Experimental study on the hemostatic effect of cyanoacrylate intended for catheter securement

2018 ◽  
Vol 20 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Sheng Zhang ◽  
Amanda R Guido ◽  
Richard G Jones ◽  
Benjamin J Curry ◽  
Angela S Burke ◽  
...  

Purpose: The use of cyanoacrylate for intravenous catheter securement is of interest to clinicians and patients, because of the superior adhesive strength and hemostatic effect of cyanoacrylate compared to current securement devices. The purpose of this study is to use novel in vitro and in vivo testing methods to analyze the hemostatic effect of a catheter securement cyanoacrylate (cyanoacrylate). Methods: An unprecedented in vitro method was performed to determine the effects of a cyanoacrylate on a customized modified activated clotting time assay and blood flow inhibition assay by exposing blood or plasma to either one or three drops of cyanoacrylate. For the in vivo testing, full-thickness incisions were made on swine, and the bleeding was scored prior to treatment and at 3, 6, 9, and 12 min after treatment. Results: The cyanoacrylate rapidly achieved hemostasis in the presence of anticoagulated whole blood, platelet-poor plasma, and non-anticoagulated whole blood, in vitro. The cyanoacrylate achieved hemostasis 12-fold faster than thromboplastin in the modified activated clotting time assay. The cyanoacrylate does not alter normal blood clotting, as measured by prothrombin time. In vivo, the bleeding score of cyanoacrylate prior to treatment and at 3, 6, 9, and 12 min after treatment were 2.3 ± 1.0, 0.3 ± 0.5, 0.2 ± 0.5, 0.2 ± 0.4, and 0.2 ± 0.4, respectively. Conclusion: This study indicates that cyanoacrylate demonstrates a potent mechanical hemostatic effect and cyanoacrylate in the presence of anticoagulated whole blood has an activated clotting time that is 12 times quicker than thromboplastin. The cyanoacrylate was found to be significantly equivalent to two known hemostatic agents, in vivo.

1981 ◽  
Author(s):  
M Hada ◽  
S Ikematsu ◽  
M Fujimaki ◽  
K Fukutake

Coagulational functions of VIIIR:AG are still unknown, while its serological significance in laboratory medicine has been established. In this study it will be analyzed the mechanism of the consumption of VIIIR:AG during the process of prolonged blood coagulation.Quantitative assay of VIIIR:AG in plasma and serum is measured by Laurell’s method using 1% agarose with anti-F.VIII rabbit serum and qualitative assay of VIIIR:AG is performed by crossed-immunoelectrophoresis with anti F.VIII rabbit serum.In 28 patients with Hemophilia A a negative relationship between serum VIIIR:AG / plasma VIIIR:AG ratio and prolongation of PTT is estimated and also a positive relationship between serum VIIIR:AG / plasma VIIIR:AG ratio and serum VIII:vW / plasma VIII:vW ratio is obtained. However, serum VIIIR:AG shows the similar quantity to plasma VIIIR:AG in the cases within normal clotting time, which have been treated by the in vitro addition of thrombin or by transfusion of AHG in vivo. When heparin or synthetic antithrombin ( MCI-9038 ) is added into normal whole blood or F.XIII deficient whole blood, the case of normal whole blood shows delayed clotting time and decrease of serum VIIIR:AG, but the case of F.XIII deficient whole blood indicates no decrease of serum VIIIR:AG. Furthermore, in those conditions change of the concentration of CIg in serum, which has been pointed out with fibrin crosslinking, indicate the similar behavior as serum VIIIR:AG.The results obtained above might suggest that serum VIIIR:AG tend to decrease in the cases with prolonged clotting time, and the F.XIII activity might be involved in the consumption mechanism of serum VIIIR:AG in such an abnormal condition, as fibrin crosslinkage could not carry out properly.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5129-5129
Author(s):  
Jawed Fareed ◽  
Debra Hoppensteadt ◽  
Omer Iqbal ◽  
Jeanine M. Walenga ◽  
Bruce E Lewis

Abstract Abstract 5129 Several generic versions of argatroban) (Mitsubishi; Tokyo, Japan) have been introduced in Japan (Argaron, Gartban, Slovastan). In addition, other generic versions of argatroban are being considered by the European and North American regulatory bodies. While the generic versions of argatroban exhibit similar antithrombin potency (Ki values), because of the differential compositional variations their anticoagulant effects in whole blood systems may differ due to their cellular and plasmatic protein interactions. Branded and generic versions of argatroban may exhibit differential anticoagulant actions in the whole blood and plasma based assays due to their differential interactions with blood cells, platelets and plasma proteins. Three generic versions of argatroban that are commercially available in Japan namely Argaron, Gartban and Slovastan and a powdered version of generic argatroban (Lundbeck) were compared with the branded argatroban. Native whole blood thrombelastographic (TEG) analysis was carried out at 0.1 ug/mL, the Activated Clotting Time (ACT) assay was carried out in a concentration range of 0–10 ug/mL, and such coagulation tests as the PT/INR, aPTT, Heptest, and calcium thrombin time were performed. Plasma retrieved from the supplemented whole blood was also assayed. Ratios of the clotting time test values from whole blood and plasma were calculated. Retrieved plasma samples were also assayed in the thrombin generation assays (TGA). All of the different versions of argatroban produced a concentration dependent anticoagulant effect in the native whole blood TEG and ACT. In the TEG, while argatroban and Slovastan showed a similar effect, Gartban, Argaron and a powdered generic showed weaker effects. Argatroban was also different in the ACT assay. At a concentration of 5 ug/ml the ACTs were, Arg 340+15.2 secs, S 297+10.5 secs, G 292.0+19.1 secs and A 285.2+21.7 secs. In the citrated whole blood systems, all agents produced a concentration dependent anticoagulant effect; however, the generic versions produced a stronger anticoagulant effect in comparison to branded argatroban (p<0.001). In the PT assay at 5 ug/mL, argatroban showed 32 ± 3 sec vs 40–50 sec for the generic products. Similarly in the aPTT, Heptest and thrombin time tests argatroban was weaker than the generic products. Differences among generic versions were also evident. Similar results were obtained in the retrieved plasma, however the ratio of whole blood over plasma varied from product to product. The IC50 of the generic and branded argatrobans in the TGA were also different. These results show that while in the thrombin inhibition assays generic and branded argatroban may show similar effects, these agents exhibit assay dependent differences in the whole blood and plasma based assays. Such differences may be more evident in the in vivo studirs where endothelial cells and other interactions may contribute to product individuality. Therefore, based on the in vitro antiprotease assays, generic argatrobans may not be considered equivalent and require a multi-parametric study. Currently available generic argatrobans may not be equivalent in the in vivo anticoagulant effects. Therefore, clinical validation of the clinical equivalence for these drugs is warranted. Disclosures: No relevant conflicts of interest to declare.


Author(s):  
Barbara Nunn

The effect of aspirin on human platelet function is usually assessed using platelet-rich plasma (PRP). Some preliminary results in vitro suggested that the effect of aspirin appears to be greater in PRP than whole blood. To explore this possibility further, a comparison of the effect of aspirin in humans ex vivo has been made taking measurements simultaneously in whole blood and PRP at 2 platelet concentrations. Blood samples (36ml) were drawn from 7 male volunteers after a light breakfast. Each took 300mg soluble aspirin and blood samples were drawn again 2 hours later. Blood was mixed with 0.1 volumes 129nM trisodium citrate. Some (30ml) was then centrifuged to prepare PRP and platelet -poor plasma (PPP) by standard techniques. Platelet concentration of some PRP was adjusted with PPP to equal that of the corresponding blood sample; the rest was adjusted to 350,000 per μl. Aggregation in response to collagen (Horm, Munich) was measured photometrically at 37°. Aggregation in 0.5ml aliquots of whole blood was measured after 4 min stirring with 154mM NaCl (control) or collagen at 37° as the fall in single platelet count determined using an Ultraflo- 100 whole blood platelet counter (Clay Adams). The concentrations of collagen producing a 50% maximal response (EC50) in PRP and blood were determined. Dose-ratios for each volunteer were calculated by dividing the EC50 obtained after aspirin by the corresponding value obtained before aspirin.The effect of aspirin was significantly (p<0.001) less in blood than PRP. Whether or not the results in whole blood more closely reflect the effect of aspirin in vivo remains to be determined.


1995 ◽  
Vol 15 (6) ◽  
pp. 748-753 ◽  
Author(s):  
Jonathan D. Emery ◽  
David W. Leifer ◽  
Glaci L. Moura ◽  
Patricia Southern ◽  
James H. Morrissey ◽  
...  

2000 ◽  
Vol 92 (6) ◽  
pp. 1594-1602 ◽  
Author(s):  
Fritz Mertzlufft ◽  
Andreas Koster ◽  
Roland Hansen ◽  
Anne Risch ◽  
Herrmann Kuppe ◽  
...  

Background The authors assessed the heparin management test in vitro in volunteers and in vivo during cardiopulmonary bypass. Methods In vitro, the heparin management test was analyzed for heparin levels between 0 and 6 IU/ml using variations in hematocrit, platelets, procoagulants, and storage time. The in vivostudies consisted of two groups: In group I (cardiopulmonary bypass &lt;/= 90 min, n = 40), anticoagulation was performed according to the activated clotting time (with or without aprotinin); in group II (cardiopulmonary bypass &gt;/= 180 min, with aprotinin) included use (n = 10) and nonuse of coumadin (n = 10) and anticoagulation according to the automated heparin dose-response assay. Tests were performed in duplicate (whole blood, two heparin management test analyzers) and compared with anti-Xa activity (plasma). Results In vitro, the results of the heparin management test (n = 1,070) correlated well with heparin concentration (r2 = 0.98). Dilution and storage time did not affect the heparin management test; a hematocrit of 60% and reduced procoagulants (10%) prolonged clotting time. In vivo, the correlation (heparin management test vs. anti-Xa) was strong in group I (r2 = 0.97 [with aprotinin] and 0.96 [without aprotinin]; n = 960) and group II without coumadin (r2 = 0.89, n = 516). In group II with coumadin, the overall correlation was r2 = 0.87 and 0.79 (n = 484), although the range varied widely (0.57-0.94, between-analyzer differences 0-47%). Conclusions The results of the heparin management test were influenced by hematocrit, plasma coagulation factors, and the heparin level, but not by use of aprotinin. The heparin management test provided reliable values in vitro in group I, and in group II without coumadin but was less reliable in group II with coumadin.


2016 ◽  
Vol 30 (6) ◽  
pp. 923-928 ◽  
Author(s):  
Junko Ichikawa ◽  
Satoshi Hagihira ◽  
Testu Mori ◽  
Mitsuharu Kodaka ◽  
Keiko Nishiyama ◽  
...  

Transfusion ◽  
2010 ◽  
Vol 50 (10) ◽  
pp. 2145-2151 ◽  
Author(s):  
Edward L. Snyder ◽  
Pamela Whitley ◽  
Tracy Kingsbury ◽  
Jeffrey Miripol ◽  
Christopher A. Tormey

1979 ◽  
Vol 42 (04) ◽  
pp. 1248-1260 ◽  
Author(s):  
Lyle F Mockros ◽  
Samuel D Hirsch ◽  
Leon Zuckerman ◽  
Joseph A Caprini ◽  
William P Robinson ◽  
...  

SummaryBolus injections of beef-lung heparin at doses of 50, 100 and 200 u/kg body weight were administered to mongrel dogs. Neutralization of the anticoagulant effect was evaluated using sequential samples withdrawn from the animals (in vivo samples) and aliquots from a 100 ml sample withdrawn from the dog at 30 minutes post-injection (in vitro samples). Tests of the activated partial thromboplastin time (APTT) and prothrombin time (PT) did not indicate the degree of anticoagulation. Tests of the whole blood clotting time (WBCT), celite- activated whole blood clotting time (ACT), and celite-activated thromboelastography (ATEG) indicated pronounced hypocoagulability immediately after the injection, followed by a fairly rapid decay in anticoagulability, and a slight Ziype/coagulability at three to four hours post injection. The results from the in vitro ATEG samples were essentially identical to those on the in vivo samples, whereas the in vitro WBCT and ACT generally indicated higher degrees of anticoagulation. Calculated half-lives of the anticoagulant effect are significantly shorter than previously reported, being 18 to 36 minutes, and slightly dose dependent. The decay of the effects, however, does not appear to follow a single exponential curve, dropping very rapidly immediately post-injection and at a somewhat slower rate 60 or more minutes post-injection.


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.


1987 ◽  
Vol 58 (02) ◽  
pp. 744-748 ◽  
Author(s):  
A R Saniabadi ◽  
G D O Lowe ◽  
J C Barbenel ◽  
C D Forbes

SummarySpontaneous platelet aggregation (SPA) was studied in human whole blood at 3, 5, 10, 20, 30, 40 and 60 minutes after venepuncture. Using a whole blood platelet counter, SPA was quantified by measuring the fall in single platelet count upon rollermixing aliquots of citrated blood at 37° C. The extent of SPA increased with the time after venepuncture, with a correlation coefficient of 0.819. The inhibitory effect of dipyridamole (Dipy) on SPA was studied: (a) 10 μM at each time interval; (b) 0.5-100 μM at 3 and 30 minutes and (c) 15 μM in combination with 100 μM adenosine, 8 μM 2-chloroadenosine (2ClAd, an ADP receptor blocker) and 50 μM aspirin. There was a rapid decrease in the inhibitory effect of Dipy with the time after venepuncture; the correlation coefficient was -0.533. At all the concentrations studied, Dipy was more effective at 3 minutes than at 30 minutes after venepuncture. A combination of Dipy with adenosine, 2ClAd or aspirin was a more effective inhibitor of SPA than either drug alone. However, when 15 μM Dipy and 10 μM Ad were added together, the inhibitory effect of Dipy was not increased significantly, suggesting that Dipy inhibits platelet aggregation independent of Ad. The increase in SPA with the time after venepuncture was abolished when blood was taken directly into the anticoagulant containing 5 μM 2ClAd. It is suggested that ADP released from the red blood cells is responsible for the increased platelet aggregability with the time after venepuncture and makes a serious contribution to the artifacts of in vitro platelet function studies.


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