Increased tissue plasminogen activator levels in patients with nonvalvular atrial fibrillation

OBJECTIVE: To determine whether plasma tissue plasminogen activator (tPA) levels (a) are higher in patients with novalvular atrial fibrillation (NVAF) than in control subjects in sinus rhythm; (b) differ between NVAF patients with and without a history of an embolic event (transient ischemic attack or embolic stroke); and (c) differ in control subjects with and without a history of thrombotic stroke. DESIGN: Cross-sectional study. SETTING: Internal medicine outpatient group practice and anticoagulation clinic in 2 teaching hospitals. PATIENTS: Seventy-four NVAF patients (24 with and 50 without a history of an embolic event), separated into 3 groups: no prior embolic event and no warfarin use (group 1), no prior embolic event and warfarin use (group 2), and prior embolic event and warfarin use (group 3). Forty control subjects in sinus rhythm (29 without and 11 with prior thrombotic stroke). OUTCOME MEASURES: Plasma tPA levels. RESULTS: The age-adjusted mean tPA levels exceeded the upper limit of normal in all 3 NVAF groups but not in the control groups. The NVAF patients had significantly higher mean tPA levels than the control subjects (p = 0.015). The levels did not differ significantly between the NVAF patients with a history of an embolic event and those without such a history. The control subjects with a history of thrombotic stroke had significantly higher mean tPA levels than the other control subjects (p = 0.03). CONCLUSIONS: NVAF patients, regardless of their history of embolic events, and control patients with a history of thrombotic stroke have higher tPA levels than subjects in sinus rhythm without a history of stroke. A prospective, longitudinal study involving NVAF patients is required to determine whether high baseline tPA levels are associated with, and perhaps causally related to, an increased risk of stroke.     

The microvesicle/CD36 complex triggers a prothrombotic phenotype in patients with non‐valvular atrial fibrillation

The mechanisms responsible for platelet activation, the prothrombotic state, in non‐valvular atrial fibrillation (NVAF) are still obscure. Microvesicles (MVs) can transfer various messages to target cells and may be helpful for exploring the detailed mechanisms. We aimed to investigate the possible mechanisms by which proatherogenic factors of NVAF contribute to platelet activation. Two hundred and ten patients with NVAF were stratified as being at ‘low to moderate risk’ or ‘high risk’ for stroke according to the CHADS2 score. Levels of platelet‐derived MVs (PMVs) and platelet activation were examined. CD36‐positive or CD36‐deficient human platelets were stimulated by MVs isolated from NVAF patients with or without various inhibitors in vitro. Levels of PMVs and platelet activation markers enhanced significantly in high‐risk patients. The MVs isolated from plasma of NVAF patients bound to platelet CD36 and activated platelets by phosphorylating the mitogen‐activated protein kinase 4/Jun N‐terminal kinase 2 (MKK4/JNK2) pathways. However, CD36 deficiency protected against MV‐induced activation of platelets. We reveal a possible mechanism of platelet activation in NVAF and suggest that the platelet CD36 might be an effective target in preventing the prothrombotic state in NVAF.     

Coagulation factor levels in non-metastatic colorectal cancer patients

There is evidence that high plasma levels of factor (F) VIII, FIX, FXI and fibrinogen are independent risk factors for venous thromboembolism. AIM: To determine the plasma concentrations of several coagulation factors and C4b-binding protein (C4BP) in a group of patients with non-metastatic colorectal cancer in order to investigate some aspects of cancer-acquired thrombophilia. METHODS: Plasma fibrinogen, FII, FV, FVII, FVIII, FIX, FX, FXI and FXII activity levels and C4BP concentrations were determined in 73 patients with non-metastatic colorectal cancer (48 colon and 25 rectum) and in 67 matched control subjects. No one in either group had had previous thrombotic events. RESULTS: Mean plasma concentrations of fibrinogen (functional and antigen), FVIII, FIX, FV and C4BP were significantly higher in colorectal cancer patients than in control subjects, while FVII and FXII levels were significantly decreased. Several correlations were found between the increased coagulation factors and C4BP concentrations, while FVII was highly correlated with FXII. CONCLUSIONS: In colorectal cancer patients high plasma fibrinogen, FVIII and FIX levels might represent further risk factors for venous thrombotic complications in the immediate post-surgery period, while decreased FVII and FXII concentrations may be an index of intravascular coagulation activation, still in a subclinical phase.     

JAK2 mutation status, hemostatic risk factors and thrombophilic factors in essential thrombocythemia (ET) patients

The recently discovered JAK2 V617F point mutation, found in 50-60% of ET patients, has been reported to be associated with a higher risk of thrombotic events. In this study, we explored if JAK2 V617F mutation, or coexisting thrombophilic and hemostatic risk factors, contributed to these complications. We examined 32 patients with ET, and looked for pathogenetic JAK2 V617F mutation and prothrombotic genes mutations: factor V Leiden, prothrombin and MTHFR. We also evaluated plasma levels of fibrinogen, factors VIII and XII, AT, protein C, protein S and serum level of homocysteine. Urokinase concentration was assessed in patients' plasma as well as platelet lysates. There was no difference in the number of thrombotic complications between ET patients with and without JAK2 mutation. However, we found a number of thrombophilic and hemostatic risk factors that could contribute to thrombotic complications in ET patients.     

Increased level of fibrinogen chains in the proteome of blood platelets in secondary progressive multiple sclerosis patients

Epidemiological studies indicate a high risk of stroke, heart failure and myocardial infarction in patients with multiple sclerosis, especially in its secondary progressive (SPMS) phase. Some ischaemic events are directly associated with abnormal platelet functions and their prothrombotic activity. Recent reports, including this study, confirm the increased activation of circulating platelets in SPMS, and also show increased platelet reactivity, among other responses, as well as strong aggregation. In this current study, we conducted a comparative analysis of the platelet proteome in SPMS patients and in healthy controls, to demonstrate the quantitative and qualitative differences likely to affect functional changes observed in SPMS. During densitometry evaluation of 2‐D fluorescence difference gel electrophoresis, we observed differences between the electrophoretic patterns of SPMS platelets and the control samples. To determine a detailed characterisation of the proteome changes in the SPMS patients’ blood platelets, in the next stage, we performed mass spectrometry of selected spots and indicated the increased presence of four proteins (fibrinogen, α‐2 macroglobulin, septin‐14 and tubulin β‐1 chain). The most important of these is the increased amount of prothrombotic protein, fibrinogen, which seems to confirm the accuracy of the imaging and potentially explains the increased risk of platelet‐origin thrombotic events. This study provides new knowledge of the potential existence of the molecular mechanisms responsible for the acceleration of the platelet pro‐coagulant function in SPMS. This can help to identify new targets for therapy, which can then be used not only in the second stage of the disease.     

Lack of Association between Stroke and Left Atrial Out-Pouching Structures: Results of a Case-Control Study

Background and Purpose

Clinical significance of out-pouching structures of the left atrium (LA) as potential embolic sources remains unclear. We sought to evaluate the association between stroke and LA out-pouching structures.

Methods

A case-control study was conducted to assess the prevalence of LA out-pouching structures in subjects with and without stroke. Case subjects were 270 stroke patients who had undergone cardiac CT. Control subjects were 270 age- and sex-matched patients without a history of stroke and who had undergone cardiac CT. Presence of LA out-pouching structures was determined by ECG-gated cardiac CT. The location of out-pouching structures was categorized as near Bachmann bundle, anterior, inferoseptal, inferior, and lateral. The prevalence, number and location of out-pouching structures and clinical characteristics were compared between the two groups.

Results

One hundred sixty eight out-pouching structures were identified in 139 stroke patients (51%), while a total of 169 out-pouching structures were found in 155 control patients (57%) (p=0.1949). The prevalence of LA out-pouching structures with different locations was not significantly different between the stroke group and control group. In the stroke group, the prevalence of out-pouching structures was not significantly different by subtypes of ischemic stroke and the prevalence of LA out-pouching structures was not different between patients with atrial fibrillation (AF) and without AF.

Conclusion

The left atrial out-pouching structures are commonly seen in a population with and without stroke with similar prevalence. Our study suggests that LA out-pouching structures are not significant risk factors of stroke.     

Impact of Rural Residence on Warfarin Use and Clinical Events in Patients with Non-Valvular Atrial Fibrillation: A Canadian Population Based Study

Background and Purpose

We studied whether anticoagulant use and outcomes differed between rural versus urban Canadian non-valvular atrial fibrillation (NVAF) patients prior to the introduction of direct oral anticoagulant drugs.

Methods

Retrospective cohort study of 25,284 adult Albertans with NVAF between April 1, 1999 and December 31, 2008.

Results

Compared to urban patients, rural patients were older (p = 0.0009) and had more comorbidities but lower bleeding risk at baseline. In the first year after NVAF diagnosis, urban patients were less likely to be hospitalized (aOR 0.82, 95%CI 0.77–0.89) or have an emergency department visit for any reason (aOR 0.61, 95%CI 0.56–0.66) but warfarin dispensation rates (72.2% vs 71.8% at 365 days, p = 0.98) and clinical outcomes were similar: 7.8% died in both groups, 3.2% rural vs. 2.8% urban had a stroke or systemic embolism (SSE) (aOR 0.92, 95%CI 0.77–1.11), and 6.6% vs. 5.7% (aOR 0.93, 95%CI 0.81–1.06) had a bleed. Baseline SSE risk did not impact warfarin dispensation (73.0% in those with high vs. 72.8% in those with low CHADS₂ score, p = 0.85) but patients at higher baseline bleeding risk were less likely to be using warfarin (69.2% high vs. 73.6% low HASBLED score, p<0.0001) in the first 365 days after diagnosis. In warfarin users, bleeding was more frequent (7.5% vs 6.2%, aHR 1.51 [95%CI 1.33–1.72]) but death or SSE was less frequent (7.0% vs 18.1%, aHR 0.60 [0.54–0.66]).

Conclusion

Warfarin use and clinical event rates did not differ between rural and urban NVAF patients in a universal access publically-funded healthcare system.     

Case-control study of risk of cerebral sinus thrombosis in oral contraceptive users who are carriers of hereditary prothrombotic conditions

Objective: To investigate whether users of oral contraceptives who are carriers of a hereditary prothrombotic condition (factor V Leiden mutation, protein C, S, or antithrombin deficiency) have an increased risk of cerebral sinus thrombosis. Design: Comparison of a prospective series of cases of cerebral sinus thrombosis with population data. Setting: Neurological teaching hospitals from different regions in the Netherlands (cases) and a representative sample of the non-institutionalised Dutch population (controls). Subjects: 40 women aged 18-54 years with cerebral sinus thrombosis (cases) and 2248 women aged 18-49 years (controls). Main outcome measure: Current use of oral contraceptives at the time of the thrombosis (cases) or at the time of the questionnaire (controls). Prevalences of a hereditary prothrombotic condition in patients and in the population with odds ratios. Results: 34 of 40 (85%) women with cerebral sinus thrombosis used oral contraceptives, versus 1007 of 2248 (45%) of the control women; the age adjusted odds ratio was 13 (95% confidence interval 5 to 37). Seven of 36 patients (19%) had a prothrombotic deficiency, versus 7% expected in the population; this corresponds to a threefold to fourfold increase in risk. In women who used oral contraceptives and also carried a prothrombotic defect, the odds ratio for cerebral sinus thrombosis was about 30 relative to women who had neither risk factor. Conclusion: The use of oral contraceptives and being a carrier of a hereditary prothrombotic condition increase the risk of and interact in a multiplicative way in the development of cerebral sinus thrombosis.

Key messages

• The use of oral contraceptives is associated with an increased risk of cerebral venous sinus thrombosis
• This risk of cerebral venous sinus thrombosis in women who use oral contraceptives is larger if there is an additional hereditary prothombotic factor (protein C, S, or antithrombin deficiency, factor V Leiden mutation)
• The association between oral contraceptives, thrombophilia, and deep vein thrombosis is also valid for cerebral sinus thrombosis
• Women do not need to stop using oral contraceptives as the absolute risk of cerebral sinus thrombosis is very small

     

Atrial fibrillation and stroke: prevalence in different types of stroke and influence on early and long term prognosis (Oxfordshire community stroke project)

OBJECTIVE--To determine in patients with first ever stroke whether atrial fibrillation influences clinical features, the need to perform computed tomography, and prognosis. DESIGN--Observational cohort study with maximum follow up of 6.5 years. SETTING--Primary care, based on 10 general practices in urban and rural Oxfordshire. SUBJECTS--Consecutive series of 675 patients with first ever stroke registered in the Oxfordshire community stroke project. MAIN OUTCOME MEASURES--Prevalence of atrial fibrillation by type of stroke; effect of atrial fibrillation on case fatality rate and risk of recurrent stroke, vascular death, and death from all causes. RESULTS--Prevalence of atrial fibrillation was 17% (95% confidence interval 14% to 20%) for all stroke types (115/675), 18% (15% to 21%) for cerebral infarction (97/545), 11% (4% to 11%) for primary intercerebral haemorrhage (7/66), and 0% (0 to 11%) for subarachnoid haemorrhage (0/33). For patients with cerebral infarction the 30 day case fatality rate was significantly higher with atrial fibrillation (23%) than with sinus rhythm (8%); the risk of early recurrent stroke (within 30 days) was 1% with atrial fibrillation and 4% with sinus rhythm. In patients who survived at least 30 days the average annual risk of recurrent stroke was 8.2% (5.9% to 10.9%) with sinus rhythm and 11% (6.0% to 17.3%) with atrial fibrillation. CONCLUSIONS--After a first stroke atrial fibrillation was not associated with a definite excess risk of recurrent stroke, either within 30 days or within the first few years. Survivors with and without atrial fibrillation had a clinically important absolute risk of further serious vascular events.     

Possible vascular-bed-specific role of interleukin-6 in young women with a history of myocardial infarction, lacunar cerebral infarction and deep vein thrombosis

The level of interleukin-6 (IL-6), a cytokine with prothrombotic properties, and its associations with metabolic, coagulation and fibrinolytic parameters were investigated in 68 young women (23-49 years, mean 40 years old) six months to six years after myocardial infarction (MI, N=22), lacunar cerebral infarction (LACI, N=16) and deep vein thrombosis (VT, N=30); all women were in the reproductive period, aged <45 years at the time of acute thrombotic event. Forty-seven age-matched women comprised a control group. Basic and multivariate analysis disclosed different patterns of IL-6 increase in all three groups of patients. In the MI group IL-6 was significantly elevated independently of factors known to increase IL-6 levels; the increase was most pronounced in patients with high lipoprotein(a). This result suggests a prothrombotic association of lipoprotein(a) with IL-6. In the whole LACI group IL-6 was not significantly increased. However, patients with elevated levels of IL-6 had abdominal obesity and elevated fibrinogen, suggesting the possibility that this combination might represent a specific risk profile. In VT group elevated IL-6 level was found in the group of previous users of oral contraceptives (OC). This might be relevant, since it is known that OC could importantly increase (previously elevated) IL-6 level in selected women. Our results suggest the hypothesis that the role of IL-6 might be vascular-bed-specific and further propose that increased IL-6 level might represent a novel, non-classical risk factor for development of MI, LACI and VT in specific subgroups of young women, which have to be clarified in further studies.     

Anticoagulants for nonvalvular atrial fibrillation (NVAF)--drug review

Vitamin K-inhibiting anticoagulants, especially warfarin, have become standard treatment for reducing the incidence of strokes and systemic emboli in patients with nonvalvular atrial fibrillation (NVAF). The randomized controlled trials that form the scientific basis for the efficacy of anticoagulants in prophylaxis of embolic events show small but statistically significant benefit with warfarin and other vitamin K inhibitors. The generalizability of these randomized trials to clinical practice is highly questionable because of the low percentage of NVAF patients from the participating institutions that entered the trials, the relatively young age of the patients, and the superior anticoagulation monitoring compared with that in general practice. Indirect comparisons of warfarin with aspirin by looking at separate meta-analyses of placebo-controlled randomized trials give potentially biased results. The meta-analyses of trials directly comparing warfarin with aspirin have diametrically opposing conclusions. In contrast to observational studies of general medical practice, randomized trials significantly underestimate the bleeding risks of warfarin. Anticoagulants for stroke prophylaxis for NVAF cause about 17,000 major bleeds in the United States per year, of which about 4000 are fatal. In 5 randomized trials with follow-up periods of 1.3-2.3 years, 10% to 38% of patients permanently discontinued anticoagulants. The 2-year average follow up of patients in the randomized trials is too short to predict the long-term impact of anticoagulation on the natural history of NVAF. Aspirin should be preferred over anticoagulants in prophylaxis against cardiogenic embolism in NVAF patients.     

The Italian START-Register on Anticoagulation with Focus on Atrial Fibrillation

START-Register – Survey on anTicoagulated pAtients RegisTer – is an independent, inception-cohort, observational, collaborative database aimed at recording prospectively the clinical history of adult patients starting anticoagulant treatment for any reason and using whatever drug. In this article we present the START-Register and give cross section baseline data focusing on non valvular atrial fibrillation (NVAF). Participants are asked to insert prospectively consecutive patients recorded as electronic file on the web-site of the registry. Required data are: demographic and clinical characteristics of patients, associated risk factors for stroke and bleeding, laboratory routine data, clinical indication for treatment, expected therapeutic range (in cases of treatment with vitamin K antagonists -VKAs). The follow-up is carried out to record: quality of treatment (for patients on VKAs), bleeding complications, thrombotic events, and the onset of any type of associated disease. To date 5252 patients have been enrolled; 97.6% were on VKAs because direct oral anticoagulants (DOAC) have been available in Italy only recently. The median age was 74 years [interquartile range (IQR) 64-80]; males 53.7%. This analysis is focused on the 3209 (61.1%) NVAF patients. Mean CHADS₂ score was 2.1±1.1, CHADSVASc score was 3.1±1.3;median age was 76 years (IQR 70-81); 168 patients (5.3%) had severe renal failure [Creatinine clearance (CrCl) <30 ml/min]. Moderate renal failure (CrCl 30-59 ml/min) was found in 1265 patients (39.5%). The analysis of the START-Register data shows that two-third of patients who started chronic anticoagulant treatment had NVAF, one-third of them was > 80 years with high prevalence of renal failure.     

Hemodynamic effects of pacing-induced tachycardia in valvular aortic stenosis.

The hemodynamic effects of tachycardia were studied in 13 patients with valvular aortic stenosis. Observations were made during sinus rhythm (average heart rate 80 beats/min) and two periods (P1 and P2) when atrial pacing increased the heart rate to 109 and 131 beats/min respectively. The cardiac index did not change, but the left ventricular stroke work index fell from 61.8 to 39.5 g X m/m2 (p less than 0.001) as the heart rate increased. The left ventricular end-diastolic pressure averaged 18 mm Hg during sinus rhythm and fell to about 11.5 mm Hg at P1 and P2 (p less than 0.001). The brachial arterial systolic pressure did not change during pacing, but the left ventricular systolic pressure fell from 208 mm Hg to 201 mm Hg during P1 (p less than 0.05) and 193 mm Hg during P2 (p less than 0.001). The mean systolic aortic valve gradient averaged 64 mm Hg during sinus rhythm and fell to 51 mm Hg during P2 (p less than 0.001), and the peak aortic valve gradient fell from 82 to 69 mm Hg during P2 (p less than 0.001). The left ventricular ejection time fraction increased from 26.9% during sinus rhythm to 31.9% during P1 (p less than 0.05) and 34.7% during P2 (p less than 0.005). Because of the prolonged left ventricular ejection time fraction and smaller stroke volume, a smaller pressure gradient developed across the stenosed valve at higher heart rates. The pacing test was of little value in assessing left ventricular function and thus is not useful during invasive investigations of valvular aortic stenosis.     

Discovery of Prognostic Biomarker Candidates of Lacunar Infarction by Quantitative Proteomics of Microvesicles Enriched Plasma

Background

Lacunar infarction (LACI) is a subtype of acute ischemic stroke affecting around 25% of all ischemic stroke cases. Despite having an excellent recovery during acute phase, certain LACI patients have poor mid- to long-term prognosis due to the recurrence of vascular events or a decline in cognitive functions. Hence, blood-based biomarkers could be complementary prognostic and research tools.

Methods and Finding

Plasma was collected from forty five patients following a non-disabling LACI along with seventeen matched control subjects. The LACI patients were monitored prospectively for up to five years for the occurrence of adverse outcomes and grouped accordingly (i.e., LACI-no adverse outcome, LACI-recurrent vascular event, and LACI-cognitive decline without any recurrence of vascular events). Microvesicles-enriched fractions isolated from the pooled plasma of four groups were profiled by an iTRAQ-guided discovery approach to quantify the differential proteome. The data have been deposited to the ProteomeXchange with identifier PXD000748. Bioinformatics analysis and data mining revealed up-regulation of brain-specific proteins including myelin basic protein, proteins of coagulation cascade (e.g., fibrinogen alpha chain, fibrinogen beta chain) and focal adhesion (e.g., integrin alpha-IIb, talin-1, and filamin-A) while albumin was down-regulated in both groups of patients with adverse outcome.

Conclusion

This data set may offer important insight into the mechanisms of poor prognosis and provide candidate prognostic biomarkers for validation on larger cohort of individual LACI patients.     

Plasma desmoplakin I biomarker of vascular recurrence after ischemic stroke

Stroke patients have a high risk of vascular recurrence. Biomarkers related to vascular recurrence, however, remain to be identified. The aim of the study was to identify, through proteomic analysis, plasma biomarkers associated with vascular recurrence within one year after the first ischemic stroke. This is a substudy (n = 134) of a large prospective multicenter study of post-stroke patients with an ischemic stroke. Plasma samples were obtained at inclusion. Among the identified proteins, only plasma levels of desmoplakin I were associated with protection against a new vascular event (Odds ratio: 0.64; 95% CI: 0.46-0.89; p = 0.009) after adjustment for hypercholesterolemia, statins and previous atherothrombotic stroke subtype. A greater number of patients without vascular recurrence had been treated with statins within three months of the recent ischemic stroke. Only patients who had been taking statins for 3 months after the ischemic stroke and did not suffer vascular recurrence over a follow-up year, have higher levels of desmoplakin I at the time of inclusion (Odds ratio 0.49; 95% CI: 0.28-0.86; p = 0.013). Increased desmoplakin I levels, determined within 1-3 months of the first ischemic stroke, could be a biomarker for statin responsiveness against a new vascular event in post-ischemic stroke patients taking statins early (1-3 months) after the ischemic stroke.     

Altered membrane fluidity and signal transduction in the platelets from patients of thrombotic stroke

Several earlier studies have implicated platelet activation with the pathogenesis of thrombotic stroke. In this report we have studied the changes in membrane physical microenvironment and signal transduction in the platelets obtained from the patients with thrombotic stroke. Aggregation induced by the synthetic agonist thrombin receptor-activating peptide was significantly enhanced (p < 0.001) in the platelets obtained from the patients. Steady-state fluorescence anisotropy measurements using diphenylhexatriene reflected a significant increase in membrane microviscosity from 3.315 (± 0.103) in the control to 4.600 (± 0.119) in the stroke. Proteins of relative mobilities of 131, 100, 47 and 38 kDa were found to remain phosphorylated on tyrosine in the resting platelets obtained from thrombotic stroke patients while they were not phosphorylated in the control counterparts. Besides, calpain, a calcium dependent thiol protease present in the platelets, was found to remain active in this disease as reflected from the proteolysis of calpain substrates. Taken together, these data indicated abnormal circulating platelets in the patients of thrombotic stroke, which could contribute to the etiopathogenesis of this disease.     

Protein C and plasma serine protease inhibitors in patients with essential hypertension]

Plasma protein C and serine protease inhibitors together with some other hemostasis parameters have been determined in 60 patients with essential hypertension. Significant decrease in protein C and alpha 2-antiplasmin levels, increased fibrinogen, fibrinopeptide A, WF: Ag, plasminogen, and prolongation of euglobulin fibrinolysis time have been observed. Results indicate hypercoagulability and fibrinolysis defect in hypertensive patients.     

Recombinant fibrinogen studies reveal that thrombin specificity dictates order of fibrinopeptide release

During cleavage of fibrinogen by thrombin, fibrinopeptide A (FpA) release precedes fibrinopeptide B (FpB) release. To examine the basis for this ordered release, we synthesized A'beta fibrinogen, replacing FpB with a fibrinopeptide A-like peptide, FpA' (G14V). Analyses of fibrinopeptide release from A'beta fibrinogen showed that FpA release and FpA' release were similar; the release of either peptide followed simple first-order kinetics. Specificity constants for FpA and FpA' were similar, demonstrating that these peptides are equally competitive substrates for thrombin. In the presence of Gly-Pro-Arg-Pro, an inhibitor of fibrin polymerization, the rate of FpB release from normal fibrinogen was reduced 3-fold, consistent with previous data; in contrast, the rate of FpA' release from A'beta fibrinogen was unaffected. Thus, with A'beta fibrinogen, fibrinopeptide release from the beta chain is similar to fibrinopeptide release from the alpha chain. We conclude that the ordered release of fibrinopeptides is dictated by the specificity of thrombin for its substrates. We analyzed polymerization, following changes in turbidity, and found that polymerization of A'beta fibrinogen was similar to that of normal fibrinogen. We analyzed clot structure by scanning electron microscopy and found that clots from A'beta fibrinogen were similar to clots from normal fibrinogen. We conclude that premature release of the fibrinopeptide from the N terminus of the beta chain does not affect polymerization of fibrinogen.     

The number and affinity of fibrinogen receptors in blood platelets of patients with ischemic stroke]

Parameters of fibrinogen binding with blood platelets (number of receptors and their affinity) have been studied in patients with ischemic stroke. Due to the increased platelet ability to aggregate in the ischemic diseases such studies seem helpful. The studies involved 13 patients with ischemic stroke. Blood platelets collected from younger patients (under 50 years) possessed significantly higher number of receptors binding fibrinogen than blood platelets of healthy individuals (p less than 0.02). These receptors significantly more strongly bound ligand than those in the control group (p less than 0.05), and in the group of older patients with stroke (less than 0.05). Fibrinogen binding to blood platelets in patients over 50 years of age did not differ significantly from that in the control group. These results may indicate, that the increased platelet aggregation might be a significant pathogenic factor of the stroke in younger patients.