P-selectin inhibition decreases post-thrombotic vein wall fibrosis in a rat model

Thanaporn, Porama; Myers, Daniel D.; Wrobleski, Shirley K.; Hawley, Angela E.; Farris, Diana M.; Wakefield, Thomas W.; Henke, Peter K.

doi:10.1067/msy.2003.249

Cited by 43 publications

(35 citation statements)

References 20 publications

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“…The dosages were based on prior experimental studies in rats. 19,20 This strategy allowed comparison of the timing of the LMWH, and we acknowledge that the prethrombosis dosing was not at prophylactic levels.…”

Section: Methodsmentioning

confidence: 99%

Vein wall re-endothelialization after deep vein thrombosis is improved with low-molecular-weight heparin

Moaveni

Lynch

Luke

et al. 2008

Journal of Vascular Surgery

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How the vein wall endothelium responds after deep vein thrombosis (DVT) has not been well documented owing to limited human specimens. This report shows that low-molecular-weight heparin accelerates or protects the endothelium and preserves medial smooth muscle cell integrity after DVT, but that this effect is limited to a relatively early time period. Although most DVT prophylaxis is pharmacologic (a heparin agent), use of nonpharmacologic measures is also common. The use of heparin prophylaxis, compared with after DVT treatment, and the acceleration of post-DVT re-endothelialization require clinical correlation.

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Section: Methodsmentioning

confidence: 99%

Vein wall re-endothelialization after deep vein thrombosis is improved with low-molecular-weight heparin

Moaveni

Lynch

Luke

et al. 2008

Journal of Vascular Surgery

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“…In contrast, exposure of whole blood to 'exogenous' TNF-, IL-1, -6 and -8 fails to activate human platelets. 198 (2) Several lines of evidence demonstrate in vivo inflammatory thrombogenesis (Route 4): (i) IL-8 enhances fibrosis in rats; 199 (ii) an earlier study has shown that P-selectin causes leukocyte accumulation to facilitate fibrin deposition 200 complementing thrombotic episodes; (iii) antibodies to cytokines and adhesion molecules attenuate venous thrombosis, 201 and (iv) P-selectin blocking antibody modifies thrombosis 202 and inhibition of P-selectin decreases vein wall fibrosis. 203 (3) Anti-inflammatory agents are anti-thrombotic, which is consistent with the view of inflammation-dependent thrombogenesis (Route 4).…”

Section: Thrombosis-inflammation Circuitmentioning

confidence: 99%

Tissue factor upregulation drives a thrombosis–inflammation circuit in relation to cardiovascular complications

Chu

2006

Cell Biochem. Funct.

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The extrinsic coagulation is recognized as an 'inducible' signalling cascade resulting from tissue factor (TF) upregulation by exposure to clotting zymogen FVII upon inflammation or tissue injury. Following the substantial initiation, an array of proteolytic activation generates mediating signals (active serine proteases: FVIIa, FXa and FIIa) that lead to hypercoagulation with fibrin overproduction manifesting thrombosis. In addition, TF upregulation plays a central role in driving a thrombosis-inflammation circuit. Coagulant mediators (FVIIa, FXa and FIIa) and endproduct (fibrin) are proinflammatory, eliciting tissue necrosis factor, interleukins, adhesion molecules and many other intracellular signals in different cell types. Such resulting inflammation could ensure 'fibrin' thrombosis via feedback upregulation of TF. Alternatively, the resulting inflammation triggers platelet/leukocyte/polymononuclear cell activation thus contributing to 'cellular' thrombosis. TF is very vulnerable to upregulation resulting in hypercoagulability and subsequent thrombosis and inflammation, either of which presents cardiovascular risks. The prevention and intervention of TF hypercoagulability are of importance in cardioprotection. Blockade of inflammation reception and its intracellular signalling prevents TF expression from upregulation. Natural (activated protein C, tissue factor pathway inhibitor, or antithrombin III) or pharmacological anticoagulants readily offset the extrinsic hypercoagulation mainly through FVIIa, FXa or FIIa inhibition. Therefore, anticoagulants turn off the thrombosis-inflammation circuit, offering not only antithrombotic but anti-inflammatory significance in the prevention of cardiovascular complications.

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“…Notably, P-selectin has a direct role in the early phases of thrombosis, and its inhibition has been shown to reduce perithrombotic inflammation and postthrombotic vein wall fibrosis in animal models, independent of the absolute size of the thrombus. 37,38 Interestingly, neonatal neutrophils and neonatal endothelial cells have been shown to exhibit decreased P-selectin expression. 39,40 Neonates also showed less severe PTS-related clinical findings compared with older children and adolescents in this study.…”

Section: Ue-dvtmentioning

confidence: 99%

Postthrombotic syndrome following upper extremity deep vein thrombosis in children

Avila¹,

Duan²,

Cipolla³

et al. 2014

Blood

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Key Points• Upper limb PTS in children depends on DVT pathogenesis (primary vs secondary) and on the age of the patient (neonates vs non-neonates).• DVT pathogenesis and thrombus resolution are independent predictors of upper limb PTS in children.Despite its relatively estimated high occurrence, the characterization of pediatric upper extremity deep vein thrombosis (UE-DVT) and of UE postthrombotic syndrome (PTS) is still lacking. We investigated the occurrence, characteristics, and predictors of UE-PTS in a cohort of children with objectively confirmed UE-DVT. Patients were analyzed in 3 groups according to DVT pathogenesis and neonatal status: primary (G1), secondary neonates (G2 neonates ), and non-neonates (G2 non-neonates ). A total of 158 children (23 G1, 25 G2 neonates , and 110 G2 non-neonates ) were included. The most common triggering factors were effort-related (87%) in G1 and central lines in G2 neonates (100%) and in G2 non-neonates (92%). PTS scores ‡1, as per the Modified Villalta Scale, were identified in 87% of primary patients, 16% of G2 neonates , and 49% of G2 non-neonates . Survival analysis showed that the time to PTS score ‡1 significantly differed among group (log-rank test P < .0001).A multivariable logistic regression showed that DVT pathogenesis and imaging-determined degree of thrombus resolution at the end of therapy were independent predictors of a PTS score ‡2. In conclusion, pediatric UE-PTS frequency and severity depend on UE-DVT pathogenesis (primary/secondary) and, within the secondary group, on patient's age. Line-related UE-PTS has a more benign course, particularly in neonates. (Blood. 2014;124(7):1166-1173

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P-selectin inhibition decreases post-thrombotic vein wall fibrosis in a rat model

Cited by 43 publications

References 20 publications

Vein wall re-endothelialization after deep vein thrombosis is improved with low-molecular-weight heparin

Vein wall re-endothelialization after deep vein thrombosis is improved with low-molecular-weight heparin

Tissue factor upregulation drives a thrombosis–inflammation circuit in relation to cardiovascular complications

Postthrombotic syndrome following upper extremity deep vein thrombosis in children

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