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Postoperative complication from hemostatic clips.

Hemostatic clips were found in a patient's bladder four months after radical retropubic prostatectomy. A calculus, which had formed on one clip, caused acute urinary retention. Inadvertent enclosure of the hemoclips within the bladder intraoperatively and early intraurethral migration of the hemoclips are possible causes of this complication. Although this problem is rarely reported, hemoclips should be used sparingly, if at all, around the vesicourethral anastomosis.

Aged↗

Hemostatic properties and serum lipoprotein binding of a heparan sulfate proteoglycan from bovine aorta.

The biologic properties of two major proteoglycans of bovine aorta, heparan sulfate proteoglycan and chondroitin sulfate-dermatan sulfate proteoglycan were compared. The heparan sulfate proteoglycan was isolated either by elastase digestion or by 4.0 M guanidine hydrochloride extraction, of aorta tissue, fractionated by CsCl isopycnic centrifugation and purified by chondroitinase ABC treatment. The first method resulted in considerably greater yield (about 70% of the total heparan sulfate proteoglycan of the tissue) than the second procedure (12% of total). The chondroitin sulfate-dermatan sulfate proteoglycan was obtained by 4.0 M guanidine-HCl extraction of aorta tissue followed by CsCl isopycnic centrifugation. The chemical composition of both heparan sulfate proteoglycan preparations was similar. Unlike the chondroitin sulfate-dermatan sulfate proteoglycan, which eluted in the void volume of Sepharose CL-6B column, the heparan sulfate proteoglycan preparations were each resolved into a high molecular weight fraction (kav = 0.18 and 0.13) and a low molecular weight fraction (kav = 0.47 and 0.36). The heparan sulfate proteoglycan preparations exhibited significantly more potent anticoagulant and platelet aggregation inhibitory activities than the chondroitin sulfate-dermatan sulfate proteoglycan. The protein core of the proteoglycan molecules did not seem to be essential for their hemostatic properties. The complex forming ability of the heparan sulfate proteoglycan with serum low density lipoproteins (LDL) was much less than that of chondroitin sulfate-dermatan sulfate proteoglycan in the presence and absence of Ca2+. Interaction between heparan sulfate proteoglycan and LDL was also much more sensitive to changes in the ionic strength of the medium than that of chondroitin sulfate-dermatan sulfate proteoglycan and the lipoprotein. Since the total sulfate content of both proteoglycans is almost similar, the smaller molecular size and hence the lower overall charge density of the heparan sulfate proteoglycan appears to be partly responsible for its low affinity for LDL. The differences in biologic properties of the two proteoglycans might have implications in the pathophysiology of cardiovascular diseases.

Animals↗

Transdermal estrogen replacement therapy: beneficial effects on hemostatic risk factors for cardiovascular disease.

OBJECTIVES: To assess the effect of estrogen replacement therapy on hemostatic risk factors for cardiovascular disease (CVD) in postmenopausal women during 2 years of treatment. METHODS: In an open prospective study, patients (n = 42) were investigated before and during 2 years of treatment, and compared to an untreated postmenopausal control group (n = 18) followed during the same period, healthy premenopausal women (n = 20) being included as a reference group for premenopausal values. The patients underwent treatment with transdermal 17 beta-estradiol (E2) (50 micrograms/24 h), oral medroxyprogesterone acetate (5 mg/day) being added for 12 days every second month. RESULTS: After 2 years of treatment there was a significant increase in t-PA antigen (P = 0.01) and a significant decrease in F VII antigen (P = 0.01). PAI-1 antigen concentrations decreased slightly. Fibrinogen concentrations were already significantly decreased at 3-month follow-up (P = 0.01), and were still low after 2 years. By contrast, at 2-year follow-up the postmenopausal control group manifested significant increases in F VII and PAI-1 antigen and slight increases in fibrinogen, which resulted in significant differences between patients and controls. Regression analysis showed the increase in the serum estradiol concentrations to be inversely correlated to the decreases in the plasma concentrations of F VII antigen (r = -0.34, P = 0.001) and fibrinogen (r = -0.35, P = 0.001). There were no changes in AT III or protein C in any group. CONCLUSIONS: The increase in serum estradiol concentrations due to replacement therapy did not adversely affect the studied components of the fibrinolytic and protein C defense system against thrombosis, and resulted in beneficial decreases in F VII antigen and fibrinogen. These findings may help to explain the beneficial effects of estrogen replacement therapy in terms of protection from cardiovascular disease.

Administration, Cutaneous↗

Effects of granulocyte colony-stimulating factor on the hemostatic system in healthy volunteers.

We previously identified a receptor for granulocyte colony-stimulating factor (G-CSFR) on platelet membranes, and reported that G-CSF enhanced ADP-induced platelet aggregation. Here, we investigated the priming effect of G-CSF on the hemostatic system in healthy volunteers given G-CSF. Following the administration of rhG-CSF (10 micrograms/kg for 30 min div) to 10 healthy volunteers, we found a significant elevation in the maximum platelet aggregation rate induced by ADP or collagen, thromboxane B2 level and amount of thrombin-antithrombin III complex. The D-D dimer and plasminogen activator inhibitor-1 showed no significant changes. These observations indicate that G-CSF administration may induce hypercoagulability in susceptible subjects. Therefore, patients or donors at risk of thrombosis or hypercoagulable state should be followed carefully after G-CSF administration.

Adenosine Diphosphate↗

The relationship between hemostatic tests and cardiovascular risk factors in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities (ECAT) Angina Pectoris Group.

Baseline data are presented of the ECAT Angina Pectoris Study. Both plasminogen activator inhibitor and fibrinogen were positively associated with a number of cardiovascular risk factors such as smoking, body mass index, and also with the presence of coronary stenosis. Results indicate a role of the hemostatic system in the progress of coronary arteriosclerosis.

Angina Pectoris↗

The influence of dietary change on hemostatic risk variables.

In the 1970s in the Diet-Antismoking Trial, of the Oslo Study, colleagues and I found that the majority of high-risk men with elevated serum cholesterol and elevated triglyceride concentrations had impaired fibrinolytic capacity. Later on, both our group and others found a similar negative correlation between serum triglyceride levels and fibrinolytic capacity. Furthermore, in a prospective study of dietary intervention in individuals with both elevated cholesterol and triglyceride levels, we found that dietary lowering of serum triglyceride levels was significantly and positively correlated with an improvement in fibrinolytic capacity. In another study, we made the same observation for the coagulation factor VII-phospholipid complex: the more the triglycerides were reduced by diet, the greater was the change in factor VII complex. This correlation was highly significant and independent of changes in serum cholesterol. Platelet function is also influenced by dietary habits, but except for the effects of a fish oil-enriched diet, few data are available about the dietary effects on platelet function. It seems, however, that in individuals with elevated lipid levels and elevated blood pressure, increased platelet reactivity is a highly prevalent finding. Many of the hemostatic risk variables are associated with the so-called "metabolic risk syndrome" characterized by an increase in serum insulin level, together with increased relative body weight, mild hypertension, hyperlipidemia, and physical inactivity. This syndrome can often be influenced favorably by life-style changes. A controlled study with interventions in diet and activity level has just been started by our group.

Adult↗

Effects of atorvastatin (10 mg) on hemostatic and inflammatory parameters in hyperlipidemic patients with angiographically proven coronary artery disease.

Hyperlipidemic patients with coronary heart disease were treated with atorvastatin, and its effects on hemostatic and inflammatory parameters were assessed. After 3 months of therapy, the plasma levels of plasminogen activator inhibitor, prothrombin fragment 1+2, highly sensitive C-reactive protein, von Willebrand factor, and fibrinogen were significantly reduced; no significant reductions were observed in lipoprotein(a) and tissue plasminogen activator antigen levels.

Aged↗

Inflammatory and hemostatic responses to repeated mental stress: individual stability and habituation over time.

An important assumption underlying psychobiological studies relating stress reactivity with disease risk is that individuals are characterized by stable response profiles that can be reliably assessed using acute psychophysiological stress testing. Previous research has mainly focused on the stability of cardiovascular, neuroendocrine, and cellular immune responses to repeated stressors, and less attention has been given to inflammatory and platelet responses. We therefore examined both average stability and individual test-retest stability of cardiovascular, neuroendocrine, hemostatic, inflammatory, and subjective responses to mental stress over two repeated stress sessions, four weeks apart. Ninety-one healthy, non-smoking men (mean age 33.2 years) completed a 3-min speech task followed by a 5-min mirror tracing task on two separate occasions. Blood samples were taken at baseline and 10 min after the stress tasks while cardiovascular activity, saliva samples, and subjective ratings were measured repeatedly. There was significant cardiovascular and cortisol activation to the stressors and stress-induced increases in plasma C-reactive protein, von Willebrand factor antigen, and platelet activation indexed by leukocyte-platelet aggregates. The magnitude of stress responses did not differ between sessions in any variable. Significant test-retest correlations between sessions were observed for baseline and stress values of all variables (r=0.47-0.74, p<.001), but reactivity (change scores) for C-reactive protein, von Willebrand factor, cortisol, and platelet activation were not significantly correlated. Our results demonstrate that the stress-induced responses did not habituate between sessions, though the small magnitude of acute inflammatory, cortisol, and platelet responses limits the test-retest reliability of stress reactivity assessments.

Adaptation, Physiological↗

Effect of valproate on hemostatic function in patients with traumatic brain injury.

OBJECTIVES: To evaluate whether valproate (VPA) resulted in laboratory or clinical evidence of a change in bleeding-related measures associated with VPA therapy in patients sustaining a traumatic brain injury. METHODS: Fibrinogen, platelet count and clot elastic shear modulus using the Thrombelastograph (TEG) coagulation analyzer were measured at baseline, 4, 14, 30, and 180 days post-injury. Clinically significant events, defined as the trigger for requiring a transfusion, were identified and evaluated as to possible treatment effects. RESULTS: Compared to baseline, the platelet count in the VPA groups was decreased on day 4, increased by 100% on day 14, and returned to baseline levels by day 30. Fibrinogen was significantly increased by day 4 and returned to baseline by day 30. The platelet count was correlated with an increase in the maximum amplitude or width of the TEG tracing; a measure of strength of the clot, suggesting that valproate did not alter the clot strength contributed by platelets. None of the clinical events requiring transfusions appeared to be treatment related. CONCLUSIONS: No serious hemostatic adverse events occurred in the trauma patients receiving VPA or phenytoin that could be attributed to treatment.

Adult↗

Effect of urinary versus recombinant follicle-stimulating hormone on platelet function and other hemostatic variables in controlled ovarian hyperstimulation.

OBJECTIVE: To determine the effect of urinary versus recombinant FSH on platelet function and hemostatic variables in women undergoing controlled ovarian hyperstimulation cycles. DESIGN: Randomized clinical study. SETTING: Major university-based infertility and in vitro fertilization unit and hemostasis laboratory. PATIENT(S): Ten healthy women (in vitro study), and 24 women undergoing routine controlled ovarian hyperstimulation cycles (in vivo study), randomly assigned to receive either urinary (u-FSH) or recombinant gonadotropin (r-FSH). INTERVENTION(S): In vitro study: effect of preincubation of plasma with u-FSH or r-FSH, in the presence or absence of estradiol, on platelet function and coagulation parameters. In vivo study: Changes in platelet function and coagulation parameters after treatment with u-FSH or r-FSH during controlled ovarian hyperstimulation cycles. MAIN OUTCOME MEASURE(S): Platelet aggregation and ATP release, activated protein C resistance ratio, free protein S. RESULT(S): In vitro study: Platelet aggregation and ATP release were significantly inhibited by u-FSH relative to r-FSH in both the presence and absence of estradiol (P=.047). In vivo study: Platelet function was significantly inhibited after treatment with u-FSH (P=.05) but not with r-FSH. In both studies, small changes of minor clinical significance were noted in activated protein C resistance and free protein S levels. CONCLUSION(S): The different platelet response to u-FSH and r-FSH may have clinical implications in selected patients, especially those at risk of thromboembolic complications, in decisions regarding the appropriate medication for controlled ovarian hyperstimulation cycles.

Activated Protein C Resistance↗

Effects of depressive symptoms and anxiety on hemostatic responses to acute mental stress and recovery in the elderly.

Depression and anxiety are prospectively associated with cardiac morbidity and mortality. Increased clotting diathesis may mediate this link. We hypothesized that there would be an association between mood and hemostatic changes that occur during and following recovery from acute mental stress. Forty-eight community-dwelling elderly subjects underwent a laboratory speech stressor task. Plasma von Willebrand factor (vWF), thrombin/antithrombin III (TAT) complexes, D-dimer, tissue-type plasminogen activator (t-PA), and type I plasminogen activator inhibitor (PAI-1) were measured at rest, after conclusion of the speech, and 14 min afterwards (recovery). Mood was assessed with the Hamilton Rating Scales for Depression (Ham-D) and Anxiety (Ham-A). Mental stress elicited a hypercoagulable state as evidenced by increases in TAT and D-dimer, and by a decrease in t-PA. Overall, hypercoagulability had increased after recovery. Ham-D scores and Ham-A scores correlated with increases in D-dimer over the testing interval (i.e. area under the curve). Ham-A (but not Ham-D) uniquely explained 8% and 17% of the variance in resting D-dimer and D-dimer area under the curve, respectively. The independent association of anxiety symptoms with resting and stress-induced fibrin formation (D-dimer) may be a mechanism linking mood with cardiovascular disease risk in the elderly.

Acute Disease↗

Comparison of levels of inflammatory markers and hemostatic factors in the patients with and without peripheral arterial disease.

INTRODUCTION: Peripheral arterial disease is one aspect of atherosclerosis, a disease associated with both inflammation and hypercoagulability. Many recent studies have focused on the diversity of mechanisms by which inflammation can promote blood clotting. However, the relationship between plasma concentrations of inflammatory and hemostatic markers and the severity of atherosclerosis is not yet well studied. We want to determine the relations among selected D-dimer, C-reactive protein, fibrinogen, prothrombin time and serum amyloid A, and the ankle brachial index in patients with and without peripheral arterial disease. MATERIALS AND METHODS: In a prospective cohort study, 45 consecutive patients with peripheral arterial disease of ankle brachial index<0.90, and 44 patients without peripheral arterial disease of ankle brachial index 0.90 to 1.50 were included. D-dimer, fibrinogen, C-reactive protein, serum amyloid A, and prothrombin time were measured at the recruitment. RESULTS: Median values of serum amyloid A, D-dimer, and C-reactive protein were significantly higher in the peripheral arterial disease group than in those without peripheral arterial disease group (p<0.001). The patients with PAD had moderately higher fibrinogen levels than without PAD (p<0.01). Prothrombin time levels were normal in both groups. In multivariable regression analyses adjusting for all blood factors as well as potential confounders, patients with peripheral arterial disease, levels of serum amyloid A, and C-reactive protein showed a highly significant, inverse association with the ankle brachial index. D-dimer and fibrinogen level increase were also found to be related to lower ankle brachial index, while no association was observed between prothrombin time levels. CONCLUSIONS: Higher C-reactive protein, serum amyloid A, and D-dimer levels are showing positive association with the presence of peripheral arterial disease. C-reactive protein and serum amyloid A levels are direct relations between the ankle brachial index and the extent of vascular inflammation.

Arteritis↗

Hemostatic abnormalities and leukocyte activation caused by infection in patients with malignant lymphoma during chemotherapy.

Hemostatic parameters were examined before and during 102 courses of chemotherapy in 42 patients with malignant lymphoma with high risk for infection. The white blood cell count was significantly reduced in all patients at days 1 and 3, but significantly increased at days 7 and 9, compared to before chemotherapy. At day 7 of chemotherapy, tissue factor (TF) mRNA levels in leukocytes were significantly increased in all patients, especially those with infection. Plasma concentrations of granulocyte elastase derived-XDP (GE-XDP) levels correlated with D-dimer levels during chemotherapy in patients with malignant lymphoma, suggesting that the elevated D-dimer is fibrin products degraded by granulocyte elastase. GE-XDP, C-reactive protein (CRP), GE-XDP and D-dimer were significantly higher in patients with infection, disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS) than those without. In patients with DIC or ARDS, TF mRNA correlated with D-dimer, and GE-XDP correlated with leukocyte count, CRP and D-dimer, suggesting that inflammatory changes due to thrombosis may cause the activation of leukocytes in patients with malignant lymphoma during chemotherapy. Activated leukocytes and granulocyte elastase may elicit a hypercoagulable state and ARDS in patients with malignant lymphoma during chemotherapy.

Aged↗

Altered hemostatic balance and endothelial activation in pregnant women with familial hypercholesterolemia.

INTRODUCTION: Patients with familial hypercholesterolemia (FH) are prone to premature cardiovascular disease. During pregnancy plasma lipids reach higher absolute values in FH than in healthy women. Pregnancy is associated with activation of coagulation and possibly also of vascular endothelium, which might further increase the risk of cardiovascular disease in FH. However, whether hemostatic and endothelial activation markers are increased in pregnant FH women compared with non-FH pregnancies, is unknown. MATERIALS AND METHODS: Activation markers of hemostasis and endothelium were analyzed in blood samples collected prospectively from 22 heterozygous FH women during pregnancy and compared with those of a reference group of 149 healthy, pregnant women. RESULTS: A procoagulant pattern was detected in both groups, but was more evident among FH women at least partly due to their enhanced thrombin generation, and because tissue factor pathway inhibitor type 1 increased in the reference group only. Furthermore, plasminogen activator inhibitor type 2 antigen increased more in FH than in the reference group. Whereas C-reactive protein, intercellular adhesion marker-1 and E-selectin did not change appreciably, vascular endothelial cell adhesion molecule 1 rose markedly in FH. CONCLUSION: Increased lipid levels as well as a net procoagulant activity and an enhanced endothelial activation possibly confer additional risks of cardiovascular disease among pregnant FH women.

Adult↗

Effects of a single, daily alcoholic beverage on lipid and hemostatic markers of cardiovascular risk.

There is substantial epidemiologic data, but limited experimental data, supporting the mortality benefit of low-dose alcohol consumption. A regimen of a single, daily alcoholic beverage was sufficient to increase both high-density lipoprotein (HDL) (4.4%, p = 0.03) and HDL2 (7.7%, p = 0.04) in men and women, but did not significantly affect hemostatic markers of cardiovascular risk.

Adult↗

Efficacy and safety of a hemostatic puncture closure device with early ambulation after coronary angiography. Angio-Seal Investigators.

A collagen hemostatic puncture closure device has been developed as an alternative to traditional manual pressure techniques for achieving effective femoral arterial hemostasis after coronary angiography. The purpose of the current study was to determine if patients receiving this device can ambulate safely at 1 hour compared with patients receiving traditional manual pressure and bed rest after sheath removal for diagnostic cardiac catheterization. Patients (n = 304) were randomized to either the device group (n = 202) with ambulation at 1 hour after sheath removal or to the manual pressure control group (n = 102) with ambulation at 4 to 6 hours after sheath removal. The device group achieved earlier time to hemostasis (0.9 +/- 3 vs 17.0 +/- 8 minutes, p = 0.0001) and faster time to outpatient discharge (5.0 +/- 4 vs 7.7 +/- 4 hours, p = 0.0001) compared with the control group. There were bleeding or vascular complications in 19 patients (9%) in the device group and in 6 patients (6%) in the manual pressure group (p = 0.397). In patients undergoing diagnostic coronary angiography, this device, compared with traditional techniques for achieving hemostasis after sheath removal, allows for faster time to effective hemostasis with resultant earlier discharge from the hospital.

Aged↗

Circadian patterns of heart rate variability, fibrinolytic activity, and hemostatic factors in type I diabetes mellitus with cardiac autonomic neuropathy.

Diabetes mellitus is associated with a marked increase in the risk of coronary events but with an altered circadian distribution that demonstrates an absent morning peak and higher infarction rate during the evening hours. To elucidate the mechanism of this phenomenon, the circadian pattern of heart rate variability was evaluated in 22 type I diabetic patients with diabetic autonomic neuropathy in conjunction with circadian changes of fibrinolytic and hemostatic factors. The circadian pattern (6 A.M. to 10 P.M. vs 10 P.M. to 6 A.M.) of 3 indexes of parasympathetic tone was evaluated using 24-hour heart rate variability analysis. The high-frequency power (3.0 +/- 0.2 vs 3.3 +/- 0.2 ms2, p = 0.08) and the percentage of RR intervals with >50 ms variation (0.47 +/- 0.18 vs 0.69 +/- 0.33 ms, p = 0.52) demonstrated no significant circadian variation. The square root of mean squared differences of successive RR intervals showed a small but significant increase during nighttime (8.5 +/- 0.7 vs 9.7 +/- 1.1 ms, p = 0.02). Fibrinolytic activity was significantly lower at 8 A.M. than at 4 P.M. (166.4 +/- 12.5 to 200.2 +/- 9.3 mm2, p = 0.0003), but with a low amplitude. Plasminogen activator inhibitor 1 showed no circadian variation. Factor VII and fibrinogen demonstrated a significant reduction from 8 A.M. to 4 P.M., but both peak and nadir values were elevated. The von Willebrand factor was markedly elevated with no circadian variation. Thus, diabetic autonomic neuropathy is associated with a loss of both the nocturnal predominance of parasympathetic activity and a prothrombotic state that persists throughout the day. These abnormalities may attenuate the relative protection from coronary events during the afternoon and nighttime.

Adult↗

Preeclampsia, delivery, and the hemostatic system.

To determine the effects of preeclampsia and delivery, the hemostatic system was evaluated before and 24 to 48 hours after delivery in 59 nulliparous patients without clinical signs of disseminated intravascular coagulation. Fifteen patients with mild preeclampsia and 18 with severe preeclampsia were compared with 26 pregnant control patients. Preeclampsia was associated with high fibronectin (p less than 0.001), low antithrombin III (p less than 0.001), and low alpha 2-antiplasmin (p less than 0.005), suggesting endothelial injury, clotting, and fibrinolysis, respectively. After delivery, fibronectin decreased only in preeclamptic patients (p less than 0.005); alpha 2-antiplasmin increased in all groups (p less than 0.001). Endothelial injury in preeclampsia appeared to resolve soon after delivery, which could contribute to the rapid clinical improvement noted in the early puerperium.

Adult↗