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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a 49-year-old man who had right hemiparesis and motor aphasia. A computed tomography revealed hypodense areas in the left frontal subcortex. A cerebral angiography demonstrated occlusion of the left distal internal carotid artery and both anterior cerebral arteries, as well as stenosis of the left internal carotid artery at the cervical portion. The second angiogram obtained a month later showed no changes. The diagnosis of atherothrombotic cerebral infarction was established on the basis of clinical profile and angiographic findings. Protein C activity and antigen levels were reduced to approximately one half of the normal level in the patient and his brother. The patient had no other risk factors for stroke. Protein C deficiency has been considered one of the risk factors for thrombotic diseases. Venous thrombosis is the most common clinical manifestation, whereas arterial thrombosis is relatively rare. It is generally believed that arterial ischemic stroke associated with protein C deficiency occurs with embolic mechanism, and atherothrombotic infarction is extremely rare. This is the first report suggesting the possibility that protein C deficiency can cause cerebral thrombosis.
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PMID:[A case of multiple cerebral arterial thrombosis due to congenital protein C deficiency]. 940 53

Postmenopausal hormone replacement therapy is associated with a reduction in the incidence of coronary heart disease. However, inconclusive results have been reported with respect to the risk of stroke, and recent studies consistently showed an increased risk of venous thromboembolism in postmenopausal women using oral estrogen. There are surprisingly few interventional studies to assess the true effects of estrogen-progestin regimens on blood coagulation and fibrinolysis, and the impact of the route of estrogen administration on hemostasis has not been well documented. Therefore, we investigated the effects of oral and transdermal estradiol/progesterone replacement therapy on hemostatic variables. Forty-five healthy postmenopausal women, aged 45 to 64 years, were assigned randomly to one of the three following groups: cyclic oral or transdermal estradiol, both combined with progesterone, or no hormonal treatment. Hemostatic variables were assayed at baseline and after a 6-month period. Pairwise differences in the mean change between the three groups were compared using nonparametric tests. Oral but not transdermal estradiol regimen significantly increased the mean value of prothrombin activation peptide (F1 + 2) and decreased mean antithrombin activity compared with no treatment. Differences in fragment F1 + 2 levels between active treatments were significant. The oral estrogen group was associated with a significant decrease in both mean tissue-type plasminogen (t-PA) concentration and plasminogen activator inhibitor (PAI-1) activity and a significant rise in global fibrinolytic capacity (GFC) compared with the two other groups. A transdermal estrogen regimen had no significant effect on PAI-1, t-PA, and GFC levels. There were no significant changes in mean values of fibrinogen, factor VII, von Willebrand factor, protein C, fibrin D-dimer, and plasminogen between and within the three groups. We conclude that oral estrogen/progesterone replacement therapy may result in coagulation activation and increased fibrinolytic potential, whereas opposed transdermal estrogen appears without any substantial effects on hemostasis. Whereas these results may account for an increased risk of venous thromboembolism in users of oral postmenopausal estrogen, they emphasize the potential importance of the route of estrogen administration in prescribing hormone replacement therapy to postmenopausal women, especially to those at high risk of thrombotic disease.
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PMID:Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial. 940 95

Thrombomodulin (TM), a key cofactor of the TM-protein C pathway, is of major biologic significance for the antithrombotic properties of endothelial cells. Yet, there is uncertainty whether TM is expressed in brain and what mechanisms govern brain endothelial anticoagulant activity. In this study, bovine brain capillaries were used as an in vitro model of the blood-brain barrier to determine factors involved in the regulation of TM expression in cerebral vasculature. Quantitative competitive-polymerase chain reaction assay revealed significant regional differences in the amount of brain capillary TM mRNA, i.e., cortical > cerebellar > pontine, consistent with the reverse transcription-polymerase chain reaction findings in which the abundance of TM mRNA was analyzed relative to beta-actin mRNA. Regional differences in TM mRNA brain capillary level correlated well with differences in protein C activation. The TM mRNA and activity were not detectable in brain parenchyma. Pathogenic mediators of ischemic stroke, interleukin 1 beta (10 U/mL), and tumor necrosis factor alpha (10 U/mL), produced a time-dependent decrease in brain capillary TM mRNA (t1/2 of 2.1 and 3.9 hours, respectively) and reduced endothelial TM activity. Incubation of brain capillaries with retinoic acid (10 mumol/L) and dibutyryl cAMP (3 mmol/L) resulted in a 4-fold increase in TM mRNA at 4 and 8 hours, respectively, followed by an increase in protein C activation. We conclude that TM at the blood-brain barrier is likely to be an important physiologic anticoagulant in brain microcirculation. Its downregulation by cytokines may contribute to ischemic brain damage and potentially could be counteracted by retinoic acid and cAMP.
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PMID:Thrombomodulin expression in bovine brain capillaries. Anticoagulant function of the blood-brain barrier, regional differences, and regulatory mechanisms. 940 3

A prothrombotic state caused by a deficiency of protein C or protein S, each an inhibitor of coagulation cascade, increases the risk of ischemic cerebrovascular accident (ICVA) in young adults. This retrospective review studies the relationship of protein C or S deficiency with childhood ICVA. From 1989 to 1995, 37 children were diagnosed by neuroimaging with ICVA unrelated to any known preexisting diagnosis. Protein C deficiency or protein S deficiency was the only identified risk factor for 5.4% (2 patients) and 13.5% (5 patients), respectively, of these 37 children. The data suggest that protein C or protein S deficiency is an important risk factor of ICVA in children.
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PMID:Protein C and S deficiency in children with ischemic cerebrovascular accident. 943 95

A 50-year-old man presented spontaneous internal carotid artery dissection with ischemic stroke. He had a history of deep venous thrombosis, and an activated protein C resistance due to factor V Leiden mutation was documented. He showed no other vascular risk factor. This unusual case puts the question whether this coagulation defect may be related to the stroke occurrence.
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PMID:Factor V Leiden mutation in a case with ischemic stroke: which relationship? A case report. 971

We analysed the results of coagulation studies in an unselected series of young adults with acute cerebral ischaemia. Our aims were (a) to determine the prevalence of coagulation disorders among these patients, (b) to investigate the relation between the presence of coagulation abnormalities and large vessel disease or potential sources of cardiac embolism and (c) to evaluate the occurrence of thrombotic events in patients with or without coagulation disorders. One hundred and twenty consecutively admitted patients (53 men, 67 women, median age 38 years, range 15-45) who presented with acute cerebral infarction (n = 89) or a transient ischaemic attack (n = 31) were evaluated. Diagnostic studies consisted of electrocardiography, echocardiography, duplex scanning, and/or angiography. Coagulation studies included activity tests of protein S, protein C, antithrombin, plasminogen, measurement of immunoglobulin G (IgG) anticardiolipin antibodies (ACLA), and a dilute prothrombin assay. Initially, 30 patients had increased ACLA titres and 28 had an abnormal dilute prothrombin assay, suggesting lupus anticoagulant. Decreased protein S, protein C and antithrombin activity were detected in 20, 3 and 3 patients, respectively, excluding patients in whom the abnormalities could be explained by the use of medication, by pregnancy or puerperium. We detected a decreased activity of plasminogen in 5 patients. The disorders could be confirmed by a second assessment in only 2 patients with a protein S deficiency, in none of the patients with a protein C or antithrombin deficiency and in 1 patient with plasminogen deficiency. However, the abnormalities persisted in 19 of 21 patients with increased anticardiolipin IgG titres and in 9 of 20 patients with lupus anticoagulant. A confirmed coagulation disorder was not associated with stroke type or vascular risk factors, but it was more common among patients with large vessel disease (odds ratio: 3.8, 95% confidence interval (CI): 1.1-12.8). Sixteen patients had a recurrent thromboembolic event, but the risk of recurrence was not increased among patients with a confirmed coagulation disorder. Our results suggest that idiopathic coagulation disorders are found in about a quarter of young stroke patients. They are difficult to predict and probably interact with other risk factors.
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PMID:Coagulation disorders in young adults with acute cerebral ischaemia. 945 24

In order to clarify the coagulation profile accompanying ischemic stroke, which may have implications on therapeutic strategies, we performed a prospective study to evaluate the hemostatic parameters in the first 24 h after the onset of cortical atherothrombotic infarct and lacunar infarction. Twenty-seven patients with cortical atherothrombotic infarction and 27 patients with lacunar infarction, diagnosed on clinical and CT-scan criteria, had blood samples taken within the first 24 h after onset of the stroke, and before anticoagulant treatment had been started. Levels of fibrinogen, von Willebrand factor, D-dimers, prothrombin factors 1 + 2, anti-thrombin III, and C-protein and S-proteins, were measured. Laboratory tests detected the following abnormalities: a protein C deficiency was observed in 1 case of cortical infarction and in 1 case of lacunar infarction; a decrease in S-protein was observed in 1 case of cortical infarction, and the presence of lupus anticoagulant in 4 cases (2 in cortical and 2 in lacunar infarction). Various degrees of coagulation activation were observed. Statistically significant activation of the coagulation was observed in the patients with cortical infarction, compared to normal patients adjusted for age: the levels of DDI were significantly raised (2298 +/- 2221 ng ml-1 vs. 750 +/- 400 ng ml-1) (p < 0.03) as were F1 + 2 levels (3.9 +/- 2.8 nmol l-1 vs. 1.5 +/- 0.9 nmol l-1). (p < 0.01). In the lacunar infarction group, there was a significant rise in F1 + 2 compared with normal patients adjusted for age (2.2 +/- 1.7 nmol l-1 vs. 1.5 +/- 0.9 nmol l-1) (p < 0.01), while the DDI level was in the normal range, when age was taken into account. In the cortical infarction group, we observed a significantly raised fibrinogen level (4.8 +/- 1.7 g l-1 vs. 3.7 +/- 1.0 g l-1) (p < 0.05) and von Willebrand factor level (271 +/- 104% vs. 178 +/- 103%) (p < 0.01) compared to the lacunar infarction group. In addition, we observed a significantly low level of S-protein in the cortical infarction group (105 +/- 29%) compared to the lacunar infarction group (127 +/- 28%) (p < 0.01). Confirmation of the role of enhanced thrombin activity in the pathogenesis of acute stroke may be an important determinant in its therapeutic management.
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PMID:Coagulation abnormalities in lacunar and cortical ischemic stroke are quite different. 947 Oct 97

It is well known that thalassemic patients exhibit an increased frequency of thrombotic events. Most individuals with resistance to activated protein C (APCR) are the result of a point mutation replacing Arg 506 with Gln in the factor V aminoacidic sequence (factor V Leiden). Recently APCR has been shown to account for up to 50% of cases of thrombophilia. In this report, we describe a 10 year old thalassemic intermedia patient heterozygous for Factor V R506Q who developed a stroke following transfusion. Coagulation laboratory values were all within the normal range and there was no evidence of a lupus anticoagulant. Computerized brain tomography showed an ischemic area in the left temporo-parietal region. At follow-up, plasma from the patient demonstrated APCR and molecular diagnostic testing revealed heterozygosity for factor V R506Q. We suggest that the heterozygosity for factor V Leiden could increase the thrombotic risk in thalassemia intermedia. We believe it may be beneficial to screen all intermedia thalassemic patients for APCR especially before starting a transfusional regimen.
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PMID:Resistance to activated protein C as a risk factor of stroke in a thalassemic patient. 949 70

Two families with type I plasminogen deficiency and APC resistance are reported. The proposita of family A suffered from ischemic stroke when taking estrogen-progesterone-containing oral contraceptive. Several hemostatic challenges in the past (ovariectomy, appendectomy, and two pregnancies) were without thrombosis. Plasminogen activity and antigen (60 and 58%, normal range 72-136 and 69-135%, respectively) were reduced, and an increased APC resistance (APC-SR= 1.55; normal range 1.8-3.00) associated with G --> A change at 1,691 nucleotide position in exon 10 of FV gene (FV Leiden) was observed. The asymptomatic son had isolated plasminogen deficiency (activity 57% and antigen 60%) whereas the asymptomatic daughter had isolated APC resistance (APC-SR = 1.61) and FV Leiden mutation. The proposita of family B, referred for superficial thrombophlebitis, had low plasminogen levels (activity 55% and antigen 53%) and APC resistance (APC-SR = 1.5) whereas the asymptomatic mother and the brother had isolated APC resistance (APC-SR = 1.62 and 1.8, respectively) and the asymptomatic father isolated plasminogen deficiency (activity 61% and antigen 62%). These data suggest that the combination of plasminogen deficiency and APC resistance probably does not significantly increase the risk of venous thrombosis. However, larger experience with additional cases is needed to definitely assess the magnitude of thrombotic risk in these families.
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PMID:Low risk of venous thrombosis in two families with combined type I plasminogen deficiency and factor V R506Q mutation. 954 82

Recent findings have indicated the association between activated protein C (APC)-resistance and cerebrovascular disease. These reports prompted us to investigate whether resistance to APC could be found in patients suffering from transient ischaemic attacks or stroke. Therefore, we studied APC-resistance in 14 young adults belonging to three different families with a history of transient ischemic attacks (TIAs) and stroke. Nine out of fourteen subjects showed APC-resistance but no deficiencies in the anticoagulant proteins AT III, PC and PS. The family history demonstrated a distribution of APC-resistance compatible with dominant autosomal inheritance. A rapid screening method to detect factor V R506Q (Leiden) mutation without sequencing or restriction enzyme digestion has been set-up after biochemical analyses. DNA analysis showed a guanine to adenine transition at nucleotide 1,691 in patients and their relatives with poor response to activated protein C detected by APTT tests. Of 14 investigated subjects and their family members, 5 were normals, 6 were heterozygotes and 3 were homozygotes for factor V mutation. The mutation, in heterozygous form, was also found in 1.3% of our normal population (n = 75). Our findings indicate a possible involvement of APC-resistance in the pathogenesis of arterial thrombosis in young adults.
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PMID:Activated protein C resistance due to a factor V mutation associated with familial ischemic stroke. 955 45


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