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Fulltext Elevated plasma tissue factor levels in neonates with umbilical arterial catheter-associated thrombosis

Tay SP, Cheong SK, Boo NY

Malays J Pathol, 2006 Jun;28(1):41-8.
PMID: 17694958 MyJurnal

Catheterization of the umbilical artery has been a useful aid in the management of sick neonates for the past few decades. However, it is associated with various complications. Reported studies strongly suggest a significant role of intravascular catheterization in the development of aortic thrombi. Increase in thrombosis of large vessels is believed to be related to mechanical injury in the catheterized vessels, which provide direct exposure of blood to tissue factor (TF), the primary cellular initiator of the extrinsic coagulation pathway. This study was conducted to determine the levels of plasma TF, tissue factor pathway inhibitor (TFPI) and D-dimer (DD) in infants with umbilical arterial catheter (UAC)-associated thrombosis. Quantification of TF was carried out using an in-house sandwich ELISA, whereas TFPI and DD levels were measured with commercial immunoassay kits. Infants with UAC inserted were found to have significantly higher levels of plasma TF (p < 0.001) than baseline levels. However, there were no significantly elevated levels of TFPI or DD. Infants with UAC-associated thrombosis demonstrated a greater increase of TF level (median: 414.5 pg/mL; range: -76.0, 6667.0) than infants without UAC-associated thrombosis (105.0 pg/mL; -976.0, 9480.0; p = 0.009) following UAC insertion. Our findings indicate that quantification and monitoring of TF levels could predict thrombus formation in infants with indwelling UAC. Following umbilical arterial catheterisation, infants with an approximately 3-fold rise in plasma TF levels were most at risk of developing abdominal aorta thrombosis as confirmed by real-time abdominal ultrasonography.

Matched MeSH terms: Fibrin Fibrinogen Degradation Products/analysis
Prevalence and Clinical Features of Pulmonary Embolism in Pregnancy and Puerperium in the Post-COVID-19 Era

Tan TL, Illa NEB, Ting SY, Chiew SC, Gan Y, Ong ZW, et al.

Matern Child Health J, 2025 Mar;29(3):428-437.
PMID: 40085386 DOI: 10.1007/s10995-025-04067-w

OBJECTIVE: Interest in pulmonary embolism (PE) has undergone a renaissance since the emergence of COVID-19 pandemic, but PE researches among pregnant mothers in this post-COVID-19 era remains scarce. This study was conducted to (a) determine PE prevalence rate among pregnant and post-partum women with suspected PE after the COVID 19 pandemic, (b) compare the clinical characteristics, laboratory findings and CT features between the PE and non-PE cohorts, and (c) validate the Pregnancy-Adapted Geneva (PAG) score in our population.
METHODS: This retrospective cross-sectional study involved the review of all maternal cases with suspected PE who underwent diagnostic CTPA in year 2022.
RESULTS: A total of 120 patients represented by 90 pregnant patients and 30 post-partum patients were included in the analysis. The prevalence rate of PE was 22.5% (27/120) and gestational diabetes mellitus prevalence rate was significantly higher (48.1% vs. 26.9%; p = 0.037) in PE cohort. Besides, the proportion of patients with moderately and extremely raised peak D-dimer levels were significantly higher among the PE cohort. In patients with PE, the position of the most proximal clot was identified as subsegmental (n = 6, 22.2%) and segmental (n = 21; 77.8%). The predicted PE risk based on PAG score demonstrated poor calibration with the observed PE risk across all three groups, namely low-risk group (2.3% vs. 15.4%), intermediate-risk group (11.6% vs. 26.3%) and high-risk groups (61.5% vs. 0.0%).
CONCLUSION: Overall, PE among pregnant and post-partum populations remain a convoluted disease without distinctive clinical features. There is a need for a prospectively validated PE risk scores to guide its clinical diagnostic pathway.

Matched MeSH terms: Fibrin Fibrinogen Degradation Products/analysis
Fulltext General Perceptions and Awareness Level among Local Residents in Penang Island toward Bats Conservation Efforts

Shafie NJ, Sah SAM, Mutalib AHA, Fadzly N

Trop Life Sci Res, 2017 Jul;28(2):31-44.
PMID: 28890759 MyJurnal DOI: 10.21315/tlsr2017.28.2.3

The population of bats has declined from year to year caused by human activities such as logging and hunting activities. Since the human factor is linked to the issues of population decline in many animal species, a community-based conservation strategy that involved local communities is needed. We conducted face-to-face surveys among residents in Penang Island to assess knowledge and awareness level toward bats conservation efforts. We collected demographic values such as age, gender, level of education, length of residency as well as their monthly income, since different group in these variable might have different perception. We found that age groups, level of education and monthly income have shown significant differences among the respondents. However, no other significant differences were indicated for by gender and length of residency. Respondent's knowledge of bats showed that the majority of the respondents were less likely to value the importance of bats in the ecosystem. We recommended stronger legal system, earlier exposure towards environmental education, well-planned urbanisation implementation and long-term monitoring programs to strengthen efforts in conserving bats in Malaysia.

Matched MeSH terms: Fibrinogen
Fulltext Coagulation Factor Activities Changes Over 5 Days in Thawed Fresh Frozen Plasma Stored at Different Initial Storage Temperatures

Noordin SS, Karim FA, Mohammad WMZBW, Hussein AR

Indian J Hematol Blood Transfus, 2018 Jul;34(3):510-516.
PMID: 30127563 DOI: 10.1007/s12288-017-0879-8

Thawed plasma is fresh frozen plasma (FFP) that has been stored for 5 days at 1-6 °C. Duration of storage and different storage temperatures might affect the coagulation factor activity in thawed FFP. This study measured the changes of coagulation factor activities over 5 days in thawed FFP and stored at two different initial storage temperatures. Thirty-six units of FFP, which consisted of nine units each from blood groups A, B, AB, and O, were thawed at 37 °C. Each unit was divided into two separate groups (Group A and Group B) based on initial storage temperature. The first group was stored at 2-6 °C for 5 days (Group A). The second group was stored at 20-24 °C for initial 6 h followed by 2-6 °C for 5 days (Group B). Prothrombin time (PT), activated partial thromboplastin time (APTT), coagulation factor activities of fibrinogen, factor (F) II, FV, FVII, FVIII, FIX, FX, and von Willebrand factor antigen (vWF Ag) were assessed at baseline after thawing, at 6 h, and on days 1, 3, and 5 of storage for both groups. All coagulation factors mean activities in both storage groups decreased significantly over 5 days of storage. The mean FVIII activity at day 5 of storage was 36.9% in Group A and 39.8% in Group B. The other coagulation factors mean activities were > 50% on day 5 of storage in both groups. The coagulation factor activities of thawed FFP stored for 5 consecutive days were reduced in the two storage groups but most of the activities were still above 30%. This study suggests that thawed FFP stored for 5 days has the potential to ameliorate coagulation factor deficiencies in affected patients.

Matched MeSH terms: Fibrinogen
Fulltext Effects of Methylene Blue, Psoralen and Riboflavin treatments on Fibrinogen and other coagulation factors level of fresh frozen plasma

Norazlina Hamzah, Faraizah Abd. Karim, Ahzad Hadi Ahmad, Narazah Mohd Yusoff

Malaysian Journal of Medicine and Health Sciences, 2018;14(201):1-9.
MyJurnal

Photochemical treatment is one of the pathogen inactivation method to treat plasma, part of a proactive approach used for blood and blood component safety. Three photochemical treatments that have been used were methylene blue, riboflavin and psoralen treatment. This study was done on Fresh Frozen Plasma (FFP) to evaluate the treatment effects of psoralen, methylene blue and riboflavin on coagulation factors level. Methods: FFP was collected from apheresis plasma units and kept at 22oC to 24oC. A sum of 90 apheresis plasma units and segments were used, separated from each bag and a part used as controls, placed in a -30oC freezer for storage, thawed, and coagulation proteins function was evaluated before and after treatment, at immediate, 30 days and 270 days storage. Results: Significant differences in fibrinogen and coagulation factor levels between before and after treatment with methylene blue, psoralen and riboflavin. However, most of the mean values in treated plasma were within reference ranges. Methylene blue treated FFP showed the lowest changes in fibrinogen and other coagulation factors level whilst riboflavin treated FFP demonstrated the highest changes in coagulation proteins concentrations especially for fibrinogen, FV, FVIII, FIX and FXII. However, FXIII showed the best recovery for all three photochemical methods with reduction level of 3% to 8% compared to pre-treatment. Storage time comparison of immediate, 30 days and 270 days was inconclusive. Conclusion: The coagulation proteins in psoralen treated FFP and MB-FFP were adequately preserved, where MB-FFP showed better preservation than other two photochemical treatments.

Matched MeSH terms: Fibrinogen
Fulltext Deep Vein Thrombosis and the Neurosurgical Patient

Rethinasamy R, Alias A, Kandasamy R, Raffiq A, Looi MC, Hillda T

Malays J Med Sci, 2019 Sep;26(5):139-147.
PMID: 31728126 MyJurnal DOI: 10.21315/mjms2019.26.5.13

Background: Neurosurgical patients are varied, encompassing cranial and spinal diseases and trauma, and are admitted under both elective and emergency settings. In all settings, neurosurgery patients are at risk of deep vein thrombosis. D-dimer and ultrasound Doppler have long been good screening and confirmatory tools for the diagnosis of deep vein thrombosis (DVT). We conducted a study to identify the factors associated with DVT among neurosurgical patients, and the overall rate of occurrence at our centre. We aimed to also compare our results to the incidence in similar studies elsewhere in which more judicious use of pharmacological prophylaxis was undertaken. We also included the Well's score to validate its usefulness in screening for DVT in our local setting.
Methods: All patients admitted into our centre were screened for eligibility and those who underwent surgery from September 2016 to September 2017 had a D-dimer screening after surgery, followed by an ultrasound Doppler if the former was positive. The choice of anticoagulant therapy was not influenced by this study, and observation of the use was in keeping with usual practices in our centre was done.
Results: A total number of 331 patients were recruited in this study, however, after the inclusion and exclusion criteria had been met, 320 patients remained eligible, i.e. suitable for analysis. The mean age of our patients was 46 years, with 66% being male patients. A majority of the cases in this study were cranial related, with only 5% being spine surgeries. On the multivariate analysis, the Well's score and the number of days in bed remained statistically significant, after adjusting for age group, gender, ethnicity, type of central venous access and type of DVT prophylaxis with an adjusted odd's ratio, and a confidence interval of 95%, and P < 0.05 for each.
Conclusion: Well's scoring and number of days in bed were independent factors affecting the rate of DVT in patients undergoing neurosurgical procedures in our centre.

Matched MeSH terms: Fibrin Fibrinogen Degradation Products
Fibrinogen isoforms as potential blood-based biomarkers of Alzheimer's disease using a proteomics approach

Rehiman SH, Lim SM, Lim FT, Chin AV, Tan MP, Kamaruzzaman SB, et al.

Int J Neurosci, 2020 Dec 15.
PMID: 33280461 DOI: 10.1080/00207454.2020.1860038

Objective: Alzheimer's disease (AD), the commonest form of dementia which is characterized by progressive decline in cognitive function, can only be definitively diagnosed after death. Although biomarkers may aid diagnosis, currently available AD biomarkers, which are predominantly based on cerebrospinal fluid and neuroimaging facilities, are either invasive or costly. Blood-based biomarkers for AD diagnosis are highly sought after due to its practicality at the clinic. This study was undertaken to determine the differential protein expression in plasma amongst Malaysian AD, mild cognitive impairment (MCI) and non-AD individuals. Methods: A proteomic approach which utilized two-dimensional differential in gel electrophoresis (2 D DIGE) was performed for blood samples from 15 AD, 14 MCI and 15 non-AD individuals. Results: Mass spectrometry (MS)-based protein identification via MALDI ToF/ToF showed that fibrinogen-β-chain (spot 64) and fibrinogen-γ-chain (spot 91) with differential expression ratio >1.5 were significantly upregulated (p fibrinogen-γ-chain was weakly but significantly (p Fibrinogen isoforms may play important roles in the vascular pathology of AD as well as neuroinflammation. As such, fibrinogen appears to be a promising blood-based biomarker for AD. Further validation of the present findings in larger population is now warranted.

Matched MeSH terms: Fibrinogen
Fulltext Serum Ischemia-Modified Albumin, Fibrinogen, High Sensitivity C- Reactive Proteins in Type-2 Diabetes Mellitus without Hypertension and Diabetes Mellitus with Hypertension: A Case-Control Study

Sushith S, Krishnamurthy HN, Reshma S, Janice D, Madan G, Ashok KJ, et al.

Rep Biochem Mol Biol, 2020 Jul;9(2):241-249.
PMID: 33178875 DOI: 10.29252/rbmb.9.2.241

Background: The objective of this study was to determine the levels of serum ischemia-modified albumin (IMA), fibrinogen (FIB) and high sensitivity C-reactive protein (hs-CRP) in type 2 diabetes mellitus (T2DM) patients with hypertension (HT) (DMT2HTN) and without HT (DMT2). Also, their association with certain biochemical and physical factors were studied to identify possible risk factors that lead to cardiovascular complications.
Methods: Fasting blood samples were collected from 35 DMT2 or DMT2HTN patients each to analyze differences in serum and plasma levels of IMA, hs-CRP, FIB, total cholesterol (TC), high and low density lipoproteins (HDL and LDL), triglyceride (TG), hemoglobin A1c (HbA1C), glycated hemoglobin and creatinine.
Results: In DMT2 and DMT2HTN patients, IMA, hs-CRP, FIB, TC, TG, HDL, LDL, glycated hemoglobin and creatinine levels, including body mass index (BMI) and waist-to-hip ratio (WHR), were significantly higher relative to healthy controls. In addition, the levels of IMA, hs-CRP and FIB levels showed a strong link to BMI, WHR, TC, TG, LDL and glycated hemoglobin. Lastly, both DMT2 and DMT2HTN patients demonstrated a significant reduction in HDL.
Conclusion: DMT2 and DMT2HTN patients have a greater risk of developing cardiovascular related complications. This study suggests that quantifying hs-CRP, IMA and FIB levels can help diagnose the risk of developing complications during the early stages of metabolic and cardiovascular disease. Overall, the specific risk factors may be used for early identification of cardiovascular complications to decrease mortality and morbidity in T2DM patients.

Matched MeSH terms: Fibrinogen
The incidence of postoperative deep vein thrombosis in Malaysia

Cunningham IG, Yong NK

Br J Surg, 1974 Jun;61(6):482-3.
PMID: 4835202
Matched MeSH terms: Fibrinogen
Using sosial cognitive theory to understand exercise maintenance in women breast cancer survivors adopting Guolin Qigong

Nadiah Diyana Tan Abdullah, Khor, Poy Hua, Mazanah Muhamad

Movement Health & Exercise, 2013;2(1):47-52.
MyJurnal

The purpose of this study is to explore and understand the exercise maintenance in women with breast cancer survivors adopting Guolin Qigong using the Social Cognitive Theory related constructs. A qualitative approach using in-depth interviews were employed in this study. 22 participants of the Malaysia Guolin Qigong Association from five regions in Peninsular Malaysia were purposely selected to participate in this study. Data was collected through a series of audiotapes during the interview sessions. They were asked on how do they maintain in their Guolin Qigong exercise. Three themes related to the Social Cognitive Theory constructs emerged from the data collected. (i) Personal Factors; (ii) Environmental Factors and (iii) Tailored Program. The belief in Guolin Qigong or in an exercise program is crucial in helping one to maintain with the exercise program and this findings is consistent with literature that those responded favourably to an exercise will have greater positive attitudes to exercise maintenance. To keep these women maintain the exercise it is important that these women have friends who understand them better to share their experiences related to their disease. It has been suggested that connecting to other survivors contributes to the survivors' positive well-being and to deal with their everyday living. Lastly, the type of exercise should be tailored to the physical condition of these women to keep them sustain the exercise. This theory can be used by the health practitioners to develop more effective interventions for increasing exercise maintenance in sedentary cancer survivors by taking into special attention personal factors particularly one's beliefs and inner motivation. Having to embark and engage into an exercise program of their preferred choice will help one to maintain an exercise program.

Matched MeSH terms: Fibrinogen
Fulltext Factors influencing consumer intentions to avoid broiler chicken meat and products in Malaysia

Huang, L.C., Goh, Y.N., Mohaidin, Z.

International Food Research Journal, 2014;21(1):181-188.
MyJurnal

Reports of bird flu outbreaks occur around the globe, posing a severe threat to the poultry
industry and consumer health. Despite the number of bird flu scares, few studies have
considered the impact on consumers’ chicken consumption intentions in a non-western context,
such as in Malaysia. The aim of this study is to determine the factors that influence consumers’
intentions to take precautions by avoiding the consumption of broiler chicken meat and
products in Malaysia when a bird flu outbreak occurs. A total of 276 online questionnaires were
disseminated using convenience sampling with 109 respondents completing the questionnaires, generating a response rate of 40.8 percent. The study results show that attitudes, subjective norms, perceived behavioral control, perceived credibility of information, and perceived risk have a significant relationship with consumer intentions to take precautions by avoiding the consumption of broiler chicken meat and products. One factor is the exception: attention towards bird flu news. These findings shed some light on understanding the extent of consumer response (i.e. consumption behavior) to future health crises (e.g. bird flu). Moreover, for policy makers, these findings may serve as a guide and a reference to food safety issues in the poultry industry, especially future bird flu scares.

Matched MeSH terms: Fibrinogen
Fulltext A Single Centre Annual Audit on Computed Tomography Pulmonary Angiogram: Demographic, Clinical Scoring System, Patients’ Outcome

Low Qin Jian, Teo Kuo Zhau, Mohd Nadzri Misni, Cheo Seng Wee

Borneo Journal of Medical Sciences, 2020;14(2):11-18.
MyJurnal

Computed tomography pulmonary angiogram (CTPA) is widely used in the investigation of suspected pulmonary embolism. CTPA is not without adverse effects as it involves intravenous contrast injection and radiation exposure. The annual incidence of pulmonary embolism is 60 – 70 per 100,000 populations and CTPA remains the commonest imaging modality1. This study aims to audit all CTPA performed at Hospital Sultanah Nora Ismail, Batu Pahat, Johor for the entire year of 2018 to illustrate the demographic data, symptoms, risk factors, clinical scoring system applied and patients’ outcome. A retrospective study was conducted to audit all CTPA performed between 1st January to 31st December 2018 via the radiology department electronic records and patients’ records. There were a total of 60 CTPA performed in the entire year of 2018 with 16 positive and 44 negative scans. Among the 16 positive scans, 7 (44%) had a Wells score above 6, 6 (38%) had a Wells score between 2 – 6 and 3 (18%) had a Wells score less than 2. Out of the 16 positive scans, 4 (25%) were known malignancy and 1 was a known case of anti-phospholipid syndrome. All 60 patients had electrographs and arterial blood gases performed prior to CTPA. D dimer was performed in 15 cases (5%). Among the 16 positive scan patients, 4 (25%) passed away during the same admission directly or indirectly related to pulmonary embolism. This annual computed tomography audit report will assist clinicians in making better diagnostic decision when dealing with patients with suspected pulmonary embolism.

Matched MeSH terms: Fibrin Fibrinogen Degradation Products
Fulltext The development of friendship instrument in chemistry and engagement of school of quantitative sciences in Universiti Utara Malaysia (UUM) students

Nurul Izzati Binti Hasnun, Nurul Aziera Binti Zainol Abidin, Nurhana Binti Roslan, Mohamad Shukri Bin Abdul Hamid

Malaysian Journal of Social Sciences and Humanities, 2019;4(8):85-112.
MyJurnal

Friendship is a topic that should be emphasized and studied, and it can be positive or negative. There are many forms of friendship that can be termed, but it may also differ from one's perspective and certain characteristics of a person. The value of friendship is very important to study in order to know the level of our friendships. In college student development, peer influence can also influence student engagement in engaging in their college activities. It can be seen in terms of involvement in sports activities, curriculum activities and more. The main purpose of this study was to develop of Friendship instrument in chemistry and engagement of SQS UUM students and find the relationships between genders with chemistry and engagement. Using Factor Analysis in order to develop valid and reliable of the friendship Instrument based on chemistry and engagement. In order to study the validity of the data, face validity was used before the instrument was distributed in which the pilot study was conducted. To determine which factor is best, the analysis uses varimax rotation and selects which component is best and meets the criteria. Normality test was used to find the data was normal or nonnormal. Spearman Correlation and Chi Square Test method used in the non-normal data to find the relationship of selected variables.

Matched MeSH terms: Fibrinogen
Fulltext Serotype-specific host responses in rhesus macaques after primary dengue challenge

Hickey AC, Koster JA, Thalmann CM, Hardcastle K, Tio PH, Cardosa MJ, et al.

Am J Trop Med Hyg, 2013 Dec;89(6):1043-57.
PMID: 24062475 DOI: 10.4269/ajtmh.13-0145

Dengue virus (DENV) is considered to be the most important arthropod-borne viral disease and causes more than 100 million human infections annually. To further characterize primary DENV infection in vivo, rhesus macaques were infected with DENV-1, DENV-2, DENV-3, or DENV-4 and clinical parameters, as well as specificity and longevity of serologic responses, were assessed. Overt clinical symptoms were not present after infection. However, abnormalities in blood biochemical parameters consistent with heart, kidney, and liver damage were observed, and changes in plasma fibrinogen, D-dimers, and protein C indicated systemic activation of the blood coagulation pathway. Significant homotypic and heterotypic serum immunoglobulins were present in all animals, and IgG persisted for at least 390 days. Serum neutralizing antibody responses were highly serotype specific by day 120. However, some heterotypic neutralizing activity was noted in infected animals. Identification of serotype-specific host responses may help elucidate mechanisms that mediate severe DENV disease after reinfection.

Matched MeSH terms: Fibrin Fibrinogen Degradation Products/analysis; Fibrinogen/analysis
Fulltext Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease

Williams HF, Mellows BA, Mitchell R, Sfyri P, Layfield HJ, Salamah M, et al.

PLoS Negl Trop Dis, 2019 Jan;13(1):e0007041.
PMID: 30695027 DOI: 10.1371/journal.pntd.0007041

Snakebite is a major neglected tropical health issue that affects over 5 million people worldwide resulting in around 1.8 million envenomations and 100,000 deaths each year. Snakebite envenomation also causes innumerable morbidities, specifically loss of limbs as a result of excessive tissue/muscle damage. Snake venom metalloproteases (SVMPs) are a predominant component of viper venoms, and are involved in the degradation of basement membrane proteins (particularly collagen) surrounding the tissues around the bite site. Although their collagenolytic properties have been established, the molecular mechanisms through which SVMPs induce permanent muscle damage are poorly understood. Here, we demonstrate the purification and characterisation of an SVMP from a viper (Crotalus atrox) venom. Mass spectrometry analysis confirmed that this protein is most likely to be a group III metalloprotease (showing high similarity to VAP2A) and has been referred to as CAMP (Crotalus atrox metalloprotease). CAMP displays both collagenolytic and fibrinogenolytic activities and inhibits CRP-XL-induced platelet aggregation. To determine its effects on muscle damage, CAMP was administered into the tibialis anterior muscle of mice and its actions were compared with cardiotoxin I (a three-finger toxin) from an elapid snake (Naja pallida) venom. Extensive immunohistochemistry analyses revealed that CAMP significantly damages skeletal muscles by attacking the collagen scaffold and other important basement membrane proteins, and prevents their regeneration through disrupting the functions of satellite cells. In contrast, cardiotoxin I destroys skeletal muscle by damaging the plasma membrane, but does not impact regeneration due to its inability to affect the extracellular matrix. Overall, this study provides novel insights into the mechanisms through which SVMPs induce permanent muscle damage.

Matched MeSH terms: Fibrinogen/metabolism
[Effect of Arvin on blood coagulation]

Vinazzer H

Wien Z Inn Med, 1971;52(8):378-92.
PMID: 5110844
Matched MeSH terms: Afibrinogenemia/etiology; Fibrinogen/metabolism
Patients with congenital hypothyroidism demonstrate different altered expression of plasma fibrinogen and haptoglobin polypeptide chains

Yong PH, Junit SM, Harun F, Hashim OH

Clin Biochem, 2006 Feb;39(2):126-32.
PMID: 16412408

To compare the plasma protein profiles of treated and untreated congenital hypothyroidism (CH) patients with those of normal control infants.

Matched MeSH terms: Fibrinogen/metabolism*
Fulltext Combined protein- and nucleic acid-level effects of rs1143679 (R77H), a lupus-predisposing variant within ITGAM

Maiti AK, Kim-Howard X, Motghare P, Pradhan V, Chua KH, Sun C, et al.

Hum Mol Genet, 2014 Aug 01;23(15):4161-76.
PMID: 24608226 DOI: 10.1093/hmg/ddu106

Integrin alpha M (ITGAM; CD11b) is a component of the macrophage-1 antigen complex, which mediates leukocyte adhesion, migration and phagocytosis as part of the immune system. We previously identified a missense polymorphism, rs1143679 (R77H), strongly associated with systemic lupus erythematosus (SLE). However, the molecular mechanisms of this variant are incompletely understood. A meta-analysis of published and novel data on 28 439 individuals with European, African, Hispanic and Asian ancestries reinforces genetic association between rs1143679 and SLE [Pmeta = 3.60 × 10(-90), odds ratio (OR) = 1.76]. Since rs1143679 is in the most active region of chromatin regulation and transcription factor binding in ITGAM, we quantitated ITGAM RNA and surface protein levels in monocytes from patients with each rs1143679 genotype. We observed that transcript levels significantly decreased for the risk allele ('A') relative to the non-risk allele ('G'), in a dose-dependent fashion: ('AA' < 'AG' < 'GG'). CD11b protein levels in patients' monocytes were directly correlated with RNA levels. Strikingly, heterozygous individuals express much lower (average 10- to 15-fold reduction) amounts of the 'A' transcript than 'G' transcript. We found that the non-risk sequence surrounding rs1143679 exhibits transcriptional enhancer activity in vivo and binds to Ku70/80, NFKB1 and EBF1 in vitro, functions that are significantly reduced with the risk allele. Mutant CD11b protein shows significantly reduced binding to fibrinogen and vitronectin, relative to non-risk, both in purified protein and in cellular models. This two-pronged contribution (nucleic acid- and protein-level) of the rs1143679 risk allele to decreasing ITGAM activity provides insight into the molecular mechanisms of its potent association with SLE.

Matched MeSH terms: Fibrinogen/genetics; Fibrinogen/metabolism
Isolation and characterization of the thrombin-like enzyme from Cryptelytrops albolabris (white-lipped tree viper) venom

Tan NH, Fung SY, Yap YH

Comp Biochem Physiol B Biochem Mol Biol, 2012 Jan;161(1):79-85.
PMID: 21983189 DOI: 10.1016/j.cbpb.2011.09.009

A thrombin-like enzyme (termed albolabrase) was isolated in purified form from the venom of Cryptelytrops albolabris (white-lipped tree viper) using high performance anion ion exchange and gel filtration chromatography. The molecular mass of albolabrase was 33.7 kDa as determined by SDS-PAGE and 35.8 kDa as determined by Superose gel filtration chromatography. The N-terminal sequence was determined to be VVGGDECNINE which is homologous to many snake venom thrombin-like enzymes. Albolabrase exhibits both arginine ester hydrolase and arginine amidase activities and the enzyme is fastidious towards tripeptide chromogenic anilide substrates. The fibrinogen clotting activity was optimum at 3mg/mL bovine fibrinogen, and showed distinct species differences in the following decreasing order: bovine fibrinogen>dog fibrinogen≈human fibrinogen>goat fibrinogen. The enzyme failed to clot both rabbit and cat fibrinogens. Reversed-phase HPLC analysis on the breakdown products of fibrinogenolytic action of albolabrase indicated that the enzyme belongs to the AB class of snake venom thrombin-like enzyme. In the indirect ELISA, IgG anti-albolabrase reacted extensively with most crotalid venoms, except with Tropidolaemus wagleri and Calloselasma rhodostoma venoms. The double sandwich ELISA, however, showed that anti-albolabrase reacted strongly only with venoms from the Trimeresurus complex, and that the results support the proposed new taxonomy changes concerning the Trimeresurus complex.

Matched MeSH terms: Fibrinogen/pharmacology
Fulltext Asymptomatic tachycardia and acute pulmonary embolism in a case of tuberculosis spondylodiscitis

Ahmedy F, Ahmad Fauzi A, Engkasan JP

Spinal Cord Ser Cases, 2018;4:43.
PMID: 29844926 DOI: 10.1038/s41394-018-0074-7

Introduction: Tachycardia, or elevated heart rate is one of the important clinical parameters considered when diagnosing pulmonary embolism (PE) based on Wells' criteria. However, tachycardia is not highly specific and commonly presents in many other conditions.
Case presentation: A 29-year-old female with incomplete paraplegia secondary to tuberculosis (TB) spondylodiscitis presented with asymptomatic sinus tachycardia. The related medical conditions, including anaemia, acute coronary syndrome, hyperthyroidism and other infective causes had been ruled out. Deep venous thrombosis was not on the list of differentials as she showed improvements in neurological and mobility functions with no clinical signs of calf pain or swelling. She had moderate risk of acute PE based on Wells' criteria with positive D-dimer testing and computed tomography pulmonary angiography (CTPA) showing thrombus formation in the left-ascending pulmonary artery.
Discussion: Acute PE may present solely with asymptomatic sinus tachycardia in TB spondylodiscitis. This caveat should provide a high index of suspicion to prevent delay in diagnosis and prevention of more sinister complications. Early stratification based on Wells' criteria for a possible diagnosis of acute PE is proven to be a useful approach in conjunction with clinical features.

Matched MeSH terms: Fibrin Fibrinogen Degradation Products

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