A numerical model of thrombosis/thromboembolism (T/TE) is presented that predicts the progression of thrombus growth and thromboembolization in low-shear devices (hemodialyzers, oxygenators, etc.). Coupled convection-diffusion-reaction equations were solved to predict velocities, platelet agonist (ADP, thromboxane A2, and thrombin) concentrations, agonist-induced and shear-induced platelet activation, and platelet transport and adhesion to biomaterial surfaces and adherent platelets (hence, thrombus growth). Single-platelet and thrombus embolization were predicted from shear forces and surface adhesion strengths. Values for the platelet-biomaterial reaction constant and the platelet adhesion strength were measured in specific experiments, but all other parameter values were obtained from published sources. The model generated solutions for sequential time steps, while adjusting velocity patterns to accommodate growing surface thrombi. Heparinized human blood was perfused (0.75 ml/min) through 580 microm-ID polyethylene flow cells with flow contractions (280 microm-ID). Thrombus initiation, growth, and embolization were observed with videomicroscopy, while embolization was confirmed by light scattering, and platelet adhesion was determined by scanning electron microscopy. Numerical predictions and experimental observations were similar in indicating: 1) the same three thrombotic locations in the flow cell and the relative order of thrombus development in those locations, 2) equal thrombus growth rates on polyethylene and silicon rubber (in spite of differing overall T/TE), and 3) similar effects of flow rate (1.5 ml/min versus 0.75 ml/min) on platelet adhesion and thrombosis patterns.

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Cold-induced platelet aggregation (CIPA) in PRP has previously been documented in connection with platelet preservation (4±15°C). This report describes hypothermia-induced platelet aggregation (HIPA) in whole blood and at temperatures used in open-heart surgery (24±32°C). HIPA (speci®cally, the formation of occlusive aggregates) was studied in human whole blood. Fresh heparinized (1.5 U/ml) human blood was cooled and maintained at target temperatures (15, 20, 24, 28, 32, or 37°C) as it¯owed (1 ml/min) through 75-cm long 1/32" internal diameter polymer conduit. The formation of aggregates in the tubing was veri®ed using optical video microscopy and was quanti®ed by a lightscattering method and a constant-pressure ®ltration method. Donors were tested at least twice at each target temperature and were classi®ed into three separate response regimes (Low, Medium, and High) on the basis of the number of aggregates and the duration of their appearance. The screening of 121 donors (average age 22.3 4.3 years) for HIPA at 24°C (the temperature of maximum response) indicated 14% High Responders, 18% Medium Responders, and 68% Low Responders. HIPA was inhibited by EDTA, citrate, PGE 1 , and Tiro®ban, but not by aspirin, and it was enhanced by elevated heparin levels. HIPA was consistently noted in the blood of a subpopulation of donors, and the associated platelet aggregates in the blood of High Responders were rigid and occlusive. It is postulated that such aggregates may contribute to cognitive dysfunction noted in patients undergoing hypothermic open-heart surgery, and that postulus is being investigated. Am.

In vitro stent-induced thromboembolism was altered by the presence of residual stenoses placed upstream or placed upstream and downstream of the stent. Heparinized (3 micro/ml) bovine blood was gravity fed through a conduit with a deployed coronary stent. Embolism was continuously monitored using a light-scattering microemboli detector, and the thrombus accumulated on the stent at the conclusion of the experiment was assessed gravimetrically. Gaussian stenoses (75% reduction in the cross-sectional area) were placed upstream or upstream and downstream of the stent to alter flow characteristics in the stent region. The presence of stenoses enhanced embolization from the stent in all cases, while end-point thrombus accumulation on the stent decreased with only an upstream stenosis present, and increased when upstream and downstream stenoses were present. Computational fluid dynamics with and without hypothetical model thrombi were used to ascertain the alterations in the flow environment caused by the stenoses and thrombi. Combining the computed hemodynamic parameters with experimental results indicated that increased radial transport of blood components and low wall shear stress provided by the stenoses and thrombi may explain the enhancement of end-point thrombus accumulation. Analysis further showed that thrombi growing at the stenosis-induced reattachment and separation points will be subjected to high shear forces which may explain the increased embolism when stenoses are present.

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