A Study of Coagulation Factors in Blood and Spinal Fluid in Multiple Sclerosis

Albright, Spencer D.; Kupfer, Henry G.; Kinne, Dixie R.

doi:10.1001/archneur.1959.03840030073008

Cited by 5 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first studies on serum coagulation factors were conducted in small MS patient cohorts and led to conflicting results. The clotting time was found shortened (23), normal (24) or prolonged (25). There was disagreement also regarding the prothrombin time since it was similarly reported either shortened (26), prolonged, (27, 28) or normal (25, 29).…”

Section: Historymentioning

confidence: 95%

“…Furthermore, thrombocytes were studied in MS with divergent results. One study reported a short clot retraction time during acute disease exacerbation (33), whereas it was found to be normal or prolonged in other works (25, 32). An elevated platelet adhesiveness and a short clot retraction time was found mainly during acute disease exacerbation (33).…”

Section: Historymentioning

confidence: 96%

“…There was disagreement also regarding the prothrombin time since it was similarly reported either shortened (26), prolonged, (27, 28) or normal (25, 29). Putnam (30) and Persson (31) showed an increase of fibrinogen especially during the exacerbations while other studies found it to be normal in 9 patients in active clinical progression except one (25) as well as in 33 MS patients except two patients with increased fibrinogen, of which one examined during a relapse (32).…”

Section: Historymentioning

confidence: 99%

See 2 more Smart Citations

A Perspective of Coagulation Dysfunction in Multiple Sclerosis and in Experimental Allergic Encephalomyelitis

Plantone¹,

Inglese

Salvetti

et al. 2019

Front. Neurol.

View full text Add to dashboard Cite

A key role of both coagulation and vascular thrombosis has been reported since the first descriptions of multiple sclerosis (MS). Subsequently, the observation of a close concordance between perivascular fibrin(ogen) deposition and the occurrence of clinical signs in experimental allergic encephalomyelitis (EAE), an animal model of MS, led to numerous investigations focused on the role of thrombin and fibrin(ogen). Indeed, the activation of microglia, resident innate immune cells, occurs early after fibrinogen leakage in the pre-demyelinating lesion stage of EAE and MS. Thrombin has both neuroprotective and pro-apoptotic effects according to its concentration. After exposure to high concentrations of thrombin, astrocytes become reactive and lose their neuroprotective and supportive functions, microglia proliferate, and produce reactive oxygen species, IL-1β, and TNFα. Heparin inhibits the thrombin generation and suppresses EAE. Platelets play an important role too. Indeed, in the acute phase of the disease, they begin the inflammatory response in the central nervous system by producing of IL-1alpha and triggering and amplifying the immune response. Their depletion, on the contrary, ameliorates the course of EAE. Finally, it has been proven that the use of several anticoagulant agents can successfully improve EAE. Altogether, these studies highlight the role of the coagulation pathway in the pathophysiology of MS and suggest possible therapeutic targets that may complement existing treatments.

show abstract

Section: Historymentioning

confidence: 95%

Section: Historymentioning

confidence: 96%

Section: Historymentioning

confidence: 99%

See 1 more Smart Citation

A Perspective of Coagulation Dysfunction in Multiple Sclerosis and in Experimental Allergic Encephalomyelitis

Plantone¹,

Inglese

Salvetti

et al. 2019

Front. Neurol.

View full text Add to dashboard Cite

show abstract

“…Overall, in the majority of investigated patients fibrinogen levels were within the normal range, despite wide variations that were not associated with the stage of the disease (130). A subsequent study in 10 MS patients explored both blood and cerebrospinal fluid (CSF) and revealed that neither had thromboplastin activity, nor significant abnormalities in blood platelet, coagulation factors, serum platelet-like activity nor fibrinogen levels (131). Despite the lack of abnormal findings, increased capillary fragility was reported (131).…”

Section: Coagulation and Hemostasis Findings In Multiple Sclerosis Pamentioning

confidence: 99%

“…A subsequent study in 10 MS patients explored both blood and cerebrospinal fluid (CSF) and revealed that neither had thromboplastin activity, nor significant abnormalities in blood platelet, coagulation factors, serum platelet-like activity nor fibrinogen levels (131). Despite the lack of abnormal findings, increased capillary fragility was reported (131).…”

Section: Coagulation and Hemostasis Findings In Multiple Sclerosis Pamentioning

confidence: 99%

Coagulation Pathways in Neurological Diseases: Multiple Sclerosis

et al. 2019

View full text Add to dashboard Cite

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.

show abstract