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PubMed2006

Circulating procoagulant microparticles in obesity.

AIM: Obesity is a risk factor for cardiovascular diseases and venous thromboembolism. Circulating procoagulant microparticles (MP) have been described in various clinical situations associated with thrombosis and in diabetic patients. The aim of this preliminary study was to evaluate the presence of MP in obese patients without any other vascular risk factor in particular diabetes. METHODS: Fifty-eight obese women <50 year-old without other cardiovascular risk factors were recruited from a single out-patient nutrition clinic. They were compared to 45 age-matched healthy normal weight controls. Main outcome was MP levels in patients and controls. Relationships between MP concentrations and parameters reflecting insulin resistance in patients were also studied. RESULTS: Obese patients were 33.3 +/- 1.2 years old and had a mean BMI of 42.4 +/- 0.9 kg/m2. There vas a greater proportion of smokers in the obese group (34.5 vs 15.6%). Mean MP levels were markedly higher in obese patients compared to controls (10.6 +/- 0.5 vs 3.2 +/- 0.3 nMPSeq, P < 0.001). There was no difference in MP concentrations between smokers and non smokers. In the obese group, there was a negative correlation between MP and BMI (r = -0.265, P < 0.05) but no relationship could be established between MP concentrations and markers of insulin resistance. CONCLUSION: This increase in circulating MP levels reflects cell activation and could account for the increased risk of thrombotic complications in obesity. Further studies are ongoing to explore the relationships between MP levels and coagulation markers and to assess the effect of weight reduction.

Adult↗

PubMed2005

Intermittent saline flushes during haemodialysis do not alleviate coagulation and clot formation in stable patients receiving reduced doses of dalteparin.

BACKGROUND: Heparin-free haemodialysis (HD) with intermittent saline flushes (ISF) in patients with bleeding risk is widely used. The aim of this study was to investigate if ISF reduce coagulation and clotting in stable patients receiving reduced doses of dalteparin. METHODS: Inclusion criteria were stable chronic HD patients >or=18 years of age and haemoglobin >or=11 g/dl. Exclusion criteria were use of warfarin and acetylsalicylic acid. Six HD sessions were evaluated per patient. Dalteparin was given as one bolus dose at start of HD (50% of the conventional dose). In HD number 1, 3 and 5, 100 ml saline solution was flushed through the filter each 30 min. In HD 2, 4 and 6, no ISF were given. Potential clotting in the bubble trap was visually observed each hour and graded on a 4-point scale: 1 = normal, 2 = fibrinous ring, 3 = clot formation and 4 = coagulated system. The dialyser was visually inspected at the end of each session: 1 = normal, 2 = a few blood stripes (affecting less than 5% of the surface fibres), 3 = many blood stripes (more than 5% of the fibres) and 4 = coagulated filter. The coagulation marker PF1+2, the platelet activation marker beta-TG and anti-FXa activity were repeatedly measured during HD. RESULTS: Six men and two women were included. In four cases (four different patients), HD was stopped due to a coagulated system, all cases on days with ISF performed. Multiple linear regression analyses with repeated measurements showed that ISF adjusted for dalteparin dose/kg significantly increased mean clot in the bubble trap, estimate (B) = 0.717, P = 0.0001 and also showed that ISF increased PF1+2, B = 0.16, P = 0.001 when adjusted for anti-FXa activity and hours of dialysis, whereas beta-TG was only borderline increased, B = 0.09, P = 0.055. CONCLUSIONS: ISF during HD does not alleviate visible clotting or intravascular coagulation activity in stable patients receiving reduced doses of dalteparin and polysulphone dialysers. Whether this applies to unstable patients with increased bleeding risk not receiving any anticoagulation remains to be shown.

Adult↗

PubMed1996

Coagulation, fibrinolysis and fibrinolysis inhibitors in haemodialysis patients: contribution of arteriovenous fistula.

BACKGROUND: End-stage renal disease (ESRD) patients, not uncommonly, might exhibit thrombotic complications, as well as they may present with a bleeding diathesis. Changes in vessel wall and/or blood flow in native arteriovenous fistula (AVF) might also augment these disarrangements, as vascular endothelium is predominantly involved in the regulation of haemostatic pathways. OBJECTIVE: This study was designed to evaluate the state of coagulation and fibrinolysis and the role of AVF on haemostatic defects, in ESRD patients on maintenance haemodialysis. METHODS: Plasma samples for prothrombin fragment 1+2, thrombin-antithrombin III complex, plasmin-alpha2 antiplasmin complex, tissue type plasminogen activator antigen, urokinase type plasminogen activator antigen, u-PA activity, plasminogen activity, alpha2-antiplasmin and alpha2-macroglobulin assays were obtained from AVF and contralateral large veins of ESRD patients and from peripheral veins of the control group. RESULTS: Our results indicate a predominant thrombotic state as evidenced by activated coagulation markers and enhanced fibrinolysis in systemic circulation of ESRD patients. However the most novel finding is the probable contribution of AVF on haemostatic activation, as proven by the statistically different and positively correlated concentrations of both coagulation, fibrinolysis, and fibrinolysis inhibitors in AVF when compared to the levels in peripheral venous circulation. CONCLUSION: In addition to systemic derangements of haemostasis in ESRD patients, AVF individually might have a substantial role in the modulation of coagulation and fibrinolytic cascade.

Adult↗

PubMed2006

Sialic acid is an inflammation marker associated with a history of deep vein thrombosis.

INTRODUCTION: Deep vein thrombosis (DVT) induces a systemic chronic inflammation and it has been associated with atherosclerosis. Increased levels of total sialic acid (TSA) have been shown to correlate with inflammation and atherosclerotic processes. The aim of this study was to investigate whether or not increased levels of TSA are associated with a history of DVT and with inflammation and coagulation markers, as well as with the lipid profile. MATERIALS AND METHODS: TSA, fibrinogen, C-reactive protein (CRP), fibrin D-dimer (D-dimer), prothrombin fragment 1+2 (F1+2), endogenous thrombin generation, cholesterol and triglycerides were measured in 68 patients who had suffered, in the previous 6-12 months, a first episode of idiopathic DVT, and in 68 age- and sex-matched healthy subjects. RESULTS: Levels of TSA, fibrinogen, CRP and D-dimer observed in patients were significantly higher than those detected in healthy subjects. TSA positively correlated with fibrinogen (R=0.47, p<0.01), cholesterol (R=0.46, p<0.01), triglycerides (R=0.38, p<0.01) and CRP (R=0.28, p<0.05). The logistic regression analysis confirmed that both high fibrinogen (> or =340 mg/dl) and cholesterol (> or =267 mg/dl) levels significantly and independently influence the TSA concentration. TSA levels above the 95th percentile of controls (>72 mg/dl) were detected in 33% of patients (OR=8.9; p<0.0001; 95% CI 2.4 to 31.7). CONCLUSIONS: Patients with a history of DVT had associated high levels of TSA. In these patients, TSA correlated to markers of inflammation activity and lipid profile. Thus, TSA appears to be a useful vascular inflammatory marker in idiopathic DVT.

Adolescent↗

PubMedDate not supplied

Effects of black cohosh (Cimicifuga racemosa) on bone turnover, vaginal mucosa, and various blood parameters in postmenopausal women: a double-blind, placebo-controlled, and conjugated estrogens-controlled study.

OBJECTIVES: In this study, the effects of the Cimicifuga racemosa (CR) preparation CR BNO 1055 on markers of bone metabolism, hormones, sex hormone-binding globulin (SHBG), lipometabolism, vaginal maturity, and routine laboratory parameters were compared with those of conjugated estrogens (CE) and placebo. DESIGN: Sixty-two postmenopausal women were included in this double-blind study. Treatment duration with CR (daily dose corresponds to 40 mg of herbal drug), CE (0.6 mg/day), or placebo was 12 weeks. Markers of bone turnover (bone-specific alkaline phosphatase, CrossLaps), estradiol, follicle-stimulating hormone, leuteinizing hormone, SHBG, triglycerides, total cholesterol, high-density cholesterol, low-density cholesterol, and routine clinical chemistry parameters were determined from blood samples. Vaginal "maturity index" was determined from vaginal smears. RESULTS: The analyses of bone turnover markers indicated beneficial effects for CR and CE on bone metabolism. CR stimulated osteoblast activity, whereas CE inhibited osteoclast activity. Whereas CE showed strong estrogenic effects on vaginal mucosa, CR showed weak estrogen-like activity. No significant effects were seen on coagulation markers and liver enzymes in the blood. CR was well tolerated. CONCLUSION: These results suggest that CR has beneficial bone remodeling and weak estrogen-like effects in the vaginal mucosa.

Adult↗

PubMed2000

Platelet activation during angiotensin II infusion in healthy volunteers.

The present study was undertaken to evaluate the effects of an intravenous infusion of angiotensin II (10 ng/kg per min) on platelet function and coagulation in vivo in 18 healthy males. The infusion increased mean arterial pressure by 23+/-2 mm Hg. Plasma beta-thromboglobulin levels, reflecting platelet secretion, increased by 66+/-24% during the infusion, as did also platelet surface expression of P-selectin as measured by flow cytometry. Platelet fibrinogen binding increased, whereas platelet aggregability, assessed by ex vivo filtragometry, was unaltered. Angiotensin II caused mild activation of the coagulation cascade with increases in plasma levels of thrombin-antithrombin complex and prothrombin fragment F1 + 2. In conclusion, angiotensin II has mild platelet-activating effects in vivo and also enhances coagulation. Markers of platelet secretion are significantly increased, whereas markers of platelet aggregability are less affected. The clinical relevance of these findings remains to be clarified.

Adult↗

PubMed2004

Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: The ATTICA Study.

OBJECTIVES: We studied the effect of the Mediterranean diet on plasma levels of C-reactive protein (CRP), white blood cell counts, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, amyloid A, fibrinogen, and homocysteine. BACKGROUND: To the best of our knowledge, the mechanism(s) by which the Mediterranean diet reduces cardiovascular risk are not well understood. METHODS: During the 2001 to 2002 period, we randomly enrolled 1,514 men (18 to 87 years old) and 1,528 women (18 to 89 years old) from the Attica area of Greece (of these, 5% of men and 3% of women were excluded because of a history of cardiovascular disease). Among several factors, adherence to the Mediterranean diet was assessed by a diet score that incorporated the inherent characteristics of this diet. Higher values of the score meant closer adherence to the Mediterranean diet. RESULTS: Participants who were in the highest tertile of the diet score had, on average, 20% lower CRP levels (p = 0.015), 17% lower IL-6 levels (p = 0.025), 15% lower homocysteine levels (p = 0.031), 14% lower white blood cell counts (p = 0.001), and 6% lower fibrinogen levels (p = 0.025), as compared with those in the lowest tertile. The findings remained significant even after various adjustments were made. Borderline associations were found regarding TNF-alpha (p = 0.076), amyloid A levels (p = 0.19), and diet score. CONCLUSIONS: Adherence to the traditional Mediterranean diet was associated with a reduction in the concentrations of inflammation and coagulation markers. This may partly explain the beneficial actions of this diet on the cardiovascular system.

Adolescent↗

PubMed2000

Polyuria and proteinuria in cystinosis have no impact on renal transplantation. A report of the North American Pediatric Renal Transplant Cooperative Study.

Because cystinotic patients are polyuric and may have severe proteinuria, each of which is a potential risk factor for graft thrombosis, preemptive transplantation for them is questionable. The objectives of this study were to characterize the changes in urine volume and protein excretion at various stages of cystinosis, determine whether there is serologic evidence of hypercoagulability, and review the clinical experience in renal transplantation in cystinotic children. The records of cystinotic patients followed at the Montreal Children's Hospital between 1992 and 1998 were reviewed. Urinary volume, protein excretion, and coagulation markers were collected to determine the glomerular filtration rate (GFR) >50 ml/min/1.73 m2, <20 ml/min/1.73 m2, before and after starting dialysis. In addition, graft failure and graft thrombosis rates were obtained from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database. Urinary volume and protein excretion remained elevated throughout different phases of the disease. Coagulation factors were within normal limits for all patients. In the NAPRTCS database there were four thromboses among the 114 patients transplanted cystinotic patients. All these occurred in cadaveric grafts and only one occurred after preemptive transplantation. Despite polyuria and severe proteinuria, children with cystinosis do not appear to be at an increased risk of graft failure or graft thrombosis.

Child↗

PubMed2006

Hypercoagulability risks among adult living liver donors.

BACKGROUND: Review of the literature is limited with respect to thrombotic risk in the living liver donor. This study examines inherent coagulable changes that occur as a result of the surgery. MATERIALS AND METHODS: At our center, we have performed 353 orthotopic adult liver transplants in the past 4 years. Of these, 20 were adult-adult right lobe living donor transplants. All living donors are alive and doing well. Of these, eight living donors were followed preoperatively and postoperatively monitoring protein C, protein S, antithrombin III, and factor VIII levels. Levels were checked at 48 hours postoperatively, as well as at 2, 4, and 6 weeks. RESULTS: All eight patients had normal levels preoperatively, although significantly low levels were identified postoperatively of these coagulation markers: protein C decreased to as low as 0%, (range 0-29; normal 50-150) within 48 hours postoperatively; protein S decreased to 3% to 40% during the same time frame (normal 50-150), and antithrombin III levels decreased to 47% to 55% (normal range 50-150%). Factor VIII levels significantly increased to >200% (normal 50- 150). All coagulation levels returned to the normal range within 4 to 6 weeks. None of the patients developed a thromboembolic event. CONCLUSIONS: We observed an imbalance of low protein C, S, and antithrombin III and elevated factor VIII levels, which have been documented as thrombotic risks in adults. Our findings suggest that the imbalance in the coagulation profile after surgery may be an independent risk factor for thrombosis beyond the surgical event, a phenomenon that requires further exploration.

Adult↗

PubMed2005

Activated cytotoxic T cells and NK cells in severe sepsis and septic shock and their role in multiple organ dysfunction.

To evaluate the role of activated cytotoxic cells in patients with severe sepsis (n = 32) or septic shock (n = 8), direct (granzymes A and B) as well as indirect markers (cytokines) for cytotoxic cell activation were measured. Elevated IL-12p40 levels had been detected in 58% of the sepsis patients, whereas only a few had detectable TNF-alpha, IFN-gamma, or IL-12p70 levels. Granzymes A and B levels were elevated in 42.5% and 22.5%, respectively. IL-12p40 inversely correlated with disease severity. Inflammatory parameters (IL-6) and coagulation markers were significantly lower and higher, respectively, in patients with elevated IL-12p40 and granzyme B levels, as compared to those with normal levels. Elevation of granzyme A directly correlated with the increase of apoptotic markers. Activated cytotoxic cells reflected by elevated granzymes A and/or B were found in 50% of our sepsis patients. This group showed a higher mortality and a worse organ function.

Adult↗

PubMed2006

The use of PEG-Hirudin in chronic hemodialysis monitored by the Ecarin Clotting Time: influence on clotting of the extracorporeal system and hemostatic parameters.

AIM: The aim of our study was to investigate the use of polyethylene glycol (PEG)-Hirudin (PEG-H) as an anticoagulant in hemodialysis including drug monitoring with the Ecarin Clotting Time (ECT) in whole blood and to compare this regimen with standard anticoagulant unfractionated heparin (UFH) for influence on hemostatic parameters and clot frequency of the extracorporeal system. PATIENTS AND METHODS: The application of PEG-H as an anticoagulant in patients on chronic HD was studied in 20 patients (12 males, 8 females) from a single center in an exploratory, open-label, controlled, single-blind, dose-finding study. The patients were divided in 2 groups with 10 patients each (Group I and II); both received 3 dialyses with UFH, thereafter Group I received 5 dialyses with PEG-H and Group II 10 dialyses with PEG-H. Starting dose of PEG-H in the first dialysis was a bolus of 0.08 mg/kg bwt, the mean dose of the following HD was 0.041 mg/kg bwt (range 0.026 0.065 mg/kg bwt). PEG-H was applied as an intravenous bolus-dose followed by a 0.9% saline as a placebo-infusion. HD was performed regularly 3 times a week. All dialysis treatments were performed exclusively with a hollow fiber dialyzer type. Fibrinogen, antithrombin III, prothrombin fragments, thrombin-antithrombin and soluble fibrin were measured with commercial tests. ECT was determined in a mechanical coagulometer. A semiquantitative score was given for the presence of clots in the extracorporeal system after each dialysis. RESULTS: PEG-H was effectively used as an anticoagulant in 150 chronic dialysis treatments using ECT as a simple monitoring method. The optimal whole blood concentration for PEG-H is 600-1000 ng/ml. Clotting in the whole extracorporeal system was decreased by 45% (p = 0.059) with PEG-H anticoagulated HD in comparison to UFH. Fibrinogen, prothrombin fragments (F1+2-fragments) and thrombin-antithrombin-complex showed no significant change in comparison with UFH, antithrombin III (AT III) increased to normal concentrations. Highly sensitive coagulation markers such as a soluble fibrin showed a significant decrease (p < 0.001) before and after HD with PEG-H compared with UFH. CONCLUSION: PEG-H can be used effectively as an alternative anticoagulant in patients on chronic HD using ECT as a simple drug monitoring method. The lower frequency of clots in the extracorporeal system, the stronger and more efficient inhibition of coagulation during HD as indicated by soluble fibrin, may have a positive influence on the disturbed blood coagulation of these patients.

Adult↗

PubMed1977

Relationship between perimetric eccentricity and retinal locus in a human eye. Comparison with theoretical calculations.

A blind but grossly normal eye was removed because of severe pain. With the patient's consent, photo-coagulation markers were placed along the horizontal meridian of the retina prior to surgery. The angular coordinates in visual space of the markers were determined by an ophthalmoscopic procedure. The loci of the markers were also determined in a flat preparation following enucleation. The relationship between retinal arc and perimetric eccentricity was found to be approximately linear up to at least 50 degrees. Our findings validate earlier theoretical calculations within this range.

Female↗

PubMed2005

Maternal fibrinogen is necessary for embryonic development.

Fibrinogen (Fg) is a precursor of fibrin, which is one of the main components of blood clots generated during the hemostatic response. Beyond its important role in hemostasis, Fg is involving in several physiologic and pathophysiologic states, such as infection, wound healing, the progression of certain types of tumors, and the severity of atherosclerosis. In addition, Fg has a critical role in maintaining pregnancy. Ovulation, fertilization, and implantation of the fertilized egg to the uterine wall can occur in afibrinogenemic women. However, all pregnancies in these patients resulted in spontaneous miscarriage. Fg supplemental therapy allows the patients to sustain the pregnancy. Mice with a total fibrinogen deficiency (FG-/-) reproduce the human experience. Despite of successes with fibrinogen supplementation, "paradoxical thrombosis" sometimes occurs, wherein supplemental therapies cause catastrophic thrombosis, such as pulmonary and mesenteric venous thrombosis. In these therapies, syncytial knots, hyaline membrane, and multiple recent infarctions with abruptio placenta were also observed. These findings indicate that the dosage regimen of Fg in afibrinogenemia-related pregnancies needs to be optimized according to other coagulation markers, such as thrombin-antithrombin complex (TAT) concentration, which represents the extent of thrombin formation. In addition, baseline thrombin assays would be helpful to predict the potential for paradoxical thrombosis during the supplemental therapy offered during pregnancy.

Adult↗

PubMed2005

Prognostic value of a simple evolving disseminated intravascular coagulation score in patients with severe sepsis.

OBJECTIVE: We postulated that the coagulopathy initiated by the inflammatory response to severe sepsis would be reflected by changes in the platelet count and prothrombin time that convey prognostic information. To examine this hypothesis, we looked at the utility of a simple evolving disseminated intravascular coagulation (DIC) score that awarded 1 point for each of the following: a) an absolute platelet count <100 x 10/L; b) a prothrombin time >15.0 secs; c) a 20% decrease in platelets; and d) a >0.3-sec increase in prothrombin time in predicting outcome in patients with severe sepsis. DESIGN: Prospective observational study. SETTING: Intensive care units of university medical center. PATIENTS: Patients were 163 critically ill severe sepsis patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were clinically classified as having capillary leak syndrome (n = 24), multiple organ failure with death from sepsis (n = 37), or multiple organ failure with recovery (n = 57) or as well (n = 45) if they showed rapid improvement in their modified Multiple Organ Dysfunction Syndrome (MODS) score (which did not score for thrombocytopenia). Patients with capillary leak syndrome had the highest Acute Physiology and Chronic Health Evaluation II score, modified MODS, and prothrombin time and the lowest platelet counts, whereas well patients had the most normal values. The simple evolving DIC score increased with worsening clinical class and was associated with worsening organ failure (increased modified MODS). Mortality rate increased from 10% for a simple evolving score of 0 to 73% for a score of 4 (p < .01). Overall, 86% of those with a score < or =1 survived, whereas 85% of those with a score of > or =2 developed multiple organ failure and half of them died from sepsis. CONCLUSIONS: The simple evolving DIC score calculated in the first 48 hrs from two readily available global coagulation markers appears to reflect the severity of the underlying disorder. It can be easily calculated at the bedside and provides useful prognostic information for the patient with severe sepsis.

Adult↗

PubMed1986

Immunohistochemical study of mononuclear phagocyte antigens in giant cell tumor of bone.

The cytogenesis of giant cell tumor of bone (GCT) was assessed by immunohistochemical methods. Three GCT were analyzed by a sensitive immunoalkaline phosphatase technique with a panel of monoclonal antibodies, including eight reacting with separate antigens previously found to be present on mononuclear phagocytes (MPs) and one specific for the endothelial marker, coagulation Factor 8. Among the MP-associated antigens evaluated were leukocyte common antigen (LCA), HLA-DR, C3b receptor, and C3bi receptor. Also incorporated in the panel were antibodies to MP-associated antigens with well-characterized tissue distribution but of currently unknown function. Constituent cells of the tumors varied in their reactions with the antibodies of the panel. Although mononuclear cells in tumor stroma were labeled with all of the antibodies against the MP markers, giant cells reacted strongly only with antibodies to LCA and the MP-associated antigen recognized by the antibody EBM11. Giant cells were weakly and focally labeled with antibodies (KB90 and UCHM1) against two additional MP-associated determinants and were unreactive with the remaining antibodies in the panel. Spindled stromal cells, which appeared to produce collagen, were not labeled with any of the antibodies in the panel. Only endothelial cells reacted with antibody to Factor 8. The results of this study suggest that giant cells of GCT are derived from stromal cells of mononuclear phagocyte lineage, and that the stromal precurser cells lose some, but not all, MP-associated antigens as they mature into giant cells.

Adolescent↗

PubMed2000

Co-administration of aprotinin and epsilon-aminocaproic acid during cardiopulmonary bypass in a swine model.

Despite the beneficial effects of pharmacological interventions to prevent bleeding and to reduce the need for autogeneic blood, there are concerns that these agents induce a prothrombotic state. The purpose of this study was to examine the coagulation phenomena influenced by the coadministration of epsilon-aminocaproic acid (EACA) and aprotinin during cardiopulmonary bypass (CPB). A swine model of CPB was utilized in this study. During 120 min of CPB, treatment animals (N = 5) received 6 x 10(6) Kiu of aprotinin and 30 grams of EACA; whereas, control animals (N = 3) received an equal volume of 0.9% saline. Indices of thrombogenicity included hematological variables, gross pathology, and circuit examination for the presence of thrombus. The application of both antifibrinolytics resulted in an increase use of heparin. Total heparin requirements were significantly different between treatment group (58,800 +/- 3493 iu) versus control group (51,000 +/- 3464 iu). D-dimer concentration was also significantly higher in the control group (500-1000 ng mL-1) than in the treatment group (250-500 ng mL-1) at 5 and 30 min postprotamine. Other coagulation markers tested were not observed to be statistically significant between groups. Thromboelastographic (TEG) index decreased in the treatment group during the surgical procedure and bypass from 2.74 +/- 2.9 to -1.36 +/- 4.1 as compared to an increase from 2.62 +/- 2.9 to 4.05 +/- 0.4 in the control group. Pathologic analysis revealed occurrences of thrombus formation in small vessels in the lung and kidney glomeruli of treatment animals. The concurrent use of both aprotinin and EACA may induce a prothrombotic or coagulant state as determined by histological assessment.

Aminocaproic Acid↗

PubMed1995

Activation of the fibrinolytic, coagulation and plasma kallikrein-kinin systems during and after open heart surgery in children.

Activation of the fibrinolytic, coagulation and plasma kallikrein-kinin systems may be responsible for some of the coagulation disorders and inflammatory sequelae seen after extracorporeal circulation. The activation pattern of these systems was studied in 10 children undergoing open heart surgery with extracorporeal circulation. Blood samples were drawn serially before, during and up to 48 h after surgery. The heparin injection induced a significant elevation of plasmin (PL) (p < 0.05) which stayed elevated during extracorporeal circulation. Antiplasmin (AP) values were reduced at wound closure, while the levels were significantly elevated 48 h postoperatively (p < 0.05). alpha 2-antiplasmin-plasmin (APP) increased significantly perioperatively peaking 10 min after the initiation of cardiopulmonary bypass (p < 0.05). The coagulation markers thrombin-antithrombin (TAT) and the prothrombin fragment F1 & 2 increased significantly, peaking at wound closure and at termination of bypass respectively (p < 0.05). Plasma kallikrein (KK) values increased significantly with subsequent decreased levels of prekallikrein (PKK) and kallikrein inhibitor (KKI) after heparin injection. The KK level stayed elevated during cardiopulmonary bypass (CPB). The proenzyme functional inhibition index (PFI index), defined as the sum of deviations from the control values for proenzyme and functional inhibition values of the coagulation, fibrinolytic and plasma kallikrein-kinin systems, correlated significantly to the duration of cardiopulmonary bypass (p < 0.05). We conclude that open heart surgery in children activates the fibrinolytic, coagulation and plasma kallikrein-kinin systems.

Antifibrinolytic Agents↗

PubMed1996

Impaired haemostatic kinetics and endothelial function in Behçet's disease.

OBJECTIVES: This study was planned to explore the alterations of endothelial functions in the prethrombotic state of Behçet's disease (BD) patients. DESIGN: Plasma levels of endothelial secretory markers, in vivo molecular haemostatic and fibrinolytic parameters were cross-sectionally determined in the study group. SETTING AND SUBJECTS: In our tertiary referral centre, 30 (13 men, 17 women) BD patients, mean age 31 +/- 7 years, and 15 (eight men, seven women) healthy volunteers, mean age 26 +/- 9 years, were eligible for inclusion in the study after obtaining their written consents. INTERVENTIONS: All plasma samples for the assays of haemostatic parameters were obtained before and after an endothelial stimulant, desmopressin acetate (DDAVP). RESULTS: We have shown that in the procoagulant phase of BD patients: (1) basal thrombomodulin concentrations are increased and could not be provoked by DDAVP infusion; (2) both thromboxane B2 and 6-keto prostaglandin F1 alpha increments occur concurrently; (3) in vivo coagulation markers are elevated and raised plasmin-alpha 2 antiplasmin complex indicates a subclinical concomitant fibrinolysis; (4) the fibrinolytic process is conveyed in a somewhat complex manner in which plasminogen activator binding kinetics might be also altered. CONCLUSIONS: Endothelial cell injury, augmented thrombotic risk with compensatory excessive fibrinolysis and alterations in endothelial cell receptor-fibrinolytic marker relations might take place in the pathogenesis and thereby modulate the natural course of haemostatic processes of BD.

Adult↗