Thrombin Time Dilution Test: A Simple Method for the Control of Heparin Therapy

1979 ◽  
Vol 42 (04) ◽  
pp. 1276-1285 ◽  
Author(s):  
Javier Pizzuto ◽  
Sergio Garcìa-Méndez ◽  
Marìa de-la-Paz Reyna ◽  
Manuel R Morales ◽  
Agustìn Avilés ◽  
...  
Keyword(s):  
Platelet Rich Plasma ◽  
Heparin Therapy ◽  
Thrombin Time ◽  
Simple Method ◽  
Adequate Dose ◽  
Heparin Activity ◽  
Time Test ◽  
Adequate Dosage ◽  
Plasma Heparin

SummaryA modification of the thrombin time test (TT), which permits quantitative measurement of plasma heparin activity during therapy is described. The prolonged TT of plasma containing heparin can be corrected by dilution with platelet-rich plasma (PRP). Clinical heparin activity is considered adequate when prolonged TT of the plasma can be corrected at dilutions of from 1:4 to 1:8 (±20%). In vitro studies of 30 PRP samples containing different amounts of heparin showed that 1:4 and 1:8 dilutions did not correct prolonged TT (P<0.05) in the presence of more than 0.2 and 0.3 U of heparin/ml respectively, indicating that the adequate dose of heparin should fall between those levels which show correction at these dilutions, using the diluted TT method.Patients treated with 100 U of heparin/kg every 4 or 6 h were studied: 52 without previous coagulation defects and 22 with disseminated intravascular coagulation (DIC). The results in the first group showed adequate dosage in 29 cases, overdosage in 12 and underdosage in 11. Hemorrhage occurred in 5 of the overdosage group. In the DIC series, 4 with underdosage of heparin did not improve; in 13 of 18 with adequate dosage, both hemorrhage and coagulapathy disappeared, while the other 5, with more severe complications did not improve. Based on these findings, the diluted TT appears to be a useful test in the assessment of heparin therapy, even in patients with previous coagulation abnormalities.

Thrombin Time Dilution Test: A Simple Method to Control Heparin Therapy

1977 ◽  
Author(s):  
J. Pizzuto ◽  
M.P. Reyna ◽  
S. García-Méndez ◽  
M.R. Morales
Keyword(s):  
Quantitative Measurement ◽  
Heparin Therapy ◽  
Thrombin Time ◽  
Simple Method ◽  
Coagulation Abnormalities ◽  
Coagulation Defects ◽  
Heparin Activity ◽  
Adequate Dosage ◽  
Plasma Heparin

A modification of thrombin time (TT) is described, allowing quantitative measurement of plasma heparin activity during therapy. When heparin-containing plasma shows prolonged TT, TT is corrected by diluting with platelets rich plasma (PRP) thus finding the adequate heparin activity; the latter is estimated when prolonged TT of test plasma is corrected by PRP in the proportion between 1:4 and 1:8 (±20%). Results of 30 PRP samples studied in vitro by adding different amounts of heparin showed that samples diluted 1:4 and 1:8 did not correct prolonged TT (P<0.05) when they contained respectively, more than 0.2 or 0.3 U of heparin/ml. Therefore within these levels of heparin one should place the adequate dosage of heparin when using this method. Patients treated with 100 U of heparin/Kg every 6 h were thus studied: 52 without previous coagulation defects and 22 with disseminated intravascular coagulation (DIC). The results in the first group showed good heparin effect in 29 cases, overdosage in 12 and un derdosage in 11. Hemorrhage ocurred in 5 of the overdosage group. In the cases of DIC, 4 with underdosage of heparin did not improve; in 11 out of 18 with adequate levels of heparin, both hemorrhage and coagulopathy dissapeared and the other 7 who had more severe complications did not improve. To sum up, the diluted TT is a very useful test to assess heparin therapy even in patients with previous coagulation abnormalities.

The Effect of Lysed Platelets on Neutralization of Heparin In Vitro with Protamine as Measured by the Activated Coagulation Time (ACT)

1991 ◽  
Vol 66 (02) ◽  
pp. 213-217 ◽  
Author(s):  
Arthur P Bode ◽  
William J Castellani ◽  
Edna D Hodges ◽  
Susan Yelverton
Keyword(s):  
Platelet Rich Plasma ◽  
Coagulation Time ◽  
Platelet Factor ◽  
Platelet Suspension ◽  
Antiheparin Activity ◽  
Unit Increase ◽  
Heparin Anticoagulation ◽  
Heparin Activity ◽  
Activated Coagulation Time

SummaryThe effect of lysed platelets on the activated coagulation time (ACT) was studied in heparinized whole blood during titration with protamine. Frozen-thawed washed platelet suspension, or a chromatography fraction thereof, or autologous frozen-thawed platelet-rich plasma was added in various dilutions to freshly drawn blood anticoagulated with 3,000 USP units/1 heparin. After a 10 min incubation, the amount of protamine needed to restore the ACT to baseline ("protamine titration dose") was determined. We found that the protamine titration dose decreased in proportion to the amount of lysed platelet material added; expressed as a percentage of the total number of platelets present, each unit increase in lysed platelets produced a 1.7% ±0.8 (SD) reduction in the protamine dose needed to normalize the ACT. A heparin activity assay showed that this effect was not due to antiheparin activity of lysed platelets such as platelet factor 4 (PF4). Our data indicate that the procoagulant activity of platelet membranes reduced the sensitivity of the ACT to heparin. These findings suggest that membranous platelet microparticles may cause an inaccurate calculation, based on the ACT, of a protamine dose to reverse heparin anticoagulation in cardiopulmonary bypass procedures.

The Flowing Clotting Time (Thrombus Formation Time) a Sensitive Test of Hypercoagulability

1969 ◽  
Vol 21 (03) ◽  
pp. 516-523
Author(s):  
H Engelberg ◽  
L. P Engelberg
Keyword(s):  
Thrombus Formation ◽  
Formation Time ◽  
Sensitive Test ◽  
Clotting Time ◽  
Reliable Test ◽  
Time Test ◽  
Plasma Heparin

SummaryThe addition of small amounts of extrinsic thromboplastin or of thrombin to blood in vitro accelerated coagulation more frequently and to a greater extent when determined by the flowing time test than when measured by the silicone clotting time, or by the blood or plasma heparin tolerance tests. Similar results were obtained when intrinsic thromboplastin formation was stimulated by contact with glass. However there was little or no acceleration of the flowing clotting time of plasma obtained from aliquots of the thromboplastin-containing blood. These results indicate that the flowing clotting time (thrombus formation time) of whole blcod is a more reliable test of hypercoagulability than previously described blood or plasma clotting time tests.

Studies On The Mechanism Of Heparin Induced Thrombocytopenia

1981 ◽  
Author(s):  
Harry L Messmore ◽  
Jawed Fareed ◽  
Zaheer Parvez ◽  
Judith M Kniffin ◽  
Grace Squillaci ◽  
...  
Keyword(s):  
Low Dose ◽  
Antithrombin Iii ◽  
Platelet Rich Plasma ◽  
Protein A ◽  
Heparin Therapy ◽  
Low Molecular Weight ◽  
Heparin Induced Thrombocytopenia ◽  
Control Serum ◽  
Heparin Fractions

Although heparin-induced thrombocytopenia is a well recognized complication of heparin therapy (low dose or therapeutic), the mechanisms involved remain to be clarified. We have studied the serum (heated to 56°C for 30min) and platelets of patients who became thrombocytopenic while receiving treatment with beef lung heparin. The in-vitro aggregation of these platelets in their own platelet rich plasma (PRP) occurred equally well with porcine mucosal (Na+ and Ca++ salts), sheep mucosal (Na+ salt) and beef lung heparins. In-vitro aggregation also occurred with low molecular weight (4-8 × 103 daltons) porcine heparin fractions. Normal PRP aggregated readily with each of these heparins when patient serum was present. We also found that the release reaction occurs as measured by luciferase coupled luminescense aggregometry. This reaction was only slightly less when aspirin-treated platelets were used. Electron microscopy of platelets aggregated with patient serum and heparin revealed intact ghosts which showed morphology identical to collagen-treated platelets after release has occurred. This activity can be removed from the patient serum with protein A-sepharose column, and can be eluted off the column with 1M acetic acid. Heparin fragments (MW 1-2 × 103 daltons) retain potent anti-Xa activity mediated through antithrombin-III. These fragments do not aggregate the platelets of PRP in the presence of patient or control serum. This suggests the possibility that ultralow MW heparin would not cause thrombocytopenia in a patient who developed it while on high MW heparin, but this remains to be proven, and individual reactions may vary.

scholarly journals Platelet Factor 4 (PF4) and Protamine Neutralisation of Heparin in Plasma

1977 ◽  
Author(s):  
R. Michalski ◽  
D.A. Lane ◽  
D. Pepper ◽  
V.V. Kakkar
Keyword(s):  
Intravenous Injection ◽  
Factor Xa ◽  
Weight Basis ◽  
Platelet Factor 4 ◽  
Assay System ◽  
Platelet Factor ◽  
Protamine Sulphate ◽  
Heparin Activity ◽  
Plasma Heparin

The ability of PF4 and protamine sulphate to neutralise heparin in plasma has been studied using a specific anti-Factor Xa assay and a KCCT assay to measure residual heparin. When heparin is added to plasma in vitro PF4 and protamine neutralise almost equivalent amounts of heparin on a weight basis, 1.0 unit of heparin being neutralised by approximately 20 μg of PF4 and 15 μg of protamine. Similar results are obtained using either of the heparin assays. However, following intravenous injection of heparin only about one half of the circulating heparin could be neutralised in vitro by PF4 or protamine when it was measured by anti-Factor Xa assay. Total neutralisation was obtained with both neutralising agents in the KCCT assay system. These results demonstrate that the choice of assay is important when a protamine titration is used to measure plasma heparin levels, and that PF4 and protamine are unable to totally neutralise circulating antithrombotic heparin activity.

In Vitro Biocompatibility of a New High Nitrogen Nickel Free Austenitic Stainless Steel

2007 ◽  
Vol 342-343 ◽  
pp. 605-608 ◽  
Author(s):  
Yi Bin Ren ◽  
Hua Juan Yang ◽  
Ke Yang ◽  
Bing Chun Zhang
Keyword(s):  
Stainless Steel ◽  
Austenitic Stainless Steel ◽  
Blood Compatibility ◽  
Platelet Rich Plasma ◽  
Clotting Time ◽  
Adhesion Test ◽  
High Nitrogen ◽  
In Vitro Biocompatibility ◽  
Time Test

The in vitro blood compatibility of a new nickel free high nitrogen austenitic stainless steel Fe-Cr-Mn-Mo-N (BIOSSN4) was studied by the kinetic clotting time test and the platelet rich plasma adhesion test in this paper. In comparison with 316L stainless steel, the kinetic clotting time of BIOSSN4 steel are longer, and only causes less activation of platelets in platelet adhesion test, which was indicated by their morphology and low spreading. The experimental results reveals that the BIOSSN4 stainless steel has better blood compatibility, the blood compatibility mechanism of steels was analyzed based on surface tension and interfacial tension between the steels and blood.

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.

Clinical Pharmacokinetics of Heparin

1980 ◽  
Vol 14 (7-8) ◽  
pp. 483-488
Author(s):  
Ralph H. Raasch
Keyword(s):  
Half Life ◽  
Significant Variable ◽  
Clotting Time ◽  
Heparin Infusion ◽  
Clinical Pharmacokinetics ◽  
Dosing Regimens ◽  
Heparin Activity ◽  
Time Test ◽  
The Difference

The pharmacokinetic literature regarding heparin is reviewed, and suggestions regarding the therapeutic use of this anticoagulant are provided. Various kinetic parameters for heparin have been reported, including half-life of pharmacological (anticoagulant) effects using in vitro clotting time tests, and half-life and clearance of heparin using assays of heparin activity. Heparin half-life is shorter, and clearance is greater, in patients with pulmonary emboli compared to patients with deep venous thrombosis. However, heparin infusion rates may be similar regardless of type of thromboembolic disease to achieve a given pharmacological endpoint. The difference in in vitro clotting time test responses among patients given similar amounts of heparin is a most significant variable in determining heparin dosing regimens, and makes continued monitoring of heparin dosage and the associated in vitro clotting time test response necessary for the rational use of this drug.

Studies on the Anti-Heparin Activity of Serum

1962 ◽  
Vol 07 (01) ◽  
pp. 188-196 ◽  
Author(s):  
T Holger-Madsen
Keyword(s):  
Plasma Level ◽  
Normal Serum ◽  
Thrombin Time ◽  
Original Activity ◽  
Platelet Poor Plasma ◽  
Normal Platelet ◽  
Heparin Resistance ◽  
Heparin Activity ◽  
Plasma Heparin

SummaryThe anti-heparin activity of serum was investigated by adding serum to normal, platelet-poor plasma and determining the heparin thrombin time.BaSO4-adsorbed serum and serum from platelet-poor plasma proved to exert a considerably less marked anti-heparin activity than plain serum. Even in platelet-poor serum, adsorbed with BaSO4 some anti-heparin activity still remained, but by far the greater part of the original activity had disappeared. In some patients, in whom determination of the plasma heparin thrombin time has shown increased heparin resistance, the serum may also exert a greater anti-heparin activity than normal serum. In patients on anticoagulant therapy with phenylindanedione even a considerable lowering of the prothrombin-proconvertin plasma level did not entail any reduction in the anti-heparin activity of the serum as compared with normal serum.

Subcutaneous Heparin Therapy In Renal Insufficiency

1981 ◽  
Author(s):  
W Salzmann ◽  
K Andrassy ◽  
E Ritz ◽  
J Koderisch
Keyword(s):  
Low Dose ◽  
Factor Xa ◽  
Repeated Administration ◽  
Heparin Therapy ◽  
Thrombin Time ◽  
Amidolytic Activity ◽  
Dose Heparin ◽  
Heparin Activity ◽  
Uremic Patients ◽  
Low Dose Heparin

It is often necessary to treat uremic patients with low dose heparin therapy,e.g. for prophylaxis of Cimino-fistula thrombosis. However, little information is available on heparin pharmacokinetics and heparin action in uremic patients. In the present study, plasma activity time profiles during low dose heparin therapy were investigated in control individuals (CO) and in uremic patients (UP). Patients and methods: Heparin levels 0;3;8;10;12;24;27;32;34 and 36 h after s.c. injection of various doses of heparin (2×7.500 IU/day for 2 days; 3×5.000 IU and 2×5.000 IU each for 2 days) were measured in 9 control individuals and in 11 uremic patients (Ccr < 10 ml/min.). Heparin activity was determined by measurements of (1) neutralisation of factor Xa-activity (Denson and Bonnar); (2) neutralisation of Xa measuring amidolytic activity (Teien and Lie); (3) PTT and thrombin time. Heparin cofactor concentrations were measured with immuno-diffusion and by measuring amidolytic activity. Results: With the dose of 2×5.000 IU heparin s.c. no difference between CO and UP was found; in contrast, peak concentrations of heparin were significantly lower in UP after 7.500 IU heparin s.c. With the dose of 3×5.000 IU heparin s.c.there was a significant (p<0.05) difference of heparin levels between CO and UP. This difference was even more pronounced after repeated administration of heparin; heparin levels in UP were markedly lower than in controls. The antithrombin III levels did not change significantly during the study. Conclusion : The results show that in order to reach a given profile of heparin activity, higher s.c. doses of heparin must be administered in uremic patients than in non-uremic controls.

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