2) central alpha2-adrenergic receptor agonists, dopamine1-adrenergic receptor agonists, potassium channel modulators, and vascular cyclic nucleotide stimulators; 3) phosphodiesterase enzyme inhibitors, and 4) angiotensin-converting enzyme inhibitors. Of the currently available intravenous vasoactive therapies, the mainstay agents are the nitrovasodilators and the dihydropyridine-type calcium channel blockers. The nitrovasodilators, a diverse group of drugs that achieve vascular relaxation by stimulating cyclic nucleotides and thereby releasing nitric oxide, include nitroglycerin and sodium nitroprusside. Although these drugs are useful, rapid development of tolerance is a drawback to nitroglycerin, while nitroprusside can cause coronary steal and increase intracranial pressure. Intravenous dihydropyridine-type calcium channel blockers inhibit mechanical responses of cardiac muscle and vascular smooth muscle by blocking inward calcium currents. Nicardipine is an arterial specific vasodilator. Treatment for vasospasm is usually empiric; pharmacologic options include nitroglycerin, but dihydropyridine calcium channel blockers and phosphodiesterase inhibitors should also be considered.

Cardiac Surgical Procedures↗
PubMed2004

Terminal complement blockade with pexelizumab during coronary artery bypass graft surgery requiring cardiopulmonary bypass: a randomized trial.

CONTEXT: Inflammation and ischemia-reperfusion injury during coronary artery bypass graft (CABG) surgery requiring cardiopulmonary bypass are associated with postoperative myocardial infarction (MI) and mortality. OBJECTIVE: To determine the efficacy and safety of pexelizumab, a C5 complement inhibitor, in reducing perioperative MI and mortality in CABG surgery. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial, including 3099 patients (> or = 18 years) undergoing CABG surgery with or without valve surgery at 205 hospitals in North America and Western Europe from January 2002 to February 2003. INTERVENTIONS: Patients were randomly assigned to receive intravenous pexelizumab (2.0 mg/kg bolus plus 0.05 mg/kg per hour for 24 hours; n = 1553) or placebo (n = 1546) 10 minutes before undergoing the procedure. MAIN OUTCOME MEASURES: The primary composite end point was the incidence of death or MI within 30 days of randomization in those undergoing CABG surgery only (n = 2746). Secondary analyses included the intent-to-treat analyses of death or MI composite at days 4 and 30 in all 3099 study patients. RESULTS: After 30 days, 134 (9.8%) of 1373 of patients receiving pexelizumab vs 161 (11.8%) of 1359 of patients receiving placebo (relative risk, 0.82; 95% confidence interval, 0.66-1.02; P =.07) died or experienced MI in the CABG surgery only population. In the intent-to-treat analyses, 178 (11.5%) of 1547 patients receiving pexelizumab vs 215 (14.0%) of 1535 receiving placebo died or experienced MI (relative risk, 0.82; 95% confidence interval, 0.68-0.99; P =.03). The trial was not powered to detect a reduction in mortality alone. CONCLUSIONS: Compared with placebo, pexelizumab was not associated with a significant reduction in the risk of the composite end point of death or MI in 2746 patients who had undergone CABG surgery only but was associated with a statistically significant risk reduction 30 days after the procedure among all 3099 patients undergoing CABG with or without valve surgery.

Aged↗
PubMed2004

Quantitative assessment of fibrinogen cross-linking by epsilon aminocaproic acid in patients with end-stage liver disease.

Analysis of the effectiveness of antifibrinolytic therapy for liver transplant recipients is hampered by lack of quantitative assays for assessing drug effects. We adapted chemical engineering tools used in polymerization studies to quantify fibrinogen cross-linking by plasma from liver transplant patients obtained before and after epsilon aminocaproic acid (EACA) therapy. A target fluorescein isothiocyanate-fibrinogen (FITC-fibrinogen) molecule was constructed; it fluoresces in a quantifiable pattern when in solution, and undergoes cross-linking in the presence of plasmin inhibitors. Cross-linking quenches the fluorescent signal, and the quenching is a quantifiable endpoint. Thus fluorescence from this reporter molecule can be used to assess functional improvement in fibrinogen cross-linking as a result of antifibrinolytic therapies, and it is sensitive to picomolar amounts of plasmin inhibitors and activators. Cross-linking of FITC-fibrinogen by patient plasma, before and after EACA therapy, was assessed using fluorescence spectrometry. Fluorescence patterns from FITC-fibrinogen indicated no significant cross-linking of the target fibrinogen as a consequence of EACA in posttreatment plasma. When the fibrinogen-FITC target was assayed without plasma in the presence of EACA at concentrations that bracket therapeutic levels (100 and 400 microg/ml), significant fluorescence quenching (target FITC-fibrinogen cross-linking) was achieved. These results suggest that fibrinogen-FITC fluorescence is sensitive enough to detect EACA activity in clinically relevant ranges, but that EACA given in usual doses is insufficient to promote fibrinogen cross-linking in patients with end-stage liver disease.

Adult↗
PubMed2004

Evaluation of a novel kallikrein inhibitor on hemostatic activation in vitro.

BACKGROUND: DX-88 is a potent kallikrein inhibitor that is being studied for the treatment of hereditary angioedema (HAE) and represents a potential alternative to aprotinin in cardiac surgical patients. The current study was designed to evaluate in vitro effects of DX-88 on coagulation in comparison with aprotinin. METHODS: Blood samples were obtained from consented 12 healthy volunteers. DX-88 or aprotinin was added to blood at 200 and 800 kallikrein inhibitory units (KIU) per milliliter for aprotinin, and at 1.1, 2.2, or 8.8 microg/ml for DX-88. Thromboelastography (TEG) was performed using celite, kaolin, or tissue factor (TF) activation. Kaolin-based activated clotting times (ACTs) were measured at different heparin levels. The whole blood prothrombin time (PT)/PTT values were also measured. The endogenous thrombin generation was assessed with a fluorogenic assay using platelet-poor plasma (PPP). RESULTS: With celite and kaolin activation of TEG, the reaction time was prolonged with DX-88 and aprotinin. With tissue factor activation, TEG parameters were not affected. DX-88 caused dose-dependent kaolin-ACT prolongation that was augmented by increasing doses of heparin. DX-88 or aprotinin had no significant effects on the PT values, but PTT values were dose-dependently prolonged. Both agents delayed the onset of thrombin generation when PTT reagent was used as a trigger, whereas no change was observed when tissue factor was used. CONCLUSION: We found that DX-88 delayed contact activator induced coagulation without affecting tissue factor mediated coagulation. For evaluation of coagulation during DX-88 therapy, the use of PT or tissue factor-activated TEG may be preferable.

Aprotinin↗
PubMed2004

The influence of red wine or white wine intake on platelet function and viscoelastic property of blood in volunteers.

Since the consumption of wine in the United States has increased in recent years, a number of patients may be admitted to the hospital on the morning of their elective surgery after having consumed wine with dinner the evening before. Research indicates that by reducing platelet aggregation, moderate alcohol consumption can protect against the development of coronary artery disease. Therefore, an alcohol consumption in the night before surgery may influence on a patient's hemostasis. This study was designed to investigate the effects of wine intake the night before surgery on platelet aggregation and thromboelastogram in healthy volunteers. Twenty-four healthy subjects participated in this randomized crossover study. Each subject drank either a half bottle (300-350 ml, approximately two glasses) of red or white wine during dinner on two separate occasions. Blood samples were taken on the morning of the scheduled wine consumption and at the same time on the morning after the wine consumption. Platelet counts, and thromboelastogram (TEG) were performed and platelet function was assessed by adenosine diphosphate (ADP) and collagen induced platelet aggregation tests. There were no significant changes in platelet number, platelet function and TEG values the morning after wine consumption, and there were no significant differences in platelet number, platelet function and TEG values between red and white wine. This study indicates that an intake of red or white wine during dinner does not affect platelet number, platelet function, or viscoelastic properties of blood the next morning. A half bottle of red or white wine intake prior to a next day's elective surgery has no significant risk of suppression of coagulation function.

Adenosine Diphosphate↗
PubMed2004

Clopidogrel (Plavix) and cardiac surgical patients: implications for platelet function monitoring and postoperative bleeding.

The use of clopidogrel (Plavix), an inhibitor of adenosine diphosphate (ADP)-induced platelet aggregation, has been proven to reduce ischemic events in cardiovascular patients, but little information is available for optimal monitoring of platelet function in patients receiving the drug preoperatively. In the first part of the study we compared different testing modalities (thrombelastography (TEG), platelet aggregometry, and whole blood aggregation) to assess platelet ADP receptor inhibition. Because clopidogrel is a pro-drug, we used an in vitro model of ADP inhibition with 5'-p-fluorosulfonylbenzoyladenosine (FSBA). FSBA at final concentration of 80 microM completely inhibited platelet aggregation but had no effect on TEG maximum amplitude (MA). In the second part of the study, antiplatelet effects of clopidogrel were clinically assessed and correlated to postoperative bleeding in 18 coronary bypass surgery patients. Preoperative TEG results were normal or hypercoagulable in clopidogrel-treated patients, although platelet aggregation responses to ADP were inhibited. Clopidogrel-treated patients who underwent cardiopulmonary bypass had a high incidence (84.6%) of platelet transfusion therapy due to increased chest tube drainage. In conclusion, we have demonstrated that normal preoperative TEG-MA does not preclude clopidogrel-induced ADP receptor blockade; however, TEG can be a reliable monitor for CPB-induced platelet dysfunction related to GPIIb/IIIa. For monitoring clopidogrel, it is necessary to perform more specific platelet function tests (aggregometry or platelet count ratio) using ADP as an activator.

Adenosine↗
PubMed2004

Hemostatic agents.

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Aminocaproic Acid↗
PubMed2004

Platelet transfusions during coronary artery bypass graft surgery are associated with serious adverse outcomes.

BACKGROUND: Platelet (PLT) transfusions are administered in cardiac surgery to prevent or treat bleeding, despite appreciation of the risks of blood component transfusion. The current analysis investigates the hypothesis that PLT transfusion is associated with adverse outcomes associated with coronary artery bypass graft surgery (CABG). STUDY DESIGN AND METHODS: Data originally collected during double-blind placebo-controlled phase III trials for licensure of Trasylol (aprotinin injection) were retrospectively analyzed. Adverse outcome data of patients (n = 1720) that received, and did not receive, perioperative PLT transfusion were compared. Logistic regression analysis was used to assess the association of perioperative adverse events with PLT transfusion. Propensity scoring analysis was used to verify results of the logistic regression. RESULTS: Patients receiving PLTs were more likely to have prolonged hospital stays, longer surgeries, more bleeding, re-operation for bleeding, and more RBC transfusions, and less likely to have full-dose aprotinin administration. Adverse events were statistically more frequent in patients that received one or more PLT transfusion. Logistic regression analysis showed that PLT transfusion was associated with infection, vasopressor use, respiratory medication use, stroke, and death. Propensity scoring analysis confirmed the risk of PLT transfusion. CONCLUSIONS: PLT transfusion in the perioperative period of CABG was associated with increased risk for serious adverse events. PLT transfusion may be a surrogate marker for sicker patients and have no causal role in the outcomes observed. However, a direct contribution to outcomes remains possible.

Aged↗
PubMed2004

The effects of argatroban on thrombin generation and hemostatic activation in vitro.

We evaluated argatroban, a direct thrombin inhibitor, as a heparin adjunct for anticoagulation. Platelet-poor plasma (PPP) was isolated from blood collected from 12 volunteers. Thrombin generation measurements were performed in donor PPP that was mixed with antithrombin (AT)-poor plasma to yield AT levels of 0%, 20%, 60%, and 100%. Effects of argatroban (0-1.0 microg/mL), heparin (0.25 U/mL), or the combination of argatroban (0.5 microg/mL) and heparin were also studied. The addition of increasing concentrations of argatroban, heparin, or both to donor PPP (AT level approximately 100%) caused progressive decreases in the lag time and peak formation of thrombin generation. Heparin (0.25 U/mL) at small AT concentrations had a minimal effect on lag time or peak thrombin formation; its effectiveness of inhibiting thrombin was directly correlated with the concentration of AT. Argatroban at 0.5 microg/mL was effective in decreasing thrombin formation at both low and normal AT levels, but it was most effective when combined with heparin. Additionally, blood samples were obtained from 47 cardiac surgical patients, and the interaction of heparin (>1.5 U/mL) and AT or argatroban on clot formation was evaluated with kaolin activated clotting times (ACTs). Significant increases of ACTs at all heparin levels were observed with the addition of argatroban (0.125 and 0.25 microg/mL). The addition of AT (0.2 U/mL) to heparinized blood samples further prolonged ACTs. In summary, we showed that argatroban, unlike heparin, could effectively reduce thrombin generation regardless of AT levels and could prolong ACTs in vitro at clinically used concentrations.

Aged↗
PubMed2004

A novel method to assess platelet inhibition by eptifibatide with thrombelastograph.

We examined a novel method to detect platelet inhibition with thrombelastography (TEG). We hypothesized that this method would be suitable for monitoring the antiplatelet effects of eptifibatide (Integrilin). Whole blood from healthy volunteers was anticoagulated with 3.2% citrate or unfractionated heparin (7 IU/mL). For the platelet aggregation test, both citrate and heparinized samples were spiked with increasing concentrations of eptifibatide (0, 0.2, 0.4, 0.8, 1.6, and 4 microg/mL). Conventional kaolin TEG was performed with citrated samples, and batroxobin-modified TEG was performed with heparinized samples, which were spiked with eptifibatide at concentrations of 0, 0.4, 0.8, 1.6, 4, 8, and 24 microg/mL. Adenosine 5'-diphosphate-induced platelet aggregation was reduced to 6.4% +/- 2.9% (citrate) and 10.3% +/- 4.8% (heparin) with eptifibatide at the concentration of 4 mug/mL. The kaolin TEG showed a decrease in maximum amplitude (MA) only at the eptifibatide concentration of 24 mug/mL and no change in alpha angle, whereas with the batroxobin-based TEG, the difference in MA and alpha angle was observed at concentrations >/=0.8 microg/mL. Additionally, the time to achieve maximum MA was much shorter for batroxobin TEG than for kaolin TEG. We conclude that the batroxobin-modified TEG is a sensitive method that detects platelet inhibition induced by eptifibatide.

Adenosine Diphosphate↗