Comparison of different algorithms for lupus anticoagulant detection: a single-center experience.

Background: The laboratory tests for lupus anticoagulant (LA) detection comprise complex and multistep coagulation testing procedures. There is no established gold standard assay or direct comparison of algorithms as recommended by different guidelines. Objectives: This study aimed to evaluate and compare the LA detection performance of different laboratory algorithms suggested by the existing guidelines. Methods: The routine LA test data of 1801 plasma samples, including 188 LA-positive and 1613 LA-negative samples, were re-evaluated by applying the algorithms recommended by existing guidelines and were interpreted using various methods. Diagnostic performance indices for each LA detection algorithm were compared with those of the other algorithms. The efficacies of the different interpretation methods were analyzed to determine a suitable interpretation methodology for each assay. Results: The diagnostic performance for detecting LA varied by the algorithm and method of interpretation used. All laboratory algorithms displayed exceptional diagnostic performance with all diagnostic parameters of >90.0%. Nearly perfect agreement was observed in all algorithms when compared to the Clinical and Laboratory Standards Institute 2014 guideline interpreted by normalized screen-to-confirm ratio (NSCR) and mixing test-specific cutoff (MTC), as a reference assay (Cohen's kappa coefficient, >0.90 [range, 0.94-1.00]). A combination of the index of circulating anticoagulant and NSCR was optimal for interpreting the activated partial thromboplastin time-based test, whereas a combination of the MTC and NSCR was suitable for the diluted Russell's viper venom time-based test. Conclusion: All laboratory algorithms showed equivalent diagnostic performance. Establishing the best method of interpretation for each assay is recommended to improve LA detection performance.

Clinical Laboratory Investigations and Antivenom Administration after Malayan Pit Viper (Calloselasma rhodostoma) Envenoming: A Retrospective Study from Southernmost Thailand.

The Malayan pit viper (MPV: Calloselasma rhodostoma) is a medically important venomous snake causing numerous envenomations in Thailand. Administration of specific snake antivenom is the only effective treatment for MPV-envenomed patients. However, inappropriate administration or misuse of snake antivenom is problematic in some remote areas of tropical countries where the snakebite envenoming rate is notable. Currently, the indications for administration of MPV antivenom are focused mainly on hematological factors. These include 1) venous clotting time > 20 min, 2) unclotted 20-minute whole-blood clotting time, 3) international normalized ratio > 1.2, 4) platelet count < 50 × 103/µL, 5) systemic bleeding, and 6) impending compartment syndrome. We aimed to determine the association between laboratory data and antivenom administration in MPV-envenomed patients. A retrospective study of data from 2016 to 2021 in Narathiwat Province, the southernmost province in Thailand, was conducted. A total of 838 MPV-bitten patients were included in this study. Local effects and systemic effects were observed in 58.8% and 27.7% of patients, respectively. Coagulopathies, which range from abnormal blood clotting to systemic bleeding, represented the majority of systemic effects. Acute kidney injury developed in 2.5% of patients. In this study, 57.3% of patients were considered appropriate antivenom recipients. Interestingly, the present study revealed that local bleeding and mild to moderate thrombocytopenia became the independent factors for inappropriate use of MPV antivenom. Reeducation and supervision regarding the rational use of snake antivenom are needed to minimize the misuse of antivenom.

Clinical Profile and Pharmacological Management of Snakebites in Community Care Units: A Retrospective Study Using Two Military Hospital Databases in South Thailand.

Snakebite envenoming is an occupational hazard in remote rural areas of South Thailand, where the highest incidence of snakebites is reported. In this work, a hospital-based retrospective study of snakebite patients from 2012 to 2022 at Fort Wachirawut Hospital and Fort Thepsatrisrisunthon Hospital, located in Nakhon Si Thammarat province, Thailand was conducted. Data from the laboratory investigation, physical examinations of snakebite victims, and clinical management, including pharmacological and non-pharmacological treatments, were evaluated. A total of 54 snakebite victims were included. The median age of patients was 49 years (IQR, 28 to 63). Males accounted for 74.1% of all participants. The majority of patients were bitten by Malayan pit vipers (68.5%), followed by unidentified snakes (18.5%), other non-venomous snakes (7.4%), and cobras (5.6%). The most common clinical manifestations were swelling (90.2%) and local pain (73.2%). One patient experienced respiratory failure following an envenoming by an unidentified venomous snake. No deaths were observed in this study. In total, 24 patients received antivenom administration (44.4%), most of whom were from Fort Wachirawut Hospital. Patients who were administered antivenom showed a median admission duration of three days (IQR, 3 to 4), compared with two days (IQR, one to three) for those who did not receive antivenom treatment (p < 0.001). In addition, paracetamol and prophylactic antibiotics, namely, amoxicillin-clavulanate and dicloxacillin, were the most common pharmacotherapies following snakebites. Overall, it was observed that these two community hospitals undertook appropriate clinical management under the standard guidelines for snakebite patients. This might be due to the effective emergency management, facilities, and clinical consultations. Finally, the management process in the medical teams also plays a crucial role in minimizing the severity of snakebite outcomes.

Validation of high concentrated thrombin time assay for unfractionated heparin monitoring.

BACKGROUND: The high concentrated thrombin time (hcTT), a thrombin time modified by increasing the thrombin concentration, is a possible alternative assay to activated partial thromboplastin time (aPTT) in unfractionated heparin (UFH) monitoring. This study aimed to determine the optimal thrombin concentration used in the hcTT assay for UFH monitoring. METHODS: A total of 30 blood samples obtained from healthy volunteers were included in this study. Thrombin concentrations of 10.0, 15.0, 20.0, and 25.0 IU/ml were used in the hcTT assay. The consistency between the hcTT and anti-FXa assays was evaluated. To validate the hcTT assay, linearity, repeatability, reproducibility, and diagnostic performance of the assay were assessed. RESULTS: The hcTT assay using thrombin concentration of 15.0 IU/ml showed a strong correlation to the anti-FXa assay with R2 of 0.72 and the Spearman's correlation coefficient (rs ) of 0.97 (95% CI, 0.96-0.98). Within-run and day-to-day run variabilities of the assay were satisfactory (all coefficients of variation <10%). We found an excellent correlation between the results which were measured using different reagents with intra- or inter-laboratory instruments. Notably, as compared to the aPTT assay, the hcTT assay showed a significantly better performance in identifying the samples which contain UFH at the supratherapeutic level, with an AUC of 0.97 vs. 0.91, p = 0.049. CONCLUSION: The hcTT assay can be used as an alternative assay for UFH therapy monitoring. A further study using clinical samples is recommended to confirm the appropriateness of the hcTT assay for clinical application.

Prevalence of and factors associated with stroke in hypertensive patients in Thailand from 2014 to 2018: A nationwide cross-sectional study.

Stroke is a significant cause of death and disability. In Thailand, it imposes a major health burden, and the prevalence of stroke is increasing, particularly in patients with hypertension (HT), diabetes mellitus (DM), and dyslipidemia (DLP). We aimed to determine the trends in the prevalence of stroke and the associated factors among Thai patients with HT. Nationwide cross-sectional studies were conducted annually in 2014, 2015 and 2018 based on data obtained from the Thailand DM/HT study. Nationally, representative patients with HT in Thailand were sampled with stratified one-stage cluster sampling. A total of 104,028 participants were included in this study. The prevalence of stroke remained constant, with prevalence rates of 4.0%, 3.8%, and 3.9% in 2014, 2015 and 2018, respectively (p for trend = 0.221). Our findings suggested that the management of stroke patients who are covered by the universal coverage scheme should be evaluated. Effective interventions, including promoting smoking cessation, attenuating cholesterol levels, and controlling blood pressure should be provided to hypertensive patients to prevent ischemic stroke. Young adults with HT should be more concerned about the possibility of stroke. The use of prophylactic low-dose aspirin should be carefully monitored to prevent hemorrhagic stroke.

Evaluation of point-of-care testing device for anemia detection: A cross-sectional method comparison study from Thailand.

BACKGROUND: A comparison study is crucial before launching a new medical device; therefore, we compared the Mission Ultra Hb Testing System with the Sysmex XN-3000 automated hematology analyzer in Thai adult males and non-pregnant adult females. METHODS: Parallel studies were conducted using discarded venous K2-ethylenediaminetetraacetic acid samples from participants requiring hematological investigations. According to the World Health Organization criteria, the participants were categorized as overall, anemia, and non-anemia for analysis. RESULTS: Three hundred participants were included in this study. In all participants, near-perfect correlation and agreement were observed between the two methods for Hb measurement (r = 0.963, p < 0.001) with an interclass correlation coefficient (ICC) of 0.981 (95% confidence interval [CI]: 0.976-0.985) and Hct measurement (r = 0.941, p < 0.001) with an ICC of 0.965 (95% CI: 0.956-0.972). The sensitivity and specificity of the device in detecting anemia were 86.2% (95% CI: 79.7-91.2) and 98.6% (95% CI: 95.2-99.8), respectively. The area under the curve was 0.976 (95% CI: 0.963-0.989). The device showed average biases of 0.76 g/dl (95% limits of agreement [LOA]: -1.03 to 2.54) for Hb measurement and -2.73% (95% LOA: -9.28 to 3.82) for Hct measurement in all participants. CONCLUSION: Agreement between the Mission Ultra Hb Testing System and Sysmex XN-3000 was observed. The device was excellent for detecting anemia. However, the essential evidence showing biases of the Hb and Hct measurements obtained from the device was revealed. Laboratory interpretation should be carefully performed, particularly at the near cut-off values.

Interrogation of novel CDK2/9 inhibitor fadraciclib (CYC065) as a potential therapeutic approach for AML.

Over the last 50 years, there has been a steady improvement in the treatment outcome of acute myeloid leukemia (AML). However, median survival in the elderly is still poor due to intolerance to intensive chemotherapy and higher numbers of patients with adverse cytogenetics. Fadraciclib (CYC065), a novel cyclin-dependent kinase (CDK) 2/9 inhibitor, has preclinical efficacy in AML. In AML cell lines, myeloid cell leukemia 1 (MCL-1) was downregulated following treatment with fadraciclib, resulting in a rapid induction of apoptosis. In addition, RNA polymerase II (RNAPII)-driven transcription was suppressed, rendering a global gene suppression. Rapid induction of apoptosis was observed in primary AML cells after treatment with fadraciclib for 6-8 h. Twenty-four hours continuous treatment further increased efficacy of fadraciclib. Although preliminary results showed that AML cell lines harboring KMT2A rearrangement (KMT2A-r) are more sensitive to fadraciclib, we found that the drug can induce apoptosis and decrease MCL-1 expression in primary AML cells, regardless of KMT2A status. Importantly, the diversity of genetic mutations observed in primary AML patient samples was associated with variable response to fadraciclib, confirming the need for patient stratification to enable a more effective and personalized treatment approach. Synergistic activity was demonstrated when fadraciclib was combined with the BCL-2 inhibitor venetoclax, or the conventional chemotherapy agents, cytarabine, or azacitidine, with the combination of fadraciclib and azacitidine having the most favorable therapeutic window. In summary, these results highlight the potential of fadraciclib as a novel therapeutic approach for AML.