1.Coagulation profile PT, FBG, FDP, D-D as disease predictors of RA and pSS inflammatory immunity.
Wenwen MIN ; Lei WAN ; Feng LI ; Yu ZHANG ; Ying WANG ; Siyu LIANG
Chinese Journal of Cellular and Molecular Immunology 2025;41(10):895-904
Objective To explore the expression of coagulation indexes in rheumatoid arthritis (RA) and dry syndrome (pSS) and their relationships with inflammation and immune function. Methods A total of 61 patients with RA who were hospitalized in the Department of Rheumatology of Anhui Provincial Hospital of Traditional Chinese Medicine from March 12 to September 9, 2024 were selected as the RA group. And 61 patients with pSS who were hospitalized in the Department of Rheumatology of the same hospital September 4, 2023, to August 17, 2024, were selected as the pSS group. 61 healthy individuals who underwent routine medical checkups at the Physical Examination Center of Anhui Provincial Hospital of Traditional Chinese Medicine during the same period were included as the control group. Baseline clinical indexes before treatment were collected from patients in each group, including prothrombin time(PT), international normalized ratio(INR), thrombia time(TT), fibrinogen(FBG), activated partial thromboplastin time(APTT), fibrin (ogen) degradation products(FDP) and D-Dimer(D-D). Results The expression levels of PT, FBG, TT, FDP, and D-D in the RA group, the pSS group, and the normal group were significantly different. The expression levels of PT, FBG, FDP, and D-D in the RA group were all higher than those in the pSS group and the control group, respectively. And the expression level of TT in the pSS group was lower than that in control group. ROC curve analysis showed that the AUC of PT was 0.638, the AUC of FBG was 0.899, the AUC of FDP was 0.866, and the AUC of D-D was 0.919 in the RA group compared with the normal group. And the AUC of coagulation indexes for joint diagnosis of RA was higher than that of the indexes detected individually. pSS group had an AUC of PT of 0.618 compared with that of the normal group. The AUC of TT was 0.645, and the AUC of coagulation indexes for the joint diagnosis of pSS was higher than the AUC of each index detected separately. Association rule analysis showed that elevated D-D in RA patients had a significant correlation with elevated hs-CRP, CCP and RF, and elevated FBG had a significant correlation with elevated hs-CRP, ESR, RF and CCP. Elevated D-D in pSS patients had a correlation with elevated hs-CRP and anti-SSA, and elevated INR has correlation with elevated hs-CRP, anti-SSA and anti-SSB. Correlation analysis showed that PT, INR, FBG, FDP, and D-D were positively correlated with CRP and ESR, and TT was negatively correlated with CRP and ESR in the RA group. FBG, FDP, and D-D were positively correlated with CRP and ESR in the pSS group. Moreover, coagulation indexes were positively correlated with immune indexes in RA group and pSS group which were all significant. The results of multiple linear regression analysis showed that FBG was a positive correlate of hs-CRP and ESR in RA patients. For PSS patients, FBG and FDP were positive correlates of hs-CRP. APTT and FBG were positive correlates of ESR. Conclusion Compared with pSS, coagulation indexes (especially PT, FBG, FDP and D-D) are more informative for the early diagnosis of RA and the judgment of the degree of the disease, and can be used as an important predictor for the confirmation of the diagnosis of RA.
Humans
;
Female
;
Male
;
Arthritis, Rheumatoid/diagnosis*
;
Middle Aged
;
Fibrin Fibrinogen Degradation Products/analysis*
;
Blood Coagulation
;
Adult
;
Fibrinogen/metabolism*
;
Partial Thromboplastin Time
;
Prothrombin Time
;
Aged
;
Inflammation/immunology*
;
ROC Curve
2.The Effect of p.Thr241Asn and p.Cys389Gly Mutations on Coagulation Factor VII Structure and Function.
Journal of Experimental Hematology 2025;33(3):853-857
OBJECTIVE:
To identify F7 gene mutations in one pedigree with congenital coagulation factor VII (FVII) deficiency and explore the effect of F7 gene mutations on the structure and function of FVII.
METHODS:
Prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured based on the one-stage assay, and PT-based one stage assay was used to detect the activity of FII, V, VII and X. Genomic DNA was extracted from the peripheral blood of family members. The sequences of all the exons and exon-intron boundaries of F7 were amplified by polymerase chain reaction (PCR) using specific primers followed by Sanger sequencing. PolyPhen-2, PROVEAN and Swiss-Pdb Viewer software were used to analyze the effect of mutations on the structure and function of FVII.
RESULTS:
The proband had a prolonged PT (33.8 s) due to low FVII activity (6.6%) and normal APTT, and had a history of epistaxis. The proband's mother and father displayed a slightly prolonged PT (13.2 and 13.9 s, respectively), and their FVII activity was 40.3% and 38.3%, respectively. The compound heterozygous c.722C>A (p.Thr241Asn) in exon 7 and c.1165T>G (p.Cys389Gly) in exon 8 of F7 gene were identified in the proband, and inherited from his father and mother, respectively. The p.Thr241Asn and p.Cys389Gly missense change were likely to have a damaging effect predicted by polyphen-2 and PROVEAN software. In silico modeling analysis showed that there was one hydrogen bond formed between wild-type Thr241 and Val249, two hydrogen bonds formed between mutant Asn241 and Val249 and between mutant Asn241 and Leu242, as well as one hydrogen bond and one disulfide bond formed between wild-type Cys389 and Leu370 and between wild-type Cys389 and Cys375, respectively. The hydrogen bond formed between mutant Gly389 and Leu370 and disulfide bond formed between mutant Gly389 and Cys375 both broke.
CONCLUSIONS
FVII deficiency in this family is caused by p.Thr241Asn and p.Cys389Gly mutation. In silico modeling may be a valuable tool for understanding amino acid residues from variants leading to congenital FVII deficiency.
Humans
;
Factor VII/genetics*
;
Mutation
;
Pedigree
;
Factor VII Deficiency/genetics*
;
Prothrombin Time
;
Partial Thromboplastin Time
;
Male
;
Female
3.Thirteen serum biochemical indexes and five whole blood coagulation indices in a point-of-care testing analyzer: ideal protocol for evaluating pulmonary and critical care medicine.
Mingtao LIU ; Li LIU ; Jiaxi CHEN ; Zhifeng HUANG ; Huiqing ZHU ; Shengxuan LIN ; Weitian QI ; Zhangkai J CHENG ; Ning LI ; Baoqing SUN
Journal of Zhejiang University. Science. B 2025;26(2):158-171
The accurate and timely detection of biochemical coagulation indicators is pivotal in pulmonary and critical care medicine. Despite their reliability, traditional laboratories often lag in terms of rapid diagnosis. Point-of-care testing (POCT) has emerged as a promising alternative, which is awaiting rigorous validation. We assessed 226 samples from patients at the First Affiliated Hospital of Guangzhou Medical University using a Beckman Coulter AU5821 and a PUSHKANG POCT Biochemistry Analyzer MS100. Furthermore, 350 samples were evaluated with a Stago coagulation analyzer STAR MAX and a PUSHKANG POCT Coagulation Analyzer MC100. Metrics included thirteen biochemical indexes, such as albumin, and five coagulation indices, such as prothrombin time. Comparisons were drawn against the PUSHKANG POCT analyzer. Bland-Altman plots (MS100: 0.8206‒0.9995; MC100: 0.8318‒0.9911) evinced significant consistency between methodologies. Spearman correlation pinpointed a potent linear association between conventional devices and the PUSHKANG POCT analyzer, further underscored by a robust correlation coefficient (MS100: 0.713‒0.949; MC100: 0.593‒0.950). The PUSHKANG POCT was validated as a dependable tool for serum and whole blood biochemical and coagulation diagnostics. This emphasizes its prospective clinical efficacy, offering clinicians a swift diagnostic tool and heralding a new era of enhanced patient care outcomes.
Humans
;
Point-of-Care Testing
;
Critical Care
;
Blood Coagulation Tests/methods*
;
Male
;
Blood Coagulation
;
Female
;
Middle Aged
;
Reproducibility of Results
;
Prothrombin Time
;
Aged
;
Adult
;
Point-of-Care Systems
4.Recurrent epistaxis with coagulation disorders in a boy aged 2 years.
Jia-Zhuo LI ; Xin TIAN ; Chu-Shu LIAO ; Xiang-Ling HE ; Cheng-Guang ZHU
Chinese Journal of Contemporary Pediatrics 2022;24(7):817-820
A boy, aged 2 years and 5 months, had recurrent epistaxis, and the coagulation function examination showed that activated partial thromboplastin time (APTT) was significantly prolonged. Further laboratory examinations showed that the prolonged APTT was not immediately corrected in the APTT correction test, with positive lupus anticoagulant and low prothrombin activity. The boy was diagnosed with hypoprothrombinemia-lupus anticoagulant syndrome. The condition was improved after treatment with glucocorticoid, immunoglobulin, and vitamin K1. The boy has been followed up for 6 months, and no epistaxis was observed. Prothrombin activity returned to normal, and lupus anticoagulant remained positive. This is a relatively rare disease, and for patients with bleeding symptoms and coagulation disorders, it is recommended to perform the tests such as APTT correction test, lupus anticoagulant testing, and coagulation factor dilution test, which can improve the detection rate of this disease, so as to achieve early diagnosis, provide rational treatment in the early stage, and improve the prognosis.
Antiphospholipid Syndrome/diagnosis*
;
Blood Coagulation Disorders
;
Child, Preschool
;
Epistaxis/etiology*
;
Humans
;
Hypoprothrombinemias/diagnosis*
;
Lupus Coagulation Inhibitor
;
Male
;
Partial Thromboplastin Time
;
Prothrombin
5.The relationship between homocysteine, coagulation dysfunction and breast cancer risk.
Zi Hao LIU ; Wei YAN ; Fang Xuan LI ; Shi Xia LI ; Jun Tian LIU
Chinese Journal of Oncology 2022;44(6):562-569
Objective: To investigate the correlation of homocysteine (HCY) and coagulation function index with the risk of breast cancer and its clinicopathological characteristics. Methods: The HCY, coagulation function test index, and clinicopathological information of female breast cancer patients (333 cases) treated in Tianjin Medical University Cancer Hospital from January 2018 to December 2018 were collected, and female patients with benign breast (225 cases) were selected during the same period for the control group. The t-test was used to compare measurement data with normal distribution, D-Dimer data were distributed discreetly and described by median, non-parametric Mann-Whitney U test was used to compare the two groups. The chi-square test was used to compare enumeration data, and the Logistic regression analysis was used for the risk analysis. Results: The levels of HCY, fibrinogen (Fbg), protein C (PC), and median D-Dimer (D-D) in peripheral blood of breast cancer patients group [(13.26±5.24) μmol/L, (2.61±0.83) g/L, (117.55±19.67)%, and 269.68 ng/ml, respectively] were higher than those in the control group [(11.58±0.69) μmol/L, (2.49±0.49) g/L, (113.42±19.82)% and 246.98 ng/ml, respectively, P<0.05]. The prothrombin time (PT), PT(INR), α2-antiplasmin (α2-AP) levels [(10.19±0.63) s, 0.91±0.07 and (110.64±13.93)%, respectively] were lower than those in the control group [(10.58±0.65) s, 0.93±0.01 and (123.81±14.77) %, P<0.05]. The serum levels of PC and median D-D in premenopausal breast cancer patients [(112.57±17.86)% and 242.01 ng/ml, respectively] were higher than those in the control group [(105.31±22.31)% and 214.75 ng/ml, respectively, P<0.05]. The levels of PT(INR), α2-AP [0.91±0.07 and (111.29±12.54)%, respectively] were lower than those of the control group[0.98±0.15 and (120.17±16.35)%, respectively, P<0.05]. The levels of HCY and median D-D in postmenopausal breast cancer patients [(14.25±5.76) μmol/L and 347.53 ng/ml, respectively] were higher than those in the control group [(11.67±2.38) μmol/L and 328.28 ng/ml, P<0.05]. The levels of PT, PT(INR), antithrombin Ⅲ (AT-Ⅲ), α2-AP levels [(10.18±0.66) s, 0.87±0.09, (97.30±12.84)% and (110.13±14.96)%] were lower than those in the control group [(10.38±0.61) s, 0.90±0.08, (102.89±9.12)%, and (127.05±12.38)%, respectively, P<0.05]. The levels of α2-AP and median D-D in T2-4 stage breast cancer patients [(111.69±14.41)% and 289.25 ng/ml, respectively] were higher than those in Tis-1 stage patients [(108.05±12.37)% and 253.49 ng/ml, respectively, P<0.05]. The levels of PT, PT (INR), Fbg, AT-Ⅲ, α2-AP, median D-D [(10.62±0.63) s, 0.95±0.06, (3.04±1.52) g/L, (103.21±9.45)%, (118.72±14.77)% and 331.33 ng/ml, respectively] in breast cancer patients with lymph node metastasis were higher than those of patients without lymph node metastasis [(10.42±0.58) s, 0.93±0.06, (2.52±0.54) g/L, (95.20±13.63)%, (106.91±13.13)% and 263.38 ng/ml, respectively, P<0.05]. In non-menopausal breast cancer patients, the level of HCY [(12.63±4.41) μmol/L] in patients with T2-4 stage was higher than that of patients with Tis-1 stage [(10.70±3.49) μmol/L, P=0.010], and the level of thrombin time [(19.35±0.90) s] of patients with T2-4 stage was lower than that of patients with Tis-1 stage [(19.79±1.23) s, P=0.015]. The levels of PT(INR), Fbg, AT-Ⅲ, α2-AP [0.97±0.56, (3.37±2.34) g/L, (102.38±8.77)% and (120.95±14.06)%] in patients with lymph node metastasis were higher than those of patients without lymph node metastasis [0.94±0.05, (2.36±0.48) g/L, (94.56±14.37)% and (109.51±11.46)%, respectively, P<0.05]. Among postmenopausal breast cancer patients, the levels of AT-Ⅲ and α2-AP in T2-4 stage patients [(98.48±11.80)% and (111.84±15.35)%, respectively] were higher than those in patients with the Tis-1 stage [(94.12±14.98)% and (105.49±12.89)%, respectively, P<0.05]. The levels of AT-Ⅲ and α2-AP in N1-3 stage patients [(103.74±9.94)% and (117.29±15.23)%] were higher than those in N0 stage patients [(95.75±13.01)% and (108.39±14.42)%, P<0.05]. Conclusions: HCY and abnormal coagulation function are related to the risk of breast cancer, T stage and lymph node metastasis in breast cancer patients.
Blood Coagulation Disorders
;
Breast Neoplasms
;
Female
;
Fibrinogen/metabolism*
;
Homocysteine
;
Humans
;
Lymphatic Metastasis
;
Prothrombin Time
6.Non-parametric clinical laboratory reference interval estimation in volunteer blood donors: An example for prothrombin time and partial thromboplastin time
Mark Angelo Ang ; Nelson Geraldino ; Ariel Vergel de Dios ; Marimin Abad-Lapuebla
Philippine Journal of Pathology 2022;7(2):23-27
Introduction:
To date, there are no reference intervals for prothrombin time (PT) and activated partial thromboplastin time (APTT) based on “normal” Filipino adults. The common practice in most laboratories is to adopt manufacturer provided values or foreign literature even if the importance of establishing or at least verifying laboratory reference intervals has been stressed by Clinical Laboratory Standards Institute (CLSI).
Objectives:
Here we aim to describe our experience in using a simple non-parametric method to generate reference intervals for PT and APTT, from healthy Filipino volunteer blood donors.
Methodology:
We used a de novo, a priori non-parametric estimation method following the CLSI guidelines on establishing reference intervals.
Results:
The non-parametric lower reference limit for PT is 12.55 seconds, with 90% confidence interval of 12.3 to 12.75 seconds. While the non-parametric upper reference limit for PT is 16.15 seconds, with 90% confidence interval of 15.55 to 16.55 seconds. The non-parametric lower reference limit for activated partial thromboplastin time is 26.12 seconds, with 90% confidence interval of 22.95 to 27.1 seconds, and the non-parametric upper reference limit for activated partial thromboplastin time is 37.44 seconds, with 90% confidence interval of 36.75 to 38.65 seconds. The PT and APTT reference intervals were different from foreign sources and manufacturer provided values in terms of interval width and values of the reference limits by 2 to 4 seconds.
Conclusion and Recommendations
Estimation of coagulation reference intervals from volunteer health blood donors is doable, simple, and practical. Collaborative multi-center efforts may be done to expand the pool of reference individuals that are included and increase the representativeness of the reference intervals generated. This simple method can also be used to generate reference intervals for other clinical laboratory assays and may also be extended to at least verify reference intervals in special populations like pregnant women, the elderly, and the pediatric population.
Prothrombin Time
;
Partial Thromboplastin Time
7.Coagulation Indexes and Their Prognostic Significance in Patients with Multiple Myeloma.
Qing-Fen LI ; Qi-Ke ZHANG ; Xiao-Fang WEI ; You-Fan FENG
Journal of Experimental Hematology 2021;29(3):791-796
OBJECTIVE:
To analyze the relationship between coagulation indexes and prognosis of patients with multiple myeloma (MM).
METHODS:
A total of 99 newly diagnosed MM patients treated in Gansu Provincial Hospital from October 2017 to October 2019 were enrolled. Plasma thromboplastin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer (D-D), platelet (PLT), and other laboratory indexes were detected. The relationship between coagulation indexes and clinical characteristics of MM patients was analyzed. The differences in survival rates among MM patients with different levels of coagulation indexes were compared, and the effect of each clinical index on the prognosis of MM patients was analyzed by univariate and multivariate.
RESULTS:
Each coagulation index was correlated to sex, disease classification and stage, and β
CONCLUSION
Coagulation function is correlated with multiple clinical indicators of patients with MM and plays an important role in their prognosis.
Blood Coagulation Tests
;
Fibrin Fibrinogen Degradation Products
;
Humans
;
Multiple Myeloma
;
Partial Thromboplastin Time
;
Platelet Count
;
Prognosis
;
Prothrombin Time
8.Clinical characteristics of 34 COVID-19 patients admitted to intensive care unit in Hangzhou, China.
Yi ZHENG ; Li-Jun SUN ; Mi XU ; Jian PAN ; Yun-Tao ZHANG ; Xue-Ling FANG ; Qiang FANG ; Hong-Liu CAI
Journal of Zhejiang University. Science. B 2020;21(5):378-387
OBJECTIVE:
This study summarizes and compares clinical and laboratory characteristics of 34 patients admitted to the intensive care unit (ICU) for complications from coronavirus disease 2019 (COVID-19) at the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China from Jan. 22 to Mar. 5, 2020.
METHODS:
A total of 34 patients were divided into two groups, including those who required noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) with additional extracorporeal membrane oxygenation (ECMO) in 11 patients. Clinical features of COVID-19 patients were described and the parameters of clinical characteristics between the two groups were compared.
RESULTS:
The rates of the acute cardiac and kidney complications were higher in IMV cases than those in NIV cases. Most patients had lymphocytopenia on admission, with lymphocyte levels dropping progressively on the following days, and the more severe lymphopenia developed in the IMV group. In both groups, T lymphocyte counts were below typical lower limit norms compared to B lymphocytes. On admission, both groups had higher than expected amounts of plasma interleukin-6 (IL-6), which over time declined more in NIV patients. The prothrombin time was increased and the levels of platelet, hemoglobin, blood urea nitrogen (BUN), D-dimer, lactate dehydrogenase (LDH), and IL-6 were higher in IMV cases compared with NIV cases during hospitalization.
CONCLUSIONS
Data showed that the rates of complications, dynamics of lymphocytopenia, and changes in levels of platelet, hemoglobin, BUN, D-dimer, LDH and IL-6, and prothrombin time in these ICU patients were significantly different between IMV and NIV cases.
Acute Kidney Injury
;
virology
;
Aged
;
Aged, 80 and over
;
Betacoronavirus
;
Blood Urea Nitrogen
;
China
;
Coronavirus Infections
;
complications
;
therapy
;
Extracorporeal Membrane Oxygenation
;
Female
;
Fibrin Fibrinogen Degradation Products
;
analysis
;
Heart Diseases
;
virology
;
Hemoglobins
;
analysis
;
Hospitalization
;
Humans
;
Intensive Care Units
;
Interleukin-6
;
blood
;
L-Lactate Dehydrogenase
;
blood
;
Lymphopenia
;
virology
;
Male
;
Middle Aged
;
Noninvasive Ventilation
;
Pandemics
;
Pneumonia, Viral
;
complications
;
therapy
;
Positive-Pressure Respiration
;
Prothrombin Time
;
Retrospective Studies
9.Level of Coagulation Function Indexes and Its Clinical Significance in Patients with Lymphoplasmacytic Lymphoma.
Xiao-Ping LIANG ; Hai-Dong WANG ; Ming-Ming SHAO ; Ni LI ; Wen-Xia HAN
Journal of Experimental Hematology 2020;28(4):1205-1209
OBJECTIVE:
To analyze the level of coagulation function indexes in patients with lymphoplasmacytic lymphoma (LPL) and its clinical significance.
METHODS:
The clinical data of 32 patients with initial LPL (LPL group) and physical examination data of 25 healthy persons (control group) who underwent physical examination in our hospital during the same period were collected. The differences of platelet (Plt), D-Dimer (D-D), fibrinogen (Fib), thrombin time (TT), prothrombin time (PT) and activated partial thrombin time (APTT) between the two groups were compared.
RESULTS:
The Plt count in LPL group [ (137.06±40.14)×10/L] was significantly lower than that in control group [ (215.07±33.25)×10/L], D-D [ (1.01±0.16) mg/L, PT [ (13.01±1.37) s] and APTT [ (40.96±7.24) s] in LPL group were significantly higher than those in control group [ (0.37±0.09) mg/L, (11.96±0.87) s, (25.07±5.13) s] (P<0.01); there was no significant difference in TT and Fib levels between the two groups (P>0.05). There was no significant difference in Plt, D-D, Fib, AP, TT and APTT among LPL patients secreting different types of immunoglobulin (Ig) (P>0.05). After treatment, the coagulation function of LPL patients returned to normal, and no death cases occurred due to hemorrhage or thrombosis.
CONCLUSION
LPL patients have hypercoagulable state blood and abnormal coagulation function, but which not closely relates to with the type of Ig secreted by patients.
Adult
;
Blood Coagulation
;
Blood Coagulation Tests
;
Humans
;
Lymphoma
;
Partial Thromboplastin Time
;
Prothrombin Time
;
Thrombosis
10.Clinical observation of 6 severe COVID-19 patients treated with plasma exchange or tocilizumab.
Song LUO ; Lijuan YANG ; Chun WANG ; Chuanmiao LIU ; Dianming LI
Journal of Zhejiang University. Medical sciences 2020;49(2):227-231
OBJECTIVE:
To observe the clinical effect of plasma exchange and tocilizumab in treatment of patients with severe coronavirus disease 2019 (COVID-19).
METHODS:
Six patients with severe COVID-19 admitted in First Affiliated Hospital of Bengbu Medical College from January 25 to February 25, 2020. Three patients were treated with plasma exchange and three patients were treated with tocilizumab. The effect on excessive inflammatory reaction of plasma exchange and tocilizumab was observed.
RESULTS:
The C-reactive protein (CRP) and IL-6 levels were significantly decreased and the lymphocyte and prothrombin time were improved in 3 patients after treatment with plasma exchange; while inflammation level was not significantly decreased, and lymphocyte and prothrombin time did not improve in 3 patients treated with tocilizumab.
CONCLUSIONS
For severe COVID-19 patients with strong inflammatory reaction, plasma exchange may be preferred.
Antibodies, Monoclonal, Humanized
;
administration & dosage
;
Betacoronavirus
;
isolation & purification
;
Coronavirus Infections
;
blood
;
immunology
;
therapy
;
Cytokine Release Syndrome
;
therapy
;
Humans
;
Pandemics
;
Plasma Exchange
;
standards
;
Pneumonia, Viral
;
blood
;
immunology
;
therapy
;
Prothrombin Time
;
Treatment Outcome


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