Routine Coagulation Tests Research Articles

A-154 Non-standard body fluid validation of d-dimer analysis of organox liver perfusate to support clinical evaluations of donor livers prior to transplantation

Abstract Background Non-standard body fluid analysis is considered a challenge to laboratories since very few have been approved by the FDA for routine testing. As medical procedures evolve, the laboratory must balance the requirement to uphold regulatory standards while also supporting procedures that improve patient care. The LUMC Liver Transplant Team recently implemented the use of the FDA-approved OrganOx Metra normothermic machine perfusion instrument for maintaining donor livers under physiologic conditions prior to transplantation. The team mitigates risk for biliary complications associated with fibrin microthrombi by perfusing a combination of alteplase rTPA with fresh frozen plasma and monitoring the prevalence of fibrin through the release of D-dimers over the course of ex situ normothermic preservation. Liver perfusate is not an FDA-approved specimen type for the analysis of D-dimer and requires laboratory verification as a compatible specimen for analysis. Methods The D-dimer HS 500 assay was performed on an ACL TOP 750 analyzer. Carry-over studies evaluated activated partial thromboplastin time (aPTT) of a normal control (citrated plasma) specimen initially, and repeatedly in-between sets of D-dimer measurements of heparinized perfusate specimen. Recovery studies were performed by mixing liver perfusate with citrated plasma spiked with D-dimer in known ratios, allowing for the calculation of an expected value of D-dimer. Results Carry-over studies measuring aPTTs of normal plasma specimens provided %CVs of 1 and 3%. Recovery of D-dimer in seven sets of independent add-mixture series (three mixed specimen per set) was on average 105% with a range from 95 to 113% recovery. Conclusions Concern for cross-contamination of perfusate specimen containing heparin anticoagulant on analyzers used to evaluate routine coagulation testing was mitigated by the results of the carry-over study, which provided %CV within the manufacturer limit for intraday precision. Recovery studies evaluating matrix effect for the analysis of D-dimer on liver perfusate generated under the LUMC liver transplant protocol indicated that the matrix of the perfusate did not impact D-dimer analysis, as compared to the FDA-approved specimen type.

Coagulation disorders in myocardial infarction with nonobstructive coronary arteries

Aim. To investigate the state of the platelet and plasma components of hemostasis in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA).Material and methods. The study included 42 patients with non-ST-segment elevation myocardial infarction (NSTEMI): MINOCA (n=24) and MI-CAD (n=18). Platelet aggregation ability in response to activation was evaluated using Solar AP2110 and LASCA aggregometers. Platelet functional activity and calcium signaling were assessed using flow cytometry methods. The plasma component of hemostasis, in addition to routine coagulation tests was evaluated using the global coagulation test "Thrombodynamics". The control groups for tests consisted of healthy volunteers.Results. When analyzing the ability of platelets to form aggregates by the aggregometry tests, it was found that platelets in the MINOCA group formed aggregates significantly worse upon ADP stimulation at various concentrations compared to the MI-CAD group. However, when platelets were stimulated with collagen, the opposite effect was observed: in the MI-CAD group, there was a noticeable decrease in aggregate formation in terms of light scattering amplitude compared to the MINOCA group. Flow cytometry using the functional platelet activity test protocol revealed that both groups showed a significantly increased platelet size after activation, reduced platelet granularity) both at rest and upon activation, significantly decreased number of procoagulant phosphatidylserine-positive platelets, and reduced dense granule release upon activation compared to healthy volunteers. The calcium signaling test showed a weakened calcium release in response to ADP in the MINOCA group compared to the MI-CAD group. In the study of the plasma component, no significant differences between the groups or deviations were found according to both routine tests and the "Thrombodynamics" test.Conclusion. Platelet activity did not differ significantly between the MINOCA and MI-CAD groups; however, in the MINOCA group, platelet activity was lower in some tests compared to the MI-CAD group. In the study of the plasma hemostasis component, normocoagulation was recorded in both groups.

Clinical, Laboratory, and Molecular Aspects of Factor V Deficiency.

Factor V (FV) is a glycoprotein that plays a pivotal role in hemostasis, being involved in coagulant and anticoagulant pathways. Congenital FV deficiency is a rare bleeding disorder with an incidence of 1 per million live births, considering the most severe homozygous form. FV deficiency is diagnosed using routine coagulation tests and FV activity assays. Several mutations, including missense, nonsense, and frameshift, have been detected in the F5 gene. Clinical symptoms are variable, ranging from mild ecchymoses and mucosal bleeding to life-threatening intracranial hemorrhage. The mainstay of treatment includes fresh-frozen plasma, preferentially virus-inactivated. In this narrative review, we provide an update of the main laboratory, molecular, clinical, and therapeutic features of inherited FV deficiency.

Analytical and Clinical Validation of a Non-Ristocetin Based VWF Assay on 2 Automated Analyzers in a Large Reference Laboratory.

Historically, von Willebrand factor (VWF) activity assays utilized ristocetin despite limitations including poor limits of detection and high imprecision. Newer VWF activity assays such as the INNOVANCE® VWF Ac assay, however, do not rely on ristocetin to measure platelet-dependent VWF function. The purpose of this study was to evaluate the analytical and clinical performance of the Siemens Healthineers INNOVANCE VWF Ac Assay on the Siemens BCS® XP and the Sysmex® CS-2500 systems in a large reference laboratory setting. Performance indicators for the INNOVANCE VWF Ac assay were the limit of quantitation (LoQ), precision, and method comparison. Method comparison studies were performed using remnant plasma patient samples from routine coagulation tests and analyzed using both the INNOVANCE VWF Ac assay and the Siemens Healthineers ristocetin-dependent BC von Willebrand Reagent. Evaluation of the INNOVANCE VWF Ac assay on the BCS® XP and CS-2500 systems demonstrated good precision and a lower LoQ compared to the BC von Willebrand Reagent. Method comparisons support the use of the INNOVANCE VWF Ac assay on the BCS® XP and CS-2500 systems to measure platelet-dependent VWF function. The INNOVANCE VWF Ac assay was able to further assist in von Willebrand disease classification in 6/7 (86%) samples when the result was below the LoQ for the BC von Willebrand Reagent (ristocetin cofactor activity). These data are consistent with the 2021 American Society of Hematology/International Society on Thrombosis and Haemostasis/National Hemophilia Foundation/World Federation of Hemophilia von Willebrand disease guidelines that suggest using newer assays such as the INNOVANCE VWF Ac assay in place of ristocetin cofactor activity assays.

Comparison of thrombodynamic methods and routine hemostasis tests in the evaluation of hypercoagulable syndrome in chronic glomerulonephritis

Nephrotic syndrome (NS) is associated with a high risk of thrombotic complications. In this group of patients, routine local tests for assessing hemostasis do not accurately reflect hypercoagulable state. Global functional tests for assessing hemostasis, including thrombodynamics (TD), are considered promising for assessing disorders in the blood coagulation system of these patients. To compare the rate of hypercoagulability according to routine hemostatic tests and TD and to evaluate the factors associated with increased risk of thrombotic complications in patients with chronic glomerulonephritis (CGN). The study included 94 patients with active CGN who were not receiving anticoagulant therapy; 63 (80.3%) patients had NS, and 31 (19.7%) had active CGN without NS. Hemostasis parameters were assessed using local coagulation tests and TD test. Using logistic regression analysis, factors associated with the risk of thrombosis were assessed. Of the 94 patients with active CGN in 63 without preventive anticoagulant therapy, hypercoagulability according to routine tests was detected in 6 (9.5%) patients with NS and in 3 (9.7%) patients without NS (p<0.05). Hypercoagulability according to the TD test was detected in 24 (53.9%) patients with NS and in 5 (32.2%) without NS (p<0.05). The formation of spontaneous clots was observed in 29 (30.9%) of patients with CGN, most of them 24 (83%) with NS. 10.6% of patients in our cohort experienced thromboembolic events. The risk of thromboembolic events according to the univariate regression analysis was associated with older age, higher lipid levels, use of glucocorticosteroids and detection of spontaneous clots by the TD test. No association of thromboembolic events with abnormalities in routine hemostasis tests was obtained. In patients with CGN with nephrotic syndrome, hypercoagulability is detected in 9.5% of cases with routine coagulation tests and in 53.9% of cases with TD test. Detection of spontaneous clots by TD test is associated with a risk of thromboembolic events.

Empirical and modified hemostatic resuscitation for liver blast injury combined with seawater immersion: A preliminary study

PurposeTo compare the effects of empirical and modified hemostatic resuscitation for liver blast injury combined with seawater immersion. MethodsThirty rabbits were subjected to liver blast injury combined with seawater immersion, and were then divided into 3 groups randomly (n = 10 each): group A (no treatment after immersion), group B (empirical resuscitation with 20 mL hydroxyethyl starch, 50 mg tranexamic acid, 25 IU prothrombin complex concentrate and 50 mg/kg body weight fibrinogen concentrate), and group C (modified resuscitation with additional 10 IU prothrombin complex concentrate and 20 mg/kg body weight fibrinogen concentrate based on group B). Blood samples were gathered at specified moments for assessment of thromboelastography, routine coagulation test, and biochemistry. Mean arterial pressure, heart rate, and survival rate were also documented at each time point. The Kolmogorov-Smirnov test was used to examine the normality of data distribution. Multigroup comparisons were conducted with one-way ANOVA. ResultsLiver blast injury combined with seawater immersion resulted in severe coagulo-fibrinolytic derangement as indicated by prolonged prothrombin time (s) (11.53 ± 0.98 vs. 7.61 ± 0.28, p＜0.001), activated partial thromboplastin time (APTT) (s) (33.48 ± 6.66 vs. 18.23 ± 0.89, p＜0.001), reaction time (R) (min) (5.85 ± 0.96 vs. 2.47 ± 0.53, p＜0.001), decreased maximum amplitude (MA) (mm) (53.20 ± 5.99 vs. 74.92 ± 5.76, p＜0.001) and fibrinogen concentration (g/L) (1.188 ± 0.29 vs. 1.890 ± 0.32, p = 0.003), and increased D-dimer concentration (mg/L) (0.379 ± 0.32 vs. 0.051 ± 0.03, p = 0.005). Both empirical and modified hemostatic resuscitation could improve the coagulo-fibrinolytic states and organ function, as indicated by shortened APTT and R values, decreased D-dimer concentration, increased fibrinogen concentration and MA values, lower concentration of blood urea nitrogen and creatine kinase-MB in group B and group C rabbits in comparison to that observed in group A. Further analysis found that the R values (min) (4.67 ± 0.84 vs. 3.66 ± 0.98, p = 0.038), APTT (s) (23.16 ± 2.75 vs. 18.94 ± 1.05, p = 0.001), MA (mm) (60.10 ± 4.74 vs. 70.21 ± 3.01, p < 0.001), and fibrinogen concentration (g/L) (1.675 ± 0.21 vs. 1.937 ± 0.16, p = 0.013) were remarkably improved in group C than in group B at 2 h and 4 h after injury. In addition, the concentration of blood urea nitrogen (mmol/L) (24.11 ± 1.96 vs. 21.00 ± 3.78, p = 0.047) and creatine kinase-MB (U/L) (85.50 ± 13.60 vs. 69.74 ± 8.56, p = 0.013) were lower in group C than in group B at 6 h after injury. The survival rates in group B and group C were significantly higher than those in group A at 4 h and 6 h after injury (p < 0.001), however, there were no statistical differences in survival rates between group B and group C at each time point. ConclusionsModified hemostatic resuscitation could improve the coagulation parameters and organ function better than empirical hemostatic resuscitation.

Congenital FⅦ Deficiency Associated with a Novel Mutation in F7 Gene

To identify the genetic mutation of coagulation factor Ⅶ ( F7) gene in a pedigree with coagulation factor Ⅶ (FⅦ) deficiency and explore the molecular pathogenesis. The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), D-dimer (DD), fibrin degradation products (FDP) and coagulation factor Ⅶ activity (FⅦ:C) of the proband and her family members were detected by Sysmex-CS5100 analyzer. All exons and exon-intron boundaries of the F7 gene were amplified by PCR followed by direct sequencing. The detected mutation was confirmed by reverse sequencing. The ClustalW software was used to analyze the conservatism of the mutant site. Pathogenicity of the mutation was assessed with Mutation Taster and PolyPhen-2 online bioinformatics software. Structure of the mutant protein was analyzed using Swiss-PdbViewer software. The results of routine coagulation tests showed that PT of the proband was markedly extended to 42.5 s, and her FⅦ:C significantly reduced to 2%. The FⅦ:C of her grandmother, mother and sister had slightly reduced to 49%, 51%, and 42%, respectively. These coagulant parameters of her father were within the normal range. Genetic analysis reveled a heterozygous G>A change at cDNA 646 in exon 6 of F7 gene in the proband, resulting in a replacement of glycine at 156 of FⅦ catalytic region with serine (p.Gly156Ser). The sequencing results of other exons and exon-intron boundaries of her F7 gene were normal. The proband's grandmother, mother and sister were all the carriers of this missense mutation except her father. Bioinformatics analysis showed that the p.Gly156Ser mutation caused polarity change of the amino acid at this site and formation of side chains, leading to increase of protein instability, which may affect catalytic activity of structural domain. Meanwhile, both Mutation Taster and PolyPhen-2 online bioinformatics software also predicted the pathogenicity of this missense mutation with high scores. The heterozygous p.Gly156Ser mutation is the direct cause of the reduced FⅦ in this proband.

Pathological changes of biochemical, hematological and coagulation analyses in patients with COVID-19 disease

The identification of patients with poor prognosis and early detection of COVID-19 disease complications are made possible by pathological analyses of routine hematological, coagulation, and biochemical tests. Interpreting analyses needs to be done within the framework of each patient’s unique clinical picture. It’s also critical to keep an eye on changes at the individual parameter level. From May 20th, 2021, to March 30th, 2024, a comprehensive search of literature was carried out using international databases, such as PubMed, Embase, Web of Science, Scopus, and the Cochrane Library, in compliance with the PRISMA guidelines. The research question was formulated using the PICO strategy. The following terms were used: biochemical parameters in COVID-19, hematological parameters in COVID-19, blood coagulation parameters in COVID-19, indicators of inflammation, and indicators of tissue damage in SARS-CoV-2. Routine hematological, coagulation, and biochemical tests are primarily used to monitor the progression of the disease and the effectiveness of treatment rather than being utilized for the established diagnosis of COVID-19 due to their low specificity. Molecular genetics and immunological techniques should be used to determine the COVID-19 disease diagnosis.

Pediatric Epistaxis-Effectiveness of Conservative Management.

Epistaxis is an emergency medical condition that sometimes requires admission to the emergency department. Pediatric epistaxis differs from epistaxis in the older population in terms of etiology, severity, and management. Our objective was to identify the distinctive features of pediatric epistaxis and determine the appropriate management. This was a retrospective study of 231 medical records of children (<18 years old) with epistaxis of a total of 1171 cases in the general population who presented to our medical center's emergency department between 2013 and 2018. Among 231 admissions, 10 children (4.3%) presented more than once. Male patients accounted for the majority of cases (64.5%), and the average age was 9.4 years. Two children were treated with aspirin because of cardiac valve disease. Anterior bleeding was detected in 101 cases (43.7%), whereas posterior origin was observed in 8 cases (3.5%). In 122 cases (52.8%), there was no active bleeding observed. Nose injury was the cause of epistaxis in 24 cases (10.4%), and 16 admissions (6.9%) followed nasal surgical interventions. Nineteen children (8%) had abnormal coagulation tests, and 7 patients (3%) received blood transfusions. Chemical cauterization was performed in 89 cases (39.3%), and anterior packing was needed in only 9 cases (3.9%). Nine children required hospitalization (3.9%), and 2 needed surgical intervention to control bleeding. Compared with the adult population, there were significantly fewer cases of active bleeding, recurrent epistaxis, anterior packing, or need for hospitalization in the pediatric population. Epistaxis is significantly less severe in the pediatric population, with only a few cases requiring major intervention. Endoscopic examination of the entire nasal cavity and routine coagulation tests are not mandatory unless there is a history of recurrent epistaxis, known coagulopathy, antiplatelet/anticoagulation therapy, or a suspicion of juvenile idiopathic angiofibroma. We suggest using absorbable packs, which offer advantages over cauterization or nonabsorbable packs.

Anti-Thrombin IgA in a Patient with Multiple Myeloma Leading to In Vitro Interference in Multiple Coagulation Tests and Confounding Diagnosis.

We report the case of a 59-year-old multiple myeloma patient in whom an anti-human thrombin IgA antibody led to prolonged in vitro coagulation times, suggesting inhibitors to all intrinsic coagulation factors in the absence of spontaneous bleeding. Routine and extensive special coagulation tests, in vivo bleeding time, and specific antibody testing were performed. Although the patient did not suffer from spontaneous bleeding and had a normal in vivo bleeding time, the anti-human thrombin IgA autoantibody affected all coagulation assays involving human thrombin in vitro, mimicking inhibitors to intrinsic coagulation factors. As the IgA paraprotein and the IgA antibody virtually disappeared after autologous stem cell transplantation, the coagulation tests also largely normalized. Antibodies to human thrombin may interfere with all coagulation assays involving thrombin, imitating a severe coagulopathy. However, in vivo they do not necessarily lead to strongly increased bleeding tendency. Complex and ambiguous coagulation abnormalities should be evaluated and treated in an interdisciplinary setting, including a highly specialized coagulation laboratory, from the beginning.

Evaluation of Clotting Parameters in Pregnant Women with Placental Blood Clots: Impact of Patient Characteristics and Assessment of Clexane Efficacy

Background: Clexane is used in pregnant women (PW) to minimize placental blood clotting (PBC) and fetal danger. Standard coagulation tests such as prothrombin time (PT), activated partial thromboplastin time (APTT), and international normalized ratio (INR) are critical for anticoagulant medication optimization. As a result, the study's goal was to evaluate the efficacy of clexane as well as adherence to the American Heart Association's recommended limits for routine coagulation tests. Methods: The study included forty normal PW as controls and forty PW with PBC as patients from Al-Mafraq Hospital in Jordan. Patients were administered daily subcutaneous injections of 40 mg of clexane as an anticoagulant, in conjunction with a daily 75 mg aspirin regimen. During the first trimester, 5 ml of venous blood were drawn from each participant. The PT, INR and APTT were measured. This assessment also considered variables including plasma fibrinogen concentration (PFC), age, body mass index (BMI), blood type, and fetal gender. Results: The mean age \(\pm\) SD were 29.6 \(\pm\) 6.2 for the patient group and 28.3 \(\pm\) 5.9 years for the control group. The changes in PT, INR, APTT and PFC between the control and patient groups were statistically significant independent of mother's age, BMI, baby gender, or blood type. Patients displayed inadequate anticoagulation with an INR of 0.8, falling below the recommended therapeutic range of 2-3 for anticoagulant treatment. Surprisingly, by the end of the clinical study, all patients under investigation had safely delivered their babies without difficulties. Conclusion: The observed rise in fibrinogen levels among patients may contribute to PBC formation, necessitating further investigation. Evaluation of the safety and efficacy of a combined 40 mg Clexane and 75 mg aspirin regimen in PW from the Al-Mafraq region, Jordan, is warranted.

Evaluation of perioperative routine coagulation testing versus thromboelastography for major liver resection - A single-arm, prospective, interventional trial (PORTAL trial).

The International Normalised Ratio (INR), which assesses the loss of procoagulant factors in the extrinsic pathway, fails to evaluate the coagulation abnormalities comprehensively after a major liver resection, which often leads to reduced synthesis of procoagulant and anticoagulant-factors. This study was conducted with an aim to study the trend and compare the results of routine coagulation tests and thromboelastography (TEG) during the perioperative period in patients undergoing major liver resections (≥3 segments). Twenty-five patients who underwent a major liver resection were enrolled. This prospective, single-arm, interventional study was performed with the primary objective of determining the serial changes in conventional coagulation tests and TEG during the perioperative period in patients undergoing major liver resections, at the preincision period, intraoperative period, postoperatively, at 48 h and on the fifth postoperative day. Transfusion requirements of blood components were also assessed with a TEG-guided replacement strategy. Spearman rank-order correlation was used to study the relationships of coagulation tests (both TEG and conventional tests) at each time point. The prothrombin time (PT)-INR was elevated in 14 patients (56%) at the intraoperative, immediate postoperative and 48-h time points in contrast to the TEG parameters, which remained normal in all patients. Blood component transfusion was avoided in 4, 11 and 10 patients at the intraoperative, immediate postoperative and 48-h time points, respectively. International Normalised Ratio overestimates the coagulopathy in patients undergoing major liver resection, and a thromboelastography-guided transfusion strategy reduces overall transfusion requirements.

Evaluation of Innovative Laboratory Tests to Predict a Thrombotic Phenotype in a Family with Dysfibrinogenemia and a Novel FGG Mutation

Background: Hypodysfibrinogenemia is a rare hereditary fibrinogen disorder characterized by quantitative and qualitative fibrinogen defects. These fibrinogen defects can cause thrombotic and hemorrhagic phenotypes. Unfortunately, predicting the phenotype in a specific patient is often not possible with routine coagulation tests. Aims: To characterize the phenotype and the genetic profile of a family with hypodysfibrinogenemia and to investigate the ability of innovative tests to predict bleeding and/or thrombotic phenotypes in asymptomatic family members. Methods: The proband, a 60-year-old woman with both bleeding and thrombotic complications who is currently on DOAC treatment, and two daughters were referred to our Hemophilia Treatment Center (HTC) for phenotypical and genotypical analysis of a congenital fibrinogen disorder (CFD). Extensive laboratory testing was done, as well as DNA-sequence analysis and molecular modelling. Thrombin generation and microfluidic testing were also performed to investigate their ability in phenotype prediction. Results: Fibrinogen activity and antigen levels led to the diagnosis of dysfibrinogenemia in the proband and hypodysfibrinogenemia in both daughters. In all three cases, the same heterozygous missense mutation in the FGG gene was uncovered. This likely pathogenic mutation leads to the p.(Tyr375Cys) amino acid change. Molecular modeling predicted possible conformational changes or covalent dimerization of the fibrinogen molecule. Thrombin generation was elevated in one daughter. Microfluidic testing showed enhanced fibrin formation in both daughters, regardless of the coagulation trigger. Conclusion: We described a family with hypodysfibrinogenemia in whom a novel heterozygous missense mutation in the FGG gene was found, possibly leading to conformational changes or covalent dimerization of the fibrinogen molecule. Furthermore we showed that microfluidic testing and thrombin generation can indicate a thrombotic phenotype in these patients, not detected with routine coagulation tests.

Assessing Pre-Operative Bleeding Risk Using INR/aPTT: A Systematic Review

Background: The prothrombin time (PT) and activated partial thromboplastin time (aPTT) are often considered “routine” tests to assess perioperative bleeding risk. The PT and its mathematical derivative, the international normalized ratio (INR), allows for monitoring of vitamin K antagonist therapy. The aPTT was developed to screen for hemophilia A and B in family members of affected individuals. Both tests perform extremely poorly as screening tests for inherited bleeding disorders. Therefore, their utility in predicting peri-operative bleeding has been questioned. Objective: The primary objective was to examine the relationship between pre-operative coagulation results and peri-operative bleeding in pediatric and adult patients undergoing elective surgery in the published literature. Methods: A systematic review was conducted using a comprehensive search of MEDLINE, EMBASE, and grey literature between 1970 to July 2022. Randomized trials and observational studies that assessed the predictive accuracy of pre-procedural INR and aPTT test results for perioperative bleeding we deemed eligible for inclusion. Two reviewers independently screened and performed data extraction. A third reviewer adjudicated decisions when consensus could not be reached. Outcomes included any bleeding events in the postoperative period. The study protocol was registered online on PROSPERO (CRD42023385588). Results: 5700 articles were screened, and 79 studies were included in the systematic review. Major surgery (N=53) types included cardiac (n=14), neurosurgery (n=11), liver transplantation or resection (n=16) and general surgery (n=12). Minor surgeries included otolaryngology procedures (n=14) and other minor surgeries/procedures (e.g. pediatric spinal anesthesia, gastrointestinal endoscopy and related procedures, thoracocentesis, hernia repair, circumcision) (n=12). Bleeding complications were rare for minor surgeries and only one out of 26 studies found an association between coagulation test results and bleeding. Thirty-two out of 37 (86.5%) papers exploring other major surgeries found no association or reported a sensitivity under 50% between coagulation test results and bleeding (see Figure 1). Seven out of 16 studies (43.8%) on liver transplantation or resection found an association between the INR and bleeding (see Figure 2). None of the studies evaluated were randomized and none of the observational studies had outcomes adjudicated in blinded fashion. Conclusion: Our findings confirm that bleeding events are rare in minor surgeries, and that coagulation testing is of limited utility in this setting. Similar conclusions can be drawn for patients undergoing major surgeries, with one exception - in patients with liver disease or liver cancer - as there may be an association between bleeding and the pre-operative INR with further studies required. Despite the absence of evidence supporting the practice, routine pre-operative coagulation testing remains prevalent, highlighting the need for targeted knowledge translation.

PB1166 The True Effect of Haemolysis Interference on Routine Coagulation Tests Using Paired Matched Samples Performed on the Sysmex CN-Series Coagulation Analyser

PB1166 The True Effect of Haemolysis Interference on Routine Coagulation Tests Using Paired Matched Samples Performed on the Sysmex CN-Series Coagulation Analyser

Bleeding Diathesis Secondary to a Heparin-Like Anticoagulant in a Patient with Multiple Myeloma—A Case Report and Review of Literature

AbstractMultiple myeloma (MM) is a clonal plasma cell disorder that commonly presents with anemia, renal failure, hypercalcemia, and lytic bone lesions. MM is also frequently associated with thrombotic complications; however, it may rarely present with bleeding diathesis. We report a case of a 42-year-old gentleman with relapsed immunoglobulin G lambda MM who presented with epistaxis, gingival bleeding, and oozing at the venepuncture site. Routine tests of coagulation revealed a prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time. The PT and aPTT failed to correct with pooled normal plasma and the patient was thus diagnosed to have an acquired heparin-like anticoagulant (HLAC). The source of this HLAC has long been debated, but recent data have demonstrated that this HLAC may be the paraproteins produced by the malignant plasma cells. The patient was treated with intravenous protamine sulfate, repeated cycles of plasma exchange, and a daratumumab-based quadruplet regimen but eventually succumbed to an intracranial hemorrhage. HLAC is a rare but potentially fatal complication of MM that must be considered when patients with MM present with bleeding diathesis.

Sepsis-induced coagulopathy is associated with new episodes of atrial fibrillation in patients admitted to critical care in sinus rhythm.

Sepsis is a life-threatening disease commonly complicated by activation of coagulation and immune pathways. Sepsis-induced coagulopathy (SIC) is associated with micro- and macrothrombosis, but its relation to other cardiovascular complications remains less clear. In this study we explored associations between SIC and the occurrence of atrial fibrillation (AF) in patients admitted to the Intensive Care Unit (ICU) in sinus rhythm. We also aimed to identify predictive factors for the development of AF in patients with and without SIC. Data were extracted from the publicly available AmsterdamUMCdb database. Patients with sepsis and documented sinus rhythm on admission to ICU were included. Patients were stratified into those who fulfilled the criteria for SIC and those who did not. Following univariate analysis, logistic regression models were developed to describe the association between routinely documented demographics and blood results and the development of at least one episode of AF. Machine learning methods (gradient boosting machines and random forest) were applied to define the predictive importance of factors contributing to the development of AF. Age was the strongest predictor for the development of AF in patients with and without SIC. Routine coagulation tests activated Partial Thromboplastin Time (aPTT) and International Normalized Ratio (INR) and C-reactive protein (CRP) as a marker of inflammation were also associated with AF occurrence in SIC-positive and SIC-negative patients. Cardiorespiratory parameters (oxygen requirements and heart rate) showed predictive potential. Higher INR, elevated CRP, increased heart rate and more severe respiratory failure are risk factors for occurrence of AF in critical illness, suggesting an association between cardiac, respiratory and immune and coagulation pathways. However, age was the most dominant factor to predict the first episodes of AF in patients admitted in sinus rhythm with and without SIC.

Increased D-dimer and fibrin degradation product levels as potential indicators for evaluating infection-related acute urticaria: a case-case-control study.

About 20% of world population suffer from acute urticaria at some stage in their lives. Recent studies showed coagulation dysfunction in chronic urticaria. The involvement of coagulation changes in acute urticaria remains unclear. Fifty-eight acute urticaria patients were enrolled in this study and divided into two groups (referred to throughout as infection-related and infection-unrelated acute urticaria). The routine laboratory parameters including coagulation tests between the two groups were compared. The correlation between coagulation tests and CRP at acute phase was also assessed. Dynamic change of routine coagulation test results at acute phase and resolving phase was compared. The potential performance of coagulation for infection indication was tested. We found D-dimer, fibrin degradation product (FDP), and fibrinogen (Fg) increased in the acute phase of infection-related acute urticaria patients. D-dimer, FDP, Fg, and APTT are positively correlated with CRP in the acute phase. D-dimer and FDP decreased in the resolving phase of infection-related acute urticaria patients. Higher D-dimer (> 0.48mg/L) and FDP (> 3.84mg/L) may indicate infection-related acute urticaria. In conclusion, in acute urticaria with low venous thromboembolism risk, D-dimer level and dynamic change can be potentially used for the infection-related clinical practice management.

Within- and between-subject biological variation of hemostasis parameters in a study of 26 healthy individuals

Abstract Objectives The study aimed to estimate the biological variation (BV) of routine coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen, in a healthy population to enhance the accuracy of laboratory results and improve diagnosis and treatment decisions. Methods The study included 26 healthy volunteers over 10 weeks; samples were collected weekly. The within-subject BV (CVI) and between-subject BV (CVG) were calculated for each parameter, and the index of individuality (II) and reference change values (RCV) were determined. All tests were performed in duplicate on the Roche Cobas T-711 coagulation analyzer. Results Fibrinogen exhibited the highest BV, with a CVI of 11 % and CVG of 17.4 %. The aPTT test had a CVI of 5.8 %, a CVG of 8.4 %, and an II of 0.91. The PT test had a CVI of 3.2 %, a CVG of 5.8 %, and an II of 0.73. The RCV values ranged from −7.5 to 8.1 for PT, −12.7 to 14.6 for aPTT, and −22.7 to 29.4 for fibrinogen. Conclusions The study underscores the significant biological variation in routine hemostasis parameters, such as PT, APTT, and fibrinogen, which impacts clinical diagnoses and treatment decisions. Despite certain limitations, the findings offer valuable insights for clinicians and suggest that future research should include more parameters for a comprehensive understanding of biological variations in hemostasis testing.

Risk Factors for Severe Clinical Course in Epistaxis Patients.

Purpose: Epistaxis is a common medical emergency that may require admission to the emergency department (ED) and treatment by an otolaryngologist. Currently, there are no widely accepted indications for hospitalization, and the decision is based on personal experience. Methods: A retrospective study of 1171 medical records of patients with epistaxis treated at our tertiary medical center ED from 2013 to 2018 with no age limit. The presence of recurrent epistaxis, a posterior source of bleeding, the need for hospitalization, the need for blood transfusion, or surgical intervention defined severe clinical course. Results: The 1171 admissions included 230 recurrent admissions for a total of 941 patients (60% males) who were treated by an otolaryngologist. The average age was 57.6 in the adult population (>15) and 6.6 in the pediatric population (≤15). Of all patients, 39% had hypertension; 39% took antiplatelet/anticoagulation therapy; 63% came during winter-a significant risk factor; 34 (2.9%) had reduced hemoglobin levels of >1gr%, but only 7 received a blood transfusion; 131 (11%) were hospitalized, and 21 (1.8%) required surgical control of the bleeding. Age (OR 1.02; CI 1.01-1.023), male sex (OR 2.07; CI 1.59-2.69), hypertension (OR 1.76; CI 1.27-2.45), and antiplatelet/anticoagulation therapy (OR 2.53; CI 1.93-3.33, OR 1.65; CI 1.11-2.44, respectively), were significantly correlated with severe clinical course. Conclusion: Epistaxis is significantly more common and severe in older male patients with hypertension or antiplatelet/anticoagulation therapy. However, few need a blood transfusion or surgical intervention. In borderline cases with no definitive indication for hospitalization, we suggest adopting these factors as indications for hospitalization due to their marked influence on the clinical course. Routine coagulation tests are indicated in patients treated with warfarin or combined antiplatelet + anticoagulation therapy.