Partial Thromboplastin Time Research Articles

A longitudinal observational study on activated partial thromboplastin time in hypothyroidism and effect of thyroxine supplementation

Background: Hypothyroidism is a common condition characterized by thyroid hormone deficiency, which, if untreated, can lead to severe health consequences and even death. Due to the wide range of clinical presentations and non-specific symptoms, hypothyroidism is primarily diagnosed biochemically. It can result from congenital thyroid abnormalities or iodine deficiency. Aims and objectives: Aim: To evaluate the correlation between hypothyroidism and Activated Partial Thromboplastin Time (aPTT) and assess the effect of thyroxine supplementation. Objective: To study the impact of levothyroxine supplementation on aPTT in hypothyroid patients. Materials and methods: This observational study was conducted at the General Medicine outpatient clinic and inpatient wards at Al-Ameen Medical College and Hospital, Vijayapura, from September 2022 to March 2024. A total of 80 hypothyroid patients of both sexes were included. TSH, Free T4, and aPTT levels were measured with appropriate aseptic precautions. Results: The majority of subjects were females (90%), with the highest proportion (31.3%) aged 26-35 years. The mean ± SD of pre-thyroxine TSH was 25.453 ± 19.9073, which significantly decreased to 4.299 ± 0.6738 post-thyroxine. aPTT values also decreased significantly post-treatment. A positive correlation was found between TSH and aPTT, while aPTT had a negative correlation with T3 and T4 levels. Conclusion: aPTT is significantly elevated in hypothyroid patients and shows a positive correlation with TSH levels. Regular monitoring of aPTT should be included in the follow-up of hypothyroid patients.

Dual guided heparin monitoring with anti-Xa and APTT during micro-axial flow pump support for cardiogenic shock

Abstract Background Precise management of unfractionated heparin (UFH) is key to avoid coagulopathic complications in patients on percutaneous mechanical circulatory support (pMCS) for cardiogenic shock (CS). While the activated partial thromboplastin time (APTT) is commonly used for this purpose, it can be affected by various laboratory factors during critical illness. Alternatively, the anti-Xa test directly measures UFH activity. We proposed a parallel anti-Xa/APTT-based protocol for UFH titration during pMCS. (1) Purpose We aimed to investigate the correlation between parallel anti-Xa/APTT measurements in a CS population on pMCS. We also evaluated mortality correlation in samples exhibiting prolonged APTT and in-range anti-Xa levels, based on fibrinogen levels and INR. Methods We assessed all CS patients with isolated left-sided ImpellaTM-support (>24h) and UFH anticoagulation monitoring per protocol at two pMCS-institutions from April-2017 to June-2022. Overall correlation between parallel anti-Xa/APTT samples was assessed by Pearson correlation coefficient (with ≤0.7 considered to confer a weak correlation). Anti-Xa levels were defined as 0.20-0.30IU/mL or 0.31-0.50IU/mL, with corresponding APTT values of 40-55s and 55-80s, respectively. Samples with prolonged APTT as compared to the in-range anti-Xa were stratified based on fibrinogen (<1.5g/dL or ≥ 1.5g/dL) and INR (<1.5 or ≥1.5) on the same day as the index sample. Mortality of patients with normal fibrinogen ànd INR was then compared to those with abnormal fibrinogen and/or INR via a Chi² test. Results Ninety-three ImpellaTM-runs (77 men, 83%) with a median age of 56 years (IQR 46-66) were analyzed. Median support was 6 days (IQR 4-12). In 2447 parallel anti-Xa/APTT samples, the Pearson correlation coefficient was 0.50 (p<0.001). Among the 1914 in-range anti-Xa samples, APPT was shortened in 460 (24%), in-range in 986 (52%) and prolonged in 468 (24%) samples. In the 59 patients with samples with prolonged APTT, two patients (with 80 samples) were excluded due to absence of fibrinogen and/or INR measurements on the same day. The mortality in patients with prolonged APTT but normal fibrinogen levels and normal INR (N=29; APTT prolongation due to FXI/FXII-consumption) was significantly lower compared to the remaining 28 patients who showed samples with reduced fibrinogen levels and/or prolonged INR (suffering from concomitant conditions) (10% vs. 32%; p=0.043). Conclusion We highlight a weak correlation between anti-Xa and APTT in an anti-Xa guided UFH anticoagulated CS population during left-sided ImpellaTM support. Patients with APTT-prolongation due to concomitant conditions with INR prolongation and/or fibrinogen shortage are at highest mortality risk. The APTT/Anti-Xa coefficient can serve as an independent risk factor whilst managing critically CS patients.

European practices on antithrombotic management during percutaneous mechanical circulatory support in adults: insights from an international survey

Abstract Background Bleeding and thrombotic complications remain a major concern in cardiogenic shock (CS) patients undergoing percutaneous mechanical circulatory support (pMCS) with veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and/or microaxial flow pumps like the Impella. Antithrombotic practices strongly determine the coagulopathic risk, but standardized protocols are lacking in this context. Purpose This survey outlines European practices on antithrombotic management in adults on pMCS for CS, making an initial effort to standardize practices, inform future trials, and enhance outcomes. Methods This online cross-sectional survey was distributed through digital newsletters and social media platforms by the Association of Acute Cardiovascular Care (ACVC) of the ESC and the European branch of the Extracorporeal Life Support Organization (EuroELSO). The survey was accessible from April 17th to May 23rd, 2023. The target population were European clinicians involved in care for adults on pMCS. Results We included 105 responses from 26 European countries. In 72.4% of the European respondents’ institutions, a standardized local anticoagulation protocol is present, with unfractionated heparin (UFH) being the predominantly used anticoagulant (Impella: 97.0%; V-A ECMO: 96.1%). Similarly, the purge solution during Impella support is most frequently UFH-based (84.1%). A bicarbonate-based purge solution (BBPS) as standard purge is reported by only 1.6%. UFH titration based on the activated partial thromboplastin time (APTT) alone is the most common practice either for Impella (43.1%) and for V-A ECMO (32.9%). A minority of 16.9% and 13.2% indicate relying on activated clotting time (ACT) for UFH-titration during Impella and V-A ECMO support, respectively. UFH-titration protocols are anti-Xa based for 12.3% (Impella) and 10.5% (V-A ECMO) of the respondents. An UFH anticoagulant protocol based on APTT and anti-Xa in parallel is the preferred option for 10.8% (Impella) and 14.5% (V-A ECMO) of the respondents. Anticoagulant targets for APTT, ACT and anti-Xa varied across institutions. The majority (83.8%) does not alter their anticoagulation management in case of combined Impella plus V-A ECMO-approach (ECMELLA). Typical thresholds for transfusion or administration of blood products without acute bleeding as indication vary substantially and are frequently not predefined. Following acute coronary syndrome without percutaneous coronary intervention (PCI), 54.0% and 42.7% administered dual antiplatelet therapy during Impella and V-A ECMO support, increasing to 93.7% and 84.0% after PCI. Conclusions Our survey validated the considerable variation in antithrombotic management in adults in CS on pMCS across European centres. There is a pressing demand for a standardized approach to antithrombotic management in this context to mitigate the impact of coagulopathic complications and, consequently, enhance outcomes.Figure 1.Figure 2.

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.

Preclinical characterisation and first-in-human results on the tolerability and pharmacodynamic effect of REGN9933, a monoclonal antibody targeting the factor XI/activated factor XI apple 2 domain

Abstract Background/Introduction Standard-of-care anticoagulants are associated with increased bleeding risk. Genetic/pharmacological data suggest coagulation factor XI (FXI) inhibition can prevent thrombosis with minimal increased bleeding risk. We present preclinical and first-in-human (FIH) data on REGN9933, a FXI-binding monoclonal Ab. Purpose To characterise REGN9933 epitope binding sites, affinities for FXI and activated FXI (FXIa), and effect on high molecular weight kininogen (HMWK)’s interaction with FXI. Also, to assess safety, tolerability and pharmacodynamics in healthy human participants (pts). Methods Epitope binding sites mapped with cryogenic electron microscopy, binding affinities determined with plasmon resonance techniques, effect on thrombin generation assessed with a thrombin generation assay, and impact on HMWK:FXI interaction analysed using ELISAs. In the FIH, Ph 1, randomised, double-blind, single-centre study, pts received a single dose of REGN9933 intravenously (IV; 3–300 mg) or subcutaneously (SC; 100 mg & 300 mg), or placebo (PBO). Primary endpoint: incidence and severity of treatment-emergent AEs (TEAEs). Other endpoints: effect of REGN9933 on activated partial thromboplastin time (aPTT) and prothrombin time (PT) to assess intrinsic and extrinsic pathway-triggered coagulation, respectively; and FXI activity. Results REGN9933 was found to bind the FXI apple 2 domain, with subnanomolar binding affinities for FXI and FXIa at 37°C, resulting in reduced thrombin generation from the intrinsic (not extrinsic) pathway. REGN9933 competed with HMWK for FXI binding in a dose-related manner. In the Ph 1 study, 56 pts received REGN9933 (IV, n=30; SC, n=12) or PBO (n=14); 42.9% and 21.4% had ≥1 TEAE, respectively (most common with REGN9933: headache, 12%; oropharyngeal pain, 5%). No serious/severe TEAEs, or TEAEs of special interest (inc. moderate/severe bleeding) reported. Laboratory tests revealed no clinically meaningful differences in the number/type of treatment-emergent potentially clinically significant values with REGN9933 vs PBO. REGN9933 resulted in dose-dependent prolongation of aPTT; aPTT mean fold change from baseline was highest with IV 300 mg after 8 hrs (2.7) and remained >2 for 36 days (Fig 1). There was no detectable effect on PT or clinically meaningful effect on bleeding time. REGN9933 supressed FXI activity in a dose-dependent manner, with suppression to approx. the lower limit of assay quantification (5%) with IV ≥30 mg (Fig 2). Conclusion(s) REGN9933 binds the FXI apple 2 domain and inhibits HMWK:FXI interaction, preventing intrinsic pathway-triggered FXI activation. FIH data showed dose-dependent inhibition of the intrinsic coagulation pathway by REGN9933, without affecting the extrinsic or common pathways. Pharmacodynamic and safety findings support continued development of REGN9933 as an anticoagulant that may carry less bleeding risk than currently approved agents.

Characterisation of the pharmacokinetic and pharmacodynamic relationship of milvexian in total knee replacement patients

Abstract Background Milvexian, an oral factor XIa inhibitor, is currently being evaluated in patients at risk for thrombotic events due to atrial fibrillation, ischaemic stroke, or acute coronary syndrome. The exposure-response relationship between clinical efficacy and safety endpoints and milvexian pharmacokinetic (PK) metrics was recently submitted as a separate publication. Characterisation of the relationship between the coagulation pharmacodynamic (PD) markers versus milvexian PK metrics at the patient level has yet to be reported. Purpose This analysis characterised the relationship between the coagulation biomarkers, activated partial thromboplastin time (aPTT) and prothrombin time (PT), and milvexian systemic exposure in patients undergoing total knee replacement (TKR) evaluated in the AXIOMATIC-TKR study. Methods A population pharmacokinetic (PopPK) model was previously developed and characterised the PK of milvexian in TKR patients well. The PK/PD relationships between observed aPTT and PT versus PopPK model estimated time-matched milvexian plasma concentrations via nonlinear mixed effects modeling. The relationship between key clinical safety endpoints (e.g., any bleeding or clinically relevant non-major bleeding) and individual PD marker change (e.g., aPTT ratio to baseline) was also explored. Results The aPTT increased with increasing plasma concentration of milvexian over the range of doses evaluated in the study (25mg QD to 200mg BID). An Emax type of model reasonably characterised the PK/PD relationship between the aPTT and model predicted time-matched milvexian plasma concentration, which is consistent with previously observed relationships in healthy volunteers. No change was observed in PT with increased milvexian exposure. No obvious relationship was identified between any (including clinically relevant non-major) bleeding and aPTT ratio to baseline. Conclusions Increased milvexian exposure is directly correlated with aPTT prolongation over the range of doses evaluated in the TKR study. There was no obvious relationship between any (including clinically relevant non-major) bleeding and aPTT ratio. The PK/PD relationship of aPTT without a parallel relationship in PT distinguishes milvexian, a FXIa inhibitor, from previously studied FXa inhibitors. These analyses were a complementary component in dose selection for the milvexian Phase 3 program. Figure 1. PK/PD relationship between aPTT (left) and PT (right) and estimated time-matched plasma concentration (AXIOMATIC-TKR study)

Lupus anticoagulant and valvular cardiac surgery.

Despite its name, lupus anticoagulant (LAC) neither exclusively occurs in lupus nor induces anticoagulation. It is an antiphospholipid antibody found in 2%-4% of the population that promotes clot formation by targeting phospholipid-protein complexes in cell membranes. However, in vitro, LAC exhibits paradoxical effects, prolonging clotting times in phospholipid-dependent assays such as Activated Partial Thromboplastin Time (APTT). This unpredictability extends to point-of-care tests like Activated Clotting Time (ACT), which are frequently used to monitor anticoagulation during cardiac surgeries involving cardiopulmonary bypass (CPB). High doses of unfractionated heparin (UFH) are administered in these procedures, but the presence of LAC complicates ACT measurements, creating challenges for both anesthesiologists and surgeons. This case report highlights the clinical implications of LAC in perioperative management, underscoring the difficulties in ensuring adequate anticoagulation during CPB.

Observation of the effect of single dose intravenous infusion of tranexamic acid on white blood cell, erythrocyte sedimentation rate and C-reactive protein after double segmental posterior lumbar interbody fusion

To observe the safety and effectiveness of single dose intravenous infusion of tranexamic acid (TXA) in dual level posterior lumbar interbody fusion (PLIF), and to explore the changes and trends in perioperative white blood cell (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Between October 2020 and September 2022, 46 patients with lumbar degenerative disease were treated with dual level PLIF, including 18 males and 28 females, with an average age of (60.24±10.68) years old, from 34 to 80 years old. They were divided into observation group and control group according to different treatment methods. There were 28 patients in the observation group, including 12 males and 16 females, with an average age of (61.04 ± 9.03) years old. There were 3 cases with lumbar disc herniation (LDH), lumbar spinal stenosis (LSS) 18 cases, lumbar spondylolisthesis (LS) 7 cases. TXA (1 g/100 ml) was administered intravenously 15 min before skin incision after general anesthesia. The control group consisted of 18 patients, including 6 males and 12 females, with an average age of (59.00±13.04) years old. There were 5 cases with LDH, LSS 9 cases, LS 4 cases, and TXA was not used. The operation time, intraoperative bleeding volume, postoperative drainage volume, postoperative deep vein thrombosis (DVT), postoperative hospital stay, postoperative activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelet (PLT), red blood cell (RBC), hemoglobin (HB), hematocrit (HCT), the first day, the fourth day, the seventh day and the last tested after operation WBC, ESR and CRP were recorded. The postoperative wounds of the patients healed well and there was no DVT. 46 patients were followed up from 3 to 6 months. The intraoperative blood loss was 400.0 (300.0, 500.0) ml and the postoperative drainage was 260.0 (220.0, 450.0) ml in the observation group, which were lower than the control group[600.0(400.0, 1000.0) ml, 395.0 (300.0, 450.0) ml], P<0.05. There was no significant difference between the two groups in operation time, postoperative hospital stay, postoperative APTT, PT, TT, FIB, PLT, RBC, HB, HCT, and postoperative WBC, ESR and CRP at different times (P>0.05). Single dose intravenous infusion of TXA can reduce the blood loss of bi-segmental PLIF, and has no significant effect on WBC, ESR and CRP after operation.

Tranexamic acid with vitamin K mixture decreases bleeding of total hip arthroplasty in a Jordanian population

Background: Bleeding of total hip arthroplasty has severe consequences on postoperative recovery. 75–90% of early bleeding after surgery and during surgery is caused by operative technical issues. tranexamic acid decreases bleeding of arthroplasty. vitamin k has late and dose sensitive effect in clotting. Methods: This retrospective investigation included subjects of middle age and of both genders scheduled for primary hip replacement at Queen Alia hospital, Jordanian Royal medical services, between March 2022 and June 2023. Subjects were classified into two groups. Group I subject were administered intravenous mixture of Tranexamic acid 10 mg/kg with vitamin K1 of 10 mg 5 min pre-skin incision followed by an infusion of Tranexamic acid 1 mg/kg/h and vitamin K1 0.2 mg/kg/h, until skin closure. Group II subjects were administered only intravenous vitamin K1 of 10 mg, 5 min pre- skin incision followed by infusion of 0.2 mg/kg/h until skin closure. Hemoglobin, packed cell volume, platelet count, prothrombin time, partial thromboplastin time and fibrinogen were tested. Bleeding and blood transfusion were remarked. Results: Group I demonstrated a remarkable less modifications in blood tests and less bleeding than group II. Group II demonstrated less bleeding after surgery. The average Hb in group I demonstrated a remarkable less reduction after surgery compared to group II. (p&lt;0.005). No blood transfusion after surgery was needed in group I. Nine (15%) patients in group II needed one unit of blood transfusion during surgery. Conclusion: Intravenous administration of Tranexamic acid with vitamin K mixture in total hip arthroplasty decreased bleeding during and after surgery and decreased the requirement for blood transfusion.

Mapping the landscape of machine learning models used for predicting transfusions in surgical procedures: a scoping review

Massive transfusion of blood products poses challenges in determining the need for transfusion and the appropriate volume of blood products. This review explores the use of machine learning (ML) models to predict transfusion risk during surgical procedure, focusing on the methodology, variables, and software employed to predict transfusion. This scoping review investigates the development and current state of machine learning models for predicting transfusion risk during surgical procedure, aiming to inform physicians about the field’s progress and potential directions.The review was conducted using the databases Cochrane, Embase, and PubMed. The search included keywords related to blood transfusion, statistical models, and surgical procedures. Peer-reviewed articles were included, while literature reviews, case reports, and non-human studies were excluded.A total of 40 studies met the inclusion criteria. The most frequently studied biological variables included haemoglobin, platelet count, international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, creatinine, white blood cells, and albumin. Clinical variables of importance included age, sex, surgery type, blood pressure, weight, surgery duration, american society of anesthesiology (ASA) status, blood loss, and body mass index (BMI). The software employed varied, with Python, R, SPSS, and SAS being the most commonly used. Logistic regression was the predominant methodology used in 20 studies.Our scoping review highlights the need for improved reporting and transparency in methodology, variables, and software used. Future research should focus on providing detailed descriptions and open access to codes of respective models, promoting reproducibility, and enhancing the clinical relevance of transfusion risk prediction models.

Establishment of an Integrated Population Pharmacokinetic/Pharmacodynamics Model of Apixaban in Chinese Healthy Population Adjusting for Key Genetic Variants.

To improve the understanding of pharmacokinetic/pharmacodynamic (PK/PD) profiles of apixaban, supporting personalised drug prescriptions for future patients. Genetic as well as nongenetic factors can affect the predictable PK and PD characteristics of apixaban. Establish a integrated popPK/PD model that adjusts for critical genetic variant. The integrated PK/PD models was characterized on the basis of PK (apixaban blood concentration) and PD (prothrombin time (PT), activated partial thromboplastin time (APTT), and anti-FXa activity) data from 181 healthy Chinese volunteers. Other investigated covariate variables included: Meaningful intrinsic and extraneous determinants, correlated markers (ABCG2, F13A1, C3, etc.). A total of 2877 PK concentration observations were included in the modeling dataset. The PK model of apixaban is adopted by single compartment model with first-order oral absorption. The estimated values of total clearance rate (CL/F), apparent distribution volume (V/F), and absorption rate constant (KA) in the final model are 3.37 l/h, 28.2 l, and 0.781 l/h, respectively. The PK model includes significance covariates such as FOOD, RBC, WT, and gene (ABCG2). The PD model of apixaban is adopted by a linear direct effect model with additive error, which was used to describe the relationship between markers such as APTT, PT, anti-FXa, versus plasma concentration. PK simulation within the modelled dose range is similar to clinical real date, while PD simulation results also show that the simulated exposure parameters is within the range of the literature. We established a comprehensive PK/PD model and used it to simulate markers level such as APTT, PT, and anti-FXa of apixaban. Individual predictive values with a dose of 2.5 mg are basically within the expected recommended range.

Time-Dependent Association of Preinjury Anticoagulation on Traumatic Brain Injury-Induced Coagulopathy: A Retrospective, Multicenter Cohort Study

BACKGROUND AND OBJECTIVES: The impact of preinjury anticoagulation on coagulation parameters over time after traumatic brain injury (TBI) has remained unclear. Based on the hypothesis that preinjury anticoagulation significantly influences the progression and persistence of TBI-induced coagulopathy, we retrospectively examined the association of preinjury anticoagulation with various coagulation parameters during the first 24 hours postinjury in 5 periods. METHODS: Data from the Japanese registry of patients with TBI aged ≥65 years admitted between 2019 and 2021 were used. Time since injury was classified into 5 categories through a graphical analysis of coagulation parameters. We examined the association between preinjury anticoagulation and the platelet count, prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), D-dimer level, and fibrinogen level during each period by analysis of covariance using 10 clinical factors as confounding factors. RESULTS: Data from 545 patients and 795 blood tests were analyzed. The patients' mean age was 78.9 years, and 87 (16%) received anticoagulation therapy. The preinjury anticoagulation group had significantly greater Rotterdam computed tomography scores and poorer outcomes at discharge than the control group, with significantly lower D-dimer levels and higher fibrinogen levels. Analysis of covariance revealed significant associations between the D-dimer level and preinjury anticoagulation within 2 to 24 hours postinjury, APTT and preinjury anticoagulation within 1 to 24 hours, and PT-INR and preinjury anticoagulation throughout all periods up to 24 hours postinjury. CONCLUSION: Despite more severe TBI signs and poorer outcomes, the preinjury anticoagulation group had significantly lower D-dimer levels, especially within 2 to 24 hours postinjury. Thus, D-dimer levels during this period may not reliably represent TBI severity in patients receiving anticoagulation therapy before injury. Preinjury anticoagulation was also associated with an elevated PT-INR and prolonged APTT from early to 24 hours postinjury, highlighting the importance of aggressive anticoagulant reversal early after injury.

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.

Measuring the impact: Severity of harm from laboratory errors in 195 tests.

This study aimed to objectively assess the potential severity of harm associated with erroneous results in 195 laboratory tests by surveying 514 specialist physicians and medical biochemistry experts. The survey obtained participants' (75 medical biochemists, 439 clinicians) opinions on severity of harm for the erroneous results of 195 tests. The comprehensive list of errors and their effects on test results were obtained from the literature, and then matched with severity of harm scores, from 1 (negligible effect) to 5 (life-threatening injury/death), obtained from the survey responses. Participants perceived tests such as cardiac biomarkers, blood gases, coagulation parameters (activated partial thromboplastin time, prothrombin time, international normalized ratio, and dimerized plasmin fragment D), critical ions (potassium, sodium), toxic trace elements (lead, mercury), and specific serum drug levels (lithium, digoxin) to have a greater potential for patient harm in case of errors. Medical biochemistry specialists assigned higher severity scores to some laboratory tests, including total bilirubin, pseudocholinesterase, platelet indices, and some drug levels (cyclosporine, methotrexate, vancomycin). A substantial agreement (91%) was observed between medical biochemists and clinicians in terms of the most frequently chosen severity of harm score. The study provided objective severity scores and identified high-risk tests for targeted quality improvement.

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.

Anticoagulant Effect of Snow mountain garlic: In Vitro Evaluation of Aqueous Extract.

Snow mountain garlic is traditionally eaten by Himalayan locals for its medicinal properties. Although different species of the genus Allium are known to have other biological effects, such as antiplatelet and antithrombotic activities, little is known about the anticoagulant effect of Snow mountain garlic, a member of the genus Allium. Therefore, the present study examined the in vitro anticoagulant effect of the aqueous extract, the lyophilized aqueous extract, and the isoflavone extract from the lyophilized aqueous extract of Snow mountain garlic in samples from 50 human blood donors. Compared to the control, concentrations of 25, 12.5, and 6.25 mg/100 µL lengthened the clotting times of prothrombin, and concentrations of 25 and 12.5 mg/100 µL lengthened the activated partial thromboplastin time (p ˂ 0.05). The isoflavone extract from the lyophilized aqueous extract containing isoflavones, organosulfur compounds, a polyphenol, and a steroid glycoside showed a significant effect (p ˂ 0.05) on the prothrombin time and the activated partial thromboplastin time at a dose of 20 µL (volume) compared to the control. The results regarding the use of Snow mountain garlic as a preventive measure and aid in treating thromboembolic disease are promising.

Thymidine phosphorylase mediates SARS-CoV-2 spike protein enhanced thrombosis in K18-hACE2TG mice

IntroductionThymidine phosphorylase (TYMP), which facilitates platelet activation and thrombosis, is significantly increased in COVID-19 patients. We hypothesize that TYMP mediates SARS-CoV-2 spike protein (SP)-induced thrombosis. Materials and methodsPlasmids encoding wildtype SP or empty vector (p3.1) were transfected into COS-7 cells, and cell lysates were prepared as a reservoir for SP or p3.1 (control), respectively. K18-hACE2TG and K18-hACE2TG/Tymp−/− mice were treated with a single dose of SP or p3.1 by intraperitoneal injection and then subjected to thrombosis studies three days later. The role of SP on inflammatory signaling activation was assessed in BEAS-2B cells. ResultsSARS-CoV-2 SP increased the expression of TYMP, resulting in the activation of STAT3 and NF-κB in BEAS-2B cells. A siRNA-mediated knockdown of TYMP attenuated SP-enhanced activation of STAT3. SP significantly promoted arterial thrombosis in K18-hACE2TG mice. SP-accelerated thrombosis was attenuated by inhibition or genetic ablation of TYMP. SP treatment did not influence ADP- or collagen-induced platelet aggregation but significantly increased platelet adhesion to fibrinogen. SP treatment also significantly shortened activated partial thromboplastin time, which was reversed and even prolonged by TYMP deficiency. Additionally, SP binds to platelet factor 4 (PF4) and TYMP. TYMP does not bind PF4 but enhances the formation of the SP/PF4 complex, which may augment the procoagulant and prothrombotic effect of PF4. ConclusionsWe conclude that SP is prothrombotic and upregulates TYMP expression, and TYMP inhibition or knockout mitigates SP-enhanced thrombosis. These findings suggest that inhibition of TYMP may be a novel therapeutic strategy for COVID-19-associated thrombosis.

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.

Residual Red Blood Cell Volume in Extracorporeal Blood Circuit After Hemodialysis: A Single-center Study.

The factors contributing to blood loss during HD procedures remain underexplored. This study aimed to quantify blood loss during HD and identify the potential factors associated with it. The study included 70 ESRD patients undergoing HD. After dialysis, the extracorporeal blood circuits were rinsed with 1,000 mL of 0.05% NH3 solution in distilled water, and hemoglobin (Hb) levels were measured. Univariate regression was used to assess the linear relationship between residual red blood cell (RBC) volume and various parameters, including HD mode, dialyzer surface area, ultrafiltration goal (UFG), hypotension during HD, blood flow rate, activated partial thromboplastin time (aPTT), and C-reactive protein (CRP). Multivariate regression was also conducted to explore the relationships among these parameters. The mean RBC volume remaining in the extracorporeal blood circuit after HD was 1.6 ± 0.9 ml (mode: 1.0, range: 0.3-6.5 ml). When converted to whole blood volume per patient, the mean blood volume was 5.3 ± 3.0 ml (median: 4.1 ml, mode: 4.0 ml, range: 1.0-19.0 ml). Multivariate analysis identified the dialyzer surface area as the only significant determinant of residual RBC volume. After HD, the remaining RBC volume in the extracorporeal blood circuit varies from 1.6 to 6.5 ml. When the RBC volume was converted to whole blood volume for each case, the blood loss ranged from 1.0 to 19.0 ml. Dialyzer surface area was the only significant determinant of residual RBC volume.

Association Between Cerebral Microbleeds and Neurological Outcomes in Patients Who Underwent Extracorporeal Membrane Oxygenation.

Cerebral microbleeds (CMBs) are common and varied in patients receiving extracorporeal membrane oxygenation (ECMO). Here, the authors describe CMB findings in patients receiving ECMO and their association with clinical factors. A total of 138 patients receiving ECMO were enrolled and categorized as venovenous and venoarterial. Blood coagulation profiles during ECMO support and Glasgow Coma Scale (GCS) scores within 7 days were recorded. Patients with CMBs exhibited prolonged activated clotting time (P<0.001), decreased fibrinogen levels (P<0.001), reduced platelet counts (P<0.001), and extended prothrombin time (P<0.001). A significant correlation (P<0.05) was observed between the presence of CMBs and most coagulation parameters among all patients. Patients with venoarterial ECMO had significantly higher activated partial thromboplastin time, activated clotting time, and prothrombin time compared with those with venovenous ECMO (all P<0.05). Patients with a less severe CMB burden exhibited higher GCS scores and better neurological injury outcomes at both 7 and 90 days. CMB burden in all patients with ECMO was significantly correlated (P<0.05) with most blood coagulation profiles and neurological injury. CMB burdens after ECMO are common, varied, and associated with a variety of clinical conditions. These findings may guide ECMO management.