Activated Partial Thromboplastin Time Values Research Articles

Heparin monitoring in ImpellaTM-supported cardiogenic shock patients: the benefit of parallel dual testing

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek Flanders. Background Coagulopathic complications often jeopardize the outcome of critically ill patients in cardiogenic shock (CS) during percutaneous mechanical circulatory support (pMCS). Therefore, meticulous management of heparin therapy is mandatory to ensure appropriate anticoagulation management. In this context, the most convenient and most frequently used test is the activated partial thromboplastin time (APTT). However, the APTT-test can be prolonged or shortened independent of the patient's anticoagulation status due to various confounding factors during critical illness (e.g., sepsis, liver failure, factor XI/XII consumption). Alternatively, the anti-Xa assay directly measures heparin activity. Therefore, to optimize heparin anticoagulation during critical illness, an anti-Xa-guided protocol for heparin titration combined with parallel APTT measurements to assess both bleeding and thrombotic risk has recently been proposed. (1) Purpose We aimed to investigate the correlation between parallel anti-Xa and APTT-measurements in an anti-Xa-guided heparin anticoagulated CS population during left-sided ImpellaTM support. Methods Between April-2017 and June-2022, all CS patients with isolated left-sided ImpellaTM-support (>24h) and heparin anticoagulation monitored by anti-Xa with APTT in parallel were assessed at two high-volume tertiary institutions. Anti-Xa was considered in range between 0.20-0.30IU/mL or 0.31-0.50IU/mL based on the patient’s profile (per center protocol, underlying atrial fibrillation or venous thromboembolism). In range APTT values were considered 40-55s and 55-80s respectively. Correlation between parallel anti-Xa and APTT values was assessed by Pearson correlation. A Pearson correlation coefficient of 0.7 or lower was considered to confer a weak correlation. Results Ninety-three ImpellaTM-patient runs (77 men, 83%) with a median age of 56 years (IQR 46-66) were analyzed. Median support duration was 6 days (IQR 4-12). In total, 2447 parallel anti-Xa/APTT samples were analyzed, showing an overall Pearson correlation coefficient of 0.50 (p<0.001) (Fig. 1A). For samples with in-range anti-Xa (N=1914), matching APPT was shortened in 460 (24%), in-range in 986 (52%) and prolonged in 468 (24%) samples (Fig. 1B). Conclusions We highlight a weak correlation between anti-Xa and APTT in an anti-Xa guided heparin anticoagulated CS population during left-sided ImpellaTM support. Heparin titration based on APTT alone would result in over- (24%) or undertitration (24%) in 48% of our cases, due to confounding factors influencing the APTT-assay in critically ill, exposing these patients to coagulopathy associated problems. Therefore, we strongly advocate a combined (anti-Xa/APTT) testing anticoagulation monitoring strategy to adequately manage the coagulation state of this critically ill population. Future trials will investigate whether this approach will effectively reduce the high coagulopathy associated morbidity and mortality on pMCS.

Anti-Xa/APTT discrepancy in heparinized ImpellaTM-supported cardiogenic shock patients can predict mortality

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek Flanders. Background Meticulous management of unfractionated heparin (UFH) is important to avoid complications in patients receiving percutaneous mechanical circulatory support (pMCS) for cardiogenic shock (CS). Whereas the anti-Xa assay directly measures UFH activity, the activated partial thromboplastin time (APTT) remains the most frequently used test. The APTT covers the intrinsic and common coagulation pathway and can be influenced by various confounding (laboratory) factors during critical illness, unrelated to the patient’s (anti)coagulation state. Purpose We investigated a CS population supported with isolated left-sided Impella™ and UFH-anticoagulation. UFH-levels were guided by anti-Xa with APTT in parallel. Here, we focus on those samples with anti-Xa in-range and discrepantly prolonged parallel APTT-measurements. We differentiated the APTT-prolongation according to reduced fibrinogen levels and/or prolonged INR (factor XI/XII consumption vs. concomitant conditions) and correlated this with mortality during Impella™-support. Methods Between April-2017 and June-2022, all CS patients with isolated left-sided ImpellaTM-support (>24h) and UFH anticoagulation monitored by anti-Xa with APTT in parallel were assessed at two high-volume tertiary institutions. In-range anti-Xa samples (between 0.20-0.30IU/mL or 0.31-0.50IU/mL based on the patient’s profile) were selected. In-range APTT values were considered between 40-55s and 55-80s respectively. Samples with prolonged APTT as compared to the in-range anti-Xa were allocated in 4 groups based on fibrinogen (<1.5g/dL or ≥ 1.5g/dL) and INR (<1.5 or ≥1.5) on the same day as the sample with prolonged APTT. 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). Among the 1914 in-range anti-Xa samples, parallel APTT was prolonged in 468 samples (24%) across 59 patients. 80 Samples from 2 patients 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; 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 (10% vs. 32%; p=0.043). Conclusions Fibrinogen-levels and INR uncover the underlying etiology in discrepant APTT-prolongation as compared to an in-range anti-Xa value in a CS population during left-sided ImpellaTM support. In patients with prolonged APTT and reduced fibrinogen (<1.5 g/dL) and/or prolonged INR (≥1.5), the risk of mortality is significantly elevated. This is due to concomitant conditions with high mortality (liver failure, sepsis, DIC,…). We advocate to monitor such patients carefully and treat them in a patient/disease tailored approach.

Exploring coagulation parameters as predictive biomarkers of Plasmodium infection: A comprehensive analysis of coagulation parameters.

Malaria affects the intravascular environment, leading to abnormal coagulation activation, prolonged prothrombin time, and activated partial thromboplastin time. Despite the high prevalence of malaria in the study area, there has been little published research on the effects of Plasmodium infection on coagulation parameters. The aim was to assess the effect of malaria on basic coagulation parameters among patients attending Dembia Primary Hospital and Makisegnit Health Center. A cross-sectional study was carried out from January to March 2020. The study involved 120 participants. Blood specimens were collected, which were analyzed using a Huma Clot Due Plus analyzer. The collected data were entered into EpiData and exported to SPSS version 21 for analysis. Non-parametric statistical methods were employed to analyze the data. The results were considered statistically significant if the p-value was less than 0.05. Individuals infected with Plasmodium exhibit coagulation disorders with elevated levels of PT (Prothrombin Time), APTT (Activated Partial Thromboplastin Time), and INR (International Normalization Ratio) in comparison to healthy controls. The median PT, APTT, and INR values for infected cases were measured at 20.5 [8.6], 39.5 [17.9], and 1.8 [0.9], respectively, while healthy controls had measurements of 15.1 [2.5], 28.8 [8.3], and 1.3 [0.2] (p ≤ 0.001). The severity of coagulation disorders increased with an increase in parasitemia levels. The type of Plasmodium species present had a significant impact on PT and INR values (p ≤ 0.001), whereas APTT did not show any significant impact across the Plasmodium species (p > 0.05). The results of this study found that malaria has a substantial impact on various blood clotting parameters, including PT, APTT, and INR. Parasitemia severity is significantly associated with extended PT and INR, implying that the higher the parasitemia, the longer it takes for blood to clot. Furthermore, the study discovered that the PT and INR levels differed based on the type of Plasmodium species responsible for the infection.

PERBEDAAN HASIL PENUNDAAN SAMPEL FFP (Fresh Frozen Plasma) 36 JAM DAN 48 JAM TERHADAP PEMERIKSAAN APTT (Activated Partial Thromboplastin Time)

Blood transfusion is the transfer of blood from one person (donor) into the vein of another person (recipient). Blood components include cellular and non-cellular components. The results of the study were conducted to determine the differences in the results of 36-hour and 48-hour FFP (Fresh Frozen Plasma) samples stored at room temperature against APTT (Activated Partial Thromboplastin Time) examination. The sample was FPP (Fress Frozen Plasma) from Dr. Sotomo Hospital Surabaya, which obtained significant results, namely there was a difference in the plasma APTT value with a delay of 36 hours, plasma with a delay of 48 hours with plasma with a delay of 30 minutes or without delay, while the plasma APTT value with a 30-minute delay as a control for the normal APTT value. The Mann-Whitney statistical test showed that there was a significant difference (p<0.05) between 30-minute plasma with 36-hour delay plasma p=0.00 and 48-hour delay plasma with p=0.000. The conclusion in the hematological examination, especially the APTT examination, if there is a delay in the examination, it should be examined no more than two hours. Keywords: Fress Frozen Plasma, Activated Partial Thromboplastin Time

Enhancing Titanium Disk Performance through In-Pack Cold Atmospheric Plasma Treatment.

While titanium dental implants have already been clinically established, ongoing research is continuously being conducted to advance the fields of osseointegration and bacterial resistance, seeking further improvements in these areas. In this study, we introduce an innovative method for treating titanium surfaces within tightly sealed packaging. Specifically, titanium discs, enclosed in surgical-grade packaging, underwent treatment using cold atmospheric plasma (CAP). The surfaces were thoroughly characterized in terms of wettability, crystalline structure, and chemical composition. Hemocompatibility analyses were conducted using blood diluted in sodium citrate (1:9) exposed to titanium discs for 30 min inside a CO2 incubator at 37 °C. Subsequently, various blood parameters were evaluated, including prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet adhesion. Microbiological analyses were also performed using Pseudomonas aeruginosa (ATCC 27853) for 4 h at 37 °C. The treatment with CAP Jet resulted in a reduction in contact angle without causing any changes in the crystalline structure. No statistically significant differences were observed in the blood parameters. The plasma-treated samples exhibited lower PT and APTT values compared to those of the control group. The surfaces treated with CAP Jet showed increased platelet activation, platelet density, and thrombus formation when compared with the untreated samples. Moreover, the treated surfaces demonstrated lower bacterial colony formation compared with other surfaces.

Effects of sodium ferulate for injection on anticoagulation of warfarin in rats in vivo

BackgroundHerb-drug interactions may result in increased adverse drug reactions or diminished drug efficacy, especially for drugs with a narrow therapeutic index such as warfarin. The current study investigates the effects of sodium ferulate for injection (SFI) on anticoagulation of warfarin from aspects of pharmacodynamics and pharmacokinetics in rats and predicts the risk of the combination use.MethodsRats were randomly divided into different groups and administered single- or multiple-dose of warfarin (0.2 mg/kg) with or without SFI of low dose (8.93 mg/kg) or high dose (26.79 mg/kg). Prothrombin time (PT) and activated partial thromboplastin time (APTT) were detected by a blood coagulation analyzer, and international normalized ratio (INR) values were calculated. UPLC-MS/MS was conducted to measure concentrations of warfarin enantiomers and pharmacokinetic parameters were calculated by DAS2.0 software.ResultsThe single-dose study demonstrated that SFI alone had no effect on coagulation indices, but significantly decreased PT and INR values of warfarin when the two drugs were co-administered (P < 0.05 or P < 0.01), while APTT values unaffected (P > 0.05). Cmax and AUC of R/S-warfarin decreased but CL increased significantly in presence of SFI (P < 0.01). The multiple-dose study showed that PT, APTT, INR, and concentrations of R/S-warfarin decreased significantly when SFI was co-administered with warfarin (P < 0.01). Warfarin plasma protein binding rate was not significantly changed by SFI (P > 0.05).ConclusionsThe present study implied that SFI could accelerate warfarin metabolism and weaken its anticoagulation intensity in rats.

Effect of High Altitude Environment on Pharmacokinetic and Pharmacodynamic of Warfarin in Rats.

High altitude environment affects the pharmacokinetic (PK) parameters of drugs and the PK parameters are an important theoretical basis for guiding the rational clinical use of drugs. Warfarin is an oral anticoagulant of the coumarin class commonly used in clinical practice, but it has a narrow therapeutic window and wide individual variation. However, the effect of high altitude environment on PK and pharmacodynamic (PD) of warfarin is unclear. The objective of this study is to investigate the effect of a high altitude environment on PK and PD of warfarin in rats. Rats were randomly divided into plain group and high altitude group and blood samples were collected through the orbital venous plexus after administration of 2 mg/kg warfarin. Warfarin concentrations in plasma samples were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and PK parameters were calculated by the non-compartment model using WinNonlin 8.1 software. Meanwhile, the expression of PXR, P-gp and CYP2C9 in liver tissues was also determined by western blotting. The effect of high altitude environment on PD of warfarin was explored by measuring activated partial thromboplastin time (APTT) and prothrombin time (PT) values and then calculated international normalized ratio (INR) values based on PT. Significant changes in PK behaviors and PD of warfarin in high altitude-rats were observed. Compared with the plain-rats, the peak concentration (Cmax) and the area under the plasma concentration-time curve (AUC) increased significantly by 50.9% and 107.46%, respectively. At the same time, high altitude environment significantly inhibited the expression of PXR, P-gp and CYP2C9 in liver tissues. The results of the PD study showed that high altitude environments significantly prolonged PT, APTT and INR values. High altitude environment inhibited the metabolism and increased the absorption of warfarin in rats and increased the effect of anticoagulant effect, suggesting that the optimal dose of warfarin for patients at high altitude should be reassessed.

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

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. 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. 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). 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.

Variation in coagulation factor activity levels cause discrepancies between activated partial thromboplastin time and anti-Xa activity for heparin monitoring: a retrospective observational study

BackgroundUnfractionated heparin (UFH) is primarily monitored using activated partial thromboplastin time (APTT). However, the recent introduction of anti-activated factor X (anti-Xa) activity testing has provided a direct evaluation of Xa inhibition by anticoagulants. This study aimed to investigate discrepancies between APTT and anti-Xa activity during UFH monitoring in critically ill patients and explore their underlying causes.MethodsThis study analyzed 271 pairs of laboratory test results from blood samples of 99 critically ill patients receiving continuous intravenous UFH. Theoretical APTT values were calculated using fitted curve equations from spiked sample measurements with anti-Xa activity. Samples were categorized into three groups based on the measurement of the APTT/theoretical APTT ratio: the lower group (< 80%), the concordant group (80–120%), and the upper group (> 120%).ResultsThe overall concordance rate between APTT and anti-Xa activity was 45%, with a 55% discrepancy rate. The lower group frequently showed apparent heparin overdoses, while coagulation factor activities in the lower and upper groups were higher and lower, respectively, than those in the concordant group. Particularly, the lower group exhibited higher factor VIII activity levels than the upper and concordant groups.ConclusionsDiscrepancies between APTT and anti-Xa activity were frequently observed, influenced by changes in coagulation factors activity levels. The lower and upper groups were classified as pseudo-heparin-resistant and coagulopathy types, respectively. Accurate monitoring of heparin in critically ill patients is crucial, especially in cases of pseudo-heparin resistance, where APTT values may wrongly indicate inadequate heparin dosing despite sufficient anti-Xa activity. Understanding these discrepancies is important for managing heparin therapy in critically ill patients.Trial registration: Not applicable.

Risk factors for coagulation inhibitor development in children with severe hemophilia A

Aim of the study: to examine the role of potential risk factors in inhibitor development in previously untreated patients (PUPs) (or minimally treated patients) with severe hemophilia A. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus). The study included 89 boys who underwent regular follow-up for severe hemophilia A at the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus) from 1998 to 2022. The median age (10th–90th percentile) at diagnosis of hemophilia was 8.0 (1.0–21.0) months, the baseline factor VIII activity was 0.7% (0.4–0.95%). Age at first exposure to factor VIII concentrate was 11.0 (1.0–31.0) months. Out of 89 patients, 23 children had severe hemophilia A with inhibitors. The cumulative incidence of inhibitors in the whole group of PUPs was 31.0 ± 5.6%. The cumulative incidence of hemophilia A with inhibitors was higher in the patients with null mutations (37.0 ± 6.9%) than in the patients with non-null mutations (6.5 ± 6.0%) (the log-rank test, p = 0.041). The use of plasma-derived FVIII concentrate (approved for use in neonates and for prophylaxis) from one manufacturer was associated (c2 = 8.53; p = 0.004) with a lower incidence of factor VIII inhibitors (up to 21.3 ± 8.5%) compared with the incidence in the group of patients treated with FVIII concentrates from different manufacturers (45.2 ± 7.8%). Age (&gt; 1 year old or &lt; 1 year old) at first exposure to FVIII had no effect on the formation of inhibitors (the log-rank test, p = 0.746). Such factors as age at diagnosis of hemophilia (odds ratio (OR) 0.99; 95% confidence interval (CI) 0.93–1.024; p = 0.991) and baseline factor VIII activity (OR 0.99; 95% CI 0.8–1.06; p = 0.09) were not associated with inhibitor development. The first measurements of activated partial thromboplastin time (APTT) ratio (patient APTT value over the APTT reference value) (OR 1.89; 95% CI 0.72–5.09; p = 0.21) and FVIII recovery in vivo (OR 0.74; 95% CI 0.27–2.01; p = 0.55) were not associated with inhibitor development either. We have confirmed that one of the main risk factors for FVIII inhibitor development is F8 gene mutations. The incidence of inhibitors among the patients who received plasma-derived FVIII concentrates (recommended for use in PUPs in the neonatal period) from one manufacturer was lower than among those who received FVIII from different manufacturers.

Anlotinib and fruquintinib co-administrated with warfarin increases the risk of bleeding: Studied from pharmacokinetic and pharmacodynamic perspectives

BackgroundRecent studies have reported a higher risk of bleeding among patients that are co-administrated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) and anticoagulant, which raises our concern about the possible TKIs-warfarin pharmacokinetic and pharmacodynamic interaction that could be life-threatening to tumor patients who take warfarin for preventing deep vein thrombosis (DVT). MethodsInfluences of anlotinib and fruquintinib on the pharmacokinetic and dynamic behavior of warfarin were estimated. Influence on the activity of cytochrome P450 (CYP450) enzymes was detected in vitro through rat liver microsomes. Quantitative analysis of blood concentration in rats was finished by a validated UHPLC-MS/MS method. Furthermore, pharmacodynamic interactions were studied in rats by monitoring prothrombin time (PT) and activated partial thromboplastin time (APTT), while Inferior vena cava (IVC) stenosis-induced DVT model was built to further investigate the antithrombotic effect after co-administration. ResultsAnlotinib inhibited the activity of cyp2c6, cyp3a1/2 and cyp1a2 in rat liver microsomes in a dose-dependent manner, meanwhile enhanced the AUC0∼t and AUC0∼∞ of R-warfarin. However, fruquintinib showed no effects on pharmacokinetics of warfarin. Anlotinib and fruquintinib co-administrated with warfarin was found to exert more significant increase on PT and APTT values than that taking warfarin alone. In IVC stenosis-induced DVT model rats, the co-administration groups significantly reduced the length of thrombus compared with the single warfarin group. ConclusionsAnlotinib and fruquintinib enhanced the anticoagulated and antithrombotic effect of warfarin. The anlotinib-induced interaction may due to the inhibition of the metabolism of warfarin. The mechanism of the pharmacodynamic interaction between fruquintinib and warfarin should be further investigated.

Selected Biomarkers of Coagulation Disturbance in Newly Diagnosed Breast Cancer Patients

Coagulation disturbance can be quite detrimental to health, whether as a primary disorder or secondary to other medical conditions. The risk of thrombosis has been previously reported in breast cancer. This case- control study purposively enrolled 50 newly diagnosed female breast cancer patients. Quick's One-stage method was used for prothrombin time (PT) and activated partial thromboplastin time (APTT) tests, while fibrin plate lysis method was used for euglobulin lysis time (ELT) assessment. Data analysis was carried out on statistical package for social sciences (SPSS) version 20.0. A p-value ≤ 0.05 was considered significant. Mean values of PT, APTT and ELT of newly diagnosed breast cancer patients were compared to values from control subjects. The ELT was significantly prolonged in the breast cancer patients compared to that of controls (p = 0.001). These measured parameters were further compared within the breast cancer group on the basis of hours of immobility per day into three categories (&lt;3 hours, 3-6 hours and &gt;6 hours). Subjects with more than 6 hours of immobility Subjects with more than 6 hours of immobility per day had significantly prolonged ELT compared to those with lesser hours of immobility. This study concludes that fibrinolytic challenge exists in breast cancer prior to commencement of treatment particularly among patients with increasing immobility.

Evaluating some haemostatic profiles and platelet aggregation in gestational diabetes mellitus subjects

Background: Hypercoagulability has been linked to an increase in risk factors, making diabetes a major cause of morbidity and mortality in low-income countries like Nigeria. This research examined some haemostatic parameters in women with gestational diabetes mellitus (GDM).Methodology: A total of 100 subjects consisting of 40 GDM, 30 non-gestational diabetes pregnant women (NGPW) attending the ante-natal clinic of the hospital and 30 women with neither diabetes nor pregnancy (NDNP) were enrolled as controls in this study. Ten milliliters of blood was collected and dispensed into an appropriate anticoagulant bottle. Prothrombin time (PT), Activated partial Thromboplastin Time (APTT), complete blood count (CBC) and fasting blood sugar (FBS) was estimated using standard techniques.Results: There was a significantly higher in the mean values of FBS, PT, APTT and WBC among GDM and NGPW when compared with NPNP (p&lt;0.05), while PCV was lower. FBS has positive correlation with PT and APTT while it shows negative correlation with platelet. APTT had a little edge over PT with higher area under the ROC curve of 0.997 than PT among GDM.Conclusion: In this study, women with GDM have considerably longer PT and APTT than NGPW and NDNP. Therefore, there may be possibility of haemorrhagic complications in gestational diabetes.

Correlation of coagulation states with prognosis of sudden deafness.

Prognosis of sudden deafness remains a challenge in clinics because of inhomogeneity of the disease. Here we report our retrospective study aimed to explore the value of coagulative markers including activated partial thromboplastin time (APTT), prothrombin time (PT), plasma fibrinogen (FIB), and plasma D-dimer in the prognosis of patients. The study included a total of 160 patients, of whom 92 had valid responses, 68 had invalid responses, and 68 had ineffective responses. APTT, PT, and the levels of FIB and D-dimer in serum were compared between the two groups, and their prognostic values were determined in terms of area under the curve (AUC) in receiver operating curve (ROC) analysis, sensitivity, and specificity. The correlations of APTT, PT, and FIB to degree of hearing loss were also assessed. Serum APTT and PT, FIB, and D-dimer levels were lower in patients with sudden deafness who responded poorly to treatments. ROC analysis showed that APTT, PT, FIB, and D-dimer had high AUC, sensitivity, and specificity for nonresponders, particularly when used in combination (AUC = 0.91, sensitivity = 86.76%, and specificity = 82.61%). Patients with a higher degree of hearing loss (>91 dB) also demonstrated significantly lower values of APTT and PT and higher levels of serum FIB and D-dimer than those with a lower degree of hearing loss. Our study demonstrated that APTT, PT, and serum levels of FIB and D-dimer could serve as strong predictors of sudden deafness, potentiating the use of these tests to identify patients who respond poorly to treatments.NEW & NOTEWORTHY Our retrospective study indicated that lower serum APTT and PT levels and higher fibrinogen (FIB) and D-dimer levels are characteristics associated with poor treatment responses among patients with sudden deafness. A combination of these levels had a high accuracy in identifying the nonresponders. APTT, PT, and serum levels of FIB and D-dimer could serve as strong predictors of sudden deafness, potentiating the use of these tests to identify patients who respond poorly to treatments.

EFFECT OF DELAYED PREPARATION OF PLATELET POOR PLASMA ON COAGULATION STUDIES AT ROOM TEMPERATURE

Objective: To determine the effect of delay in the preparation of platelet poor plasma (PPP) on prothrombin time (PT) and activated partial thromboplastin time (APTT) at room temperature (RT). Material and Methods: It was a cross sectional study, conducted at Chughtai Institute of Pathology from January 2022 to June 2022. Total 100 healthy individuals, both males and females, participated in the study. Centrifugation of four citrated blood samples was done at 4000 g for 10 minutes at RT; first sample at 0 hour (h), second sample at 4 h, third sample at 8 h and fourth sample at 24 h. PT and APTT were run on each PPP using Sysmex CS-1600.The values at different times were noted and compared through careful statistical analysis of the observed parameters. Results: There was statistically significant difference for PT at 24h storage time when compared with baseline value at 0h (P value 0.0017) but no clinically relevant change up to 24h (&lt;10% percent change). For APTT at RT, statistically significant difference was noted at storage time of 8h (P value 0.0001) and 24h (P value &lt;0.0001) but a clinically relevant change was noted only at 24h (&gt;10% percent change). Conclusion: Blood samples for PT and APTT without centrifugation can be stored for up to 24 hours for PT at RT and for up to 4 hours for APTT at RT. PT and APTT values will not be affected if centrifugation of citrated sample is done within 1 hour of collection and transported at RT in small aliquots. Key Words: Prothrombin time, Activated partial thromboplastin time, Platelet poor plasma, Pre analytical, Centrifugation

Prognostic models for survival and consciousness in patients with primary brainstem hemorrhage.

Primary brainstem hemorrhage (PBSH) is one of the most catastrophic spontaneous intracerebral hemorrhage diseases, with a mortality rate of 70-80%. We explored the predictive factors for survival and consciousness in patients with PBSH (ClinicalTrials.gov ID: NCT04910490). We retrospectively reviewed 211 patients with PBSH admitted to our institution between January 2014 and October 2020. Clinical outcomes included the 30-day survival rate and the 90-day consciousness rate as evaluated by the National Institutes of Health Stroke Scale score. Multiple logistic regression analysis was performed. The overall 30-day survival rate of 211 patients with PBSH was 70%. Several predictive factors including hematoma volume, hematoma location, activated partial thromboplastin time (APTT) upon admission, and therapeutic strategy were significantly related to 30-day survival. Compared with conservative treatment, stereotactic aspiration in our prediction model is strongly associated with improved 30-day survival (odds ratio, 6.67; 95% confidence interval, 3.13-14.29; P < 0.001). The prognosis prediction model of 90-day consciousness including factors such as mydriasis, APTT value, hematoma location, and hematoma volume upon admission has a good predictive effect (AUC, 0.835; 95% confidence interval, 0.78-0.89; P < 0.001). In patients with PBSH, conscious state upon admission, coagulation function, hematoma volume, hematoma location, and therapeutic strategy were significantly associated with prognosis. Stereotactic aspiration could significantly reduce the 30-day mortality rate.

Significance of Haematological Variates in Determining Risk of Cardiovascular Complications Post SARS-CoV-2 Infection: A Prospective Cohort Study

Introduction: Coronavirus Disease-2019 (COVID-19) is an ongoing global pandemic. Changes in haematological variables in patients with COVID-19 are emerging as important features of the disease. These changes in haematological variables may provide significant clues in the prognosis post Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. Aim: To determine the significance of various haematological variables in cardiac outcomes post SARS-CoV-2 infection. Materials and Methods: This was a prospective cohort study conducted at Prince Faisal bin Khalid Cardiac Centre, Abha, Kingdom of Saudi between March 2021 and October 2021. A total of 59 patients who were infected with SARS-CoV-2 with or without cardiac complaints were involved. Demographic, clinical, and laboratory data were recorded. Leukocyte counts, Neutrophil Counts, Lymphocyte counts, Neutrophil to Lymphocyte Ratio (NLR), platelet counts, Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), and D-Dimer were assessed and compared between subjects who developed Cardiovascular Complications (CVC+ group) and the subjects who did not develop CVC post SARS-CoV-2 infection (CVCgroup). Statistical analyses were performed using R scripting language and R Studio (version 1.2.5033, Orange Blossom). For continuous variables, t-test (for normally distributed) and MannWitney U test (for non normally distributed) were employed. For categorical data, Chi-square test (c2 ) was used. A p-value &lt;0.05 was considered significant. Results: Among all the haematological variables assessed, Neutrophil counts (p&lt;0.0001), NLR (p&lt;0.0001), and PT (p&lt;0.0001) were highly significant for developing CVC post SARS-CoV-2 infection. Additionally, Leukocyte counts (p=0.028), Lymphocyte counts (p=0.0002), APTT (p=0.036), and D-dimer (p=0.022) also showed statistical significance for developing CVC post-SARSCoV-2 infection. Conclusion: Haematological testing is easily available, inexpensive, and provides almost instant results. Therefore, assessing haematological variables like Leukocyte counts, Neutrophil counts, Lymphocyte counts, NLR, PT, APTT, and D-Dimer values post SARS-CoV-2 infection can help doctors identify patients at higher risk of developing CVC and guide their interventions accordingly. This can potentially help in reducing the occurrence of cardiovascular complications.

Performance evaluation of the Sysmex CN-6000-automated coagulation analyzers for routine coagulation tests.

The Sysmex CN-6000 is a novel automated multiparameter coagulometer that performs clotting, chromogenic and immunological assays, and platelet aggregation tests in a single system. Here we evaluated its performance of routine coagulation assays. The precision, linearity, carryover and establishment of reference ranges of the CN-6000, as well as correlations between it and the currently used Diagnostica Stago STA-R Max were determined according to Clinical and Laboratory Standards Institute guidelines. The evaluated parameters included prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FBG), antithrombin (AT), d-dimers (DDi), and fibrin and FBG degradation products (FDP). The intra-run and inter-run precisions of the six tests were determined using normal and pathological control materials; all coefficients of variation were acceptable and within the allowable ranges. The CN-6000 showed excellent linearity for FBG, AT, DDi, and FDP (R = 0.999-1.00). Passing-Bablok regression (R2 > 0.95) demonstrated good agreement between the analyzers. In the carryover study, APTT, PT, FBG, AT, DDi, and FDP values were all acceptable. The establishing reference intervals revealed that each manufacturer's range was acceptable. Significant differences were observed in the APTT reference range because of using different detection systems and reagents. The CN-6000 analyzer showed reliable performance and good correlation with the currently used STA-R Max automated hemostatic analyzer. As CN-6000 uses an optical clot-detection method, its reference ranges for PT and APTT are lower than those of the STA-R Max; thus, the difference should be considered before its use.

Evaluation the effect of oral contraceptive pills on coagulation profile in Sudanese women in Shendi -Sudan

The most side effects associated with hormonal contraceptive use is predisposition to higher risk of thromboembolic phenomena. Progestins have antiplasmin and antithrombin activity. Its increase platelet count and aggregability, thus predisposing to hypercoagulability. A descriptive cross-sectional study was conducted in Shendi - Sudan during the period from April to August 2018 to evaluate the effect of contraceptive pills on coagulation tests (Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and platelets count). A total of eighty women were selected as volunteers according to inclusion criteria and considered as case, and other forty women not taken these pills, were selected and considered as control group. Seven ml of fresh venous blood were collected after filling the questionnaire, about (4.5) ml of blood was drawn in trisodium citrate solution as anticoagulant and (2.5) ml was drawn in EDTA container to perform the platelet count by using hematology analyzer (Mindray bc-3000), citrated blood was centrifuged at 3000 round/min for 15 minutes for preparation of platelets poor plasma (PPP). The PPP were tested for the PT and APTT by using the coagulometer instrument (Clot). The results revealed that the mean of APPT, PT and platelet count in test group was (33.4 seconds, (14.0) seconds and 519.000c/cmm) respectively, while in control group was (30.7 seconds, (13.4) seconds and 271.000c/cmm) respectively. Statistical analysis showed that there was significant variation in APTT value in test group when compared with control group with P value of (&lt; 0.05), also there was no significant variations was noticed in PT and with P value of (&gt; 0.05), and significant variation was observed in count of platelet with P. value (&lt;0.005) which indicate the hypercoagulability, significant changes were noticed between age groups, type of oral contraceptives and duration of uses. This study concludes that OCP users had more tendency of hypercoagulability and therefore these women are at higher risk of thromboembolic effects.

Population pharmacokinetic analysis for dabigatran etexilate in Chinese patients with non-valvular atrial fibrillation.

We aimed to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model from healthy Chinese subjects and real-world non-valvular atrial fibrillation (NVAF) patients. We also investigated meaningful intrinsic and extrinsic factors and related biomarkers for bleeding events. We characterized the integrated PK/PD models based on rich PK/PD data [dabigatran concentration, activated partial thromboplastin time (APTT), prothrombin time (PT), and anti-factor IIa (anti-FIIa) activity] from 118 healthy volunteers and sparse PD data [APTT, PT, and anti-FIIa] from 167 patients with NVAF after verifying the model extrapolation performance. We also documented the correlations between PD biomarkers and clinically relevant bleeding events over one year. Next, we used the final integrated PK/PD model (a two-compartment, linear model with first-order absorption) to evaluate the influence of dosage and individual covariates on PD parameters. The age, high-density liptein cholesterol (HDL-C), and creatinine clearance (CrCL) improved the PK model fit. The linear direct-effects PD model described the correlation between APTT, PT, and anti-FIIa and plasma concentration. CrCL improved the PD model fit. Anti-FIIa was more sensitive to the increase in dabigatran exposure than APTT and PT in the PD model. Therefore, fixed dabigatran doses could be prescribed for patients with NVAF without adjusting for age and HDL-C. We observed an elevated bleeding tendency with higher peak and trough values of APTT, PT, and anti-FIIa. Randomized studies should be performed to evaluate the efficacy and safety of low-dose dabigatran in Chinese patients with NVAF.