Fibrinopeptide A Levels Research Articles

Transient intermittent lymphocyte activation is responsible for the instability of angina.

Blood clotting activation is an important component of the inflammatory response; the outbursts of unstable angina are usually associated with increased thrombin formation and coronary mural thrombosis. To investigate 1) whether monocyte activation is responsible for the enhanced thrombin formation during bursts of unstable angina and 2) what mechanism(s) might be responsible for monocyte activation, we studied patients with unstable angina (n = 31), stable effort angina (n = 23), left endoventricular thrombosis (n = 8), and control subjects (n = 44), measuring plasma fibrinopeptide A (FPA) levels and the capacity of monocytes to express procoagulant activity (PCA) and of lymphocytes to modulate this expression. Patients with unstable angina and patients with endoventricular thrombosis had significantly (p less than 0.0001) higher FPA plasma levels than patients with effort angina and control subjects. However, only monocytes from unstable angina patients expressed significantly increased PCA characterized as tissue factor-like activity (units/10(5) monocytes, median and range; 120, 1.1-463.2 versus 10.8, 0.8-39.1 in control subjects; p less than 0.0001 versus the other groups). When 14 patients with unstable angina were restudied 8-12 weeks later, they showed neither elevated plasma FPA levels nor monocyte PCA. In unstable angina patients, there was a correlation between FPA and PCA (r = 0.56, p less than 0.001). For expression of PCA by monocytes, both an incubation of at least 2 hours with lymphocytes and direct monocyte-lymphocyte contact were needed. In reconstitution and cross-mixing experiments, only lymphocytes from patients with active unstable angina induced the expression of PCA by monocytes from both control and patient groups. The results demonstrate that the increased thrombin formation in unstable angina patients is due to the expression of tissue factor-like activity by activated monocytes. The monocyte activation appears to be a part of a lymphocytic cell-instructed response intermittently triggered by unknown factors.

Preventing increased fibrin formation during percutaneous transluminal coronary angioplasty through activated clotting time-controlled heparin treatment

Background: A combination of heparin and aspirin is currently used to prevent coronary thrombosis in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). However, the ideal heparin dosage for this use has not been established. In this study we examined a biochemical method for evaluating heparin regimens used during interventional procedures. Methods: We measured the levels of fibrinopeptide A (FPA) in plasma and in 24-hour urine samples to examine the effects of heparin on fibrin formation in 37 patients undergoing PTCA and receiving two different dose regimens of heparin. A total of 18 patients received a standard dose of heparin (10,000 IU) immediately before the PTCA procedure (group 1); in another 19 patients the dosage was adjusted so that an activated clotting time (ACT) of greater than 300 seconds (20,500 ± 6600 IU) was established before the PTCA procedure began (group 2). Results: In group 1 the plasma FPA level increased from 1.9 ± 1.0 ng/mL before to 4.2 ± 1.2 ng/mL after PTCA (P< 0.01) and levels in urine increased from 3.9 ± 1.6 ng before to 9.9±2.8 μg after PTCA (P< 0.01). In group 2 there was no significant change in the FPA level in plasma or urine with PTCA. Although no major bleeding complications occurred in either group, the hematocrit nadir after PTCA was lower in group 2 (P< 0.05). Conclusions: Percutaneous transuminal coronary angioplasty may be associated with an increase in fibrin formation as measured by FPA levels in plasma or in 24-hour urine samples. Adjusting heparin dose with respect to ACT may prevent this increase in fibrin formation.

Thrombin activity resides on LVAD Dacron inflow and outflow grafts.

Patients on left ventricular assist devices (LVADs) are at increased risk for thromboembolism, and they experience elevations in platelet release and thrombin activity indices during device implantation. The Dacron grafts that lead from the ventricle to the LVAD and back to the aorta may harbor thrombin activity and protect this thrombin from anticoagulant action. To investigate this possibility, specimens isolated from LVAD grafts at the time of device explantation or implantation were incubated with citrated platelet poor plasma (cPPP), cPPP and 2 U/ml of heparin, cPPP and 2 U/ml of recombinant hirudin (r-hirudin), or cPPP and 50 U/ml of heparin. Thrombin activity was measured by the increase in incubated cPPP fibrinopeptide A (FPA) concentrations over cPPP FPA levels, without material contact. A chromogenic substrate for thrombin verified the effects seen. Thrombin activity was found at comparable levels on both the inflow and outflow LVAD grafts at explantation. This activity was not inhibited by low concentrations of heparin, but 50 U/ml of heparin and 2 U/ml of r-hirudin reduced the activity. At graft implantation (after preclotting), thrombin activity was higher than at explantation, but susceptibility to inhibition by heparin was also significantly greater. These results confirm that the LVAD Dacron grafts harbor surface thrombin activity resistant to anticoagulation that may be a primary source for LVAD thrombogenicity.

Prophylactic antithrombin III administration during pregnancy immediately reduces the thrombin hyperactivity of congenital antithrombin III deficiency by forming thrombin-antithrombin III complexes

We examined the changes of haemostatic molecular markers after antithrombin III (AT III) administration in a 22-year-old woman with congenital AT III deficiency in the third trimester of pregnancy who did not have thrombosis. Various markers including fibrinopeptide A (FPA), thrombin-antithrombin I complex (TAT), prothrombin fragment F1+2 (F1+2), plasmin- α 2antiplasmin, D-dimer, β -thromboglobulin, and platelet factor 4 were measured before and just after 3,000 U of AT III concentrate, which was given three times per week from the 34 week of pregnancy until delivery. Just after AT III administration, F1+2 and FPA levels decreased on most occasions, while TAT sometimes increased. Plasma FPA levels were markedly decreased on all 8 occasions when the plasma FPA levels was above 2.0 ng/ml before AT III administration. Plasma FPA levels were always ≧ 6.4 ng/ml before AT III administration on the 4 occasions when TAT increased to above 115 %. The changes of plasma F1+2 levels were significantly correlated with the AT III level. These results suggest that prophylactic AT III administration in the third trimester immediately inactivates intravascular thrombin to form TAT and reduce the plasma FPA level. Thus, the transient TAT elevation following AT III administration may not only be due to extraction of thrombin from the fibrin clots of thrombi but also to intravascular thrombin which is not attached to thrombi. FPA is the best molecular marker for thrombin hyperactivity and it should be monitored in AT III -deficient pregnant women in the third trimester.

Persistent generation of thrombin after acute myocardial infarction.

During the acute phase of myocardial infarction, the generation of thrombin is reflected in the sudden rise of fibrinopeptide A (FPA) and the thrombin-antithrombin III (TAT) complex in blood. We have systematically determined the FPA and TAT plasma concentrations over a period of 14 days after acute myocardial infarction in 100 patients. Mean levels of both thrombin markers were the highest on admission, remained elevated over the following few days, and then gradually declined after day 5. Still, by the end of the first week two thirds of the patients had distinctly elevated TAT and FPA levels, and by the end of the second week such an abnormality was present in half of them. Continuous intravenous heparin infusion at a dose of 20,000 units/day, administered for 1 week to patients who had either received (n = 21) or not received (n = 17) streptokinase, led to a significant depression (p less than 0.05) of thrombin markers over the first 48 hours, an effect that did not persist over the subsequent days of treatment. In patients not assigned to heparin treatment, those in heart failure had significantly (p less than 0.05) higher mean TAT and FPA values on days 3, 5, and 7 compared with patients in whom heart failure was absent. Infarct extension, pulmonary embolism, and death were also associated with a rise in one or both thrombin markers, often preceding the onset of clinical symptoms. Thrombinogenesis was not accompanied by changes in mean plasma concentrations of prothrombin, antithrombin III, or alpha 2-macroglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of two dosages of subcutaneous low molecular weight heparin (Parnaparin) and of unfractionated heparin on fibrin formation and lipolysis in acute myocardial infarction

Although low molecular weight heparins (LMWH) have been extensively investigated for the prophylaxis and treatment of venous thromboembolism in surgical environments, few data in acute myocardial infarction are available in the literature. In this study two dosages of a new LMWH, Parnaparin, and unfractionated heparin (UF) were investigated in 50 pts with acute myocardial infarction. 20 pts received UF (15.000 units, three subcutaneous injections, Group 1), 20 pts received Parnaparin (6.400 units, single injection, Group 2) and 10 pts received a higher dose of Parnaparin (12.800 units, single injection, Group 3). Similar fibrinopeptide A (FpA) levels were observed in Group 1 and Group 2. In Group 3 the dosage of Parnaparin resulted in a significant prolongation of the APTT and in lower FpA levels. Fibrin formation was decreased by Parnaparin in a concentration-dependent way, according to both the anti-Xa activity and the APTT ratio. Parnaparin did not result in a significant increase in free fatty acid concentration, in comparison with UF. Thus, Parnaparin may offer the advantage of a single subcutaneous injection in patients with acute myocardial infarction.

Effects of long-term treatment with warfarin on fibrinogen, FPA, TAT, and D-dimer in patients with coronary artery disease

Sixty-four patients undergoing aorto-coronary bypass surgery were randomized to receive antithrombotic treatment with acetylsalicylic acid (ASA), 300 mg/d (n = 30) or warfarin, INR = 2.5 – 4.2 (n = 34 ). The levels of fibrinogen, thrombin - antithrombin III complexes (TAT), fibrinopeptide A (FPA) and D-dimer were assessed before surgery and 9 months postoperatively. In the warfarin treated group the fibrinogen levels were increased after 9 months, while the levels of TAT, FPA and D-dimer were decreased. In the ASA group TAT levels were increased at 9 months, whereas no significant changes in fibrinogen, FPA or D-dimer from baseline were noted. Thus, a reduced activation of the coagulation system has been demonstrated during long-term treatment with warfarin in patients with coronary artery disease.

Diagnostic efficacy of the D-Dimer assay in disseminated intravascular coagulation (DIC)

The D-Dimer (D-D) assay for measuring cross-linked fibrin degradation products is now available for the clinical laboratory. We combined this assay with other tests to assess patients with diagnosed or suspected DIC. Also, a small group of patients (20) with deep venous thrombosis (DVT) were studied. The D-D test, antithrombin-III assay, FDP titer, fibrinopeptide-A level, protamine sulfate test, fibrinogen, prothrombin time, and activated partial thromboplastin time were used. The D-D test was abnormal in 93.7%, the AT-III level was abnormal in 87.5%, the fibrinopeptide-A level was abnormal in 89.5%, and the FDP titer was elevated in 83.7% of patients with DIC. When assessing patients found not to have confirmed DIC the D-D assay was abnormal in 20%, the AT-III level was abnormal in 6%, and the fibrinopeptide-A level was elevated in 13%. We conclude the D-Dimer assay to be a useful molecular marker of hemostasis in diagnosing DIC and this test will often discriminate between those patients with or without DIC, especially when used with the AT-III and fibrinopeptide-A assays. Of the battery of tests used in this study, the most useful, in descending order of efficacy, appear to be the D-dimer assay (93.7% abnormal), the fibrinopeptide-A titer (89.5% abnormal), the AT-III level (87.5% abnormal), and the FDP titer (83.7% abnormal).

Activation of the coagulation pathway during ongoing allergic cutaneous reactions in humans

The levels of histamine, fibrinopeptide A (FPA), and IgG were determined in chamber fluids overlying sites of antigen versus buffer incubation for up to 7 hours in seven atopic and four antigen-nonreactive subjects. Significant increases in histamine were observed at antigen versus buffer sites in the atopic subjects throughout the 7-hour period. FPA and IgG levels were higher in antigen than in buffer sites from 0 to 5 hours in the atopic subjects. Furthermore, FPA levels correlated with the magnitude of induration at 6 hours after antigen injection in atopic subjects. There were no differences in the levels of histamine, FPA, or IgG at antigen versus buffer sites in the skin test-negative subjects. We suggest that the combination of vascular leakage of proteins, induced by vasoactive mediator release, and activation of these proteins during ongoing cutaneous reactions is responsible for fibrin formation that contributes to the pathophysiology of late-phase allergic responses in the skin.

Does thrombin prevent cerebral vasospasm following aneurysmal subarachnoid haemorrhage?

Fibrinopeptide A (FPA) levels which have been shown to be a quantitative index of thrombin generation, were measured in blood and cerebrospinal fluid (CSF) samples from patients following subarachnoid haemorrhage (SAH) and from a control population. The levels found in samples obtained in patients following SAH are compared with those found in controls and also correlated with clinical grade on admission as assessed by the Glasgow Coma Score and the World Federation of Neurological Surgeons' grading system, and with the amount of subarachnoid blood seen on CT, the occurrence of ischaemic deterioration, the occurrence of low-density change on CT, the presence of vasospasm on angiography, clinical outcome as assessed by the Glasgow Outcome Score 3 months following the ictus, and the incidence of ischaemia as a cause of death or disability as assessed 3 months following the ictus. The levels of FPA found in blood and CSF from patients following SAH were significantly raised when compared with those found in controls. There was significant correlation between blood FPA levels and the amount of subarachnoid blood seen on initial CT. CSF FPA levels had a statistically significant correlation with outcome as assessed at 3 months post-ictus. No statistically significant correlation was found between blood or CSF FPA levels and any of the other variables studied.

Antithrombotic Properties of Dermatan Sulphate (MF 701) in Haemodialysis for Chronic Renal Failure

The therapeutic potential of the glycosaminoglycan (GAG), dermatan sulphate (DS), as an antithrombotic agent in humans has yet to be established. We have performed dose ranging studies of DS to determine its effectiveness as an antithrombotic agent in patients (n = 6-8) undergoing haemodialysis for chronic renal failure. In an initial study, Study 1, i.v. bolus doses of 2-4 mg/kg and 5-6 mg/kg DS were given to patients dialysing with polyacrylonitrile hollow fibre (PAN HF) membranes. In a second crossover study, Study 2, performed using cuprophane hollow fibre (CHF) membranes, i.v. bolus doses of 3 mg/kg and 6 mg/kg DS were compared to a standard unfractionated heparin (UFH) regime that has been shown previously to inhibit fibrin formation. Further infusion studies, Study 3 and Study 4 evaluated the antithrombotic efficacy of an i.v. DS bolus of 3 mg/kg plus an i.v. infusion of DS 0.6 mg kg-1 h-1 and a DS bolus of 5 mg/kg plus an infusion of 1 mg kg-1 h-1 over 5 h, respectively. These studies were compared to standard UFH regimes in a randomised crossover design. Plasma levels of fibrinopeptide A (FPA) and thrombin-antithrombin (TAT) were used as markers of fibrin formation and thrombin generation during dialysis using both membranes. The changes in DS concentration following administration of the different doses were similar in Studies 1 and 2. However, the effectiveness of DS as an anticoagulant appeared to depend markedly on the different dialyser types used in the two studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Coagulation Activation Following Estrogen Administration to Postmenopausal Women

We investigated coagulation system activation following estrogen treatment in 29 healthy postmenopausal women. Study participants received conjugated estrogens at 0.625 and 1.25 mg per day, and placebo for 3-month periods in a randomized crossover protocol. Blood samples were obtained on two consecutive days at the end of each treatment period for immunoassays of F1+2 and fibrinopeptide A (FPA), markers of factor Xa action on prothrombin and thrombin action on fibrinogen in vivo, respectively. Treatment with estrogens at a dose of 0.625 or 1.25 mg resulted in significant increases in mean F1+2 levels of 40 and 98%, respectively, and in mean FPA levels of 37 and 71%, respectively. The measurements of F1+2 were significantly higher in women receiving 1.25 mg of estrogen than 0.625 mg. We also observed significant declines in the levels of antithrombin III and total protein S antigen. Immunologic levels of protein C increased modestly at only the 1.25 mg estrogen dose level. These data indicate that low doses of oral estrogens (< or = 1.25 mg per day) frequently increase the amount of thrombin generated in vivo. Our observations may help to explain the increased thrombotic risk that has been observed with higher doses of this medication (> or = 2.5 mg).

Increased coagulation activity of the pleura after tube drainage and quinacrine instillation in malignant pleural effusion

Chronic malignant pleural effusions are usually treated with an intrapleurally administered irritant that creates an inflammatory reaction. The induced inflammation results in fibrin deposition and termination of fluid exudation. In the present study several factors in the coagulation system in the pleural fluid were followed during treatment with tube drainage and quinacrine instillation into the pleural space. In the chronic exudative phase before treatment, both thrombin activity and fibrinopeptide A (FPA), were present at low levels. During treatment the levels increased markedly. Beta-thromboglobulin, a platelet marker, showed a similar pattern. Prothrombin, antithrombin III, prekallikrein and kallikrein inhibiting activity showed no such variations in activity. The high thrombin activity and FPA level induced by treatment reflect an active process of fibrin formation which seems to play an important role in arresting chronic pleural exudation.

Plasma levels of plasminogen activator inhibitor type 1, beta- thromboglobulin, and fibrinopeptide A before, during, and after treatment of acute myocardial infarction with alteplase

Plasma levels of plasminogen activator inhibitor type-1 (PAI-1), beta-thromboglobulin (beta TG), and fibrinopeptide A (FPA) were followed over 24 hours in 30 patients treated with alteplase for acute myocardial infarction. Samples were taken at baseline (T Oh), after 90 minutes (under alteplase, no heparin, T 1.5h), after 120 minutes (under alteplase and heparin, T 2h), 30 minutes after thrombolytic therapy (T 3.5h), as well as 12 hours (T 12h) and 24 hours (T 24h) after baseline. PAI-1 antigen levels (55 +/- 9 ng/mL at T Oh, mean +/- SEM) decreased to 35 +/- 5 (T 1.5h) and 40 +/- 6 (T 2h) ng/mL under alteplase, before increasing to 84 +/- 22 (T 3.5h), 130 +/- 30 (T 12h), and 64 +/- 7 (T 24h) ng/mL after therapy, P less than .001. A high baseline PAI-1 activity (18 +/- 3 ng/mL) decreased to 2.0 +/- 0.4 (T 1.5h) and 1.7 +/- 0.2 (T 2h) under alteplase and increased to 32 +/- 5 (T 12h) and 19 +/- 3 (T 24h) ng/mL after therapy (P less than .0001). beta TG levels (339 +/- 105 ng/mL at T Oh) decreased to 203 +/- 48 (T 2h), 154 +/- 51 (T 3.5h), 187 +/- 40 (T 12h), and 142 +/- 32 (T 24h) ng/mL under heparin (P less than .01). FPA levels (34 +/- 9 ng/mL at T Oh) increased to 85 +/- 15 ng/mL under alteplase alone (T 1.5h) and normalized under heparin (11 +/- 4, 6 +/- 2, 4 +/- 2, and 3 +/- 1 ng/mL at T 2h, T 3.5h, T 12h, and T 24h, respectively). A high level of FPA at T 3.5h correlated with reocclusion (33 +/- 12 ng/mL, n = 4 v 2.9 +/- 0.5 ng/mL, n = 21, P less than .005). We conclude that plasma levels of PAI-1 antigen as well as activity markedly increase after alteplase therapy of acute myocardial infarction. The high activity of PAI-1 and decreasing beta TG levels suggest that platelets do not contribute significantly to this phenomenon. The marked increase of FPA levels under recombinant tissue-type plasminogen activator alone and its normalization under heparin emphasize the important role of concomitant anticoagulation in controlling further intravasal fibrin generation under alteplase.

Plasma Levels of Plasminogen Activator Inhibitor Type 1, β-Thromboglobulin, and Fibrinopeptide A Before, During, and After Treatment of Acute Myocardial Infarction With Alteplase

Abstract Plasma levels of plasminogen activator inhibitor type-1 (PAI-1), beta- thromboglobulin (beta TG), and fibrinopeptide A (FPA) were followed over 24 hours in 30 patients treated with alteplase for acute myocardial infarction. Samples were taken at baseline (T Oh), after 90 minutes (under alteplase, no heparin, T 1.5h), after 120 minutes (under alteplase and heparin, T 2h), 30 minutes after thrombolytic therapy (T 3.5h), as well as 12 hours (T 12h) and 24 hours (T 24h) after baseline. PAI-1 antigen levels (55 +/- 9 ng/mL at T Oh, mean +/- SEM) decreased to 35 +/- 5 (T 1.5h) and 40 +/- 6 (T 2h) ng/mL under alteplase, before increasing to 84 +/- 22 (T 3.5h), 130 +/- 30 (T 12h), and 64 +/- 7 (T 24h) ng/mL after therapy, P less than .001. A high baseline PAI-1 activity (18 +/- 3 ng/mL) decreased to 2.0 +/- 0.4 (T 1.5h) and 1.7 +/- 0.2 (T 2h) under alteplase and increased to 32 +/- 5 (T 12h) and 19 +/- 3 (T 24h) ng/mL after therapy (P less than .0001). beta TG levels (339 +/- 105 ng/mL at T Oh) decreased to 203 +/- 48 (T 2h), 154 +/- 51 (T 3.5h), 187 +/- 40 (T 12h), and 142 +/- 32 (T 24h) ng/mL under heparin (P less than .01). FPA levels (34 +/- 9 ng/mL at T Oh) increased to 85 +/- 15 ng/mL under alteplase alone (T 1.5h) and normalized under heparin (11 +/- 4, 6 +/- 2, 4 +/- 2, and 3 +/- 1 ng/mL at T 2h, T 3.5h, T 12h, and T 24h, respectively). A high level of FPA at T 3.5h correlated with reocclusion (33 +/- 12 ng/mL, n = 4 v 2.9 +/- 0.5 ng/mL, n = 21, P less than .005). We conclude that plasma levels of PAI- 1 antigen as well as activity markedly increase after alteplase therapy of acute myocardial infarction. The high activity of PAI-1 and decreasing beta TG levels suggest that platelets do not contribute significantly to this phenomenon. The marked increase of FPA levels under recombinant tissue-type plasminogen activator alone and its normalization under heparin emphasize the important role of concomitant anticoagulation in controlling further intravasal fibrin generation under alteplase.

Dose Finding Study of a Low Molecular Weight Heparin, Innohep, in Haemodialysis

A pilot investigation was performed with Innohep, a low molecular weight (LMWH) preparation (peak maximum molecular mass 3,000-6,000), to determine possible dose regimens for patients undergoing regular maintenance haemodialysis for chronic renal failure. Results from this study suggested that suppression of macroscopic clot formation and fibrinopeptide A (FPA), a marker of fibrin formation, could be achieved following bolus injections rather than bolus injections and an infusion. On the basis of these preliminary findings, a randomised crossover study was performed in eight patients undergoing regular maintenance haemodialysis for 5-7 h to determine the effective antithrombotic dose of this LMWH. Single i.v. bolus doses of 1,250 AFXa u, 2,500 AFXa u and 5,000 AFXa u (n = 7-8) were compared to an UFH regime of 5,000 iu + 1,500 iu/h. Excessive clot formation in the dialyser bubble trap, necessitating additional UFH to enable completion of a prolonged (up to 7 h) dialysis, was observed in all patients on the 1,250 AFXa u dose (mean duration of dialysis prior to UFH, 3 h) but in a single patient only receiving the other LMWH doses. A dose-related response in the AFXa activity, measured by chromogenic substrate (CS) assay was seen in the three LMWH groups, with levels declining significantly (p less than 0.05) from 1-7 h. This contrasted with the constant levels maintained during dialysis with UFH. FPA levels were significantly elevated after 2 h following the 1,250 AFXa u bolus and after 4 h following the 2,500 AFXa u bolus. There was no significant difference in FPA levels between the 5,000 AFXa u bolus and UFH.(ABSTRACT TRUNCATED AT 250 WORDS)

Effective Prophylaxis of Thrombosis by Antithrombin III Concentrate in a Pregnant Woman with Congenital Antithrombin III Deficiency: Relations between Plasma Antithrombin III Activity and the Plasma Levels of Hemostatic Molecular Markers

The value of antithrombin III (AT III) concentrate and a standard criterion for its use were examined in a pregnant woman with congenital AT III deficiency by continuous monitoring of plasma AT III activity and the plasma levels of hemostatic molecular markers. The rates of improvement of various markers after AT III administration (frequency of improvement/frequency of administration) were as follows: fibrinopeptide A (FPA) 82%, D-dimer 70%, fibrinopeptide B beta 15-42 73%, beta-thromboglobulin 60%, and platelet factor 4 50%. There was no significant correlation between the plasma AT III activity and all plasma FPA values, but FPA values of over 3.9 ng/ml showed a significant negative correlation with AT III activity: AT III activity (%) = -6.59 x FPA (ng/ml) + 125, r = -0.851, p less than 0.02. We therefore recommend continuous monitoring of the plasma FPA level and administration of AT III concentrate when the FPA level is elevated. According to the regression line shown above, plasma AT III activity should be raised to 100% to keep the FPA level below 6.0 ng/ml with 95% confidence limit.

A comparative study on the effects of a monophasic pill containing desogestrel plus 20 μg ethinylestradiol, a triphasic combination containing levonorgestrel and a monophasic combination containing gestodene on coagulatory factors

The changes in haemostasis during oral contraception are related to the ethinylestradiol dose present in the formulation taken by the patient. An open, randomized longitudinal study was performed to evaluate and compare the effects that low-dose oral contraceptives (OCs) containing different doses of ethinylestradiol exert on the haemostatic system. Eighty-nine healthy women, aged 18-45 years, were randomly assigned to treatment with 3 different OCs: a monophasic pill containing 30 micrograms of ethinylestradiol plus 75 micrograms of gestodene (GSD/30) (30 subjects), a triphasic pill containing levonorgestrel (TRI/LNG) (28 subjects), a monophasic pill containing 20 micrograms ethinylestradiol plus 150 micrograms of desogestrel (DOG/20) (31 subjects). From every woman, blood samples were collected before treatment and at the 3rd and 6th cycle of pill intake. The number of platelets significantly increased (p less than 0.01) during treatment with TRI/LNG. Fibrinogen plasma values were significantly increased (p less than 0.05) only in women treated with the preparation GSD/30. Fibrinopeptide A (FPA) plasma levels significantly increased (p less than 0.01) during treatment with the pills TRI/LNG and GSD/30, but the levels of FPA were unchanged in the group treated with DOG/20. The overall results of this study confirm that the effects of OCs on haemostasis are dependent on the ethinylestradiol dose. Moreover, they suggest that with reduction of the ethinylestradiol component to 20 micrograms, the effects of OCs on haemostasis seem to be virtually eliminated.

Changes of Coagulation and Fibrinolysis in Patients with Liver Cirrhosis

Liver disease is associated with complex coagulation and fibrinolytic defects. In this study we assayed molecular marker levels for coagulation and fibrinolysis, i. e. plasma fibrinopeptide A (FPA), fibrinopeptide Bβ1-42 (Bβ1-42), fibrino peptide Bβ15-42 (Bβ15-42), tissue-type plasminogen activator antigen (t-PA antigen) and activity (t-PA activity), plasminogen activator inhibitor (PAI), D-dimer, plasminogen, α2 plasmin inhibitor (α2 PI), α2 PI-plasmin-complex (PIC), ATIII and serum FDP-E in 31 patients with liver cirrhosis for investigated the state of coagulation and fibrinolyssis in liver cirrhosis.All these molecular markers changed significantly compared with the value in normal subjects. As for coagulation, hypercoagulable state was observed because of increment FPA level and one of the reasons of this state maight be decrease of ATIII synthesis. As for fibrinolytic state, accelerated fibrinolysis was observed because of increment of PIC, Bβ1-42, D-dimer, FDP-E, Bβ15-42. In addition, these changes might be induced through accelerated secondary fibrinolysis, increment of t-PA by decleased clearance of circulating PA and diminished α2 PI synthesis.And the variation of t-PA antigen level was well correlated to plasminogen, α2 PI, ATIII and Ch-E, measuring of t-PA antigen level was useful to evaluate liver function in the patients with liver cirrhosis.

A prospective study of haemostatic parameters in relation to the clinical course of myeloproliferative disorders

Platelet function and the clinical course of the disease were prospectively investigated in 29 patients with myeloproliferative disorders. Serial determinations (median: 5 investigations per patient within 17 months) of platelet aggregation, plasma and intraplatelet concentrations of beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), and of fibrinopeptide A (FPA) plasma levels were carried out. In the chronic phase of polycythaemia vera, patients with thrombohaemorrhagic complications during the study period had higher platelet count, more severe platelet aggregation defects, and increased plasma levels of beta TG and FPA compared to patients without complications. However, thrombohaemorrhagic complications were not predicted by changes in these parameters in the individual patient during the chronic disease phase. When patients with chronic myelogenous leukaemia entered blast crisis, bleeding complications were related to thrombocytopenia, impaired platelet function and low intraplatelet concentrations of beta TG and PF4. Cytoreduction by chemotherapy in the chronic phase of CML did not alter beta TG and PF4 plasma levels, whereas treatment of polycythaemia rubra vera by venesection favourably influenced platelet alpha-granule secretion and increased intraplatelet concentrations of beta TG and PF4.