Thrombus Size Research Articles

TO STUDY THE CLINICAL AND ETIOPATHOLOGICAL PROFILE IN PROSTHETIC VALVE DYSFUNCTION-A SINGLE CENTRE EXPERIENCE.

Valvular heart disease affects millions has significant morbidity and mortality, further increased even after valve replacement when associated with Prosthetic valve dysfunction(PVD). The risk of Prosthetic valve thrombosis(PVT) and thromboembolic events is higher for prosthetic valve(PV) in mitral position. The annual incidence rate of PVT ranges from 0.1% to5.7%. Determining the main etiology of PVD is crucial as the treatment differs for each also its important to identify the optimal antithrombotic therapies to prevent PVD/PVT. In our observational study, 32 patients enrolled. (21)65.6% are female and (11)34.4% males with age from 20 to 66 yrs. Most PVD noted in Mitral Valve(93.8%). Non obstructive Prosthetic Valve Thrombosis is most common PVD seen in 16(50%)patients, 8(25%) had obstructive Prosthetic Valve Thrombosis, 6(18.75%) had Prosthetic Valve Endocarditis/vegetations, 2(6.25%) had pannus formation.Thromboembolic features seen in 3 patients. 12(37.5%) patients are asymptomatic, 6(18.75%) with mild dyspnea and 6(18.75%) with heart failure and shock. Mean INR is 1.58±0.6 with only 5(15.62%) on therapeutic range. The mean INR with Non obstructive PVT is 1.91±0.4 and with obstructive PVT is 1.0±0.2. 27(84.36%) on lower side of therapeutic INR and the frequency of monitoring is less. 18(56.25%) had normal PV gradient and the gradient increased in 14(43.75%) patients. The mean mitral valve (MV) gradient is 9.5±6.9, MV Vmax 2.2±0.6, MV VTI 2.5±0.6, MV PHT 158±91.9, MV EOA 1.65±0.8. Thrombus size varies from 2 to 8.1mm in diameter. 26 patients had TTK chitra valve and 6 patients with St Jude- bileaflet, and data is limited to compare both. On treatment 6 patients underwent thrombolysis, 2 reoperated, 24 heparinized and acitrom dose titred , one patient expired, 6 patients with PV endocarditis/vegetation managed with higher antibiotics and anticoagulation. Prosthetic valve dysfunction is not uncommon. Non obstructive PVT is the commonest PVD noted missed PVT results in increased mortality

The state of platelet and plasma hemostasis as a predictor of coronary blood flow in patients with acute myocardial infarction.

Aim To study the relationship of the platelet function and plasma homeostasis with the blood flow in the infarct-related artery (IRA) and with the course of acute myocardial infarction (AMI).Material and methods This study included 93 patients with AMI (75 patients with ST-elevation AMI and 18 patients without ST segment elevation). 63 patients had TIMI 0-1 blood flow in the IRA and 30 patients had TIMI 2-3. Rotational thromboelastometry, impedance aggregometry, the endothelium-dependent vasodilation (EDVD) test, and the thrombodynamics test were performed for all patients. The primary clinical endpoint included the totality of in-hospital complications of AMI, and the secondary endpoint included the totality of out-of-hospital complications of AMI. Major bleedings (BARC 3-5) and minor bleedings (BARC 1-2) were evaluated separately.Results Patients with IRA TIMI 0-1 flow were characterized by a shorter blood clotting time (BCT), larger thrombus size and density, more intense platelet aggregation induced by arachidonic acid and ADP, and lower values of the EDVD test. It was found that the parameters of platelet aggregation induced by arachidonic acid (AUC Asa) in combination with BCT allowed assessment of the severity of IRA blood flow disorder (sensitivity 76 %, specificity 71 %) in patients with AMI, regardless of the presence of ST segment elevation on the ECG. In addition, the incidence of the primary endpoint was greater in patients with IRA TIMI 0-1 flow (41.3% and 16.7%, respectively; p=0.015). In patients with TIMI 2-3 flow in the long-term period of the disease, the incidence of minor bleedings was significantly higher (8.5% and 30.4 %, respectively; p=0.045).Conclusion Compared to patients with preserved blood flow, patients with AMI and IRA TIMI 0-1 flow are characterized by endothelial dysfunction and more intense processes of thrombogenesis and platelet aggregation. It has been shown for the first time that the combination of two simple criteria for assessing hemostasis (AUC Asa; BCT) allows assessment of the degree of IRA blood flow disorder in patients with AMI.

Postoperative In-Stent Thrombus Formation Following Frozen Elephant Trunk Total Arch Repair.

ObjectivesOur aim was to investigate the occurrence and clinical consequence of postoperative in-stent thrombus formation following the frozen elephant trunk (FET) procedure.MethodsPostoperative computed tomography angiography (CTA) scans of all 304 patients following the FET procedure between 04/2014 and 11/2021 were analysed retrospectively. Thrombus size and location were assessed in multiplanar reconstruction using IMPAX EE (Agfa HealthCare N.V., Morstel, Belgium) software. Patients’ characteristics and clinical outcomes were evaluated between patients with and without thrombus formation.ResultsDuring the study period, we detected a new postoperative in-stent thrombus in 19 patients (6%). These patients were significantly older (p = 0.009), predominantly female (p = 0.002) and were more commonly treated for aortic aneurysms (p = 0.001). In 15 patients (79%), the thrombi were located in the distal half of the FET stent-graft. Thrombus size was 18.9 mm (first quartile: 12.1; third quartile: 33.2). Distal embolisation occurred in 4 patients (21%) causing one in-hospital death caused by severe visceral ischaemia. Therapeutic anticoagulation was initiated in all patients. Overstenting with a conventional stent-graft placed within the FET stent-graft was the treatment in 2 patients (11%). Outcomes were comparable both groups. Female sex (p = 0.005; OR: 4.289) and an aortic aneurysm (p = 0.023; OR: 5.198) were identified as significant predictors for thrombus development.ConclusionPostoperative new thrombus formation within the FET stent-graft is a new, rare, but clinically highly relevant event. The embolisation of these thrombi can result in dismal postoperative outcomes. More research is therefore required to better identify patients at risk and improve perioperative treatment.

Secondary ferroptosis promotes thrombogenesis after venous injury in rats

BackgroundIron accumulation significantly accelerates thrombosis after vascular injury. The role of the ferroptosis pathway induced by iron overload in thrombosis has not been previously elucidated. In this study, we answer certain obscure questions regarding the contribution of ferroptosis to deep vein thrombosis (DVT) and explore new and potential mechanisms of thrombogenesis. MethodsAfter inducing mechanical injury to establish a DVT model with rats, liproxstatin-1 (an inhibitor of ferroptosis) was administered to inhibit ferroptosis in the injured venous rat tissue. Thrombus characteristics and ferroptosis biomarkers were evaluated. Proteomic and comprehensive bioinformatics analyses were performed to elucidate the potential mechanism by which injury affects DVT. ResultsFerroptosis is characteristic of injured venous tissues and mainly manifests in tissue as increased reactive oxygen species (ROS), malondialdehyde (MDA), and iron levels and decreased glutathione (GSH) level; mitochondrial membrane potential disruption; and abnormal expression of protein markers. In this study, administration of liproxstatin-1 before injury did not affect the rate of trauma-induced thrombogenesis but affected DVT progression, as indicated by reduced thrombus size and attenuated hypercoagulability. Differences between control, DVT and liproxstatin-1 treatment predominantly affected pathways of complement/coagulation cascades, glycolysis/gluconeogenesis, ferroptosis and so on. Transferrin receptor 1 (TFRC), lipocalin 2 (LCN2) and thrombospondin 1 (THBS1) were identified as hub proteins in ferroptosis and coagulation cascades. ConclusionFerroptosis is involved in mechanical injury-induced DVT. Inhibition of ferroptosis through liproxstatin-1 treatment can ameliorate symptoms. These findings suggest a previously unknown mechanism by which ferroptosis induced by iron accumulation contributes to thrombosis.

Neutrophils Mediate Pulmonary Artery Thrombosis In Situ.

Pulmonary embolism is a life-threatening condition, which can result in respiratory insufficiency and death. Blood clots occluding branches of the pulmonary artery (PA) are traditionally considered to originate from thrombi in deep veins (usually in legs). However, growing evidence suggests that occlusion of the vessels in the lungs can develop without preceding deep vein thrombosis (DVT). In this work, we used an inferior vena cava (IVC) complete ligation model of DVT in Wistar rats to explore the possibility and mechanisms of PA thrombosis under the conditions where all routes of thrombotic mass migration from peripheral veins are blocked. We demonstrate that rats both with normal and reduced neutrophil counts developed thrombi in the IVC, although, neutropenia caused a substantial decrease in thrombus size and a shift from fresh fibrin toward mature fibrin and connective tissue inside the thrombus. Massive fibrin deposition was found in the PA branches in the majority of DVT rats with normal neutrophil counts, but in none of the neutropenic animals. Neutrophil ablation also abolished macroscopic signs of lung damage. Altogether, the results demonstrate that thrombi in the lung vasculature can form in situ by mechanisms that require local neutrophil recruitment taking place in the DVT setting.

A nitric oxide-donor pravastatin hybrid drug exerts antiplatelet and antiatherogenic activity in mice

Aim of the present study was to compare the lipid-lowering, antithrombotic and antiatherogenic properties of NCX-6550, nitropravastatin, a nitric-oxide donating derivative of pravastatin, with those of pravastatin in hypercholesterolemic mice. LDL receptor-deficient mice (LDLR–/–) on a normal diet (ND) showed enhanced cholesterol levels as compared to wild type (WT) mice (6.8±1.2 mmol/L and 2.8±0.82 mmol/L, respectively). High fat diet (HFD) induced a large enhancement of cholesterolemia in LDLR–/– mice (23.7±5.7 mmol/L, p<0.0001 vs LDLR–/– ND and WT mice. Treatment with NCX 6550 (48 mg/kg), but not with equimolar pravastatin, reduced cholesterol in LDLR–/–HFD. Platelet adhesion to collagen under high shear rate (3000 sec–1) was significantly higher in LDLR–/– than in normal mice, and further enhanced in LDLR–/–HFD (-27%, p<0.0001 vs untreated). NCX 6550 (48 mg/kg), but not pravastatin, reduced platelet adhesion, especially in LDLR–/–HFD. U46619-induced platelet aggregation ex vivo was also inhibited by NCX 6550 (48 mg/kg) but not by the parent compound. Finally, photochemically-induced acute (1 hr) femoral artery thrombosis and delayed (21 days) intimal thickening was assessed. Thrombus size was larger in LDLR–/– on HFD than in normocholesterolemic mice (0.46±0.04 vs 0.18±0.08 mg) and it was reduced by NCX 6550 (48 mg/kg) (0.08±0.02 mg, p<0.0001), but not by pravastatin (0.4±0.01 mg p=NS). Intimal thickening was greater in hypercholesterolemic than in normal mice (I/M normal=0.53±0.16, LDLR–/–=1.1±0.15, LDLR–/–HFD=1.75 ±0.25). Both NCX 6550 and pravastatin reduced intimal thickening in normal (-95% and -74.5%, respectively) and LDLR–/– mice (-98% and -91%), while in strongly hyperlipidemic animals (LDLR–/–HFD) NCX 6550 was more effective than pravastatin (-98% vs -65%, p<0.0001). NCX 6550 shows greater antithrombotic and antiatherogenic activity than pravastatin in highly hypercholesterolemic mice.

MicroRNA-136-5p from Endothelial Progenitor Cells-released Extracellular Vesicles Mediates TXNIP to Promote the Dissolution of Deep Venous Thrombosis.

Endothelial progenitor cells-released extracellular vesicles (EPCs-EVs) have previously been reported to promote the dissolution of deep venous thrombosis (DVT) through delivery of microRNA (miR). Given that, this research was projected to search the relative action of EPCs-EVs transferring of miR-136-5p in DVT. From EPCs transfected with miR-136-5p agomir or antagomir, EVs were extracted and then injected into DVT mice. Meanwhile, based on the treatment with EPCs-EVs loading miR-136-5p antagomir, silenced thioredoxin-interacting protein (TXNIP) lentivirus was injected into DVT mice to perform the rescue experiments. Afterwards, the length and weight of venous thrombosis, EPC apoptosis and inflammatory factors, plasmin, fibrinogen, and thrombin-antithrombin were measured. miR-136-5p and TXNIP expression in DVT mice, and their targeting relationship were evaluated. miR-136-5p expression was suppressed and TXNIP expression was elevated in DVT mice. EPCs-EV reduced the length and weight of venous thrombosis, suppressed cell apoptosis and inflammatory reaction, as well as elevated level of plasmin, and reduced levels of fibrinogen and thrombin-antithrombin in DVT mice. Restored miR-136-5p loaded by EPCs-EV further attenuated DVT but EPCs-EV transfer of depleted miR-136-5p resulted in the opposite consequences. miR-136-5p targeted TXNIP and silenced TXNIP rescued the effect of EPCs-EV transfer of depleted miR-136-5p on DVT. miR-136-5p from EPCs-EV suppresses TXNIP expression to reduce the thrombus size in DVT, offering a promising treatment target for DVT.

Complete primary aortic ascending thrombosis resolution after dabigatran therapy.

A 36-year-old man visited hospital with chest pain and shortness of breath since a few days. There was no medical history. Due to troponin elevation 0.07 µg/L (normal <0.04 µg/L), a triple rule out computed tomography (CT) was performed and showed an extensive thrombosis starting from the aortic arch across to the brachiocephalic artery, measuring 25 × 35 mm, irregular, polylobular, in the ascending aortic lumen, 5 cm below the aortic arch, and bilateral pulmonary embolism (Panels A and B). No clue for dissection or other wall pathologies were found, normal size of the ascending aorta, no sign of intramural haematoma, no hypercoagulable disease in the medical history, or blood investigations. Aortic ascending thrombus in a non-aneurysmal aorta is an extremely rare event and has potentially very severe complications, with a life-threatening risk of myocardial infarction and cerebral embolization. After 2 weeks of intravenous heparin administration, the CT follow-up showed no change of the thrombus size and we decided to prescribe dabigatran 150 mg b.i.d. The patient felt very well and therefore he refused surgical resection, despite of heart team consensus. After 8 weeks, we find the thrombus getting smaller in the suprasternal echocardiographic view compared with the first imaging (Video still image E and see Supplementary material online, Video S1). After 3 months, there was a complete resolution in the suprasternal echocardiographic view (Video still image F and see Supplementary material online, Video S2). The use of dabigatran leads to complete resolution and prevented the recurrence of the disease during 2-year follow-up (Panels C and D).

Surrogates of the Left Ventricular Thrombus Resolution: A Retrospective Data Review.

The left ventricular thrombus is one of the serious complications of ischemic cardiomyopathy. In this study, we aimed to search for the independent factors to predict the resolution of left ventricular thrombus. This retrospective study included all patients with coronary artery disease, aged above 18 years old, and with the thrombus at the apical location of the left ventricle. Demographic, clinical, and echocardiographic characteristics of the patients were recorded. Major adverse cardiovascular events developed within the follow-up period were recorded. The time in the therapeutic range of each patient was calculated. The presence of left ventricular thrombus beyond 180 days despite warfarin usage was classified as persistent left ventricular thrombus. The study included 174 subjects (169 males and 5 females). The mean age of the study population was 54.5 ± 11.0 years. The number of patients in whom the left ventricular thrombus resolved with treatment in less than 180 days was 56 (32.2%). Median anticoagulation time in the study population was 252 [150-480] days and the meantime in the therapeutic range of the patients was 54 ± 19%. The time in therapeutic range value of the groups was similar (P=.593). It was found that concomitant clopidogrel use (P=.003) and left ventricular thrombus area (P < .001) were the independent predictors of left ventricular thrombus resolution within less than 180 days in the logistic regression analysis. Concomitant use of clopidogrel was found to be associated with left ventricular thrombus resolution but left ventricular thrombus size was related to left ventricular thrombus persistency. Although standard 3-6 months of anticoagulation is advised for left ventricular thrombus, considering the presence of these predictors in such patients may guide the physicians to individualize the treatment.

Anticoagulation as secondary prevention of massive lung thromboses in hospitalized patients with COVID-19

Anticoagulation as secondary prevention of massive lung thromboses in hospitalized patients with COVID-19

Surrogates of the Left Ventricular Thrombus Resolution: A Retrospective Data Review.

The left ventricular thrombus is one of the serious complications of ischemic cardiomyopathy. In this study, we aimed to search for the independent factors to predict the resolution of left ventricular thrombus.This retrospective study included all patients with coronary artery disease, aged above 18 years old, and with the thrombus at the apical location of the left ventricle. Demographic, clinical, and echocardiographic characteristics of the patients were recorded. Major adverse cardiovascular events developed within the follow-up period were recorded. The time in the therapeutic range of each patient was calculated. The presence of left ventricular thrombus beyond 180 days despite warfarin usage was classified as persistent left ventricular thrombus.The study included 174 subjects (169 males and 5 females). The mean age of the study population was 54.5 ± 11.0 years. The number of patients in whom the left ventricular thrombus resolved with treatment in less than 180 days was 56 (32.2%). Median anticoagulation time in the study population was 252 [150-480] days and the meantime in the therapeutic range of the patients was 54 ± 19%. The time in therapeutic range value of the groups was similar (P=.593). It was found that concomitant clopidogrel use (P=.003) and left ventricular thrombus area (P < .001) were the independent predictors of left ventricular thrombus resolution within less than 180 days in the logistic regression analysis.Concomitant use of clopidogrel was found to be associated with left ventricular thrombus resolution but left ventricular thrombus size was related to left ventricular thrombus persistency. Although standard 3-6 months of anticoagulation is advised for left ventricular thrombus, considering the presence of these predictors in such patients may guide the physicians to individualize the treatment.

Predictors of Thrombus Dissolution in the Left Atrial Appendage in Patients with Persistent Nonvalvular Atrial Fibrillation

The aim of this study is to identify factors influencing the likelihood of the thrombus dissolution in the left atrial appendage in patients with persistent nonvalvular atrial fibrillation. Material and methods. A repeated transesophageal echocardiography was performed in 88 patients with persistent nonvalvular atrial fibrillation and with the left atrial appendage thrombus at the first transesophageal echocardiography. Results. The second transesophageal echocardiography was performed on average 30.0 (22.0; 40.0) days after the first one, the thrombus dissolution in the left atrial appendage was revealed in 60 (68.2%) patients. The multivariate logistic regression analysis showed that the chances of the thrombus dissolution increased by 5.789 (1.907–17.568) times with the thrombus size not more 25 mm, by 5.318 (1.325–21.353) times with the left atrial appendage emptying flow velocity not less 20 cm/s and 3.687 (1.229–11.059) times when prescribing the direct oral anticoagulants, and not warfarin. Combination of two or more factors give the probability of the thrombus dissolution of more than 89.6%. Conclusion. The probability of the thrombus dissolution in left atrial appendage in patients with persistent nonvalvular atrial fibrillation increases with a small thrombus size, a high the left atrial appendage emptying flow velocity, and if direct oral anticoagulants were prescribed.

Study on the dynamic changes of peripheral platelet-to-lymphocyte ratio in the prognosis of neoadjuvant chemotherapy patients with gastric cancer

Objective: To investigate the significance of platelet lymphocyte ratio (PLR) before and after neoadjuvant chemotherapy in advanced gastric cancer (AGC). Methods: The medical records of 247 AGC patients who underwent surgery between May 2015 and October 2016 were retrospectively reviewed. The relationship between PLR value and its changes before and after neoadjuvant therapy and clinicopathological features and prognosis was further analyzed. Results: △PLR was defined according to the different states of PLR before and after neoadjuvant therapy. If negative value was defined as"Reduced Group"(138) and positive value or 0 was defined as "Unreduced group"(109). There were statistical differences between the two groups of△PLR in tumor size, nerve invasion, presence or absence of vascular tumor thrombus, ypT staging, ypN staging, ypTNM staging, and pathological response (all P<0.05), but there was no statistical difference between age, gender, and postoperative adjuvant chemotherapy (all P>0.05). Survival analysis showed that the 5-year disease-free survival rates between the two groups were 39.0% and 54.0%, respectively (P=0.025); the 5-year overall survival rates between the two groups were 41.8% and 58.1%, respectively (P=0.035); the difference were statistically significant. Multivariate analysis showed that ypT3-4 stage, ypN3b stage and △PLR were independent risk factors for 5-year disease-free survival rate (HR=2.731/2.676, 95%CI: 1.026-7.268/1.014-6.985; HR=4.717, 95%CI: 1.922-11.579; HR=2.854, 95%CI: 1.117-4.124; all P<0.05) and 5-year overall survival rate (HR=3.226/2.655, 95%CI: 1.280-9.227/0.945-7.548; HR=4.550, 95%CI: 1.842-11.239; HR=2.897, 95%CI: 1.049-5.251; all P<0. 05). Conclusion: △PLR can better predict the prognosis of AGC patients receiving neoadjuvant chemotherapy.

Specific inhibition of the transporter MRP4/ABCC4 affects multiple signaling pathways and thrombus formation in human platelets.

The multidrug resistance protein 4 (MRP4) is highly expressed in platelets and several lines of evidence point to an impact on platelet function. MRP4 represents a transporter for cyclic nucleotides as well as for certain lipid mediators. The aim of the present study was to comprehensively characterize the effect of a short-time specific pharmacological inhibition of MRP4 on signaling pathways in platelets. Transport assays in isolated membrane vesicles showed a concentration-dependent inhibition of MRP4-mediated transport of cyclic nucleotides, thromboxane (Tx)B2 and fluorescein (FITC)-labeled sphingosine-1-phosphate (S1P) by the selective MRP4 inhibitor Ceefourin-1. In ex vivo aggregometry studies in human platelets, Ceefourin-1 significantly inhibited platelet aggregation by about 30-50% when ADP or collagen was used as activating agents, respectively. Ceefourin-1 significantly lowered the ADP-induced activation of integrin aIIbb3, indicated by binding of FITC-fibrinogen (about 50% reduction at 50 mM Ceefourin-1), and reduced calcium influx. Furthermore, pre-incubation with Ceefourin-1 significantly increased PGE1- and cinaciguat-induced vasodilator-stimulated phosphoprotein (VASP) phosphorylation, indicating increased cytosolic cAMP as well as cGMP concentrations, respectively. The release of TxB2 from activated human platelets was also attenuated. Finally, selective MRP4 inhibition significantly reduced both the total area covered by thrombi and the average thrombus size by about 40% in a flow chamber model. In conclusion, selective MRP4 inhibition causes reduced platelet adhesion and thrombus formation under flow conditions. This finding is mechanistically supported by inhibition of integrin aIIbb3 activation, elevated VASP phosphorylation and reduced calcium influx, based on inhibited cyclic nucleotide and thromboxane transport as well as possible further mechanisms.

The effect of Bruton's tyrosine kinase inhibitor ibrutinib on atherothrombus formation under stenotic flow conditions

BackgroundBruton's kinase (Btk) is critical for collagen-triggered platelet signal transduction. The Btk inhibitor ibrutinib has been shown to selectively block platelet adhesion to atherosclerotic plaque material under laminar arterial flow. However, this has not been studied under a shear gradient, which is characteristic for atherothrombosis. ObjectiveTo determine the effect of ibrutinib treatment on in vitro thrombus formation on collagen and atherosclerotic plaque material in the absence or presence of a shear gradient. MethodsBlood was obtained from patients with chronic lymphocytic leukemia, mantle-cell lymphoma and Waldenström macroglobulinemia with and without ibrutinib treatment and perfused through a microfluidic channel with(out) 60% stenosis over Horm type I collagen or human atherosclerotic plaque homogenate. ResultsAt a constant shear rate of 1500 s−1, platelet deposition was significantly decreased in blood from haematological malignancy patients treated with ibrutinib as compared to untreated patients, on atherosclerotic plaque material but not on collagen. However, thrombus size, stability, and height, were reduced on both plaque material and collagen. An increase in shear rate up to 3900 s−1, as induced by 60% stenosis, resulted in decreased platelet deposition and thrombus parameters on plaque material but not on collagen when compared to a laminar shear of 1500 s−1. Ibrutinib treatment decreased platelet deposition and thrombus parameters even further around the stenosis. ConclusionTreatment of patients with haematological disorders with the Btk inhibitor ibrutinib reduces in vitro platelet deposition, thrombus size and contraction on human atherosclerotic plaque around a stenosis when compared to patients not receiving ibrutinib.

Inhibition of factor Xa activity, platelet aggregation, and experimentally induced thrombosis by Sparstolonin B

Background: Sparstolonin B (SsnB) is an isocumarin compound extracted from medicinal plants such as Sparganium stoloniferum and Scirpus yagara with well documented anti-inflammatory activity. Here we examined if SsnB also possesses antithrombotic activity and the underlying mechanisms. Methods: Anti-thrombotic effects of SsnB were determined by measuring in vitro/ex vivo/in vivo clotting times, platelet aggregation assay, production and activity of factor Xa, nitric oxide, and expressions of relative proteins. Results: Treatment with SsnB prolonged the clotting time of human platelet-poor serum at concentrations comparable to the clinical anticoagulant rivaroxaban (as a positive control) and inhibited human platelet aggregation induced by adenosine diphosphate (ADP) or the thromboxane A2 analog U46619. SsnB also inhibited U46619-induced and ADP-induced phosphorylation of phospholipase C (PLC)γ2/protein kinase C (PKC) and intracellular calcium mobilization, both of which are required for platelet aggregation. In addition, SsnB inhibited expression of the cell adhesion factors P-selectin and PAC-1. SsnB increased production of the vasodilator nitric oxide and suppressed secretion of the vasoconstrictor endothelin-1 from ADP- or U46619-treated human umbilical vein endothelial cells. Further, SsnB reduced coagulation factor Xa (FXa) catalytic activity and production by endothelial cells as well as FXa-induced platelet aggregation. Conclusion: Finally, SsnB injection reduced thrombus formation time, number, size, and related mortality in mouse models of thromboembolism. SsnB is a promising antithrombotic agent targeting both FXa and platelet aggregation pathways, which can overcome the side effects of existing antithrombotic agents.

Can a negative D-Dimer Test help in ruling out the diagnosis of Cerebral Venous Thrombosis?

Background: The D-dimer test has a diagnostic role in pulmonary embolism (PE) and deep vein thrombosis (DVT). In a low-risk patient with negative D-dimer, PE or DVT can safely be ruled out. This work aims at investigating whether the D-dimer has a similar role in cerebral vein thrombosis (CVT) diagnosis. Methods: A literature review was performed in PubMed, Google scholar, and BestBETs electronic resources to identify studies published from 1996 to July 2021 that assess D-dimer&apos;s diagnostic accuracy and report its sensitivity and specificity in CVT diagnosis. The AMSTAR tool was used to assess the quality of the included studies. Results: Out of 66 non-duplicated citations, 15 articles were relevant to our clinical question. Eight articles were included in one of the retrieved meta-analyses, and four articles were excluded during data collection because of unclear results. Two systematic reviews and meta-analyses1,2 and one cohort study3 were included for the systematic review. The selection process is shown in Figure 1. The studies are reported with details of author, publication date, population details, and results are shown in Table 1. Most of the studies show that D–dimer has a high sensitivity which is estimated to be around 93% to 97% in CVT diagnosis. However, its sensitivity is affected by age, thrombus sizes, and the method used in D-dimer assay. A review shows that more CVT extension and earlier presentation, prior to 2 weeks, were correlated with higher D-dimer levels. Unfortunately, most of the studies are not high-quality studies, with variable designs, population, and reference standard tests. The studies showed that D-dimer could help predict CVT in combination with risk factors and clinical presentation. Conclusion: Normal D-dimer only should not be used to exclude CVT. There is a probability of using D-dimer in CVT risk scoring and pre-imaging negotiation, and for that purpose, larger and higher-quality studies are needed.

Continuum modeling of thrombus formation and growth under different shear rates

Obstruction of blood flow due to thrombosis is a major cause of ischemic stroke, myocardial infarction, and in severe cases, mortality. In particular, in blood wetting medical devices, thrombosis is a common reason for failure. The prediction of thrombosis by understanding signaling pathways using computational models, lead to identify the risk of thrombus formation in blood-contacting devices and design improvements. In this study, a mathematical model of thrombus formation and growth is presented. A biochemical model of platelet activation and aggregation is developed to predict thrombus size and shape at the site of vascular injury. Computational fluid dynamics using the finite volume method is employed to compute the velocity and pressure fields which are influenced by the growing thrombi. The passive transport of platelets, agonists, the platelet activation kinetics, their adhesion to the growing thrombi and embolization of platelets are solved by a fully coupled set of convection–diffusion–reaction equations. The thrombogenic surface representing blood-contacting material or injured blood vessel was incorporated into the model as a surface flux boundary condition to initiate thrombus formation. The blood is considered as a Newtonian fluid, while the thrombus is treated as a porous medium. The results are compared with in vitro experiments of a microfluidic chamber at an initial inlet venous shear rate of 200s−1 using a pressure–inlet boundary condition. The thrombus development due to agonist concentrations and change in the shear rate as well as thromboembolism for this benchmark problem is successfully computed. Furthermore, to extend the current model to a physiologically relevant configuration, thrombus formation in a blood tube is simulated. Two different heterogeneous reaction rates for platelet aggregation are used to simulate thrombus growth under a constant inlet flow rate. The findings show that the thrombus shape can be substantially altered by the hemodynamic conditions, increase in the shear rate and due to the combined effects of shear induced platelet activation and the heterogeneous reaction rates. It is also concluded that the model is able to predict thrombus formation in different physiological and pathological hemodynamics.

Neutrophil Recruitment in Arterial Thrombus and Characteristics of Stroke Patients with Neutrophil-Rich Thrombus.

Neutrophils contribute to thrombosis. However, there is limited information on the temporal course of neutrophil recruitment in thrombosis, the contribution of neutrophils to thrombus growth, and the characteristics of stroke patients with neutrophil-rich thrombi. After inducing carotid artery thrombosis in Institute of Cancer Research mice using ferric chloride, aged thrombi were produced by ligating the distal portion of the carotid artery in mice for 0.5, 1, 2, 3, 6, or 24 h. For thrombus analysis in stroke patients, we used registry data and thrombi that were obtained during intra-arterial thrombectomy. Immunohistochemistry was performed to determine thrombus composition. In the thrombi of 70 mice, Ly6G positive cell counts (neutrophils) and histone H3-positive cell counts increased in a time-dependent manner (both p<0.001). Ly6G-positive cell count was strongly correlated with histone H3-positive cell counts (r=0.910, p<0.001), but not with thrombus size (p=0.320). In 75 stroke patients, atrial fibrillation and cardioembolism were more frequent in the higher neutrophil group (32/37, 86.5%) than in the lower neutrophil group (19/38, 50%) (p=0.002). The median erythrocyte fraction was higher [52.0 (interquartile range 39.9-57.8)] in the higher neutrophil group than in the lower neutrophil group [40.3 (interquartile range 23.5-53.2)]. The fraction of neutrophils was positively correlated with that of erythrocytes (R=0.35, p=0.002). Neutrophils were recruited and increased in arterial thrombosis in a time-dependent manner; however, they were not associated with the growth of formed thrombi. Neutrophil fractions in the thrombi of stroke patients appeared to be associated with atrial fibrillation and erythrocyte fraction.

Unraveling the Mystery of Young Stroke

A 38-year-old male presented with a history of acute-onset hemiparesis 6 months back. On evaluation, he was found to have eosinophilia. Echocardiography was done which revealed a thrombus in the left atrium attached to the posterior mitral leaflet. The rest of the cardiac chambers were normal. Diagnosis of idiopathic hypereosinophilic syndrome was made after extensive evaluation. The patient was started on steroids and oral anticoagulation, following which eosinophil count and size of thrombus reduced.