RIBAVIRIN: STUDIES OF THE EFFECTS OF THE ANTIVIRAL DRUG ON PLATELET FUNCTION

1987 ◽  
Author(s):  
T M Cosgriff ◽  
P G Canonico ◽  
L Hodgson ◽  
D Parrish ◽  
T Chapman ◽  
...  
Keyword(s):  
Platelet Function ◽  
Influenza A ◽  
Platelet Rich Plasma ◽  
Antiviral Drug ◽  
Hemorrhagic Fever ◽  
Lassa Fever ◽  
Chinese Patients ◽  
Platelet Dysfunction ◽  
Drug Induced ◽  
Syncytial Virus

Ribavirin is a broad-spectrum antiviral drug which is presently undergoing testing in patients with AIDS-related complex. It has also been shown to have activity against respiratory syncytial virus, Sicilian sandfly fever virus, influenza A and B viruses, as well as several hemorrhagic fever viruses. It has proved effective in clinical trials in Lassa fever and shows promise as therapy for hemorrhagic fever with renal syndrome. Because platelet dysfunction may contribute significantly to hemostatic impairment in viral hemorrhagic fever, the effects of ribavirin on platelet function were measured in rhesus monkeys after daily injections of 100 mg/kg IM for 14 days. Drug administration led to a significant increase in platelet count associated with megakaryocyte hyperplasia but had no effect on aggregation of platelet-rich plasma (PRP) in response to either collagen (1.6 μg/ml) or ADP (10 μM/ml). Aggregation in whole blood was also unaffected. Addition of ribavirin to human PRP in concentrations up to 0.5 mg/ml had no effect on aggregation in response to collagen, ADP, or epinephrine (5 μg/ml). Preliminary data from Chinese patients treated with ribavirin for hemorrhagic fever with renal syndrome also reveal no evidence of drug-induced platelet dysfunction as indicated by normal aggregation and release reactions to collagen (3 μg/ml) and ADP (10 μM/ml). Bone marrow studies of megakaryocyte number and ploidy are presently underway to further characterize drug-associated thrombocytosis

Use of Ribavirin in the Treatment of Respiratory Syncytial Virus Infection

PEDIATRICS ◽  
1993 ◽  
Vol 92 (3) ◽  
pp. 501-504
Author(s):  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antiviral Drug ◽  
Hemorrhagic Fever ◽  
Lassa Fever ◽  
Human Infection ◽  
Double Blind ◽  
Course Of Illness ◽  
Syncytial Virus ◽  
Tract Disease

Ribavirin is an antiviral drug that was approved by the Food and Drug Administration in 1986 for aerosol treatment of serious respiratory syncytial virus (RSV) infections in hospitalized children. Ribavirin has a broad spectrum of antiviral activity in vitro, where it inhibits replication of RSV, influenza, parainfluenza, adenovirus, measles, Lassa fever, and Hantaan viruses. Proof of efficacy for human infection has been obtained in double-blind placebo-controlled studies of RSV,1,2 Lassa fever, and Korean hemorrhagic fever. Presently, only anecdotal reports support the efficacy of this drug for treatment of measles or parainfluenza. Ribavirin treatment for RSV infections has been controversial because of the aerosol route of administration, concern for potential toxicity for exposed persons, cost, and the unpredictable and highly variable course of illness in the absence of specific therapy. These issues necessitate ongoing review of ribavirin therapy and the following updated recommendations by the American Academy of Pediatrics. BACKGROUND RSV Disease Respiratory syncytial virus is the most important cause of lower respiratory tract disease in infants and young children. Disease usually appears in yearly outbreaks in the winter or spring, and essentially all children become infected during their first 3 years of life. The number of infected infants who require hospitalization has been estimated to range from 1 to 50 per 1000 in different locations. Currently, the mortality rate in hospitalized infants who previously were healthy is low (less than 1%). In infants with underlying diseases, however, the mortality can be much higher. Conditions that increase the risk of severe or fatal RSV infection are cyanotic or complicated congenital heart disease (including pulmonary hypertension); underlying pulmonary disease, especially bronchopulmonary dysplasia; prematurity; and immunodeficiency disease or therapy causing immunosuppression at any age.

Clinical Review of Ribavirin

1987 ◽  
Vol 8 (5) ◽  
pp. 215-218 ◽  
Author(s):  
Mark Eggleston
Keyword(s):  
Herpes Zoster ◽  
Influenza A ◽  
Viral Infections ◽  
Face Mask ◽  
Lassa Fever ◽  
Severe Respiratory Syncytial Virus ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Significant Addition ◽  
Infants And Young Children

AbstractThe recent approval of ribavirin aerosol for the treatment of severe respiratory syncytial virus (RSV) in infants and young children is a significant addition to the antiviral drugs available today. When administered as an aerosolized form by face mask or mist tent for 20 to 21 hours per day, ribavirin effectively decreases the symptoms of RSV infection and the shedding of RSV virus.Studies of other viral infections such as viral hepatitis, influenza A and B, Lassa fever, genital herpes, and herpes zoster have demonstrated promising, but inconclusive results. Further studies are needed to justify ribavirin therapy for these indications.

scholarly journals Influence of Imidazole Carboxamide on Platelet Function

1977 ◽  
Author(s):  
P. Kubisz ◽  
P. Klener ◽  
S. Cronberg
Keyword(s):  
Platelet Function ◽  
Light Transmission ◽  
Platelet Rich Plasma ◽  
Cytostatic Drug ◽  
Bleeding Tendency ◽  
Platelet Dysfunction ◽  
Freezing And Thawing ◽  
Trade Name ◽  
Coagulation And Fibrinolysis

Imidazol carboxamide (DTIC, NSC-45388) is a cytostatic drug used in the treatment of malignant melanoma under the trade name of DacarbazinR, MSD. Its influence on platelet function, blood coagulation and fibrinolysis was investigated in vitro.At a concentration of 160 µg/ml it inhibited the increase in light transmission induced in platelet-rich plasma by standardized freezing and thawing. It also retarded the retraction of reptilase clots. This therefore indicated a stabilizing effect on the platelets at this dosage.At a concentration of 40 μg/ml the drug did not significantly influence the platelet function in vitro.This concentration corresponds to therapeutic plasma levels. At current dosage of the drug any bleeding tendency due to platelet dysfunction therefore seems unlikely.

A Quick Method for Screening Platelet Dysfunctions Using the Whole Blood Lumi-Aggregometer

1984 ◽  
Vol 51 (02) ◽  
pp. 154-156 ◽  
Author(s):  
Carol M Ingerman-Wojenski ◽  
Melvin J Silver
Keyword(s):  
Platelet Function ◽  
Whole Blood ◽  
Electrical Impedance ◽  
Platelet Rich Plasma ◽  
Clinical History ◽  
Platelet Dysfunction ◽  
Quick Method ◽  
Platelet Function Disorders ◽  
Function Defect ◽  
Sensitive Method

SummaryPatients who present with a clinical history suggesting a bleeding disorder are often tested initially for a clotting defect rather than for platelet dysfunction, due to the length of time necessary to complete a platelet function study in platelet-rich plasma. We have developed a sensitive method for measuring platelet aggregation and release of ATP employing the Whole Blood Lumi-Aggregometer. This method makes it possible to quickly detect patients who require further study for possible platelet function disorders such as cyclooxygenase deficiency, storage-pool defect, thrombasthenia, and von Willebrand’s disease. The results obtained with this electrical impedance instrument do not differ from those obtained with the conventional optical method. However, it is now possible to recognize a platelet function defect within 30 min of obtaining a 5 ml sample of citrated whole blood. Further, platelets of unusual size or density are not lost to testing through centrifugation.

Evaluation of Platelet Dysfunction In Children: Improved Detection and Efficiency

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1446-1446
Author(s):  
Diane J. Nugent ◽  
Ryan Roberts ◽  
Peggy Nakagawa
Keyword(s):  
Platelet Function ◽  
Mutational Analysis ◽  
Light Transmission ◽  
Platelet Rich Plasma ◽  
Clot Formation ◽  
Activity Levels ◽  
Food History ◽  
Platelet Dysfunction ◽  
Light Transmission Aggregometry ◽  
Arachadonic Acid

Abstract Abstract 1446 Currently, there is no single assay that will detect platelet function abnormalities in all individuals. We prospectively studied 369 patients with a strong history of bruising and mucosal membrane bleeding for possible platelet dysfunction following documentation of normal Von Willebrand antigen and activity levels. In an effort to evaluate platelet function under more diverse conditions we chose to simultaneously evaluate 1) aggregation using platelet rich plasma and light transmission aggregometry (LTA), 2) adhesion under high shear using the Platelet Function Analyzer (PFA-100, ADP-collagen, and Epinephrine-collagen cartridges) and 3) platelet initiated clot formation using heparinized whole blood and the two standard mapping agonists, arachadonic acid (AA) and ADP (Hemascope Thromboelastograph Analyzer). Of the 369 platelet evaluations performed, 87 patients (24%) were found to be normal in all three assays with all agonists. On repeated assays with increased attention to medication and food history, an additional 152 patients were felt to have a transient or acquired dysfunction which improved or normalized on further testing. Leaving 130 patients with persistent bleeding and documented abnormalities on one or more of the assays used. There were no patients with only Collagen (CN) or arachadonic acid (AA) aggregation alone on LTA. Using LTA, there was one patient with combined CN and ADP aggregation defect only, another with AA and EPI absent aggregation only, and one with only AA and Thrombin receptor agonist peptide (TRAP) aggregation abnormalities. A summary of the remaining 127 patients are displayed in the table below:Abnormal AssayLTA EPILTA ADPLTA ADP + EPILTA ADP, EPI CNLTA ADP, EPI, AALTA ADP, EPI CN, AAPFA and PLT Mapping ONLYNumber201240841825M/F3M/17F6M/6F16M/24F1M/7F1M/3F8M/10F12M/13FPFA1M/2F4M7M/4F01M01M/3FPlt Mapping2M/2F1M/2F3F1F009M/7FBoth PFA and Mapping1M0001F2M/9F2M/3F Summary: By using a combination of three assays, we were able to identify 25 additional patients with significant platelet dysfunction detected with abnormal platelet mapping or PFA-100 despite normal light transmission aggregometry. Patients with the most abnormalities on aggregation, also demonstrated abnormal adhesion and platelet initiated clot formation. However, the use of PFA-100 and/or platelet mapping alone would miss the majority of patients with aggregation defects. In the future, the unique combination of platelet function defects as measured by these assays, and future technologies, will not only improve detection, but also facilitate phenotype to genotype associations and expedite mutational analysis. Disclosures: Off Label Use: Rituximab to treat ITP.

Effect of Aspirin on the Thrombelastogram of Human Blood

1973 ◽  
Vol 30 (03) ◽  
pp. 494-498 ◽  
Author(s):  
G de Gaetano ◽  
J Vermylen
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Platelet Function ◽  
Human Blood ◽  
Platelet Rich Plasma ◽  
Plasma Samples ◽  
Release Reaction ◽  
Platelet Release

SummaryThrombelastograms of both native blood and re-calcified platelet-rich plasma samples taken from subjects given a single oral dose of aspirin (1 gram) were not significantly different from the pretreatment recordings. Aspirin also did not modify the thrombelastogram when preincubated in vitro with platelet-rich plasma at concentrations inhibiting the platelet “release reaction” by collagen. Thrombelastography therefore cannot evaluate the effect of aspirin on platelet function.

Newborn Platelet Dysfunction: a Storage Pool and Release Defect

1976 ◽  
Vol 36 (01) ◽  
pp. 200-207 ◽  
Author(s):  
Donald G. Corby ◽  
Thomas F. Zuck
Keyword(s):  
Specific Activity ◽  
Platelet Rich Plasma ◽  
Adenine Nucleotides ◽  
Blood Platelets ◽  
Newborn Infants ◽  
Specific Radioactivity ◽  
High Dose ◽  
Platelet Dysfunction ◽  
Paired Samples ◽  
Normal Adults

SummaryPer cent aggregation, release and content of adenine nucleotides, and specific radioactivity were evaluated in citrated platelet-rich plasma (PRP) prepared from paired samples of maternal and cord blood. Platelets of newborn infants aggregated normally in response to high dose ADP (20 μM), strong collagen suspensions, and thrombin; however, when compared with PRP from the mothers or from normal adults, per cent aggregation in response to lower concentrations of ADP (2 μM), weak collagen, and part particularly epinephrine was markedly reduced. Nucleotide release after stimulation of the newborns’ PRP with the latter two inducers was also impaired. ATP and ADP content of the newborns’ platelets was also significantly less than that of their mothers or of normal adults, but specific activity was normal. The data suggest that the impairment of ADP release in the platelets of newborn infants is due to decreased sensitivity to external stimuli. Since metabolic ATP is necessary for the platelet release reaction, it is postulated that the platelet dysfunction results from a lack of metabolic ATP.

Effects of Halothane on Platelet Function

1980 ◽  
Vol 44 (03) ◽  
pp. 143-145 ◽  
Author(s):  
J Dalsgaard-Nielsen ◽  
J Gormsen
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Rich Plasma ◽  
Human Platelets ◽  
Halothane Anaesthesia ◽  
Inhibition Of Platelet Aggregation ◽  
Transient Impairment ◽  
High Concentrations ◽  
Uptake And Release ◽  
Platelet Functions

SummaryHuman platelets in platelet rich plasma (PRP) incubated at 37° C with 0.3–2% halothane for 5–10 min lost the ability to aggregate with ADP, epinephrine and collagen.At the same time uptake and release of 14C-serotonin was inhibited. When halothane supply was removed, platelet functions rapidly returned to normal. However, after high concentrations of halothane, the inhibition of platelet aggregation was irreversible or only partially reversible.The results suggest that halothane anaesthesia produces a transient impairment of platelet function.

The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

1973 ◽  
Vol 30 (02) ◽  
pp. 315-326
Author(s):  
J. Heinz Joist ◽  
Jean-Pierre Cazenave ◽  
J. Fraser Mustard
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Barbituric Acid ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Primary Response ◽  
Sodium Pentobarbital ◽  
Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

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