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PubMed1999

Can the laboratory assay of protein C activity assist in monitoring the hemostatic function in pre-eclampsia?

Published reports do not agree about whether protein C activity is non-significantly changed or decreased in a hypercoagulable state induced by pre-eclampsia without hemolysis-elevated liver enzyme/low platelet (HELLP) syndrome. In order to assess the relationship between this anticoagulant and enhanced hemostasis, levels of protein C activity, thrombin-antithrombin complexes, soluble fibrin, fibrin D-dimers and antithrombin were determined in 30 pre-eclampsia patients without the HELLP syndrome, in 22 normal pregnant women in gestational weeks 30-35, and in 13 non-pregnant controls. Levels of thrombin-antithrombin complexes, soluble fibrin and D-dimers increased (P < 0.05) whereas antithrombin decreased (P < 0.05) in patients with pre-eclampsia, compared with normal pregnant women. Levels of protein C did not differ significantly between patients with pre-eclampsia, normal pregnant women and controls (P > 0.05). The 5th and 95th percentiles of protein C levels in normal pregnant women were 0.53 and 1.30 U/ml, respectively; levels between these two values could be considered physiological. When the pre-eclampsia patients were subdivided according to these percentiles, none belonged to the subgroup with protein C < or = 5th percentile; 23% (seven of 30) fell into the subgroup with protein C > or = 95th percentile. Elevated levels of hypercoagulation markers were shown in the groups whose protein C fell within 5th-95th or > or = 95th percentiles (P < 0.05), compared with normal pregnant women. Concentrations of protein C and thrombin-antithrombin complex were significantly correlated (r = 0.69, P > 0.05) in patients with pre-eclampsia. In summary, in subjects with pre-eclampsia without the HELLP syndrome, protein C activity may be similar to that in normal pregnant women. However, such a 'physiological' anticoagulant level in association with the enhanced thrombin generation and fibrin formation does not necessarily reflect a physiological capability of coagulation. Thus, assays of protein C activity might not always assist in monitoring the hemostatic function during pre-eclamptic pregnancy.

Adult↗
PubMedDate not supplied

Hemostatic profiles of HeartMate ventricular assist device recipients.

Candidates for ventricular assist devices often have hepatic dysfunction and concomitant coagulation abnormalities. Factors II, V, VII, XI, plasminogen, fibrinopeptide A (FpA), and D-dimers were measured in 19 HeartMate (ThermoCardiosystems, Inc., Woburn, MA) patients before device implantation; at 6 hr, 24 hr, and 2 weeks postimplantation; and before explantation. Ten patients had entry hepatic dysfunction (total bilirubin > 2 mg/dl; aspartate and alanine aminotransferases > 60 U/L); nine had normal hepatic function. All except one patient received perioperative aprotinin; all received only aspirin and dipyridamole after surgery. At preimplant, both patient groups had subnormal factor II, V, VII, XI, and plasminogen with elevated FpA and D-dimer. By 2 weeks postimplant, these factor levels had normalized, except for FpA and D-dimer levels, which suggest ongoing remodeling of fibrin deposits on the device surfaces. No statistically significant differences in the assayed hemostatic markers were observed between the two patient groups. Clinically, 15/19 (79%) patients survived to cardiac transplantation; 3/19 (16%) patients required reoperation for early bleeding. All three had low factor VII and XI; two of three also had hepatic dysfunction and subnormal levels of factor II and V. Most patients with entry hepatic dysfunction improve after device implantation; all four deaths were in patients with persistent hepatic dysfunction despite circulatory support.

Blood Coagulation Factors↗
PubMed1996

Effects of sodium ozagrel on hemostatic markers and cerebral blood flow in lacunar infarction.

The present study was designed to examine the effects of sodium ozagrel on hemostatic markers and cerebral blood flow in lacunar infarction. Ten cases of lacunar infarction in which sodium ozagrel was given (administered group), 10 cases of lacunar infarction in which sodium ozagrel was not given (nonadministered group), and 10 age-matched controls in which cerebrovascular diseases were absent but risk factors were similar to those of the patients (control group) were studied. Intravenous infusion of 80 mg of sodium ozagrel was done twice a day for 2 weeks. Platelet factor 4, beta-thromboglobulin, and fibrinopeptide A were significantly higher in the administered and nonadministered groups than in the control group at the time of admission. Platelet factor 4, beta-thromboglobulin, fibrinopeptide A, and thromboxane B2 were decreased significantly by the administration of sodium ozagrel. The blood flow in the cerebral cortex was significantly lower in the administered and nonadministered groups than in the control group. The blood flows around the infarcted area, in the cerebral cortex, and in the cerebral white matter were significantly increased by the administration of sodium ozagrel. Sodium ozagrel is considered to decrease platelet aggregation and increase cerebral blood flow by decreasing thromboxane A2, which has a platelet-aggregating and a vasoconstricting action. Sodium ozagrel is considered to be effective in the acute phase of lacunar infarction.

Aged↗
PubMed1999

Time course and prognostic significance of hemostatic changes in sepsis: relation to tumor necrosis factor-alpha.

OBJECTIVES: To describe the time course and prognostic significance of tumor necrosis factor-alpha (TNF-alpha) levels and hemostatic abnormalities in clinical sepsis. DESIGN: Prospective, observational study with sequential measurements in an inception cohort. SETTING: An emergency department in a university teaching hospital. Patients were followed up until they either left the hospital or died. PATIENTS: During a 1-yr period, 43 adult patients were selected from all emergency department patients who met the established criteria for sepsis. Excluded were patients with either organ dysfunction or septic shock at the time of admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected serially (day of admission and on days 3, 5, and 7) to determine TNF-alpha, platelet count, fibrinogen, factor VII, antithrombin III, tissue-type plasminogen activator activity, plasminogen activator inhibitor activity, plasminogen, and alpha2-antiplasmin. Fibrinopeptide A was measured only on the day of admission. Data were analyzed to determine whether admission values or serially obtained values within 7 days were useful in predicting outcome. Thirteen patients died and 30 survived. On admission, assay values indicated that platelet count and antithrombin III were significantly lower than normal (as observed in 50 healthy adults). Fibrinogen, plasminogen activator inhibitor type 1, tissue-type plasminogen activator, fibrinopeptide A, and TNF-alpha were higher than normal, whereas concentrations of factor VII, plasminogen, and alpha2-antiplasmin were in the normal range. No differences were detected in the admission values between survivors and nonsurvivors, except for antithrombin III. However, subsequent values of some variables demonstrated a difference between survivors and nonsurvivors. Survivors showed increasing platelet count and antithrombin III values compared with nonsurvivors, in whom the values remained low, with no significant changes during the study period. High TNF-alpha levels were found in both groups, but only survivors experienced progressive decrease during the observation period. CONCLUSIONS: Early clinical sepsis is characterized by high plasma levels of TNF-alpha and by activation of the coagulation and fibrinolysis systems. Longitudinal analysis of some variables (antithrombin III, platelet count, and TNF-ea) showed some differences with time between the survivor and nonsurvivor groups, but we feel that such differences were not large enough to be predictive in individual patients.

APACHE↗
PubMed2000

Changes of the hemostatic network in critically ill patients--is there a difference between sepsis, trauma, and neurosurgery patients?

OBJECTIVE: To study the time course of coagulation data in intensive care patients. DESIGN: Prospective, descriptive study. SETTING: Clinical investigation on a surgical and neurosurgical intensive care unit of a university hospital. PATIENTS: Fifteen patients with severe trauma (injury severity score, 15 to 25), 15 sepsis patients secondary to major surgery, and 15 neurosurgery patients (cancer surgery) were studied. INTERVENTIONS: Standardized intensive care therapy. MEASUREMENTS AND MAIN RESULTS: Standard coagulation data and molecular markers of coagulation activation and fibrinolytic activity (soluble thrombomodulin, protein C, free protein S, thrombin/antithrombin III complex, plasmin-alpha 2-antiplasmin complex, tissue plasminogen activator, platelet factor 4, beta-thromboglobulin were measured from arterial blood samples on the day of admission to the intensive care unit (trauma/neurosurgery patients) or on the day of diagnosis of sepsis (baseline value) and serially during the next 5 days. Antithrombin III, fibrinogen, and platelet counts were highest in neurosurgery patients but without significant differences between sepsis and trauma patients. Thrombin/antithrombin III complex increased in the sepsis patients (from 22.6+/-4.2 microg/L to 39.9+/-6.8 microg/L), but decreased in trauma (from 40.2+/-5.1 microg/L to 17.6+/-4.0 microg/L) and neurosurgery patients (from 28.2+/-4.2 microg/L to 16.2+/-3.8 microg/L). Tissue plasminogen activator increased in the sepsis patients (from 14.4+/-3.9 microg/L to 20.7+/-3.8 microg/mL) and remained almost unchanged in the other two groups. Soluble thrombomodulin plasma concentration increased significantly in the sepsis group (max, 131.8+/-22.5 ng/mL), while it remained elevated in the trauma (max, 75.5+/-5.9 ng/mL) and was almost normal in the neurosurgery patients. Protein C and free protein S remained decreased only in the sepsis group. CONCLUSIONS: Alterations of the hemostatic network were seen in all three groups of critically ill patients. Hemostasis normalized in the neurosurgery patients and posttraumatic hypercoagulability recovered within the study period. By contrast, monitoring of molecular markers of the coagulation process demonstrated abnormal hemostasis in the sepsis patients during the entire study period indicating ongoing coagulation disorders and abnormalities in fibrinolysis in these patients.

Adult↗
PubMed1988

Effects of contrast media on the hemostatic and thrombotic mechanisms.

The hemostatic and thrombotic mechanisms represent complex biologic systems. When a vessel is severed, a platelet plug begins to form, followed by activation of the coagulation mechanism to form thrombin, which converts fibrinogen to fibrin. The formation of thrombin also requires platelet coagulant activities, which help keep fibrin formation localized at the site of vessel wall damage. The thrombo-hemorrhagic balance represents a complicated homeostatic biologic system; this system has many control mechanisms, but its balance is rather fragile. Our studies show that the new nonionic contrast media induce far fewer changes in the thrombo-hemorrhagic balance than the ionic media.

Blood Coagulation↗
PubMedDate not supplied

The hemostatic effect of fibrin glue on graft donor sites.

One of the main uses of topical fibrin glue is hemostasis. Fibrin glue from pooled human plasma has been used in Europe for many years. It was used for fixation of skin grafts as early as 1944. Because of the risk of hepatitis and now of acquired immunodeficiency syndrome, this compound has not been approved by the U.S. Food and Drug Administration for use in the United States. It is now possible to make fibrin glue from a single unit of blood. Many blood banks have this capability, and burn centers in the United States are beginning to report its use in skin grafting procedures performed on patients with burns. In an effort to document a hemostatic effect, a prospective double-blind study was designed. Donor sites of patients with burns undergoing skin grafting were studied to provide a uniform wound; anatomic location varied, particularly with respect to gravity. Half of each donor site was sprayed with thrombin and fibrin glue, and the other half was sprayed with thrombin and placebo. A large absorbent pad was placed over the gauze dressing, and all dressings were collected and weighed by the investigators at 6 and 18 hours after the operation. Ten patients have been studied to date. In five patients slightly more bleeding occurred in the site treated with fibrin. One patient had no difference, and four had slightly less bleeding on the donor site treated with fibrin. No significant difference could be found in this initial study group.(ABSTRACT TRUNCATED AT 250 WORDS)

Burns↗
PubMed1993

Sex hormones and hemostatic risk factors for coronary heart disease in men with hypertension.

OBJECTIVE AND DESIGN: It has been hypothesized that risk factors for coronary heart disease in men are linked and that the underlying factor linking them may be an alteration in the sex hormone milieu. As a test of this hypothesis, sex hormones and fibrinogen, factor VII and plasminogen activator inhibitor (PAI-1), hemostatic factors recently shown to be risk factors for myocardial infarction, were measured in men with hypertension and in healthy control subjects. RESULTS: The fasting serum testosterone and free testosterone levels were decreased and the plasma factor VII and PAI-1 levels increased in the men with hypertension. CONCLUSION: These findings are consistent with the stated hypothesis.

Blood Coagulation Factors↗
PubMed2000

Effect of micronized fenofibrate on plasma lipoprotein levels and hemostatic parameters of hypertriglyceridemic patients with low levels of high-density lipoprotein cholesterol in the fed and fasted state.

A randomized, double-blind, placebo-controlled study was undertaken in 20 hypertriglyceridemic men [plasma triglyceride (TG), >2.3 mM] with low levels (<0.9 mM) of high-density lipoprotein cholesterol (HDL-C) to investigate the ability of micronized fenofibrate (Tricor or Lipidil; 200 mg/day) to affect atherogenic and thrombogenic plasma risk factors in the fed and fasted state. Each patient underwent (a) 4 weeks of dietary stabilization, (b) 8 weeks of treatment with fenofibrate or placebo, (c) a 5-week washout period, and (d) 8-weeks of treatment with the alternative medication. An oral fat-loading test (1 g fat/kg body weight) was carried out after both treatment periods. Before treatment, patients had a mean (+/- SD) total plasma TG of 3.31+/-0.93 mM; total C, 5.75+/-0.89 mM; HDL-C, 0.71+/-0.09 mM; and low-density lipoprotein (LDL)-C, 3.40+/-0.68 mM. Compared with placebo, fenofibrate reduced fasting TG levels by 36%, and triglyceride-rich lipoprotein (TRL, d<1.006 g/ml) -TG, and TRL-C levels by approximately 40%. In the postprandial state, fenofibrate reduced total TG, TRL-TG, TRL-C, TRL-apoC-III, and TRL-apoE levels by -35% (all values of p<0.01). Fasted and fed HDL-C and apoA-I levels were increased -10%, and total cholesterol/HDL cholesterol ratios were decreased -15% by fenofibrate. No significant differences were observed in mean LDL-C and LDL-apoB levels. A 6% increase in the LDL-C/LDL-apoB ratio during fenofibrate treatment indicated a shift to larger, more buoyant LDL particles. A small, but statistically significant (p<0.01) increase was observed in fasted and fed Lp(a) levels during fenofibrate treatment. Hemostatic parameters were not significantly affected by fenofibrate, except for a 12-15% decrease (p<0.05) in fibrinogen levels in the fasted and fed state, and a significant increase (43%; p<0.05) in fasting levels of plasminogen activator-inhibitor-1. These data demonstrate that micronized fenofibrate is highly effective, in both the fed and fasted state, in reducing TRL lipids and apolipoproteins, and in reducing plasma fibrinogen levels of men with an atherogenic lipoprotein profile.

Adult↗
PubMed1998

Trauma and thermal injury: comparison of hemostatic and cytokine changes in the acute phase of injury.

BACKGROUND: Initiated either by thermal injury or mechanical trauma, the systemic inflammatory response syndrome stimulates activation of coagulation and fibrinolysis, evolving into a subclinical disseminated intravascular coagulation. METHOD: Hemostatic parameters, interleukin-6, and endothelin plasma levels were compared in burn and trauma patients. Nineteen patients with major burn injury (> or = 40% total body surface area) were compared with 35 trauma patients with Injury Severity Scores > 25 on day 1 and days 5 to 8. RESULTS: Thrombin-antithrombin levels were significantly higher in trauma patients than in burn patients (p < 0.0001) on day 1, and endothelin was significantly higher on days 1 and 5 (p < 0.0001) in trauma patients than in burn patients. Interleukin-6 plasminogen activator inhibitor-1, and tissue plasminogen activator levels were elevated above normal limits on both days in both groups. CONCLUSION: There was a difference in the degree and level to which homeostasis was perturbed between the two groups. The mechanism of injury did not affect the initiation of subclinical disseminated intravascular coagulation and cytokine release, and the physiologic response remained the same.

Adult↗
PubMed2001

Dose-response and coagulation and hemostatic factors.

PURPOSE: The purpose of this study was to evaluate the dose-response relations of regular physical activity on platelet function, blood coagulation factors, and fibrinolytic factors, on the basis of studies with appropriate experimental design. METHODS: MEDLINE-based literature search supplemented with relevant review articles and other individual articles was used. The review concentrates on controlled randomized clinical trials on the impact of regular physical exercise on platelet function, and on blood coagulation and fibrinolytic factors. RESULTS: Physical exercise acutely activates platelets and the fibrinolytic system, and some factors of the blood coagulation cascade. These findings, the earliest of which were published already in the 1960s, are mainly derived from uncontrolled observations. These studies have led to the conclusion that unbalanced activation of the hemostatic system during acute exercise may be part of the mechanisms for sudden cardiac events during or shortly after heavy physical exercise. The effects of regular physical exercise on various aspects of platelet function, blood coagulation, and fibrinolysis have been the object in only a few controlled randomized trials. With the exception of data on platelet function, the results remain contradictory. CONCLUSION: Controlled randomized clinical trials with adequate statistical power and experimental study designs with subjects of different ages and health status are warranted for the evaluation of the dose-response issues to clearly delineate the preventive and therapeutic potential of regular physical exercise.

Adult↗
PubMed1992

Different aprotinin applications influencing hemostatic changes in orthotopic liver transplantation.

The effect of different aprotinin applications on hemostatic changes and blood product requirements in orthotopic liver transplantation was investigated in a prospective, open, and randomized study. From November 1989 to June 1990, 13 patients received aprotinin as a bolus of 0.5 Mill. Kallikrein inactivator units (KIU) on three occasions in the course of an OLT, whereas 10 other patients were treated with continuous aprotinin infusion of 0.1-0.4 Mill. KIU/hr. Before and after reperfusion of the graft liver, signs of hyperfibrinolysis, measured by thrombelastography, were significantly lower in the infusion group. Tissue-type plasminogen activator (t-PA) activity increased during the anhepatic phase but to a significantly lesser extent in the infusion group. Blood product requirements during OLT were tendentiously higher in the bolus group but not significantly so. However, the use of packed red blood cells was significantly lower in the postoperative period, whereas there was no significant difference in fresh frozen plasma requirements between the two groups. All 23 patients have survived, and only one woman of each group required retransplantation due to severe host-versus-graft reactions. Furthermore, we investigated the perfusate of the graft liver in both groups and detected signs of a decreased t-PA release in the infusion group. Our results demonstrate an advantage of aprotinin given as continuous infusion over bolus application in OLT.

Aprotinin↗
PubMed1993

Hemostatic changes in heart transplant recipients and their relationship to accelerated coronary sclerosis.

Hemostasis was assessed in 115 steady-state heart transplant recipients (HTRs) and compared with that of 23 age-matched healthy controls and 21 age-matched patients with ischemic heart disease (IHD). Compared with the controls, the HTRs had increased levels of fibrinogen (mean and 95% confidence limits of 4.50 [4.32-4.68] g/L versus 3.47 [3.07-3.87] g/L, P < 0.001), factor VIIC (1.16 [0.98-1.21] IU/ml versus 0.99 [0.89-1.10] IU/ml, P < 0.001), and von Willebrand factor antigen (1.72 [1.58-1.88] IU/ml versus 1.00 [0.80-1.26] IU/ml, P < 0.001). HTRs had increased antithrombin III activity (P = 0.002) and protein C activity (P = 0.002), with a decrease in total protein S levels (P < 0.001) but no change in free protein S levels. Stepwise discriminant analysis of hemostatic variables showed that fibrinogen was the best discriminator of the three groups, classifying 55.6% of HTR, 40% of IHD, and 66.7% of the controls. More marked prothrombotic changes were found in HTRs transplanted for IHD than for other causes; this reached significance for prothrombin (P = 0.048), factor IX (P = 0.003), and poor fibrinolytic activity as measured by euglobulin clot lysis time (P = 0.008). The HTRs with accelerated coronary sclerosis (ACS) tended to have the most prothrombotic changes; this reached significance with factor IX (P = 0.03). In conclusion, HTRs have perturbed hemostasis; the net effects of these changes are prothrombotic. The relationship between prothrombotic changes and ACS merits further studies.

Adult↗
PubMed2001

Value or desirability of hemorheological-hemostatic parameter changes as endpoints in blood lipid-regulating trials.

High levels of plasma lipids have been recognized as a major risk factor in the development and progression of atherosclerosis, and to influence hemorheological factors that may predispose to thrombotic complications. Lipid-lowering interventions have been associated with a significant reduction of morbidity and mortality. Several mechanisms have been postulated for the observed clinical effect. Serum lipid-regulating therapies may reduce cardiovascular risk not only by altering the arterial wall, improving disturbed endothelial function, atherogenesis and plaque stability, but also through their antithrombogenic effects and influence on blood flow properties associated with hyperlipidemia. In this article, we will review the recent literature and discuss the value of hemorheological-hemostatic findings as surrogate endpoints for clinical trials in dyslipidemic patients.

Blood Platelets↗
PubMed1979

Clinical and laboratory diagnosis of hemostatic disorders in newborn infants.

We describe a microtechnology for the study of the coagulation system in newborn infants. Interpretation of results demands an understanding of the techniques used and the nature of the control population from which normal values are drawn. We have examined two syndromes which represent the majority of hemostatic disorders of sick newborn infants. The first is thrombocytopenia resulting from bacterial infections in which there are minimal changes in the levels of blood coagulation factors and little tendency to bleed. The second is a syndrome of disseminated intravascular coagulation in which there is a profound disturbance in the coagulation mechanism, relatively little change in platelet counts, a severe hemorrhagic diathesis, and widespread ischemic necrosis.

Bacterial Infections↗
PubMed2003

Prevention of cerebrospinal fistulae and reduction of epidural scar with new surgical hemostat device in a porcine laminectomy model.

STUDY DESIGN: In a porcine laminectomy model, a standard dural/arachnoid incision was made and tested for cerebrospinal fluid leak after material application. Sites were graded for scar formation and healing response at 3 weeks. OBJECTIVE: This study compares effectiveness of CoStasis, Tissucol, and suture for prevention of cerebrospinal fluid leaks and epidural scar formation after spinal dural incisions. SUMMARY OF BACKGROUND DATA: Cerebrospinal fluid leaks following cranial and spinal surgery are potentially serious complications. Epidural scar formation is exacerbated by improper control of hemostasis. A hemostatic agent with dural sealant properties may be advantageous. METHODS: Total laminectomy was performed at three levels in seven pigs. At each level, a uniform 1.5 cm incision was made in the dura and arachnoid. A single suture was placed to approximate the edges and sites were treated with one of three methods: CoStasis, Tissucol, or no treatment. At sacrifice, 3 weeks later, epidural scar was graded, pressure testing of some sites was done, and tissue for histologic sections was harvested. RESULTS: CoStasis and Tissucol produced immediate dural sealing when the valsalva maneuver was applied. One suture-only site leaked. At sacrifice, all sites were sealed. CoStasis and Tissucol had less scar formation than control sites. Pressure testing results were similar at CoStasis and Tissucol sites. CONCLUSION: CoStasis and Tissucol have comparable effectiveness in sealing CSF leaks immediately and at 3 weeks after complete laminectomy. CoStasis demonstrated comparable performance to Tissucol with less epidural scar formation than primary suture alone.

Animals↗
PubMed2004

Safer transurethral resection of the prostate: coagulating intermittent cutting reduces hemostatic complications.

PURPOSE: Transurethral resection of the prostate (TURP) is still the gold standard for the surgical treatment of symptomatic benign prostatic hyperplasia. However, the associated morbidity and blood loss remain concerns. A coagulating intermittent cutting (CIC) device with constant voltage pulses and controlled pulse intervals was recently developed. The impact of CIC on bleeding and blood transfusion rates as well as the occurrence of the TUR syndrome were investigated. MATERIALS AND METHODS: From January 2000 to July 2002, 271 consecutive patients with symptomatic benign prostatic hyperplasia underwent TURP with the CIC device. In addition to blood transfusion rates, serum hemoglobin and electrolytes were determined in all patients immediately before and after TURP. RESULTS: The mortality rate in the 271 patients subjected to TURP was 0.0%. Mean decrease in hemoglobin after TURP was 1.08 mg/dl. Intraoperative and postoperative blood transfusions were required in 7 patients (2.6%), and clinical signs of the transurethral resection syndrome were noted in 1.1% of patients. CONCLUSIONS: Coagulating intermittent cutting dramatically improves the safety of TURP by decreasing intraoperative and postoperative blood loss, and the rate of blood transfusions. With this blood sparing device we anticipate a lower incidence of hemostatic complications from TURP.

Adult↗
PubMed2005

Hemostatic factors as predictors of stroke and cardiovascular diseases: the FINRISK '92 Hemostasis Study.

We carried out a prospective cohort study to determine whether the plasma levels of fibrinogen, plasminogen, factor VII and lipoprotein (a) are predictors of ischemic stroke and all cardiovascular disease (CVD) events. The FINRISK '92 Hemostasis Study included a random sample of 2372 participants, who were followed-up from winter 1992 to 31 December 2001. During the follow-up, 75 ischemic stroke and 145 coronary events occurred. Of these, 169 were observed among participants free of known CVD at baseline. In this group, fibrinogen and plasminogen were positively associated with the risk of a CVD event with hazard ratios of 1.22 [95% confidence interval (CI), 1.05-1.41] and 1.22 (95% CI, 1.03-1.44), respectively, after adjusting for age, sex and conventional risk factors. Factor VII:C was associated with risk of a future CVD event only among persons with positive history of CVD at baseline (hazard ratio, 1.32; 95% CI, 1.00-1.73). Factor VII antigen was not associated with CVD risk. None of the measured hemostatic factors was a predictor of ischemic stroke events, with the possible exception of lipoprotein (a), which had a borderline significant association (hazard ratio, 1.25; 95% CI, 0.99-1.58). In conclusion, the present study supports the observations that fibrinogen and plasminogen are significant predictors of CVD events, independently of conventional risk factors.

Biomarkers↗