Clot Detection Research Articles

Prediction of Thrombus Formation within an Oxygenator via Bioimpedance Analysis.

Blood clot formation inside the membrane oxygenator (MO) remains a risk in extracorporeal membrane oxygenation (ECMO). It is associated with thromboembolic complications and normally detectable only at an advanced stage. Established clinical monitoring techniques lack predictive capabilities, emphasizing the need for refinement in MO monitoring towards an early warning system. In this study, an MO was modified by integrating four sensor fibers in the middle of the hollow fiber mat bundle, allowing for bioimpedance measurement within the MO. The modified MO was perfused with human blood in an in vitro test circuit until fulminant clot formation. The optical analysis of clot residues on the extracted hollow fibers showed a clot deposition area of 51.88% ± 14.25%. This was detectable via an increased bioimpedance signal with a significant increase 5 min in advance to fulminant clot formation inside the MO, which was monitored by the clinical gold standard (pressure difference across the MO (dp-MO)). This study demonstrates the feasibility of detecting clot growth early and effectively by measuring bioimpedance within an MO using integrated sensor fibers. Thus, bioimpedance may even outperform the clinical gold standard of dp-MO as a monitoring method by providing earlier clot detection.

Method comparison between two hemostasis analyzers: STARMax3 and Cobast511

The STARMax3 (Stago, France) and Cobas t511 (Roche Diagnostics, Germany) are two automated hemostasis analysers that can be used to perform a wide range of tests. The STARMax3 uses a mechanical clot detection system to measure coagulation times, while the Cobas t511 uses optical detection. The aim of this study was to compare the analytical performance of these two analysers using fresh plasma samples with or without a risk of interference due to hemolysis or lipemia. For plasma samples without interference, acceptable agreement was observed for prothrombin time (PT) (n =55), activated partial thromboplastin time (APTT) (n =56), fibrinogen (n =56) and factor II (n =43) with R² of 0.907, 0.963, 0.979 and 0.968 respectively. For factor V (n =43) and D-dimers (n =45), agreement was less acceptable, with respective R² of 0.756 and 0.887, but with no clinical impact. For hemolysed samples, acceptable results were observed for PT, fibrinogen and D-dimers, but three results were clinically discordant for APTT, and STARMax3 offered greater robustness for processing highly lipemic samples.

The quantified method for blood clot detection in the extraction socket

Background Currently, there is no objective and quantified measurement for detecting blood clots during extraction socket hemostasis. It has relied solely on clinical observation, even when conducting clinical research by using extraction sockets as samples. This study aimed to assess the in vitro reliability and clinical-relevant validity of a new objective measurement providing quantified data called blood clot detection (BCD) using a standard capillary tube. Methods The in vitro part of the study was conducted using surplus blood samples from ten healthy participants. Two identical sets of blood samples in simulation reservoirs mimicking bleeding sockets were prepared for reliability tests. Then, the capillary tubes were concurrently placed in the reservoirs. The blood-filled distances were measured. The part of clinical-relevant validity study was conducted in sixteen extraction sockets from each healthy participant. Clinical observation and BCD measurement were evaluated by two calibrated assessors. The total duration of the assessment was a 30-minute. Results The distances of the blood-filled capillary tube were decreased by time. Test and retest reliability analysis of the BCD measurement showed an excellent intraclass correlation coefficient of 0.980 (0.968 to 0.988). The medians of blood-filled distance categorized by clinical observation into active bleeding, sluggish oozing, and clot formation were 13.0 mm (Q1 = 11.7, Q3 = 13.8), 5.6 mm (Q1 = 4.3, Q3 = 7.0), and 0.9 mm (Q1 = 0.5, Q3 = 1.3), respectively. The blood-filled distance of the clot formation group was significantly less than the active bleeding and sluggish oozing (p<0.001). Therefore, the BCD measurement also significantly indicated the completion of extraction socket hemostasis Conclusions A distance of blood-filled in capillary tube of 0.9 mm from the BCD measurement significantly ensured complete clot formation. The BCD measurement proved to be a quantified tool for objectively measuring hemostasis of bleeding socket.

A Study of the Mean Platelet Volume and Plasma Fibrinogen in Type Two Diabetes Mellitus Patients Versus Healthy Controls and Their Role as Early Markers of Diabetic Microvascular Complications.

Background Mean platelet volume (MPV) is considered an emerging biological marker of platelet function and activity. Higher MPV has been scientifically linked to diabetes mellitus, metabolic syndrome, stroke, and coronary artery disease. Plasma fibrinogen is a circulating glycoprotein, serving as an acute inflammatory marker ultimately leading to enhanced atherogenic plaque formation. We conducted this study to evaluate the crucial role of MPV and plasma fibrinogen, which showed elevated levels in diabetes mellitus patients compared to non-diabetic healthy individuals. This study also elaborates on the pivotal role that MPV and plasma fibrinogen levels play in the pathogenesis of microvascular complications, which progress and eventually lead to mortality in patients with type 2 diabetes mellitus. Methodology This study is a single-center hospital-based study including120 type 2 diabetes mellitus patients and 120 healthy non-diabetic individuals. It is across-sectional and observational study. The study wasconductedover a period of one and a half years in a medical college and hospital in a semi-urban locality in Western Maharashtra, India. We obtained informed written consent from the patients. All patients underwent thorough clinical assessment, and data were collectedusing proformas, which were latertabulated and entered in Microsoft Excel sheets. Later, the statistical data analysis was performed.Plasma fibrinogen was performed by photo-optical clot detection. MPV was analyzed by coulter principle in the central laboratory department of the parent institute. Patients above 18 years with cases of type 2 diabetes mellitus with or without any related complications, while the controls are healthy non-diabetic individuals attending the outpatient and inpatient departments of General Medicine. We excluded patients under the age of 18 years, those diagnosed with type 1 diabetes mellitus, hematological conditions associated with anemia and abnormal platelet counts, pregnant females, any acute or chronic infections, patients currently on antiplatelet medication and other drugs affecting the platelets, and all critical patients. Results The majority of patients in our study were in the age group of 41-50 years, with 49.2% having one or more microvascular complications of diabetes mellitus. In our study, out of 120 cases, 3.3% and 23.3% had raised MPV and fibrinogen levels, respectively, above the normal range. When compared with males and females, there was no statistically significant difference in the mean value of MPV and fibrinogen. On the t-test (p < 0.05), there was a statistically significant difference in the mean value of MPV and fibrinogen level between diabetics with and without microvascular complications. The t-test (p < 0.05) showed that there was a statistically significant difference among cases in the mean values of MPV and plasma fibrinogen in relation to retinopathy, nephropathy, and neuropathy, which are all microvascular complications of diabetes. Conclusion The study reveals higher levels of MPV and fibrinogen in diabetic patients compared to non-diabetic healthy individuals. In addition,higher levels of MPV and fibrinogen were present in patients with microvascular complications, correlated with age and diabetes duration.

Computer based visualization of clot structures in extracorporeal membrane oxygenation and histological clot investigations for understanding thrombosis in membrane lungs.

Extracorporeal membrane oxygenation (ECMO) was established as a treatment for severe cardiac or respiratory disease. Intra-device clot formation is a common risk. This is based on complex coagulation phenomena which are not yet sufficiently understood. The objective was the development and validation of a methodology to capture the key properties of clots deposed in membrane lungs (MLs), such as clot size, distribution, burden, and composition. One end-of-therapy PLS ML was examined. Clot detection was performed using multidetector computed tomography (MDCT), microcomputed tomography (μCT), and photography of fiber mats (fiber mat imaging, FMI). Histological staining was conducted for von Willebrand factor (vWF), platelets (CD42b, CD62P), fibrin, and nucleated cells (4', 6-diamidino-2-phenylindole, DAPI). The three imaging methods showed similar clot distribution inside the ML. Independent of the imaging method, clot loading was detected predominantly in the inlet chamber of the ML. The μCT had the highest accuracy. However, it was more expensive and time consuming than MDCT or FMI. The MDCT detected the clots with low scanning time. Due to its lower resolution, it only showed clotted areas but not the exact shape of clot structures. FMI represented the simplest variant, requiring little effort and resources. FMI allowed clot localization and calculation of clot volume. Histological evaluation indicated omnipresent immunological deposits throughout the ML. Visually clot-free areas were covered with leukocytes and platelets forming platelet-leukocyte aggregates (PLAs). Cells were embedded in vWF cobwebs, while vWF fibers were negligible. In conclusion, the presented methodology allowed adequate clot identification and histological classification of possible thrombosis markers such as PLAs.

Simplified Method for Removing Direct Oral Anticoagulant Interference in Mechanical Coagulation Test Systems-A Proof of Concept.

Direct oral anticoagulants (DOACs) cause unwanted interference in various hemostasis assays, including lupus anticoagulant (LA) testing, where false positive and false negative identification may occur. DOAC Stop (DS) is an activated charcoal (AC) product used to specifically and effectively adsorb DOACs from test plasma. This process normally requires plasma treatment, centrifugation and plasma separation prior to tests, but inexperienced operators may also inadvertently transfer residual AC particles, thereby potentially adversely affecting clot detection. We hypothesized that residual DS might not be problematic for mechanical clot detection. We therefore investigated the potential impact of DS and a new DS liquid (DS-L) product on clotting tests using a mechanical clot detection system. Varying concentrations of DS were added to normal and abnormal plasmas with and without DOAC presence. Clotting tests including PT, APTT and dRVVT were performed directly in the analyzer without plasma/DS centrifugation. DS up to double the recommended treatment level had only minor effects on all test results, despite completely obscuring visibility in the plasma/reagent mix. This confirms that the centrifugation step may be able to be omitted when using mechanical detection systems. Should DS carryover into treated plasmas occur, this should not cause issues with testing performed on mechanical clot-sensing devices. Moreover, we hypothesize that DS can be used directly in these systems, without the need for centrifugation, thereby simplifying its many potential applications.

Abstract TP274: Challenging the Guidelines or Merely an Observation on Transthoracic Echocardiography

Introduction: Accurate detection of left atrial appendage (LAA) clot is critical in patients before Balloon Mitral Valvotomy (BMV). There is an elevated risk of thrombus formation and ischemic stroke in Rheumatic Heart Disease (RHD). The yearly prevalence of new stroke is 3-7.5% in RHD. Transesophageal Echocardiogram (TEE) has traditionally been the gold standard for LAA clot detection. But it is semi-invasive and have risks. The need for alternatives in this clinical context has prompted this comparative study. Hypothesis: Visualizing LAA on Transthoracic Echocardiogram (TTE) is facile in severe mitral stenosis due to increased LAA size, which is vital for stroke prevention. Methods: In this comparative study, we assessed the diagnostic accuracy of TTE as a non-invasive alternative to TEE for LAA clot detection in patients scheduled for BMV. A total of 150 patients admitted to a tertiary hospital underwent both TTE and TEE before BMV, with TEE as the reference standard for evaluation. Results: The mean age of our study population was 41.4 years, the majority were females (64.7%). The incidence of thrombus in TEE was 30%, with a significant difference in females (37%) vs. males (17%). TTE missed LAA clots in 18.8%, this discrepancy rate was 6% in males and 26% in females, signifying a significant reduction in clot detection in females. TEE exhibited no such limitations in clot detection between genders. TTE displayed sensitivity of 98% and specificity of 81%. The accuracy rate of TTE was 43.3%.Pearson Correlation coefficient and Fishers Exact test confirms significance. The non-invasive nature of TTE, devoid of procedural complexities, positions it as a Cost-effective option. Conclusion: Our study provides compelling evidence supporting the hypothesis that TTE is an effective and practical alternative to TEE for LAA clot detection in RHD patients Further studies are needed in this regard so that the current Class 1C recommendation for TEE before any BMV may need to be revised.

Early Blood Clot Detection Using Forward Scattering Light Measurements Is Not Superior to Delta Pressure Measurements.

The occurrence of thrombus formation within an extracorporeal membrane oxygenator is a common complication during extracorporeal membrane oxygenation therapy and can rapidly result in a life-threatening situation due to arterial thromboembolism, causing stroke, pulmonary embolism, and limb ischemia in the patient. The standard clinical practice is to monitor the pressure at the inlet and outlet of oxygenators, indicating fulminant, obstructive clot formation indicated by an increasing pressure difference (ΔP). However, smaller blood clots at early stages are not detectable. Therefore, there is an unmet need for sensors that can detect blood clots at an early stage to minimize the associated thromboembolic risks for patients. This study aimed to evaluate if forward scattered light (FSL) measurements can be used for early blood clot detection and if it is superior to the current clinical gold standard (pressure measurements). A miniaturized in vitro test circuit, including a custom-made test chamber, was used. Heparinized human whole blood was circulated through the test circuit until clot formation occurred. Four LEDs and four photodiodes were placed along the sidewall of the test chamber in different positions for FSL measurements. The pressure monitor was connected to the inlet and the outlet to detect changes in ΔP across the test chamber. Despite several modifications in the LED positions on the test chamber, the FSL measurements could not reliably detect a blood clot within the in vitro test circuit, although the pressure measurements used as the current clinical gold standard detected fulminant clot formation in 11 independent experiments.

Variable Performance of Lupus Anticoagulant Testing: The Australasian/Asia-Pacific Experience.

Lupus anticoagulant (LA) is one of three tests identified as laboratory criteria for definite antiphospholipid syndrome (APS). The other two tests are anticardiolipin antibody (aCL) and anti-β2-glycoprotein I (aβ2GPI) antibody. The presence of LA is assessed using clot-based tests, while the presence of aCL and aβ2GPI is assessed by immunological assays. Since no test can be considered 100% sensitive or specific for LA, current guidelines recommend using two different clot-based assays reflecting different principles, with the dilute Russell viper venom time (dRVVT) and activated partial thromboplastin time (aPTT) recommended. Initially, LA-sensitive reagents are used to screen for LA, and then, in "screen-positive" samples, LA-"insensitive" reagents are used to confirm LA. Because LA assays are based on clot detection, anything that can interfere with fibrin clot development may affect test results. In particular, in addition to LA, the tests are also sensitive to the presence of a wide range of clinical anticoagulants, reflecting preanalytical issues for testing. We provide updated findings for LA testing in our geographic region, using recent data from the Royal College of Pathologists of Australasia Quality Assurance Programs, an international external quality assessment program with approximately 120 participants. Data show a wide variety of assays in use, especially for aPTT testing, and variable outcomes in reported numerical values with these assays when assessing proficiency samples. dRVVT testing mostly comprised reagents from three main manufacturing suppliers, which also showed differences in numerical values for the same homogeneous tested samples. Nevertheless, despite the use of different test reagents and processes, >98% of participants correctly identified LA-negative samples as LA-negative and LA-positive samples as LA positive. We hope our findings, reflecting on the heterogeneity of test processes and test data, help improve diagnostic testing for LA in the future.

A-323 Pre-analytic Interference in PT and PTT Measurement using Mechanical vs Optical Clot Detection

Abstract Background Mechanical clot-detection is commonly thought to be less susceptible to optical pre-analytic interference. Pediatric specimens are particularly prone to be hemolyzed and/or icteric. Our hospital laboratory approached an impending change in coagulation instrumentation from mechanical (STAGO) to optical (IL) with some trepidation. We, therefore, performed a detailed comparison of plasma samples containing a broad range of hemoglobin, bilirubin, and triglyceride using IL reagents (RecombiPlasTin2G, SynthASil) on the TOPS 550 and a manual method on the STart 4. Methods 7 independent pools (5 normal, 2 prolonged) of residual citrated plasma were supplemented with hemoglobin, bilirubin, or triglyceride up to 1000 mg/dL, 150 mg/dL, or 750 mg/dL, respectively, or with equal volumes of vehicle as control. Supplementation was confirmed and quantified by measuring HIL indices on a Roche Cobas 6000. PT and PTT were performed in duplicate on each experimental and control sample on the TOPS and STart systems. Imprecision of the two systems was monitored at two levels throughout the study. Results Imprecision (n = 20) of the TOPS PT and PTT assays ranged from 1.4–3.1% (CV). Imprecision (n = 20) of the STart PT and PTT assays ranged from 1.9–18.3% (CV). PT and PTT on both platforms were not impacted by hemolysis or lipemia up to an H index of 1000 and an L index of 500, respectively. As shown in the Figure, PT and PTT in normal pools on both platforms were significantly prolonged by the presence of bilirubin above an I-index of 30. Results were similar in the prolonged pools. Data points are the means (± SD) of 10 determinations across the 5 normal plasma pools for experimental (●) and control specimens (○). Conclusion Mechanical clot detection did not show superior resistance to pre-analytic interference vs an optical clot detection method.

Automated Intracranial Clot Detection: A Promising Tool for Vascular Occlusion Detection in Non-Enhanced CT.

(1) Background: to test the diagnostic performance of a fully convolutional neural network-based software prototype for clot detection in intracranial arteries using non-enhanced computed tomography (NECT) imaging data. (2) Methods: we retrospectively identified 85 patients with stroke imaging and one intracranial vessel occlusion. An automated clot detection prototype computed clot location, clot length, and clot volume in NECT scans. Clot detection rates were compared to the visual assessment of the hyperdense artery sign by two neuroradiologists. CT angiography (CTA) was used as the ground truth. Additionally, NIHSS, ASPECTS, type of therapy, and TOAST were registered to assess the relationship between clinical parameters, image results, and chosen therapy. (3) Results: the overall detection rate of the software was 66%, while the human readers had lower rates of 46% and 24%, respectively. Clot detection rates of the automated software were best in the proximal middle cerebral artery (MCA) and the intracranial carotid artery (ICA) with 88-92% followed by the more distal MCA and basilar artery with 67-69%. There was a high correlation between greater clot length and interventional thrombectomy and between smaller clot length and rather conservative treatment. (4) Conclusions: the automated clot detection prototype has the potential to detect intracranial arterial thromboembolism in NECT images, particularly in the ICA and MCA. Thus, it could support radiologists in emergency settings to speed up the diagnosis of acute ischemic stroke, especially in settings where CTA is not available.

Viscoelastic testing: Critical appraisal of new methodologies and current literature.

United States Food and Drug Administration (FDA)-approved viscoelastic testing (VET) methodologies have significantly changed in the last 10 years, with the availability of cartridge-based VET. Some of these cartridge-based methodologies use harmonic resonance-based clot detection. While VET has always allowed for the evaluation of real-time clot formation, cartridge-based VET provides increased ease of use as well as greater portability and robustness of results in out-of-laboratory environments. Here we review the use of VET in a variety of clinical contexts, including cardiac surgery, trauma, liver transplant, obstetrics, and hypercoagulable states such as COVID-19. As of now, high quality randomized trial evidence for new generation VET (TEG 6s, HemoSonics Quantra, ROTEM sigma) is limited. Nevertheless, the use of VET-guided transfusion algorithms appears to result in reduced blood usage without worsening of patient outcomes. Future work comparing the new generation VET instruments and continuing to validate clinically important cut-offs will help move the field of point-of-care coagulation monitoring forward and increase the quality of transfusion management in bleeding patients.

398 Towards Catheter-Clot Engagement Detection Via Classification of Vacuum and Motion Signature During Aspiration Thrombectomy

INTRODUCTION: While acute ischemic stroke caused by large vessel occlusion is effectively treated with aspiration thrombectomy, procedural success depends on the quality of engagement between the catheter tip and the thrombus. Currently, there is no method to identify whether the catheter tip is truly in contact with the clot surface. Poor thrombus engagement can result in failure of recanalization. METHODS: An in vitro arterial occlusion was modeled with Tygon tubing representing the blood vessel and a synthetic thrombus made from TrueClot simulants. A 6Fr microcatheter was controllably inserted into the mock vessel until it contacted the synthetic thrombus. A motorized syringe and pressure sensor were connected proximally to the catheter to precisely control and measure the cyclic vacuum excitation in the catheter. The cyclic vacuum excitation was performed with a stroke of ±0.5 mm at 2 Hz, 4 Hz, and 8 Hz at catheter-clot distances of 150 mm, 20 mm, 10 mm, 5 mm, and in contact on 17 different clot models. Control and sensing data was collected at 1000 Hz frequency. For each catheter-clot distance, 1000 vacuum measurements were collected and pressure traces were saved. The change in the pressure mean per a change in insertion depth of the catheter was used to train a support vector machine (SVM) classifier that confirms clot contact. RESULTS: Using 30% of the clot model samples to train the SVM classifier and the remaining samples for validation, the quality of classification was determined. The accuracy (and F1 score) of clot detection at 2 Hz, 4 Hz, and 8 Hz were 98.31% (95.65%), 100% (100%), and 93.22% (80.00%) respectively. CONCLUSIONS: Accurate detection of catheter-clot contact is feasible via small excitation of the aspiration syringe and concurrent measurement of vacuum pressure.

Bioimpedance Analysis as Early Predictor for Clot Formation Inside a Blood-Perfused Test Chamber: Proof of Concept Using an In Vitro Test-Circuit.

Clot formation inside a membrane oxygenator (MO) due to blood-to-foreign surface interaction represents a frequent complication during extracorporeal membrane oxygenation. Since current standard monitoring methods of coagulation status inside the MO fail to detect clot formation at an early stage, reliable sensors for early clot detection are in demand to reduce associated complications and adverse events. Bioimpedance analysis offers a monitoring concept by integrating sensor fibers into the MO. Herein, the feasibility of clot detection via bioimpedance analysis is evaluated. A custom-made test chamber with integrated titanium fibers acting as sensors was perfused with heparinized human whole blood in an in vitro test circuit until clot formation occurred. The clot detection capability of bioimpedance analysis was directly compared to the pressure difference across the test chamber (ΔP-TC), analogous to the measurement across MOs (ΔP-MO), the clinical gold standard for clot detection. We found that bioimpedance measurement increased significantly 8 min prior to a significant increase in ΔP-TC, indicating fulminant clot formation. Experiments without clot formation resulted in a lack of increase in bioimpedance or ΔP-TC. This study shows that clot detection via bioimpedance analysis under flow conditions in a blood-perfused test chamber is generally feasible, thus paving the way for further investigation.

Benchmark dataset for clot detection in ischemic stroke vessel-based imaging: CODEC-IV

We present an annotated dataset for the purposes of creating a benchmark in Artificial Intelligence for automated clot detection. While there are commercial tools available for automated clot detection on computed tomographic (CT) angiographs, they have not been compared in a standardized manner whereby accuracy is reported on a publicly available benchmark dataset. Furthermore, there are known difficulties in automated clot detection – namely, cases where there is robust collateral flow, or residual flow and occlusions of the smaller vessels – and it is necessary to drive an initiative to overcome these challenges. Our dataset contains 159 multiphase CTA patient datasets, derived from CTP and annotated by expert stroke neurologists. In addition to images where the clot is marked, the expert neurologists have provided information about clot location, hemisphere and the degree of collateral flow. The data is available on request by researchers via an online form, and we will host a leaderboard where the results of clot detection algorithms on the dataset will be displayed. Participants are invited to submit an algorithm to us for evaluation using the evaluation tool, which is made available at together with the form at https://github.com/MBC-Neuroimaging/ClotDetectEval.

CORRELATION BETWEEN PLASMA FIBRINOGEN WITH DAS28 SCORE IN RHEUMATOID ARTHRITIS: A HOSPITAL BASED STUDY

Rheumatoid arthritis (RA) is a chronic systemic illness affecting joints and extra-articular structures and is the most prevalent kind of inammatory arthritis worldwide. Patients of rheumatoid arthritis have increase risk of cardiovascular disease as compared to general population. Local inammation of the affected joints, manifesting as joint pain and swelling, generally represents the clinical disease activity in RAand is measured by various joint indices like Disease Activity Score 28 (DAS 28) and Clinical Disease Activity Index (CDAI). Fibrinogen is the major determinant of plasma viscosity and it represents link between inammation, thrombosis and cardiovascular risk. The aim was to study the association of plasma brinogen with Disease activity score in rheumatoid arthritis and to compare levels of plasma brinogen in patients with rheumatoid arthritis with healthy population. Materials And Methods:This study was a cross sectional study done in 70 subjects ( 35 diagnosed RApatient by ACR 1987 criteria and 35 healthy subjects) in Assam Medical College and hospital from June 2021- May 2022.The quantitive determination of plasma brinogen was done using clot detection method. We also measured ESR using Westergren's method. Statistical analysis was done using SPSS software. Results: The mean value of plasma brinogen was 381.143±43.71 in rheumatoid arthritis versus 314.285±46.29 in controls. This difference was statistically signicant &lt;0.001.On evaluating brinogen level and DAS28 score, it was noted that patient with higher DAS28 had signicantly higher brinogen level (p&lt;0.01). Conclusion: This study concluded that plasma brinogen is signicantly elevated in patients with active rheumatoid arthritis and is signicant with increasing severity of the disease. As brinogen is the risk factor for cardiovascular disease it can also be added in routine monitoring of disease activity along with other parameters

Comparison of susceptibility-weighted angiography (SWAN) and T2 gradient-echo sequences for the detection of acute cerebral venous thrombosis.

To assess the diagnostic accuracy and lesion conspicuity of susceptibility-weighted angiography (SWAN) and T2* for the clot detection in acute cerebral venous thrombosis (CVT) by comparison with contrast-enhanced MR venography. Venous thrombi detection and conspicuity were assessed by two readers for 18 venous segments on both T2*, SWAN source images, 2D SWAN reformats matching with T2*, and 3D SWAN images (SWAN-MinIP). Images obtained with the three reading techniques were systematically scored and compared to CE MRV findings, in a blinded fashion, per patient and per segment, and compared to each other. In 30 patients, 137 thrombosed venous segments were evaluated. The sensitivity of T2*, SWAN source images, 2D SWAN, and SWAN MinIP were, respectively, of 89.3%/82.1%, 82.1%, and 82.1% for dural sinus thrombosis and of 100%/100%/100%/96.6% for cortical venous thrombosis. There were significant differences in thrombus detection between T2* and SWAN: T2* versus SWAN source images and 2D SWAN (p = 0.04) and versus SWAN MinIP (p = 0.03). There were no significant differences between the three modalities of SWAN images. T2* was more sensitive than all SWAN images for both sigmoid sinus thrombosis and intracranial internal jugular vein thrombosis (p = 0.04). Inter-observer agreement was slightly superior with T2* (p < 0.05). In this small cohort, SWAN sequence at 3T did not yield additional value for thrombus detection in acute CVT compared to T2*. This study highlights SWAN's greatest weakness both for diagnostic accuracy and lesion conspicuity compared to T2* for acute venous clot detection near the skull base.

Fibrinogen Longmont: A Clinically Heterogeneous Dysfibrinogenemia with Discrepant Fibrinogen Results Influenced by Clot Detection Method and Reagent.

Fibrinogen Longmont: A Clinically Heterogeneous Dysfibrinogenemia with Discrepant Fibrinogen Results Influenced by Clot Detection Method and Reagent.

Biomarkers of thromboinflammation correlate to COVID-19 infection and admission status in emergency department patients

BackgroundCOVID-19-associated coagulopathy is incompletely understood. ObjectivesTo characterize thrombin generation, Von Willebrand Factor (VWF), neutrophil extracellular traps (NETs), and their role in COVID-19 risk stratification in the emergency department (ED). Patients/methodsPlasma samples from 67 ED COVID-19 patients were compared to 38 healthy volunteers (HVs). Thrombin generation (calibrated automated thrombogram, CAT) was expressed as lag time (LT, min), peak height (PH, min), and time to peak (ttPeak, min). Citrullinated nucleosomes and histones were quantified with ELISA, VWF antigen and activity (IU/dL) through latex immunoassay, Factor VIII (IU/dL) through one-stage optical clot detection, and VWF multimers with Western blot densitometry. Wilcoxon testing and multivariable logistic regression were performed. Results presented as median [Q1, Q3]; p < 0.05 significant. ResultsCOVID-19 patients had longer LT (4.00 [3.26, 4.67]; 2.95 [2.67, 3.10], p < 0.001) and ttPeak (7.33 [6.33, 8.04]; 6.45 [6.00, 7.50], p = 0.004), greater VWF antigen (212 [158, 275]; 110 [91, 128], p < 0.001) and Factor VIII levels (148 [106, 190]; 106 [86, 129], p < 0.001), with decreased high molecular weight multimers (Normalized multimer ratio 0.807 [0.759, 0.869]; 0.891 [0.858, 0.966], p < 0.001), than HVs. COVID-19 patients requiring admission from the ED had longer LT and ttPeak with greater VWF antigen and Factor VIII levels than those not admitted. Two and three variable models of CAT parameters and VWF correlated with COVID-19 and admission status (C-statistics 0.677 to 0.922). ConclusionsThrombin generation kinetics and VWF levels, independent of NETs, may have a role in predicting admission need for COVID-19 patients.

Laboratory methods for monitoring argatroban in heparin-induced thrombocytopenia.

The Summary of Product Characteristics for the direct thrombin inhibitor argatroban states monitoring should be by activated partial thromboplastin time (APTT), with a target range of 1.5-3.0 times the patients' baseline APTT. APTT may be influenced by coagulopathies, lupus anticoagulant and raised FVIII levels. Previous studies have shown sensitivity differences of APTT reagents to argatroban. Some recent publications have favoured the use of anti-IIa methods to determine the plasma drug concentration of argatroban. This study aims to compare the anti-IIa assays: Hemoclot thrombin inhibitor assay (HTI) and Ecarin chromogenic assay (ECA) alongside the APTT. Residual plasma of 25 samples from 8 patients (3 with COVID-19 and HIT: n=18, 5 with HIT: n=7) was tested at two sites: site A: Sysmex CS5100 by HTI and APTT (Actin FS and SynthASil), and also on Stago STA Compact Max: ECA and APTT (CK Prest); and site B: Stago STA R Max 2 by ECA and APTT (Cephascreen). Mean APTT ratio was 1.96 (Actin FS), 1.84 (SynthASil), 1.59 (CK Prest) and 2.48 (Cephascreen). Mean argatroban concentration by HTI was 0.60µg/mL and by ECA was 0.65µg/mL (site A) and 0.70µg/mL (site B). There was a poor correlation to HTI in APTT ratios (range r2 =.0235-0.4181) with stronger correlations between ECA methods to HTI (r2 =.8998 site A, r2 =.8734 site B). This study confirms previous publications on the unsuitability of APTT and expands this by being multisited and included APTT reagents that use mechanical clot detection. Both anti-IIa methods are more suitable.