Deep Vein Thrombosis (DVT) Prophylactic Team Activity to Support DVT Prevention Protocol for the Purpose of the Prophylaxis of Pulmonary Thromboembolism (PTE) and Operation.

Objective: In 2017, the Medical Accident Investigation and Support center in Japan released an analysis of acute pulmonary thromboembolism (PTE) related mortality. This recommendation called for maintaining a "team in charge of PTE's risk assessment, prevention, diagnosis and treatment" and preventing PTE through team activities. Therefore, we recommended establishing a deep vein thrombosis (DVT) prevention team. Before this recommendation, a multidisciplinary DVT prevention team was established in our hospital, with excellent outcomes. In the current study, we report the results of the DVT prevention team. Methods: Our multidisciplinary team consisted of several departments: Cardiovascular Surgery, ward nurses, medical safety managers, and clerks. The following themes were launched: 1) preparation of DVT prevention protocol; 2) preparation of DVT preventive manual; 3) regular round for evaluating DVT preventive measures; 4) staff education. The protocol's strong point was that nurses evaluated patients over 16-year-old with Wells' score for DVT on admission. We retrospectively investigated the diagnosis rate of DVT and PTE for 9 months before and after protocol operation. Results: The diagnosis rate of DVT was significantly improved after protocol implementation (before: 0.06% vs. after: 0.56%, p=0.0017). However, no significant difference was observed in the diagnosis rate of PTE before and after the protocol execution (before: 0.03% vs. after: 0.07%, p=0.98). Conclusion: Our DVT prophylactic protocol improved the diagnostic rate of DVT resulting in a decrease of PTE in our hospital. (This is a translation of Jpn J Phlebol 2019; 30(3): 285-293.).

A synthetic tryptophan metabolite reduces hemorrhagic area and inflammation after pulmonary radiofrequency ablation in rabbit nonneoplastic lungs.

PURPOSE: The purpose of this study was to determine the effect of a synthetic tryptophan metabolite, tranilast [N-(3,4-dimethoxycinnamoyl)-anthranilic acid], on inflammatory and hemorrhagic areas after pulmonary radiofrequency ablation (RFA) in rabbits. MATERIALS AND METHODS: Percutaneous RFA using a 17-gauge LeVeen electrode was performed in normal rabbit lungs. The rabbits were divided into tranilast-treated (300 mg/kg/day, orally) and control groups (n = 24/group). The effects of tranilast were evaluated using multidetector-row computed tomography (CT), histology, and immunohistochemistry immediately after RFA on days 1, 7, 14, and 28. RESULTS: Oral administration of tranilast significantly reduced the size of ablated lesions assessed using CT and histology on days 7 and 14. Furthermore, it reduced the hemorrhagic areas on day 7 and inflammatory areas on day 14, but did not affect the areas of coagulation necrosis on days 1, 7, 14, and 28. Immunohistochemical analysis showed an increase in the ratio of CD163-positive macrophage areas to rabbit macrophage (RAM11)-positive pan-macrophage areas and a decrease in the number of nuclear factor-κB-positive nuclei and CD31-positive microvessels in the tranilast group on days 7 and/or 14. CONCLUSIONS: The results suggest that tranilast modulates the repair process after pulmonary RFA through macrophage accumulation, suppression of inflammation, and angiogenesis.

Diagnostic usefulness of an amino acid tracer, α-[N-methyl-(11)C]-methylaminoisobutyric acid ( (11)C-MeAIB), in the PET diagnosis of chest malignancies.

OBJECTIVES: Although positron emission tomography (PET) using [(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) is established as one of the first-choice imaging modalities in the diagnosis of chest malignancies, there are several problems to solve in clinical practice, such as false positive uptake in inflammatory diseases. The aim of this study was to evaluate the clinical usefulness of an amino acid tracer, α-[N-methyl-(11)C]-methylaminoisobutyric acid ((11)C-MeAIB), in the diagnosis of chest malignancies, in combination with (18)F-FDG. SETTING: Fifty-nine cases (57 patients, 66 ± 12 years old) who consulted to our institution for the wish to receive differential diagnosis of chest diseases were included. Purpose of the studies were as follows: differential diagnosis of newly developed lung nodules, n = 22; newly developed mediastinal lesions, n = 20; and both, n = 17 (including lung cancer: n = 19, lymphoma: n = 1, other cancers: n = 2, sarcoidosis: n = 15, non-specific inflammation: n = 18, other inflammatory: n = 4, respectively). Whole-body static PET or PET/CT scan was performed 20 and 50 min after the IV injection of (11)C-MeAIB and (18)F-FDG, respectively. RESULTS: (11)C-MeAIB uptake of malignant and benign lesions was statistically different both in pulmonary nodules (p < 0.005) and in mediastinal lesions (p < 0.0005). In visual differential diagnosis, (11)C-MeAIB showed higher results (specificity: 73 %, accuracy: 81 %), compared to those in (18)F-FDG (60, 73 %, respectively). In cases of sarcoidosis, (11)C-MeAIB showed higher specificity (80 %) with lower uptake (1.8 ± 0.7) in contrast to the lower specificity (60 %) with higher uptake of (18)F-FDG (7.3 ± 4.5). CONCLUSIONS: (11)C-MeAIB PET/CT was useful in the differential diagnosis of pulmonary and mediastinal mass lesions found on CT. (11)C-MeAIB PET or PET/CT showed higher specificity than that of (18)F-FDG PET/CT in differentiating between benign and malignant disease. Our data suggest that the combination of (18)F-FDG and (11)C-MeAIB may improve the evaluation of chest lesions, when CT and (18)F-FDG PET/CT are equivocal.

The usefulness of (18)F-FDG PET/MRI fusion image in diagnosing pancreatic tumor: comparison with (18)F-FDG PET/CT.

PURPOSE: This study aimed at demonstrating the feasibility of retrospectively fused (18)F FDG-PET and MRI (PET/MRI fusion image) in diagnosing pancreatic tumor, in particular differentiating malignant tumor from benign lesions. In addition, we evaluated additional findings characterizing pancreatic lesions by FDG-PET/MRI fusion image. METHODS: We analyzed retrospectively 119 patients: 96 cancers and 23 benign lesions. FDG-PET/MRI fusion images (PET/T1 WI or PET/T2WI) were made by dedicated software using 1.5 Tesla (T) MRI image and FDG-PET images. These images were interpreted by two well-trained radiologists without knowledge of clinical information and compared with FDG-PET/CT images. We compared the differential diagnostic capability between PET/CT and FDG-PET/MRI fusion image. In addition, we evaluated additional findings such as tumor structure and tumor invasion. RESULTS: FDG-PET/MRI fusion image significantly improved accuracy compared with that of PET/CT (96.6 vs. 86.6 %). As additional finding, dilatation of main pancreatic duct was noted in 65.9 % of solid types and in 22.6 % of cystic types, on PET/MRI-T2 fusion image. Similarly, encasement of adjacent vessels was noted in 43.1 % of solid types and in 6.5 % of cystic types. Particularly in cystic types, intra-tumor structures such as mural nodule (35.4 %) or intra-cystic septum (74.2 %) were detected additionally. Besides, PET/MRI-T2 fusion image could detect extra benign cystic lesions (9.1 % in solid type and 9.7 % in cystic type) that were not noted by PET/CT. CONCLUSIONS: In diagnosing pancreatic lesions, FDG-PET/MRI fusion image was useful in differentiating pancreatic cancer from benign lesions. Furthermore, it was helpful in evaluating relationship between lesions and surrounding tissues as well as in detecting extra benign cysts.

Pharmacokinetic alteration of (99m)Tc-MAG3 using serum protein binding displacement method.

INTRODUCTION: When a radiopharmaceutical is simultaneously administered with a medicine that has high affinity for the same plasma protein, the radiopharmaceutical is released at higher concentrations in blood, leading to enhanced transfer into target tissues. This is known as the serum protein binding displacement method. In this study, we investigated the pharmacokinetic alteration of technetium-99m-labeled mercaptoacetylglycylglycylglycine ((99m)Tc-MAG3) using the serum protein binding displacement method. METHODS: Rat and human serum protein binding rates of (99m)Tc-MAG3 were measured by ultrafiltration with or without displacers of human serum albumin (HSA) binding sites I and II (200µM and 400µM loading). Male Wistar rats were injected with (99m)Tc-MAG3 (740kBq/0.3mL saline) via the tail vein, and biodistribution was assessed at 2, 5, 10 and 15min. Dynamic whole-body images were obtained for (99m)Tc-MAG3 (11.1MBq/0.3mL saline)-injected rats, with or without HSA displacers. RESULTS: (99m)Tc-MAG3 strongly bound to HSA (87.37%±2.13%). Using HSA site I displacers, the free fraction of (99m)Tc-MAG3 increased significantly (1.20 to 1.47 times) when compared with controls. For biodistribution and imaging, rapid blood clearance was observed with bucolome (BCL) loading, which is an HSA site I displacer. With BCL loading, peak times for rat renograms were respectively shifted from 240s to 110s, and from 170s to 120s. CONCLUSIONS: We found that (99m)Tc-MAG3 bound to the HSA binding site I. It was confirmed that pharmacokinetic distribution of (99m)Tc-MAG3 is altered by presence of BCL, which leads to increases in the free fraction of (99m)Tc-MAG3, and BCL produced rapid blood clearance and fast peak times on rat renograms. The serum protein binding displacement method using (99m)Tc-MAG3 and BCL, a safe displacer for humans, may be applicable to clinical study and lead to better diagnostic images with shorter waiting times and lower radiation doses for patients.

Loss of cellular viability in areas of ground-glass opacity on computed tomography images immediately after pulmonary radiofrequency ablation in rabbits.

PURPOSE: To determine cellular viability of lung parenchyma and neoplastic cells in areas of ground-glass opacity (GGO) on computed tomography (CT) images immediately after pulmonary radiofrequency ablation (RFA) in rabbits. MATERIALS AND METHODS: A LeVeen RFA electrode was placed percutaneously into rabbit lungs with or without metastatic VX2 tumors. Five minutes later, seven isolated lungs were imaged by use of a multi-detector row CT scanner, and the images were compared with histological features. The cellular viability of the lung tissues was assessed by nicotinamide adenine dinucleotide hydrogen (NADH) staining in eight normal lungs and in three lungs with multiple metastatic tumors. RESULTS: All lung lesions appeared as bilayered structures with a central, dense, attenuated area and an outer area of GGO on CT images, and as three-layered structures on macroscopic and microscopic images 5 min after RFA. The GGO areas approximately corresponded to the outer two layers in macroscopic images that were exudative and congestive on microscopic images. Staining for NADH was significantly reduced in the GGO and densely attenuated areas with or without tumor tissue staining compared with the non-ablated area. CONCLUSIONS: Our results suggest that an area of GGO that appears on CT immediately after RFA can be effectively treated by RFA.

The agreement of left ventricular function parameters between (99m)Tc-tetrofosmin gated myocardial SPECT and gated myocardial MRI.

OBJECTIVE: The aim is to compare and evaluate the agreement of quantification of left ventricular functional parameters obtained by two different methods, (99m)Tc-tetrofosmin gated myocardial perfusion SPECT (MPS) and cardiac magnetic resonance imaging (CMR). METHODS: Ten healthy male volunteers participated. Gated MPS data were acquired using 32 frames, which were also combined into 16- and 8-frame data set for the investigation. Gated CMR data were acquired using 8, 16 and 32-frame for the different sets. All examinations were conducted in resting and at exercise conditions. Quantitative measurements of end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular ejection fraction (LVEF), peak ejection rate (PER), peak filling rate (PFR) and time to peak filling (TTPF) were done for each study, respectively. Finally, we evaluated the concordance of parameters between gated MPS and gated CMR by % difference and Bland-Altman plot analysis. RESULTS: LVEF showed favorable concordance in both rest and exercise conditions (% differences were around 10%). PER, PFR and TTPF also showed good concordances in rest conditions, under 32-frame gated collections particularly (% differences were around 10%). In exercise conditions, although the concordances were relatively good, certain variances were noted (% differences were around 20-25%). Regarding left ventricular volumes, the concordance were worse in both conditions (% differences were around 30-40%). CONCLUSIONS: In quantifying of left ventricular function parameter, gated CMR provides similar quantitative values comparing with gated MPS except for ventricular volumes in rest conditions. In contrast, there were certain variations except for LVEF in exercised examinations. When we follow patients by the same cardiac parameters with CMR and MPS, using parameters across the two modalities proved to be possible under rest condition. However, it is limited at exercise condition.

Comparison of diagnostic and prognostic capabilities of ¹8F-FDG-PET/CT, ¹³¹I-scintigraphy, and diffusion-weighted magnetic resonance imaging for postoperative thyroid cancer.

PURPOSE: The first aim of this study was to compare the detectability of metastasis of postoperative differentiated thyroid cancer (DTC) among (131)I whole body scintigraphy (IWBS), fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), and diffusion-weighted magnetic resonance imaging (DWI). The second aim was to clarify the association between the image pattern and prognosis. MATERIALS AND METHODS: We evaluated 70 postoperative DTC patients on both a patient basis and an organ basis (lymph nodes, lung, bone), and we analyzed the correlation between the image pattern and the prognosis. RESULTS: For the patient-basis analysis, the detectability by IWBS, PET/CT, and DWI was 67.1%, 84.2%, and 57.6%, respectively. IWBS provided complementary information to that provided by PET/CT in 11 of 70 (15.7%) cases. For the organ-basis analysis, IWBS was the best detector for lymph node metastasis (72.4%). PET/CT was superior to IWBS for detecting metastasis of bone (85.7% vs. 71.4%) and lung (94.1% vs. 62.7%). For the correlation analysis, PET and DWI positivity were the factors predicting a poor prognosis. CONCLUSION: PET/CT was the best modality for detecting metastases in postoperative DTC patients, although IWBS provided complementary information. Because PET/CT and DWI gave similar information (e.g., positivity) suggesting poor prognoses, the combination of IWBS and DWI might be the method of choice for monitoring postoperative DTC.

MR signal change in venous thrombus relates organizing process and thrombolytic response in rabbit.

Venous thrombus is subsequently organized and replaced by fibrous connective tissue. However, the sequential changes in venous thrombi are not reliably detected by current noninvasive diagnostic techniques. The purpose of this study is to reveal whether magnetic resonance (MR) can detect venous thrombus, define thrombus age and predict thrombolytic responses. Thrombus in the rabbit jugular vein was imaged with a 1.5-T MR system at 4 h and at 1, 2 and 4 weeks using three-dimensional (3D) fast asymmetric spin echo T2-weighted (T2W) and 3D-gradient echo T1-weighted (T1W) sequences. The jugular veins were histologically assessed at each time point. Magnetic resonance imaging (MRI) was also performed in vivo before and 30 min after tissue plasminogen activator (t-PA) administration. The thrombi in MRI were comparable in size to histological sections. The signal intensity (SI) of thrombi at 4 h was heterogeneously high or low on T2W or T1W images, respectively. The SI of thrombi on T2W images decreased time-dependently, but increased on T1W images at 1 and 2 weeks. Morphological analysis showed time-dependent decreases in erythrocyte, platelet and fibrin areas and time-dependent increases in smooth muscle cell, macrophage, collagen and iron areas. The t-PA administration significantly decreased thrombus volume at 4 h but not at 1, 2 and 4 weeks. Venous thrombosis can be reliably and noninvasively detected by MRI. Measurement of SI might support assessments of thrombus age and thrombolytic response.

MR and US imaging for breast cancer patients who underwent conservation surgery after neoadjuvant chemotherapy: comparison of triple negative breast cancer and other intrinsic subtypes.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is commonly utilized to treat operable breast cancer. The purpose of this study was to review the findings of ultrasonography (US) and magnetic resonance (MR) imaging in patients treated with breast conservation surgery (BCS) after NAC with a focus on intrinsic subtypes. METHODS: Eighty-six patients underwent BCS after NAC. The tumors were classified into four subgroups by receptor status. US and MR were performed before and after NAC. The tumor diameters in US and MR after NAC were examined for correlations with pathological tumor distances in the specimens from BCS after NAC. RESULTS: The correlation coefficient (r) of US to pathological tumor size was 0.3 in all tumors, 0.6 in HER2-type tumors, and 0.7 in triple negative breast cancers (TNBC). The correlation coefficient of tumor size in MR to pathological tumor size was 0.9 in TNBC, and other correlations were not statistically significant. CONCLUSIONS: The correlation between tumor size in MR and pathological tumor size in triple negative breast cancers corresponded best. This information is one of the clues to selecting patients for BCS after NAC.

Predictive value of Tc-99m galactosyl human serum albumin liver SPECT on the assessment of functional recovery after partial hepatectomy: a comparison with CT volumetry.

OBJECTIVE: Predicting liver functional reserve is important before partial hepatectomy. However, it is difficult to predict using morphologic imaging modalities, such as CT and MRI. In this study, we assess the usefulness of galactosyl human serum albumin (GSA) scintigraphy in predicting liver function recovery. METHODS: We performed 99mTc-GSA scintigraphy before operation in 56 patients. Each patient was administered 185 MBq of 99mTc-GSA by intravenous injection. Serial images were taken immediately after the administration for 40 min. SPECT images were obtained to make a functional map. We calculated the functioning parameter residual GSA-Rmax (GSA-RL) using analysis software developed by Dr.N. Shuke. In addition, we compared GSA-RL with the morphological parameter residual liver volume (RLV-CT) calculated by conventional CT and serum albumin (Alb) or cholinesterase (ChE). We analyzed the correlation between imaging parameters and the postoperative recovery periods of serum albumin (r-Alb) and cholinesterase (r-ChE) and the values at 1 and 3 months for serum albumin (1M-Alb, 3M-Alb) and cholinesterase (1M-ChE, 3M-ChE). RESULTS: We found significant correlations between GSARL and r-Alb, r-ChE, 1M-Alb, 3M-Alb, 1M-ChE and 3M-ChE, but not between RLV-CT and the same parameters. CONCLUSION: The GSA-RL calculated by 99mTc GSASPECT was a useful parameter for predicting postoperative liver function recovery that should be implemented before partial hepatectomy.

The reproducibility of deep-inspiration breath-hold (18)F-FDG PET/CT technique in diagnosing various cancers affected by respiratory motion.

BACKGROUND: The deep-inspiration breath-hold PET/CT (DIBH PET/CT) technique improves the limitations of diagnosing a lesion located in an area influenced by respiratory motion that results in spatial misregistrations caused by respiration between PET and CT. However, its reproducibility with regard to calculating the maximal standardized uptake value (SUV(max)) and metabolic volume (MV) in DIBH PET/CT has not been elucidated. OBJECTIVE: The purpose of this study was to investigate the reproducibility of the DIBH PET/CT technique including calculating the SUV(max) and the MV. METHODS: Sixty patients with various cancers were enrolled. The subjects had 47 abdominal lesions and 28 chest lesions. All patients demonstrated a misregistered image in the early whole-body image taken 50 min after FDG intravenous infusions. We added the delayed spot images 40 min after the first image. On the delayed image, we performed both conventional techniques with non-breath-hold (NBH) and the DIBH technique. In the four times DIBH technique, we obtained the coefficient of variance (CV) in calculating these indices for evaluating reproducibility. RESULTS: The SUV(max) value with DIBH showed an increase of 16.1-60.1% compared with that measured by NBH. The mean value of CV was 5.5 in thoracic lesions and 6.3 in abdominal lesions. The values of MV with DIBH showed a decrease of 14.0-20.1% compared with those measured by NBH. Regarding reproducibility, mean value of CV was 7.1 in thoracic lesions and 11.9 in abdominal lesions. CONCLUSION: The DIBH technique improves the inaccurate quantification of both SUV(max) and MV. Although the CV value of SUV(max) with DIBH technique is better in thoracic lesions compared with that in abdominal lesions, the reproducibility was acceptable.

[Usefulness of metabolic volume and total lesion glycolysis for predicting therapeutic response in cancer therapy by 18F-FDG PET/CT].

PURPOSE: The current study was done to evaluate the usefulness of predicting capability of FDG PET/CT indices in therapeutic response of malignant tumor. METHODS: Series of FDG PET/CT were performed at both pre- and after therapy for 70 lesions of 58 patients with malignant tumor. Three months after the 2nd PET/CT, follow up CT was performed for determining the final therapeutic effect. We calculated various indices including SUVmax, the metabolic volume (MV) and the total lesion glycolysis (TLG). We calculated four kinds of indices, TLG50, TLG75, MV50 and MV75 based on the different threshold. Then we calculated deltaSUVmax, deltaMV50, deltaMV75, deltaTLG50 and deltaTLG75 from a change of these indices. Finally, we compared the predictive capability of these five indices in therapeutic response of malignant tumor. RESULTS: In the cancer therapy effect prediction, both deltaTLG75 and deltaTLG50 were significantly higher than SUVmax by using receiver operating-characteristic (ROC) curve analysis. The prognostic capability of deltaSUVmax for therapeutic response with sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 85.7%, 59.5%, 58.5%, 86.2% and 70.0%; deltaTLG75 96.4%, 69.0%, 67.5%, 96.7% and 80.0%; and deltaTLG50 96.4%, 76.2%, 73.0%, 97.0% and 84.3%, respectively. By the use of deltaTLG75 or deltaTLG50, the predictive ability for therapeutic response improved significantly compared to that by the use of deltaSUVmax. CONCLUSION: In the prediction for therapeutic response of various cancers by using FDG PET/CT, Total lesion glycolysis (TLG) was the most useful index.

Atherosclerotic lesions rich in macrophages or smooth muscle cells discriminated in rabbit iliac arteries based on T1 relaxation time and lipid content.

RATIONALE AND OBJECTIVES: Atherothrombosis usually occurs on macrophage- and lipid-rich unstable plaque, but rarely on smooth muscle cell (SMC)-rich stable plaque. Magnetic resonance imaging (MRI) has been extensively applied for noninvasive vascular imaging. We therefore investigated whether MRI provides valuable information about the characteristics of atherosclerotic vessels using rabbit models of macrophage-rich or SMC-rich atherosclerotic arteries. MATERIALS AND METHODS: Rabbits were fed with a conventional (CD group, n = 3) or 0.5% cholesterol (ChD group, n = 3) diet for 1 week before and 3 weeks after balloon injury of the left iliac arteries. Three weeks later, these arteries were investigates by 1.5 T MRI and by conventional angiographic imaging, followed by histological and immunohistochemical analyses. RESULTS: Three weeks after balloon injury, injured iliac arteries of both groups formed neointima with luminal stenosis. Conventional and MRI angiographic findings of the luminal diameter significantly and positively correlated. T1 relaxation time was significantly shorter and the lipid content was much higher in injured arteries from the ChD than from the CD group. The injured arteries from the ChD also contained more macrophages and less SMCs that those from the CD group. The T1 relaxation time and lipid content in injured arteries negatively and positively correlated with the degree of macrophage accumulation, respectively. CONCLUSION: These results showed that MRI could provide valuable information about luminal stenosis and the characteristics of atherosclerotic vessels in rabbits.

Factor VIII contributes to platelet-fibrin thrombus formation via thrombin generation under low shear conditions.

INTRODUCTION: Thrombus growth under low blood flow velocity plays an important role in the development of deep venous thrombosis (DVT). Increased plasma levels and activities of coagulation factor VIII (FVIII) comprise risk factors for DVT and pulmonary thromboembolism. OBJECTIVE: To localize FVIII in human venous thrombi of DVT and to determine whether FVIII contributes to thrombus formation under low shear conditions. METHODS: The localization of FVIII in venous thrombi obtained from patients with DVT was examined by immunohistochemistry. The role of FVIII in thrombus formation was investigated using a flow chamber system. Venous blood from healthy volunteers were incubated with an anti-FVIII monoclonal antibody (VIII-3776) or non-immunized mouse IgG(1). Blood samples were perfused on immobilized type III collagen at wall shear rates of 70/s and 400/s and then the surface area covered by platelets and fibrin was morphometrically evaluated. Prothrombin fragment 1+2 (PF1+2) generation was measured before and after perfusion. RESULTS: Venous thrombi of DVT comprised a mixture of platelets, fibrin and erythrocytes. Factor VIII appeared to be colocalized with glycoprotein IIb/IIIa, fibrin and von Willebrand factor in the thrombi. VIII-3776 specifically recognized the light chain of FVIII and prolonged the activated partial thromboplastin time (aPTT), but not prothrombin time (PT). The antibody significantly reduced platelets and fibrin covering, as well as PF1+2 generation at wall shear rates of 70/s and 400/s. CONCLUSIONS: These results suggest that FVIII contributes to platelet aggregation and fibrin formation via thrombin generation under low shear conditions.