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

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.

2007 ◽  
Vol 342-343 ◽  
pp. 605-608 ◽  
Author(s):  
Yi Bin Ren ◽  
Hua Juan Yang ◽  
Ke Yang ◽  
Bing Chun Zhang

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.


1980 ◽  
Vol 14 (7-8) ◽  
pp. 483-488
Author(s):  
Ralph H. Raasch

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.


1969 ◽  
Vol 22 (02) ◽  
pp. 344-350
Author(s):  
H Engelberg

SummaryEvidence has been presented that thrombin formation and coagulation are the major processes involved in the formation of the clot-thrombus when blood is rotated in the Chandler loop, and that platelet aggregation is secondary to thrombin formation. It is suggested that the test be called the flowing clotting time or the clot-thrombus formation time.


1968 ◽  
Vol 20 (03/04) ◽  
pp. 596-602
Author(s):  
N. D Giordano ◽  
M Radivoyevitch ◽  
E Goodsitt

SummaryAn in vitro study was performed with 14 hemophilia-A patients, using a simple wheel with an electrically driven motor to form thrombi.The findings are discussed in relationship to normal thrombi and a direct comparison was made in regard to rate of thrombus formation, thrombus length and morphological differences.A relationship between the above and clinical severity of the disease with some speculations on the possible role played by white and red cells on thrombus formation time, was also presented.


1979 ◽  
Vol 42 (04) ◽  
pp. 1276-1285 ◽  
Author(s):  
Javier Pizzuto ◽  
Sergio Garcìa-Méndez ◽  
Marìa de-la-Paz Reyna ◽  
Manuel R Morales ◽  
Agustìn Avilés ◽  
...  

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.


2010 ◽  
Vol 30 (04) ◽  
pp. 212-216 ◽  
Author(s):  
R. Jovic ◽  
M. Hollenstein ◽  
P. Degiacomi ◽  
M. Gautschi ◽  
A. Ferrández ◽  
...  

SummaryThe activated partial thromboplastin time test (aPTT) represents one of the most commonly used diagnostic tools in order to monitor patients undergoing heparin therapy. Expression of aPTT coagulation time in seconds represents common practice in order to evaluate the integrity of the coagulation cascade. The prolongation of the aPTT thus can indicate whether or not the heparin level is likely to be within therapeutic range. Unfortunately aPTT results are highly variable depending on patient properties, manufacturer, different reagents and instruments among others but most importantly aPTT’s dose response curve to heparin often lacks linearity. Furthermore, aPTT assays are insensitive to drugs such as, for example, low molecular weight heparin (LMWH) and direct factor Xa (FXa) inhibitors among others. On the other hand, the protrombinase-induced clotting time assay (PiCT®) has been show to be a reliable functional assay sensitive to all heparinoids as well as direct thrombin inhibitors (DTIs). So far, the commercially available PiCT assay (Pefakit®-PiCT®, DSM Nutritional Products Ltd. Branch Pentapharm, Basel, Switzerland) is designed to express results in terms of units with the help of specific calibrators, while aPTT results are most commonly expressed as coagulation time in seconds. In this report, we describe the results of a pilot study indicating that the Pefakit PiCT UC assay is superior to the aPTT for the efficient monitoring of patients undergoing UFH therapy; it is also suitable to determine and quantitate the effect of LMWH therapy. This indicates a distinct benefit when using this new approach over the use of aPPT for heparin monitoring.


1990 ◽  
Vol 63 (02) ◽  
pp. 220-223 ◽  
Author(s):  
J Hauptmann ◽  
B Kaiser ◽  
G Nowak ◽  
J Stürzebecher ◽  
F Markwardt

SummaryThe anticoagulant effect of selected synthetic inhibitors of thrombin and factor Xa was studied in vitro in commonly used clotting assays. The concentrations of the compounds doubling the clotting time in the various assays were mainly dependent on their thrombin inhibitory activity. Factor Xa inhibitors were somewhat more effective in prolonging the prothrombin time compared to the activated partial thromboplastin time, whereas the opposite was true of thrombin inhibitors.In vivo, in a venous stasis thrombosis model and a thromboplastin-induced microthrombosis model in rats the thrombin inhibitors were effective antithrombotically whereas factor Xa inhibitors of numerically similar IQ value for the respective enzyme were not effective at equimolar dosageThe results are discussed in the light of the different prelequisiles and conditions for inhibition of thrombin and factor Xa in the course of blood clotting.


1993 ◽  
Vol 70 (03) ◽  
pp. 448-453 ◽  
Author(s):  
Ole Nordfang ◽  
Hanne I Kristensen ◽  
Sanne Valentin ◽  
Per Østergaard ◽  
Johnny Wadt

SummaryThe anticoagulant activities of Tissue Factor Pathway Inhibitor (TFPI), heparin and hirudin were compared in intrinsic (APTT) and extrinsic (PT) activated clotting assays. In contrast to the thrombin inhibitor hirudin, heparin was 10 fold more potent in the APTT assay than in the PT assay, indicating that inhibition of intrinsic activation is important for the anticoagulant activity of heparin as measured in an APTT assay. TFPI was most potent in the PT assay and the effect of TFPI was most pronounced in the presence of other anticoagulants (heparin and hirudin). The activities of the two natural anticoagulants antithrombin III (ATIII) and TFPI were compared in a PT assay with very dilute tissue factor. In this assay system TFPI in normal plasma affected the clotting time more than ATIII in the plasma. However, when heparin was added ATIII was the major anticoagulant, but profound Prolongation of the clotting time was only seen when TFPI was also added. In an ATIII deficient plasma heparin did not augment the effect of TFPI, showing that the increased effect of TFPI in the presence of heparin is dependent on the anticoagulant activity of ATIII/heparin. The effect of TFPI at prolonged clotting times was also illustrated by the significant effect of blocking TFPI in the plasma from warfarin-treated patients. Thus TFPI is a major anticoagulant in normal plasma and the effect of TFPI is especially seen at prolonged clotting times.


1991 ◽  
Vol 65 (04) ◽  
pp. 355-359 ◽  
Author(s):  
E Gray ◽  
J Watton ◽  
S Cesmeli ◽  
T W Barrowcliffe ◽  
D P Thomas

SummaryThe in vitro anticoagulant activities of recombinant desulphatohirudin (r-hirudin) were studied in the activated partial thromboplastin time (APTT) and the thrombin generation test : systems. In the APTT at concentrations below 5 μg/ml, r-hirudin showed a dose-response curye. At concentrations above 5 μg/ml, the plasma became unclottable, but in the thrombin generation test , at least 10 μg/ml of r-hirudin was required for full inhibition of thrombin generation. The antithrombotic effect was assessed using a rabbit venous stasis model; 150 μg/ml r-hirudin completely prevented thrombus formation at 10 and 20 min stasis. At antithrombotic dose, the mean bleeding time ratio measured in a rabbit ear template model, was not prolonged over control values. At higher doses, the bleeding time ratios were higher than those observed for the same dosage of heparin. These data indicate that while r-hirudin is an effective antithrombotic agent, antithrombotic doses have to be carefully titrated to avoid excessive bleeding.


1980 ◽  
Vol 44 (02) ◽  
pp. 081-086 ◽  
Author(s):  
C V Prowse ◽  
A E Williams

SummaryThe thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vitro tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo.These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.


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