Abnormal Hemostasis Research Articles

Comparison of tissue factor-activated versus citrated native thromboelastography in dogs with suspected hemostatic abnormalities.

Viscoelastic testing methods, including thromboelastography (TEG) and rotational thromboelastometry, have an advantage over traditional tests of coagulation due to their ability to reflect in vivo hemostasis and predict need for transfusion of blood products more accurately. TEG in clinical settings is most often performed on citrated whole blood samples that are recalcified at the time of analysis, with or without the addition of an activator of coagulation. To date, superiority of the use of an activator in canine patients with abnormal hemostasis has not been demonstrated. We compared the use of tissue factor-activated (TF) TEG with citrated native (CN) TEG in dogs with suspected hemostatic abnormalities. Forty-five of 79 enrolled dogs with suspected abnormal hemostasis had an abnormal MA value. There was very high correlation between CN samples and TF-activated samples for alpha, K, MA, and R; there was a high correlation for LY30 and LY60. Categorical agreement for CN- and TF-activated TEG classification of hypercoagulable and hypocoagulable cases based on MA was good to very good, with 91% and 97% categorical agreement, respectively. No difference was found in the variance for any TEG variable between the 2 methods of analysis. For canine patients with suspected abnormal hemostasis, use of CN or TF-activated TEG appears acceptable. Monitoring of coagulation should be done with the same method; methods may not be used interchangeably.

Patients with Waldenström macroglobulinemia have impaired platelet and coagulation function

AbstractClinical features in patients with the B-cell lymphoma, Waldenström macroglobulinemia (WM), include cytopenias, immunoglobulin M (IgM)–mediated hyperviscosity, fatigue, bleeding, and bruising. Therapeutics such as Bruton's tyrosine kinase inhibitors (BTKis) exacerbate bleeding risk. Abnormal hemostasis arising from platelet dysfunction, altered coagulation or vascular impairment have not yet been investigated in patients with WM. Therefore, this study aimed to evaluate hemostatic dysfunction in samples from these patients. Whole blood (WB) samples were collected from 14 patients with WM not receiving therapy, 5 patients receiving BTKis and 15 healthy donors (HDs). Platelet receptor levels and reticulation were measured by flow cytometry, plasma thrombin generation with or without platelets by fluorescence resonance energy transfer assay, WB clotting potential by rotational thromboelastometry, and plasma soluble glycoprotein VI (sGPVI) and serum thrombopoietin (TPO) by enzyme-linked immunosorbent assay. Donor platelet spreading, aggregation, and ability to accelerate thrombin generation in the presence of WM-derived IgM were assessed. WM platelet receptor levels, responses to physiological agonists, and plasma sGPVI were within normal ranges. WM platelets had reduced reticulation (P = .0012) whereas serum TPO levels were increased (P = .0040). WM plasma displayed slower thrombin generation (P = .0080) and WM platelets contributed less to endogenous thrombin potential (ETP; P = .0312). HD plasma or platelets incubated with IgM (50-60 mg/mL) displayed reduced spreading (P = .0002), aggregation (P < .0001), and ETP (P = .0081). Thus, alterations to thrombin potential and WB coagulation were detected in WM samples. WM IgM significantly impaired hemostasis in vitro. Platelet and coagulation properties are disturbed in patients with well-managed WM.

Sensitivity and specificity of strategies to identify patients with hemostasis abnormalities leading to an increased risk of bleeding before scheduled intervention: the Hemorisk study

BackgroundPreoperative identification of patients with hemostasis abnormalities leading to an increased bleeding risk is based on routine hemostasis tests: prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet count. Because of their low predictive performance, guidelines recommend replacing them with structured bleeding risk questionnaires, but none is validated in this population. ObjectivesTo assess the diagnostic accuracy of 3 strategies, performed at the preanesthesia visit before scheduled interventions, and to identify patients with hemostasis abnormalities leading to an increased bleeding risk MethodsA multicenter study was performed in 7 French academic hospitals, involving patients scheduled for surgical intervention, without antiplatelet/anticoagulant treatment. The 3 strategies consisted of 1-a structured screening questionnaire; 2-PT, APTT, and platelet count ordered in selected patients; and 3-systematic PT, APTT, and platelet count. The reference standard comprised von Willebrand factor activity/antigen, factor (F)VIII, FIX, FXI, platelet function analyzer, and, when required, FII, FV, FX, and FVII and hemostasis consultation. ResultsEighteen (1.2%) of 1484 patients had a hemostasis abnormality leading to an increased bleeding risk according to reference standard. In the overall cohort, sensitivity of the questionnaire-based strategy was 50% (95% CI, 26%-74%; specificity, 87% [95% CI, 85%-88%]); sensitivity was 0% (95% CI, 0%-41%) in men vs 82% (95% CI, 48%-98%) in women. For selective routine tests, sensitivity was 33% (95% CI, 13%-59%) and specificity 97% (95% CI, 96%-98%). Corresponding values for systematic routine tests were 44% (95% CI, 22%-69%) and 93% (95% CI, 91%-94%). ConclusionSensitivity was low for all 3 strategies investigated. The structured screening questionnaire had clinically acceptable diagnostic accuracy only in women.

Prothrombin complex concentrate for emergency surgery in patients on oral Xa-inhibitors

BackgroundIt is uncertain whether prothrombin complex concentrate (PCC) improves hemostasis in patients on treatment with oral factor Xa-inhibitors (XaI) who require emergency surgery. ObjectivesTo evaluate whether, in patients with therapeutic levels of oral XaI, preoperative PCC prevents excessive bleeding during and after emergency surgery and is not associated with thrombotic complications. MethodsWe conducted a prospective cohort study wherein a fixed 2000 IU dose of 4-factor PCC was given to patients taking oral XaI with plasma XaI levels of at least 75 ng/mL before the emergency surgery with an expected blood loss of at least 50 mL. Patients were followed for 30 days. The primary efficacy outcome was the incidence of normal or mildly abnormal surgical hemostasis, as assessed by the surgeon; primary safety outcome was the incidence of thromboembolic events within 7 days. ResultsWe included 20 patients, of which 50% were female, on apixaban (75%) or rivaroxaban (25%) with median XaI level of 128 ng/mL (range, 77-497 ng/mL). The median duration of surgery was 2 hours 42 minutes (range, 15 minutes to 8 hours 17 minutes). Normal or mildly abnormal hemostasis was observed in 16 patients (80%); 2 patients had moderately abnormal and 2 had severely abnormal hemostasis, 1 each of those was considered due to local or technical factors. There were 4 deaths (20%) secondary to underlying disease and 1 incidental pulmonary embolism in a patient with cancer. ConclusionA fixed dose of PCC appears to control hemostasis in patients with therapeutic plasma levels of apixaban or rivaroxaban requiring emergency surgery.

The bile acid receptor TGR5 inhibits platelet activation and thrombus formation

Liver failure and cirrhosis are characterized by abnormal hemostasis with aberrant platelet activation. In particular, the consequences of cholestatic liver disease and molecular mechanisms, including the role of bile acids leading to impaired platelet responses, are not well understood. Here, we demonstrate that bile acids inhibit human and murine platelet activation, adhesion and spreading, leading to reduced thrombus formation under flow conditions. We identified the G-protein coupled receptor TGR5 in platelets and provide support for its role as mediator of bile acid-induced impairment of platelet activation. In the liver, TGR5 couples to Gαs proteins, activates the adenylate cyclase to induce a transient cAMP rise and stimulates the MAPK signaling pathway to regulate cholangiocyte proliferation, hepatocyte survival and inflammation. In this report, we demonstrate that the genetic deficiency of TGR5 in mice led to enhanced platelet activation and thrombus formation, suggesting that TGR5 plays an important role in hemostasis. Mechanistically, platelet inhibition is achieved by TGR5 mediated PKA activation and modulation of AKT and ERK1/2 phosphorylation. Thus, this report provides evidence for the ability of TGR5 ligands to reduce platelet activation and identifies TGR5 agonism as a new target for the prevention of cardiovascular diseases.

A284 EVALUATING THE INCIDENCE OF MAJOR GASTROINTESTINAL BLEEDING IN PATIENTS WITH CIRRHOSIS ON ANTICOAGULATION THERAPY: A TERTIARY SINGLE CENTRE EXPERIENCE

Abstract Background Patients with chronic liver disease, especially those with cirrhosis, face an increased risk of bleeding and thrombosis due to hemostasis dysregulation. In such cases, prescribing anticoagulation therapy requires a cautious approach, given the inherent risk-reduction in thrombosis alongside a suspected elevated bleeding risk. Aims Perform a retrospective study to evaluate anticoagulation safety and gastrointestinal bleeding incidence in cirrhotic patients. Methods A retrospective study was conducted at the University Hospital of London Health Sciences Centre, involving patients who attended outpatient hepatology clinics between 2010 and 2022. To be eligible, patients had to be 18 years or older and have confirmed cirrhosis through imaging, radiology, or pathology. They were monitored for up to 5 years for the primary outcome, which was major gastrointestinal bleeding requiring hospitalization. Exclusions included patients with underlying hematologic or thrombotic conditions contributing to abnormal hemostasis beyond cirrhosis and those who underwent liver transplantation. Descriptive statistics were provided, such as means and standard deviations for continuous variables, and proportions/percentages for categorical ones. Group comparisons utilized the Student's t-test for continuous variables and chi-squared tests for categorical variables. Univariate and multivariate logistic regression were employed to calculate odds ratios and their associated 95% confidence intervals for the primary outcome Results We retrospectively enrolled 300 patients, with 34.0% having cirrhosis and anticoagulation history. The average age was 63.1 years [95% CI 61.7 – 64.6], and 43.7% were female. Atrial fibrillation was the primary reason for anticoagulation (53.9%). Cirrhotic patients on anticoagulation had a 13.1% bleeding rate, while those without had 18.6% (p-value = 0.207, not significant). Univariate analysis suggested a possible link between anticoagulation and bleeding risk (OR 1.51 [95% CI 0.79 – 2.89]). No covariates predicted bleeding in univariate logistic regression. In multivariate analysis adjusting for age and sex, the odds ratio remained at 1.50 [95% CI 0.78 – 2.88]. The study hints at a higher bleeding risk in cirrhotic patients on anticoagulation, but more statistical power is needed, either through a larger sample or a multicenter approach. Conclusions To further investigate the association between anticoagulation and bleeding risk in cirrhotic patients, a larger multicentre study with increased enrollment is required. Nonetheless, interim findings do suggest the potential existence of an associated bleeding risk in cirrhotic patients undergoing anticoagulation therapy, albeit with a small observed effect size and uncertain clinical significance. Funding Agencies None

Biological Abnormalities of Hemostasis in Patients with Epistaxis or Menorrhagia in Yaoundé, Cameroon.

In Cameroon, screening and diagnosis of minor hemorrhagic syndromes remain difficult and few research studies have been done to assess the magnitude of future bleeding risk and the burden of these disorders on quality of life. Epistaxis and menorrhagia are the two leading causes of bleeding disorders in the world population. The aim of this study was to investigate the biological abnormalities of hemostasis in patients with epistaxis and menorrhagia. From January to December 2021, we conducted a cross-sectional study in six hospitals with a gynecology and ENT department. We selected patients who presented epistasis or menorrhagia through clinical file and made them pass an interview and biological exams. Venous blood collected on EDTA tube allowed us to measure full blood count, thin blood smear, and blood grouping. PT, APPT, and fibrinogen assay were measured from citrate platelet-poor plasma. This plasma stored at -20°C for a maximum of 3 months allowed us to measure vWF : Ag and vWF : CBA ELISA. The bleeding time was measured at the time of sampling. In total, our study population consisted of 60 patients aged 01-45 years. Epistaxis (40%) and menorrhagia (29%) were the two main causes of bleeding complaints in our study, in addition to gingivorrhagia (15%) and prolonged bleeding after injury (03%). Almost 60% of the population had at least one abnormal hemostasis parameter. The main abnormalities found were low von Willebrand factor (30.19%), presence of macroplatelets (16.98%), prolonged bleeding time (15.09%), prolonged PT (15.09%), and low platelet count (¬07.55%). In Cameroon, bleeding disorders manifested by epistaxis and menorrhagia are mainly caused by abnormalities of primary hemostasis.

Co-existence of hematological disease in cardiac patients presented with chest pain

Abstract Introduction The important association between hematological disorders and cardiovascular system originates within multiple points of interface, ranging from heart and its structural constituents, coronary arteries and veins, cerebrovascular, pulmonary and peripheral vasculature. Any anomaly of either of the blood components can severely affect the blood flow and blood viscosity which finally leads to thrombosis. Objective This study will help clinicians to evaluate those patients having hematological abnormality and are having potential prothrombotic state due to abnormal hemostasis. Rationale Introducing cardiac health screening in patients with any hematological disease can improve the quality of life of these patients. Material and methods This cross sectional analytical study was conducted in hematology Department of Peshawar institute of Cardiology after approval from hospital ethical and research committee. Study duration was 6 months. All patients were subjected to detailed history, clinical examination. Demographic (Age, Gender) and relevant clinical information. Investigation like CBC, coagulation profile, hemolytic profile, Chest X-ray, ECG, Echo, Angiography findings were used to monitor patient’s clinical status. Results Out of 43 patients, 08 cases (18.60%) presented were of benign hematological disorder and the rest 35 cases (81.40%) presented with malignant hematological disorders. A significant P- value of (0.000) was observed in patients with malignant hematological disorder in association with benign hematological disorders. Conclusion From our study findings, several local and international platforms data, it can be concluded that those hematological abnormalities which have direct or indirect association with thromboembolic events can present with cardiac manifestation in the form of chest pain or acute myocardial injury at any stage of disease process. Therefore, clinicians must evaluate patients having hematological abnormality and are having potential prothrombotic state due to abnormal hemostasis for cardiac manifestation of the disease as well.

FcγRIIa - dependent platelet activation identified in COVID-19 vaccine-induced immune thrombotic thrombocytopenia-, heparin-induced thrombocytopenia, streptokinase- and anisoylated plasminogen-streptokinase activator complex-induced platelet activation.

Coronavirus disease 2019 (COVID-19), which was caused by the coronavirus - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was globally responsible for remarkable morbidity and mortality. Several highly effective vaccines for COVID-19 were developed and disseminated worldwide within an unprecedented timescale. Rare but dangerous clotting and thrombocytopenia events, and subsequent coagulation abnormalities, have been reported after massive vaccination against SARS-CoV-2. Soon after their global rollout, reports of a morbid clinical syndrome following vaccination with adenovirus-DNA-based vaccines appeared. In the spring of 2021, reports of a novel, rare and morbid clinical syndrome, with clinically devastating and fatal complication after vaccination with adenovirus-based coronavirus vaccines (Janssen/Johnson & Johnson and Astra-Zeneca vaccines) led to a brief suspension of their use by several countries. Those complications were associated with unusual cerebral and splanchnic venous thrombosis, and circulating autoantibodies directed against anti-platelet factor 4 (PF4), a protein secreted from platelets, leading to the designation: Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT). The reported VITT incidence remains very low and does not affect the overall benefit of immunization, however, if left untreated, VITT can be debilitating or even fatal. VITT resembled specific adverse drugs' reactions that also involved the production of autoantibodies and subsequent abnormal platelet activation through platelet FcγRIIa. These unusual but well-documented drug reactions were heparin-induced thrombocytopenia (HIT), streptokinase- (SK), and anisoylated plasminogen-streptokinase activator complex- (APSAC) associated with platelet-activating antibodies. There was considerable overlapping of clinical features between VITT, COVID-19 and these adverse drugs' reactions. We review the phenomenon of VITT against the backdrop of shared and common mechanisms that underlie HIT-, SK-, and APSAC-platelet FcγRIIa-dependent platelet activation. An understanding of VITT's pathogenesis may be achieved by comparing and contrasting VITT-, HIT-, SK- and APSAC-induced platelet activation mechanisms, their respective physiopathology and similarities. Discussing these conditions in parallel provides insight into complex immunological disorders and diseases associated with abnormal hemostasis and thrombosis in particular.

Thrombotic Risk in Children with Idiopathic Nephrotic Syndrome in Abidjan, Ivory Coast

Aims: The objective of this study was to evaluate the thrombotic risk in children of Abidjan suffering with the idiopathic nephrotic syndrome (INS).&#x0D; Study Location and Period: This study was conducted in 56 children with INS, aged 24 to 144 months and followed up at the pediatric nephrology unit of the University Hospital of Yopougon. It took place from January 2021 to April 2022. Blood samples were taken in that unit for each child. Blood counts and albumin levels were performed at the laboratory of biology and medical research of the National Institute of Public Health (INSP) in Adjamé. Fibrinogen, factors V, VII, VIII, IX, antithrombin III (ATIII), protein C, protein S and D-dimers were measured at Laboratory Longchamp of Plateau.&#x0D; Methodology: In each child, blood samples were collected by venipuncture on dry tubes, with sodium citrate and EDTA. Blood counts were performed on Sysmex XT 2000i, albumin levels on Cobas C311 and haemostasis parameters on Sysmex CS1600.&#x0D; Results: Of the 56 children recruited, hypoalbuminemia &lt; 30 g/L was found in 35 (62.5%) children. The most common haemostasis abnormalities were increased D-Dimer in 35 (62.5%) children, hyperfibrinemia in 34(60.7%) children, increased protein C in 31 (55.3%) children, thrombocytosis in 29 (51.8%) children. ATIII and protein S deficiencies were found in 16 (28.6%) and 11 (19.6%) children respectively. Thrombosis risk was present in 36 (64.3%) children. A significant association was found between albuminemia &lt; 20 g/L and ATIII &lt; 70%.&#x0D; Conclusion: There is a thrombotic risk in children with INS, which may be increased by hypoalbuminemia &lt; 20 g/L.

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.

Expert consensus on critical values of hemorrhagic diseases (2023 version)

Hemorrhagic diseases are common clinical diseases characterized by abnormal hemostasis or coagulation mechanisms caused by various reasons, which seriously threaten the life safety of patients. Rapid and accurate diagnosis, as well as timely and appropriate treatment, are crucial for improving clinical outcomes. This consensus aims to comprehensively evaluate the critical state of patients with hemorrhagic disease from multiple perspectives, such as laboratory, radiographic, and ultrasound examinations. Through the compilation of relevant literature and wide-ranging expert opinions, a preliminary expert consensus on critical values of hemorrhagic diseases has been formulated to help optimize clinical care for these patients.

Association between acute complications in PMM2-CDG patients and haemostasis anomalies: Data from a multicentric study and suggestions for acute management

ObjectivesPatients with PMM2-CDG develop acute events (stroke-like episodes (SLEs), thromboses, haemorrhages, seizures, migraines) associated with both clotting factors (factor XI) and coagulation inhibitors (antithrombin, protein C and protein S) deficiencies. The aim of the study was to correlate acute events to haemostasis and propose practical guidelines. MethodsIn this multicentric retrospective study, we evaluated clinical, radiological, haemostasis and electroencephalography data for PMM2-CDG patients hospitalized for acute events. Cerebral events were classified as thrombosis, haemorrhage, SLE, or “stroke mimic” (SM: normal brain imaging or evoking a migraine). ResultsThirteen patients had a total of 31 acute episodes: 27 cerebral events with 7 SLEs, 4 venous thromboses, 4 haemorrhages (3 associated with thrombosis), 15 SMs at a mean age of 7.7 years; 4 non-cerebral thromboses, one of which included bleeding. A trigger was frequently involved (infection, head trauma). Although sometimes normal at baseline state, factor XI, antithrombin and protein C levels decreased during these episodes. No correlation between haemostasis anomalies and type of acute event was found. DiscussionAcute events in PMM2-CDG are not negligible and are associated with haemostasis anomalies. An emergency protocol is proposed for their prevention and treatment (https://www.filiere-g2m.fr/urgences). For cerebral events, brain Magnetic Resonance Imaging with perfusion weight imaging and diffusion sequences, electroencephalogram and haemostasis protein levels guide the treatment: anticoagulation, antithrombin or fresh frozen plasma supplementation, antiepileptic therapy. Preventing bleeding and thrombosis is required in cases of surgery, prolonged immobilization, hormone replacement therapy. ConclusionAcute events in PMM2-CDG are associated with abnormal haemostasis, requiring practical guidance.

Clues of incomplete reversal of heparin in cardiac surgery.

In our center, an unusual rate of patients had abnormalities of hemostasis in immediate postoperative period of cardiac surgery. Our objectives were to identify the cause of these sudden hemostasis abnormalities and to evaluate the performances of point of care coagulation testing. In this prospective and descriptive study, we included 33 consecutive patients undergoing elective cardiac surgery for 1month. Heparin-induced anticoagulation and calculation of the protamine dose were tested by the Hemostasis Management System Plus device (Medtronic, Minneapolis, MN, USA). Fifteen minutes after the end of the protamine infusion, activated clotting time (ACT), activated partial thromboplastin time and anti Xa activity were measured. In case of unusual clinical bleeding, a Quantra analysis (Stago, HemoSonics LLC, Charlottesville, VA) was added. Residual antiXa activity >0.2 IU/mL after neutralization was present in 44% of patients. Our investigation concluded incomplete heparin reversal. There was no association between cellular reinfusate and the presence of heparin. The unusual rate of hemostasis abnormalities was explained by a less efficient protamine reversal of heparin. ACT and Clot Time Ratio (CTR, Quantra system) correlated with AntiXa with Spearman's coefficients of 0.85 (p < .0001) and 0.95 (p = .0012), respectively. About ACT, a threshold of 150 seconds had a sensitivity of 85% [58-97] and a specificity of 85% [58-97%] for detection of AntiXa>0.2. For CTR, a threshold of 1.4 had a sensitivity of 67% [30-94] and a specificity of 100% [18-100]. The use of point of care coagulation testing is effective in detecting incomplete reversal of heparin.

Characteristics of Products of Fibrinogen Origin in the Presence of Anti- SARS-CoV-2 IgG in the Bloodstream.

The hemostasis system has been extensively investigated in patients in the acute phase of coronavirus disease 2019 (COVID-19). In contrast, the post-COVID syndrome is a poorly known entity, and there is a lack of information on the mechanisms underlying the hemostasis abnormalities in the post-COVID period. To analyze the potential changes in the parameters of the hemostasis system in the post- COVID period in the plasma of donors with different titers of anti-SARS-CoV-2 IgG. The plasma from 160 donors who had recovered from COVID infection was used in the study. Based on the results of the Abbott SARS-CoV-2 IgG serological assay, all donors were divided into several groups: 5 ± 3 (n = 20); 55 ± 5 (n = 20); 65 ± 5 (n = 20); 75 ± 5 (n = 20); 85 ± 5 (n = 20); 95 ± 5 (n = 20); 125 ± 5 (n = 20); 175 ± 5 (n = 20) Index (S/C). A total of 20 healthy individuals without anti-SARS-CoV-2 IgG constituted the control group. Key laboratory parameters, such as fibrinogen concentrations, soluble fibrin monomer complex (SFMCs), and Ddimer, were investigated. In addition, the qualitative composition of the fraction of SFMCs was analyzed. The slight increase in the concentration of fibrinogen, SFMCs, and D-dimers in some donor groups have been found, which could cause the development of hemostasis disorders. In the fraction of SFMCs, the increase in the number of protein fragments with a molecular weight of less than 250 kDa and an increase in the level of proteins with a molecular weight of more than 270 kDa was revealed. The obtained results indicated the relationship between the changes in the parameters of the hemostasis system and the titers of anti-SARS-CoV-2 IgG in donors in the post-COVID period. It can be assumed that donors with higher titers of anti-SARS-CoV-2 IgG (>55 ± 5 Index (S/C)) are more prone to hemostasis abnormalities in the post-COVID period since a pronounced imbalance in the levels of SFMCs and D-dimer characterizes them. The appearance of protein fragments of different molecular weights in the fraction of SFMC points to uncontrolled activation of biochemical processes involving molecules of fibrinogenic origin. Additional studies are required to elucidate the role of anti-SARS-CoV-2 IgG in the post-COVID period.

Alteration of Coagulation Profile in Preeclampsia And Eclampsia Patients At Tertiary Level Hospital

Background: Preeclampsia and eclampsia is associated with a risk of abnormal hemostasis that occurs most commonly secondary to thrombocytopenia. Automated analyze technique measures whole blood coagulation and has been used to manage coagulation defects in obstetric patients. Objective: To find out the alteration of coagulation profile beyond physiological level in preeclampsia and eclampsia patients for early detection and planning of management. Method: It was a observation type of cross sectional study carried out Department of Obs&amp; Gynae, Dhaka Medical College Hospital, Dhaka. Severe pre-eclamptic and eclamptic patients admitted in the department of Obstetrics &amp;Gynaecology, Dhaka Medical College Hospital during the period of July 2018 to December 2018. Data were collected as predesigned data collection sheet and for coagulation profile. Collection of venous sample about 5ml of blood were done without a pressure cuff allowing the blood to enter the syringe by continuous free flow and sending to the laboratory for coagulation assay by automated analyzer Sysmex CA500. Results: In this study mean age was 26.94 years, majority 56% age group was 26-30 years of age. The mean gestational age was 32.36 weeks. All the coagulation parameters were altered in 6% of the patients, 4 parameters were altered in 10% of the patients, 3 parameters were altered in 16% of the patients 2 and 1 parameters were altered in 24% and 44% patients respectively. Regarding coagulation profile, thrombocytopenia was present in 22% patients, prothombin time was prolonged in 10% of the patients, APTT was prolonged in 20% of the patients, and fibrinogen level was reduced in 40% of the patients and FDP was elevated 32% of the patients. Out of 50 severe preeclamptic and eclamptic patients, 6% of the patients developed DIC in whom all the coagulation parameters were altered. Conclusion: In this study, in patients of severe pre-eclampsia and eclampsia 22% patients had thrombocytopenia. 6% of the patients had alteration of all the coagulation parameters. Coagulation indices were altered not only in the patients with reduced platelet count but also in the patients with normal platelet count. Among the patients, 6% of the patients developed DIC, PPH developed in 12% of the patients and maternal death occurred in 4% of the patients. J Dhaka Med Coll. 2021; 30(2) : 214-219

Precision Navigation of Venous Thrombosis Guided by Viscosity-Activatable Near-Infrared Fluorescence.

Thrombus are blood clots formed by abnormal hemostasis in blood vessels and are closely associated with various diseases such as pulmonary embolism, myocardial infarction and stroke. Early diagnosis and treatment of thrombus is the key to reducing the high risk of thrombotic disease. Given that early thrombus is small in early size, free instability, wide regional distribution and fast formation, it is urgent to develop all-inclusive detection methods that combine high signal-to-noise ratio, in situ dynamic and rapid in-depth tissue imaging. Near-infrared (NIR) fluorescence imaging, with its excellent high spatiotemporal resolution and tissue penetration depth, is a powerful technique for direct visualization of thrombotic events in situ. Considering the fibrin highly expressed in the thrombus is a typical thrombotic target. Moreover, the viscosity of the thrombus is markedly higher than its surroundings. Therefore, we developed a fibrin-targeting and viscosity-activating thrombus NIR fluorescent probe (TIR-V) for high-resolution and high-sensitivity in situ lighten-up thrombus. TIR-V has the advantages of good thrombus targeting, significant "off-on" fluorescence specific response to viscosity, bright NIR fluorescence and good biocompatibility. The thrombus is clearly delineated by a high signal-to-noise ratio NIR fluorescence imaging, enabling imaging detection and precise navigation of thrombotic regions. This work demonstrates the potential of TIR-V as a bifunctional probe for definitive diagnostic imaging and direct navigation of thrombotic lesions in clinical applications.

Detection of Hemostasis Abnormalities in Type 2 Diabetes Mellitus Using Thromboelastography.

Type 2 DM (T2DM) is associated with inflammation and vascular dysfunction which impact hemostasis. Thromboelastography (TEG) as a hemostasis assessment method, is not routinely applied in T2DM. We aimed to detect hemostasis abnormalities by using the TEG method in association with glycemic levels and type of therapy among T2DM patients. A cross-sectional study was conducted among T2DM patients attending the Endocrinology Clinic of Saiful Anwar Hospital, Indonesia. Glycemic profiles were determined using fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPPG), and glycosylated hemoglobin (HbA1c). Therapy for T2DM was classified into insulin and non-insulin regimens. The primary and secondary hemostasis profile were examined using TEG and was classified as hypo- hyper- and normo-coagulable states. A total of 57 T2DM patients were included. Kruskal-Wallis test did not reveal a significant association between glycemic profiles and groups of hemostasis. However, the median HbA1c was higher in the hypercoagulable group of primary hemostasis and fibrinolysis. The median FPG and 2hPPG were higher in the normo-coagulable group of secondary hemostasis. Logistic regression did not indicate a significant association between type of therapy for diabetes and hemostasis profile. This study did not find significant associations between glycemic levels and type of DM therapy with hemostasis profiles using the TEG method in patients with T2DM.

Hemostatic Abnormalities in Gaucher Disease: Mechanisms and Clinical Implications.

Gaucher disease (GD) is a rare inherited lysosomal metabolism disorder, characterized by an accumulation into lysosomes of reticuloendothelial cells, especially in the bone marrow, spleen, and liver of β-glucosylceramide and glucosyl sphingosine, which is its deacylated product. Impaired storage is responsible for a chronic inflammatory state at the sites of accumulation and together represents the pathophysiological cause of GD. GD is a progressive, multi-organ chronic disorder. Type 1 GD is the most prevalent form, with heterogeneous multisystem involvement and different severity of symptoms at any age. Hematological involvement is consistent, and a bleeding tendency is frequent, particularly at diagnosis. Several coagulation and primary hemostasis abnormalities are observed in GD. Bleeding manifestations are rarely severe and usually mucocutaneous. Post-operative, delivery, and post-partum hemorrhages are also common. Thrombocytopenia, platelet function defects, and clotting abnormalities, alone or variably associated, contribute to increase the risk of bleeding in GD. Enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) are the two specific available treatments effective in improving typical hematological symptoms and abnormalities, including those of hemostasis. However, the use of medication to potentiate hemostasis may be also useful in defined clinical situations: recent starting of ERT/SRT, surgery, delivery, and life-threatening bleeding.

A demonstration of factor XI contributing to hemostasis in the absence of factor XII

Factor XIa (FXIa), the activated form of the plasma zymogen FXI, is a trypsin‐like protease that contributes to thrombin generation and hemostasis primarily by activating factor IX (FIX).1 In humans, severe FXI deficiency may cause excessive bleeding with trauma or surgery, particularly when injury involves the mouth, nasopharynx, or urinary tract.2,3 Bleeding severity varies, and many individuals who are FXI deficient do not experience abnormal hemostasis. A variable trauma‐induced bleeding disorder has also been reported in FXI‐deficient dogs,4 cats,5 and cattle.