scholarly journals Assessment of whole blood coagulation with a microfluidic dielectric sensor

2018 ◽  
Vol 16 (10) ◽  
pp. 2050-2056 ◽  
Author(s):  
D. Maji ◽  
M. De La Fuente ◽  
E. Kucukal ◽  
U. D. S. Sekhon ◽  
A. H. Schmaier ◽  
...  
Author(s):  
Sina Pourang ◽  
Debnath Maji ◽  
Ujjal D. S. Sekhon ◽  
Anirban Sen Gupta ◽  
Michael A. Suster ◽  
...  

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1882-1882
Author(s):  
Sina Pourang ◽  
Michael A Suster ◽  
Pedram Mohseni ◽  
Lalitha V Nayak

Abstract Background: There is an intimate link between inflammation and thrombosis, and patients with pro-inflammatory/infectious disorders develop a hypercoagulable state. Extant coagulation assays are unable to distinguish the pro-coagulant state of a patient's blood, require 2-3 mL of blood, and take 2-3 hours for processing. These assays are also typically examined in plasma and do not represent the contribution of blood cellular elements that participate in thrombosis in vivo. Thus, a point-of-care device for rapid, comprehensive assessment of whole blood coagulation is crucial to ensure appropriate and timely evaluation in critically ill patients. We have introduced a microfluidic sensor (ClotChip) that uses dielectric spectroscopy to provide such an assessment in a handheld platform. We have shown in clinical studies in patients with a hypocoagulable state that ClotChip is sensitive to both coagulation factor and platelet defects, allowing for a global assessment of blood coagulation status using <10 µL of whole blood and in <30 min. In this study, we optimized ClotChip to assess the blood coagulation status in patients with a hypercoagulable state. Methods: Citrated blood samples from 12 patients with a diagnosis of sepsis and 11 healthy donors as controls were obtained under an IRB-approved protocol and tested with ClotChip within 2 hours of collection. ClotChip readout curve was calculated as the temporal variation of blood dielectric permittivity at 1 MHz, and the time to reach a permittivity peak (T peak) was taken as an indicator of coagulation time based on our prior studies. To increase the sensitivity of the ClotChip T peak parameter to a hypercoagulable state, we used two different anticoagulants, recombinant thrombomodulin (rTM) and activated protein C (APC). To optimize the anticoagulant concentration, whole blood samples from healthy donors were treated in vitro with lipopolysaccharide to mimic a pro-coagulant state of blood and tested with ClotChip after adding various concentrations of rTM and APC. We concluded that a concentration of 5 µg/mL for rTM and 10 µg/mL for APC would result in an optimal change in T peak for detecting the pro-coagulant state. Since heparin (or lovenox) is routinely used in hospitalized patients, sepsis and control samples were pretreated with hepzyme at a final concentration of 2 IU/mL to reverse the heparin effect. The T peak parameter was measured and compared in (i) hepzyme only-, (ii) rTM-, and (iii) APC-treated samples. Data are reported as mean ± standard deviation. Two-tailed t test is used to test for statistical significance between groups, and P < 0.05 is considered statistically significant. In box-and-whiskers plots, the box represents the range from the first to the third quartile, the horizontal line represents the median, plus sign (+) represents mean of the data; whiskers extend to the maximum and minimum data values, and dots represent individual subject data. Results: In hepzyme only-treated samples, T peak was significantly prolonged at 478±137 sec in sepsis samples, as compared to 357±58 sec in controls (Figs. 1A, 1B). rTM treatment resulted in T peak of 503±128 sec for sepsis samples and 443±81 sec for controls, whereas APC treatment resulted in T peak of 1,095±850 sec for sepsis samples and 477±71 sec for controls (Figs. 1A, 1B). Although T peak was prolonged at baseline in hepzyme only-treated sepsis samples, no further prolongation was noted with rTM treatment (difference in T peak of 24±94 sec; Fig. 1C), as compared to rTM-treated controls (difference in T peak of 85±40 sec; Fig. 1C). However, with a difference in T peak of 616±804 sec, the APC-treated sepsis samples exhibited T peak prolongation when compared to hepzyme only-treated sepsis samples, whereas the APC-treated controls did not (difference in T peak of 119±64 sec; Fig. 1D). A comparison between the APC- and rTM-treated samples revealed a significant prolongation of T peak in sepsis samples (difference in T peak of 591±815 sec) when compared to controls (difference in T peak of 30±66 sec; Fig. 1E). Conclusions: Our studies identify a unique coagulation profile in sepsis patient blood using a microfluidic dielectric sensor. These data suggest that the addition of rTM or APC can enhance the sensitivity of the ClotChip T peak parameter for detecting the pro-coagulant state in whole blood. Ongoing studies are examining the coagulation profile in other pro-inflammatory and infectious states. Figure 1 Figure 1. Disclosures Suster: XaTek Inc.: Consultancy, Current holder of stock options in a privately-held company, Patents & Royalties, Research Funding. Mohseni: XaTek Inc.: Consultancy, Current holder of stock options in a privately-held company, Patents & Royalties, Research Funding. Nayak: BioChip Labs: Current Employment.


1987 ◽  
Author(s):  
S D Blair ◽  
S B Javanvrin ◽  
C N McCollum ◽  
R M Greenhalgh

It has been suggested that mortality due to upper gastrointestinal haemorrhage may be reduced by restricting blood transfusion [1], We have assessed whether this is due to an anticoagulant effect in a prospective randomised trial.One hundred patients with severe, acute gastrointestinal haemorrhage were randomised to receive either at least 2 units of blood during the first 24 hours of admission, or no blood unless their haemaglobin was lessthan 8g/dl or they were shocked. Minor bleeds and varices were excluded As hypercoagulation cannot be measured using conventional coagulation tests, fresh whole blood coagulation was measured by the Biobridge Impedance Clotting Time (ICT). Coagulation was assessed at 24 hour intervals and compared to age matched controls with the results expressed as mean ± sem.The ICT on admission for the transfusion group (n=50) was 3.2±0.2 mins compared to 10±0.2 mins in controls. This hyper-coagulable state was partially reversed to 6.4±0.3 mins at 24 hours (p<0.001). The 50 allocated to receive no blood had a similar ICT on admission of 4.4±0.4 mins but the hypercoagulable state was maintained with ICT at 24 hours of 4.320.4 mins. Only 2 patients not transfused rebled compared to 15 in the early transfusion group (p<0.001). Five patients died, and they were all in the early transfusion group.These findings show there is a hypercoagulable response to haemorrhage which is partially reversed by blood transfusion leading to rebleeding


1966 ◽  
Vol 46 (4) ◽  
pp. 463-471
Author(s):  
Joseph Beeman ◽  
Alma Miller ◽  
Sam CAmarena

1997 ◽  
Vol 3 (2_suppl) ◽  
pp. 215-217 ◽  
Author(s):  
S. Nagai ◽  
A. Kurata ◽  
R. Tanaka ◽  
K. Irikura ◽  
Y. Miyasaka ◽  
...  

We chronologically determined whole blood coagulation time during continuous heparin administration, and investigated optimal doses of heparin in thirty-seven vascular surgery cases. ACT was determined with Hemochron 401. Heparin (2000 IU) was administered by bolus injection at the beginning of intravascular surgery, which was followed by continuous injection of 20 to 160 IU/kg/h. ACT determined before and 30 minutes after heparin administration were compared. There were no complications. ACT was maintained at a nearly constant level by continuous heparin administration. The dose of heparin required to maintain ACT at a level 1.5 to 2 times the initial level was 20 to 60 IU/kg/h. ACT was prolonged by more than three times in two of the ten subjects who were given heparin at a dose of 70 IU/kg/h or more. Continuous administration of heparin allowed maintenance of ACT at a nearly constant level during intravascular surgery. ACT was maintained within the range which is believed to be effective for prevention of thrombus formation (approximately 1.5 to 2.0 times larger than the initial level) by continuous administration of 20 to 60 IU/kg/h of heparin. ACT was, however, prolonged to more than three times the initial level in some subjects who were given 70 IU/kg/h or higher doses, suggesting the risk of a bleeding tendency. Accordingly, it is ideal to continue heparin administration at appropriate doses, while measuring ACT. The results of our study should serve as a useful standard for meeting this goal.


2009 ◽  
Vol 144 (1) ◽  
pp. 99-106 ◽  
Author(s):  
Ole H. Larsen ◽  
Niels Clausen ◽  
Egon Persson ◽  
Mirella Ezban ◽  
Jørgen Ingerslev ◽  
...  

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