One lithium level >1.0 mmol/L causes an acute decline in eGFR: findings from a retrospective analysis of a monitoring database

Objectives Lithium is a mainstay of bipolar disorder treatment, however, there are still differences in opinion on the effects of lithium use on renal function. The aim of this analysis was to determine if there is an association between short-term exposure to various elevated lithium levels and estimated-glomerular filtration rate (eGFR) at ≤3 months, 6 months (±3 months) and 1 year (±3 months) follow-up. Setting Norfolk-wide (UK) lithium register and database. Participants 699 patients from the Norfolk database. Primary outcome measures eGFR change from baseline at ≤3 months, 6 months (±3 months) and 1 year (±3 months) after exposure to a lithium level within these ranges: 0.81–1.0 mmol/L (group 2), 1.01–1.2 mmol/L (group 3) and 1.21–2.0 mmol/L (group 4). The reference group was patients whose lithium levels never exceeded 0.8 mmol/L. Results Compared to the reference group, groups 3 and 4 showed a significant decrease in eGFR in the first 3 months after exposure (p=0.047 and p=0.040). At 6 months (±3 months) postexposure group 4 still showed a decline in eGFR, however, this result was not significant (p=0.298). Conclusions These results show for the first time that a single incident of a lithium level >1.0 mmol/L is associated with a significant decrease in eGFR in the following 3 months when compared to patients whose lithium levels never exceeded 0.8 mmol/L. It is still not known whether the kidneys can recover this lost function and the impact that more than a single exposure to a level within these ranges can have on renal function. These results suggest that lithium level monitoring should be undertaken at least every 3 months, in line with current UK guidelines and not be reduced further until the impact of more than one exposure to these lithium levels has been fully established

Exploring what patients think when answering the Interpersonal Skills Questionnaire (ISQ): A ‘think aloud’ study

Background: The Interpersonal Skills Questionnaire (ISQ) was developed to collect patient feedback on consultation skills of practitioners. However, it has not yet been evaluated with pharmacists. Objective: To explore the thinking process of patients as they completed the ISQ following a consultation with a pharmacist. Methods: A qualitative think aloud (TA) methodology was used to explore patients' thinking while completing the ISQ following a consultation with a pharmacist. The study was conducted in secondary care with outpatients ≥18 years old. Interviews were carried out in rounds and were informally analysed (i.e., by writing notes while listening to recordings) to identify any associated major problem(s). Discussions were held between researchers to determine whether changes were needed based on patients' comments. Results: Eight patients in total (50% females) participated in this study (mean age: 48 years). Three rounds of TA were conducted. Most items of the ISQ were interpreted similarly by all participants with no major problems necessitating refining the ISQ. Conclusions: Modification of the ISQ was unnecessary as interviews demonstrated no major problems with its use. The ISQ is thus a potentially suitable tool to collect patient feedback on pharmacists' consultations

Periprocedural antithrombotic management for lumbar puncture: Association of British Neurologists clinical guideline

Lumbar puncture (LP) is an important and frequently performed invasive procedure for the diagnosis and management of neurological conditions. There is little in the neurological literature on the topic of periprocedural management of antithrombotics in patients undergoing LP. Current practice is therefore largely extrapolated from guidelines produced by anaesthetic bodies on neuraxial anaesthesia, haematology groups advising on periprocedural management of antiplatelet agents and anticoagulants, and by neuroradiology on imaging-guided spinal procedures. This paper summarises the existing literature on the topic and offers recommendations to guide periprocedural antithrombotic management for LP, based on the consolidation of the best available evidence. ​. [Abstract copyright: © Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.

Severe platelet dysfunction in NHL patients receiving ibrutinib is absent in patients receiving acalabrutinib

The Bruton’s tyrosine kinase (Btk) inhibitor ibrutinib induces platelet dysfunction and causes increased risk of bleeding. Off-target inhibition of Tec is believed to contribute to platelet dysfunction and other side-effects of ibrutinib. The second generation Btk inhibitor acalabrutinib was developed with improved specificity for Btk over Tec. We investigated platelet function in patients with Non-Hodgkin Lymphoma (NHL) receiving ibrutinib or acalabrutinib by aggregometry and by measuring thrombus formation on collagen under arterial shear. Both patient groups had similarly dysfunctional aggregation responses to collagen and collagen-related peptide (CRP-XL) and comparison with mechanistic experiments in which platelets from healthy donors were treated with the Btk inhibitors suggested that both drugs inhibit platelet Btk and Tec at physiological concentrations. Only ibrutinib caused dysfunctional thrombus formation, while size and morphology of thrombi following acalabrutinib treatment were of normal size and morphology. We found that ibrutinib but not acalabrutinib inhibited SFKs and that SFKs have a critical role in platelet adhesion to collagen that is likely to underpin unstable thrombus formation observed in ibrutinib patients. We found that platelet function was enhanced by increasing levels of vWF and FVIII ex vivo by addition of intermediate purity FVIII (haemate P) to blood from patients, resulting in consistently larger thrombi. We conclude that acalabrutinib avoids major platelet dysfunction associated with ibrutinib therapy, and platelet function may be enhanced in patients with B-cell NHL by increasing plasma vWF and FVIII

Farnesoid X receptor and liver X receptor ligands initiate formation of coated platelets

The liver X receptors (LXRs) and farnesoid X receptor (FXR) have been identified in human platelets. Ligands of these receptors have been shown to have nongenomic inhibitory effects on platelet activation by platelet agonists. This, however, seems contradictory with the platelet hyper-reactivity that is associated with several pathological conditions that are associated with increased circulating levels of molecules that are LXR and FXR ligands, such as hyperlipidemia, type 2 diabetes mellitus, and obesity. We, therefore, investigated whether ligands for the LXR and FXR receptors were capable of priming platelets to the activated state without stimulation by platelet agonists. Treatment of platelets with ligands for LXR and FXR converted platelets to the procoagulant state, with increases in phosphatidylserine exposure, platelet swelling, reduced membrane integrity, depolarization of the mitochondrial membrane, and microparticle release observed. Additionally, platelets also displayed features associated with coated platelets such as P-selectin exposure, fibrinogen binding, fibrin generation that is supported by increased serine protease activity, and inhibition of integrin αIIbβ3. LXR and FXR ligand-induced formation of coated platelets was found to be dependent on both reactive oxygen species and intracellular calcium mobilization, and for FXR ligands, this process was found to be dependent on cyclophilin D. We conclude that treatment with LXR and FXR ligands initiates coated platelet formation, which is thought to support coagulation but results in desensitization to platelet stimuli through inhibition of αIIbβ3 consistent with their ability to inhibit platelet function and stable thrombus formation in vivo

Alternatives to allogeneic platelet transfusion

Allogeneic platelet transfusions are widely used for the prevention and treatment of bleeding in thrombocytopenia. Recent evidence suggests platelet transfusions have limited efficacy and are associated with uncertain immunomodulatory risks and concerns about viral or bacterial transmission. Alternatives to transfusion are a well-recognised tenet of Patient Blood Management, but there has been less focus on different strategies to reduce bleeding risk by comparison to platelet transfusion. Direct alternatives to platelet transfusion include agents to stimulate endogenous platelet production (thrombopoietin mimetics), optimising platelet adhesion to endothelium by treating anaemia or increasing von Willebrand factor levels (desmopressin), increasing formation of cross-linked fibrinogen (activated recombinant factor VII, fibrinogen concentrate or recombinant factor XIII), decreasing fibrinolysis (tranexamic acid or epsilon aminocaproic acid) or using artificial or modified platelets (cryopreserved platelets, lyophilised platelets, haemostatic particles, liposomes, engineered nanoparticles or infusible platelet membranes). The evidence base to support the use of these alternatives is variable, but an area of active research. Much of the current randomised controlled trial focus is on evaluation of the use of thrombopoietin mimetics and anti-fibrinolytics. It is also recognised that one alternative strategy to platelet transfusion is choosing not to transfuse at all

Elevated plasminogen activators are associated with hematoma progression in spontaneous intracerebral hemorrhage

Endogenous fibrinolysis might lead to hematoma progression in spontaneous intracerebral hemorrhage (ICH). We studied plasma biomarkers of fibrinolysis and hemostasis in twenty-two patients with ICH and nine healthy controls (HC) in a single-center study. Patients with ICH had significantly higher D-dimer and plasmin-alpha-2-antiplasmin complexes compared to HC. At baseline, patients with hematoma progression had higher urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) and lower plasminogen levels, compared to those with no progression. 24-hour and day-7 matrix metalloproteinase-9 (MMP-9) was significantly increased in patients with hematoma progression

Fresh frozen plasma for cardiovascular surgery.

Background Fresh frozen plasma (FFP) is a blood component containing procoagulant factors, which is sometimes used in cardiovascular surgery with the aim of reducing the risk of bleeding. The purpose of this review is to assess the risk of mortality for patients undergoing cardiovascular surgery who receive FFP. Objectives To evaluate the risk to benefit ratio of FFP transfusion in cardiovascular surgery for the treatment of bleeding patients or for prophylaxis against bleeding. Search methods We searched 11 bibliographic databases and four ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2015), MEDLINE (OvidSP, 1946 to 21 April 2015), EMBASE (OvidSP, 1974 to 21 April 2015), PubMed (epublications only: searched 21 April 2015), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (searched 21 April 2015). We also searched the references of all identified trials and relevant review articles. We did not limit the searches by language or publication status. Selection criteria We included randomised controlled trials in patients undergoing major cardiac or vascular surgery who were allocated to a FFP group or a comparator (no plasma or an active comparator, either clinical plasma (any type) or a plasma-derived blood product). We included participants of any age (neonates, children and adults). We excluded studies of plasmapheresis and plasma exchange. Data collection and analysis Two authors screened all electronically derived citations and abstracts of papers identified by the review search strategy. Two authors assessed risk of bias in the included studies and extracted data independently. We took care to note whether FFP was used therapeutically or prophylactically within each trial

Patient feedback questionnaires to enhance consultation skills of healthcare professionals: a systematic review

Objective: To identify patient feedback questionnaires that assess the development of consultation skills (CSs) of practitioners. Methods: We conducted a systematic search using seven databases from inception to January 2017 to identify self-completed patient feedback questionnaires assessing and enhancing the development of CSs of individual practitioners. Results were checked for eligibility by three authors, and disagreements were resolved by discussion. Reference lists of relevant studies and open grey were searched for additional studies. Results: Of 16,312 studies retrieved, sixteen were included, describing twelve patient feedback questionnaires that were mostly designed for physicians in primary care settings. Most questionnaires had limited data regarding their psychometric properties, except for the Doctor Interpersonal Skills Questionnaire (DISQ). Most studies conducted follow-up, capturing positive views of practitioners regarding the process (n = 14). Feedback was repeated by only three studies, demonstrating different levels of improvement in practitioners’ performance. Conclusion: Identified questionnaires were mainly focused on physicians, however, to support using patient feedback, questionnaires need to be validated with other practitioners. Practice implications: Several patient feedback questionnaires are available, showing potential for supporting practitioners’ development. Valid questionnaires should be used with appropriate practitioners in developing more evidence for the impact they may have on actual consultations

Cancer complicated by thrombosis and thrombocytopenia: still a therapeutic dilemma

Individuals who have thrombocytopenia and cancer-associated thrombosis (CAT) are difficult to manage because they have a high risk of bleeding and recurrent thrombosis. The International Society on Thrombosis and Haemostasis guidelines for the management of thrombocytopenia in patients with CAT suggest two main approaches: either complete anticoagulation with transfusion support if necessary, or dose-modified anticoagulation while the platelet count is <50×109/L. Nevertheless, rather than being based on information from randomized controlled trials (RCTs), these recommendations were based on expert consensus. Recent research from two different countries has shown how this cohort’s management and results vary widely. While the United Kingdom study, Cancer-Associated Venous Thrombosis and Thrombocytopenia, found no significant differences in bleeding or recurrent thrombosis between full dose and modified dose groups, the North American Thrombocytopenia Related Outcomes with Venous thromboembolism study demonstrated a significantly lower risk of bleeding events in those receiving modified dose anticoagulation compared to full dose, without an increased risk of recurrent VTE. Therefore, an RCT is required to assess the best course of action for patients with CAT and thrombocytopenia. To define the standard of care for the management of patients with CAT and thrombocytopenia, a full-scale trial called the START randomized trial (STrategies for Anticoagulation in patients with thRombocytopenia and cancer-associated Thrombosis) is an international, multi-site pilot study that compares the use of platelet transfusions plus higher dose anticoagulation to modified dose anticoagulation in patients with thrombocytopenia and CAT receiving anticoagulation