scholarly journals MP13: IMPORTANT ROLE OF PROTHROMBIN TIME (PT) AND PARTIAL THROMBOPLASTIN TIME (PTT) IN PREDICTING TPA-RELATED HEMORRHAGIC TRANSFORMATION

2016 ◽  
Vol 64 (3) ◽  
pp. 810.1-810
Author(s):  
W Deng ◽  
T Wickham ◽  
D McMullin ◽  
K Feeney ◽  
FS Buonanno ◽  
...  
Keyword(s):  
Real Time ◽  
Clinical Utility ◽  
Roc Analysis ◽  
Neurovascular Unit ◽  
Hemorrhagic Transformation ◽  
Proof Of Concept ◽  
Vascular Effects ◽  
D Dimer ◽  
Iv Tpa

Purpose of StudyIV tPA is not routinely followed by blood work due to its reputed short half life. While there has been much focus on tPA's extra-vascular effects on the neurovascular unit in the context of hemorrhagic transformation (HT), little is known about its intravascular efficacy, where it has its intended effect. Emerging data suggest that tPA may be most effective in microvasculature and IV therapy may be a good adjunct to intra-arterial therapy. We previously found that the effect of tPA can last more than 72 hr after stroke onset. Now, we report that even routine blood labs can potentially predict HT.Methods Used72 storke patients with IV tPA were recruited on IRB approval. Clinical coagulation profile (PT, PTT, fibrinogen and D-dimer) were performed at 12, 24, 72 hr post tPA. Patients on medications (e.g. anticoagulants) or with conditions (e.g. liver dysfunction, infection) that may affect these labs were excluded.Summary of ResultsCompared to those without HT, HT patients had significantly higher PT and PTT (Fig A,B) as early as 12 hr post IV tPA and throughout the first 3 days of treatment. ROC analysis suggested PT/PTT at 12 and 24 hr has potential to predict tPA-induced HT (Fig C,D. PT: AUC=0.848, p=0.001; PTT: AUC=0.877; p=0.003).ConclusionsHigher PT/PTT level within 72 hr of IV tPA is early marker of tPA-induced HT. Whether these routine labs have value in symptomatic hemorrhage will require further study in a larger cohort. But this proof-of-concept study suggests that tPA efficacy can potentially be followed in real time. The development of a reliable blood test would be of clinical utility to gauge thrombolytic efficacy in real time to guide and triage adjunct treatments.Abstract MP13 Figure 1

scholarly journals A Proof of Concept of the Role of TDM-Based Clinical Pharmacological Advices in Optimizing Antimicrobial Therapy on Real-Time in Different Paediatric Settings

2021 ◽  
Vol 12 ◽  
Author(s):  
Milo Gatti ◽  
Pier Giorgio Cojutti ◽  
Caterina Campoli ◽  
Fabio Caramelli ◽  
Luigi Tommaso Corvaglia ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Real Time ◽  
Antimicrobial Therapy ◽  
Turnaround Time ◽  
Antimicrobial Treatment ◽  
Therapeutic Drug ◽  
Proof Of Concept ◽  
Paediatric Patients ◽  
Dosing Regimens

Introduction: Antimicrobial treatment is quite common among hospitalized children. The dynamic age-associated physiological variations coupled with the pathophysiological alterations caused by underlying illness and potential drug-drug interactions makes the implementation of appropriate antimicrobial dosing extremely challenging among paediatrics. Therapeutic drug monitoring (TDM) may represent a valuable tool for assisting clinicians in optimizing antimicrobial exposure. Clinical pharmacological advice (CPA) is an approach based on the correct interpretation of the TDM result by the MD Clinical Pharmacologist in relation to specific underlying conditions, namely the antimicrobial susceptibility of the clinical isolate, the site of infection, the pathophysiological characteristics of the patient and/or the drug-drug interactions of cotreatments. The aim of this study was to assess the role of TDM-based CPAs in providing useful recommendations for the real-time personalization of antimicrobial dosing regimens in various paediatric settings.Materials and methods: Paediatric patients who were admitted to different settings of the IRCCS Azienda Ospedaliero-Universitaria of Bologna, Italy (paediatric intensive care unit [ICU], paediatric onco-haematology, neonatology, and emergency paediatric ward), between January 2021 and June 2021 and who received TDM-based CPAs on real-time for personalization of antimicrobial therapy were retrospectively assessed. Demographic and clinical features, CPAs delivered in relation to different settings and antimicrobials, and type of dosing adjustments were extracted. Two indicators of performance were identified. The number of dosing adjustments provided over the total number of delivered CPAs. The turnaround time (TAT) of CPAs according to a predefined scale (optimal, <12 h; quasi-optimal, between 12–24 h; acceptable, between 24–48 h; suboptimal, >48 h).Results: Overall, 247 CPAs were delivered to 53 paediatric patients (mean 4.7 ± 3.7 CPAs/patient). Most were delivered to onco-haematological patients (39.6%) and to ICU patients (35.8%), and concerned mainly isavuconazole (19.0%) and voriconazole (17.8%). Overall, CPAs suggested dosing adjustments in 37.7% of cases (24.3% increases and 13.4% decreases). Median TAT was 7.5 h (IQR 6.1–8.8 h). Overall, CPAs TAT was optimal in 91.5% of cases, and suboptimal in only 0.8% of cases.Discussion: Our study provides a proof of concept of the helpful role that TDM-based real-time CPAs may have in optimizing antimicrobial exposure in different challenging paediatric scenarios.

scholarly journals Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain

2019 ◽  
Vol 116 (11) ◽  
pp. 5108-5117 ◽  
Author(s):  
Clifford M. Cassidy ◽  
Fabio A. Zucca ◽  
Ragy R. Girgis ◽  
Seth C. Baker ◽  
Jodi J. Weinstein ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Dorsal Striatum ◽  
Dopamine Metabolism ◽  
Dopamine Neurons ◽  
Nigrostriatal Pathway ◽  
Proof Of Concept ◽  
Promising Tool ◽  
Proxy Measure

Neuromelanin-sensitive MRI (NM-MRI) purports to detect the content of neuromelanin (NM), a product of dopamine metabolism that accumulates with age in dopamine neurons of the substantia nigra (SN). Interindividual variability in dopamine function may result in varying levels of NM accumulation in the SN; however, the ability of NM-MRI to measure dopamine function in nonneurodegenerative conditions has not been established. Here, we validated that NM-MRI signal intensity in postmortem midbrain specimens correlated with regional NM concentration even in the absence of neurodegeneration, a prerequisite for its use as a proxy for dopamine function. We then validated a voxelwise NM-MRI approach with sufficient anatomical sensitivity to resolve SN subregions. Using this approach and a multimodal dataset of molecular PET and fMRI data, we further showed the NM-MRI signal was related to both dopamine release in the dorsal striatum and resting blood flow within the SN. These results suggest that NM-MRI signal in the SN is a proxy for function of dopamine neurons in the nigrostriatal pathway. As a proof of concept for its clinical utility, we show that the NM-MRI signal correlated to severity of psychosis in schizophrenia and individuals at risk for schizophrenia, consistent with the well-established dysfunction of the nigrostriatal pathway in psychosis. Our results indicate that noninvasive NM-MRI is a promising tool that could have diverse research and clinical applications to investigate in vivo the role of dopamine in neuropsychiatric illness.

Abstract WP254: The Predictive Potential of Prothrombin Time (PT) and D-Dimer for tPA-related Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Wenjun Deng ◽  
Bo Song ◽  
Sherry H-Y Chou ◽  
Lindsay Fisher ◽  
Maxwell Oyer ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Prothrombin Time ◽  
Time Window ◽  
Predictive Ability ◽  
Coagulation Factors ◽  
Hemorrhagic Transformation ◽  
Stroke Patients ◽  
Wide Range ◽  
D Dimer ◽  
Iv Tpa

Background: IV tissue plasminogen activator (tPA) is an efficacious treatment of acute ischemic stroke. However, the utilization of tPA has been deterred by its hemorrhagic complications. Our previous exploratory study found that following tPA administration, ischemic stroke patients with hemorrhagic transformation (HT) had a significantly longer prothrombin time (PT) than those without HT. Here we aim to study the effect of post-tPA parenchymal hemorrhage on a wide range of coagulation labs in a lager cohort of patients. Method: 308 consecutive ischemic stroke patients with IV tPA were recruited in accordance with IRB approval. Clinical coagulation profiles were analyzed at 6, 12, 24, 36, 48 and 72 hr post IV tPA. Patients on anticoagulants or having other conditions (e.g. liver and kidney dysfunctions) that may affect these labs were excluded. Result: As determined by head CT scan, 16 patients (5.19%) developed post-tPA hemorrhage. Compared to patients without tPA related hemorrhage, patients with hemorrhage had significantly higher levels of PT within the first 24 hr post tPA (Figure 1A), and PT levels at 6 hr have the potential to predict subsequent hemorrhage (Figure 1C, AUC = 0.753, p = 0.003). Moreover, D-Dimer remained at high levels even after 48 hr (Figure 1B), suggesting sustained fibrinolysis abnormality or possibly indicating active bleeding. D-Dimer levels at 24 and 48 hr were also predictive of tPA-induced bleed (Figure 1D, AUC = 0.827, p = 0.007). Conclusion: Our results suggest PT and D-Dimer as early markers of tPA-induced hemorrhage in ischemic stroke patients. Their differential predictive ability at different time points may offer the possibility to monitor the clinical efficacy of tPA over a longer time window to guide adjunct treatment. Studies in additional coagulation factors in an expanded patient cohort are ongoing.

scholarly journals High Pretreatment Plasma D-Dimer Levels Are Associated with Poor Prognosis in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphomas Treated with Immunochemotherapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4219-4219
Author(s):  
Atsushi Tanaka ◽  
Yoshimitsu Shimomura ◽  
Tomohiro Yabushita ◽  
Takayuki Ishikawa
Keyword(s):  
Overall Survival ◽  
Poor Prognosis ◽  
Roc Analysis ◽  
Newly Diagnosed ◽  
Prognostic Role ◽  
Ann Arbor ◽  
Ecog Ps ◽  
D Dimer ◽  
Large B Cell

Abstract Introduction: The International Prognostic Index (IPI) is the most commonly used tool for predicting the survival of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Several clinical factors are being investigated to establish novel prognostic tools that can predict survival more simply and precisely. Plasma levels of D-dimer, a degradation product of fibrin, reflect the activation of coagulation and fibrinolysis. Tissue factors and cytokines released by tumor cells can activate fibrin formation, leading to tumor proliferation and migration. Pretreatment plasma D-dimer levels have been reported to correlate with survival in several types of malignancies, although few reports have assessed the prognostic role of plasma D-dimer levels in DLBCL. This study aimed to investigate the relationship between pretreatment plasma D-dimer levels and overall survival in patients with newly diagnosed DLBCL. Methods: We retrospectively identified 521 patients with DLBCL who were treated with anthracycline-based immunochemotherapy at our institution from January 2005 to December 2017. We excluded 130 patients who lacked records of pretreatment D-dimer levels. The remaining 391 patients were enrolled in this study. The primary endpoint was 5-year overall survival (OS), which was assessed with the Kaplan-Meier method. The optimal cut-off value of D-dimer levels to predict survival was determined using the receiver operating characteristic curve (ROC) analysis. Based on the cut-off value, patients were divided into two groups: the high D-dimer (HD) and low D-dimer (LD) groups. We compared the 5-year OS between the two groups using the log-rank test. Univariate and multivariate analyses for survival were performed using the Cox proportional hazard model. Adjusted covariates included age, Eastern Cooperative Oncology Group performance status (ECOG-PS), lactate dehydrogenase (LDH) levels, Ann-Arbor stages, and number of extranodal sites. Results: The median age of the subjects was 70 (range: 30-92) years. Two hundred and twelve patients (54.2%) were male, and 198 patients (50.6%) had a high-intermediate or high IPI score. The median D-dimer level was 1.4 (range: 0.1-197.0) µg/ml. The cut-off value of D-dimer was determined to be 1.0 µg/ml based on ROC analysis (area under the curve: 0.92, sensitivity: 100.0%, specificity: 83.3%). Compared with the LD group (<1.0 µg/ml, n = 135), the HD group (≥1.0 µg/ml, n = 256) comprised significantly more patients with bad ECOG PS (≥2), high LDH levels (≥250 IU/l), advanced Ann-Arbor stages (III or IV), many extranodal sites (≥2), and high IPI scores (Table 1). With the median follow-up period of 30.5 (range: 0.1-162) months, the 5-year OS of the entire cohort was 65.5% (95% confidence interval [CI]: 59.8-70.6%). The 5-year OS was significantly shorter in the HD group than in the LD group (58.9%, [95% CI: 51.8-65.3%] vs. 77.8%, [95% CI: 67.4-85.2%], p < 0.001, Figure). Univariate analysis identified HD vs. LD (hazard ratio [HR]: 2.65 [95% CI: 1.65-4.26], p < 0.001) to be significantly associated with the worse 5-year OS, which remained significant in the multivariate analysis (HR: 1.94, [95% CI: 1.17-3.21], p = 0.010, Table 2). Conclusions: High pretreatment plasma D-dimer levels were associated with poor prognosis in patients with newly diagnosed DLBCL independent of the IPI score. Further studies are needed to confirm the prognostic role of D-dimer levels in patients with DLBCL. Disclosures No relevant conflicts of interest to declare.

Staring Down Death

Crisis ◽  
2016 ◽  
Vol 37 (3) ◽  
pp. 212-217 ◽  
Author(s):  
Thomas E. Joiner ◽  
Melanie A. Hom ◽  
Megan L. Rogers ◽  
Carol Chu ◽  
Ian H. Stanley ◽  
...  
Keyword(s):  
Suicide Risk ◽  
Clinical Utility ◽  
Blink Rate ◽  
Specific Task ◽  
Careful Planning ◽  
Eye Blink ◽  
Eye Blinks ◽  
Potential Clinical Utility ◽  
The Relationship

Abstract. Background: Lowered eye blink rate may be a clinically useful indicator of acute, imminent, and severe suicide risk. Diminished eye blink rates are often seen among individuals engaged in heightened concentration on a specific task that requires careful planning and attention. Indeed, overcoming one’s biological instinct for survival through suicide necessitates premeditation and concentration; thus, a diminished eye blink rate may signal imminent suicidality. Aims: This article aims to spur research and clinical inquiry into the role of eye blinks as an indicator of acute suicide risk. Method: Literature relevant to the potential connection between eye blink rate and suicidality was reviewed and synthesized. Results: Anecdotal, cognitive, neurological, and conceptual support for the relationship between decreased blink rate and suicide risk is outlined. Conclusion: Given that eye blinks are a highly observable behavior, the potential clinical utility of using eye blink rate as a marker of suicide risk is immense. Research is warranted to explore the association between eye blink rate and acute suicide risk.

Investigations into the Clinical Utility of Latex D-Dimer in the Diagnosis of Deep Venous Thrombosis

1993 ◽  
Vol 69 (01) ◽  
pp. 008-011 ◽  
Author(s):  
Cedric J Carter ◽  
D Lynn Doyle ◽  
Nigel Dawson ◽  
Shauna Fowler ◽  
Dana V Devine
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Lower Limb ◽  
Clinical Utility ◽  
Rapid Test ◽  
Fibrin Degradation Product ◽  
Current Form ◽  
Non Invasive ◽  
Clinically Significant ◽  
D Dimer

SummaryThe serial use of non-invasive tests has been shown to be a safe method of managing outpatients who are suspected of having lower limb deep venous thrombosis (DVT). Objective testing has shown that the majority of these outpatients do not have venous thrombosis. A rapid test to exclude DVT in these patients, without the need for expensive and inconvenient serial non-invasive vascular testing, would have practical and economic advantages.Studies measuring the fibrin degradation product D-dimer using enzyme-linked immunoassays (EIA) in patients with veno-graphically proven DVT suggest that it should be possible to exclude this condition by the use of one of the rapid latex bead D-dimer tests.We have examined 190 patients with suspected DVT using both a latex and an EIA D-dimer assay. The latex D-dimer test used in this study was negative in 7 of the 36 proven cases of DVT. This sensitivity of only 80% is not sufficient to allow this type of assay, in its current form, to be used as an exclusion test for DVT. The same plasma samples were tested with an EIA assay. This information was used to mathematically model the effects of selecting a range of D-dimer discriminant cut off points for the diagnosis of DVT. These results indicate that 62% of suspected clinically significant DVT could have this diagnosis excluded, with a 98% sensitivity, if the rapid latex or equivalent D-dimer test could be reformulated to measure less than 185 ng/ml of D-dimer.

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