Biochemical Behavior, Influence on Cell DNA Condition, and Microbiological Properties of Wool and Wool-Copper Materials.

The paper presents the study concerning the preparation and physio-chemical and biological properties of wool-copper (WO-Cu) materials obtained by the sputter deposition of copper onto the wool fibers. The WO-Cu material was subjected to physio-chemical and biological investigations. The physio-chemical investigations included the elemental analysis of materials (C, N, O, S, and Cu), their microscopic analysis, and surface properties analysis (specific surface area and total pore volume). The biological investigations consisted of the antimicrobial activity tests of the WO-Cu materials against colonies of Gram-positive (Staphylococcus aureus) bacteria, Gram-negative (Escherichia coli) bacteria, and fungal mold species (Chaetomium globosum). Biochemical-hematological tests included the evaluation of the activated partial thromboplastin time and pro-thrombin time. The tested wool-copper demonstrated the ability to interact with the DNA in a time-dependent manner. These interactions led to the DNA's breaking and degradation. The antimicrobial and antifungal activities of the WO-Cu materials suggest a potential application as an antibacterial/antifungal material. Wool-copper materials may be also used as customized materials where the blood coagulation process could be well controlled through the appropriate copper content.

Role of CES1 and ABCB1 Genetic Polymorphisms on Functional Response to Dabigatran in Patients with Atrial Fibrillation.

Background: Dabigatran etexilate is a pro-drug hydrolyzed into dabigatran by carboxylesterases (CES) and is a substrate of the P-Glycoprotein encoded by the adenosine-triphosphate-binding cassette sub-family B member (ABCB)1 genes. We evaluated the functional response to dabigatran according to different CES1 and ABCB1 single-nucleotide polymorphisms (SNPs) in patients with atrial fibrillation (AF). Methods: A total of 100 consecutive patients with AF taking dabigatran were enrolled by two Italian centers. A venous blood sample was drawn for genetic determinations, as well as a measurement of the diluted thrombin time (dTT) and drug plasma concentrations, at the trough and peak. The main objective was the relationship between the dTT values and CES1 rs2244613, CES1 rs8192935 and ABCB1 rs4148738 SNP while on two different dabigatran doses (110 and 150 mg BID). Results: A total of 43 patients were on a 110 mg dabigatran dose and 57 on 150 mg. The DTT values at the trough and at peak were not different among patients with different CES1 rs2244613 and CES1 rs8192935 genotypes, regardless of the dabigatran dose. In patients on 150 mg dabigatran, the dTT values at the trough were 77 (44-111) ng/mL in patients with the ABCB1 rs4148738 heterozygous CT genotype vs. 127 (85-147) ng/mL in the wild-type CC genotype vs. 110 (47-159) ng/mL in the mutant trait TT genotype (p = 0.048). In patients with the ABCB1 rs4148738 CT genotype, OR for having dTT values at a trough below the median was 3.21, 95% CI 1.04-9.88 (p = 0.042). Conclusions: ABCB1 rs4148738 CT heterozygous is associated with the reduced anticoagulant activity of dabigatran at the trough in patients receiving the higher dose regimen.

Association of prothrombin time, thrombin time and activated partial thromboplastin time levels with preeclampsia: a systematic review and meta-analysis.

BACKGROUND: Preeclampsia (PE), an obstetric disorder, remains one of the leading causes of maternal and infant mortality worldwide. In individuals with PE, the coagulation-fibrinolytic system is believed to be among the most significantly impacted systems due to maternal inflammatory responses and immune dysfunction. Therefore, this systematic review and meta-analysis aimed to assess the association of prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) levels with preeclampsia. METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Articles relevant to the study, published from July 26, 2013, to July 26, 2023, were systematically searched across various databases including PubMed, Scopus, Embase, and Hinari. The methodological quality of the articles was evaluated using the Joanna Briggs Institute critical appraisal checklist. Utilizing Stata version 14.0, a random-effects model was employed to estimate the pooled standardized mean difference (SMD) along with the respective 95% CIs. The I2 statistics and Cochrane Q test were utilized to assess heterogeneity, while subgroup analyses were performed to explore its sources. Furthermore, Egger's regression test and funnel plot were employed to assess publication bias among the included studies. RESULTS: A total of 30 articles, involving 5,964 individuals (2,883 with PE and 3,081 as normotensive pregnant mothers), were included in this study. The overall pooled SMD for PT, APTT, and TT between PE and normotensive pregnant mothers were 0.97 (95% CI: 0.65-1.29, p < 0.001), 1.05 (95% CI: 0.74-1.36, p < 0.001), and 0.30 (95% CI: -0.08-0.69, p = 0.11), respectively. The pooled SMD indicates a significant increase in PT and APTT levels among PE patients compared to normotensive pregnant mothers, while the increase in TT levels among PE patients was not statistically significant. CONCLUSIONS: The meta-analysis underscores the association between PE and prolonged PT and APTT. This suggests that evaluating coagulation parameters like PT, APTT, and TT in pregnant women could offer easily accessible and cost-effective clinical indicators for assessing PE. However, multicenter longitudinal studies are needed to evaluate their effectiveness across various gestational weeks of pregnancy.

Urinary protein and coagulation-fibrinolysis indicators in preeclampsia: Expression and significance.

This study investigates the expression and significance of urinary protein and coagulation-fibrinolysis indicators in preeclampsia, categorized into mild preeclampsia (109 cases) and severe preeclampsia (97 cases) based on disease severity. Additionally, 110 patients with gestational hypertension (gestational hypertension group) were included for comparative analysis. General information, laboratory indicators, urinary protein, and coagulation-fibrinolysis indicator levels were collected for each group. Significant differences were observed in blood pressure among groups (P < .05), while uric acid, serum creatinine, aspartate transaminase, alanine transaminase, and triglycerides showed no significant differences (P > .05). Total cholesterol, triglycerides, and low-density Lipoprotein levels in severe preeclampsia were higher than those in mild preeclampsia and gestational hypertension groups, whereas high-density lipoprotein, albumin, and platelet levels were lower in severe preeclampsia. No significant differences were observed in prothrombin time or D-dimer levels among groups (P > .05). Urinary protein, urinary protein quantification, activated partial thromboplastin time, thrombin time, and fibrinogen were identified as influencing factors for adverse maternal and infant outcomes in severe preeclampsia patients. The study concludes that urinary protein and coagulation-fibrinolysis indicators are elevated in preeclampsia, particularly in severe preeclampsia cases, suggesting their potential use as diagnostic influencing factors for severe preeclampsia.

Short-Term Mortality in Hospitalized Patients with Congestive Heart Failure: Markers of Thrombo-Inflammation Are Independent Risk Factors and Only Weakly Associated with Renal Insufficiency and Co-Morbidity Burden.

Congestive heart failure (CHF) is associated with significant morbidity and mortality. There has been renewed interest in using thrombo-inflammatory markers as prognostic tools in patients with CHF. To determine if thrombo-inflammatory markers are independent risk factors for 28-day mortality in hospitalized CHF patients, we retrospectively analyzed admission data extracted from 2008 consecutive patients admitted with a diagnosis of CHF to Zigong Fourth People's Hospital. Multivariate Cox proportional hazards analysis demonstrated that the thrombo-inflammatory markers thrombin time, platelet/lymphocyte ratio (PLR), and D-dimer level were independent predictors of mortality. In addition, variables reflecting the severity of CHF (New York Heart Association class > 2), impaired renal function (elevated serum creatinine [SCr]), impaired organ perfusion (elevated BUN), and chronic liver disease were also independent predictors of mortality. Thrombo-inflammatory biomarkers were only weakly associated with SCr and the burden of co-morbidity, suggesting that thrombo-inflammation may in large part be attributable to CHF itself and that, moreover, its presence may confer an increased risk of mortality. Further large-scale prospective studies are needed to determine the existence and the consequences of a thrombo-inflammatory phenotype among patients with CHF.

The effect of argatroban on early neurological deterioration and outcomes in minor ischemic stroke: preliminary findings.

Background: Minor ischemic stroke (MIS) is associated with early neurological deterioration (END) and poor prognosis. Here, we investigated whether argatroban administration can mitigate MIS-associated END and improve functional outcomes by monitoring activated partial thrombin time (APTT). Methods: Data were collected for patients with MIS admitted to our hospital from January 2019 to December 2022. Patients were divided into a dual antiplatelet therapy (DAPT) group (aspirin + clopidogrel) and an argatroban group (aspirin + argatroban). Those in the latter group who achieved a target APTT of 1.5-3-fold that of baseline and <100 s at 2 h after argatroban infusion were included in the argatroban subgroup. The primary outcome was the END rate of the DAPT group versus that of the argatroban group or the argatroban subgroup. Secondary outcomes included the proportion of patients with modified Rankin Scale (mRS) 0-2 at 7 and 90 days. In addition, baseline date were compared between patients with and without END in the argatroban group. Results: 363 patients were included in the DAPT group and 270 in the argatroban group. There were no significant differences in any above outcome between them. 207 pairs were included in the DAPT group and the argatroban subgroup after 1:1 propensity score matching (PSM). Significant differences were observed in the proportion of END (OR, 2.337; 95% CI, 1.200-4.550, p = 0.011) and mRS 0-2 at 7 days (OR, 0.624; 95% CI, 0.415-0.939, p = 0.023), but not in mRS 0-2 at 90 days or the hemorrhagic events between the two groups. In the argatroban group, univariate analysis showed that the rate of diabetes (OR, 2.316; 95% CI, 1.107-4.482, p = 0.023), initial random blood glucose (OR, 1.235; 95% CI, 1.070-1.425, p = 0.004), drinking history (OR, 0.445; 95% CI, 0.210-0.940, p = 0.031) or those reaching the target APTT (OR, 0.418; 95% CI, 0.184-0.949, p = 0.033) was significantly different among patients with and without END. However, there were no statistical differences in these parameters between them following multivariate analysis. Conclusion: In patients with MIS, argatroban administration and reaching the target APTT can reduce the incidence of END and improve short-term functional prognosis.

International council for standardisation in haematology recommendations on fibrinogen assays, thrombin clotting time and related tests in the investigation of bleeding disorders.

This guidance was prepared on behalf of the International Council for Standardisation in Haematology (ICSH) by an international working group of clinicians and scientists. The document focuses on tests and assays used for the assessment of fibrinogen function, particularly in the scenario of bleeding disorders. Thrombin clotting time (TT) is used as a screening test in some laboratories and also has some utility when direct anticoagulants are in use. The Clauss fibrinogen assay remains the method of choice for the assessment of fibrinogen function, but there are some situations where the results may be misleading. Prothrombin time derived fibrinogen assays are frequently used, but should be interpreted with caution; the results are not interchangeable between different methods and fibrinogen can be overestimated in certain clinical scenarios. Viscoelastic point of care methods may be helpful in emergency situations, while Reptilase time (and similar tests) are useful combined with TT in distinguishing heparin contamination of samples (i.e., if an incorrect blood draw is suspected) and the presence of direct thrombin inhibitors. Fibrinogen antigen assays should be used in the investigation of functional fibrinogen abnormalities; fibrinogen antigen and genetic testing are recommended in the confirmation of congenital fibrinogen disorders. The following recommendations for fibrinogen function assessment are based on published literature and expert opinion and should supplement local regulations and standards.

Comparisons between diluted thrombin time, ecarin chromogenic assays, and UPLC-MS for plasma level dabigatran quantification: Results from DRIVING study.

INTRODUCTION: The knowledge of dabigatran levels is helpful for decision-making in specific situations such as urgent surgery or when the question of reversal arises (uncontrolled bleeding, eligibility for thrombolysis). However, a limited number of observational studies are available regarding comparisons between quantification methods. The objective of the study was to compare dabigatran plasma levels using three assays including the reference method (high-performance liquid chromatography coupled with mass spectrometry), focusing on the agreement around the 30-50 ng/mL clinically relevant thresholds. METHODS: Sixty healthy volunteers from DRIVING trial (NCT01627665) were given a single 300-mg dabigatran etexilate dose. Serial blood samplings were performed at pre-defined time points (0 to 24 h). We analyzed plasma samples using ultra-performance-liquid chromatography coupled with tandem mass spectrometry (UPLC-MS) (dabigatran reference method); ii/diluted thrombin time (dTT) (Hemoclot-DTI-Hyphen-Biomed); iii/ecarin-based chromogenic assay (ECA-II-Stago). RESULTS: Nine hundred sixty samples were analyzed using the three assays (2759 values). dTT and ECA-II values were highly correlated with those of UPLC-MS (Deming regression). Most values >50 ng/mL were higher using dTT and ECA-II compared to UPLC-MS: biases were constant, +14% and +16% with dTT and ECA-II, respectively (Bland-Altman plots), suggesting that active metabolites accounted for ~15% of thrombin inhibition. Regarding values <30 ng/mL, 30-50 ng/mL, or ≥50 ng/mL, the agreement probability between dTT and ECA-II was of 90.6% [88.4-92.5] (Cohen's kappa coefficient 0.84). CONCLUSION: dTT and ECA-II assays rapidly provide accurate dabigatran-level results for clinical practice, both assays being suitable in emergency, taking into account the thrombin inhibitory effect of dabigatran metabolites.

Blood Coagulation Activities of Cotton-Alginate-Copper Composites.

Alginate-based materials have gained significant attention in the medical industry due to their biochemical properties. In this article, we aimed to synthesize Cotton-Alginate-Copper Composite Materials (COT-Alg(-)Cu(2+)). The main purpose of this study was to assess the biochemical properties of new composites in the area of blood plasma coagulation processes, including activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT). This study also involved in vitro antimicrobial activity evaluation of materials against representative colonies of Gram-positive and Gram-negative bacteria and antifungal susceptibility tests. The materials were prepared by immersing cotton fibers in an aqueous solution of sodium alginate, followed by ionic cross-linking of alginate chains within the fibers with Cu(II) ions to yield antimicrobial activity. The results showed that the obtained cotton-alginate-copper composites were promising materials to be used in biomedical applications, e.g., wound dressing.

Systemic anticoagulation in ECMO.

While unfractionated heparin (UFH) remains the mainstay of anticoagulation during pediatric extracorporeal life support, direct thrombin inhibitors (DTIs) are increasingly used. In this article, we will review most recent evidence regarding utilization of both UFH and DTIs and compare their known advantages and disadvantages. We will present anticoagulation monitoring strategies during ECMO and outline the most recent Extracorporeal Life Support Organization's anticoagulation guidelines, however with the caveat that there are no true consensus recommendations for anticoagulation management in pediatric ECMO. With these updates, we will serve as the bedside clinician's refresher on common practices for anticoagulation during "routine" ECMO. We will additionally highlight special circumstances, including high risk surgical procedures during ECMO, in which adjustments in anticoagulation and/or addition of antifibrinolytic therapy might mitigate risk.

The Evaluation of Clot Waveform Analyses for Assessing Hypercoagulability in Patients Treated with Factor VIII Concentrate.

BACKGROUND: Regular prophylactic therapy has become an increasingly common treatment for severe hemophilia. Therefore, hypercoagulability-a potential risk factor of thrombosis-is a cause for concern in hemophilic patients treated with a high dose of FVIII concentrate. In clot waveform analysis (CWA)-thrombin time (TT), a small amount of thrombin activates clotting factor VIII (FVIII) instead of fibrinogen, resulting in FVIII measurements using CWA-TT with a small amount of thrombin. METHODS: The coagulation ability of patients treated with FVIII concentrate or emicizumab was evaluated using activated partial thromboplastin time (APTT), TT and a small amount of tissue factor-induced FIX activation assay (sTF/FIXa) using CWA. RESULTS: The FVIII activity based on CWA-TT was significantly greater than that based on the CWA-APTT or chromogenic assay. FVIII or FVIII-like activities based on the three assays in plasma without emicizumab were closely correlated; those in plasma with emicizumab based on CWA-TT and chromogenic assays were also closely correlated. CWA-APTT and CWA-TT showed different patterns in patients treated with FVIII concentrates compared to those treated with emicizumab. In particular, CWA-TT in patients treated with FVIII concentrate showed markedly higher peaks in platelet-rich plasma than in platelet-poor plasma. CWA-APTT showed lower coagulability in hemophilic patients treated with FVIII concentrate than in healthy volunteers, whereas CWA-sTF/FIXa did not. In contrast, CWA-TT showed hypercoagulability in hemophilic patients treated with FVIII concentrate. CONCLUSIONS: CWA-TT can be used to evaluate the thrombin bursts that cause hypercoagulability in patients treated with emicizumab. Although routine APTT evaluations demonstrated low coagulation ability in patients treated with FVIII concentrate, CWA-TT showed hypercoagulability in these patients, suggesting that the evaluation of coagulation ability may be useful when using multiple assays.

Prognostic assessment of lung adenocarcinoma patients with early-staging diseases: a nomogram based on coagulation-related factors.

OBJECTIVES: Early-stage lung adenocarcinoma (ADC) has a great heterogeneity in prognosis that is difficult to evaluate effectively. Thus, we developed and validated an effective nomogram prognostic model based on the clinical and laboratory characteristics of stage I-IIA ADC. METHODS: We included 1585 patients with pathologically diagnosed stage I-IIA ADC who underwent surgery at Shanghai Pulmonary Hospital. The nomogram was constructed based on the peripheral blood test and coagulation test indicators and evaluated using Calibration plots, concordance index, decision curve analysis and the X-tile software. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method and the Cox proportional hazard regression model. The primary end point of this study was RFS. RESULTS: Thrombin time and 4 clinical indicators for RFS were integrated into nomograms. A favourable agreement between the nomogram prediction and validation was observed in the calibration curves for RFS probabilities. The concordance index of the nomogram to predict RFS was 0.736 (95% confidence interval, 0.717-0.755). Moreover, significant differences were shown between the high-risk and low-risk groups in RFS and OS (P < 0.001) after effective cut-off values of risk points were found based on the nomogram. CONCLUSIONS: We established and validated a prognostic nomogram including thrombin time to predict RFS and OS of stage I-IIA ADC patients. This nomogram provided an effective prediction ability for the prognosis of stage I-IIA ADC patients.

Preoperative Fibrinogen Levels and Function as Predictive Factors for Acute Bleeding in the Hematoma Cavity After Burr Hole Drainage in Patients with CSDH.

OBJECTIVE: Burr hole drainage (BHD) is the primary surgical intervention for managing chronic subdural hematoma (CSDH). However, it can lead to postoperative complications such as acute bleeding within the hematoma cavity and hematoma recurrence. The objective of this study is to identify the risk factors for these complications and develop a predictive model for acute hematoma cavity bleeding after BHD in patients with CSDH. METHODS: This study presents a retrospective cohort investigation conducted at a single center. The clinical dataset of 308 CSDH patients who underwent BHD at a hospital from 2016 to 2022 was analyzed to develop and assess a prognostic model. RESULTS: The nonbleeding group exhibited a significant correlation between fibrinogen (FIB) and thrombin time (TT), whereas no correlation was observed in the bleeding group. Notably, both FIB and TT were identified as risk factors for postoperative acute bleeding within the hematoma cavity. We developed a prognostic model to predict the occurrence of postoperative acute bleeding within the hematoma cavity after BHD in patients with CSDH. The model incorporated FIB, TT, coronary artery disease, and Glasgow Coma Scale scores. The model exhibited good discrimination (area under the curve: 0.725) and calibration (Hosmer-Leeshawn goodness of fit test: P > 0.1). Furthermore, decision curve analysis demonstrated the potential clinical benefit of implementing this prediction model. CONCLUSIONS: The predictive model developed in this study can forecast the risk of postoperative acute bleeding within the hematoma cavity, thus aiding clinicians in selecting the optimal treatment approach for patients with CSDH.

Thrombin Time is a Diagnostic Biomarker of Sudden Sensorineural Hearing Loss and Predicts the Prognosis.

OBJECTIVES: The aim of this study is to determine whether thrombin time (TT) could be used as diagnostic biomarkers and predict the prognosis for sudden sensorineural hearing loss (SSNHL). METHODS: Sixty-one patients diagnosed with SSNHL and 65 people who underwent physical examination were recruited. Data on the patient's background, clinical course, and laboratory findings were collected. SSNHL patients were divided into the effective and ineffective groups according to the hearing recovery from the treatment and were assessed by binary logistic regression. Receiver-operating characteristic (ROC) analysis was carried out for the best discriminating cutoff value of the biomarker with the corresponding sensitivity and specificity was calculated. RESULTS: The SSNHL group exhibited prolonged TT (19.11 ± 1.12 seconds) compared to the control group (17.58 ± 2.18 seconds, P < .001). Binary logistic regression analysis found a significant positive association between TT and SSNHL and was observed with an odds ratio (OR) 1.769 [95% confidence interval (CI) 1.344-2.330, P < .001] in the unadjusted model. Even after adjustment using the variables included in the multivariate models, TT was significantly predictive of SSNHL. A TT cutoff value of 17.65 seconds provides optimal separation between patients with SSNHL and controls in the ROC analysis [Area Under the Curve (AUC) 0.773, 95% CI 0.689-0.856; sensitivity, 0.918; and specificity, 0.569]. TT in the effective group of SSNHL patients was shorter (18.76 ± 1.06 seconds) than that in the ineffective group (19.43 ± 1.09 seconds, P = .018). The cutoff value of TT as progress predictors was 19.85 seconds. The TT < 19.85 seconds showed an effective rate 59.09% (26/44) higher than 17.65% (3/17) of TT ≥ 19.85 seconds. CONCLUSIONS: TT is a potential biomarker of SSNHL and is independently associated with the prognosis of patients with SSNHL.

Development and validation for multifactor prediction model of sudden sensorineural hearing loss.

Background: Sudden sensorineural hearing loss (SSNHL) is a global problem threatening human health. Early and rapid diagnosis contributes to effective treatment. However, there is a lack of effective SSNHL prediction models. Methods: A retrospective study of SSNHL patients from Fujian Geriatric Hospital (the development cohort with 77 participants) was conducted and data from First Hospital of Putian City (the validation cohort with 57 participants) from January 2018 to December 2021 were validated. Basic characteristics and the results of the conventional coagulation test (CCT) and the blood routine test (BRT) were then evaluated. Binary logistic regression was used to develop a prediction model to identify variables significantly associated with SSNHL, which were then included in the nomogram. The discrimination and calibration ability of the nomogram was evaluated by receiver operating characteristic (ROC), calibration plot, and decision curve analysis both in the development and validation cohorts. Delong's test was used to calculate the difference in ROC curves between the two cohorts. Results: Thrombin time (TT), red blood cell (RBC), and granulocyte-lymphocyte ratio (GLR) were found to be associated with the diagnosis of SSNHL. A prediction nomogram was constructed using these three predictors. The AUC in the development and validation cohorts was 0.871 (95% CI: 0.789-0.953) and 0.759 (95% CI: 0.635-0.883), respectively. Delong's test showed no significant difference in the ROC curves between the two groups (D = 1.482, p = 0.141). Conclusion: In this study, a multifactor prediction model for SSNHL was established and validated. The factors included in the model could be easily and quickly accessed, which could help physicians make early diagnosis and clinical treatment decisions.

Assays to Monitor Bivalirudin.

Bivalirudin (Angiomax, Angiox) is a parenteral direct thrombin inhibitor (DTI) that is used for patients with heparin-induced thrombocytopenia (HIT), where heparin cannot be used due to the risk of thrombosis. Bivalirudin is also licensed for use in cardiology procedures (e.g., percutaneous transluminal coronary angioplasty; PTCA). Bivalirudin is a synthetic analogue of hirudin found in the saliva of the medicinal leech and has a relatively short half-life of ~25 min. Several assays can be used to monitor bivalirudin; these include the activated partial thromboplastin time (APTT), activated clotting time (ACT), ecarin clotting time (ECT), an ecarin-based chromogenic assay, thrombin time (TT), the dilute TT, and the prothrombinase-induced clotting time (PiCT). Drug concentrations can also be measured using liquid chromatography tandem mass spectrometry (LC/MS) and clotting or chromogenic-based assays with specific drug calibrators and controls.

Novel Monitoring and Dose Adjustment of Argatroban, a Direct Thrombin Inhibitor, to Maintain Therapeutic Anticoagulation in a Patient With Antiphospholipid Antibody Syndrome, Heparin-Induced Thrombocytopenia, and COVID-19 Pneumonia.

In patients who require systemic anticoagulation, a reliable monitoring method is required to ensure anticoagulation is maintained within the correct therapeutic window and patients are treated appropriately. When titrating direct thrombin inhibitors (DTIs), dilute thrombin time (dTT) measurements have been demonstrated to be more reliable and accurate than activated partial thromboplastin time (aPTT) measurements and thus often the preferred DTI assessment. However, a clinical need arises when both dTT measurements are not readily available and aPTT measurements are unreliable. CASE SUMMARY: A 57-year-old woman with a history of antiphospholipid antibody syndrome, heparin-induced thrombocytopenia, and multiple prior deep venous thromboses and pulmonary emboli was admitted with COVID-19 pneumonia and intubated due to hypoxic respiratory failure. Argatroban was initiated in place of her home medication warfarin. However, the patient had a prolonged aPTT value at baseline and overnight dTT assay measurements were limited at our institution. A multidisciplinary team of hematology and pharmacy clinicians created a modified patient-specific aPTT target range and argatroban dosing was titrated accordingly. Subsequent aPTT values in the modified target range corresponded to therapeutic dTT values, indicating therapeutic anticoagulation was successfully achieved and maintained. Patient blood samples were additionally evaluated retrospectively using an investigational novel point-of-care test that detected and quantified the argatroban anticoagulant effect. CONCLUSIONS: Therapeutic anticoagulation with a DTI in a patient with unreliable aPTT measurements can be achieved with use of a modified patient-specific aPTT target range. Early validation of an investigational rapid testing alternative for DTI monitoring is promising.

The magnitude and associated factors of coagulation abnormalities among liver disease patients at the University of Gondar Comprehensive Specialized Hospital Northwest, Ethiopia, 2022.

BACKGROUND: Liver disease is any condition that affects the liver cells and their function. It is directly linked to coagulation disorders since most coagulation factors are produced by the liver. Therefore, this study aimed to assess the magnitude and associated factors of coagulation abnormalities among liver disease patients. METHODS: A cross-sectional study was conducted from August to October 2022 among 307 consecutively selected study participants at the University of Gondar Comprehensive Specialized Hospital. Sociodemographic and clinical data were collected using a structured questionnaire and data extraction sheet, respectively. About 2.7 mL of venous blood were collected and analyzed by the Genrui CA51 coagulation analyzer. Data were entered into Epi-data and exported to STATA version 14 software for analysis. The finding was described in terms of frequencies and proportions. Factors associated with coagulation abnormalities were analyzed by bivariable and multivariable logistic regression. RESULT: In this study, a total of 307 study participants were included. Of them the magnitude of prolonged Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) were 68.08% and 63.51%, respectively. The presence of anaemia (AOR = 2.97, 95% CI: 1.26, 7.03), a lack of a vegetable feeding habit (AOR = 2.98, 95% CI: 1.42, 6.24), no history of blood transfusion (AOR = 3.72, 95% CI: 1.78, 7.78), and lack of physical exercise (AOR = 3.23, 95% CI: 1.60, 6.52) were significantly associated with prolonged PT. While the presence of anaemia (AOR = 3.02; 95% CI: 1.34, 6.76), lack of vegetable feeding habit (AOR = 2.64; 95% CI: 1.34, 5.20), no history of blood transfusion (AOR = 2.28; 95% CI: 1.09, 4.79), and a lack of physical exercise (AOR = 2.35; 95% CI: 1.16, 4.78) were significantly associated with abnormal APTT. CONCLUSION: Patients with liver disease had substantial coagulation problems. Being anemic, having a transfusion history, lack of physical activity, and lack of vegetables showed significant association with coagulopathy. Therefore, early detection and management of coagulation abnormalities in liver disease patients are critical.

Monitoring Direct Thrombin Inhibitors With Calibrated Diluted Thrombin Time vs Activated Partial Thromboplastin Time in Pediatric Patients.

OBJECTIVES: Activated partial thromboplastin time (aPTT) is the primary test used to monitor intravenous (IV) direct thrombin inhibitors (DTIs) but has many limitations. The plasma diluted thrombin time (dTT) has shown better correlation with DTI levels than aPTT. This study compared dose-response curves for dTT and aPTT in pediatric patients receiving argatroban and bivalirudin. METHODS: A retrospective review of pediatric patients treated with argatroban (n = 45) or bivalirudin (n = 14) monitored with dTT and aPTT. RESULTS: The dTT assay was calibrated to report DTI concentrations in µg/mL for argatroban and bivalirudin with good analytic sensitivity and specificity. The dTT was fivefold more likely to show a stable dose-response slope than the aPTT (P < .0002; odds ratio, 4.9). For patients in whom both dTT and aPTT showed a significant correlation between dose and assay results, dTT had a higher average correlation factor compared with aPTT (P = .007). Argatroban dose-response slopes showed more inter- and intrapatient variation than bivalirudin (dose-response slope coefficient of variation, 132% vs 52%). CONCLUSIONS: The dTT assay was more likely to show a stable dose response and have a stronger correlation with DTI dose than aPTT. Argatroban shows more variation in dose response than bivalirudin.

Effect of silymarin on blood coagulation profile and osmotic fragility in carbon tetrachloride induced hepatotoxicity in male Wistar rats.

Reports about the impact of Carbon tetrachloride (CCl4) hepatotoxicity on coagulation profile have been inconsistent. Multiple investigators have however demonstrated the effectiveness of silymarin in the resolution of anomalies induced by CCl4, although the effect of silymarin on the impact of CCl4 hepatotoxicity, especially coagulation profile and osmotic fragility have not been investigated. The liver, the primary site for the secretion of coagulation proteins, can become impaired in CCl4 hepatotoxicity, and silymarin reportedly increases hepatic protein synthesis as part of its hepatoprotective mechanism. This study assessed the effect of silymarin on blood coagulation profile and erythrocyte osmotic fragility in CCl4 induced hepatotoxicity in rats. Twenty male Wistar rats were allocated into four groups (n = 5) at random, namely: Control, CCl4 given CCl4 (1 ml/kg) administered intraperitoneally twice a week, Silymarin (S) given silymarin (100 mg/kg/day) orally, and S+CCl4 given silymarin (100 mg/kg/day) orally and (1 ml/kg) CCl4 one hour after, intraperitoneally twice a week for a duration of four weeks. Results showed protraction of activated partial thromboplastin time and thrombin time, increased erythrocyte osmotic fragility, liver damage, dyslipidemia, oxidative stress and lipid peroxidation in rats given CCl4. Silymarin attenuated most of these effects as observed from comparison between CCl4 and S+CCl4 rats. The findings of this study suggests that pretreatment with silymarin attenuated disruption in coagulation profile and erythrocyte osmotic fragility in CCl4 induced hepatotoxicity in Wistar rats.