Coagulation Tests Research Articles

The Bleeding Edge: Managing Coagulation and Bleeding Risk in Patients with Cirrhosis Undergoing Interventional Procedures.

This review addresses the peri-procedural bleeding risks in patients with cirrhosis, emphasizing the need for careful coagulation assessment and targeted correction strategies. Liver disease presents a unique hemostatic challenge, where traditional coagulation tests may not accurately predict bleeding risk, complicating the management of procedures like paracentesis, endoscopic therapy, and various interventional procedures. As such, this paper aims to provide a comprehensive analysis of current data, guidelines, and practices for managing coagulation in cirrhotic patients, with a focus on minimizing bleeding risk while avoiding unnecessary correction with blood products. The objectives of this review are threefold: first, to outline the existing evidence on bleeding risks associated with common invasive procedures in cirrhotic patients; second, to evaluate the efficacy and limitations of standard and advanced coagulation tests in predicting procedural bleeding; and third, to examine the role of blood product transfusions and other hemostatic interventions, considering potential risks and benefits in this delicate population. In doing so, this review highlights patient-specific and procedure-specific factors that influence bleeding risk and informs best practices to optimize patient outcomes. This review progresses through key procedures often performed in cirrhotic patients. The discussion begins with paracentesis, a low-risk procedure, followed by endoscopic therapy for varices, and concludes with high-risk interventions requiring advanced hemostatic considerations. Each chapter addresses procedural techniques, bleeding risk assessment, and evidence-based correction approaches. This comprehensive structure aims to guide clinicians in making informed, evidence-backed decisions in managing coagulation in cirrhosis, ultimately reducing procedural complications and improving care quality for this high-risk population.

Handheld Point-of-Care Devices for Snakebite Coagulopathy: A Scoping Review.

Venom-induced consumption coagulopathy (VICC) is a common complication of snakebite that is associated with hypofibrinogenemia, bleeding, disability, and death. In remote tropical settings, where most snakebites occur, the 20-minute whole blood clotting test is used to diagnose VICC. Point-of-care (POC) coagulation devices could provide an accessible means of detecting VICC that is better standardized, quantifiable, and more accurate. In this scoping review, the mechanistic reasons that previously studied POC devices have failed in VICC are considered, and evidence-based recommendations are made to prioritize certain devices for clinical validation studies. Four small studies have evaluated a POC international normalized ratio (INR) device in patients with Australian Elapid, Daboia russelii, and Echis carinatus envenoming. The devices assessed in these studies either relied on a thrombin substrate endpoint, which is known to underestimate INR in patients with hypofibrinogenemia, have been recalled due to poor accuracy, or have since been discontinued. Sixteen commercially available POC devices for measuring INR, activated clotting time, activated partial thromboplastin time, fibrinogen, D-dimer, and fibrin(ogen) degradation products have been reviewed. POC INR devices that detect fibrin clot formation, as well as a novel POC device that quantifies fibrinogen were identified, which show promise for use in patients with VICC. These devices could support more accurate allocation of antivenom, reduce the time to antivenom administration, and provide improved clinical trial outcome measurement instruments. There is an urgent need for these promising POC coagulation devices to be validated in prospective clinical snakebite studies.

Ciraparantag Does Not Remove Anticoagulant Activities In Vitro, but DOAC-Stop™ May Mitigate Ciraparantag-Associated Interferences in Coagulation Testing

Anticoagulants can complicate the interpretation of routine and specialised coagulation assays. Several methodologies have been developed to minimise or eliminate anticoagulant-associated interferences; however, no ‘universal methodology’ that encompasses different anticoagulant classes is currently available. Ciraparantag is a promising reversal agent that can bind both direct oral anticoagulants (DOACs) and heparin-like anticoagulants. As such, we aimed to investigate whether ciraparantag could be employed as a ‘universal’ anticoagulant chelator in vitro. Human plasma was spiked with ascending concentrations of ciraparantag, with or without DOACs or heparin, and assayed for routine coagulation parameters. Ciraparantag had minimal effects on coagulation testing when added to human plasma at concentrations similar to pharmacokinetic maxima; however, ciraparantag did not remove DOAC- or heparin-associated activities in vitro, which was likely due to the preferential chelation of anionic substances in the coagulation reagents. In contrast, DOAC-Stop™, a commercial activated charcoal-based adsorbent, efficiently removed both DOAC- and ciraparantag-associated interferences. In conclusion, although ciraparantag is not effective as a ‘universal’ anticoagulant chelator in vitro, we report that activated charcoal-based adsorbents may be clinically useful in situations where laboratory investigations are complicated by the presence of DOACs and/or ciraparantag.

Haemophagocytic lymphohistiocytosis triggered by cytomegalovirus reactivation in an immunosuppressed patient with pauci-immune glomerulonephritis

We report on a 67-year-old male patient admitted to the Internal Medicine department for fever, joint pain and exertional dyspnoea. Two months before his admission, the patient had been diagnosed with pauci-immune necrotising glomerulonephritis, for which he had been treated with rituximab and corticosteroids. Upon admission the patient was stable, but within a few hours he became unstable as liver failure and acute cytopaenia occurred. Blood investigations revealed cytopaenia, altered coagulation tests, high ferritin, triglycerides, lactate dehydrogenase and C-reactive protein levels, and severe cytocholestasis. A liver echography was normal. The patient had been transferred to the intensive care unit to receive supportive support when the cytomegalovirus polymerase chain reaction (CMV-PCR) test came back positive. The diagnosis of haemophagocytic lymphohistiocytosis associated with a CMV infection and/or reactivation in an immunosuppressed patient was made. Specific treatment was administrated, along with symptomatic treatment. The patient clinically improved during hospitalisation with complete resolution of symptoms.

Recurrent Early Pregnancy Loss and Congenital Thrombophilia: A Prospective Study.

Background/Objectives: This study aims to investigate the role of congenital single nucleotide thrombophilia in young females with early recurrent pregnancy loss (RPL). Methods: We studied 120 pregnant females with RPL and 80 matched females as a control with no RPL. Females were aged ≤ 35 years, had at least two consecutive first-trimester RPLs, and the acquired cause of RPL was excluded. A matched control group of 80 pregnant women with no RPL was studied. Coagulation tests included prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), a Factor XIII functional assay, and detecting IgM and IgG anti-beta2-Glycoprotein I (β2GPI) antibodies by an ELISA. The DNA samples were tested for Factor V Leiden, Factor II G20210A, Methylenetetrahydrofolate reductase (MTHFR C677T, A1298C), FXIII V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G, endothelial protein C receptor (EPCR) A4600G, and endothelial protein C receptor (EPCR) G4678C. Results: Of the single nucleotide gene mutations investigated, the most relevant mutations were MTHFR C677T, MTHFR A1298C, heterozygous FXIII Val34Leu, and heterozygous FXIII 1694 C>T. Each of them conferred a statistically significant effect. There was a statistically significant protective role for the endothelial protein C receptor (EPCR) A2/A2, wild FXIII Val34Leu, and heterozygousFXIII1694 C>T. Conclusions: Our findings suggest the important role of congenital single nucleotide thrombophilia mutations in young Middle Eastern women with early RPL, particularly MTHFR mutations and FXIII Val34Leu. We found a protective effect of EPCR A2/A2, wild FXIIIVal34Leu, and heterozygous FXIII1694 C>T. We recommend additional studies to explore detrimental factors and protective factors.

Urgent Reversal of Direct Oral Anticoagulants in Critical and Life-Threatening Bleeding: A Multidisciplinary Expert Consensus.

Direct oral anticoagulants (DOACs) are increasingly being used due to their improved efficacy/safety ratio and lower clinical and economic burden when compared to vitamin K antagonists. However, bleeding is still the most frequent complication associated with DOACs, and although rare, bleeding episodes can be life-threatening or critical. The impact of DOAC anticoagulation activity during a bleeding event must be evaluated according to patient clinical assessment, dosage and time from last intake, the presence of comorbidities (especially kidney and liver dysfunction), and, whenever possible, coagulation tests. Unfortunately, DOACs' anticoagulation activity is not easily or usually detectable in routine common coagulation testing. Specific DOAC tests allow for specific drug monitoring, but they are too time consuming, and are usually unavailable in routine emergency practice. If a clinically relevant DOAC plasma concentration is assumed or proven in a severe bleeding scenario, DOAC reversal is needed to restore hemostasis. This experts' consensus provides a narrative review about DOAC reversal and practical life-threatening bleeding management in several scenarios (trauma, intracranial hemorrhage and gastrointestinal bleeding), focusing on the selection of patients to whom specific reversal agents should be given.

Preoperative bleeding risk assessment in cardiac surgery patients

One of the most important aspects in achieving successful outcomes in cardiac surgery is the evaluation of the risk of bleeding during and after the procedure. Preoperative anemia, intraoperative bleeding, and transfusion therapy contribute to a cumulative risk of adverse events. Given the limitations of traditional coagulation tests, a more comprehensive and patient-centered approach is necessary. Factors affecting the risk of bleeding should be considered from the perspective of both individual patient characteristics and the specific type and extent of the planned surgical intervention. The risk assessment should be informed by individual and familial history, as well as previous episodes of bleeding or other relevant information. The use of bleeding risk scales can play a crucial role in this process, providing valuable insights into the likelihood of bleeding complications. In conclusion, a comprehensive approach that takes into account the unique characteristics of each patient and the specific details of the surgical procedure is essential for minimizing the risk of complications and ensuring successful outcomes.

Cirrhosis Progression Is Not Associated with Clinically Significant Alterations in Global Hemostasis Assessed by Thromboelastography.

(1) Background: Cirrhosis is associated with frequent alterations in standard coagulation tests that do not adequately reflect hemostasis. Thromboelastography provides a global assessment of coagulation and evaluates the functional status of clotting factors, fibrinogen, platelets, and fibrinolysis. The study aimed to assess whether liver disease severity leads to progressive alterations in the thromboelastography-based assessment of coagulation. (2) Methods: Consecutive patients with cirrhosis and abnormal standard coagulation tests (at least one of International Normalized Ratio > 2, platelet count < 50 × 103/µL, fibrinogen < 200 mg/dL) were analyzed using native thromboelastography. (3) Results: A total of 106 patients were included, of whom 69 (65.1%) had a normal thromboelastography. While the standard coagulation tests were significantly worse in patients in the Child C group (n = 62, 58.5%) than in patients staged in Child A and B, no significant differences existed between any of the thromboelastography variables. Of the 50 patients (47.1%) with an International Normalized Ratio > 2, only two patients (4%) had features of hypocoagulation, while 26% had features of hypercoagulability on thromboelastography. Patients with a platelet count < 50 × 103/µL had significantly lower platelet function as assessed by thromboelastography, yet only eight patients (20%) met the criteria for platelet transfusion. A thromboelastography-based transfusion protocol might lead to a 94.6% reduction in blood product transfusion indications in a simulation where the included patients would require interventional procedures. (4) Conclusion: Standard coagulation tests showed a poor correlation with thromboelastography. Based on thromboelastography, patients with severe, decompensated liver disease have a preserved hemostasis balance despite abnormal standard coagulation tests. Therefore, standard coagulation tests should not be used to guide the administration of blood products in patients with cirrhosis.

Coagulation studies are frequently ordered in emergency department chest pain patients and do not change emergency department management

BackgroundDespite research findings, implementation into clinical practice is often delayed. Coagulation panels are still ordered as part of an emergency department (ED) chest pain evaluation, despite multiple studies showing that it is unnecessary and does not change management. ObjectiveOur primary outcome is to determine if the practice of ordering coagulation studies (PT/INR) is still occurring in ED chest pain patients. Our secondary outcome is to determine if abnormal results change management. MethodsWe performed an IRB approved retrospective chart review of patients with chest pain presenting to three rural-community EDs over 49 months. Medical students, blinded to the study intent, performed data abstraction using the approach of Gilbert and Lowenstein to determine if coagulation testing (PT/INR) was ‘indicated’ based on a preexisting condition (ie liver disease) or medication use (warfarin). Next, the data abstractors determined if the abnormal coagulation results prompted a therapeutic intervention or change in the management in the ED. ResultsWe randomly identified 1,200 patients with chest pain before covid-19 and, after exclusions, analyzed 830 patient charts. 440 patients (53.0%) had coagulation panels completed, but they were only indicated in 55 of the 440 patients (12.5%). Of the 385 patients without indications, 378 (98.2%) had an INR level in the normal range and 7 patients (1.8%) had an elevated INR. None of these 7 patients had a change in ED management. ConclusionsIn this multicenter study, 53% of ED patients with chest pain had coagulation studies ordered. Only 12.5% were indicated. None of the abnormal results changed management.

Role of Laboratory Tests in Enhancing Diagnosis and Treatment Planning for Dentists: A Review of Evidence-Based Practices.

The purpose of this review is to simplify and guide dentists through the main laboratory investigations frequently used in dentistry for diagnosis and patient management. It emphasizes the critical role of laboratory tests in dental practice, highlighting their significance for accurate diagnosis, effective treatment planning, and ongoing monitoring of oral health. Systemic conditions often manifest through oral symptoms, making laboratory assessments essential for identifying undiagnosed health issues that may impact dental treatment outcomes.A comprehensive literature search was conducted using PubMed and Google Scholar to gather relevant studies, ensuring a thorough examination of existing knowledge on the subject. This review defines commonly used laboratory tests, including complete blood count (CBC), coagulation tests, hemoglobin A1c (HbA1c), liver function tests, immunological assays, and microbiological and virological evaluations. Each test provides valuable insights into patient health, aiding in the detection of conditions such as anemia, diabetes, and liver disease, which can complicate dental procedures. By adopting an evidence-based, personalized approach to patient care, dental professionals can enhance safety and treatment success. This article underscores the necessity of integrating laboratory assessments into routine dental practice, promoting a holistic understanding of patient health and improving overall treatment outcomes.

Coagulopathy and acute pancreatitis: pathophysiology and clinical treatment.

Coagulopathy is a critical pathophysiological mechanism of acute pancreatitis (AP), arising from the complex interplay between innate immune, endothelial cells and platelets. Although initially beneficial for the host, uncontrolled and systemic activation of coagulation cascade in AP can lead to thrombotic and hemorrhagic complications, ranging from subclinical abnormalities in coagulation tests to severe clinical manifestations, such as disseminated intravascular coagulation. Initiation of coagulation activation and consequent thrombin generation is caused by expression of tissue factor on activated monocytes and is ineffectually offset by tissue factor pathway inhibitor. At the same time, endothelial-associated anticoagulant pathways, in particular the protein C system, is impaired by pro-inflammatory cytokines. Also, fibrin removal is severely obstructed by inactivation of the endogenous fibrinolytic system, mainly as a result of upregulation of its principal inhibitor, plasminogen activator inhibitor type 1. Finally, increased fibrin generation and impaired break down lead to deposition of (micro) vascular clots, which may contribute to tissue ischemia and ensuing organ dysfunction. Despite the high burden of coagulopathy that have a negative impact on AP patients' prognosis, there is no effective treatment yet. Although a variety of anticoagulants drugs have been evaluated in clinical trials, their beneficial effects are inconsistent, and they are also characterized by hemorrhagic complications. Future studies are called to unravel the pathophysiologic mechanisms involved in coagulopathy in AP, and to test novel therapeutics block coagulopathy in AP.

Comparative Assessment of Thermal Damage Induced by Bipolar Forceps in a Bovine Liver.

Bipolar electrocautery systems in neurosurgical procedures may induce thermal damage to adjacent tissues, especially neural tissues. Therefore, it is crucial to control thermal spread from the tips of bipolar forceps into adjacent tissues. The goal of this study was to compare the thermal damage induced in unintended adjacent tissues during coagulation with 6 different bipolar forceps. Fresh ex vivo bovine liver tissues were coagulated with 6 different bipolar forceps: Aesculap® nonstick, Atlas Choice™, ISOCOOL®, SilverGlide®, Spetzler™-Malis®, and VersaTru® (45 trials per bipolar forceps). For all forceps, coagulation was performed with a power setting of 35 Malis units, 1-mm tip spacing, and 3-second activation time. Tissue samples were evaluated for the extent of thermal damage (30 trials per bipolar forceps). Tissue temperatures were measured with thermocouples placed in the tissues (15 trials per bipolar forceps). The area and maximum depth of thermal damage were measured manually with image analysis software. The injury area induced by ISOCOOL® and Atlas Choice™ bipolar forceps was significantly less than that of the Aesculap® nonstick (P < .001), SilverGlide® (P < .001), Spetzler™-Malis® (P < .001), and VersaTru® (P < .001). The areas of thermal injury caused by the ISOCOOL® and Atlas Choice™ forceps were not statistically significantly different from each other (P = .08). Lesions from the ISOCOOL® and Atlas Choice™ forceps showed significantly less depth of injury than the Aesculap® nonstick (P = .001), SilverGlide® (P < .001), Spetzler™-Malis® (P < .001), and VersaTru® (P < .001). There was no statistically significant difference in the depth of thermal injury between the ISOCOOL® and Atlas Choice™ forceps (P = 1.0). Bipolar forceps that effectively limit excessive thermal dissipation reduce the risk of unintended injury to adjacent or peripheral tissues. In an ex vivo bovine liver model, coagulation tests with ISOCOOL® and Atlas Choice™ bipolar forceps resulted in less depth and lower mean injury areas compared with other forceps.

Adult celiac disease presented with celiac crisis: Report of two cases

Two patients (case 1: 29 years old and case 2: 66 years old. female) with no known medical history of chronic diseases, including celiac disease, presented to the hospital with prolonged diarrhea, weight loss, and severe hypocalcemia at different times. They were admitted to the hospital for hemodynamic instability in the setting of severe dehydration and electrolyte disturbances. Physical examination revealed a positive trousseau sign in Case 1. The typical laboratory features of both cases were low magnesium, low potassium, low vitamin D, low ferritin, and prolonged coagulation tests. In addition to those labs, case 2 also has metabolic acidosis. In both cases, the titers of the tissue transglutaminase IgA and IgG and the anti-endomysium antibody were high, and the histopathology of the duodenal biopsy was consistent with villous atrophy, crypt hyperplasia, and an increase in intraepithelial lymphocytes, suggesting celiac disease. Both cases responded quickly to treatment with a gluten-free diet, fluid, electrolyte, vitamin D, and K replacements, and were discharged. Celiac crisis is a rare presentation of celiac disease characterized by acute, severe metabolic imbalances resulting in high mortality and morbidity, with severe diarrhea, hypoproteinemia, and metabolic and electrolyte disturbances. It is typically seen in children under 2 years of age but can also be encountered in adulthood. Most cases respond to gluten cessation, nutritional support, and rarely steroid treatment.

Decreased Circulating Red Cell Mass Induced by Intravenous Acepromazine Administration Alters Viscoelastic and Traditional Plasma Coagulation Testing Results in Healthy Horses.

Coagulopathy is common in equine critical illness, with its early recognition being crucial for patient management and prognosis. In vitro viscoelastic (VE) hypercoagulability with decreased RCM/PCV has been demonstrated in dogs but not horses. Our objective was to evaluate the effects of acepromazine-induced (0.1 mg/kg IV) decreased RCM on VE and plasma coagulation parameters using a prospective interventional study of eight adult horses. Complete blood count (CBC), fibrinogen, prothrombin time (PT), partial thromboplastin time (PTT), packed cell volume (PCV), total solids (TS), and VCM Vet™ VE testing performed at baseline (T0), 1 h (T1), and 12 h (T2) post acepromazine administration. Splenic volume was determined ultrasonographically. The results were analyzed using one-way repeated measures ANOVA with Tukey's post hoc HSD test to determine the effect of time (sample). PCV decreased 13% points following acepromazine administration from T0 to T1 (p < 0.001), remaining decreased at T2 (p < 0.001). Splenic volume increased from T0 to T1 (p = 0.04) and was not different from baseline at T2. Maximal clot formation (MCF) increased from T0 (p = 0.03). PTT decreased from T0 to T1 and increased at T2 (p = 0.03). No other coagulation parameters were significantly altered. This study demonstrates a non-inflammatory acute model of anemia in horses that impacts VE and plasma-based testing.

An Uncommon Case of Plasmodium vivax Malaria with Disseminated Intravascular Coagulation: Rare Case Report with Review of Literature.

Malaria is a severe health issue in India despite government efforts. Malaria has many complications, some of which can be life-threatening. Disseminated intravascular coagulation (DIC) is a prominent malaria complication, besides renal failure, cerebral malaria, pulmonary edema, and anemia. We report a young man with Plasmodium vivax malaria who developed septic shock due to DIC. A 25-year-old male had a fever, abdominal pain, vomiting, and nausea for 5 days. On clinical examination, the patient was in distress and had a fever of 102.6°F with a blood pressure of 86/46 mmHg. A complete blood count revealed anemia, leukocytopenia, and severe thrombocytopenia. Peripheral blood smear findings showed a P. vivax parasite in red blood cells with the presence of a few schistocytes. Further coagulation tests showed raised prothrombin, partial thromboplastin time, and d-dimer. DIC and septic shock required critical care unit admission. Conservative treatment with artesunate and lumefantrine completely cured him. This unusual case shows that P. vivax causes severe malaria and its morbid consequences. It stresses early diagnosis and treatment to prevent mortality and morbidity.

Trauma-induced coagulopathy across age pediatric groups: A retrospective cohort study evaluating testing and frequency.

Trauma-induced coagulopathy (TIC) is associated with negative outcomes. Pediatric TIC has been described most often in older children. Children undergo normal developmental hemostasis, but it is unknown how this process impacts the risk of TIC across childhood. To understand variations in coagulation testing and TIC across pediatric age groups. We evaluated testing patterns of coagulation studies at presentation and over the first 72 h of hospitalization by pediatric age group at a large, Level I trauma center, 2015-2020. The frequency of TIC was determined using published, age-specific reference ranges and controlling for injury severity. We performed subgroup analyses of those with isolated severe traumatic brain injury (TBI) and those who presented directly from the scene of injury. Data from 2409 pediatric patients were available; 333 patients had isolated severe TBI. Children <1 year were least likely to be tested for TIC at presentation and over the first 72 h, even among the most injured. Fibrinogen testing was uncommon, regardless of injury severity. TIC was common: 22% of patients had TIC at presentation and 35% by 72 h. Greater injury severity was associated with TIC. Children 1-4 and 5-9 years had a higher frequency of TIC at presentation and over 72 h compared to older children in the least injured cohort. We saw no difference in frequency of TIC between age groups in the subset with isolated severe TBI. Using age-specific criteria, patients most often met TIC criteria by INR/PT, followed by platelet count, and least commonly by aPTT. The presence of TIC was associated with in-hospital mortality (OR 4.10, 95% CI 2.06-8.17). Significant sampling bias exists in clinical data collection among injured children and adolescents. Contrary to previous reports and using age-specific TIC criteria, younger children are not at lower risk of TIC than older children when controlling for injury severity.

Viscoelastic Hemostatic Testing as a Diagnostic Tool for Hypercoagulability in Liver Transplantation: A Narrative Review.

Liver transplantation is a complex surgical procedure in which various forms of coagulation dysfunction can occur, including perioperative hypercoagulability. The hemostasis balance in liver graft recipients with end-stage liver disease can shift to thrombosis or haemorrhage, depending on the associated risk factors and clinical conditions. Hypercoagulability can result in serious complications such as thromboembolism, which can affect the vessels of the newly transplanted liver graft. Standard coagulation tests (SCTs), such as prothrombin time and activated partial thromboplastin time (aPTT), have a poor ability to diagnose and monitor an early stage of hypercoagulability. Recent studies demonstrated that viscoelastic hemostatic elastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), are promising alternative tools for diagnosing hypercoagulability disorders. VETs measure clotting and clot formation time, clot strength (maximum clot firmness), fibrin and platelet contribution to clot firmness, and fibrinolysis, which makes them more sensitive in identifying liver graft recipients at risk for thrombosis as compared with SCTs. However, developing evidence-based guidelines for the prophylaxis and treatment of hypercoagulability based on VET results is still needed.

Estimation of Gestational Age-Specific Reference Intervals for Coagulation Assays in a Neonatal Intensive Care Unit Using Real-World Clinical Data

Abstract Interpretation of coagulation testing in neonates currently relies on reference intervals defined from adult cohorts. These likely do not reflect the normative values for neonates, in whom immature synthesis of vitamin K-dependent factors may contribute to this divergence. Direct reference interval estimation studies are difficult, particularly in neonatal populations; however, advances in indirect estimation may allow us to infer normative distributions from routinely collected clinical data. To accomplish this, initial coagulation testing results from all patients admitted to a level IV neonatal intensive care unit between 1/1/2018 - 1/1/2023 were extracted from the electronic health record and analyzed. Results prior to June 2021 were performed on the viscosity-based STA Compact Max (Diagnostica Stago. Parsippany, NJ, USA). Afterward, results were performed on a nephelometry-based ACL Top (Instrumentation Laboratory. Bedford, MA, USA). Specimens collected after transfusion of blood products were excluded. Prothrombin times (PT) and international normalized ratios (INR) were available for 1,117 neonates, while activated partial thromboplastin times (aPTT) were available for 790 neonates. The 95% confidence intervals (CI) of the median PT for extremely preterm, very preterm, preterm and term neonates were [19 - 21s], [18 - 22s], [17 - 19s] and [17 - 18s]. For INR, the CI were [1.6 - 1.8], [1.5 - 1.8], [1.4 - 1.6], and [1.4 - 1.5]. For aPTT, the CI were [51 - 61s], [47 - 58s], [45 - 50s], and [42 - 46s]. Indirect reference intervals (IRIs) were then estimated across gestational age groups (binning all patients delivered at less than 37 weeks into one preterm category) using refineR. The IRI for PT was 10 - 24s for preterm,10 - 22s for term, and 10 - 24s for all neonates. The IRI for INR was 0.7 - 2.1 for preterm, 0.8 - 1.8 for term, and 0.8 - 1.9 for all neonates. The IRI for aPTT was 24.5 - 68.4s for preterm, 24.7 - 58.2s for term, and 25 - 62.3s for all neonates. When compared to currently reported reference intervals, the lower limits of the IRI were similar to currently reported reference intervals; however, the upper limits of the IRIs were 1.3 - 1.8 times higher than current reference intervals. Theoretically, implementation of these IRIs would lead to a 3-fold decrease in the number of results flagged as abnormal. In conclusion, IRIs for coagulation assays estimated from neonates using routine clinical data show substantial divergence from current reference intervals in their upper limits, possibly due to the decreased factor concentrations seen prior to liver maturation. If implemented, these IRIs would substantially reduce the proportion of abnormal results. Future work will explore whether switching to these reference intervals could lead to a reduction in unnecessary transfusions or improved clinical outcomes.

Utilizing Artificial Intelligence to Reconcile Indeterminate Lupus Anticoagulant Panel Results

Abstract Lupus anticoagulant (LA) is one laboratory criterion for diagnosing antiphospholipid antibody syndrome (APS), a condition associated with hypercoagulability, pregnancy complications, and death. LA diagnosis requires a complex panel, often performed at a specialized laboratory. Ruling out false positive or transient LAs requires ≥ two positive tests ≥ 12 weeks apart. Most LA tests are negative, with small subsets resulting positive or indeterminate. Indeterminates leave clinicians with limited understanding of appropriate clinical follow-up. Thus, the International Society on Thrombosis and Hemostasis discourages weak resulting nomenclature such as “indeterminate.” Our study used artificial intelligence to predict LA indeterminate results as positive or negative, identifying patients requiring further testing. This IRB approved study reviewed nearly 4000 LA tests performed from 2019-2023. Parameters included CBC, thromboelastography, renal/hepatic function assays, coagulation tests, antiphospholipid antibodies and LA tests. LA test components included screening tests (APTT, Dilute Russel Viper Venom Test (DRVVT) screen), mixing studies (1:1 APTT mix, DRVVT mix), phospholipid-dependent confirmation (DRVVT, hexagonal phase, platelet neutralization), and factor VIII. A positive LA test fulfilled 4 criteria: at least one positive screening test, mixing study and phospholipid-dependent assay and factor VIII inhibitor exclusion. An LA panel meeting 2-3 criteria resulted indeterminate. Studies meeting &amp;lt;2 criteria were negative. This analysis was performed using Machine Intelligence Learning Optimizer (MILO) platform which displays the performance of multiple models. MILO was trained with two classifications: positive and negative cases. Data was split into training (100 training positives; 100 negatives) and testing (primary and secondary validation) sets (100 positives; 1388 negatives). LA panels affected by drug interactions (9.4%) or containing incomplete datasets (21%) were excluded. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) determined model efficacy. 2903 negative (84%), 318 positive (9.1%), and 246 indeterminate (7.1%) LA results were included from 3467 patients. Only 84 of the 246 indeterminate patients (34%) were retested. Of these, 28 remained indeterminate, 43 became negative and 13 resulted positive. The best performing MILO models were the K-nearest neighbor (KNN) and logistic regression. The ability of these models to determine which indeterminate cases would become positive or negative was evaluated. KNN displayed the highest specificity (0.88) and PPV (0.57). All models had a high NPV and specificity due to substantive exposure to negative cases for the training and testing. Exclusion of some parameters did not improve the performance of the models. However, even the best model (various KNN models) had low sensitivity and PPV due to a small pool of positive training/testing cases and a much smaller group of indeterminate LA with subsequent positive results. Creating models accurately predicting indeterminate cases that may become positive enables appropriate clinical follow-up. Thus, improving model accuracy will require a larger sample size of positive indeterminates with follow-up.

Preservation of coagulation function by normothermic machine perfusion in liver transplant as evidenced by thromboelastography parameters

The use of normothermic machine perfusion over static cold storage in liver transplantation has been shown to reduce post-transplant risks of early allograft dysfunction, primary nonfunction, and ischemic cholangiopathy, and its increasing use has played a role in the expanded utilization of marginal livers. While studies have demonstrated improved clinical outcomes utilizing normothermic machine perfusion over static cold storage preservation, real-time intraoperative data reflecting the quality and viability of normothermic machine perfusion livers is limited. This retrospective, single-center study compared normothermic machine perfusion vs static cold storage livers in first-time liver transplant recipients through the evaluation of synthetic coagulation function as measured by thromboelastography and conventional coagulation testing. Secondarily, transfusion utilization between the two cohorts were reviewed. 186 liver transplant recipients receiving allografts from donors after circulatory death were included in the study, of which 99 (53%) allografts were preserved in static cold storage, and 87 (47%) allografts were placed on the TransMedics Organ Care System. Study findings showed normothermic machine perfusion livers supported with the TransMedics Organ Care System were associated with increased synthetic coagulation function and less excess fibrinolysis in the post-reperfusion period compared to static cold storage livers, and that these findings were better reflected in real-time with thromboelastography monitoring vs conventional coagulation testing. Following reperfusion, there was a significant decrease in the transfusion of blood products in the normothermic machine perfusion group compared with that in the static cold storage group. Overall, we determined that the use of intraoperative thromboelastography can provide real-time data to assess one aspect of reperfusion liver quality and viability.