THROMBOXANE AND PROSTACYCLIN GENERATION IN CHILDREN UNDERGOING CARDIAC BYPASS SURGERY

1987 ◽  
Author(s):  
M Mclaren ◽  
C Shiach ◽  
B Gibson ◽  
J Pollock ◽  
G D O Lowe ◽  
...  

Children undergoing surgery involving cardiac bypass frequently have problems with post-operative bleeding, more so than children having the same length of surgery but without cardiac bypass. Although the platelet count is known to fall during bypass surgery it also falls in otter groups of surgical patients inwhom post-operative bleeding is nota problem. The passage of blood through the bypass machine may cause damage to the platelets which may therefore be functionally abnormal after surgery and thus promote bleeding. We studied eight patients undergoing cardiac bypass surgery aged between 4 and 14 years.All had similar operating conditions and non-pulsatile , membrane oxygenatory bypass. Each patient was sampled immediately prior to surgery after being anaesthetised and 30 minutes and 24 hours post-operatively. Platelet count, anti thrombin III and proteinC levels fell significantly consistent with activation of platelets and coagulation. Plasma levels of beta-thromboglobulin, thromboxane B2 and prostacyclin metabolites (all measured by radioimmunoassay) were elevated in most patients 30 minutes after surgery, but had usually returned to normal levels 24 hours later. We conclude that cardiac bypass in children causes transient activation of platelets and the thromboxane/prostacyclin pathways: the relationship to bleeding requires further study.

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2096-2096
Author(s):  
Eric Mou ◽  
Colin Murphy ◽  
Jason Hom ◽  
Lisa Shieh ◽  
Neil Shah

Introduction Platelets are transfused prophylactically to prevent hemorrhage in a variety of patient populations. However, guidelines indicate that prophylactic platelet transfusions in patients with platelet counts above 50k/uL are usually not indicated, with notable exceptions including those undergoing neurological or cardiac bypass surgery. Common minor procedures such as paracentesis, central line placement, and lumbar puncture have been safely performed at platelet counts below 50k/uL. Despite this evidence, our institution incurred approximately 10 million dollars (USD) in direct platelet costs in 2017, with nearly 40% of platelet transfusions are occurring when the patient's platelet count exceeded 50k/uL. Given the significant financial impact of, and potential adverse effects associated with inappropriate platelet transfusion, we implemented a best practice advisory (BPA) in our electronic medical record (EMR) in order to better characterize patterns of platelet transfusion orders in patients with platelet counts >50k/uL. Methods An EMR-embedded BPA was activated in the inpatient hospital setting of a large, tertiary care academic medical center on May 1, 2019, and triggered whenever a platelet transfusion order was placed on an admitted patient whose most recent documented platelet count was >50k/ul. To inform the comparative impact of BPA alerts on provider behavior, alerts were randomized at the patient level to trigger either in standard or silent fashion. For standard alerts, the BPA appeared on-screen, informing the provider that their platelet transfusion order was potentially inappropriate and citing supportive evidence. Providers had the option of following or overriding the alert (Figure 1). In case of alert override, a pre-specified or free text justification was requested. Pre-specified options included upcoming neurosurgery, cardiac bypass surgery, known qualitative platelet defects, or patients taking antiplatelet drugs. Charge data were based on charges for platelet transfusion orders as listed in the hospital charge master. Results From May 1, 2019 to July 30, 2019, the alert fired 181 times (Figure 2). Alerts were silently triggered in 64 (35%) cases. Of the 117 active alerts, 23 (20%) were followed and 94 (80%) were overridden. The most common reasons for alert override included prophylactic transfusions ahead of non-cardiac and non-neurosurgical operations (18%), upcoming cardiac bypass surgery (18%), qualitative platelet defects (12%), active central nervous system (CNS) bleeding (12%), and active non-CNS bleeding (7%). The estimated cost savings associated with followed alerts was $18,170 USD. Discussion Our BPA was effective in reducing instances of platelet transfusion orders by 20% over a three-month period, translating to an estimated annual savings of nearly $70,000 USD in hospital charges. Conversely, the 80% alert override rate indicates that platelet transfusion in patients with platelet counts >50k/uL remains common, occurring in a variety of contexts. Potentially appropriate reasons for platelet transfusions included orders in the setting of cardiovascular bypass surgery, active CNS bleeding, or qualitative platelet defects, representing circumstances in which platelet thresholds are often set higher than 50k/uL. Alternatively, 25% of alert overrides occurred in potentially inappropriate contexts, including patients undergoing non-cardiovascular/non-neurosurgical procedures and patients with non-CNS active bleeding, settings where routinely targeting a platelet threshold >50k/uL is not supported by evidence. As a result of our study's randomized design, future directions include comparative analyses between patient care encounters in which alerts were silently versus visibly triggered, allowing for rigorous determination as to whether providers' interaction with our BPA influences subsequent rates of potentially inappropriate platelet utilization as compared to a control group. Overall, our findings show that platelets are frequently ordered in potentially inappropriate settings, and that reducing these orders imparts significant financial savings. These results provide an impetus for interventions directed at educating providers on appropriate platelet ordering practices, in order to further reduce unnecessary expenditures and optimize patient care. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1159-1159
Author(s):  
Thomas L. Ortel ◽  
Ian Welsby ◽  
David F Kong ◽  
John A. Heit ◽  
Elizabeth Krakow ◽  
...  

Abstract Abstract 1159 Background. Heparin induced thrombocytopenia (HIT) is an immune disorder where platelets are activated by antibodies to a complex of platelet factor 4 antigen and heparin (PF4/H), leading to thrombocytopenia (HIT) and, potentially, thrombosis (HITT). Documentation of anti-PF4/H antibodies in addition to the appropriate clinical findings is essential for making a diagnosis of HIT. In the post-cardiac bypass surgery setting, however, the frequency of elevated anti-PF4/H antibodies is high, whereas the frequency of clinical HIT or HITT is relatively uncommon. Several studies have shown that the presence of anti-PF4/H antibodies may be associated with an increased frequency of adverse outcomes, even in the absence of clinical HIT. The primary objective of this study was to determine the relationship between a positive PF4/H antibody in the postoperative setting with adverse thromboembolic events occurring up to 3 months after cardiac surgery. Methods. Patients undergoing cardiac surgery who were not going to be treated with chronic anticoagulation postoperatively were eligible for this multi-center prospective cohort study. Data were collected daily during hospitalization, and then at 30 and 90 days after surgery using a structured interview format with a standardized questionnaire that included all thrombotic as well as hemorrhagic events, platelet counts, and utilization of antithrombotics in the postoperative setting. The primary outcome variable was a composite endpoint comprising arterial and venous thrombotic events and other miscellaneous events compatible with HIT, as well as death attributable to an event compatible with HIT. Citrated plasma was collected at baseline, pre-discharge (∼4–5 days after surgery), and the 30 day follow-up visit, processed, and stored at −80°C for testing. Laboratory analyses included an anti-PF4/H antibody ELISA (GTI, Waukesha, WI) on all samples, a high-heparin confirmatory test on samples with an OD reading >0.40, and a serotonin release assay (SRA) on all postoperative samples with an OD reading >0.40. A sample size of 800 patients was estimated in order to detect a 3% difference in thromboembolic events assuming a 2 to 10-fold increase risk attributable to seropositivity. Chi-squared testing was used to test the relationship between the primary outcome and postoperative anti-PF4/H levels. Results. Informed consent was obtained from 1030 eligible patients between August 2006 and May 2009, and laboratory and follow-up data were analyzable for 1016 patients. Thirty-day antibody data were available for 888 patients, and fully complete laboratory and 90-day follow-up data were available for 815 patients. The average age was 62 ± 12 years, and 73% of participants were male. A total of 769 patients underwent coronary artery bypass grafting and 237 underwent valve repair or replacement. During the entire study period, there were 17 (1.7%) deaths, 46 thromboembolic events in 44 patients (4.3%), and 25 hemorrhagic events in 24 patients (2.4%). Using an OD cutoff of 0.40 for the ELISA, 339 patients (33.4%) were positive for anti-PF4/H antibodies at the time of discharge, and 630 patients (62%) were positive by day 30. There was no correlation between seropositivity for anti-PF4/H antibodies at the day of discharge or at day 30 and the primary outcome (p=0.47 and 0.73, respectively). Incorporating the high-heparin confirmatory step did not improve the relationship between positive antibody results and the primary outcome. Using a higher cut-off value for the anti-PF4/H antibody ELISA of 1.0 decreased the number of patients with positive results (96 patients at the time of discharge [9.4%] and 221 patients at the 30-day follow-up visit [21.8%]), but this did not improve the relationship between antibody positivity at the day of discharge or day 30 and the primary clinical endpoint, since most patients with the primary endpoint had an ELISA OD below 1.0 (75th percentile of 0.90; 90th percentile of 1.22). Similarly, using the SRA did not identify a relationship between assay results and outcome. Conclusions. The presence of anti-PF4/H antibodies in the postoperative setting following cardiac bypass surgery is not associated with an increased risk for thromboembolic complications. Positive anti-PF4/H results in this clinical setting should be interpreted with caution and only in the context of clinical suspicion for HIT. Disclosures: Ortel: Instrumentation Laboratory: Consultancy; Eisai: Research Funding; GSK: Research Funding. Welsby:CSL Behring: Speaker; CSL Behring: Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Principal Investigator. Heit:Daiichi Sankyo: Honoraria; Ortho-McNeil Janssen: Honoraria; Covidien: Honoraria.


2016 ◽  
Vol 15 (6) ◽  
pp. 438-446 ◽  
Author(s):  
Erin W Tang ◽  
Jeremy Go ◽  
Andrea Kwok ◽  
Bonnie Leung ◽  
Sandra Lauck ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4148-4148
Author(s):  
Prashanti Atluri ◽  
Jennifer Kujawa ◽  
Alexander Hindenburg

Abstract It has been demonstrated that neutrophils activate macrophages via the heparin binding protein, thus possibly contributing to the incidence of heparin induced thrombocytopenia (HIT). It would follow that the incidence of thrombocytopenia and its sequelae may be reduced by using leukoreduced blood in patients undergoing cardiac bypass surgery. We had a unique opportunity to study this hypothesis at our institution. Due to a policy change all patients undergoing cardiac bypass surgery received LR blood intra-operatively prior to April 2005. Subsequent to this period non-LR blood was utilized in all patients. A retrospective chart review of 197 non-LR and 316 LR patients was done. The platelet count on admission, the first five days post- op, the day of discharge, the percent drop in platelet count post-op and heparin antibody (HA) test were obtained. Thrombocytopenia was defined as an overall drop in platelet count by > 50%. The CABG and the non-CABG patients were looked at separately. The results are as follows: Percent of patients with > 50% drop in platelet count: all patients CABG patients non-CABG patients leukoreduced arm 64% 62.4% 73.3% non-leukoreduced arm 64.6% 61.7% 82.1% Fisher’s exact test p = 0.92 p = 0.92 p = 0.57 Percent of patients with heparin antibody positivity: all patients CABG patients non-CABG patients leukoreduced arm (n=81) 24.7% 23.3% 28.6% non-leukoreduced arm (n=39) 30.8% 35.5% 12.5% Fisher’s exact test p = 0.51 p = 0.23 p = 0.63 In both the LR and non-LR populations there is only a 0.6% difference in the number of patients with a > 50% platelet drop. The relative risk is 1.01 with the 95% confidence interval of (0.88, 1.15). This is a relatively narrow confidence interval reflective of the relatively large sample size. Heparin antibody testing was not done on all the patients. Only those with persistent or profound thrombocytopenia had the test ordered. Overall heparin antibody positivity in both cohorts was not statistically different. The LR arm had a slightly higher positivity rate overall. The risk ratio is 1.25 indicating that the non-LR arm is 25% more likely to have a positive antibody test compared to the LR arm. The higher positivity rate in non-CABG patients may be due to the more complex nature of the surgery relative to CABG surgery. The non-CABG group has a higher percent of heparin antibody positivity in the LR arm. This inconsistency may be secondary to the smaller sample size of this group. In both the CABG or non-CABG groups, there was no statistically significant difference in the percent platelet drop or heparin antibody positivity. One can conclude that leukoreduction of red blood cell products during cardiac surgery does not significantly impact on thrombocytopenia or the development of HIT.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1053-1053
Author(s):  
Stephanie L. Perry ◽  
Nicole L. Whitlatch ◽  
Thomas L. Ortel

Abstract Depending on the clinical setting, anti-platelet factor 4 (PF4)/heparin antibodies may be present in the absence of manifestations of heparin-induced thrombocytopenia (HIT), such as after bypass surgery. In addition, some patients have heparin-independent antibodies (ie, no inhibition of antibody binding in the ELISA with added heparin), but the clinical significance of a negative confirmatory result is unknown. Current recommendations for patients with HIT include treatment with a direct thrombin inhibitor (DTI) for up to 4 weeks. To assess current practice at a tertiary care center, we performed a retrospective analysis of patients with anti-PF4/heparin antibodies at Duke University Medical Center from January to July 2005, investigating diagnostic criteria, co-morbid conditions, therapeutic interventions, and outcomes. Anti-PF4/heparin antibody titers were determined by ELISA using a confirmatory step with excess heparin. A positive confirmatory result was defined as >50% decrease in antibody binding in the presence of heparin. Of 59 patients with PF4/heparin antibodies, 50 had positive confirmatory results. For the confirm-positive patients, median platelet count nadir was 51,000±51,776/μL and % decrease from baseline was 71%±25%. Median peak PF4/heparin antibody titer was 0.9±0.8 AU. Seven patients were on the cardiology service, 15 were post-cardiac bypass surgery, 18 were on general medicine, and 4 were on general surgery. Sixteen patients (32%) had other potential causes for thrombocytopenia. Fifteen patients had thromboembolic events (TE); 12 had TE prior to the diagnosis of HIT (24%) and 3 patients sustained TE within 2 days of the positive test result. Twenty-six patients (52%) were treated with a DTI. Seven (of 21 evaluated) sustained bleeding complications requiring discontinuation of therapy. Six patients treated with a DTI died, 4 of whom had TE. Twenty-four patients were not treated with a DTI: 10 did not meet clinical criteria for HIT and 3 had bleeding complications that precluded DTI therapy. Of the remaining 11 patients not treated with a DTI, two died; one with sepsis, one with sepsis and stroke. One sustained DVT, but was therapeutic on warfarin at home when the positive ELISA result returned. Eight had no TE. Nine of the 59 patients had anti-PF4/heparin antibodies with a negative confirmatory test. Median platelet count nadir was 57,000±24,947/μL and % decrease from baseline was 62%±16%. Median peak PF4/heparin titer was 0.93±0.89 AU. Three patients were on the cardiology service, 1 was post-cardiac bypass surgery, 1 was on general surgery, and 4 were on general medicine. Eight patients had other causes for thrombocytopenia. Five patients sustained TE: one with lung cancer, one with clot on a central catheter, one with DIC and sepsis, and two with acute coronary syndromes at presentation. Only 1 patient with a negative confirmatory test was felt to have HIT, and that patient was treated with a DTI. One patient died with sepsis. In conclusion, anti-PF4/heparin antibodies are detected in diverse patient populations who frequently have additional risk factors for thrombocytopenia and thrombosis. Negative confirmatory results in the PF4/heparin ELISA were more frequently obtained in patients who did not meet clinical criteria for HIT. The decision to use a DTI in patients with anti-heparin PF4 antibodies must be individualized, since bleeding complications are frequent. Some patients with anti-heparin PF4 antibodies and no TE may not require treatment with a DTI, but this observation needs to be confirmed prospectively.


1988 ◽  
Vol 59 (02) ◽  
pp. 273-276 ◽  
Author(s):  
J Dawes ◽  
D A Pratt ◽  
M S Dewar ◽  
F E Preston

SummaryThrombospondin, a trimeric glycoprotein contained in the platelet α-granules, has been proposed as a marker of in vivo platelet activation. However, it is also synthesised by a range of other cells. The extraplatelet contribution to plasma levels of thrombospondin was therefore estimated by investigating the relationship between plasma thrombospondin levels and platelet count in samples from profoundly thrombocytopenic patients with marrow hypoplasia, using the platelet-specific α-granule protein β-thromboglobulin as control. Serum concentrations of both proteins were highly correlated with platelet count, but while plasma β-thromboglobulin levels and platelet count also correlated, there was no relationship between the number of platelets and thrombospondin concentrations in plasma. Serial sampling of patients recovering from bone marrow depression indicated that the plasma thrombospondin contributed by platelets is superimposed on a background concentration of at least 50 ng/ml probably derived from a non-platelet source, and plasma thrombospondin levels do not simply reflect platelet release.


1981 ◽  
Vol 45 (03) ◽  
pp. 204-207 ◽  
Author(s):  
Wolfgang Siess ◽  
Peter Roth ◽  
Peter C Weber

SummaryPlatelets have been implicated in the development of atherosclerotic and thrombotic vascular diseases. Evaluation of platelet aggregation in relation to endogenously formed compounds which affect platelet function may provide information of clinical and pharmacological relevance. We describe a method in which thromboxane B2 (TXB2) formation was analyzed following stimulation of platelet-rich plasma (PRP) with ADP, 1-epinephrine, collagen, and arachidonic acid. In addition, we determined platelet sensitivity to prostacyclin following ADP- and collagen-induced platelet aggregation. The parameters under study were found to depend on the platelet count in PRP, on the type and dose of the aggregating agent used, and on the test time after blood sampling. By standardization of these variables, a reliable method was established which can be used in clinical and pharmacological trials.


1985 ◽  
Vol 53 (01) ◽  
pp. 070-074 ◽  
Author(s):  
G Mallarkey ◽  
G M Smith

SummaryThe mechanism of collagen-induced sudden death in rabbits was studied by measuring blood pressure (BP), heart rate, ECG, the continuous platelet count and the plasma levels of thromboxane B2 (TxB2) and 6-keto prostaglandin Fia (6-keto PGF1α). Death was preceded by myocardial ischaemia and a sharp fall in BP which occurred before any fall in platelet count was observed. The calcium entry blockers (CEBs), verapamil, nifedipine and PY 108-068 protected the rabbits from sudden death without any significant effect on the decrease in the platelet count or increase in plasma TxB2 levels. 6-keto PGF1α could not be detected in any plasma samples. Indomethacin and tri-sodium citrate also protected the rabbits but significantly reduced the fall in platelet count and plasma TxB2. In vitro studies on isolated aortae indicated that verapamil non-specifically inhibited vasoconstriction induced by KC1, adrenaline and U46619 (a thromboxane agonist). It is concluded that CEBs physiologically antagonize the vasoconstricting actions of platelet-derived substances and that it is coronary vasoconstriction that is primarily the cause of death.


2010 ◽  
Vol 25 (2) ◽  
pp. 185-194
Author(s):  
Anna Svedberg ◽  
Tom Lindström

Abstract A pilot-scale fourdrinier former has been developed for the purpose of investigating the relationship between retention and paper formation (features, retention aids, dosage points, etc.). The main objective of this publication was to present the R-F (Retention and formation)-machine and demonstrate some of its fields of applications. For a fine paper stock (90% hardwood and 10% softwood) with addition of 25% filler (based on total solids content), the relationship between retention and formation was investigated for a microparticulate retention aid (cationic polyacrylamide together with anionic montmorillonite clay). The retention-formation relationship of the retention aid system was investigated after choosing standardized machine operating conditions (e.g. the jet-to-wire speed ratio). As expected, the formation was impaired when the retention was increased. Since good reproducibility was attained, the R-F (Retention and formation)-machine was found to be a useful tool for studying the relationship between retention and paper formation.


Sign in / Sign up

Export Citation Format

Share Document