1.Coagulation and platelet profiles of COVID-19 patients admitted to a COVID Referral Center from March 2020 to December 2022
Ivana Ungajan-Galapon ; Karen Damian ; Nelson Geraldino
Philippine Journal of Pathology 2024;9(1):11-16
		                        		
		                        			Objective:
		                        			This study aimed to determine the demographic profiles of admitted COVID-19 patients, the association of coagulation and platelet tests on COVID-19 severity and compare the coagulation and platelet profile across the spectrum of the disease in terms of severity among adult COVID-19 patients admitted to the Philippine General Hospital from March 2020 to December 2022.
		                        		
		                        			:
		                        			Methodology. Medical records of a sample of adult COVID-19 patients admitted to the emergency room of the Philippine General Hospital from March 2020 to December 2022 were reviewed. The demographics, initial COVID-19 diagnosis and initial coagulation and platelet test results were gathered and tabulated. Comparison of the initial coagulation and initial platelet results were made per disease category.
		                        		
		                        			Results:
		                        			Three hundred eighty-five (385) patients were included; 194 were males, and 191 were females. The mean age of all patients was 56.18 years old. There was a total of 30 patients classified as mild and 105 patients are under moderate category. 141 patients were classified as severe, whereas 109 patients were classified as critical. Platelet count test and Activated Partial Thromboplastin Time (APTT) were mostly normal in all disease categories.  Prothrombin time was normal in a majority of patients from the mild and severe categories. INR and D-dimer were all elevated mostly in all disease categories.
		                        		
		                        			Conclusion
		                        			Platelet counts and APTT were mostly normal in all disease categories. Prothrombin time and D-dimer had a significant association with disease severity. Platelet count, APTT and INR did not show significant association with disease severity. Prothrombin time, APTT, INR and D-dimer means had significant differences versus disease categories.
		                        		
		                        		
		                        		
		                        			Partial Thromboplastin Time
		                        			;
		                        		
		                        			 OVID-19
		                        			;
		                        		
		                        			 Patient Acuity
		                        			
		                        		
		                        	
2.Analysis of a Chinese pedigree affected with Hereditary coagulation factor Ⅺ deficiency due to variant of F11 gene.
Huanhuan WANG ; Suting JIANG ; Huinan XIA ; Lihong YANG ; Yanhui JIN ; Mingshan WANG
Chinese Journal of Medical Genetics 2023;40(11):1319-1323
		                        		
		                        			OBJECTIVE:
		                        			To explore the molecular pathogenesis of a Chinese pedigree affected with Hereditary coagulation factor Ⅺ (FⅪ) deficiency due to variants of the F11 gene.
		                        		
		                        			METHODS:
		                        			A male proband with Hereditary coagulation factor Ⅺ deficiency who was admitted to the First Affiliated Hospital of Wenzhou Medical University due to urinary calculi on November 30, 2020 and his family members (7 individuals from 3 generations in total) were selected as the study subjects. Clinical data of the proband were collected, and relevant coagulation indices of the proband and his family members were determined. Genomic DNA of peripheral blood samples was extracted for PCR amplification. All exons, flanking sequences, and 5' and 3' untranslated regions of the F11 gene of the proband were analyzed by direct sequencing. And the corresponding sites were subjected to sequencing in other family members. The conservation of amino acid variation sites was analyzed by bioinformatic software, and the effect of the variant on the protein function was analyzed. Variants were graded based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).
		                        		
		                        			RESULTS:
		                        			The proband was a 36-year-old male. His activated partial thromboplastin time (APTT) was 89.2s, which was significantly prolonged. The FⅪ activity (FⅪ:C) and FⅪ antigen (FⅪ:Ag) were 2.0% and 3.5%, respectively, which were extremely reduced. Both the proband and his sister were found to harbor compound heterozygous variants of the F11 gene, including a c.689G>T (p.Cys230Phe) missense variant in exon 7 from their father and a c.1556G>A (p.Trp519*) nonsense variant in exon 13 from their mother. Conservation analysis indicated the Cys230 site to be highly conserved. The c.1556G>A (p.Trp519*) variant was known to be pathogenic, whilst the c.689G>T variant was classified as likely pathogenic (PM2+PM5+PP1+PP3+PP4) based on the ACMG guidelines.
		                        		
		                        			CONCLUSION
		                        			The c.689G>T and c.1556G>A compound heterozygous variants of the F11 gene probably underlay the pathogenesis of FⅪ deficiency in this pedigree.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			3' Untranslated Regions
		                        			;
		                        		
		                        			East Asian People
		                        			;
		                        		
		                        			Factor XI/genetics*
		                        			;
		                        		
		                        			Factor XI Deficiency/genetics*
		                        			;
		                        		
		                        			Partial Thromboplastin Time
		                        			;
		                        		
		                        			Pedigree
		                        			
		                        		
		                        	
3.Analysis of APTT Mixing Test Results in Factor Ⅷ Inhibitor-Positive Hemophilia Patients.
Li-Hua ZHANG ; Zhi-Qiang XIE ; He ZHUANG ; Mei-Hua WANG ; Ying-Ping CAO
Journal of Experimental Hematology 2023;31(6):1791-1796
		                        		
		                        			OBJECTIVE:
		                        			To analyze the results of activated partial thromboplastin time (APTT) mixing test in coagulation factor Ⅷ inhibitor-positive hemophilia patients, so as to increase the value of APTT mixing test in the screen of factor Ⅷ inhibitor.
		                        		
		                        			METHODS:
		                        			Eighty plasmas samples with different titers of coagulation factor Ⅷ inhibitors had been collected and diluted for routine immediate APTT mixing test and at 37 ℃ 2 hours incubation APTT mixing test. Fifteen samples were selected for immediate and normal temperature incubation for 15 min, 30min, 1 hour, 2 hours and 37 ℃ for 30 min, 1 hour, 2 hours APTT mixing test.
		                        		
		                        			RESULTS:
		                        			The results of APTT mixing test were significantly correlated with the titers of coagulation factor Ⅷ inhibitors. The ROC curve result showed that the best diagnostic cut-off value for 2 hours incubation APTT mixing test at 37 ℃ to determine the presence or absence of coagulation factor Ⅷ inhibitors was 43.8 s (sensitivity and specificity was 85.90% and 100%, respectively), while the best diagnostic cut-off value for distinguishing high-titer and low-titer Ⅷ inhibitors was 52.4 s (sensitivity and specificity was 98.18% and 95.65%, respectively). The critical coagulation factor Ⅷ inhibitor titer that could not be corrected by immediate APTT was 5.14 BU/ml, while that could not be corrected by 37 ℃ 2 hours incubation APTT was 1.31 BU/ml. Paired samples t -test was performed on the APTT mixing test results at different times and temperatures, and the differences were statistically significant (P < 0.05).
		                        		
		                        			CONCLUSIONS
		                        			The APTT mixing test can be used as a screening index for coagulation factor Ⅷ inhibitors. APTT mixing test result shows a significant time-temperature dependence with lower titers of coagulation factor Ⅷ inhibitor. Patients with hemophilia who cannot be corrected by immediate APTT mixing test should be alert to the possibility of high titer of coagulation factor Ⅷ.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Factor VIII
		                        			;
		                        		
		                        			Hemophilia A/diagnosis*
		                        			;
		                        		
		                        			Blood Coagulation Tests/methods*
		                        			;
		                        		
		                        			Partial Thromboplastin Time
		                        			;
		                        		
		                        			Blood Coagulation Factors
		                        			
		                        		
		                        	
4.Analysis of High-Risk Clinical Factors of Early Death in Secondary Hemophagocytic Lymphohistiocytosis.
Jin-Li ZHU ; Fan WU ; Lin-Hui HU ; Zhi-Min ZHAI
Journal of Experimental Hematology 2023;31(6):1866-1871
		                        		
		                        			OBJECTIVE:
		                        			To explore the high-risk clinical factors of early death in patients with secondary hemophagocytic lymphohistiocytosis (sHLH), and further identify the clinical factors related to the rapid progression of sHLH in the short term.
		                        		
		                        			METHODS:
		                        			The clinical manifestations, laboratory examination and prognosis of sHLH patients were retrospectively analyzed. Continuous variables were grouped by median, univariate and multivariate Cox regression analysis and Kaplan-Meier survival curve were used to explore the risk factors affecting early death of sHLH. Then, a nomogram model was established with independent risk factors, Bootstrap resampling method was used for verification, and consistency index (C-index) and calibration curve were used to detect the prediction accuracy.
		                        		
		                        			RESULTS:
		                        			A total of 126 sHLH patients were enrolled, with a median age of 48.5(16-88) years, including 74 males and 52 females. Fifty-five patients (43.6%) died within 30 days, including 39 males and 16 females. Univariate regression analysis showed that lymphocyte count <0.45×109/L, platelet count (PLT) <39.5×109/L, prothrombin time (PT)≥13.3 s, activated partial thromboplastin time (APTT)≥39.7 s, albumin (ALB) <25.9 g/L, lactate dehydrogenase (LDH)≥811 U/L, creatinine (Cr) ≥67 μmol/L and procalcitonin (PCT)≥0.61 ng/ml were risk factors for death within 30 days in sHLH patients. Multivariate regression analysis showed that lymphocyte count <0.45×109/L, APTT≥39.7 s and ALB <25.9 g/L were independent risk factors for death within 30 days in sHLH patients. A nomogram model was established based on the above three risk factors, its C-index was 0.683, and the calibration chart showed good agreement between the observed and predicted values of sHLH.
		                        		
		                        			CONCLUSIONS
		                        			Lymphopenia, prolonged APTT, and hypoalbuminemia are risk factors for early death of sHLH patients. Early identification and positive intervention are expected to reduce early mortality in sHLH patients. The nomogram model based on the above risk factors provides a method for clinicians to evaluate sHLH.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Lymphohistiocytosis, Hemophagocytic/complications*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Risk Factors
		                        			;
		                        		
		                        			Partial Thromboplastin Time
		                        			;
		                        		
		                        			Albumins
		                        			
		                        		
		                        	
5.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
		                        			
		                        		
		                        	
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.Analysis of bleeding risk in percutaneous renal biopsy in Tibet.
Lei ZHANG ; Guo Liang LI ; Zong Hui DANG ; Ling Jie WU ; Li Jun LIU
Journal of Peking University(Health Sciences) 2021;53(2):298-301
		                        		
		                        			OBJECTIVE:
		                        			To observe the postoperative bleeding after percutaneous renal biopsy (PRB) in Tibet, To analyze and summarize the risk factors associated with bleeding in high altitude patients to improve the safety of surgery.
		                        		
		                        			METHODS:
		                        			A retrospective analysis of 150 cases of PRB in the Department of Nephrology, People's Hospital of Tibet Autonomous Region from May 2016 to May 2018 were carried out, and the correlations between the potential risk factors (gender, age, blood pressure, hemoglobin, platelet, serum creatinine) and postoperative bleeding events were analyzed.
		                        		
		                        			RESULTS:
		                        			During the study period, the 150 patients receiving procedure of PRB were enrolled in our hospital, with an average age of (41.2±15.6) years, of whom 58.7% (88/150) were male, 41.3% (62/150) were female, and major bleeding complications occurred in 12 biopsies (8.0%, 12/150). Six cases for men and women, respectively. The mean age in the bleeding group seemed to be higher than that in the non-bleeding group [(48.3±20.0) years vs. (40.6±15.1) years, P=0.099]. There was no significant difference in the incidence of hypertension, hemoglobinemia, urea nitrogen and prothrombin time between the two groups. The level of serum creatinine in the hemorrhage group seemed to be higher than that in the non-bleeding group (P=0.090), and the time of the hemorrhagic group was longer than that in the non-bleeding group (P=0.069). The platelet count in the bleeding group was significantly lower than that in the non-bleeding group (P < 0.05). Multivariate Logistic regression analysis showed that the prolonged activation of partial prothrombin time and lower platelet count had a relatively high risk of bleeding, which was statistically significant (P=0.079, P=0.082).
		                        		
		                        			CONCLUSION
		                        			PRB is safe and reliable on the whole in plateau areas; Old age, low platelet count, decreased renal function and prolonged activated partial coagulation time are related to postoperative bleeding of PRB, and hyperhemoglobin is not a risk factor for bleeding. High hemoglobin is not a risk factor for postoperative bleeding of PRB at high altitude.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Biopsy
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Hemorrhage/etiology*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Partial Thromboplastin Time
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Risk Factors
		                        			;
		                        		
		                        			Tibet
		                        			
		                        		
		                        	
8.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
		                        			
		                        		
		                        	
9.Design of Detection Module in Coagulometers Based on Dual-magnetic Circuit Beads Method.
Shaomin LI ; Xingwei ZHANG ; Junfang QIN ; Yongjie ZHAO ; Zhaohong XIE ; Xinjian LU ; Qihao LIU
Chinese Journal of Medical Instrumentation 2021;45(2):145-152
		                        		
		                        			
		                        			Coagulometer, known as blood coagulation analyzer, is a product that can provide accurate test results for medical diagnosis and treatment analysis by detecting a series of items closely related to thrombosis and hemostasis in coagulation reaction. On the basis of previous traditional methods, and with our deep understanding about the principles of hemagglutination detection, we propose a hemagglutination detection method by using the dual-magnetic circuit beads method. Then, the corresponding hemagglutination detection module is designed. The coagulation time of plasma can be measured by detecting the movement of the magnetic beads when the magnetic field intensity is appropriate. The activated partial thromboplastin time(APTT) of plasma is tested when the most suitable magnetic field intensity is found. The results preliminarily show that this blood coagulation test method is valid and the corresponding test module has a potential value in business.
		                        		
		                        		
		                        		
		                        			Blood Coagulation
		                        			;
		                        		
		                        			Blood Coagulation Tests
		                        			;
		                        		
		                        			Magnetic Phenomena
		                        			;
		                        		
		                        			Magnetics
		                        			;
		                        		
		                        			Partial Thromboplastin Time
		                        			
		                        		
		                        	
10.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
		                        			
		                        		
		                        	
            

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