Normal plasma antithrombin activity in patients with relapsing–remitting and secondary progressive multiple sclerosis

Campos-de-Magalhães, Marilza; Almeida, Adílson José de; Papaiz-Alvarenga, Regina; Gadelha, Telma; Morais-de-Sá, Carlos Alberto; Alves-Leon, Soniza Vieira

doi:10.1016/j.clineuro.2008.11.016

Cited by 6 publications

(4 citation statements)

References 32 publications

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“…However, these increased activities do not seem to be balanced by increased activity of PC, a key inhibitor (136). Similarly, plasma AT activity was reported to show no differences in MS patients or associations with periods of relapses or remissions (143).…”

Section: Coagulation and Hemostasis Findings In Multiple Sclerosis Pamentioning

confidence: 99%

Coagulation Pathways in Neurological Diseases: Multiple Sclerosis

et al. 2019

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Significant progress has been made in understanding the complex interactions between the coagulation system and inflammation and autoimmunity. Increased blood-brain-barrier (BBB) permeability, a key event in the pathophysiology of multiple sclerosis (MS), leads to the irruption into the central nervous system of blood components that include virtually all coagulation/hemostasis factors. Besides their cytotoxic deposition and role as a possible trigger of the coagulation cascade, hemostasis components cause inflammatory response and immune activation, sustaining neurodegenerative events in MS. Early studies showing the contribution of altered hemostasis in the complex pathophysiology of MS have been strengthened by recent studies using methodologies that permitted deeper investigation. Fibrin(ogen), an abundant protein in plasma, has been identified as a key contributor to neuroinflammation. Perturbed fibrinolysis was found to be a hallmark of progressive MS with abundant cortical fibrin(ogen) deposition. The immune-modulatory function of the intrinsic coagulation pathway still remains to be elucidated in MS. New molecular details in key hemostasis components participating in MS pathophysiology, and particularly involved in inflammatory and immune responses, could favor the development of novel therapeutic targets to ameliorate the evolution of MS. This review article introduces essential information on coagulation factors, inhibitors, and the fibrinolytic pathway, and highlights key aspects of their involvement in the immune system and inflammatory response. It discusses how hemostasis components are (dys)regulated in MS, and summarizes histopathological post-mortem human brain evidence, as well as cerebrospinal fluid, plasma, and serum studies of hemostasis and fibrinolytic pathways in MS. Studies of disease-modifying treatments as potential modifiers of coagulation factor levels, and case reports of autoimmunity affecting hemostasis in MS are also discussed.

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Section: Coagulation and Hemostasis Findings In Multiple Sclerosis Pamentioning

confidence: 99%

Coagulation Pathways in Neurological Diseases: Multiple Sclerosis

et al. 2019

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“…Following our studies in EAE and thrombin inhibitors, there have been several recent publications including those examining plasma antithrombin activity in patients with relapsing-remitting and secondary progressive MS. 64 A major publication in field has utilized brain samples from patients with MS for proteomic analysis of active MS lesions and found that comparative proteomic profiles identified tissue factor and protein C inhibitor within chronic active plaque samples, suggesting dysregulation of molecules associated with coagulation. In vivo administration of hirudin or recombinant activated protein C reduced disease severity in EAE and suppressed Th1 and Th17 cytokines in astrocytes and immune cells.…”

Section: Coagulation In Encephalitismentioning

confidence: 99%

Coagulation in Inflammatory Diseases of the Central Nervous System

Chapman

2013

Semin Thromb Hemost

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Thrombin and other proteases involved in coagulation also have the potential to stimulate inflammation in the brain to a large extent through the protease-activated receptors (PARs). Such exposure of the brain to increased levels of coagulation factors is more likely to occur during vasculitis and activation of intrinsic coagulation in the brain and may cause inflammatory diseases such as multiple sclerosis. There is growing evidence from animal models and human brain samples that links upregulation of coagulation factors to inflammatory central nervous system (CNS) disease. Evidence includes measures of thrombin-like activity, levels of its receptors, PARs, and inhibitors of the coagulation pathway. The major receptor for thrombin, PAR-1, has now been definitively located to the synapse and node of Ranvier and its excessive activation leads to blocks in long-term potentiation and in nerve conduction. There is growing evidence that modulating coagulation in models of CNS inflammatory disease has beneficial clinical effects. These findings suggest that coagulation-like pathways play a significant role in the pathogenesis of inflammatory diseases in the CNS and present a viable target for therapeutic strategies.

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“…McNemar test allowed us to consider the comparable data coming from the well-trained sonographers: the characteristics and parameters showed no statistical differences between themselves (p=ns). Neither antithrombin activity [18] seems to have different values within patients suffering from SP form, PP form of MS and control group. Unfortunately, we could not calculate the accuracy of the method because patients did not undergo venography, i.e.…”

Section: Discussionmentioning

confidence: 79%

Multigate Quality Doppler Profiles and Morphological/Hemodynamic Alterations in Multiple Sclerosis Patients

Ciccone

Galeandro²,

Scicchitano³

et al. 2012

CNR

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Venous echo-color-Doppler (ECD) showed that chronic cerebrospinal venous insufficiency (CCSVI) syndrome is related to multiple sclerosis (MS). Study aims were to assess interobserver variability in ultrasound evaluation of MS patients and to relate echo-markers to MS clinical symptoms and the disability degree. 277 MS patients (117 men, mean age 43.05+10.04 years) admitted to the Neurology Department of Bari University General Hospital, underwent clinical, Expanded Disability Status Scale (EDSS) evaluation, and a cerebro-venous system ECD evaluation. Two operators reevaluated 32 patients to calculate interobserver variability. McNemar test confirmed the procedure reproducibility between two operators (p=ns). Septa/membranes correlated with deep cerebral veins reflux [right: 16% absence vs. 58% presence, p < 0.0001; left: 26% vs. 50%, p < 0.0001]; their absence in Primary Progressive (PP) MS form [right: 11% vs. 2%, p < 0.001; left: 12% vs. 2%, p < 0.001]. Internal jugular veins (IJVs) reflux absence was in Relapsing-remitting (RR) form [right: 60% vs. 74%, p=0.036; left: 56% vs. 85%, p < 0.0001] like hemodynamically significant stenosis [right: 57% vs. 69%, p=0.033; left: 49% vs. 73%, p < 0.001] not present in PP [right: 11% vs. 2%, p < 0.001; left: 10% vs. 3%, p=0.009]. A supine IJVs blocked flow was related to the EDSS class [right: 4.8±1.5 vs. 5.4±1.4, p=0.006; left: 4.7±1.6 vs. 5.5±1.2, p < 0.0001]; its absence was linked to RR [right: 60% vs. 76%, p=0.016; left: 58% vs. 79%, p < 0.001]. ECD has an important value in MS patients with IJV anomalies detection and a good interobserver procedure reproducibility. MS is associated with CCSVI, although further studies are needed.

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Normal plasma antithrombin activity in patients with relapsing–remitting and secondary progressive multiple sclerosis

Cited by 6 publications

References 32 publications

Coagulation Pathways in Neurological Diseases: Multiple Sclerosis

Coagulation Pathways in Neurological Diseases: Multiple Sclerosis

Coagulation in Inflammatory Diseases of the Central Nervous System

Multigate Quality Doppler Profiles and Morphological/Hemodynamic Alterations in Multiple Sclerosis Patients

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