Control of Heparin Therapy - is There a Need?

1979 ◽  
Author(s):  
E.W. Salzman
Keyword(s):  
Continuous Infusion ◽  
Clinical Results ◽  
Heparin Therapy ◽  
Clinical Settings ◽  
Antithrombotic Activity ◽  
Laboratory Control ◽  
Clinical Events ◽  
Coagulation Tests ◽  
Coagulation Kinetics ◽  
Risk For Bleeding

The argument for laboratory control of heparin treatment rests on 2 issues: 1, that the response to heparin varies from patient to patient and from time to time, and 2, that the clinical results are improved by laboratory control.The theoretical basis for lab control is strong. AT III levels vary and are reduced in thrombotic states. Heparin’s absorption and rate of degradation vary; its survival is shorter after pulmonary embolism.The clinical evidence that lab control prevents bleeding is weak. When heparin is given by intermittent injection, bleeding is not avoided by lab tests. Even with continuous infusion, coagulation tests may identify a group at high risk for bleeding, but lower values are no guarantee against hemorrhage.The case for lab control to assure an anti thrombotic effect is stronger. Clotting test values correlate with recurrent thromboembolism, particularly when heparin is given by continuous infusion. Thromboembolism recurs more ofter after smaller doses or after a poor APTT response to a larger dose. Other clinical settings are analogous: e.g., cardiopulmonary bypass and hemodialysis. New tests may correlate better with clinical events by measuring end products of heparin’s antithrombotic activity rather than its action on coagulation kinetics: e.g., fibrinopeptide A, fibrin monower, thrombin-antithrombin complexes, prothrombin fragments, and products of platelet activation.

scholarly journals Venous Thromboembolism: A Comparison of Treatment with Intermittent Constant Dosage Heparin and Continuous Infusion with Laboratory Control

1977 ◽  
Author(s):  
M.J. Mant ◽  
B. O’Brien ◽  
M.G. Grace
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Massive Pulmonary Embolism ◽  
Heparin Therapy ◽  
Minor Bleeding ◽  
Continuous Administration ◽  
Laboratory Control ◽  
Radiologic Findings ◽  
Clinical Diagnoses ◽  
Progressive Respiratory Failure

We are conducting a prospective randomized trial comparing the treatment of venous thromboembolism for 10 days with constant dosage intermittent (I) I.V. heparin 5000 u 4 hrly and with continuous (C) I.V. heparin in comparable dosage with daily dosage adjustment designed to maintain activated partial thromboplastin times between 1½ and 2½ × control values. Patients with massive pulmonary embolism are excluded.Fifty-five patients have now received I heparin and 50 C heparin. Age and sex distributions, clinical diagnoses and factors potentially predisposing to hemorrhage were similar in the 2 groups. The clinical diagnosis was radiologically confirmed in 80 of the 105 patients. Although no patients have had a certain pulmonary embolus during treatment 5 in each group had suggestive clinical and/or radiologic findings. Pain or tenderness occurred at a new site or in an asymptomatic leg in 7 patients on I heparin and in 13 on C heparin. Hemorrhage occurred in 18 patients on I and 16 on C heparin. Major bleeding occurred in 7 patients and was spontaneous in 5 of these, in each group. Minor bleeding occurred in 15 patients on I heparin and 12 on C heparin. Some of these also had major bleeding. No patients have died of bleeding. One patient has died from progressive respiratory failure due to the original emboli. These preliminary results demonstrate that, although mortality is low, both hemorrhage and clinical features suggestive of recurrent thromboembolism are common during the first 10 days of heparin therapy. They also suggest’that continuous administration of heparin with laboratory control may have no significant advantages over the simpler intermittent constant dosage treatment regimen.

scholarly journals PCN428 SCALABLE PREDICTION OF CANCER PATIENT CLINICAL EVENTS IN REAL WORLD CLINICAL SETTINGS

2019 ◽  
Vol 22 ◽  
pp. S519
Author(s):  
J. Ransom ◽  
A. Galaznik ◽  
R. Buderi ◽  
C. McLean ◽  
A. Shilnikova ◽  
...  
Keyword(s):  
Cancer Patient ◽  
Real World ◽  
Clinical Settings ◽  
Clinical Events

scholarly journals Viscoelastic Tests in the Evaluation of Haemostasis Disturbances in SARS-CoV2 Infection

2020 ◽  
Vol 33 (13) ◽  
Author(s):  
Anabela Rodrigues ◽  
Teresa Seara Sevivas ◽  
Carla Leal Pereira ◽  
André Caiado ◽  
António Robalo Nunes
Keyword(s):  
Platelet Count ◽  
Clinical Status ◽  
High Rate ◽  
Clinical Settings ◽  
Bleeding Events ◽  
Anticoagulation Management ◽  
Laboratory Findings ◽  
Thrombotic Risk ◽  
Reactive Protein ◽  
Coagulation Tests

COVID-19 associated coagulopathy is a dysfunction of severe SARS-CoV-2 infection, characterized by significantly increased fibrinogen, D-dimer and C reactive protein and normal to near-normal prothrombin time, activated partial thromboplastin time and platelet count. Hypercoagulopathy and hypofibrinolysis coexist and are detected by viscoelastic tests. These features, when associated with immobilization and intrinsic risk factors (age, obesity, comorbidities, drugs) of the patient, can trigger thromboembolic events, despite thromboprophylaxis. The lungs are the first and most severely damaged organ. To date, most patients have exhibited hypercoagulability on viscoelastic tests not detected by standard coagulation tests. A high rate of thrombotic events was reported, suggesting that it should be considered as a cause of clinical deterioration in intensive care and potentially other clinical settings. In advanced stage, COVID-19 associated coagulopathy, fibrinogen and platelet count can decrease significantly, depending on the severity of clinical status resembling consumptive coagulopathy. In this stage, bleeding events can occur, especially if the patient is under extracorporeal membrane oxygenation (ECMO). Viscoelastic tests are very useful tools to assess hypercoagulability and hypofibrinolysis (not detectable by standard coagulation tests) in critically ill SARS-CoV-2 patients with COVID-19 associated coagulopathy and look like very promising tools for anticoagulation management. However, further research needs to be carried out to determine whether abnormal viscoelastic tests alone or in combination with other clinical or laboratory findings can identify patients at increased thrombotic risk. Clinical trials to evaluate hypercoagulability using viscoelastic tests and the need for personalized dosage of anticoagulation in SARS-CoV-2 patientsare quickly emerging.

Heparin Standardization

1979 ◽  
Author(s):  
T. Exner ◽  
E. Uhr ◽  
K.A. Rickard
Keyword(s):  
Continuous Infusion ◽  
Factor Xa ◽  
Clinical Results ◽  
The Other ◽  
Animal Blood ◽  
Dose Heparin ◽  
Normal Plasma ◽  
Straight Line ◽  
Human Use

Heparin is a major therapeutic item in any hospital and although local supplies are assumed to meet BP criteria, physicians often note differences in clinical results when the source of a supply is altered. BP and USP specifications require testing of heparins using animal blood thromboplastin tests - conditions which may not be particularly relevant to human use. A new method for determining heparin potency relative to a standard involves making equal dilutions of these heparins in several patients’ plasmas and determining the PTTK’s. The ratios of these PTTK’s to the initial PTTK of each plasma, when plotted for one heparin against the other, fall on a straight line and may be treated in the same way as recently proposed for thromboplastin calibration by the WHO. Features of heparin vary in importance depending on the particular application. Heparin used at high levels during bypass should be completely neutralizable by protamine. Mini-dose heparin needs to be standardised in terms of factor xa inactivation rate whereas that used for routine continuous infusion might best be standardised from its effect in vitro on the PTTK of normal plasma. We have recently investigated 3 tests for assessing heparins. 1. effect of their in vitro addition on the PTTK of normal plasma. 2. effect on factor xa inactivation. 3. protamine neutralisability as detected by the PTTK. The latter test was most accurate, demonstrating significant differences between sources of heparin and detecting variations in batch potency previously suspected by clinicians.

APPLICATION OF THE ROUTINE PHOTOMETRIC COAGULATION ASSAYS PT, APTT AND FIBRINOGEN TO A CENTRIFUGAL ANALYZER

1987 ◽  
Author(s):  
K Bartl ◽  
H Lill ◽  
A Dessauer
Keyword(s):  
Degradation Products ◽  
Oral Anticoagulant Therapy ◽  
Heparin Therapy ◽  
Performance Data ◽  
Coagulation System ◽  
Routine Laboratory ◽  
Coefficients Of Variation ◽  
Coagulation Tests ◽  
Viii And Ix ◽  
Measuring Signal

The vast majority of coagulation tests in the routine laboratory are the global assays PT, APTT and the single factor determination of fibrinogen. We developed a convenient ilystem consisting of these photometric assays and the Cobas® Bio equipped with an external calculator. By use of this system all three determinations are possible from the same sample cup. For a profile of all 3 parameters, a sample through-put of about 60 per hours is possible. For PT and APTT determinations, the photometric assays on basis of chromogenic substrates are used. The time is measured, until defined amounts of p-nitroani1ine are split off from the substrate by the thrombin formed. Fibrinogen is measured in a kinetic turbidimetric reaction during fibrin formation by batroxobin. The performance data are as follows: The coefficients of variation for the PT assay (25 μl of sample and 225 μl of reagent) are 0.5-1 % (X = 31,9 sec or 115,0 sec respectively, n = 20). The normal range is 70-120 %, the therapeutic range 12-27 %. The assay is extremely sensitive for the factors VII, V, X and II. It is both suited for the control of oral anticoagulant therapy and the screening of factor deficiencies. The CV values for the APTT assay (20 μl of sample, 200 μl of reagent and 20 μl of starting reagent) are 0,5-1,3 % for normal plasma samples. The normal value ranges from 36-58 sec. Plasma with 0.3 USP units heparin/ml yields 80 sec (ratio = 1,6). Factor VIII and IX levels of 50 % prolong the APTT ratio for about 1,3 or 1,2 respectively. The data of the clinical evaluation proved the assay suitable for the control of the heparin therapy and the screening of the endogeneous coagulation system. The fibrinogen assay (20 μl of undiluted sample and 300 μl of reagent) shows a linear relationship between measuring signal and concentration from 50-800 mg/dl. The correlation with the functional clotting assay to Clauss is rather good (r = 0,98). There is only a slight interference due to fibrin(ogen) degradation products compared to the clotting test. The performance data and the clinical data make the system Cobas® Bio and the sensitive photometric assays an interesting alternative to the conventional clotting tests in the routine laboratory.

Analysis Of Heparin Monitoring

1981 ◽  
Author(s):  
J A Caprini ◽  
S J Rabadi ◽  
J P Vagher ◽  
J Mitchell
Keyword(s):  
Body Weight ◽  
Continuous Infusion ◽  
Clinical Symptoms ◽  
Heparin Therapy ◽  
Bleeding Complications ◽  
Minor Bleeding ◽  
Daily Dose ◽  
Group 2 ◽  
Heparin Monitoring ◽  
Dose Change

Forty-six thrombosis patients were treated for a total of 437 days with continuous pump infusion heparin therapy. A bolus injection (50 units heparin/kg body weight) was followed by continuous infusion (14.2 units/kg/hour). The patients were randomized into 3 groups, daily coagulation profiles performed, and heparin dose adjusted by the following criteria: 1. no daily dose change unless indicated by clinical symptoms; 2. daily dose adjusted to yield an APTT 1.5 to 2X control; 3. daily dose adjusted to yield a negative TEG index.Group 2 received the most heparin, had the highest body weight, and greater incidence of minor bleeding ( + hemo- test urine and/or stool)(5 point drop in hematocrit).APTT values over 100 sec were seen in 44.4% of patients without bleeding and 52.5% with bleeding complications. Unmeasurable TEG graphs (SLT) were seen in 14.8% of patients without bleeding and 57.9% with bleeding. However, the combination of APTT over 100 sec and SLT were associated with 87.5% incidence of bleeding.The safety of continuous infusion heparin therapy is seen by the 2.2% incidence of major recurrent thrombosis and 2.2% major bleeding with or without laboratory monitoring. The combination of APTT and TEG was predictive of bleeding in 87.5% of cases. The TEG graph can be used to detect activated samples eliminating inconsistent APTT results.

scholarly journals Standartization of Heparin Therapy in Nyocardial Infarction

1977 ◽  
Author(s):  
J. Zahavi ◽  
S. Smetana
Keyword(s):  
Continuous Infusion ◽  
Significant Negative Correlation ◽  
Heparin Therapy ◽  
Plasma Fibrinogen ◽  
Heparin Dose ◽  
Interindividual Variations ◽  
Time Control ◽  
Daily Dose ◽  
Heparin Activity ◽  
Plasma Heparin

Sixty patients with myocardial infarction were randomized for intravenous 10 days heparin therapy, 400 U/ kg/ 24 hrs. In 20 of them, sodium heparin was injected every 6 hours and in another 20, by a continuous infusion preceded by a bolus of 50 U/kg. The remaining 20 patients were used as controls. Blood was drawn pre and 1-4 hours post heparin injection and then twice daily for the following tests: heparin tolerance, activated partial thromboplastin time (APTT), heparin half life and level. During continuous drip, theurapeutic anticoagulation (TA), 1,5–2,5 time control APTT levels, was maintained most of the time with daily and interindividual variations. When heparin was injected intermittently (I), TA was achieved only in the first 3–4 hours. In addition, a significant negative correlation between plasma fibrinogen and APTT, as well as a positive one between APTT and plasma heparin level, were found. These results suggest that heparin dose should be individualized during continuous infusion and when it is injected I, frequency of injections should not exceed 4 hours and the daily dose must presumably be higher then 400 U/kg, Plasma fibrinogen seems to be an important factor influencing negatively the heparin activity and should be considered during anticoagulant therapy with heparin.

Quantitative Lung Ultrasound Comet Measurement: Method and Initial Clinical Results

2015 ◽  
Vol 39 (1-3) ◽  
pp. 37-44 ◽  
Author(s):  
William F. Weitzel ◽  
James Hamilton ◽  
Xianglong Wang ◽  
Joseph L. Bull ◽  
Alan Vollmer ◽  
...  
Keyword(s):  
Quantitative Measurement ◽  
Lung Ultrasound ◽  
Clinical Results ◽  
Image Processing Algorithm ◽  
Lung Water ◽  
Dialysis Treatment ◽  
Clinical Events ◽  
Negative Findings ◽  
Ultrasound Signal ◽  
Signal Processing Methods

Background/Aims: Recently, ultrasound signals termed ‘lung water comets' associated with pulmonary edema have been correlated with adverse clinical events in dialysis patients. These comets fluctuate substantially during the ultrasound exam highlighting the need for objective quantitative measurement methods. Methods: We developed an image-processing algorithm for the detection and quantification of lung comets. Quantification measures included comet number (comet count) and the fraction of the ultrasound beams with comet findings (comet fraction). We used this algorithm in a pilot study in 20 stable dialysis outpatients to identify associations between ultrasound comets and clinical parameters including blood pressure (BP), percent blood volume reduction on dialysis (%BV), ejection fraction (EF), and ultrafiltration on dialysis (UF). Results: Positive findings included associations with lung comet measurements with pre-dialysis Diastolic BP (r = 0.534, p = 0.015), subject age (r = -0.446, p = 0.049), and a combination of EF and end dialysis %BV reduction (r = -0.585, p = 0.028). Comet fraction and comet count were closely correlated due to the inherent relationship between these two metrics (r = 0.973, p < 0.001). Negative findings included ultrasound comets that did not change from beginning to end of dialysis (p = 0.756), and were not significantly correlated with single dialysis treatment UF (p = 0.522), subject body weight (p = 0.208), or BMI (p = 0.358). Conclusions: Ultrasound signal processing methods may help quantify lung ultrasound comets. Additional findings include algorithmic lung comet measurement that did not change significantly during single dialysis sessions in these stable outpatients, but were associated with cardiovascular and fluid status parameters.

scholarly journals Heparin Pharmacokinetics

1977 ◽  
Author(s):  
C. A. M. de Swart ◽  
J. W. N. Akkerman ◽  
A. Nijmeijer ◽  
J. J. Sixma
Keyword(s):  
Continuous Infusion ◽  
Heparin Therapy ◽  
Anticoagulant Effect ◽  
High Rate ◽  
Binding Studies ◽  
Close Relationship ◽  
Antibody Complex ◽  
Heparin Activity ◽  
Effect Binding ◽  
Sepharose 4B

In heparin therapy different schedules for safe and effective treatment have been advocated,but they are not based on firm knowledge of the pharmacokinetics of heparin. We report on the application of two tests (diluted APTT test according to Marder and anti-Xa assay according to Yin) to the study of the pharmacokinetics of the anticoagulant effect of four commercially available brands of heparin. The drug was administered as a single large bolus or by continuous infusion. In contrary to reported pharmacokinetics a non exponential disappearance was observed after single dosis administration. Continuous infusion allowed a mathematical description of elimination of heparin activity,in which two mechanisms could be demonstrated. Pirstly, a mechanism which is saturable and eliminates heparin activity at low levels at a high rate. Secondly, a mechanism which is linearly related to heparin activity. Studies carried out on the elimination of 35S heparin showed that the disappearance of the radioactivity differed from that of the anticoagulant effect. Binding studies with an antibody directed against antithrombin III which was insolubilized on Sepharose 4B showed a close relationship between the disappearance of that part of the radiolabel that bound to the Sepharose-antibody complex and the disappearance of the anticoagulant effect.

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