This paper describes extending plug-based microfluidics to handling complex biological fluids such as blood, solving the problem of injecting additional reagents into plugs, and applying this system to measuring of clotting time in small volumes of whole blood and plasma. Plugs are droplets transported through microchannels by fluorocarbon fluids. A plug-based microfluidic system was developed to titrate an anticoagulant (argatroban) into blood samples and to measure the clotting time using the activated partial thromboplastin time (APTT) test. To carry out these experiments, the following techniques were developed for a plug-based system: (i) using Teflon AF coating on the microchannel wall to enable formation of plugs containing blood and transport of the solid fibrin clots within plugs, (ii) using a hydrophilic glass capillary to enable reliable merging of a reagent from an aqueous stream into plugs, (iii) using bright-field microscopy to detect the formation of a fibrin clot within plugs and using fluorescent microscopy to detect the production of thrombin using a fluorogenic substrate, and (iv) titration of argatroban (0-1.5 μg/mL) into plugs and measurement of the resulting APTTs at room temperature (23 °C) and physiological temperature (37 °C). APTT measurements were conducted with normal pooled plasma (platelet-poor plasma) and with donor's blood samples (both whole blood and platelet-rich plasma). APTT values and APTT ratios measured by the plug-based microfluidic device were compared to the results from a clinical laboratory at 37°C. APTT obtained from the on-chip assay were about double those from the clinical laboratory but the APTT ratios from these two methods agreed well with each other. This paper describes the development of a plug-based microfluidic system capable of titrating an anticoagulant drug, argatroban, into human blood samples and measuring the resulting clotting times. A method for injecting reagents into flowing plugs is also described. Determining the correct dose of an anticoagulant drug is important, as too little of the drug will not be effective while too much of the drug can result in uncontrolled bleeding. Argatroban directly inhibits the active site of thrombin, an essential enzyme in the coagulation cascade. 1 This inhibitor is an effective treatment for heparin-induced thrombocytopenia (HIT). 2 Heparin is a common anticoagulant used to treat thromboembolic diseases and to prevent thrombosis * To whom correspondence should be addressed. E-mail: r-ismagilov@uchicago.edu.. † Department of Chemistry and Institute for Biophysical Dynamics. ‡ Department of Radiology. SUPPORTING INFORMATION AVAILABLEAdditional information as noted in the text: a movie of the merging junction with the hydrophilic glass capillary, where CaCl 2 solution is injected into a plug containing whole blood; a movie of a single plug being followed through a microchannel as a fibrin clot formed within the plug; and characterization of the size of the aqueous plug and the carrier fluid spacing between ...

Methods Determining

Hemostasis is the complex biochemical network that controls blood clotting. We previously described a chemical model that mimicked the dynamics of hemostasis based on a simple regulatory mechanisma threshold response due to the competition between production and removal of activators. Here, we used human blood plasma in phospholipid-coated microfluidic channels to test predictions based on this mechanism. We demonstrated that, for a given geometry of channels, clot propagation from an obstructed channel into a channel with flowing blood plasma is dependent on the shear rate in the channel with flowing blood plasma. If confirmed in vivo, these results may explain clot propagation from a small vessel to a larger, clinically relevant vessel. In addition, these results would further validate the use of modular mechanisms, simplified chemical models, and microfluidics to study complex biochemical networks.

Inferior vena caval filters have been shown to be effective in the prevention of pulmonary embolism, with low morbidity and mortality associated with their implantation. Awareness of potential complications can further decrease the risk of filter placement and lead to early detection and management of complications to improve clinical outcomes. The purpose of this article is to review the procedure-related and delayed complications associated with inferior vena caval filters.

TIPS creation in thrombosed portal vein is possible and might be a treatment option in certain patients.