MyMedR

Displaying all 7 publications

Abstract:

Sort:

Cerebral venous thrombosis associated with antithrombin III deficiency

Lee MK, Ng SC

Aust N Z J Med, 1991 Oct;21(5):772-3.
PMID: 1759929
Matched MeSH terms: Intracranial Embolism and Thrombosis/blood*
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: Thrombosis/blood
Fulltext An in-house ELISA method for quantification of circulating tissue factor

Tay SP, Cheong SK

Malays J Pathol, 2002 Jun;24(1):45-51.
PMID: 16329555

Tissue Factor (TF) is a low molecular weight transmembrane glycoprotein that initiates the clotting protease cascade. It is considered to be the principal regulator of the extrinsic coagulation pathway, hemostasis and thrombosis, as well as inflammation and cellular immune response. An in-house two-step direct sandwich ELISA (enzyme-linked immunosorbent assay) for immunological quantification of plasma TF was successfully developed. The assay employed a monoclonal antibody against human TF (1:400 dilution; 1250 ng/ml) and peroxidase-conjugated anti-TF IgG (1:1000 dilution; 2000 ng/ml) as capture and detecting antibodies respectively, whilst tetramethylbenzidine/H2O2 were utilized as substrates. Titration curves of recombinant TF were linear within 10 to 4000 pg/ml, with a detection limit of 36.31 pg/ml. It demonstrated low intra- (2.50 - 9.23 CV%) and inter-assays (5.65 - 13.57 CV%) variability, as well as satisfactory analytical recovery (91.55 - 103.95%) and good parallelism. The assay developed was intended to be applied for measurement of plasma TF levels in patients with thrombotic disorders.

Matched MeSH terms: Thrombosis/blood
Fulltext The formyl peptide fMLF primes platelet activation and augments thrombus formation

Salamah MF, Ravishankar D, Vaiyapuri R, Moraes LA, Patel K, Perretti M, et al.

J Thromb Haemost, 2019 Jul;17(7):1120-1133.
PMID: 31033193 DOI: 10.1111/jth.14466

Essentials The role of formyl peptide receptor 1 (FPR1) and its ligand, fMLF, in the regulation of platelet function, hemostasis, and thrombosis is largely unknown. Fpr1-deficient mice and selective inhibitors for FPR1 were used to investigate the function of fMLF and FPR1 in platelets. N-formyl-methionyl-leucyl-phenylalanine primes platelet activation and augments thrombus formation, mainly through FPR1 in platelets. Formyl peptide receptor 1 plays a pivotal role in the regulation of platelet function.
BACKGROUND: Formyl peptide receptors (FPRs) play pivotal roles in the regulation of innate immunity and host defense. The FPRs include three family members: FPR1, FPR2/ALX, and FPR3. The activation of FPR1 by its high-affinity ligand, N-formyl-methionyl-leucyl-phenylalanine (fMLF) (a bacterial chemoattractant peptide), triggers intracellular signaling in immune cells such as neutrophils and exacerbates inflammatory responses to accelerate the clearance of microbial infection. Notably, fMLF has been demonstrated to induce intracellular calcium mobilization and chemotaxis in platelets that are known to play significant roles in the regulation of innate immunity and inflammatory responses. Despite a plethora of research focused on the roles of FPR1 and its ligands such as fMLF on the modulation of immune responses, their impact on the regulation of hemostasis and thrombosis remains unexplored.
OBJECTIVE: To determine the effects of fMLF on the modulation of platelet reactivity, hemostasis, and thrombus formation.
METHODS: Selective inhibitors for FPR1 and Fpr1-deficient mice were used to determine the effects of fMLF and FPR1 on platelets using various platelet functional assays.
RESULTS: N-formyl-methionyl-leucyl-phenylalanine primes platelet activation through inducing distinctive functions and enhances thrombus formation under arterial flow conditions. Moreover, FPR1 regulates normal platelet function as its deficiency in mouse or blockade in human platelets using a pharmacological inhibitor resulted in diminished agonist-induced platelet activation.
CONCLUSION: Since FPR1 plays critical roles in numerous disease conditions, its influence on the modulation of platelet activation and thrombus formation may provide insights into the mechanisms that control platelet-mediated complications under diverse pathological settings.

Matched MeSH terms: Thrombosis/blood
Fulltext The endogenous antimicrobial cathelicidin LL37 induces platelet activation and augments thrombus formation

Salamah MF, Ravishankar D, Kodji X, Moraes LA, Williams HF, Vallance TM, et al.

Blood Adv, 2018 11 13;2(21):2973-2985.
PMID: 30413433 DOI: 10.1182/bloodadvances.2018021758

Platelet-associated complications including thrombosis, thrombocytopenia, and hemorrhage are commonly observed during various inflammatory diseases such as sepsis, inflammatory bowel disease, and psoriasis. Despite the reported evidence on numerous mechanisms/molecules that may contribute to the dysfunction of platelets, the primary mechanisms that underpin platelet-associated complications during inflammatory diseases are not fully established. Here, we report the discovery of formyl peptide receptor 2, FPR2/ALX, in platelets and its primary role in the development of platelet-associated complications via ligation with its ligand, LL37. LL37 acts as a powerful endogenous antimicrobial peptide, but it also regulates innate immune responses. We demonstrate the impact of LL37 in the modulation of platelet reactivity, hemostasis, and thrombosis. LL37 activates a range of platelet functions, enhances thrombus formation, and shortens the tail bleeding time in mice. By utilizing a pharmacological inhibitor and Fpr2/3 (an ortholog of human FPR2/ALX)-deficient mice, the functional dependence of LL37 on FPR2/ALX was determined. Because the level of LL37 is increased in numerous inflammatory diseases, these results point toward a critical role for LL37 and FPR2/ALX in the development of platelet-related complications in such diseases. Hence, a better understanding of the clinical relevance of LL37 and FPR2/ALX in diverse pathophysiological settings will pave the way for the development of improved therapeutic strategies for a range of thromboinflammatory diseases.

Matched MeSH terms: Thrombosis/blood
Effect of menopause on platelet activation markers determined by flow cytometry

Roshan TM, Normah J, Rehman A, Naing L

Am J Hematol, 2005 Dec;80(4):257-61.
PMID: 16315264

Pre-menopausal women have a lower risk of cardiovascular disease compared to post-menopausal women. Cardiovascular disease is more age dependent in women than in men. The association of platelet activation and cardiovascular thrombotic events is well established. Standardized techniques were used to evaluate platelet activation markers by flow cytometry, using 3-color analysis (CD 61PerCP, CD 62P, and PAC-1) in 49 post-menopausal (mean +/- SD age, 56.16 +/- 33.51 years) and 42 pre-menopausal (age, 39.38 +/- 7.07 years) women. Results of our study showed a significant increase in CD 62P in post-menopausal women as compared to the pre-menopausal group (2.66 +/- 4.26% vs. 0.52 +/- 2.71%, P < 0.001). Similarly, PAC-1 was significantly increased in post-menopausal women (21.54 +/- 2.48% vs. 3.70 +/- 2.31%, P < 0.001). Furthermore, there was a significant association of CD 62P with serum estradiol in both groups. PAC-1 was significantly associated with age in both groups. The results suggest the role of platelets in the increased incidence of thrombotic events and disease in post-menopausal women.

Matched MeSH terms: Thrombosis/blood
Effects of amount and type of dietary fats on postprandial lipemia and thrombogenic markers in individuals with metabolic syndrome

Teng KT, Chang CY, Kanthimathi MS, Tan AT, Nesaretnam K

Atherosclerosis, 2015 Sep;242(1):281-7.
PMID: 26232169 DOI: 10.1016/j.atherosclerosis.2015.07.003

Postprandial lipemia has been reported to affect endothelial function by thrombogenic and inflammatory pathways. We set out to investigate the impact of a) specific amount (50 g vs 20 g fat), and b) type of fatty acids (saturated, monounsaturated or n-6 polyunsaturated fatty acids; SFA, MUFA, PUFA) on postprandial lipemia, thrombogenic and inflammatory factors in metabolic syndrome subjects.

Matched MeSH terms: Thrombosis/blood