Inherited protein C deficiency and nonhemorrhagic arterial stroke in young adults

Camerlingo, M.; Finazzi, Guido; Casto, L.; Laffranchi, C.; Barbui, Tiziano; Mamoli, A

doi:10.1212/wnl.41.9.1371

Cited by 69 publications

(35 citation statements)

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“…648 Deficiencies of protein C, protein S, or antithrombin III in adults are rare (<1% population) but are associated with increased risk for venous thrombosis. 672 Although case reports 657 and 1 observational cohort study 673 have suggested an association between inherited protein C deficiency and increased risk for ischemic stroke, 674,675 this finding has not been confirmed in case-control studies and meta-analyses. 657 Thus, these rare conditions are of uncertain significance in adults with ischemic stroke.…”

Section: Inherited Thrombophiliasmentioning

confidence: 98%

Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack

Kernan¹,

Ovbiagele²,

Black³

et al. 2014

Stroke

3,949

1,326

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The aim of this updated guideline is to provide comprehensive and timely evidence-based recommendations on the prevention of future stroke among survivors of ischemic stroke or transient ischemic attack. The guideline is addressed to all clinicians who manage secondary prevention for these patients. Evidence-based recommendations are provided for control of risk factors, intervention for vascular obstruction, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke. Recommendations are also provided for the prevention of recurrent stroke in a variety of specific circumstances, including aortic arch atherosclerosis, arterial dissection, patent foramen ovale, hyperhomocysteinemia, hypercoagulable states, antiphospholipid antibody syndrome, sickle cell disease, cerebral venous sinus thrombosis, and pregnancy. Special sections address use of antithrombotic and anticoagulation therapy after an intracranial hemorrhage and implementation of guidelines.

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Section: Inherited Thrombophiliasmentioning

confidence: 98%

Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack

Kernan¹,

Ovbiagele²,

Black³

et al. 2014

Stroke

3,949

1,326

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“…[31][32][33][34] Caseseries studies reported prevalence rates of 0% to 23%. 32,[35][36][37][38][39][40] Hereditary fibrinolytic defects such as plasminogen deficiency have a reported prevalence of 0% to 2.7% in casecontrol and case-series studies of ischemic stroke patients aged Ͻ45 years. 32,35,37,39 These data do not permit calculation of cumulative prevalence rates.…”

Section: Hereditary Coagulation Defectsmentioning

confidence: 99%

Diagnostic Testing for Coagulopathies in Patients With Ischemic Stroke

Bushnell

Goldstein

2000

Stroke

152

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Background-Hypercoagulable states are a recognized, albeit uncommon, etiology of ischemic stroke. It is unclear how often the results of specialized coagulation tests affect management. Using data compiled from a systematic review of available studies, we employed quantitative methodology to assess the diagnostic yield of coagulation tests for identification of coagulopathies in ischemic stroke patients. Summary of Review-We performed a MEDLINE search to identify controlled studies published during 1966 -1999 that reported the prevalence of deficiencies of protein C, protein S, antithrombin III, plasminogen, activated protein C resistance (APCR)/factor V Leiden mutation (FVL), anticardiolipin antibodies (ACL), or lupus anticoagulant (LA) in patients with ischemic stroke. The cumulative prevalence rates (pretest probabilities) and positive likelihood ratios for all studies and for those including only patients aged Յ50 years were used to calculate posttest probabilities for each coagulopathy, reflecting diagnostic yield. The cumulative pretest probabilities of coagulation defects in ischemic stroke patients are as follows: LA, 3% (8% for those aged Յ50 years); ACL, 17% (21% for those aged Յ50 years); APCR/FVL, 7% (11% for those aged Յ50 years); and prothrombin mutation, 4.5% (5.7% for those aged Յ50 years). The posttest probabilities of ACL, LA, and APCR increased with increasing pretest probability, the specificity of the tests, and features of the patients' history and clinical presentation. Conclusions--The pretest probabilities of coagulation defects in ischemic stroke patients are low. The diagnostic yield of coagulation tests may be increased by using tests with the highest specificities and by targeting patients with clinical or historical features that increase pretest probability. Consideration of these data might lead to more rational ordering of tests and an associated cost savings. (Stroke. 2000;31:3067-3078.)

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“…[2,3,5,15,18,22,23,51,62,79,80,84,100,101] These changes can be found from a few minutes up to 2 weeks after the onset of brain ischemia. It is not clear, however, whether these hemostatic abnormalities precede or follow the neurological event.…”

Section: Hemostatic Theorymentioning

confidence: 98%

“…[112] Resistance to the effects of APC (due to the mutation in factor V gene and homocysteinemia) is closely linked to venous thrombosis in humans [111] and could also be a potential hemostatic risk factor for stroke and heart attack. Recent studies in stroke populations have examined protein C antigen and protein C zymogen activity after in vitro addition of snake venom, or other exogenous activators, [3,18,23,80] as well as the activity of the circulating antithrombotic enzyme, APC. [51] It has been reported that low plasma protein C levels were related to poor outcome after stroke and may have been caused by protein C depletion because of excessive thrombin generation and rapid APC clearance.…”

Section: Antithrombotic Mechanismsmentioning

confidence: 99%

Antithrombotic, procoagulant, and fibrinolytic mechanisms in cerebral circulation: implications for brain injury and protection

Zloković

1997

FOC

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Maintaining a delicate balance among anticoagulant, procoagulant, and fibrinolytic pathways in the cerebral microcirculation is of major importance for normal cerebral blood flow. Under physiological conditions and in the absence of provocative stimuli, the anticoagulant and fibrinolytic pathways prevail over procoagulant mechanisms. Blood clotting is essential to minimize bleeding and to achieve hemostasis; however, excessive clotting contributes to thrombosis and may predispose the brain to infarction and ischemic stroke. Conversely, excessive bleeding due to enhanced anticoagulatory and fibrinolytic mechanisms could predispose the brain to hemorrhagic stroke. Recent studies in the author's laboratory indicate that brain capillary endothelium in vivo produces thrombomodulin (TM), a key cofactor in the TM-protein C system that is of major biological significance to the antithrombotic properties of the blood-brain barrier (BBB). The BBB endothelium also expresses tissue plasminogen activator (tPA), a key protein in fibrinolysis, and its rapid inhibitor, plasminogen activator inhibitor (PAI-1). The procoagulant tissue factor is normally dormant at the BBB. There is a vast body of clinical evidence to document the importance of hemostasis in the pathophysiology of brain injury. In particular, functional changes caused by major stroke risk factors in the TM-protein C, tPA/PAI-1, and tissue factor systems at the BBB may result in large and debilitating infarctions following an ischemic insult. Thus, correcting this hemostatic imbalance could ameliorate drastic CBF reductions at the time of ischemic insult, ultimately resulting in brain protection. Delineation of the molecular mechanisms of BBB-mediated hemostasis will likely contribute to future stroke prevention efforts and brain protection strategies.

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Inherited protein C deficiency and nonhemorrhagic arterial stroke in young adults

Cited by 69 publications

References 0 publications

Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack

Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack

Diagnostic Testing for Coagulopathies in Patients With Ischemic Stroke

Antithrombotic, procoagulant, and fibrinolytic mechanisms in cerebral circulation: implications for brain injury and protection

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