New method to differentiate between lupus anticoagulants, progressive coagulation inhibitors and coagulation factor deficiencies in the mixing tests.

INTRODUCTION: Mixing tests in activated partial thromboplastin time (APTT) are used for the differentiation between lupus anticoagulants (LA), coagulation inhibitors, and factor deficient samples with APTT prolongation. However, the indexes for the differentiation have not been established. The present study aimed to develop new mixing test indexes for the differentiation. METHODS: Twenty-six LA-positive, 8 progressive coagulation factor VIII inhibitor, and 35 coagulation deficient samples were employed. APTT were measured for normal plasma, patient plasma, and mixing plasma prepared at a ratio of 1:1 proportion in both without incubation and 2 h-incubation. New two parameters named as ALD50 and mixture plasma-patient plasma after Warming change rate Subtraction (WaS) calculated from the clotting times of normal, 1:1 mixing and patient samples with/without 2 h-incubation were established. In the samples with WaS result of <10.2%, ALD50 of ≥87.8%, and < 87.8% were defined as LA and coagulation factor deficiency, respectively, and WaS of ≥10.2% defined progressive coagulation factor inhibitors. RESULTS: Sensitivity and specificity to LA were 80.8% and 93.0% for ALD50, and sensitivity and specificity to progressive coagulation factor inhibitor were 100.0% and 100.0% for WaS, respectively. The agreement between sample classification and WaS-ALD50 was 88.4% (61/69). CONCLUSIONS: ALD50 and WaS showed acceptable sensitivity and specificity to LA and progressive coagulation factor inhibitor, respectively. These indexes would be useful for the differentiation between LA, factor deficiency, and progressive coagulation factor inhibitor in the mixing tests.

Comparison of results obtained using clot-fibrinolysis waveform analysis and global fibrinolysis capacity assay with rotational thromboelastography.

Global fibrinolysis assays detect the fibrinolysis time of clot dissolution using tissue-type plasminogen activator (tPA). Two such assays, clot-fibrinolysis waveform analysis (CFWA) and global fibrinolysis capacity (GFC) assay, were recently developed. These were compared with rotational thromboelastography (ROTEM). Healthy donor blood samples were divided into four groups based on tPA-spiked concentrations: 0, 100, 500, and 1000 ng/mL. CFWA and GFC fibrinolysis times, including 4.1 µg/mL and 100 ng/mL tPA in the assays, were determined, denoted as CFWA-Lys and GFC-Lys, respectively. Statistical differences were recognized between tPA concentrations of 0 and 500/1000 ng/mL for CFWA-Lys, and 0 and 100/500/1000 ng/mL for GFC-Lys. The correlation coefficients with lysis onset time (LOT) of extrinsic pathway evaluation and intrinsic pathway evaluation in ROTEM were statistically significant at 0.610 and 0.590 for CFWA-Lys, and 0.939 and 0.928 for GFC-Lys, respectively (p-values < 0.0001 for all correlations). Both assays showed significant correlations with ROTEM; however, the GFC assay proved to have better agreement with ROTEM compared with the CFWA assay. These assays have the potential to reflect a hyperfibrinolysis status with high tPA concentrations.

Age-related variation in coagulation factors in non-valvular atrial fibrillation patients receiving direct oral anticoagulants.

Age is a significant risk factor for ischemic stroke. However, the influence of aging on coagulation parameters in non-valvular atrial fibrillation (NVAF) patients treated with direct oral anticoagulants (DOACs) remains unclear. A total of 775 samples were collected from 224 NVAF patients receiving apixaban, edoxaban or rivaroxaban. The samples were categorized into three age groups: (i) ≤ 64 years, (ii) 65-74 years, and (iii) ≥ 75 years (apixaban: N = 48, 108, 119; edoxaban: N = 63, 68, 126; rivaroxaban: N = 115, 90, 38, respectively). Coagulation parameters including fibrinogen (Fbg), factor II, factor V, factor VII, factor X, and D-dimer, were compared between the three age groups for each drug. The slopes in the correlation between drug concentrations and modified diluted prothrombin time (mdPT) were also assessed. Fbg and factor V increased with age, while factor II and factor X decreased. Factor VII and D-dimer showed no significant differences across age categories. The slope in response to drug concentrations was similar between the age groups. In NVAF patients treated with apixaban, edoxaban and rivaroxaban, some coagulation parameters exhibited age-related variation. However, the response of mdPT to drug concentration was consistent across age categories.

Characterization and Usefulness of Clot-Fibrinolysis Waveform Analysis in Critical Care Patients with Enhanced or Suppressed Fibrinolysis.

INTRODUCTION: Recently, clot-fibrinolysis waveform analysis (CFWA), which is a coagulation and fibrinolysis global assay based on assessing the activated partial thromboplastin time with tissue-type plasminogen activator, was developed. This study aimed to investigate the characteristics of CFWA using plasma samples from patients in the critical care unit. MATERIALS AND METHODS: The fibrinolysis times using CFWA were measured in 298 plasma samples. These samples were divided into three groups based on the reference interval (RI) of fibrinolysis time using CFWA: shortened group, less than RI; within group, within RI; prolonged group, more than RI. The coagulation and fibrinolysis markers, including D-dimer, plasmin-α2 plasmin inhibitor complex (PIC), fibrin monomer complex (FMC), plasmin-α2 plasmin inhibitor (α2-PI), plasminogen (Plg), and fibrinogen (Fbg) were analyzed and compared among the three groups. RESULTS: The FMC level decreased in the order of shortened, within, and prolonged groups, and the decrease was statistically significant among all three group pairs. The opposite tendency was observed for Fbg and fibrinolysis-related markers of α2-PI and Plg, and significant differences were recognized in all pair comparisons except for between within and prolonged groups in Plg. The mean values of the fibrinolysis markers D-dimer and PIC in all three groups were higher than the cut-off values, and the PIC value differed significantly between the within and prolonged groups. CONCLUSION: The fibrinolysis reaction was detected in all three groups, but the status differed. CFWA has the potential to reflect the fibrinolysis status in one global assay.

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

BACKGROUND: Unfractionated 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. METHODS: This 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%). RESULTS: The 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. CONCLUSIONS: Discrepancies 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.

Evaluation of newly-developed modified diluted prothrombin time reagent in non-valvular atrial fibrillation patients with direct oral anticoagulants: A comparative study with conventional reagents.

INTRODUCTION: A single assay to assess the effect of the direct FXa inhibitor is needed clinically because prothrombin (PT) assay is not yet sensitive enough for accurate evaluation. We developed modified diluted prothrombin time (mdPT) assay showing a high reactivity to direct FXa inhibitors based on prothrombin time (PT) reagent. The purpose of this study was to evaluate the reactivity of mdPT to direct FXa inhibitors comparing to that of commercial PT reagents and diluted prothrombin time (dPT). METHODS: The correlation and slopes of mdPT against the drug concentrations by anti-Xa assay were compared to those of the four commercial reagents of PT or dPT in 275, 257, and 243 clinical samples collected from non-valvular atrial fibrillation (NVAF) patients who are prescribed apixaban, edoxaban or rivaroxaban for stroke prevention, respectively. RESULTS: The correlation coefficient (95% confidence interval) of mdPT against apixaban, edoxaban, and rivaroxaban was 0.818 (0.775-0.854), 0.914 (0.892-0.932), and 0.814 (0.766-0.852), respectively. The slope (95% confidence interval) of mdPT for apixaban, edoxaban, and rivaroxaban was 0.0068 (0.0063-0.0075), 0.0076 (0.0072-0.0080), and 0.0072 (0.0065-0.0078), respectively, which were higher than that of four commercial PT and dPT reagents, ranging within 0.0006-0.0023, 0.0017-0.0038, and 0.0016-0.0057 (all, p < 0.001), respectively. CONCLUSION: Compared with other PT and dPT reagents, mdPT reagent showed sharper slope to all direct FXa inhibitors, and higher correlation to apixaban and comparable correlation to edoxaban and rivaroxaban. This new reagent is expected to be a coagulation screening assay having a consistently high response to any types of direct FXa inhibitors.

Thrombin generation capacity is enhanced by low antithrombin activity and depends on the activity of the related coagulation factors.

BACKGROUND: Supplementation with antithrombin (AT) concentrates is now common in the treatment of congenital and acquired AT deficiency. However, there is no established consensus on the target and timing of supplementation. We aimed to elucidate the effects of AT deficiency on the balance between coagulation activation and inhibition using a thrombin generation assay as in vitro global assay. METHODS: Samples were prepared by admixing commercially acquired AT-deficient plasma with < 1% AT activity with pooled normal plasma. The AT activity in each sample was adjusted to 100, 90, 70, 50, 40, 30, 10, 5, and < 1%. A thrombin generation assay was performed in each sample. AT concentrate-spiked samples were also prepared by adjusting the AT activities in four types of the concentrates: one recombinant and three plasma-derived AT concentrates. The final targeted AT activities in the samples were adjusted to 100, 50, 30, and 5% by spiking each concentrate into the AT-deficient plasma. We also prepared samples with five levels of prothrombin time (PT) % in coagulation factors with the AT activity fixed at 30% by dilution by mixing AT-deficient plasma and normal plasma with Owren's veronal buffer to adjust the coagulation factor activities in several proportions. The theoretical target PT% values were 100, 66, 50, 40, and 30%. A thrombin generation assay was performed on all samples. RESULTS: The ability to generate thrombin depended on the AT activity, and the amount of thrombin generation was increased as AT was decreased. Additionally, the amount of thrombin generation was changed significantly when AT activity was ≤ 50%, indicating that AT suppressed thrombin generation. In particular, thrombin generation was remarkable when AT activity was < 30%, and it can be assumed that the prognosis is poor due to organ failure from thrombotic tendency. CONCLUSIONS: The results presented in this basic research were found to be consistent with the clinical findings to date. The mechanism by which 30-50% of AT activity is set as the clinical boundary was elucidated by the thrombin generation assay.

Applying index of circulating anticoagulant to mixing tests with lupus anticoagulant screen and confirm reagents can distinguish with high specificity between lupus anticoagulants and direct factor Xa inhibitors.

BACKGROUND: Lupus anticoagulants (LA) are detected by prolongation of clotting times for dilute Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT) screening tests. Direct oral anticoagulants (DOACs) can interfere with both screening and confirmatory tests. The present study aimed to investigate the influence of direct factor Xa inhibitors (DiXaIs) on screen, confirm and mixing tests and establish a method for differentiation from other sample types. MATERIALS AND METHODS: A total of 257 samples including nonanticoagulated LA positive, LA positive with DiXaIs, factor deficiency, FVIII inhibitors, warfarin and non-APS DiXaIs were tested. APTT reagents Cephen LS/Cephen and dRVVT reagents LA1/LA2 were used, respectively, to screen/confirm the study group. Index of circulating anticoagulant (ICA) was calculated from clotting times based on the following formula as ICA screening and ICA confirmation. ICA= (1:1 Mix sample - Normal pooled plasma) / Screen patient x 100. An ICA matrix was established which suggested the presence of a DiXaI when both ICA screening and confirmation were above the cut-off. When only ICA screening is elevated, LA is suspected. RESULTS: Sensitivity and specificity of the ICA matrix were 52.2% and 92.8% for DiXaIs and 38.1% and 96.7% for LA in APTT, and 61.2% and 92.9% for DiXaIs and 22.2% and 88.4% for LA in dRVVT, respectively. CONCLUSION: The ICA matrix achieved high specificity with a lower apparent sensitivity for DiXaI samples comparatively to other devices but due only to less interferences: the matrix could contribute to differentiating DiXaIs from LA in samples where anticoagulation status is unknown.

Updates on Anticoagulation and Laboratory Tools for Therapy Monitoring of Heparin, Vitamin K Antagonists and Direct Oral Anticoagulants.

Anticoagulant drugs have been used to prevent and treat thrombosis. However, they are associated with risk of hemorrhage. Therefore, prior to their clinical use, it is important to assess the risk of bleeding and thrombosis. In case of older anticoagulant drugs like heparin and warfarin, dose adjustment is required owing to narrow therapeutic ranges. The established monitoring methods for heparin and warfarin are activated partial thromboplastin time (APTT)/anti-Xa assay and prothrombin time - international normalized ratio (PT-INR), respectively. Since 2008, new generation anticoagulant drugs, called direct oral anticoagulants (DOACs), have been widely prescribed to prevent and treat several thromboembolic diseases. Although the use of DOACs without routine monitoring and frequent dose adjustment has been shown to be safe and effective, there may be clinical circumstances in specific patients when measurement of the anticoagulant effects of DOACs is required. Recently, anticoagulation therapy has received attention when treating patients with coronavirus disease 2019 (COVID-19). In this review, we discuss the mechanisms of anticoagulant drugs-heparin, warfarin, and DOACs and describe the methods used for the measurement of their effects. In addition, we discuss the latest findings on thrombosis mechanism in patients with COVID-19 with respect to biological chemistry.

Characterization of fibrin/fibrinogen degradation products reagents and their utility in critical care patients with enhanced fibrinolysis.

INTRODUCTION: Fibrin/fibrinogen degradation products (FDP) values reflect coagulation and fibrinolysis status, and FDP levels are helpful for diagnosis and classification of disseminated intravascular coagulation (DIC). FDP measurement has always played a key role in diagnosing DIC, a phenomenon that has recently gained renewed attention because of its occurrence in coronavirus disease 2019 (COVID-19) patients. Although the evaluation of FDP is crucial for the management of critical care, the variability among FDP reagents is unclear. In this study, we aimed to compare LIASAUTO P-FDP with three FDP reagents and investigate their characteristics. METHODS: In total, 172 plasmas samples were used in the correlation. The sample data were divided into three groups including negative, no and positive discrepancy based on the discrepancy percentages calculated from each correlation between LIASAUTO P-FDP and other three reagents. D-dimer, plasmin-α2 plasmin inhibitor complex (PIC), fibrin monomer complex (FMC), fibrinogen (Fbg) and Plasmin-α2 Plasmin Inhibitor (α2 PI) were measured and included in data analysis. RESULTS: The positive discrepancy groups showed higher D-dimer, PIC and FMC values than the negative discrepancy groups. The data indicated that LIASAUTO P-FDP had higher reactivity to D-dimer than other reagents and the values were elevated in the fibrinolysis-enhanced samples with various FDP fragments. CONCLUSION: LIASAUTO P-FDP displayed the reactivity towards various fibrin/fibrinogen degradation products, and it might be useful for DIC diagnosis because the fibrinolytic status differed in the DIC types and stages.

Expert consensus regarding standardization of sample preparation for clotting time assays.

Accurate clotting time assay results are vital, as the test is employed to indicate the amount of oral anticoagulant to be prescribed, while it is also used for screening the hemorrhagic and thrombotic diseases. The procedure chosen for preparation of a patient blood sample including centrifugation can contribute to significant differences in the results obtained. Thus, for the purpose of proposing a standardized method to appropriately prepare blood samples prior to assay, the Japanese Society of Laboratory Hematology organized the Working Group for Standardization of Sample Preparation for Clotting Time Assays (WG). Following reviews of previously announced guidelines and original experimental results, consensus was obtained by the WG, with the main findings as follows. (1) The recommended anticoagulant in the blood collection tube is sodium citrate solution at 0.105-0.109 M (3.13-3.2%). (2) Whole blood samples should be stored at room temperature (18-25 ˚C) within 1 h of collection from the patient. (3) For plasma preparation, centrifugation at 1500 × g should be performed for at least 15 min or at 2000 × g for at least 10 min at room temperature. (4) After the plasma sample is prepared, it should be stored at room temperature and assayed within 4 h.

Lupus anticoagulant assay cut-offs vary between reagents even when derived from a common set of normal donor plasmas.

BACKGROUND: Multicenter studies reveal that diagnostic efficacy of lupus anticoagulant (LA) assays is enhanced if cut-offs are locally generated. However, a potential confounder is the inevitable use of separate normal donor populations. OBJECTIVES: Generate cut-offs for multiple LA reagents with the same analyzer and normal donor plasmas. METHODS: Cut-offs for screen ratio, confirm ratio, percent correction of screen ratio by confirm ratio, and normalized screen/confirm ratio (NSCR) were derived from the same 50 normal donor plasmas for screen and confirm pairs for two dilute Russell's viper venom time reagents, LA1/LA2 and HEMOCLOT™ LA-S/LA-C, and two APTTs, Actin FSL/FS and Cephen LS/Cephen. The cut-offs were challenged with plasmas from 20 triple-positive APS patients and 25 plasmas from LA-negative, thrombotic patients. RESULTS: Cut-offs for screen ratio, confirm ratio, percent correction, and NSCR, respectively, were 1.12/1.08/8.3/1.09 for LA1/LA2; 1.17/1.10/13.6/1.13 for HEMOCLOT™ LA-S/LA-C; 1.12/1.13/9.7/1.10 for Actin FSL/FS; 1.09/1.13/11.0/1.11 for Cephen LS/Cephen. LA1 and LA-S screens were elevated in 19/20 and 16/20 triple-positive plasmas, respectively, while 20/20 were detected with both via integrated interpretation ie, percent correction or NSCR irrespective of screen elevation. Actin FSL and Cephen LS screens were elevated in 17/20 and 19/20 triple-positive plasmas, respectively, while one more LA was detected with Actin FSL via integrated interpretation, but not for Cephen LS. Integrated interpretation suggested 5/25 LA-negative plasmas contained weak LA (two with Actin FSL/FS, two with LA1/LA2, one with LA-S/LA-R). CONCLUSIONS: Employing the same normal donor plasmas and analytical platform does not compensate for between-reagent differences when generating LA assay cut-offs.

Ruling out lupus anticoagulants with mixing test-specific cutoff assessment and the index of circulating anticoagulant.

BACKGROUND: Lupus anticoagulant (LA) is classified in the antibody family that is recognized in antiphospholipid syndrome. Mixing tests are recommended for LA detection, and either a mixing test-specific cutoff (MTC) or index of circulating anticoagulant (ICA) is used for the interpretation. Although we previously showed MTC had higher sensitivity for LA than ICA, there are few studies investigating specificity. OBJECTIVES: To investigate specificity of multiple activated partial thromboplastin time (APTT) and diluted Russell's viper venom time (dRVVT) reagents for inhibitors using plasmas with non-LA causes of prolonged clotting times, interpreted with MTC and ICA. METHODS: Seventy-six factor-deficient samples (either artificially prepared, hereditary deficiency, or warfarin), and 12 inhibitors (either coagulation factor inhibitors, rivaroxaban, or apixaban) were used. Samples were tested with 4 APTTs, 1 dilute APTT (dAPTT), and 2 dRVVT reagents, and all elevated screen ratios were followed up with mixing tests. Frequencies of corrected and not-corrected results were calculated. RESULTS: The frequency of MTC and ICA corrected results, suggesting factor deficiency, were 5% to 43% and 79% to 100%, respectively, except for dAPTT, where MTC and ICA performed similarly. Frequencies of MTC and ICA not-corrected results, suggesting inhibition, were 29% to 100% and 25% to 67%, respectively. CONCLUSIONS: The data indicate that MTC has a tendency to generate not-corrected mixing tests in factor-deficient, warfarin, and other inhibitor samples, while ICA exhibited higher specificity. When we perform the mixing test and interpret the data, it is important to understand the characteristics of the indexes for maximizing the diagnostic potential of mixing test.

Paired APTTs of low and high lupus anticoagulant sensitivity permit distinction from other abnormalities and achieve good lupus anticoagulant detection rates in conjunction with dRVVT.

INTRODUCTION: A prolonged activated partial thromboplastin time (APTT) may be indicative of a specific or multiple factor deficiency, therapeutic anticoagulation, presence of a nonspecific factor inhibitor, or lupus anticoagulant (LA). Recently, pairing of the LA-sensitive APTT and standard APTT reagents, Cephen LS and Cephen, respectively, has been shown to be effective in LA detection. The present study aimed to evaluate the usefulness of this reagent pair for discriminating between causes of APTT elevation and the detection of LA in conjunction with dilute Russell's viper venom time (dRVVT). METHODS: Plasma samples from 50 normal and 105 non-anticoagulated LA-positive patients in routine dRVVT and/or dilute APTT (dAPTT) via the percent correction formula were employed. Cephen LS/Cephen and dRVVT reagents LA1/LA2 were used to screen/confirm, respectively. Thirty-four symptomatic LA-negative, 25 warfarinised non-antiphospholipid syndrome, 6 coagulation inhibitors, 17 samples with hereditary elevated APTT, and 24 FVIII/IX/XI/XII and 17 FII/V/X artificial single deficiency plasmas were used. RESULTS: Thirty-three samples out of 105 (31%) were LA-positive in Cephen LS/Cephen. The total percent positivity in Cephen LS/Cephen and LA1/LA2 pairs was 89.1% against samples with the routine dRVVT/dAPTT double positive. The percent corrections of Cephen LS/Cephen in the routine dAPTT/dRVVT positive group were significantly higher than those in all other groups. CONCLUSIONS: The percent correction of the APTT reagent pair showed higher values in LA-positive samples. The combination will be useful with respect to differentiating LA from other abnormal samples and is effective in LA detection when paired with dRVVT.

Lupus anticoagulant mixing tests for multiple reagents are more sensitive if interpreted with a mixing test-specific cut-off than index of circulating anticoagulant.

BACKGROUND: Lupus anticoagulant (LA) is classified in the antibody family that is recognized as antiphospholipid antibodies. Guidelines for LA detection recommend mixing test interpretation with either a mixing test specific cut-off (MTC) or index of circulating anticoagulant (ICA). We previously evidenced that MTC was superior to ICA in detecting the in vitro inhibition of LA with a single dilute APTT (activated partial thromboplastin time) and dRVVT (diluted Russell's viper venom time) pairing. OBJECTIVES: The objective in the present study was to compare the LA diagnostic effectiveness of MTC and ICA by multiple APTT and dRVVT reagents. METHODS: One hundred-five samples from non-anticoagulated patients positive for LA in the dilute APTT (dAPTT) and dRVVT reagent pairing employed for diagnostic examination were performed by undiluted and in a 1:1 mix with normal pooled plasma with four additional APTT reagents and another dRVVT reagent (dRVVT B). RESULTS: Frequencies of MTC and ICA positivity were determined from samples LA positive in undiluted plasma. MTC positivity in mixing test were 63%, 77%, 80%, 84%, 46%, 81%, and 72% in 4 APTT, dAPTT and 2 dRVVT, respectively. ICA positivity were 47%, 67%, 58%, 54%, 42%, 47%, and 29%, respectively. There were no samples of ICA-positive/MTC-negative with any reagent. CONCLUSIONS: The data indicate that MTC is superior to ICA for LA detection in mixing tests in multiple reagents and reagent types. Although mixing tests may make weak LA samples appear negative, the efficacy of LA detection can be improved by the method to interpret the results.

Basic Evaluation of the Newly Developed "Lias Auto P-FDP" Assay and the Influence of Plasmin-α2 Plasmin Inhibitor Complex Values on Discrepancy in the Comparison with "Lias Auto D-Dimer Neo" Assay.

BACKGROUND: Laboratory determination of fibrin/fibrinogen degradation products (FDP) levels, along with that of the D-dimer, is important for assessing the fibrinolytic situation. Recently, we developed a new FDP reagent "Lias Auto P-FDP", which can detect various FDP fragments. The purpose of this study was to evaluate the basic performance of the newly developed Lias Auto P-FDP and compare it with Lias Auto D-Dimer Neo assay. METHODS: The within-run precision of Lias Auto P-FDP and Lias Auto D-Dimer was determined 20 times in low and high value controls. The between-day precision was evaluated five times a day for five days. The linearity study was performed by diluting high value samples for 2 - 10-fold and 2 - 8-fold. The comparative study was performed using 172 patient samples with elevated FDP values. For the discrepancy analysis, the samples were divided into three groups by the discrepancy percentage between the FDP and D-dimer values. The groups were defined as follows: lower discrepancy group, less than -20%; no discrepancy group, -20% to 20%; upper discrepancy group, more than 20%. RESULTS: The coefficient of variation % (CV%) in within-run and between-day precision were within 3.8% for both FDP and the D-dimer. The correlation coefficients were more than 0.999 and the linearity was high. In the comparative study, the values of FDP were higher than that of the D-dimer in all samples. The median FDP and D-dimer values of lower discrepancy, no discrepancy, and upper discrepancy groups were 11.8, 20.3, and 51.4, and 8.0, 11.3, and 13.1, respectively. FDP showed an increasing tendency but D-Dimer showed constant values. Thus, the possible cause of discrepancy between FDP and D-dimer values were the elevated FDP values. In addition, the values of plasmin-α2 plasmin inhibitor complex (PIC) in the upper discrepancy group were higher than that of the lower and no discrepancy groups, indicating progression of fibrinolysis. CONCLUSIONS: In this study, we evaluated the newly developed Lias Auto P-FDP reagent and confirmed that the basic performance was acceptable. FDP was elevated in samples with high PIC values, which indicated progression of fibrinolysis. Determination of fibrinolysis conditions by FDP measurement is important.