RATIONAL FOR A DYNAMIC TEST TO INVESTIGATE POTENTIAL VASCULAR FIBRINOLYSIS IN PATIENTS AT RISK OF PERSISTENT THROMBOSIS

1987 ◽  
Author(s):  
Y Sultan ◽  
A Harris ◽  
G Strauch ◽  
D De Lauture ◽  
A Venot
Keyword(s):  
At Risk ◽  
Fibrinolytic Activity ◽  
Defense Mechanism ◽  
Dynamic Test ◽  
Normal Subjects ◽  
Vascular Wall ◽  
Venous Occlusion ◽  
Routes Of Administration ◽  
Before And After ◽  
Patients At Risk

Defense mechanism against intravascular clot formation is dependant upon the release of free tissue plasminogen activator (t-PA) from the vascular wall. To investigate this function a dynamic test is necessary to differenciate patients at risk of persistant thrombosis from patients who possess potential capacity to dissolve intravascular clots. In the present study, three different routes of administration of DDAVP and venous occlusion (VO) were applied to 9 healthy young volunteers in order to determine the best stimulus and the best test to assess individual capacity of releasing free t-PA in circulation. DDAVP was intravenously administered at a dose of 0,4 pg/kg body weight, and intranasally at a dose of 300 pg by two different preparations drops and spray. The same volunteers were also submitted to VO on 2 occasions after 1 H and after 10 mn of rest. In blood samples collected before and after the stimulation, t-PA activity and antigen, t-PA inhibitor (PAI) and euglobulin lysis time (ELT) were measured. Only one stimulus (IV DDAVP) and one test (t-PA activity in euglobulins) identified 100 per cent of normal subjects as capable of developing increased fibrinolytic activity. All other stimuli and especially VO pointed out absence of fibrinolytic response in several normal subjects, for exemple t-PA activity in euglobulins was found enhanced in all 9 subjects after IV DDAVP but in only five after VO. In addition, some tests such as ELT were found to be not sensitive enough to detect t-PA activity release. This study also showed that after DDAVP injection, PAI abruptly decreased in correlation with the release of t-PA activity. However t-PA activity can reach high levels in blood although PAI is still measurable suggesting that after release t-PA activity is not immediatly inhibited by PAI and that they can both coexist. These results demonstrate that the choice of the stimulus and the test to measure fibrinolytic activity have to be carefully determined to identify patients at risk of persistent thrombosis.

FIBRINOLYTIC ACTIVITY OF ARMS AND LE6S IN PERIPHERAL VENOUS HYPERTENSION IN MAN

1987 ◽  
Author(s):  
M R Carriero ◽  
F Annoni ◽  
L Mussoni ◽  
C Cerletti ◽  
G de Gaetano
Keyword(s):  
Hydrostatic Pressure ◽  
Fibrinolytic Activity ◽  
Diastolic Pressure ◽  
Venous Blood ◽  
Normal Subjects ◽  
Venous Occlusion ◽  
Venous Hypertension ◽  
Average Increase ◽  
Before And After

Spontaneous fibrinolytic activity of venous specimens Is greater In the arms than in the legs of normal subjects. This difference might be caused by the different hydrostatic pressure In arms and legs. We tested, on standard fibrin plates, the fibrinolytic activity of euglobulins prepared from venous blood obtained from arms and legs of normal subjects and patients with chronic peripheral hypertension. Normal subjects (26-38 yrs old, n=5) were tested both before and after 10 min venous occlusion (V0) of an arm and after 10 min occlusion of a leg. V0 was obtained by applying the cuff of a sphlgmomanometer at a pressure value Intermediate between systolic and diastolic pressure. Patients (39-64 yrs old, n=7) were tested both before and after V0 of the arm and after 10 min orthostatic posture (mean 100 mmHg). For each Individual the fibrinolytic activity In the arm before V0 was considered as basal value of both the arm and the leg. In normal subjects fibrinolytic activity Induced by V0 was greater In the arm than In the leg (262.9°74.9 versus 165.5°52.9 mm2). The average Increase of fibrinolytic activity after V0 was 3.4 (arms) and 2.1 (legs). In patients with peripheral venous hypertension fibrinolytic activity was 298.3°46.7 mm2 In the arm and 131.1 °19.2 mm2 In the leg. The average Increase Induced by VO In the arm was 3.5 while the activity of the legs after orthostatic pressure was 1.6. In conclusion patients with peripheral venous hypertension did not show any reduced fibrinolytic response after VO of the arms. Fibrinolytic activity in patients" legs after orthostatic pressure was also similar to that In the legs of volunteers after venous occlusion.

Trastuzumab-Induced Cardiotoxicity: Clinical and Prognostic Implications of Troponin I Evaluation

2010 ◽  
Vol 28 (25) ◽  
pp. 3910-3916 ◽  
Author(s):  
Daniela Cardinale ◽  
Alessandro Colombo ◽  
Rosalba Torrisi ◽  
Maria T. Sandri ◽  
Maurizio Civelli ◽  
...  
Keyword(s):  
At Risk ◽  
Cardiac Dysfunction ◽  
Troponin I ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Trastuzumab Therapy ◽  
Before And After ◽  
Patients At Risk ◽  
Prognostic Implications

Purpose Treatment of breast cancer with trastuzumab is complicated by cardiotoxicity in up to 34% of the patients. In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated. Patients and Methods In total, 251 women were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of > 10 units and below 50%. Recovery from TIC was defined as LVEF increase above 50%. Results TIC occurred in 42 patients (17%) and was more frequent in patients with TNI elevation (TNI+; 62% v 5%; P < .001). Twenty-five patients (60%) recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35% v 100%; P < .001). At multivariate analysis, TNI+ was the only independent predictor of TIC (hazard ratio [HR], 22.9; 95% CI, 11.6 to 45.5; P < .001) and of lack of LVEF recovery (HR, 2.88; 95% CI,1.78 to 4.65; P < .001). Conclusion TNI+ identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.

A Pharmacist-Driven Glycemic Control Protocol to Reduce the Rate of Severe Hypoglycemia in High-Risk Patients

2020 ◽  
pp. 001857872097389
Author(s):  
Colleen A. Cook ◽  
Victor Vakayil ◽  
Kyle Pribyl ◽  
Derek Yerxa ◽  
John Kriz ◽  
...  
Keyword(s):  
At Risk ◽  
High Risk ◽  
Glycemic Control ◽  
Risk Reduction ◽  
Severe Hypoglycemia ◽  
Diabetic Patients ◽  
Control Protocol ◽  
Before And After ◽  
Patients At Risk ◽  
Acceptance Rates

Purpose: Hospital pharmacists contribute to patient safety and quality initiatives by overseeing the prescribing of antidiabetic medications. A pharmacist-driven glycemic control protocol was developed to reduce the rate of severe hypoglycemia events (SHE) in high-risk hospitalized patients. Methods: We retrospectively analyzed the rates of SHE (defined as blood glucose ≤40 mg/dL), before and after instituting a pharmacist-driven glycemic control protocol over a 4-year period. A hospital glucose management team that included a lead Certified Diabetes Educator Pharmacist (CDEP), 5 pharmacists trained in diabetes, a lead hospitalist, critical care and hospital providers established a process to first identify patients at risk for severe hypoglycemia and then implement our protocol. Criteria from the American Diabetes Association and the American Association of Clinical Endocrinologists was utilized to identify and treat patients at risk for SHE. We analyzed and compared the rate of SHE and physician acceptance rates before and after protocol initiation. Results: From January 2015 to March 2019, 18 297 patients met criteria for this study; 139 patients experienced a SHE and approximately 80% were considered high risk diabetes patients. Physician acceptance rates for the new protocol ranged from 77% to 81% from the year of initiation (2016) through 2018. The absolute risk reduction of SHE was 9 events per 1000 hospitalized diabetic patients and the relative risk reduction was 74% SHE from the start to the end of the protocol implementation. Linear regression analysis demonstrated that SHE decreased by 1.5 events per 1000 hospitalized diabetic patients (95% confidence interval, −1.54 to −1.48, P < .001) during the 2 years following the introduction of the protocol. This represents a 15% relative reduction of SHE per year. Conclusion: The pharmacist-driven glycemic control protocol was well accepted by our hospitalists and led to a significant reduction in SHE in high-risk diabetes patient groups at our hospital. It was cost effective and strengthened our physician-pharmacist relationship while improving diabetes care.

Fibrinolytic activity before and after venous occlusion in thrombotic cases

1990 ◽  
Vol 4 ◽  
pp. 61
Author(s):  
J. Zamboulakis ◽  
C. Tsoukala ◽  
S. Liapi ◽  
T. Mandalaki
Keyword(s):  
Fibrinolytic Activity ◽  
Venous Occlusion ◽  
Before And After

ASPIRIN DOES NOT INHIBIT FIBRINOLYTIC ACTIVITY IN TIA PATIENTS AFTER VENOUS OCCLUSION

1987 ◽  
Author(s):  
M R Carriero ◽  
G Pintucci ◽  
M N Castagnoli ◽  
R Colombo ◽  
B Lombardi ◽  
...  
Keyword(s):  
Fibrinolytic Activity ◽  
Normal Subjects ◽  
Venous Occlusion ◽  
Inhibitory Effect ◽  
High Dose ◽  
Dose Aspirin ◽  
Serum Thromboxane ◽  
Fibrinolytic Potential ◽  
Single Blind ◽  
High Dose Aspirin

We have recently shown that In normal subjects aspirin (1,300 mg) and Indobufen (400 mg), a new cyclo-oxygenase Inhibitor structurally unrelated to salycilate, lower the fibrinolytic activity, without modifying t-PA antigen levels, after venous occlusion (VO). The aim of this study was to investigate whether aspirin reduces fibrinolytic response to VO also In patients with TIA. These patients were selected In view of controlled clinical trials showing reduction of TIA recurrency and stroke by treatment with high dose aspirin. Six males (56-65 yrs old), with previous TIA (< 1 year) were selected; the presence of diffuse atherothrombotlc lesions was demonstrated by doppler sonography and angiography. All patients were given, ten days apart, aspirin (600 mg daily x 2) or Indobufen (200 mg daily x 2) following a randomized cross-over single blind scheme. In all patients 10 minutes VO applied before any drug administration, Induced activation of the fibrinolytic system as assessed by euglobulin lysis area on fibrin plates (from 226±47 to 643±57 mm2), t-PA antigen (from 13.8± 1.0 to 40.9±3.1 ng/ml) and PA-1 activity (from 39.5+5.0 to 14.8±1.6 AU/ml). Neither aspirin nor Indobufen Ingestion resulted In any Inhibitory effect on fibrinolytic response to VO while both drugs suppressed serum thromboxane 02 generation by more than 98%. In conclusion high dose aspirin and Indobufen do not Impair the fibrinolytic potential In TIA patients with atherothrombotlc lesions. The reasons for the different behaviour of patients In respect to young healthy volunteers remain to be established.

scholarly journals Antibody Responses in HIV-Infected Patients With Advanced Immunosuppression and Asymptomatic Cryptococcal Antigenemia

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Admire Hlupeni ◽  
Antonio Nakouzi ◽  
Tao Wang ◽  
Kathryn F Boyd ◽  
Tariro A Makadzange ◽  
...  
Keyword(s):  
At Risk ◽  
T Cell ◽  
Characteristic Curve ◽  
Information Criteria ◽  
Immunoglobulin M ◽  
Cd4 T Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Before And After ◽  
Plasma Antibody ◽  
Patients At Risk

Abstract Background There are no host biomarkers of risk for HIV-associated cryptococcal meningitis (CM) except CD4+ T-cell deficiency. At present, serum cryptococcal antigen (CrAg) screening of those with CD4 &lt;100 cells/µL is used to identify persons at risk for HIV-associated CM. We determined if plasma antibody profiles could discriminate CrAg+ from CrAg- patients. Methods We performed serological analyses of 237 HIV-infected asymptomatic Zimbabwean patients with CD4 &lt;100 cells/µL; 125 CrAg- and CrAg+ but cerebrospinal fluid CrAg- by CrAg lateral flow assay. We measured plasma immunoglobulin M (IgM), immunoglobulin G (IgG) 1, and IgG2 concentrations by Luminex, and titers of Cryptococcus neoformans (Cn) glucuronoxylomannan (GXM) polysaccharide and naturally occurring Laminarin (natural Lam, a β-(1–3)-glucan linked polysaccharide)-binding IgM and IgG by enzyme-linked immunosorbent assay. Results GXM-IgG, -IgM, and -IgG2 levels were significantly higher in CrAg+ patients, whereas natural Lam-IgM and Lam-IgG were higher in CrAg- patients before and after adjustment for age, sex, and CD4 T-cell count, despite overlap of values. To address this variability and better discriminate the groups, we used Akaike Information Criteria to select variables that independently predicted CrAg+ status and included them in a receiver operating characteristic curve to predict CrAg status. By inclusion of CD4, GXM-IgG, GXM-IgM, and Lam-IgG, -IgG2, and -IgM, this model had an 80.4% probability (95% confidence interval, 0.75–0.86) of predicting CrAg+ status. Conclusions Statistical models that include multiple serological variables may improve the identification of patients at risk for CM and inform new directions in research on the complex role that antibodies may play in resistance and susceptibility to CM.

The Effect of Rapid Screening for Methicillin-ResistantStaphylococcus aureus(MRSA) on the Identification and Earlier Isolation of MRSA-Positive Patients

2010 ◽  
Vol 31 (4) ◽  
pp. 374-381 ◽  
Author(s):  
Eilish Creamer ◽  
Anthony Dolan ◽  
Orla Sherlock ◽  
Toney Thomas ◽  
John Walsh ◽  
...  
Keyword(s):  
At Risk ◽  
Predictive Value ◽  
Tertiary Care ◽  
Turnaround Time ◽  
Rapid Screening ◽  
Pcr Assay ◽  
Period 2 ◽  
Before And After ◽  
Patients At Risk ◽  
Risk Patients

Objectives.(1) To determine whether rapid screening with polymerase chain reaction (PCR) assays leads to the earlier isolation of patients at risk for methicillin-resistantStaphylococcus aureus(MRSA) colonization, (2) to assess compliance with routine MRSA screening protocols, (3) to confirm the diagnostic accuracy of the Xpert MRSA real-time PCR assay (Cepheid) by comparison with culture, and (4) to compare turnaround times for PCR assay results with those for culture results.Design.Before-and-after study conducted in a 700-bed acute tertiary care referral hospital. Study periods were (1) a 5-week period before PCR testing began, (2) a 10-week period when the PCR assay was used, and (3) a 5-week period after PCR testing was discontinued.Results.Among 489 at-risk patients, MRSA was isolated from 20 (33%) of 60 patients during period 1, 77 (22%) of 349 patients during period 2, and 18 (23%) of 80 patients during period 3. Twenty-two (27%) of 82 at-risk patients were not screened during period 1, compared with 40 (10%) of 389 at-risk patients not screened during period 2 (P< .001). More MRSA-positive patients were preemptively isolated during periods 1 and 3 compared with period 2 (34 [24%] of 140 vs 28 [8%] of 389;P< .001); however, more MRSA-positive patients were isolated after notification of MRSA-positive results during period 2 (47 [13%] of 349) compared with periods 1 and 3 (2 [1%] of 140;P< .001). The sensitivity, specificity, positive predictive value, and negative predictive value of the PCR assay were 95%, 97%, 82%, and 99%, respectively. The mean turnaround time from receipt of specimens in the laboratory to PCR assay result was 2.6 hours.Conclusions.Rapid screening with the Xpert MRSA PCR assay facilitated compliance with screening policies and the earlier isolation of MRSA-positive Patients. Discrepant results confirm that PCR testing should be used as a screening tool rather than as a diagnostic tool.

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