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Biomedical subjects

S Glazer

Publications and source records attributed to S Glazer.

At least 19 recordsLinked to original sources
PubMed2001

Rapid assessment of glycoprotein IIb/IIIa blockade with the platelet function analyzer (PFA-100) during percutaneous coronary intervention.

BACKGROUND: The platelet function analyzer PFA-100 (Dade Behring, Miami, Fla) evaluates platelet function by determining the time to occlusion of an aperture in a membrane coated with collagen and adenosine diphosphate or epinephrine as whole blood flows under shear stress conditions. Platelet aggregation causes aperture occlusion, and results are reported as closure time (CT). Interindividual variability is observed in the level of platelet inhibition achieved with use of the current abciximab dosing regimen (0.25-mg/kg bolus + 10-microg/min infusion for 12 hours). The relationships between specific levels of platelet inhibition and clinical efficacy and safety have not been fully established. METHODS AND RESULTS: We prospectively studied platelet function in 27 patients receiving abciximab during percutaneous coronary intervention. This evaluation included determinations of platelet-rich plasma aggregometry, receptor occupancy studies (D3 assay), and CT measurements at baseline and 10 minutes, 4 hours, 12 hours, and 24 hours after the bolus. All patients received abciximab, aspirin, and heparin; patients undergoing coronary stent implantation received aspirin and ticlopidine after the procedure. CT results were reported within 10 minutes after initiation of testing. For 96% of patients, CT was 300 seconds (maximum CT) immediately after abciximab bolus and remained so throughout the infusion. At 24 hours we observed variable recovery from platelet inhibition and in 72% of patients CT returned to normal (< or =130 seconds). CONCLUSIONS: Findings with the PFA-100 were similar to results observed with platelet aggregometry and receptor occupancy measurements. Most patients treated with abciximab exhibit normalized platelet function at 24 hours despite moderate levels of receptor occupancy, suggesting dissociation between occupancy and function.

Abciximab↗
PubMed1997

Recombinant factor VIIa corrects prothrombin time in cirrhotic patients: a preliminary study.

BACKGROUND & AIMS: Cirrhotic patients with a prolonged prothrombin time (PT) are known to have low levels of factor VII. Because the current modalities to correct this problem are not ideal, recombinant factor VIIa (rFVIIa) may be useful in correcting the prolonged PT observed in the coagulopathy of cirrhosis. The aim of this study was to evaluate the effectiveness of rFVIIa in nonbleeding volunteer patients with the coagulopathy of cirrhosis. METHODS: A preliminary, single-center, dose-escalation trial was performed. Cirrhotic patients with a PT of > 2 seconds above the upper limit of the reference value received an intramuscular injection of vitamin K. Ten patients whose PT did not correct to within 2 seconds above the control of the upper limit of the reference value were given three successive dosages of rFVIIa (5, 20, and 80 micrograms/kg) during a 3-week period. RESULTS: The mean PT transiently corrected to normal in all three dosage groups. No adverse effects were noted. There was no evidence of the induction of disseminated intravascular coagulation. CONCLUSIONS: This preliminary trial shows rFVIIa to be effective in transiently reversing the prolonged PT in a select group of nonbleeding cirrhotic patients. These preliminary observations support conducting a large-scale efficacy trial.

Adult↗
PubMed1996

Clinical experience with recombinant factor VIIa in patients with thrombocytopenia.

Platelets play a central role in primary hemostasis. The role of the coagulation mechanism during early stages of hemostasis is less clear, although increasing evidence is emerging indicating the ultimate importance of the factor VII (FVII)-tissue factor-dependent coagulation system in providing the first thrombin molecules necessary for the platelet activation to occur. Supporting this, early fibrin formation has been reported to occur within the bleeding time wound and infusion of recombinant FVIIa (rFIIa) has been shown to shorten the bleeding time in rabbits. We have investigated whether infusion of rFVIIa would enhance fibrin formation in bleeding time wounds in patients with thrombocytopenia as reflected by a shortening of the bleeding time. A reduction of the bleeding time was found in 55/105 cases (52%). The decrease was significantly more pronounced when the platelet count exceeded 20 x 10(9)/l. With the exception of an anaphylactoid reaction in 1 patient, no major adverse reactions related to the study drug were observed. Nine infusions of rFVIIa were given to 8 thrombocytopenic patients with overt bleeding. One patient received two infusions. Bleeding decreased in all patients and stopped in 6 patients.

Adolescent↗
PubMed1996

Immunological aspects of recombinant factor VIIa (rFVIIa) in clinical use.

Patients, receiving rFVIIa for treatment of bleeding disorders, have been followed for specific antibody formation. No antibodies against FVII were demonstrated in 170 patients, with hemophilia, or with acquired inhibitors to clotting factors. Of 6 FVII-deficient patients, one overdosed patient developed antibodies to human FVII. There was no indication of de novo formation of antibodies to potential contaminating foreign protein, which could be correlated to the rFVIIa treatment. Except for the FVII-deficient population, which may represent a risk group, rFVIIa appears to be immunologically safe for use in patient groups with bleeding disorders, including hemophilia A and B patients.

Animals↗
PubMed1995

Blocking of tissue factor pathway inhibitor (TFPI) shortens the bleeding time in rabbits with antibody induced haemophilia A.

Tissue factor (TF)/FVIIa initiates coagulation by activating factor IX (FIX) and factor X (FX). Tissue factor pathway inhibitor (TFPI)-FXa complexes form and inhibit TF/FVIIa. Blocking of TFPI may facilitate haemostasis initiated by FVIIa/TF thereby compensating for impaired FIX/FVIII-dependent coagulation. This hypothesis was tested in a study using rabbits made temporarily haemophilic by the injection of antibodies against FVIII. These rabbits were given i.v. injections of anti-TFPI IgG antibodies and 40 min later bleeding was initiated by cutting the nail including the apex of the cuticle. Injection of anti-TFPI IgG shortened the bleeding time significantly from 26 min to 11 min (normal mean bleeding time in non-haemophilia rabbits: 5 min). Treatment with anti-TFPI IgG also resulted in a shortening of the haemophilic aPTT to a level slightly longer than the normal aPTT. In addition, the prolonged dilute TF clotting time was shortened by the anti-TFPI IgG treatment. Thus, both bleeding and coagulation parameters indicated that blocking of TFPI may be potentially haemostatic in haemophilia.

Animals↗
PubMed1994

Pharmacokinetics and pharmacodynamics of recombinant factor VIIa.

OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics of recombinant activated factor VII (rFVIIa). METHODS: Single-dose pharmacokinetics of three dose levels (17.5, 35, and 70 micrograms/kg) of rFVIIa were investigated in 15 patients with hemophilia with severe factor VIII or factor IX deficiency (with or without inhibitors) while they were in the nonbleeding state and during bleeding episodes. Factor VII clotting activity (FVII:C) was determined 5 minutes before and at 10, 20, and 50 minutes and 2, 4, 6, 8, 12, and 24 hours after rFVIIa administration. Model-independent pharmacokinetic analysis of FVII:C plasma concentration-time data included determination of plasma clearance, mean residence time, and volume of distribution. rFVIIa recovery was determined from the plasma FVII:C observed 10 minutes after administration. Pharmacodynamic assessments of prothrombin time, activated partial thromboplastic time, and Factor X values obtained concurrently with FVII:C samples were performed. RESULTS: Sufficient data to allow pharmacokinetic parameter calculation were available for 25 nonbleeding episodes in 11 patients (17.5 micrograms/kg, n = 8; 35 micrograms/kg, n = 9; 70 micrograms/kg, n = 8) and for five bleeding episodes in three patients (17.5 micrograms/kg, n = 2; 35 micrograms/kg, n = 2; 35 micrograms/kg, n = 1). Recovery was calculated during 27 nonbleeding and 17 bleeding episodes. rFVIIa distribution volume is two to three times that of plasma. Median clearance was low--31.0 ml/hr.kg in nonbleeding episodes and 32.5 mg/hr.kg in bleeding episodes. In nonbleeding episodes, median mean residence time was 3.44 hours and median half-life was 2.89 hours. In bleeding episodes, the elimination rate appears to be higher, with a median mean residence time of 2.97 hours and a median half-life of 2.30 hours. Recovery was 45.6% during nonbleeding conditions and 43.5% during bleeding episodes (p = 0.0006); it was statistically lower with the highest dose level than with the 17.5 and 35 micrograms/kg doses (p = 0.007). A significant statistical relationship was observed between values of the prothrombin time and activated partial thromboplastin time, and values of FVII:C with use of maximum effect model. CONCLUSIONS: The pharmacokinetics of rFVIIa are linear in the dose range evaluated. The results suggest potential value of prothrombin time determination in the monitoring of rFVIIa therapy.

Adolescent↗
PubMed1993

Recombinant activated factor VII in the treatment of bleeding episodes in patients with inherited and acquired bleeding disorders.

The FVIII/FIX by-passing agent, rFVIIa, offers an alternative approach to the treatment of hemophilia patients as well as nonhemophiliacs with antibodies against FVIII/FIX. Such treatment can be administered regardless of the inhibitor titer in these patients, and rFVIIa is active hemostatically in hemophilia B patients also. It is easy to administer but seems to need repeated dosing at 2 to 3-hour intervals, at least initially, in patients with severe bleeding, with a dose of 70 to 100 micrograms/kg body weight required to induce hemostasis. Depending on the severity of the bleeding the dose intervals may be prolonged to every 3 hours for 1 to 2 days or until clinical improvement is observed. Thereafter, the dosage interval can be increased to every 4 hours if continued therapy is required.

Blood Coagulation Disorders↗
PubMed1993

Safety and initial clinical efficacy of three dose levels of recombinant activated factor VII (rFVIIa): results of a phase I study.

The safety and efficacy of recombinant DNA-produced factor VIIa (rFVIIa) was investigated in 15 haemophilic patients in non-bleeding states and during bleeding episodes (mild to moderate joint bleed). Patients with severe haemophilia A without inhibitors (n = 4), haemophilia A with inhibitors (n = 10), and haemophilia B with inhibitor (n = 1) received one or more doses of rFVIIa during 32 non-bleeding study episodes and 23 bleeding episodes. The study was an open, uncontrolled, dose-escalation (17.5 micrograms/kg, 35 micrograms/kg, 70 micrograms/kg) trial. Physical evaluation, laboratory assessment, and immunology testing were conducted at baseline, monthly for 3 months and every 3 months thereafter. The immediate safety of rFVIIa was assessed by monitoring of D-dimer, fibrinogen, platelet count, antithrombin III, thrombin-antithrombin complex, and alpha 2-antiplasmin 5 min before and at multiple times throughout the following 24 h. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) values were also obtained. Pain, swelling, joint circumference, and range of motion were recorded before administration of the initial dose of rFVIIa in bleeding patients and at 6, 12, and 24 h. Haemostatic response to rFVIIa was observed in patients with severe VIII and IX deficiency with and without inhibitors. Therapy with rFVIIa was judged effective in 19 of the 22 evaluable bleeding episodes at one or more time points. The 35 micrograms/kg and 70 micrograms/kg doses were associated with higher response rates at 6 and 12 h compared to the 17.5 micrograms/kg dose level. A second dose of rFVIIa was administered in 20 of the 22 bleeding episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Experience with recombinant factor VIIA in an infant hemophiliac with inhibitors to FVIII:C undergoing emergency central line placement. A case report.

An infant boy with severe factor VIII (FVIII) deficiency hemophilia and antibodies against coagulation FVIII is presented. This case is unique from the point of view of the young age of development and recognition of inhibitors to the FVIII and because this patient received recombinant factor VIIa (rFVIIa), prior to a life-saving surgical procedure. Conventional treatment options had been exhausted. The inhibitor was an IgG antibody that had rapidly increased to 100 Bethesda Units (BU). A broviac central line was placed to provide i.v. access for the purpose of treatment. Porcine FVIII had been used but an inhibitor rapidly developed to that product. Using rFVIIa, hemostasis was secured for placement of a second central line and to stop life-threatening mucosal bleeding. rVIIa was an effective treatment alternative for the management of this patient with inhibitors.

Autoantibodies↗
PubMed1992

Measurement of basal levels of factor VIIa in hemophilia A and B patients.

Previous results, presented in abstract form, indicate that replacement of thromboplastin with a mixture of phospholipid and truncated soluble tissue factor apoprotein results in a coagulation assay that can directly measure plasma factor VIIa levels without interference from zymogen factor VII (Atherosclerosis Thromb 11:1544a, 1991 [abstr]). We have exploited the specificity and sensitivity of such a factor VIIa specific coagulation assay to directly assess the in vivo relationship of factor VIII and factor IX on the production of factor VIIa levels under nonthrombotic and nonstimulatory conditions. Normal individuals (n = 20) were found to possess an average circulating factor VIIa level corresponding to 4.34 +/- 1.57 ng/mL, or approximately 1% of their total factor VII antigen. Severe factor VIII deficient patients (n = 13) possessed a slightly lower but statistically significant (P less than .01) decrease in their basal factor VIIa levels (2.69 +/- 1.52 ng/mL), corresponding to approximately 60% of that observed in normal individuals. On the other hand, severe factor IX deficient patients (n = 7) were found to possess even lower levels of factor VIIa corresponding to 0.33 +/- 0.15 ng/mL, or less than 10% of that observed in normal individuals. Measurement of total factor VII antigen levels shows that the variation in basal factor VIIa levels stems from differences in the degree of factor VII activation as opposed to differences in factor VII antigen levels. Our present data are consistent with the hypothesis that factor IXa is the principal in vivo activator of factor VII under basal conditions.

Factor VIIa↗
PubMed1992

Extrahepatic portal vein aneurysm: report of a case treated by thrombectomy and aneurysmorrhaphy.

Extrahepatic portal vein aneurysm is a rare condition with only 15 cases before ours being reported in the English literature. The etiology is thought to be congenital, secondary to portal hypertension or associated with abnormal weakness of the vein wall. It often presents in conjunction with major gastrointestinal bleeding, but may occur with minimal or no symptoms. Diagnosis is made with color duplex ultrasound, computed tomographic scan, venous phase mesenteric angiography, magnetic resonance imaging, or splenoportography. Thrombosis, rupture, and pressure effects are the major complications of portal vein aneurysm. Shunting procedures are recommended in cases with portal hypertension secondary to liver disease. We report the first case treated by thrombectomy and aneurysmorrhaphy with a successful 10 year follow-up. This procedure should be considered to preserve portal vein flow when portal hypertension is absent or is secondary to the aneurysm itself.

Adult↗
PubMed1992

Management of hemophilia patients with inhibitors.

rFVIIa seems to offer an alternative in the treatment of hemophiliacs as well as nonhemophiliacs with antibodies against FVIII/FIX. The treatment can be given regardless of the inhibitor titer in those patients and is also hemostatically active in hemophilia B patients. It is easy to administer but seems to need a repeated dosing at 2- to 3-hour intervals, at least initially in severe bleedings. A dose of 70 to 100 micrograms/kg body weight seems to induce hemostasis. Depending on the severity of the bleeding, the dose intervals may then be prolonged to 3 hours for 1 to 2 days or until clinical improvement is observed. Thereafter, the dosage interval can be increased to 4 hours if continued therapy is indicated.

Factor IX↗
PubMed1991

Systemic local anesthetics in pain control.

Analgesia has been reported as a potential effect of systemically administered local anesthetics for over four decades. Interest in the use of these drugs as analgesics has been stimulated by the advent of oral formulations and the findings of several controlled studies that suggest efficacy of these preparations in neuropathic pain syndromes. We review the pharmacology of local anesthetics and critically evaluate the medical literature describing the analgesic consequences of systemic administration. The data extant support their analgesic effect in selected pain syndromes.

Acute Disease↗