Lysis Of Thrombus Research Articles

Relationship between lipoprotein(a) and endogenous fibrinolytic status in patients with STEMI

Abstract Background The risk of myocardial infarction is at least doubled in individuals with lipoprotein(a) (Lp[a]) levels >90th percentile.[1] Lp(a) may exert pro-thrombotic effects by impairing fibrinolysis. Lp(a) has a high degree of homology to plasminogen and can competitively inhibit tissue plasminogen activator (tPA)-mediated plasminogen activation and tPA-mediated clot lysis.[2] Furthermore, Lp(a) stimulates the activity of plasminogen activator inhibitor-1, the major inhibitor of the fibrinolytic system. In patients with ST-segment elevation myocardial infarction (STEMI), impaired endogenous fibrinolysis is a strong, independent risk factor for recurrent cardiovascular events,[3] but the drivers of this are not fully understood. Whether impaired endogenous fibrinolysis is related to increased Lp(a) levels in patients with STEMI, is not known. Purpose We aimed to assess the relationship between Lp(a) and endogenous fibrinolysis in patients with STEMI. Methods In a prospective, observational study, venous blood samples were drawn from patients presenting with STEMI immediately before revascularisation, after dual antiplatelet therapy but before heparin administration. Endogenous fibrinolysis was measured immediately in non-anticoagulated whole blood using the point-of-care Global Thrombosis Test, which measures the time for occlusive thrombus formation under high shear (occlusion time) and the time for spontaneous lysis of the thrombus (lysis time).[3] Assessment of Lp(a) levels, measured by particle enhanced immunoturbidimetric assay, was performed with paired plasma samples, standardized against the International Federation of Clinical Chemistry reference material SRM2B for nmol/L. Lp(a) >32 nmol/L is associated with increased risk of ischaemic heart disease. Results A total of 80 patients were included (age 64±14y, 25% females and 86% Caucasian). There was a positive correlation between Lp(a) level and lysis time (r = 0.330, P = 0.003) (Figure 1). Lysis time was significantly longer in patients with Lp(a) >32 nmol/L (2782 [1626-3683] vs. 1725 [1259-2955] s, P = 0.044). Using a cut-point of lysis time ≥2500 s previously associated with a significantly increased cardiovascular risk in patients with STEMI, we showed that Lp(a) was significantly higher in patients with lysis time ≥2500 s (40 (22-111) vs. 18 (7-73) nmol/L, P = 0.045). Table 1 shows the relationship between clinical characteristics and Lp(a) and lysis time. Lp(a) level was higher in non-Caucasian patients. There was no correlation between Lp(a) and occlusion time (r = 0.156, P = 0.168). Conclusion In patients with STEMI, longer endogenous fibrinolysis time is related to higher Lp(a) level. Raised Lp(a) levels may, in part, contribute to impaired endogenous fibrinolysis. Future studies are required to assess whether reduction in Lp(a) with novel therapies currently in phase 3 trials can favourably modulate fibrinolysis and improve clinical outcomes.Figure 1

Clinical case of successful thrombolysis in a newborn with thrombosis of the left renal vein

Thrombosis occurring in the neonatal period is a nosology with a large number of complications, often leading to disability and death. This article highlights the successful treatment of a newborn child with renal vein thrombosis using systemic thrombolysis. A clinical case of successful systemic thrombolysis in a full-term boy in the early neonatal period with thrombosis of the left renal vein and transition of the floating part of the thrombus to the inferior vena cava is presented. A child aged 3 days was admitted to the neonatal intensive care unit from a maternity hospital, where thrombosis was suspected. Gross hematuria was observed. Laboratory data revealed thrombocytopenia and increased levels of fibrinogen and D-dimer. Ultrasound showed a sharp increase in the volume of the left kidney, a diffuse change in its parenchyma, a sharp depletion of blood flow, and accumulation of fluid in the perinephric tissue on the left, and a thrombus was observed in the lumen of the left renal vein with the presence of a floating part extending into the inferior vena cava. Thrombolytic therapy with the drug alteplase was started in combination with an infusion of unfractionated heparin. Doses were selected based on coagulogram parameters. On day 2 of therapy, hematuria resolved. On day 4 of therapy, the alteplase infusion was completed, and heparin therapy was continued. On day 13, the child was switched to a low-molecular-weight-heparin therapy. Dynamic ultrasound revealed size reduction, recanalization and further thrombus lysis, and normalization of intrarenal blood flow and kidney size. No renal dysfunction was recorded during observation. The child was transferred to the further care unit at aged 14 days and was discharged home at the age of 25 days in satisfactory condition on ongoing anticoagulant therapy under outpatient supervision of a hematologist. During follow-up observation at aged 1.5 months of life, no clinical, laboratory, and ultrasound indicators of renal function disorders were noted. Currently, there are no approved recommendations and protocols for individual thrombosis in newborns, although this particular age group is due to the vulnerability of hemostasis to the development of a thrombotic process.

Comparison of standard and global hemostasis assays in cord and peripheral blood of newborns.

Umbilical cord blood is used for the testing of various parameters in newborns. However, data on its applicability for hemostasis assays is insufficient. To evaluate whether umbilical cord blood can be used for standard tests, thromboelastometry and thrombodynamics for preterm and term newborns. 187 newborns were included in the study. Blood was taken from the umbilical cord and by venipuncture of the newborn. Clotting times, fibrinogen, D-dimer, thromboelastometry and thrombodynamics were measured. Clotting times and fibrinogen indicated a hypocoagulable shift, while thromboelastometry and thrombodynamics showed a hypercoagulable shift in hemostasis in umbilical cord blood compared to newborn blood. D-dimer indicated an enhanced process of thrombus lysis in newborn blood compared to cord blood. Collecting blood into a tube with the addition of a contact pathway inhibitor did not significantly change the global assay parameters in either umbilical cord blood or newborn blood. In the thrombodynamics assay, spontaneous clotting was detected but suppressed by the addition of a tissue factor inhibitor. Hemostasis in cord and newborn blood differs for both global and standard tests. Hypercoagulability in newborns registered with the global assay thrombodynamics is associated with the presence of tissue factor in the blood. 1. We found a hypercoagulation shift in newborns compared with the adult references, possibly due to the presence of tissue factor in blood. 2. Blood coagulation is enhanced in cord blood compared with blood sampled from the vein of a newborn according to thromboelastometry and thrombodynamics assays. 3. Clotting times and fibrinogen concentrations in cord blood differ from these parameters in newborn blood. 4. Studying of the (patho)physiological features of hemostasis in newborns should consider differences in cord blood and vein sampled blood.

Purification and Characterization of a Small Thermostable Protease from Streptomyces sp. CNXK100.

Proteases derived from Streptomyces demonstrate numerous commendable properties, rendering it extensively applicable in biotechnology and various industrial sectors. This study focused on the purification and characterization of the thermostable protease obtained from Streptomyces sp. CNXK100. The purified protease exhibited an estimated molecular weight of 27 kDa, with optimal activity at 75°C and pH 8.0. Notably, the enzyme remained active even without any metal ions and fully active in the presence of Na+, K+, Mg2+, and Cu2+metal ions. The kinetic parameters were determined with a KM value of 3.13 mg/ml and a Vmax value of 3.28 × 106 U/mg. Furthermore, the protease has demonstrated notable stability when subjected to a treatment temperature of up to 65°C for 60 minutes, and across a broad pH range extending from 5.0 to 10.0. This protease also demonstrated resilience against a spectrum of harsh conditions, including exposure to organic solvents, surfactants, bleaching agents, and proteolytic enzymes. Additionally, the enzyme maintained its activity following treatment with commercial detergents, accomplishing complete thrombus lysis at a concentration of 2.50 mg/ml within 4 hours. Remarkably, the protease exhibited stability in terms of activity and protein concentration for 70 days at 4°C. These findings underscore the potential industrial applications of the thermostable protease from Streptomyces sp. CNXK100.

R-tPA Resistance Is Specific for Platelet-Rich Stroke Thrombi and Can Be Overcome by Targeting Nonfibrin Components.

Resistance to r-tPA (recombinant tissue-type plasminogen activator) is a well-known but poorly understood phenomenon that hampers successful recanalization in patients with acute ischemic stroke. Using clinically relevant thrombi from patients with acute ischemic stroke, we investigated if and how thrombus composition impacts r-tPA-mediated lysis. In addition, we explored strategies to overcome r-tPA resistance. Thrombi were split into 2 parts, 1 of which was used for thrombolysis and the other for detailed histological analysis. Thrombolysis was performed in normal human plasma using r-tPA alone, using r-tPA in combination with DNase-1 or using r-tPA in combination with N,N'-diacetyl-l-cystine. Thrombus lysis was calculated as the percentage of residual thrombus weight compared with its initial weight and the degree of lysis was linked to thrombus composition determined via histology. Interestingly, we found that the efficacy of r-tPA-mediated thrombolysis was strongly correlated with the composition of the thrombi. Thrombi containing high amounts of red blood cells and low amounts of DNA and von Willebrand Factor were efficiently degraded by r-tPA, whereas thrombi containing low amounts of red blood cells and higher amounts of DNA and von Willebrand Factor were resistant to r-tPA. Importantly, combination of r-tPA with DNase-1 or N,N'-diacetyl-l-cystine significantly and specifically improved the lysis of these r-tPA-resistant thrombi. Using patient thrombus material, our results for the first time show that the composition of stroke thrombi largely determines their susceptibility to r-tPA-mediated thrombolysis. Red blood cell-poor thrombi have a specific resistance to r-tPA, which can be overcome by targeting nonfibrin components using DNase-1 or N,N'-diacetyl-l-cystine.

Chemical Adjustment of Fibrinolysis.

Fibrinolysis is the process of the fibrin-platelet clot dissolution initiated after bleeding has been stopped. It is regulated by a cascade of proteolytic enzymes with plasmin at its core. In pathological cases, the balance of normal clot formation and dissolution is replaced by a too rapid lysis, leading to bleeding, or an insufficient one, leading to an increased thrombotic risk. The only approved therapy for emergency thrombus lysis in ischemic stroke is recombinant tissue plasminogen activator, though streptokinase or urokinase-type plasminogen activators could be used for other conditions. Low molecular weight compounds are of great interest for long-term correction of fibrinolysis dysfunctions. Their areas of application might go beyond the hematology field because the regulation of fibrinolysis could be important in many conditions, such as fibrosis. They enhance or weaken fibrinolysis without significant effects on other components of hemostasis. Here we will describe and discuss the main classes of these substances and their mechanisms of action. We will also explore avenues of research for the development of new drugs, with a focus on the use of computational models in this field.

Role of factor XIII in ischemic stroke: a key molecule promoting thrombus stabilization and resistance to lysis

BackgroundActive coagulation factor XIII (FXIII) catalyzing crosslinking of fibrin and other hemostatic factors plays a key role in clot stability and lysis. ObjectivesTo evaluate the effect of FXIII inhibition in a mouse model of ischemic stroke (IS) and the role of activated FXIII (FXIIIa) in clot formation and lysis in patients with IS. MethodsA ferric chloride IS murine model was performed before and after administration of a FXIIIa inhibitor (FXIIIinh). Thromboelastometry in human and mice blood was used to evaluate thrombus stiffness and lysis with FXIIIinh. FXIIIa-dependent fibrin crosslinking and lysis with fibrinolytic drugs (tissue plasminogen activator and tenecteplase) were studied on fibrin plates and on thrombi and clotted plasma of patients with IS. Finally, circulating and thrombus FXIIIa were measured in 85 patients with IS. ResultsFXIIIinh administration before stroke induction reduced infarct size, α2-antiplasmin (α2AP) crosslinking, and local microthrombosis, improving motor coordination and fibrinolysis without intracranial bleeds (24 hours). Interestingly, FXIII blockade after stroke also reduced brain damage and neurologic deficit. Thromboelastometry in human/mice blood with FXIIIinh showed delayed clot formation, reduced clot firmness, and shortened tissue plasminogen activator lysis time. FXIIIa fibrin crosslinking increased fibrin density and lysis resistance, which increased further after α2AP addition. FXIIIinh enhanced ex vivo lysis in stroke thrombi and fibrin plates. In patients with IS, thrombus FXIII and α2AP were associated with inflammatory and hemostatic components, and plasma FXIIIa correlated with thrombus α2AP and fibrin. ConclusionOur results suggest a key role of FXIIIa in thrombus stabilization, α2AP crosslinking, and lysis resistance, with a protective effect of FXIIIinh in an IS experimental model.

Relationship between intrathrombotic appearance of HSP27 and HSP70 and thrombus ages in a murine model of deep vein thrombosis

Heat shock proteins (HSPs) are molecular chaperones whose primary function is cytoprotection, supporting cell survival under (sub) lethal conditions. They have been implicated in various diseases such as inflammatory diseases and cancer due to their cytoprotective and immunomodulatory effects, and their biological mechanisms have been studied. Central family members include, HSP27, which is induced by various stimuli such as heat shock, hypoxia, hyperoxia, ultraviolet exposure, and nutritional deficiency, and HSP70, which is homeostatically expressed in many organs such as the gastrointestinal tract and has anti-cell death and anti-inflammatory effects. In this study, HSP27 and HSP70 were investigated during thrombus formation and dissolution in a deep vein thrombosis model by immunohistochemistry to determine their involvement in this process and whether their expression could be used as a forensic marker. In the process of thrombus formation and lysis, HSP27 and HSP70 were found to be expressed by immunohistochemical analysis. The role of inhibitors of HSP27 and HSP70 in the pathogenesis of thrombosis in mice was also investigated. When HSP27 or HSP70 inhibitors were administered, thrombi were significantly smaller than in the control group on day 5 after inferior vena cava ligation, indicating pro-thrombotic effects HSP27 and HSP70. If HSP27- or HSP70-positive cells were clearly visible and easily identifiable in the thrombus sections, the thrombus was presumed to be more than 10 days old. Thus, the detection of intrathrombotic HSP27 and HSP70 could forensically provide useful information for the estimation of thrombus ages. Collectively, our study implied that both HSP27 and HSP70 might be molecular targets for thrombus therapy and that the detection of HSP-related molecules such as HSP27 and HSP70 could be useful for the determination of thrombus ages.

Left ventricular thrombosis with peripheral embolization in several vascular zones – clinical case

We present a clinical case of a 49-year-old man admitted in severe general condition and echocardiographic evidence of a thrombotic mass in the left ventricle. Due to a peripheral embolization clinic, catheter-directed thrombolysis (CDT) followed by anticoagulant therapy was performed. This resulted in lysis of the left ventricular thrombus and reperfusion of the emboli in the peripheral arteries. Due to residual occlusion of the left anterior tibial artery, amputation of the front part of the foot of the left lower limb was required. As a result of the treatment, stabilization of the patient’s condition and withdrawal of the amputation line as distal as possible was achieved. The patient had severe left ventricular systolic dysfunction and highgrade mitral regurgitation, necessitating discussion of further management.

Plasma D-dimer as a biomarker for the early classification of common acute ischemic stroke subtypes in Indonesia

BackgroundD-dimer is a well-known marker for abnormal hemostasis in acute ischemic stroke (AIS), indicating the presence of fibrin degradation due to thrombus formation and lysis. The diagnostic performance of D-dimer for different AIS types in the Indonesian population has not been established. The aim of this study is to compare the plasma D-dimer levels in three of the most common AIS subtypes in Indonesia; the cardioembolic, large artery atherosclerosis (LAA), and small-vessel occlusion (SVO), and to determine its most optimal diagnostic performance.ResultsIn this cross-sectional study, 64 subjects with confirmed AIS diagnosis at the Wahidin Sudirohusodo General Hospital Makassar between June and October 2019 were recruited. Plasma D-dimer levels were measured and grouped according to the subtype of acute ischemic stroke based on the TOAST classification. A significant difference was observed between the D-dimer levels across the three AIS subtypes, with an average D-dimer of 2.93 ± 1.7, 1.27 ± 0.81, and 0.56 ± 0.46 µg/ml in the cardioembolic, LAA, and SVO subtypes, respectively. As a marker of cardioembolic stroke, an optimal cut-off was determined to be 1.52 µg/ml, yielding a sensitivity of 84.44% (CI 71.22–92.25% and specificity of 84.21% (CI 62.43–94.48%).ConclusionPlasma D-dimer levels varied significantly between the cardioembolic, LAA, and SVO subtypes of AIS, with the highest D-dimer level in the cardioembolic subtypes. As a marker of cardioembolic stroke, an optimal cut-off was determined to be 1.52 µg/mL, yielding a sensitivity and specificity of 84.44% and 84.21%, respectively.

Toll-like receptor 4 deficiency in mice impairs venous thrombus resolution.

Objective: Toll-like receptor 4 (TLR4) is crucial to the development of sterile inflammatory responses. The deep venous thrombosis resolution (DVT) is similar to sterile inflammation, so we hypothesize that TLR4 is involved. Methods and Results: We evaluated the effects of TLR4 deficiency on thrombus lysis in vivo, and explored the mechanisms in vitro. DVT mouse model was established by inferior vena cava (IVC) ligation. After the IVC ligation (1, 3, and 7d), the mice were euthanized to collect the venous thrombus. The Tlr4-/- mice had significantly elevated weight/length ratios of thrombi at 3 and 7d and increased collagen content at 3d after IVC ligation, in addition to significantly lesser intrathrombus infiltration of neutrophils and macrophages, lower monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) expression in thrombus tissue sections and homogenates, and lower pro-MMP-9 activity at 3d after IVC ligation than wild-type mice. After 7days of IVC ligation, VEGF, IFNβ, and MCP-5 protein expression were decreased in venous thrombus from Tlr4-/- mice. 2ml of 3% thioglycolate was injected intraperitoneally and peritoneal exudate was collected 3days later from Tlr4-/- and wild type mice respectively. The intraperitoneal macrophages were isolated from adherent culture after centrifugation. Lipopolysaccharide (LPS) can activate TLR4/NF-κB signalling pathway in a concentration-dependent manner, initiated p65 nuclear translocation, IκBα phosphorylation and degradation, MMP-9 and MCP-1 transcription in WT intraperitoneal macrophages but not in Tlr4-/- intraperitoneal macrophages. Conclusion: TLR4 is involved in venous thrombosis resolution through NF-κB pathway. Loss of TLR4 in mice impairs the process.

Effect of Recombinant Tissue Plasminogen Activator and 120-kHz Ultrasound on Porcine Intracranial Thrombus Density.

Surgical intervention for the treatment of intracerebral hemorrhage (ICH) has been limited by inadequate lysis of the target thrombus. Adjuvant transcranial ultrasound exposure is hypothesized to improve thrombolysis, expedite hematoma evacuation and improve clinical outcomes. A juvenile porcine intracerebral hemorrhage model was established by direct infusion of autologous blood into the porcine white matter. Thrombi were either not treated (sham) or treated with recombinant tissue plasminogen activator alone (rt-PA only) or in combination with pulsed transcranial 120-kHz ultrasound (sonothrombolysis). After treatment, pigs were euthanized, the heads frozen and sectioned and the thrombi extracted. D-Dimer and thrombus density assays were used to assess degree of lysis. Both porcine and human D-dimer assays tested did not have sufficient sensitivity to detect porcine D-dimer. Thrombi treated with rt-PA with or without 120-kHz ultrasound had a significantly lower density compared with sham-treated thrombi. No enhancement of rt-PA-mediated thrombolysis was noted with the addition of 120-kHz ultrasound (sonothrombolysis). The thrombus density assay revealed thrombolytic efficacy caused by rt-PA in an in vivo juvenile porcine model of intracerebral hemorrhage. Transcranial sonothrombolysis did not enhance rt-PA-induced thrombolysis, likely because of the lack of exogenous cavitation nuclei.

Bilateral lysis of aortic saddle thrombus with early tissue plasminogen activator (BLASTT): a prospective, randomized, placebo-controlled study in feline acute aortic thromboembolism.

The aim of this study was to investigate the impact of tissue plasminogen activator (TPA) on the treatment of feline aortic thromboembolism (FATE). Cats diagnosed with FATE involving ⩾2 limbs were enrolled in a prospective, multicenter, double-blinded, randomized, placebo-controlled study within 6 h of an event. Diagnosis was made by clinical findings and one confirmatory criterion. Cats received placebo or TPA (1 mg/kg/h with the first 10% by bolus). All cats received pain control and thromboprophylaxis. The primary outcome was a change from baseline in a published limb score at 48 h. Secondary outcomes included 48 h survival, survival to discharge and complication proportions. Statistical analyses included pattern-mixture models, logistic regression and Fisher's exact, Student's t- and Mann-Whitney-Wilcoxon tests. Based on a power analysis, 40 cats were enrolled; however, only 20 survived to 48 h (TPA, n = 12; placebo, n = 8 [P = 0.34]). There was a statistically significant improvement in limb scores compared with baseline for both groups (P <0.001). Limb score at 48 h was 1 point lower (better) in the TPA group (P = 0.19). Thrombolysis had no statistically significant effect on 48 h survival (P = 0.22). Lower affected limb lactate was associated with better 48 h survival (odds ratio 1.53, 95% confidence interval 1.08-2.17; P = 0.02). The survival to discharge rates were 45% (TPA) and 30% (placebo; P = 0.51). Complications in the TPA and placebo groups included acute kidney injury (22% and 19%, respectively; P = 1.00) and/or reperfusion injuries (33% and 19%, respectively; P = 0.45). Survival and complication rates of acute FATE were not different with or without thrombolysis. High in-hospital mortality decreased the statistical power to detect a statistically significant difference between treatments with regard to our primary outcome.

Guiding Drug Through Interrupted Bloodstream for Potentiated Thrombolysis by C-Shaped Magnetic Actuation System In Vivo.

Fast and effective thrombolysis using tissue plasminogen activator (tPA) is limited by the poor delivery efficiency of thrombolytic drugs, which is induced by an interrupted bloodstream and delayed recanalization. Existing magnetic micro/nanodrug-loaded robots used for targeted thrombotic therapy are limited by the complexity of the clinical verification of nanodrugs and the limited space of magnetic actuation systems. Herein, a general drug delivery strategy based on mass transportation theory for thrombolysis is presented, and an open space C-shaped magnetic actuation system with laser location and ultrasound imaging navigation for in vivo evaluation is developed. tPA can be guided through an interrupted bloodstream to the thrombi by the locomotion of magnetic nanoparticle swarms (MNSs), thereby improving the thrombolysis efficacy. Notably, this strategy is able to quickly establish a life channel to achieve time-critical recanalization, which is typically inaccessible using native tPA. Both in vitro and in vivo thrombolysis experiments demonstrate that the thrombus lysis efficacy significantly increases after the application of the MNS under a rotating magnetic field. This study provides an anticipated C-shaped magnetic actuation system for in vivo validation and also presents a clinically feasible drug delivery strategy for targeted thrombolytic therapy with minimal systemic tPA exposure.

The association of anticoagulation therapy characteristics with left atrial thrombus lysis in patients with nonvalvular persistent atrial fibrillation

Purpose. The aim of this study was to reveal the effect of the duration and characteristics of anticoagulant therapy on the clot dissolution in the left atrial appendage (LAA) in patients with persistent atrial fibrillation (AF).Material and methods. The repeat transesophageal echocardiography was performed in 68 patients with persistent AF, because the thrombus was detected in the LAA during the first examination. Of these, 37 (54.4%) patients started or continued to receive warfarin and 31 (45.6%) patients continued to receive the direct oral anticoagulants. Transesophageal echocardiography was repeated after 3-5 weeks. One follow-up examination was for 53 patients, two follow-up examination was for 11 patients and three follow-up examination was for 4 patients. Cox regression analysis was performed to identify factors affecting the likelihood of clot dissolution and Kaplan-Meier survival analyses with log-rank tests were used to compare the clot dissolution time.Results. The chance of the LAA thrombus lysis is 50% after 35.0 ± 3.7 days of receiving anticoagulants. This time is reduced to 30.0 ± 1.4 days for small thrombus (no more than 18 mm), and it increases to 45.0 ± 7.4 days (p = 0.038) for large thrombus. The dissolution time of small thrombus depends on the characteristics of the treatment: the median of the dissolution curve is 24.0 ± 3.7 days when the patients received the direct oral anticoagulants, and the median of the dissolution curve is 40.0 ± 7.2 days (p = 0.009), if the patients received warfarin. The dependence of the dissolution time of large thrombus on the characteristics of treatment did not found.Conclusion. The LAA thrombus dissolution time in patients with atrial fibrillation depends on their size, and the dissolution time of small thrombi depends on the characteristics of anticoagulant therapy.

Successful Conservative Treatment of a Complicated Aortic Thrombus in a Woman with Factor V Leiden Mutation.

Thrombus in the aortic trunk is a rare complication. We report the case of a 63-year-old patient with a factor V Leiden mutation in whom an aortic arch thrombus was discovered accidentally. Conservative treatment was initiated with therapeutic anticoagulation with low-molecular-weight heparin leading to complete thrombus lysis after 3 months but associated shortly after anticoagulation initiation with a large splenic and limited renal infarctions.LEARNING POINTSIntra-aortic thrombus is rarely diagnosed on routine CT examination.Even a complicated aortic arch thrombus can be successfully treated with conservative anticoagulation.Vascular systemic embolisms are possible after therapeutic anticoagulation is started.

A risk score for iliofemoral patients with deep vein thrombosis

ObjectiveDeep vein thrombosis (DVT) is a common condition with a high risk of post-thrombotic morbidity, especially in patients with a proximal thrombus. Successful iliofemoral clot removal has been shown to decrease the severity of post-thrombotic syndrome. It is assumed that earlier thrombus lysis is associated with a better outcome. Generally, the earlier IFDVT is confirmed, the earlier thrombus lysis could be performed. d-Dimer levels and Wells score are currently used to assess the preduplex probability for DVT; however, some studies indicate that the d-dimer value varies depending on the thrombus extent and localization. Using d-dimer and other risk factors might facilitate development of a model selecting those with an increased risk of IFDVT that might benefit from early referral for additional analysis and adjunctive iliofemoral thrombectomy. MethodsAll consecutive adult patients from a retrospective cohort of STAR diagnostic center (primary care) in Rotterdam suspected of having DVT between September 2004 and August 2016 were assessed for this retrospective study. The diagnostic workup for DVT including Wells score and d-dimer were performed as well as complete duplex ultrasound examination. Patients with objective evidence of DVT were categorized according to thrombus localization using the Lower Extremity Thrombolysis classification. Logistic regression analysis was done for a model predicting IFDVT. The cut-off value of the model was determined using a receiver operating characteristic curve. ResultsA total of 3381 patients were eligible for study recruitment, of whom 489 (14.5%) had confirmed DVT. We developed a multivariate model (sensitivity of 77% and specificity of 82%; area under the curve, 0.90; 0.86-0.93) based on d-dimer, Wells score, age, and anticoagulation use, which is able to distinguish IFDVT patients from all patients suspected of DVT. ConclusionsThis multivariate model adequately distinguishes IFDVT among all suspected DVT patients. Practically, this model could give each patient a preduplex risk score, which could be used to prioritize suspected IFDVT patients for an immediate imaging test to confirm or exclude IFDVT. Further validation studies are needed to confirm potential of this prediction model for IFDVT.

No difference in thrombotic profile of patients with ACS with obstructive CAD and MINOCA

Abstract Introduction Acute coronary syndrome (ACS) is caused by disruption of an atherosclerotic plaque with initiation of thrombosis, and outcome determined by the balance between prothrombotic drivers and the efficacy of endogenous fibrinolysis. Most patients have obstructive coronary artery disease (CAD), with high shear forces and turbulent flow across severe stenoses enhancing platelet activation. Recognition that some ACS patients have myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) has led to a search to identify drivers behind such presentations. Purpose To assess and compare the thrombotic status of patients with MINOCA and those with ACS due to obstructive CAD. Methods In a prospective observational study in patients with ACS, thrombotic and thrombolytic status was assessed from venous blood using the point-of-care Global Thrombosis Test, assessing time to in vitro occlusive thrombus formation under high shear (occlusion time,OT) and time taken for spontaneous lysis of the thrombus (lysis time,LT). Blood was taken after dual antiplatelet therapy loading, but before fondaparinux or heparin administration. Those with renal or hepatic impairment, bleeding diathesis, thrombocytopenia or on anticoagulation were excluded. MINOCA diagnosis was made according to the Fourth Universal Definition of MI, in the absence of obstructive CAD (no lesion ≥50%) and excluding patients with 1) other overt causes for elevated troponin, 2) overlooked obstructive CAD, and 3) nonischaemic causes for myocyte injury, according to the American Heart Association 2019 recommendation. Patients with Type 2, 4 and 5 MI were excluded. Results We assessed 746 patients, of whom 621 (83%) had ST-segment elevation MI (STEMI) and the rest non-STEMI. Of these, 706 (95%) had obstructive CAD and 40 (5%) had MINOCA. Apart from sex (78% obstructive CAD patients were male vs 50% MINOCA patients), cardiovascular risk factors were similar in MINOCA and obstructive CAD patients (smoking 28 vs 31%, p=0.615; hypertension 35 vs 47%, p=0.153; diabetes 20 vs 20%, p=0.948; hyperlipidaemia 30 vs 36%, p=0.475 and family history of premature CAD 35 vs 35%, p=1.000). There was no difference in time to form occlusive thrombus (OT 424 [371–471] vs 395 [287–512] s, p=0.093) or in endogenous fibrinolysis (LT 1450 [1082–2099] vs 1582 [1252–2130] s, p=0.178) between MINOCA and obstructive CAD patients. Even after propensity score matching with a ratio of 3:1 for clinical characteristics, there was no difference between patients with MINOCA and those with obstructive CAD, with respect to thrombus formation (OT 424 [371–471] vs 430 [300–538] s, p=0.602) or endogenous fibrinolysis (LT 1470 [1082- 2099] vs 1494 [1140–2074] s, p=0.625). Conclusion Amongst patients with ACS, those with MINOCA exhibit similar thrombotic profiles to patients with obstructive CAD with ACS. This represents a potential therapeutic target to modulate risk post myocardial infarction in patients with MINOCA and requires further research. Funding Acknowledgement Type of funding source: None

Hemodynamic Analysis of VenaTech Convertible Vena Cava Filter Using Computational Fluid Dynamics.

The VenaTech convertible filter (VTCF) has been widely used as an inferior vena cava (IVC) filter to prevent fatal pulmonary embolism in patients. However, its hemodynamics that greatly affect the filter efficacy and IVC patency are still unclear. This paper uses computational fluid dynamics with the Carreau model to simulate the non-Newtonian blood flows around the VTCF respectively deployed in the normal, reverse and three converted states in an IVC model. The results show that the prothrombotic stagnation zones are observed downstream from the normal, reverse and small open VTCFs, with the streamwise length is nearly eight times the IVC diameter. The no-slip boundary conditions of the thin-wire VTCF arms lead to the “viscous block” effect. The viscous block accelerates the blood flow by 5–15% inside the IVC and enhances the filter wall shear stress up to nearly 20 times that of the IVC only, which contributes to clot capture and thrombus lysis. The relative flow resistance is defined to evaluate the filter-induced resistance on the IVC blood flow that can be regarded as an index of IVC patency with the filter deployment. The flow resistance of the normal VTCF deployment increases dramatically by more than 60% compared with that of the IVC only and is a little higher (6%) than that of the reverse case. As the VTCF converts to a fully open configuration, the flow resistance gradually decreases to that of no filter. This work shows that even very thin VTCF arms can result in the viscous block effect and may cause significant hemodynamic impacts on clot capture, potential thrombosis and flow impedance inside the IVC. The present study also shows that CFD is a valuable and feasible in silico tool for analyzing the IVC filter hemodynamics to complement in vivo clinical and in vitro experimental studies.

Reperfusion therapies in pulmonary embolism–state of the art and expert opinion: A position paper from the “Unité de Soins Intensifs de Cardiologie” group of the French Society of Cardiology

Acute pulmonary embolism is a frequent cardiovascular emergency with an increasing incidence. The prognosis of patients with high-risk and intermediate-high-risk pulmonary embolism has not improved over the last decade. The current treatment strategies are mainly based on anticoagulation to prevent recurrence and reduce pulmonary vasculature obstruction. However, the slow rate of thrombus lysis under anticoagulation is unable to acutely decrease right ventricle overload and pulmonary vasculature resistance in patients with severe obstruction and right ventricle dysfunction. Therefore, patients with high-risk and intermediate-high-risk pulmonary embolism remain a therapeutic challenge. Reperfusion therapies may be discussed for these patients, and include systemic thrombolysis, catheter-directed therapies and surgical thrombectomy. High-risk patients require systemic thrombolysis, but may have contraindications as a result of the high risk of bleeding. In addition, intermediate-high-risk patients should not receive systemic thrombolysis, despite its high efficacy, because of prohibitive bleeding complications. Recently, percutaneous reperfusion techniques have been developed to acutely decrease pulmonary vascular obstruction with lower-dose or no thrombolytic agents and, thus, potentially higher safety than systemic thrombolysis. Some of these techniques improve key haemodynamic variables. Cardiac surgical techniques and venoarterial extracorporeal membrane oxygenation as temporary circulatory support may be useful in selected cases. The development of pulmonary embolism centres with multidisciplinary pulmonary embolism teams is mandatory to enable adequate use of reperfusion and improve outcomes. We aim to present the state of the art regarding reperfusion therapies in pulmonary embolism, but also to provide guidance on their indications and patient selection.