Beta-Thromboglobulin (βTG) And Platelet Factor 4 (PF4) In Patients With Acute Myocardial Infarction (M.I.)

βTG and PF4 were measured by RIA in 22 patients within 12 hours from the onset of the illness and thereafter daily for 7 days. βTG and PF4 plasma levels showed a sharp increase within two days from M.I. in 19 (87%) patients. In 13 of these subjects these values returned in the normal range in 3-4 days, showing often a second peak on the 5th-6th days (silent deep vein thrombosis ?) . Patients with persistent high values of βTG and PF4 always had clinical and electrocardiographic signs of persistent myocardial ischaemia. βTG and PF4 plasma levels were not in correlation neither with the extent of the necrosis (as derived from electrocardiographic and enzymatic data) nor with some complications as arrytmias or pump failure. These data do not support the hypothesis that the increased values of βTG and PF4 in these patients must be referred to mural thrombus formation. In fact, this event is uncostant and usually associated with massive trnsmural necrosis. We suggest that platelet activation is associated with myocardial ischaemia rather than necrosis but it is unclear if this is a primary or a secondary phenomenon.

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Transcriptome profiling reveals the endogenous sponging role of LINC00659 and UST-AS1 in high altitude induced thrombosis

Thrombosis and Haemostasis ◽

10.1055/a-1390-1713 ◽

2021 ◽

Author(s):

Prabhash Kumar Jha ◽

Aatira Vijay ◽

Amit Prabhakar ◽

Tathagata Chatterjee ◽

Velu Nair ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

High Altitude ◽

Expression Profile ◽

Thrombus Formation ◽

Pearson Correlation ◽

Coagulation Cascade ◽

Protein Coding ◽

Vein Thrombosis ◽

Protein Coding Genes ◽

Deep Vein

Background: The pathophysiology of Deep vein thrombosis (DVT) is considered as multifactorial, where thrombus formation is interplay of genetic and acquired risk factors. A little is known about the expression profile and roles of lncRNAs in human subjects developing DVT at high altitude. Methods: Using RNAseq, we compared peripheral blood mRNA and lncRNA expression profile in human High Altitude deep Vein Thrombosis (HA-DVT) patients with high altitude control subjects. We used DESeq to identify differentially expressed (DE) genes. We annotated the long noncoding RNAs using NONCODE 3.0 database. In silico putative lncRNA-miRNA association study unravels the endogenous miRNA sponge associated with our candidate lncRNAs. These findings were validated by siRNA knockdown assay of the candidate lncRNAs conducted in primary endothelial cells. Results: We identified 1524 DE mRNA and 973 DE lncRNAs. Co-expressed protein-coding genes analysis resulted in a list of 722 coexpressed protein-coding genes with a Pearson correlation coefficients >0.7. The functional annotation of co-expressed genes and putative proteins revealed their involvement in the hypoxia, immune response and coagulation cascade. Through its miRNA response elements (MREs) to compete for miR-143 and miR-15, lncRNA-LINC00659 and UXT-AS1 regulates the expression of prothrombotic genes. Furthermore, in vitro RNA interference (siRNA) simultaneously suppressed lncRNAs and target gene mRNA level. Conclusions: This transcriptome profile describes novel potential mechanisms of interaction between lncRNAs, the coding genes, miRNAs and regulatory transcription factors that define the thrombotic signature and may be used in establishing lncRNAs as biomarker in HA-DVT.

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Correction: preventing and treating deep vein thrombosis (3 February, pages 9–12)

Drug and Therapeutics Bulletin ◽

10.1136/dtb.30.16.64 ◽

1992 ◽

Vol 30 (16) ◽

pp. 64-64

Keyword(s):

Deep Vein Thrombosis ◽

Normal Range ◽

Control Value ◽

Vein Thrombosis ◽

Upper Limit ◽

Dose Heparin ◽

Deep Vein ◽

Adjusted Dose ◽

Prophylaxis Strategy

In the table entitled ‘Anti-thrombotic prophylaxis strategy’ we gave the desired APTT range for the ‘adjusted dose heparin regimen’ as 1.5–2.5 times the control value. The aim should be to maintain the APTT at 1.5 times control (upper limit of ‘normal’ range), and no higher.

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Abstract 14771: Iron Plays a Role in the Thrombus Formation of a Rat Model of Deep Vein Thrombosis

Circulation ◽

10.1161/circ.130.suppl_2.14771 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Makiko Oboshi ◽

Yoshiro Naito ◽

Hisashi Sawada ◽

Toshihiro Iwasaku ◽

Yoshitaka Okuhara ◽

...

Keyword(s):

Gene Expression ◽

Deep Vein Thrombosis ◽

Cardiovascular Diseases ◽

Rat Model ◽

Thrombus Formation ◽

Dietary Iron ◽

Iron Restriction ◽

Vein Thrombosis ◽

Type Plasminogen Activator ◽

Deep Vein

Introduction: Deep vein thrombosis (DVT) is a major cause of pulmonary thromboembolism. On the other hand, iron is an essential element for maintaining physiological homeostasis in the body, whereas excess iron leads to toxicity and free radical damage. Hence, iron accumulation is associated with the pathogenesis of several cardiovascular diseases. We have previously reported that dietary iron restriction (IR) prevents the development of hypertension and chronic kidney disease (CKD) in animal models of several cardiovascular diseases. In addition, we have shown that intracellular iron transport protein, transferrin receptor 1 (TfR1), is involved in the mechanism of several cardiovascular diseases. In this study, we hypothesized that iron and TfR1 play roles in the pathogenesis of DVT. We investigate the effects of dietary IR on the thrombus formation and resolution in a rat model of DVT. Methods: We performed the ligation of inferior vena cava to induce DVT in 8-week-old male Sprague-Dawley rats. After the ligation, rats were given either a normal diet (DVT group) or iron-restricted diet (DVT+IR group). The thrombus was harvested at 5days after the ligation. Results: At first, TfR1 expression was increased in the thrombus of a rat model of DVT, suggesting that iron and TfR1 play roles in the pathogenesis of DVT. Interestingly, dietary iron restriction reduced the thrombus size compared with the DVT group (180±17 mg/cm vs 135±13 mg/cm, DVT vs DVT+IR ; p < 0.05). Intrathrombotic collagen content was diminished in the DVT+IR group compared with the DVT group. Intrathrombotic gene expression and activity of matrix metalloproteinase (MMP)-9 were increased in the DVT+IR group compared with the DVT group. In addition, the numbers of CD68 positive cells in the thrombus were fewer in the DVT+IR group than in the DVT group. Furthermore, intrathrombotic gene expression of urokinase-type plasminogen activator and tissue-type plasminogen activator was higher in the DVT+IR group than in the DVT group. Conclusions: These results suggest that iron plays a role in the pathogenesis of DVT.

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Establishing a normal range for d-dimer levels through pregnancy to aid in the diagnosis of pulmonary embolism and deep vein thrombosis

Journal of Thrombosis and Haemostasis ◽

10.1111/j.1538-7836.2004.00776.x ◽

2004 ◽

Vol 2 (7) ◽

pp. 1202-1204 ◽

Cited By ~ 60

Author(s):

M. Morse

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Normal Range ◽

Vein Thrombosis ◽

Deep Vein ◽

D Dimer

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Abstract 54: Peptidylarginine Deiminase 4-dependent Generation of Neutrophil Extracellular Traps is Crucial for Deep Vein Thrombosis in Mice

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.33.suppl_1.a54 ◽

2013 ◽

Vol 33 (suppl_1) ◽

Author(s):

Kimberly Martinod ◽

Melanie Demers ◽

Tobias A Fuchs ◽

Siu Ling Wong ◽

Alexander Brill ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Thrombus Formation ◽

Vena Cava ◽

Peptidylarginine Deiminase ◽

Wild Type ◽

Chromatin Decondensation ◽

Peptidylarginine Deiminase 4 ◽

Vein Thrombosis ◽

Deep Vein ◽

Deficient Mice

Introduction Histone hypercitrullination by the enzyme peptidylarginine deiminase 4 (PAD4) leads to nuclear chromatin decondensation that is needed for neutrophil extracellular trap (NET) formation. NETs consist of chromatin and granule proteins that are released into the extracellular environment. NETs were shown to be involved in thrombosis by promoting coagulation and platelet adhesion and were identified in the thrombus scaffold in animal models of deep vein thrombosis (DVT). Objective Whether NETs are involved in the pathogenesis of DVT or whether they are merely a consequence of neutrophil recruitment to the thrombus is unknown. We hypothesized that NET formation would be impaired in PAD4-deficient mice during deep vein thrombosis and that this may affect thrombus formation and/or stability. Methods PAD4-deficient mice are incapable of citrullinating histones and therefore fail to decondense chromatin during NETosis. We performed the inferior vena cava stenosis model of DVT in wild-type or PAD4-/- mice. Intravital microscopy was done to assess leukocyte vessel wall interaction in PAD4 deficiency. Results We induced NET formation in isolated peripheral blood mouse neutrophils with ionomycin and found that PAD4-/- neutrophils had a complete inability to produce NETs (WT, 20.65±2.61% NETs; PAD4-/-, not detected. n=4). Leukocyte-endothelial interactions in PAD4-/- mice were not impaired upon induction of systemic Weibel-Palade body release (WT, 55.2±11.8; PAD4-/-, 62.0±17.5 cells/min, n=5-6). In the DVT model, while a majority (9/10) of wild-type mice formed a thrombus 48 hours after stenosis, only 1 of 11 PAD4-/- mice formed a thrombus. Thrombus formation could be rescued by infusions of isolated WT bone marrow neutrophils into PAD4-/- mice, and extracellular H3Cit+ areas were seen within these thrombi. This data suggests that neutrophil PAD4 was essential for thrombus formation in deep veins. Conclusion NETs comprise a crucial part of the pathologic thrombus scaffold, and here we report that the lack of NETs inhibits pathological thrombosis. Chromatin decondensation initiated by PAD4 in neutrophils is a key player in the formation of deep vein thrombi and targeting neutrophil histone modification could be a new way to prevent DVT.

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Increase of Thrombin-Antithrombin III (TAT) Complex Plasma Levels in Thromboembolic Diseases during Thrombolysis

10.1055/s-0038-1643676 ◽

1987 ◽

Author(s):

R Seitz ◽

G Pratorius ◽

R Blanke ◽

B B Strauer

Keyword(s):

Thrombolytic Therapy ◽

Plasma Levels ◽

Vein Thrombosis ◽

Complex Plasma ◽

In Vitro Effects ◽

Immuno Assay ◽

Enzyme Immuno Assay ◽

Deep Vein

Recently an enzyme immuno assay of thrombin-antithrombinlll complex (TAT) plasma levels was developed by PELZER et al. (Thromb. Haemost. 54:24,1985). This test appears to be useful in the detection of intravasal thrombin generation, since all of 17 patients (pts.) with pulmonary embolism and 15 of 16 pts. with deep vein thrombosis (DVT) showed elevated values above 3 ng/ml.In 9 pts. with acute myocardial infarction (AMI) the TAT levels increased significantly (p 0.001) 3 to 6 hours after thrombolytic therapy with 1.5 million units streptokinase (SK) over 30 minutes. A concomitant increase of fibrinopeptide A (FPA) levels (p=0.048) was observed. In contrast, 8 AMI pts. treated with heparin showed an insignificant increase of TAT and FPA. In 7 DVT pts. the TAT levels rose significantly (p 0.001) within 6 hours after start of urokinase (UK) infusion, while the FPA levels were enhanced prior to treatment and showed no further increase.In order to assess the in vitro effects of SK and UK on TAT levels, clots obtained by recalcification of citrated plasma were incubated in heparin (2 units/ml) plasma. An increase of TAT occurred after addition of SK or UK, which was less pronounced when the clots were rinsed extensivly or squeezed before incubation. When SK or UK were added to plasma in the absence of a clot, still a small increase of TAT occurred which was absent in saline controls.The data suggest that SK and UK action is associated with the generation of TAT complexes. In vivo, thrombin or thromboplastic material might be released by enhanced "wash out" from the recanalized coronary artery or from the reperfused in-farcted myocardium. Thrombin might also be released from binding sites on fibrin clots or fibrinogen. It is conceivable that these findings contribute to the understanding of reocclusion of infarct vessels after thrombolytic therapy. This points to the importance of careful anticoagulation in patients receiving thrombolytic therapy.

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Prevention effect of orally active heparin derivative on deep vein thrombosis

Thrombosis and Haemostasis ◽

10.1160/th06-02-0077 ◽

2006 ◽

Vol 96 (08) ◽

pp. 149-153 ◽

Cited By ~ 12

Author(s):

Sang Kim ◽

Dong Lee ◽

Choong Kim ◽

Hyun Moon ◽

Youngro Byun

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Venous Thrombosis ◽

Thrombus Formation ◽

Sprague Dawley ◽

Vein Thrombosis ◽

Sprague Dawley Rats ◽

Acid Conjugate ◽

Deep Vein ◽

Orally Active

SummaryThe use of heparin as the most potent anticoagulant for the prevention of deep vein thrombosis and pulmonary embolism is nevertheless limited, because it is available to patients only by parenteral administration. Toward overcoming this limitation in the use of heparin, we have previously developed an orally active heparin-deoxycholic acid conjugate (LMWH-DOCA) in 10% DMSO formulation. The present study evaluates the anti-thrombogenic effect of this orally active LMWH-DOCA using a venous thrombosis animal model with Sprague-Dawley rats. When 5 mg/kg of LMWH-DOCA was orally administered in rats, the maximum anti-FXa activity in plasma was 0. 35 ± 0. 02, and anti-FXa activity in plasma was maintained above 0. 1 IU/ml [the minimum effective anti-FXa activity for the prevention of deep venous thrombosis (DVT) and pulmonary embolism (PE)] for five hours. LMWH-DOCA (5 mg/kg, 430 IU/kg) that was orally administered reduced the thrombus formation by 56. 3 ± 19. 8%;on the other hand, subcutaneously administered enoxaparin (100 IU/kg) reduced the thrombus formation by 36. 4 ± 14. 5%. Also, LMWH-DOCA was effectively neutralized by protamine that was used as an antidote. Therefore, orally active LMWH-DOCA could be proposed as a new drug that is effective for the longterm prevention of DVT and PE.

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