Hispidulin-rich fraction of Clerodendrum fragrans Wild. (Sesewanua) dissolving microneedle as antithrombosis candidate: A proof of concept study.

Existing conventional antithrombosis drugs have caused many side effects, opening up opportunities for the development of new thrombotic drugs. There is potential to use the hispidulin-rich fraction of sesewanua (HRFS) as a new antithrombotic. The oral route limitation of hispidulin, as a low water solubility and non-polar compound, can be addressed. This study explores the potential of HRFS in the form of dissolving microneedles (DMN). The formula was created using polymers such as polyvinyl alcohol (PVA), polyvinyl pyrrolidone K-30 (PVP), and non-ionic surfactant. Ex vivo permeation studies found that 184.95 µg/cm2 of hispidulin was released 60 h after the best formulation. After 14 days of applying HRFS-DMN, the anticoagulant and antioxidant activity in male albino rats showed higher Activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) values and lower Inter Cellular Adhesion Molecule-1 (ICAM-1) values. No statistically significant differences were found between the effects of two and four HRFS-DMN and the injection of heparin at a dosage of 200 IU per kilogram. However, notable distinctions were observed when comparing HRFS-DMN to negative controls, oral and quercetin as positive controls at anti-ICAM activity. The findings confirmed the feasibility of HRFS-DMN for thrombosis and its effectiveness in delivering Hispidulin (HIS) into the bloodstream. This DMN is non-irritating, safe, and painless, showing promising outcomes in enhancing the efficacy of thrombosis treatment via the transdermal route.

Blood Coagulation Activities and Influence on DNA Condition of Alginate-Calcium Composites Prepared by Freeze-Drying Technique.

The aim of this research was to synthesize and characterize alginate-calcium composites using a freeze-drying method, with a focus on their potential applications in biomedicine. This study specifically explored the biochemical properties of these composites, emphasizing their role in blood coagulation and their capacity to interact with DNA. Additionally, the research aimed to assess how the cross-linking process influences the structural and chemical characteristics of the composites. Detailed analyses, including microscopic examination, surface area assessment, and atomic absorption spectrometry, yielded significant results. The objective of this study was to examine the impact of calcium chloride concentration on the calcium content in alginate composites. Specifically, the study assessed how varying concentrations of the cross-linking solution (ranging from 0.5% to 2%) influence the calcium ion saturation within the composites. This investigation is essential for understanding the physicochemical properties of the materials, including calcium content, porosity, and specific surface area. The results are intended to identify the optimal cross-linking conditions that maximize calcium enrichment efficiency while preserving the material's structural integrity. The study found that higher calcium chloride concentrations in alginate cross-linking improve the formation of a porous structure, enhanced by two-stage freeze-drying. Increased calcium levels led to a larger surface area and pore volume, and significantly higher calcium content. Furthermore, assays of activated partial thromboplastin time (aPTT) showed a reduction in clotting time for alginate composites containing calcium ions, indicating their potential as hemostatic agents. The aPTT test showed shorter clotting times with higher calcium ion concentrations, without enhanced activation of the extrinsic clotting pathway. The developed alginate material with calcium effectively supports hemostasis and reduces the risk of infection. The study also explored the capacity of these composites to interact with and modify the structure of plasmid DNA, underscoring their potential for future biomedical applications.

DNA/RNA heteroduplex technology with cationic oligopeptide reduces class-related adverse effects of nucleic acid drugs.

Antisense oligonucleotides (ASOs) are a therapeutic modality for incurable diseases. However, systemic injection of gapmer-type ASOs causes class-related toxicities, including prolongation of activated partial thromboplastin time (aPTT) and thrombocytopenia. We previously reported that cholesterol-conjugated DNA/RNA heteroduplex oligonucleotides (Chol-HDOs) exhibit significantly enhanced gene-silencing effects compared to ASOs, even in the central nervous system, by crossing the blood-brain barrier. In the present study, we initially evaluated the effect of the HDO structure on class-related toxicities. The HDO structure ameliorated the class-related toxicities associated with ASOs, but they remained to some extent. As a further antidote, we have developed artificial cationic oligopeptides, L-2,4-diaminobutanoic acid oligomers (DabOs), which bind to the phosphates in the major groove of the A-type double-helical structure of HDOs. The DabO/Chol-HDO complex showed significantly improved aPTT prolongation and thrombocytopenia in mice while maintaining gene-silencing efficacy. Moreover, the conjugation with DabOs effectively prevented cerebral infarction, a condition frequently observed in mice intravenously injected with high-dose Chol-HDO. These approaches, combining HDO technology with DabOs, offer distinct advantages over conventional strategies in reducing toxicities. Consequently, the DabO/HDO complex represents a promising platform for overcoming the class-related toxicities associated with therapeutic ASOs.

Reduce energy consumption in your laboratory - switch ultra-low temperature freezers from - 80 °C to -70 °C. A pilot study on short term storage of plasma samples for coagulation testing.

It is common practice in laboratories to store biological samples in ultra-low temperature (ULT) freezers. There is growing interest in raising the temperature of ULT freezers in order to save energy and reduce expenses, as energy conservation becomes increasingly important and sustainable laboratory practices gain popularity. In our laboratory, plasma samples are stored for three months for diagnostic purposes. We therefore took the opportunity to investigate the effect of two different storage temperatures (-70 °C vs -80 °C), on activated partial thromboplastin time (APTT), factor VIII (FVIII), international normalized ratio (INR) and factor VII (FVII) measurements on paired plasma samples collected from 26 individuals after three months of storage. Automated coagulation analysers CS-5100 and ACL TOP were used to perform the tests. We found no consistent difference between the two storage temperatures for any of the four coagulation parameters (all p-values > 0.05). We conclude that the temperature of ULT freezers used to store plasma samples for APTT, FVIII, INR, and FVII measurements can be safely increased from -80 to -70 °C without affecting the stability of the samples.

Evaluation of anti-XA-guided versus APTT-guided management of intravenous unfractionated heparin in patients requiring a durable ventricular assist device.

OBJECTIVE: The objective of this study was to compare the effectiveness and safety of anti-Xa-guided management versus aPTT-guided management of intravenous (IV) unfractionated heparin (UFH) in patients with a durable ventricular assist device (VAD). MATERIALS AND METHODS: This was a retrospective study conducted at a single academic medical center. Patients were included if they had a durable VAD and were managed using aPTT-guided UFH management from May 2019 to May 2020 or were managed using anti-Xa-guided UFH management from May 2021 to December 2021. The primary outcome of the study was the median time to goal anticoagulation post-initiation of UFH. Secondary outcomes included the percentage of time within the therapeutic range and the incidence of thromboembolic and bleeding complications. RESULTS: The study included 23 patients, 12 of whom were managed using anti-Xa-guided UFH, and 11 were managed using aPTT-guided UFH. The treatment arm using anti-Xa-guided UFH demonstrated a faster time to therapeutic anticoagulation goal range with a median time of 21.3 h [IQR = 12.2-34.8] compared to 37.3 h [IQR = 41-74] in the aPTT-guided UFH treatment arm (P = 0.03). In addition, the anti-Xa-guided UFH arm had a higher percentage of time within the therapeutic range, 76 % [IQR = 64.25-96.25] compared to 53 % [IQR = 41-74] in the aPTT-guided UFH arm (P = 0.04). Both arms had no significant differences in major bleeding events (P = 0.59) or clinically relevant minor bleeding events (P = 0.60) among patients. There was no incidence of thromboembolic events in either treatment arm. CONCLUSION: Based on this single-center experience, anti-Xa-guided UFH management resulted in a faster time to therapeutic anticoagulation and a longer time within the desired therapeutic range. The results suggest that anti-Xa-guided monitoring may be superior to UFH-guided monitoring in patients with a durable VAD.

Difference in activated partial thromboplastin time values with two different reagents according to C-reactive protein values.

BACKGROUND: Activated partial thromboplastin time (APTT) is susceptible to reagent composition. This study aimed to investigate a large number of specimens and determine the cause of discrepancies. METHOD: This study included 18,994 subjects who underwent coagulation tests at our hospital from May 2020 to December 2020. Measuring reagents included HemosIL SynthASil APTT (APTT-SS, Instrumentation Laboratory) and Coagpia APTT-N (APTT-N, Sekisui Medical). RESULTS: A total of 451 patients demonstrated APTT-N of >39 seconds and an APTT-N/SS ratio of >1.3. A C-reactive protein (CRP) level of ≥1.4 mg/L demonstrated a significant positive correlation, with a higher APTT-N/SS indicating higher CRP levels. All 28 subjects receiving no anticoagulants and who had remaining specimens underwent a cross-mixing test (CMT). Of them, 17 were suspected for lupus anticoagulant (LA) by both the waveform shape and the index of circulating anticoagulant (ICA) value, 6 by the ICA value, and 5 were difficult to determine. CONCLUSION: This study revealed that the APTT-N prolongation correlated with CRP degree and the transient involvement of LA in CMT results due to CRP. This study indicated various reactivities depending on the assay reagents used. Further testing is warranted if LA is suspected, considering the patient's background.

Evaluation of an integrated activated partial thromboplastin time (Cephen LS/Cephen) for the detection of lupus anticoagulant.

INTRODUCTION: It is recommended to use two chronometric assays of different principles for the diagnosis of lupus anticoagulant (LA), consisting in diluted Russell Viper Venom Time (dRVVT) and activated Partial Thromboplastin Time (aPTT). Yet, there are only a few integrated aPTT assays; this study aims to evaluate one of them: Cephen LS/Cephen (Hyphen Biomed). METHOD: 249 samples of patients were included in this study. Normal reference ranges were determined with platelet-poor plasma (PPP) from healthy blood donors. Performances were then evaluated by comparing Cephen LS/Cephen test results to the results of the laboratory's reference assay for the diagnosis of LA and to clinical data, both on non-anticoagulated and anticoagulated patients' samples (Unfractioned heparin (UFH), Low Molecular Weight Heparin (LMWH), Vitamin K Antagonists (VKA) and apixaban). Interference of UFH, LMWH and VKA were also evaluated thanks to spiking experiment of increasing heparin concentrations or factor deficiency. RESULTS: Cephen LS/Cephen test had 48.6% sensitivity towards LA. Although UFH and VKA seemed to interfere with this assay and were likely to cause false negative, LMWH and apixaban did not. Finally, combination of Cephen LS/ Cephen with dRVVT had 89.0% sensitivity. CONCLUSION: Cephen LS/Cephen seems relevant for LA diagnosis, in combination with dRVVT, and might be used in patients undergoing LMWH or apixaban therapy.

Bioclinical features of haemophilia patients in Benin in 2023: Towards better care.

OBJECTIVE: To analyse the demographic, clinical and laboratory data of Beninese patients with haemophilia. METHOD: A prospective survey was conducted in three different hospitals of Benin from April 2021 to March 2022, to analyse clinical and biological features of patients with haemophilia previously diagnosed or identified based on personal/family history. RESULTS: A total of 101 patients were studied, 97 with haemophilia A and 4 with haemophilia B, including 26 new cases identified after family investigation. Their median age was 11 years, and the most frequent initial manifestations were cutaneous-mucosal haemorrhages (29.70%) and post-circumcision haemorrhages (25.74%). Previous joint bleedings were present in 77% of them, with an arthropathy in 65 cases, which particularly affected the knees (75%), elbows (41%) and ankles (29%). Factor VIII (FVIII) levels combined with activated partial thromboplastin time (APTT) values did not always enable, as would be expected, the distinction between severe and moderate haemophilia, since they were >1 IU/dl in 31 of 74 patients with APTT > 80 s, and between 1 and 2 IU/dl in 26 other cases with previous joint haemorrhages, including 18 with chronic arthropathy. Therefore, for these patients, severe haemophilia could not be excluded, and this uncertainty probably reflects technical difficulties affecting the pre-analytical and analytical stages of the APTT and FVIII/IX assays. CONCLUSION: Our study proved that haemophilia is a significant reality in Benin, but also remains under-diagnosed in some districts of the country. In addition, more reliable biological tests are needed in the future to better define the severity of the disease and improve treatment of patients.

Evaluating Factor VIII Concentrates Using Clot Waveform Analysis.

Background/Objectives: FVIII reagent activity varies across different assays, as well as activated partial thromboplastin time (APTT) reagents. The hemostatic ability of various FVIII reagents was examined via clot waveform analysis (CWA). Methods: APTT was measured using 12 APTT reagents, a small amount of tissue factor-induced FIX activation (sTF/FIXa) and a small amount of thrombin time (sTT) in order to examine 10 FVIII reagents and reference plasma (RP) using CWA. FVIII activity was measured using CWA-APTT, a chromogenic assay, or CWA-sTT. Results: Although the peak time (PT) and peak height (PH) of the CWA-APTT were markedly different in different FVIII reagents using several APTT reagents, the PTs of CWA-APTT were generally normal or shortened and the PHs of CWA-APTT were generally lower than those of RP. The FVIII activity varied, as evaluated using APTT, and was higher when using the CWA-sTT method than the APTT or chromogenic methods. CWA-sTT showed an elevated second peak of first DPH in all FVIII reagents, and both CWA-sTF/FIXa and CWA-sTT were enhanced using APTT reagents. Conclusions: Our evaluation of the hemostatic ability of FVIII reagents varied among APTT reagents. CWA-sTT can be used to further evaluate the hemostatic ability of an FVIII concentrate based on thrombin burst.

Standardization of Anti-Xa Assay and its Comparison with Activated Partial Thromboplastin Time for Monitoring Unfractionated Heparin Therapy.

Monitoring of anticoagulant activity of unfractionated heparin (UFH) is primarily done with activated partial thromboplastin time (aPTT), which is affected by many factors. Anti-Xa assays are considered to overcome these factors and may provide a better method for monitoring patients on UFH with a narrow therapeutic range. This study aimed to compare the effectiveness of aPTT and anti-Xa assays in UFH monitoring. A prospective non-randomized study was carried out in two stages: first, the anti-Xa assay was standardized using kit instructions; each sample was then analyzed by both tests. The outcomes of the two assays were compared and assessed for agreement of maintaining therapeutic anticoagulant levels. These levels for anti-Xa assay were between 0.3 and 0.7 IU/ml, while it was 1.5-2.5 times the control for aPTT assay. Below this range was regarded as subtherapeutic, and above this as supratherapeutic. A total of 90 samples were tested and analyzed using both assays. Most of them (> 70%) were noted to be in subtherapeutic levels with both tests. The overall concordance was 73.3%, and the estimated kappa value was 0.483 (0.396-0.57). The correlation between aPTT and anti-Xa assay was 0.74 (p < 0.001). With anti-Xa levels in the therapeutic range, aPTT levels were in subtherapeutic in 60% and supratherapeutic in 13.3% cases. Although both the testing strategies had a good agreement and correlation, discordance was observed in interpretative values with anti-Xa levels in therapeutic range and aPTT levels in non-therapeutic range. Its clinical implications need to be evaluated further in future studies.

Glycemia and Coagulation in Patients with Glioblastomas.

BACKGROUND: Glioblastomas are among the most malignant tumors which, despite aggressive treatment, currently have an abysmal prognosis. These lesions are known to cause local and systemic perturbations in the coagulation system, leading to neoangiogenesis and a high risk of venous thromboembolism. Indeed, there have been multiple proposals of the coagulation system being a possible target for future treatment of these patients. However, nonselective anticoagulant therapy has proven suboptimal and leads to a significant increase of intracranial hemorrhage. Thus, recognizing factors that lead to hypercoagulation is considered paramount. Hyperglycemia is a well-known prothrombotic factor, a fact that has received little attention in neuro-oncology. We previously hypothesized that patients with brain tumors could be highly susceptible to iatrogenic glycemia dysregulation. Here, we analyzed the connection between glycated hemoglobin (HbA1c) and the routine coagulation markers (D-dimers, prothrombin time and activated partial thromboplastin time [aPTT]) in patients with de novo intracranial glioblastomas. METHODS: Included in this study were 74 patients who were operated on in 2 hospitals: Clinical Hospital Dubrava, Zagreb, Croatia; University Hospital Center Split, Split, Croatia; and University Hospital de la Princesa, Madrid, Spain. RESULTS: We found a significant inverse correlation between HbA1c and aPTT (ρ = -0.379; P = 0.0009). We also found a significant inverse correlation between Ki67 immunoreactivity and aPTT (ρ = -0.211; P = 0.0082). No connection was found between HbA1c and D-dimers or prothrombin time. CONCLUSIONS: Our results suggest that patients with hyperglycemia, with a more proliferative glioblastoma, could in fact have their coagulation profile significantly disrupted, primarily through the intrinsic coagulation pathway. Such findings could have great clinical importance. Further research in this area could help to elucidate the vicious connection between glioblastomas and coagulation and to combat this deadly disease.

International Council for Standardization in Haematology (ICSH) recommendations for the performance and interpretation of activated partial thromboplastin time and prothrombin time mixing tests.

This guidance document has been prepared on behalf of the International Council for Standardization in Haematology (ICSH). The aim of the document is to provide guidance and recommendations for the performance and interpretation of activated partial thromboplastin time (APTT) and prothrombin time (PT) plasma mixing tests in clinical laboratories in all regions of the world. The following areas are included in this document: preanalytical, analytical, postanalytical, and quality assurance considerations as they relate to the proper performance and interpretation of plasma mixing tests. The recommendations are based on good laboratory practice, published data in peer-reviewed literature, and expert opinion.

Design of Apoptotic Cell-Inspired Particles as a Blood Coagulation Test.

The blood coagulation test is an indispensable test for monitoring the blood coagulation and fibrinolysis functions. Currently, activated partial thromboplastin time (APTT) is the most widely used approach to coagulation testing. However, APTT reagents need to be optimized due to the fact that they are unstable, highly variable, and cannot be easily controlled. In this study, we created apoptotic cell-inspired methacryloyloxyethyl phosphorylserine (MPS) particles for blood coagulation as an alternative to conventional APTT reagents. Particle size could be controlled by changing the concentration of the polymer. The blood coagulation ability of particles was stable at different environmental temperatures. Moreover, the procoagulant activity could be enhanced by increasing the concentration to 0.06 mg/mL and reducing the size of the particles to around 900 nm. Fibrin clotted by particles showed no significant difference from that formed by APTT regent Actin FSL. We propose that MPS particles are a potential alternative to Actin FS for the application of blood coagulation tests.

The Impact of Cytokines on Coagulation Profile in COVID-19 Patients: Controlled for Socio-Demographic, Clinical, and Laboratory Parameters.

Background: Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and coagulation parameters concerning socio-demographic, clinical, and laboratory characteristics. Methods: Our study included patients hospitalized during the second wave of COVID-19 in the Republic of Serbia. We collected socio-demographic, clinical, and blood-sample data for all patients. Cytokine levels were measured using flow cytometry. Results: We analyzed data from 113 COVID-19 patients with an average age of 58.15 years, of whom 79 (69.9%) were male. Longer duration of COVID-19 symptoms before hospitalization (B = 69.672; p = 0.002) and use of meropenem (B = 1237.220; p = 0.014) were predictive of higher D-dimer values. Among cytokines, higher IL-5 values significantly predicted higher INR values (B = 0.152; p = 0.040) and longer prothrombin times (B = 0.412; p = 0.043), and higher IL-6 (B = 0.137; p = 0.003) predicted longer prothrombin times. Lower IL-17F concentrations at admission (B = 0.024; p = 0.050) were predictive of higher INR values, and lower IFN-γ values (B = -0.306; p = 0.017) were predictive of higher aPTT values. Conclusions: Our findings indicate a significant correlation between pro-inflammatory cytokines and coagulation-related parameters. Factors such as the patient's level of education, gender, oxygen-therapy use, symptom duration before hospitalization, meropenem use, and serum concentrations of IL-5, IL-6, IL-17F, and IFN-γ were associated with worse coagulation-related parameters.

Clinical guidance for unfractionated heparin dosing and monitoring in critically ill patients.

INTRODUCTION: Unfractionated heparin is a widely used anticoagulant in critically ill patients. It has a well-established safety profile and remains an attractive option for clinicians due to its short half-life and reversibility. Heparin has a unique pharmacokinetic profile, which contributes to significant inter-patient and intra-patient variability in effect. The variability in anticoagulant effect combined with heparin's short half-life mean close monitoring is required for clinical efficacy and preventing adverse effects. To optimize heparin use in critically ill patients, effective monitoring assays and dose adjustment strategies are needed. AREAS COVERED: This paper explores the use of heparin as an anticoagulant and optimal approaches to monitoring in critically ill patients. EXPERT OPINION: Conventional monitoring assays for heparin dosing have significant limitations. Emerging data appear to favor using anti-Xa assay monitoring for heparin anticoagulation, which many centers have successfully adopted as the standard. The anti-Xa assay appears have important benefits relative to the aPTT for heparin monitoring in critically ill patients, and should be considered for broader use.

APTT critical value establishment in four different reagent/instrument systems based on single factor deficiencies.

INTRODUCTION: There are significant differences in the activated partial thromboplastin time (APTT) critical values reported in different studies, most of which does not make recommendations for any specific clear detection systems. The International Council for Standardization in Hematology (ICSH) recommends that APTT critical values be established based on the reagent type, coagulation factor sensitivity and heparin response. The objective of this study was to establish APTT critical values by using different reagents and based on single coagulation factor deficiencies. METHODS: The APTT values were determined in commercial endogenous coagulation factor-deficient plasma at concentrations of 1 IU/dL, 2 IU/dL, 5 IU/dL, 10 IU/dL, 20 IU/dL, and 30 IU/dL by using four assay systems. The retrospective collection of data from patients who lacked factor VIII (FVIII), FIX, or FXI alone was performed. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic accuracy of APTT for identifying patients with an endogenous coagulation factor activity < 5 IU/dL. RESULTS: The APTT values in the plasma samples with the same concentrations of endogenous coagulation factors were significantly different among the four assay systems (P < 0.001). The suggested critical values of APTT were 40.0 s for Sysmex CS5100 (Actin FSL), 58.0 s for Sysmex CS5100 (Actin), 51.8 s for STA-R Evolution (STA-PTTA), and 64.8 s for ACL TOP 700 (HemosIL SynthasIL). On the basis of the ROC curve, the optimal threshold values for APTT (STA-PTTA) were 55.8 s in patients with a simple deficiency of FVIII (sensitivity = 100%, specificity = 85.7%, area under the ROC curve (AUC) = 0.982), 54.3 s in patients with a simple deficiency of FIX (sensitivity = 100%, specificity = 92.9%, AUC = 0.986), and 71.7 s in patients with a simple deficiency of FXI (sensitivity = 100%, specificity = 94.1%, AUC = 0.992), which were closer (difference of 0.6-2.5 s) to the cutoff points for commercial plasma at equal factor levels. CONCLUSIONS: APTT critical values need to be established for different reagents based on the presence of a single coagulation factor deficiency.

Safety of Tonsillectomy and/or Adenoidectomy in Pediatric Patients with Prolonged Activated Partial Thromboplastin Time and Factor XII Deficiency.

Objective: To evaluate the safety and feasibility of tonsillectomy and/or adenoidectomy (T&A) in pediatric patients with prolonged activated partial thromboplastin time (APTT) and coagulation factor deficiency. Methods: A prospective study was admitted to the children undergoing T&A at our institution between October 2019 and January 2020, specifically focusing on preoperative coagulation function. Within this group, we identified 5 patients exhibiting prolonged APTT and coagulation factor deficiencies, constituting the experimental group, and 10 patients matched by gender and age with normal blood coagulation function were selected as the control group. Comparative analyses between the two groups were conducted, focusing on surgical duration, intraoperative bleeding volume, duration of hospital stay, and postoperative complications such as active bleeding across the groups. At the six-month postoperative mark, a reassessment of coagulation functions and factor assays was conducted within the experimental group. Results: No statistically significant differences were discovered in terms of surgical duration or bleeding volume when comparing the experimental subgroups with their respective control counterparts. Furthermore, there were no incidences of postoperative active bleeding observed in any of the groups. Notably, postoperative APTT values (32.7 ± 1.7s) exhibited a significant disparity compared to preoperative levels (43.7 ± 1.8s, p < 0.01). Coagulation factors demonstrated normalization, evidenced by a significant difference in postoperative Factor XII levels (40.2 ± 5.4%) compared to preoperative levels (63.1 ± 5.9%, p < 0.01). Conclusion: Prolonged APTT with FXII factor deficiency does not show a significant bleeding tendency and is not a contraindication for T&A surgery. Post T&A surgery, children with abnormal coagulation function and deficient clotting factors show significant improvement compared to pre-surgery. It is important to consider that chronic inflammation in adenoids and tonsils may contribute to the prolongation of APTT and the manifestation of Factor XII deficiency.

Activated partial thromboplastin time predicts mortality in patients with severe fever with thrombocytopenia syndrome: A multicenter study in north China.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high lethality. This study aimed to determine whether prolonged activated partial thromboplastin time (APTT) predicted SFTS mortality. Methods: SFTS patients were enrolled from 6 hospitals in the north China. Subjects were divided into training cohort and 5 externally validation cohorts. The least absolute shrinkage and selection operator Cox regression model was performed to screen potential prognostic factors. Risk factors were analyzed using multivariable regression models. Prognostic models were established by Cox regression and random survival forest (RSF) methods, and evaluated regarding discrimination, validity and clinical benefit. Time-dependent receiver operating characteristic (ROC) curve was used to evaluate the predictive effectiveness of variables. Results: 1332 SFTS cases were included, in which 211 patients died. Six potential prognostic factors were screened, and pulse, breath, APTT and aspartic transaminase (AST) were independently associated with mortality in both training cohort (Yantai, N = 791) and external validation cohort (N = 541). APTT was steadily correlated with the fatality (HR: 1.039-1.144; all P < 0.01) in each five sub-validation cohorts (Dandong, Dalian, Tai'an, Qingdao and Beijing). RSF model with variables of APTT, AST, pulse and breath had considerable prognostic effectiveness, which APTT showed the highest prognostic ability with the area under the curve of 0.848 and 0.787 for 7-day and 14-day survival, respectively. Survival differences were found between high and low levels of APTT for mortality using 50s as the optimal cut-off. Conclusions: SFTS patients have prolonged APTT, which is an independent risk factor for fatality. APTT≥50s was recommended as a biomarker to remind physicians to monitor and treat patients more aggressively to improve clinical prognosis.

[How to interpret and pursue a prolonged quick time or APTT]. / Orientation diagnostique devant une anomalie du TP ou du TCA.

The standard hemostasis workup [quick time (QT), and activated partial thrombin time (APTT)] is very commonly prescribed but its interpretation is often difficult for practitioners who are not specialized in hemostasis. Here, we review the principles of the diagnostic approach to these tests. Only a very basic knowledge of the coagulation cascade is necessary to identify which clotting factor tests to prescribe and to interpret the results. Deficiency in several clotting factors suggests liver dysfunction, disseminated intravascular coagulation (DIC) or vitamin K deficiency. If a single factor is deficient, we review the different causes of acquired deficiencies and briefly discuss the characteristics of the different congenital defects, which generally require specialized management. Lupus anticoagulant is a common and generally benign cause of prolonged APTT to be aware of, which is not related to a hemorrhagic risk. A good knowledge of the diagnostic approach to abnormal QT or APTT generally allows the resolution of the most common situations.

Elevated Activated Partial Thromboplastin Time as a Predictor of 28-Day Mortality in Sepsis-Associated Acute Kidney Injury: A Retrospective Cohort Analysis.

Purpose: To address the critical mortality rates among sepsis-associated acute kidney injury (SA-AKI) patients, early prognosis is vital. This study investigates the relationship between coagulation indices and the 28-day mortality rate in patients with SA-AKI. Patients and Methods: This study was a retrospective cohort analysis including patients with SA-AKI admitted to the First Hospital of Fujian Medical University as a training cohort (n = 119) and patients admitted to the Third People's Hospital of Fujian University of Traditional Chinese Medicine as a validation cohort (n = 51). We examined the relationship between coagulation indices and 28-day mortality in SA-AKI, the cumulative mortality at different activated partial thromboplastin time (APTT) levels, and the nonlinear relationship between APTT and 28-day mortality. Receiver operating characteristic curves were plotted, and the area under the curve was calculated to assess the predictive power of APTT. Finally, subgroup analyses were performed to assess the robustness of the association. Results: Overall, 119 participants with a mean±standard deviation age of 70.47±15.20 years were included in the training cohort: 54 died, 65 survived. According to univariate and multivariate COX regression analyses, APACHE II score, CRP level, Lac level, and APTT level were independent risk factors for 28-day adverse prognosis. After controlling for some variables, an elevated baseline APTT (≥ 37.7 s) was associated with an elevated risk of 28-day mortality (HR, 1.017; 95% CI, 1.001-1.032), and Kaplan-Meier analyses further confirmed the increased mortality in the group with a higher APTT. The same results were shown when the validation cohort was analyzed (HR, 1.024; 95% CI, 0.958-1.096). Subgroup analyses showed the stability of the association between APTT and poor prognosis in SA-AKI. Conclusion: In essence, APTT elevation is synonymous with increased 28-day mortality rates, indicating a poor prognosis in SA-AKI scenarios.