Comparison of patient intake of ticagrelor, prasugrel, or clopidogrel on restoring platelet function by donor platelets.

BACKGROUND: Bleeding complications are a common side effect in patients under dual antiplatelet (anti-PLT) therapy. PLT transfusion provides a treatment option for these patients. However it is currently unclear if, and to what extent, P2Y12 inhibitors influence PLT function of donor PLTs and if patients taking these medications are likely to benefit from PLT transfusions. STUDY DESIGN AND METHODS: We investigated the effect of blood and plasma of clopidogrel-, prasugrel-, and ticagrelor-treated patients on PLT function of blood from healthy volunteers in flow cytometry, light transmission aggregometry, and multiple electrode aggregometry (MEA). RESULTS: Our results demonstrate that clopidogrel had no and prasugrel had only mild effects on donor PLT function, but the reversible P2Y12 inhibitor ticagrelor completely abolished adenosine diphosphate-mediated PLT activation in all assays tested. We further show that ticagrelor itself and not elevated adenosine concentrations in patient plasma were responsible for the observed effects. Moreover, we show that a modified MEA assay could provide a simple and rapid tool to allow determination of whether patients are likely to benefit from PLT transfusions. CONCLUSION: Our results provide novel insights into potential differences between the P2Y12 inhibitors on donor PLT function in an in vitro setting, which may provide implications for future PLT transfusion strategies in these patients.

Posttraumatic stress disorder after high-dose-rate brachytherapy for cervical cancer with 2 fractions in 1 application under spinal/epidural anesthesia: incidence and risk factors.

PURPOSE: To investigate the psychological consequences of high-dose-rate brachytherapy with 2 fractions in 1 application under spinal/epidural anesthesia in the treatment of locally advanced cervical cancer. METHODS AND MATERIALS: In 50 patients with locally advanced cervical cancer, validated questionnaires were used for prospective assessment of acute and posttraumatic stress disorder (ASD/PTSD) (Impact of Event Scale-Revision), anxiety/depression (Hospital Anxiety and Depression Scale), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30/Cervical Cancer 24), physical functioning (World Health Organization performance status), and pain (visual analogue scale), before and during treatment and 1 week and 3 months after treatment. Qualitative interviews were recorded in open format for content analysis. RESULTS: Symptoms of ASD occurred in 30% of patients 1 week after treatment; and of PTSD in 41% 3 months after treatment in association with this specific brachytherapy procedure. Pretreatment predictive variables explain 82% of the variance of PTSD symptoms. Helpful experiences were the support of the treatment team, psychological support, and a positive attitude. Stressful factors were pain, organizational problems during treatment, and immobility between brachytherapy fractions. CONCLUSIONS: The specific brachytherapy procedure, as performed in the investigated mono-institutional setting with 2 fractions in 1 application under spinal/epidural anesthesia, bears a considerable risk of traumatization. The source of stress seems to be not the brachytherapy application itself but the maintenance of the applicator under epidural anesthesia in the time between fractions. Patients at risk may be identified before treatment, to offer targeted psycho-social support. The patients' open reports regarding helpful experiences are an encouraging feedback for the treatment team; the reported stressful factors serve as a basis for improvement of patient management, especially regarding pain control.

Intravenous nonopioid analgesic drugs in chronic low back pain patients on chronic opioid treatment: a crossover, randomised, double-blinded, placebo-controlled study.

BACKGROUND: Addition of nonopioid analgesic drugs reduces pain and opioid requirements in acute low back pain. In noncancer chronic low back pain (CLBP), the efficacy of a combined regimen to reduce breakthrough pain has not been proven so far. OBJECTIVE: Evaluation of the effects of intravenous (i.v.) nonopioid analgesic drugs on pain intensity and lumbar mobility in CLBP patients on chronic opioid therapy. DESIGN: Randomised, placebo-controlled, double blinded, crossover study. SETTING: Vienna General Hospital, Austria, from December 2002 to May 2004. PATIENTS: Thirty-six adults with CLBP on chronic opioid therapy. Inclusion criteria are as follows: American Society of Anesthesiologists' physical status less than 3, visual analogue scale (VAS) more than 4 and no known allergy to any of the used drugs. INTERVENTION: After written informed consent and VAS assessment, any oral nonopioid analgesic drug (NSAIDs, metamizol, paracetamol) was replaced by placebo 10 days before the first test infusion as a washout period. Coanalgesics (anticonvulsants, antidepressants) were maintained. Each patient received randomly four i.v. test infusions of diclofenac 75 mg (and orphenadrine 30 mg), parecoxib 40 mg, paracetamol 1 g and isotonic saline. A washout time of 72 h was allowed between each infusion. MAIN OUTCOME MEASURES: Primary outcome was as follows: VAS pain intensity (0 to 100 mm) at inclusion, before and within 30 min after infusion. Secondary outcomes were as follows: Roland-Morris questionnaire, McGill pain questionnaire and a test panel of physical functioning for spinal mobility, muscular endurance, balance and coordination. The differences in means of the above assessments among the groups were analysed. RESULTS: We found an improvement in VAS from the day of inclusion to the day of each appointment. We observed no improvement in pain intensity (VAS) or in any of the physical functioning tests immediately before versus after administration of the four i.v. drugs. Reductions in sensory, affective and cognitive dimensions of the McGill pain questionnaire were statistically significant in the diclofenac group. A trend of McGill pain questionnaire improvement existed in the other groups. CONCLUSION: The present data show that the anticipation of an i.v. infusion of nonopioid analgesic drug improves VAS significantly, probably through expectation-related mechanisms. However, single dose i.v. infusions of nonopioid analgesic drugs fail to improve pain intensity and spinal mobility in CLBP patients on chronic opioid treatment, even immediately after the infusion.

Heparin-induced effects of prothrombin complex concentrates in thromboelastometry.

BACKGROUND: Prothrombin complex concentrates (PCC) are currently used to treat congenital or acquired coagulation factor deficiency. In case of serious bleeding caused by new oral anticoagulant agents, reversing treatment with PCC is under debate. PCC preparations mostly contain heparin to prevent thromboembolic events. In factor VIII and IX deficient plasma, Takeyama et al. observed in vitro a heparin effect at appropriate concentrations of PCCs. The aim of the present experiment was to investigate the heparin effect of four factor-PCC at clinically relevant concentrations in whole blood. In an in vitro experiment, we compared the PCC preparation used in the experiments of Takeyama with a high heparin content to a new heparin-free PCC preparation. METHOD: After ethics committee approval and written informed consent, the citrated whole blood was obtained from ten healthy volunteers. We tested heparin-containing Prothromplex(®) and heparin-free Cofact(®) at concentrations of 0.31, 0.63, and 1.25 IU/ml. Protamine was added to another set of samples (1:1 heparin:protamine). We used the NATEM test in the rotational thromboelastometer ROTEM(®). RESULTS: In the heparin PCC preparation, we observed a significant (p < 0.001) concentration-dependent prolongation in CT and CFT, even at the lowest concentration. MCF was also significantly reduced. The heparin effect was reversible by protamine. The heparin-free PCC did not affect the onset of coagulation. The interpretation of the alpha-angle showed no increased thrombus formation in heparin-free PCC preparation. CONCLUSION: Our results extend the report of Takeyama et al. At clinically relevant PCC concentrations, the heparin effect was significant in thromboelastometry. The heparin content of PCCs should be considered in clinical routine.