Free protein S deficiency: a possible association with cerebrovascular occlusion.

Sacco, Ralph L.; Owen, John; Mohr, J. P.; Tatemichi, T. K.; Grossman, Betty A.

doi:10.1161/01.str.20.12.1657

Cited by 70 publications

(29 citation statements)

References 17 publications

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“…To date, three studies have reported on a possible association between PS deficiency and arterial thromboembolism. One study showed a higher than the expected prevalence of decreased free PS levels in patients with ischaemic stroke, but this study did not contain a control group (Sacco et al, 1989). In the second study, free PS deficiency was demonstrated in 21% of cases (patients admitted to the hospital for ischaemic stroke) vs. 20% of controls (matched hospitalized patients) (Mayer et al, 1993).…”

Section: Discussionmentioning

confidence: 82%

“…This was because of lower free PS levels in type I deficient subjects and a free PS cut-off level far below the lower limit of its normal range. of arterial thromboembolism (Sacco et al, 1989;Mayer et al, 1993;Rudnicka et al, 2001). We present the results of a large family cohort study designed to assess the absolute risk of venous and arterial thromboembolism, respectively, in relatives from type I and type III PS deficient families.…”

Section: Discussionmentioning

confidence: 99%

“…A difference in risk between subjects with type I and type III deficiency, together with variation in the distribution of both types of PS deficiency among the studied populations may explain this discrepancy, although these types were not distinguished. Another issue to be clarified regards the supposed association of PS deficiency and an increased risk of arterial thromboembolism (Sacco et al, 1989;Mayer et al, 1993;Rudnicka et al, 2001).…”

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confidence: 99%

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Difference in absolute risk of venous and arterial thrombosis between familial protein S deficiency type I and type III. Results from a family cohort study to assess the clinical impact of a laboratory test‐based classification

Brouwer

Veeger²,

Schaaf

et al. 2005

Br J Haematol

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SummaryHereditary protein S (PS) deficiency type I is an established risk factor for venous thromboembolism. Contradictionary data on type III deficiency suggests a difference in risk between both types. We studied 156 first degree relatives (90% of eligible relatives) from type I deficient probands (cohort 1) and 268 (88%) from type III deficient probands (cohort 2) to determine the absolute risk of venous and arterial thromboembolism. Annual incidences of venous thromboembolism were 1AE47 and 0AE17 per 100 person-years in deficient and non-deficient relatives in cohort 1 [relative risk (RR) 8AE9; 95% confidence interval (CI) 2AE6-30AE0], and 0AE27 vs. 0AE24 in cohort 2 (RR 0AE9; 95% CI 0AE4-2AE2). Type III deficiency was demonstrated in 20% of non-deficient relatives in cohort 1 and the annual incidence in this subgroup was 0AE70 (RR 4AE3;0AE95-19AE0). The cut-off level of free PS to identify subjects at risk was 30%, the lower limit of its normal range (65%). PS deficiency was not a risk factor for arterial thromboembolism. In conclusion, type I deficiency was found to be a strong risk factor for venous thromboembolism, in contrast with type III deficiency. This was because of lower free PS levels in type I deficient subjects and a free PS cut-off level far below the lower limit of its normal range. of arterial thromboembolism (Sacco et al, 1989;Mayer et al, 1993;Rudnicka et al, 2001). We present the results of a large family cohort study designed to assess the absolute risk of venous and arterial thromboembolism, respectively, in relatives from type I and type III PS deficient families. Keywords Materials and methods Study populationThe study contained two cohorts of PS deficient families, registered in our hospital from 1987 to 2003. Probands were consecutive patients with documented venous thromboembolism or premature atherosclerosis, i.e. any arterial thromboembolic event before the age of 50 years, in whom PS deficiency type I or type III were established. Their firstdegree relatives older than 15 years of age were identified by pedigree analysis and enrolled in the study after informed consent was obtained. Cohort 1 contained families with inherited PS deficiency type I and cohort 2 families with inherited PS deficiency type III.Detailed information about previous episodes of venous and arterial thromboembolism, exposure to exogenous risk factors for venous thromboembolism, risk factors for atherosclerosis, and anticoagulant prophylaxis or treatment were collected, using a standard questionnaire and reviewing medical records when appropriate. In women, the use of oral contraceptives and their obstetric history were documented. Blood samples for PS measurements were taken after clinical data had been collected. The study was approved by the institutional review board of our hospital. DefinitionsVenous thromboembolism was considered established if deep vein thrombosis was confirmed by compression ultrasound or venography, and pulmonary embolism by ventilation/perfusion lung scanning, spiral computed tomog...

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Difference in absolute risk of venous and arterial thrombosis between familial protein S deficiency type I and type III. Results from a family cohort study to assess the clinical impact of a laboratory test‐based classification

Brouwer

Veeger²,

Schaaf

et al. 2005

Br J Haematol

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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%

“…Several clinical studies have indicated that patients with acute brain infarction have disturbances in the anticoagulant mechanism, [80,101] as well as impaired fibrinolysis. [100] It has been suggested that these hemostatic abnormalities could be regarded as risk factors for brain infarction.…”

mentioning

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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Coagulation Studies

Furie¹,

and²,

Kistler³

2004

Transient Ischemic Attacks

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Free protein S deficiency: a possible association with cerebrovascular occlusion.

Cited by 70 publications

References 17 publications

Difference in absolute risk of venous and arterial thrombosis between familial protein S deficiency type I and type III. Results from a family cohort study to assess the clinical impact of a laboratory test‐based classification

Difference in absolute risk of venous and arterial thrombosis between familial protein S deficiency type I and type III. Results from a family cohort study to assess the clinical impact of a laboratory test‐based classification

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

Coagulation Studies

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