[Show abstract][Hide abstract] ABSTRACT: Candidatus Neoehrlichia is increasingly being recognized worldwide as a tickborne pathogen. We report a case of symptomatic neoehrlichiosis in an immunocompetent Austria resident who had recently returned from travel in Tanzania. The use of Anaplasmataceae-specific PCR to determine the duration of antimicrobial therapy seems reasonable to avert recrudescence.
Full-text · Article · Feb 2016 · Emerging infectious diseases
[Show abstract][Hide abstract] ABSTRACT: Aims:
The local pulmonary inflammatory response has a different temporal and qualitative profile compared with the systemic inflammatory response. Although glucocorticoids substantially down-regulate the systemic release of acute-phase mediators, it is not clear whether glucocorticoids have comparable inhibitory effects in the human lung compartment. Therefore we compared the anti-inflammatory effects of a pure glucocorticoid agonist, dexamethasone, on bronchoalveolar-lavage and blood cytokine concentrations in response to bronchially instilled endotoxin.
In this randomized, double-blind and placebo-controlled trial, 24 volunteers received dexamethasone or placebo and had endotoxin instilled into a lung segment and saline instilled into a contralateral segment, followed by bronchoalveolar-lavage.
Bronchially instilled endotoxin induced a local and systemic inflammatory response. Dexamethasone strongly blunted the systemic interleukin-6 and C-reactive protein release. In sharp contrast, dexamethasone left the local release of acute-phase mediators in the lungs virtually unchanged, i.e. bronchoalveolar lavage levels of interleukin-6 were only 18% lower and levels of interleukin-8 were even higher with dexamethasone compared to placebo, but the differences between treatments were not statistically significant (P = 0.07 and P = 0.08, respectively). Yet dexamethasone had inhibitory effects on pulmonary protein extravasation and neutrophil migration.
This trial demonstrates a remarkable dissociation between systemic anti-inflammatory effects of glucocorticoids and protective effects on the capillary-leak on the one hand and surprisingly low anti-inflammatory effects in the lungs on the other hand.This article is protected by copyright. All rights reserved.
No preview · Article · Dec 2015 · British Journal of Clinical Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Objective:
To assess the prevalence, characteristics and prognosis of overt disseminated intravascular coagulation (DIC) in adult emergency department (ED) patients and identify markers of poor outcome.
Materials and methods:
In a chart review study, we analysed the occurrence of overt DIC in all patients (n=1 001 727) attending the University's ED from 2003 to 2014 applying the ISTH DIC score. The primary outcome measure was 30-day mortality. Logistic regression analysis was used to determine predictors of mortality.
The initial inter-rater reliability in the diagnosis of DIC was 0.85 [κ; 95% confidence interval (CI), 0.77-0.92]. The main DIC precipitators were malignancy (47%), cardiovascular diseases (CVD, 27%) and sepsis (16%). Hyperfibrinolytic DIC occurred in 27% of patients and was over-represented in those with cardiac arrest (68%). Thirty-day mortality (52%) was inversely associated with fibrinogen levels on admission [adjusted odds ratio, 0.49; 95% CI: 0.30-0.82; P=0.006]. Afibrinogenaemia implied an even 10-fold increased risk of dying (crude odds ratio, 10.0; 95% CI: 3.2-31.4; P<0.001). D-dimer and platelet count had no predictive value. Appropriate ICD-10 coding for DIC was present in only 1.8% of cases.
Overt DIC is a rare but underdiagnosed event in ED patients. In this collective, cardiac arrest is a dominant cause of DIC presenting with a fibrinolytic phenotype. The degree of hypofibrinogenaemia on admission strongly and linearly predicted early death.
No preview · Article · Dec 2015 · European Journal of Emergency Medicine
[Show abstract][Hide abstract] ABSTRACT: Chikungunya virus has become a global health threat, spreading to the industrial world of Europe and the Americas; no treatment or prophylactic vaccine is available. Since the late 1960s much effort has been put into the development of a vaccine, and several heterogeneous strategies have already been explored. Only two candidates have recently qualified to enter clinical phase II trials, a chikungunya virus-like particle-based vaccine and a recombinant live attenuated measles virus-vectored vaccine. This review focuses on the current status of vaccine development against chikungunya virus in humans and discusses the diversity of immunization strategies, results of recent human trials and promising vaccine candidates.
No preview · Article · Nov 2015 · Human Vaccines and Immunotherapeutics
[Show abstract][Hide abstract] ABSTRACT: Background:
Platelets play an important role in coagulation activation. P2Y12-receptor inhibition may be beneficial in inflammatory states.
Prasugrel, a potent, irreversible inhibitor of P2Y12 receptor induced platelet activation may reduce coagulation activation in a human LPS model.
A double-blind, randomized, crossover trial with a minimum washout period of 6 weeks was performed. Sixteen subjects were randomly assigned to a treatment group that received prasugrel or placebo two hours prior to infusion of a bolus of LPS (2ng/kg bodyweight), while four subjects were assigned to a control group receiving prasugrel or placebo without LPS. Histone-complexed DNA (hcDNA), coagulation and platelet specific parameters were measured by enzyme immunoassay. Leukocyte aggregate formation was analyzed by flow cytometry, and thromboelastometry was performed.
LPS infusion markedly activated coagulation. However, prasugrel did not reduce changes in prothrombin fragments F1+2, thrombin-antithrombin complexes, microparticle associated tissue factor, CD 40 ligand, P-selectin, platelet leukocyte aggregation, hcDNA levels or the coagulation profile measured by thromboelastometry. hcDNA plasma levels increased approximately six-fold after LPS infusion in both treatment groups, but not in the control groups.
Potent irreversible P2Y12 inhibition by prasugrel does not affect LPS induced coagulation activation. hcDNA plasma levels increased six-fold after infusion of LPS, indicating the formation of neutrophil extracellular traps during sterile inflammation.
No preview · Article · Nov 2015 · Clinical Science
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Plasma histamine levels and D-dimer predict disease severity and mortality in advanced septic shock. We hypothesized that increased plasma histamine levels parallel coagulation activation and yield prognostic significance already at a very early stage of bacteremia.
Patients and methods:
This prospective controlled cohort study enrolled 72 consecutive non-surgical non-ICU-ward inpatients with newly culture-diagnosed bacteremia and a Pitt Bacteremia score ≤2 to determine the extent of histamine and D-dimer release and their predictive role on outcome at the earliest stage of blood stream infection. Age-matched healthy adults served as internal controls (n=36). A binominal logistic regression and a Cox proportional hazards regression analysis were performed to ascertain the effects of D-dimer and histamine on in-hospital mortality.
In contrast to plasma histamine, D-dimer levels were significantly higher within hours of culture-proven bacteremia. In-hospital mortality occurred in 17%. Histamine levels were neither associated with D-dimer level (r=0.04; p>0.05) nor with ICU admissions (r=0.06; p>0.05) and outcome (crude OR 0.8, 95% CI 0.3-1.9; p=0.6). In contrast, early-elevated D-dimer levels predicted mortality: the odds to die increased with the D-dimer level, and was 12.6 (crude OR, 95% CI 3-52; p=0.001) in patients with a D-dimer ≥4μg/mL (n=13).
Histamine levels are elevated in only few patients (4%) with newly diagnosed bacteremia. Our findings suggest that D-dimer, but not plasma histamine, could be a promising marker of lethality already at a very early stage of blood stream infection.
Full-text · Article · Nov 2015 · European Journal of Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: Background:
Morphine decreases the concentrations and effects of clopidogrel, which could lead to treatment failure in myocardial infarction.
To clarify whether more potent P2Y12-inhibitors may provide an effective alternative, we examined drug-drug interactions between morphine and prasugrel.
Twelve healthy volunteers received 60 mg prasugrel with placebo or 5 mg morphine intravenously in a randomized, double-blind, placebo-controlled, cross-over trial. Pharmacokinetics were determined by liquid chromatography tandem mass spectrometry, and prasugrel effects were measured by platelet function tests.
Morphine neither diminished total drug exposure (AUC), which was the primary endpoint, nor significantly delayed drug absorption of prasugrel. However, morphine reduced maximal plasma concentrations (C max) of prasugrel active metabolite by 31 % (p = 0.019). Morphine slightly, but not significantly, delayed the onset of maximal inhibition of platelet plug formation under high shear rates (30 vs. 20 min). Whole blood aggregation was not influenced.
Although morphine significantly decreases the maximal plasma concentrations of prasugrel active metabolite, it does not diminish its effects on platelets to a clinically relevant degree in healthy volunteers. However, it should be considered that the observed decrease in C max of prasugrel active metabolite caused by morphine co-administration may gain relevance in STEMI patients.
Clinical trial registration:
NCT01369186, EUDRA-CT#: 2010-023761-22.
Full-text · Article · Oct 2015 · Clinical Research in Cardiology
[Show abstract][Hide abstract] ABSTRACT: Background:
Our recent drug interaction trial with clopidogrel shows that morphine decreases the concentrations and pharmacodynamic effects of clopidogrel, which could lead to treatment failure in susceptible individuals. We hypothesized that the pharmacodynamic consequences of drug-drug interactions would be less between morphine and ticagrelor.
Materials and methods:
Twenty-four healthy subjects received a loading dose of 180mg ticagrelor together with placebo or 5mg morphine intravenously in a randomized, double-blind, placebo-controlled, cross-over trial. Pharmacokinetics were determined by liquid chromatography tandem mass spectrometry, and ticagrelor pharmacodynamic effects were measured by platelet function tests (whole blood platelet aggregation: Multiplate, platelet plug formation: PFA-100, vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay).
Concomitant i.v. injection of morphine slows drug resorption of ticagrelor and its active metabolite (p<0.05) by one hour and decreases plasma levels of ticagrelor and its active metabolite by 25-31% (p<0.03) and the drug exposure (area under the curve) by 22-23% (p<0.01). Importantly, however, the pharmacodynamic effects of ticagrelor on platelet aggregation in whole blood, platelet plug formation, and VASP phosphorylation are not affected by morphine.
Morphine co-administration moderately decreases ticagrelor plasma concentrations but does not inhibit its pharmacodynamic effects in healthy volunteers within 6 hours after drug administration. Limitations of our trial include the investigation in healthy volunteers under standardized conditions, which does not necessarily reflect a realistic emergency scenario. This article is protected by copyright. All rights reserved.
Full-text · Article · Oct 2015 · European Journal of Clinical Investigation
[Show abstract][Hide abstract] ABSTRACT: To date, no study has systematically investigated the impact of drowning-induced asphyxia on hemostasis. Our objective was to test the hypothesis that asphyxia induces bleeding by hyperfibrinolytic disseminated intravascular coagulation.
A 2,100-bed tertiary care facility in Vienna, Austria, Europe.
All cases of drowning-induced asphyxia (n = 49) were compared with other patients with cardiopulmonary resuscitation (n = 116) and to patients with acute promyelocytic leukemia (n = 83). Six drowning victims were investigated prospectively. To study the mechanism, a forearm-ischemia model was used in 20 volunteers to investigate whether hypoxia releases tissue plasminogen activator.
Eighty percent of patients with drowning-induced asphyxia developed overt disseminated intravascular coagulation within 24 hours. When compared with nondrowning cardiac arrest patients, drowning patients had a 13 times higher prevalence of overt disseminated intravascular coagulation at admission (55% vs 4%; p < 0.001). Despite comparable disseminated intravascular coagulation scores, acute promyelocytic leukemia patients had higher fibrinogen but lower d-dimer levels and platelet counts than drowning patients (p < 0.001). Drowning victims had a three-fold longer activated partial thromboplastin time (124 s; p < 0.001) than both nondrowning cardiac arrest and acute promyelocytic leukemia patients. Hyperfibrinolysis was reflected by up to 1,000-fold increased d-dimer levels, greater than 5-fold elevated plasmin antiplasmin levels, and a complete absence of thrombelastometric clotting patterns, which was reversed by antifibrinolytics and heparinase. Thirty minutes of forearm-ischemia increased tissue plasminogen activator 31-fold (p < 0.001).
The vast majority of drowning patients develops overt hyperfibrinolytic disseminated intravascular coagulation, partly caused by hypoxia induced tissue plasminogen activator release. Antifibrinolytics and heparinase partially reverse the abnormal clotting patterns. Severe activated partial thromboplastin time prolongation may be a marker of combined hyperfibrinolytic afibrinogenemia and autoheparinization in drowning-related asphyxia.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially.
Full-text · Article · Aug 2015 · Critical care medicine
[Show abstract][Hide abstract] ABSTRACT: A biological rhythm in platelet function is well known. Multiple electrode aggregometry (MEA) is a widely used assay to measure platelet aggregability. Rivaroxaban is a new oral anticoagulant frequently used in an increasing number of indications. In this randomized, crossover trial we investigated whether a biological rhythm exists in MEA measurements and potential effects of rivaroxaban on platelet aggregation. Sixteen healthy volunteers were included in the study and blood samples were obtained at 08:00, 12:00, 16:00 and 20:00 h. Each subject was tested without rivaroxaban intake first and randomly assigned to 3 days of rivaroxaban intake at 08:00 or 3 days of rivaroxaban intake at 20:00 h and vice versa. In MEA measurements, a significant increase in platelet aggregation after addition of ristocetin at 12:00 h compared to other investigated time-points (122 ± 8 AU at 12:00 h vs. 109 ± 9 AU at 08:00 h, 114 ± 10 AU at 16:00 h and 103 ± 8 AU at 20:00 h, p = 0.027) could be detected. There was no biological rhythm detectable using other agonists (ADP, arachidonic acid, thrombin-receptor activating peptide-6). After rivaroxaban intake at 08:00 h an increased ristocetin-induced platelet aggregation was measured in the next morning (126 ± 4 AU (rivaroxaban at 08:00 h) vs. 109 ± 9 AU (no rivaroxaban), 111 ± 6 AU (rivaroxaban at 20:00 h; p = 0.002). No other effects of rivaroxaban on platelet function were found. We detected a biological rhythm in ristocetin-induced platelet aggregation with a peak at 12:00 h (noon). No influence of selective Xa inhibition on platelet aggregation was detected.
No preview · Article · Jul 2015 · Scandinavian journal of clinical and laboratory investigation
[Show abstract][Hide abstract] ABSTRACT: Absent or severely diminished activity of ADAMTS13 (A Disintegrin And Metalloprotease with a ThromboSpondin type 1 motif, member 13) resulting in the intravascular persistence and accumulation of highly thrombogenic ultra large von Willebrand factor (UL-VWF) multimers is the pathophysiological mechanism underlying thrombotic thrombocytopenic purpura. Reduced VWF-cleaving protease levels, however, are not uniquely restricted to primary thrombotic microangiopathy (TMA), e. g. thrombotic thrombocytopenic purpura, but also occur in other life-threatening thrombocytopenic conditions: severely decreased ADAMTS13 activity is seen in severe sepsis, disseminated intravascular coagulation (DIC) and complicated malarial infection. The clinical relevance of these secondary thrombotic microangiopathies is increasingly recognised, but its therapeutic implications have not yet been determined. The presence of a secondary TMA in certain diseases may define patient groups which possibly could benefit from ADAMTS13 replacement or a VWF-targeting therapy. This short-review focuses on the role of UL-VWF multimers in secondary TMA and discusses the potential of investigational therapies as candidates for the treatment of TTP. In conclusion, prospective clinical trials on the effectiveness of protease replacementin vivo seem reasonable. Carefully selected patients with secondary TMA may benefit from therapies primarily intended for the use in patients with TTP.
No preview · Article · Dec 2014 · Thrombosis and Haemostasis
[Show abstract][Hide abstract] ABSTRACT: Background
Accidental hypothermic cardiac arrest is associated with unfortunate prognosis and large studies are rare. We therefore have performed an outcome analysis in patients that were admitted to Vienna University Hospital with the diagnosis of accidental hypothermic cardiac arrest.
This study employed a retrospective outcome analysis of prospectively collected data in a selected cohort of hypothermic cardiac arrest patients. We screened 3800 cardiac arrest patients, treated at our department between 1991 and 2010, for eligibility. Inclusion criteria were cardiac arrest with a body core temperature ≤28 °C and return of spontaneous circulation.
A total of 18 patients who achieved return of spontaneous circulation were analysed. Nine patients (50%) achieved survival in good neurologic condition (defined as cerebral performance category CPC 1 or 2). Accidental hypothermia with consecutive cardiac arrest was caused by intoxication in most cases (67%). These patients had a better outcome than patients with other causes of accidental hypothermic cardiac arrest (OR = 28; 95%KI 2-37.9; p < 0,01). Hypothermia associated typical ECG changes after return of spontaneous circulation (Osborne waves) were more frequent in the surviving population (OR 16; 95%KI 1.3-19.5; p = 0.05).
Accidental hypothermic cardiac arrest in a central European urban area is rare. Prognosis was excellent in patients where hypothermic cardiac arrest was caused by intoxication.
[Show abstract][Hide abstract] ABSTRACT: To date, due to the rarity, tumor biology and carcinogenesis of small bowel adenocarcinoma (SBA), the disease has been explored insufficiently and immunophenotyping and molecular characterization have not been finalized. This knowledge gap consecutively leads to an overt lack of diagnostic and therapeutic recommendations. In the current study, we provide our experience with the treatment of SBA, and demand for cross-national data pooling to enable unlimited information transfer and higher powered study. A comprehensive database of all patients with SBA was established and consecutively reviewed for clinicopathohistological data, information concerning preoperative evaluation, surgical and chemotherapeutical treatment, as well as outcome parameters. Patients underwent curative intended surgery (42.4%; n=14), adjuvant chemotherapy (CTX) following resection (36.4%; n=12) or palliative care (21.2%; n=7). The majority of patients were diagnosed at an advanced disease stage (pT3, 36.4%; pT4, 39.4%) and the duodenum was the most common tumor site (57.1%; n=20). Complete surgical resection was achieved in 88.5% of patients, while postoperative complications occurred in 19.4%. Within a mean follow-up period of 31.4 months, 17 patients succumbed to the disease following a median survival time of 11 months. Mean overall survival (OS) was 47.4, 25.3 and 9.8 months for surgically, surgically and chemotherapeutically and palliatively treated patients, respectively. Early surgical resection remains the mainstay in the treatment of localized SBA, since it is associated with a prolongation of OS. The role of neoadjuvant and adjuvant CTX has not yet been defined. Thus, since no consensus exists on the adequate treatment of these malignancies, we demand an international collaboration and cross-national data pooling to pave the way for the implementation of evidence-based standard care operating procedures.
[Show abstract][Hide abstract] ABSTRACT: Gastroesophageal reflux disease (GERD) is a common chronic disease requiring adequate treatment since it represents one major cause of development of Barrett's esophagus and eventually carcinoma. Novel laparoscopic magnetic sphincter augmentation for GERD was evaluated prospectively.
A total of 23 patients with GERD underwent minimally invasive implantation of LINX™ Reflux Management System. Primary outcome measures were overall feasibility, short-term procedure safety and efficacy. Secondary GERD-related quality of life was assessed.
All implantations were performed without serious adverse events. A significant decrease in all major GERD complaints were found: heartburn: 96%-22% (p<0.001); bloating: 70%-30% (p=0.006); respiratory complaints: 57%-17% (p=0.039); sleep disturbance: 65%-4% (p<0.001). A four-week follow-up reduction of ≥50% of proton pump inhibitor (PPI) dose was achieved in over 80% of patients. Self-limiting difficulty in swallowing was found in 70% within four weeks. One patient required for endoscopic dilation. GERD-related quality of life improved significantly.
LINX™ implantation is a standardized, technically simple, safe and well-tolerated expeditious procedure.
No preview · Article · May 2014 · Anticancer research
[Show abstract][Hide abstract] ABSTRACT: Introduction IC43 is a recombinant outer membrane protein-based vaccine against Pseudomonas aeruginosa (P. aeruginosa) consisting of OprF- and OprI- epitopes (Opr, outer membrane protein; OprF/I, OprF/OprI hybrid vaccine) with an N-terminal His 6 tag (Met-Ala-(His)6-OprF 190-342-OprI 21-83). Objectives The study aimed to confirm the optimal dose of IC43 in adults with regard to immunogenicity, safety, and tolerability after vaccination with three different dosages of IC43, compared with placebo, and to investigate a potential immune-enhancing effect of the adjuvant, aluminum hydroxide. Subjects were randomly allocated in a 1:1:1:1:1 ratio to one of five treatment groups: 50, 100, or 200 µg IC43 with adjuvant, 100 µg IC43 without adjuvant, or placebo (0.9% sodium chloride) and two intramuscular injections were given in the deltoid region 7 d apart. Results The primary immunogenicity analysis of OprF/I-specific IgG antibody titers on day 14 demonstrated statistically significant differences among treatment groups (P<0.0001), with a significantly higher immune response detected in each IC43 treatment group compared with placebo. From day 0 to day 14, a ≥ 4-fold increase in OprF/I-specific immuneglobulin G (IgG) antibody titers were observed in>90% of subjects in all IC43 treatment groups in the per-protocol (PP) and intention-to-treat (ITT) populations; a ≥ 50-fold titer increase was observed in 42.6% subjects including all IC43 treatment groups. On day 90, OprF/I-specific IgGs started to decline in all IC43 treatment groups but remained significantly higher until 6 mo compared with placebo. Assessment of functional antibody induction by opsonophagocytic assay (OPA) followed a similar pattern compared with OprF/I-specific IgG kinetics. At day 14, a ≥ 2-fold increase in OPA titer was observed in 54.5% subjects within all IC43 treatment groups. An increase in antibody avidity index was observed after the second vaccination. At day 14,>96% of subjects in each IC43 treatment group had detectable OprF/I-specific IgG antibodies. Anti-histidine IgG antibody titers peaked on day 14 and were reduced on day 90 in all IC43 treatment groups. OprF/I-specific IgG secreted by antibody-secreting cell (ASC) was detected in all IC43 groups by B-cell ELIspot after the second vaccination and up to 6 mo. All vaccinations were safe and well tolerated up to the maximum cumulative dosage of 400 µg IC43. Conclusion IC43 doses equal to or greater than 50 µg were sufficient to induce a plateau of IgG antibody responses in healthy volunteers. Higher doses, whether adjuvanted or non-adjuvanted, were not more effective. Methods In this phase I, randomized, placebo-controlled, observer-blinded, multicenter clinical trial, 163 healthy volunteers (18-65 y) were randomly assigned to five treatment groups (1:1:1:1:1). Three groups received IC43 with adjuvant: 50 µg (n = 32), 100 µg (n = 33), or 200 µg (n = 33). One group received IC43 100 µg without adjuvant (n = 32), and one group received placebo (0.9% sodium chloride) (n = 33). Each subject received two intramuscular vaccinations, separated by a 7-d interval (days 0 and 7) (Fig. 1). Humoral immune response was assessed by measurement of outer membrane protein F/I (OprF/I)-specific antibodies determined by enzyme-linked immunosorbent assay (ELISA), anti-histidine antibodies determined by ELISA, and functional antibody activity determined by opsonophagocytic assay (OPA), up to 6 mo post-vaccination. Antibody avidity was measured on days 7 and 14 from samples that had detectable vaccine antibody-specific immunoglobulin G (IgG) antibody titers. At the Austrian site only, the B-cell ELIspot assay was used to determine specific ASC responses. Safety was assessed using adverse event monitoring and clinical laboratory tests. Local and systemic tolerability was recorded in a subject diary for 7 d after each vaccination and by investigators up to 6 mo post-vaccination.
No preview · Article · Sep 2013 · Human Vaccines & Immunotherapeutics
[Show abstract][Hide abstract] ABSTRACT: Patients on antiplatelet therapy have a higher incidence of bleeding complications. Reversal of antiplatelet drug effects is an important issue at trauma or emergency departments. For old and conventional anticoagulants, reversal strategies are established. While the effects of ticagrelor are reversible, developing a method to restore platelet function in patients is of importance due to its longer half-life (approximately 8 h), compared with other P2Y12 -inhibitors.
We report an ex vivo model to reverse the effects of the novel and highly effective P2Y12 -inhibitor ticagrelor in 20 healthy volunteers. To normalize platelet reactivity, we added increasing amounts of autologous platelet-rich plasma (PRP) to whole blood which was obtained 3 h after the intake of 180 mg of ticagrelor. Platelet aggregation was assessed by whole blood multiple electrode aggregometry (MEA), which is based on impedance aggregometry.
The basal ADP-induced platelet aggregation averaged 71 ± 16 U (Units). Ticagrelor decreased ADP-induced platelet aggregation to 16 ± 8 U. A clear dose-response was obtained after spiking whole blood with increasing amounts of PRP. It is estimated that ≥2 units of apheresis platelet concentrates will be necessary to completely restore baseline platelet aggregation in the majority of patients after ticagrelor.
Platelets dose dependently improve ex vivo platelet aggregation of subjects after a loading dose of 180 mg of ticagrelor, making transfusion of platelet concentrates potentially useful in bleeding patients and those who need to undergo emergency surgery.
Full-text · Article · Aug 2013 · European Journal of Clinical Investigation