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PubMed2003

Processing and transfusion of residual cardiopulmonary bypass volume: effects on haemostasis, complement activation, postoperative blood loss and transfusion volume.

The aim of this prospective randomized study was to compare the effects of the transfusion of unprocessed and cell saver-processed residual cardiopulmonary bypass (CPB) volume on haemostasis, complement activation, postoperative blood loss and transfusion requirements after elective cardiac surgery. Blood samples were taken at eight points in time, perioperatively. Haematological data, including haemoglobin, haematocrit and platelet counts as well as coagulation parameters, including activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen and the fibrinolytic parameter D-dimers, were measured from each blood sample. For the assessment of complement activation, the total complement CH50 was analysed. In addition, postoperative blood loss and transfusion requirements were measured during the first 24 hours, postoperatively. The results of the study showed impaired haemostasis after the transfusion of both unprocessed and processed CPB volume. No significant differences were found between the groups in the measured coagulation parameters. Nor was a significant difference found in the complement concentration. However, in patients transfused with unprocessed CPB volume, a significantly (p = 0.019) higher amount of blood loss was found, postoperatively. In the same group of patients, the number of units of allogeneic erythrocyte concentrate suspension transfused was also significantly (p = 0.023) higher during the first 24 hours, postoperatively, compared to the patients transfused with processed CPB blood. The number of units of fresh frozen plasma and platelet suspension transfused was not significantly different between the groups. In conclusion, processing CPB volume in combination with processing peroperative blood loss may result in reducing the volume of transfusion needed of allogeneic blood products.

Aged↗
PubMed2002

Global fibrinolytic capacity is decreased in polycystic ovary syndrome, suggesting a prothrombotic state.

The polycystic ovary syndrome (PCOS) is associated with an increased risk of cardiovascular disease (CVD). Insulin resistance (IR), hyperandrogenism, and dyslipidemia are well-known cardiovascular risk factors in PCOS. Impaired fibrinolysis could also contribute to the development of CVD in PCOS. Global fibrinolytic capacity (GFC) is a recently developed method, which is reflected by the amount of generated D-dimer when the fibrinolysis of a freeze-dried fibrin clot is stopped by introducing aprotinin. GFC is sensitive to all the factors involved in the process of fibrinolysis. We evaluated whether women with PCOS have any alterations in the GFC and other essential hemostatic parameters. Fifty-nine nonobese, normal glucose-tolerant women with PCOS (age, 22.9 +/- 4.4 yr; body mass index, 23.0 +/- 2.4 kg/m(2) ) and 23 age- and body mass index-matched healthy controls participated. We measured GFC and triglycerides; total cholesterol; HDL-cholesterol (HDL-C); lipoprotein-a; prothrombin time; partial thromboplastin time; thrombin time; antithrombin III; factors II, V, VII, and X; fibrinogen; plasminogen; antiplasmin; and D-dimer. Serum glucose and insulin (at baseline and during a 75-g 2-h oral glucose tolerance test) were also measured, and IR was assessed by homeostatic model assessment. GFC was significantly lower in the PCOS group, compared with the control group (2.49 +/- 1.6 vs. 5.95 +/- 2.43 microg/ml, P < 0.001). All the other coagulation and fibrinolysis parameters were comparable between the two groups. The PCOS group had lower HDL-C and higher IR values. GFC was correlated with testosterone and free testosterone negatively and with HDL-C positively. There was no correlation between GFC and any of the IR parameters. Our results suggest that women with PCOS have impaired fibrinolysis, as reflected by the decreased GFC. This impairment is not related to the IR and may increase the risk of CVD in PCOS.

Adult↗
PubMed2003

Effects of anticoagulant from Spirodela polyrhiza in rats.

A fibrinolytic protease was purified from an Oriental medicinal herb, Spirodela polyrhiza (Choi, H. S., et al., Biosci. Biotechnol. Biochem., 65, 781-786 (2001)). The protease hydrolyzed not only fibrin but also fibrinogen. The enzyme had an anticoagulant activity measured with activated partial thromboplastin time, thrombin time, and prothrombin time in rat plasma. It doubled all three at 69, 29, and 221 nM, respectively. The protein had anticoagulant activity when given intravenously and orally. The maximum delay in the activated partial thromboplastin time was at the dose of 0.52 and 4.2 mg/kg for intravenous and oral administration, respectively. This protein may be useful in clinical applications for anticoagulation.

Animals↗
PubMed1999

Development of heparin antagonists with focused biological activity.

Heparin, a complex glycosaminoglycan, has long been used to temporarily render the blood incoagulable during extracorporeal circulation, cardiovascular surgery, and other arterial interventions. But bleeding complications are especially common when the arterial tree is violated, occurring in as many as 10-15% of cases. For cardiovascular surgery and many related interventions, protamine has long been the standard antagonist when acute and complete neutralization of heparin s anticoagulant effect is necessary. Protamine s efficacy is related in part to its total net cationic charge, but unfortunately so is its toxicity. For these reasons, there is renewed interest in developing heparin antagonists which will replace the use of protamine. At Commonwealth Biotechnologies, Inc., we have used a rationale design approach for the preparation of a family of low molecular weight helix peptides which bind heparin with high affinity. For each of the new compounds, we have assessed their ability to bind heparin using isothermal titration calorimetry and circular dichroism spectrometry and have examined potential complexes formed with the anticoagulant pentasaccharide unit of heparin using molecular modeling techniques. The biological potencies of these compounds were assessed in ex vivo experiments where their ability to compete with antithrombin for binding heparin was determined. The best of the compounds, designated HepArrestTM, is highly effective in reversing heparin-mediated and HepArrest is a safer drug than protamine because of reduced adverse hemodynamic side effects compared with those associated with protamine. HepArrest binds low molecular weight heparins and causes reversal of anticoagulation by low molecular weight heparins, as determined by activated partial thromboplastin time, thrombin time, or factor Xa neutralization assays. These highly promising preclinical results indicate that HepArrest is a novel heparin neutralizing agent that may well fill a substantial unmet need for vascular surgeons and cardiac anesthesiologists who perform coronary artery bypass grafts and several other major vascular surgeries, as well as for cardiologists and interventional radiologists.

Animals↗
PubMed2000

Hemostatic defects in massive transfusion: rapid diagnosis and management.

Severe hemostatic defects that occur during massive transfusion are related to the volume of blood transfused, preexisting hemostatic abnormalities, concomitant pathologic changes, and therapeutic maneuvers. The relative role of each factor in the bleeding can be rapidly determined by using routine clinical laboratory tests. This determination requires an understanding of the properties of selected clotting factors, what coagulation screening tests measure, how these tests behave as the levels of factors change, and test profiles characteristic of different defects. Screening tests include platelet count, prothrombin time, partial thromboplastin time, thrombin time, and fibrinogen level. These tests are generally available on an emergent basis and can be completed within 25 minutes. The pattern associated with hemodilution is universal in massive transfusion. Patterns characteristic of the other pathologic processes that may be encountered are simply superimposed on the characteristics of hemodilution. Successful management of the contributing causes of bleeding depends on the administration of the appropriate blood components in the dose necessary to ensure that the levels of platelets and clotting factors are returned to and maintained at hemostatic levels.

Blood Coagulation Disorders↗
PubMedDate not supplied

[Role of oxidative stress as a component of critical states in the genesis of hemostatic disorders].

The effect of oxidative stress (OS) on hemostasis parameters was studied in model systems Fe(2+)-ascorbic acid-EDTA and Fe(2+)-EDTA-H2O2. Blood recalcification time, thrombin time, activated partial thromboplastin time, prothrombin index, the content of fibrinogen, antithrombin III, soluble fibrin-monomer complexes, platelet count and aggregation activity were evaluated. Parameters characterizing the severity of OS were measured: protein concentrations of carbonyl and sulfhydryl groups and level of malonic dialdehyde. OS was found to induce changes in the hemostasis system, promoting the progress of intravascular coagulation during the formation of critical state. The authors conclude that antioxidants should be added to combined therapy of blood clotting disorders in critical patients.

Adult↗
PubMed1975

Blood coagulation studies in children with surface hemangiomas.

Thirty patients with surface hemangiomas were investigated for any latent coagulopathy. Whole blood clotting time, kaolin cephalin clotting time, prothrombin time, thrombin time and platelet counts did not differ significantly from the control group values. The values of plasma fibrinogen, euglobulin lysis time and serum levels of fibrinogen degradation products remained within the normal ranges but their mean values were significantly different from those of healthy children. The findings may be attributed to a chronic incipient type of "consumption coagulopathy" occurring locally in the hemangiomas.

Adolescent↗
PubMed2002

Expanding perfusion services through mobile point-of-care coagulation monitoring.

Current trends in cardiac surgery have challenged perfusionists to seek diversification of services. Point-of-care coagulation (POCC) monitoring represents a desirable area of perfusion service expansion. The purpose of the study was to create a series of hemostatic conditions to assess the functionality of POCC monitors to identify specific coagulopathies with identifiable profiles for algorithm development. Fresh (< 4 h) bovine blood, anticoagulated with anticoagulant citrate dextrose, was adjusted to a hematocrit of 30.0 +/- 2.0%. Hypofibrinogenemia < or = 90 mg/dL), thrombocytopenia (< or = 70,000/mm3), platelet dysfunction (850 microg/mL of nitroglycerin/mL of blood) and hyperfibrinolysis (0.40 units of urokinase/mL of blood) were created. Five POCC devices were used to evaluate activated clotting time, thrombin time, fibrinogen, platelet function, prothrombin time, activated partial thromboplastin time and thromboelastograph. Results are reported as percentage change from control for each test (abtract table). [table: see text] Each test performed showed specificity and sensitivity for certain coagulopathies, however variability amongst monitors was encountered. In conclusion, the development of a mobile cart incorporating POCC monitors with knowledge of specific coagulopathic conditions may expand perfusion service.

Algorithms↗
PubMedDate not supplied

[Temperature regimen of extracorporeal circulation during aortocoronary bypass surgery].

The purpose of the study is to comparatively evaluate the impact of normo- and hypothermic perfusion on acid-base balance (ABB), gas blood composition, metabolic parameters, and hemostasis. Fifty patients undergone multiple aortocoronary bypass under extracorporeal circulation (EC) were examined. Twenty four patients and 26 (Groups 1 and 2, respectively) had been operated on under normo- and hypothermia. The groups did not differ in age, body weight, the duration of an operation, the number of shunts, the time of EC, and myocardial ischemia. ABB, gas blood composition, the concentrations of hemoglobin, lactate, fibrinogen, prothrombin time, thrombin time, activated partial thromboplastin time, activated coagulation time, blood coagulation time as described by Leigh-White, the count of platelets, and ADP-induced platelet aggregation in the early postperfusion and postoperative periods, following 24 and 48 hours after surgery. There were no significant differences in the values of ABB, gas blood composition, blood lactate levels in patients from both groups. However, metabolic acidosis, elevated blood lactate concentrations were more frequently encountered in Group 2 patients, which suggests that hypothermia prduces a more aggressive effect on systemic homeostasis. Impact of normo- and hypothermia on the coagulative link of homeostasis was not revealed. Nevertheless, hypothermic EC halved the functional activity of platelets, which has a substantial effect on the size of postoperative blood loss.

Acidosis↗
PubMed1992

[Normal values of hemoglobin, hematocrit, blood coagulation factors, and fibrinolysis in New Zealand white rabbits].

PURPOSE: To assess the normal rates of several haematological parameters along with coagulation and fibrinolysis values. MATERIAL AND METHODS: Male white New Zealand rabbits weighting between 1.5 and 2.5 kg. were used in variable amounts for each test (117-102). The following haematological determinations were carried out: haemoglobin, haematocrit, platelet count, and peripheral blood cell morphology. Prothrombin time, kaolin-activated partial thromboplastin time and thrombin time were assessed as well. Fibrinogen, plasminogen, prothrombin, factor V, factor X and factor XIII assays were also performed, along with tests for fibrinolytic activity and assay of fibrin and fibrinogen degradation products. All tests were compared with samples of pooled human and rabbit plasma. A statistical study was carried out including mean, mode, standard deviation, variation coefficient, confidence interval and chi square test plus Kolmogorow-Smirnoff test for normality assessment. RESULTS: The curves attained after plotting the figures for haematocrit, haemoglobin, platelet count, kaolin-activated partial thromboplastin time, thrombin time and factors II and X approached the normal values (p > 0.05). Asymmetric curves were achieved for fibrinogen, prothrombin time and plasminogen (p < 0.005). Rabbit anti-fibrinogen serum reacted with rabbit plasma and fibrinogen, but failed to react against human samples. No fibrin and/or fibrinogen degradation products were detected and no fibrinolytic activity was observed on fibrin plate assays. CONCLUSIONS: White New Zealand rabbits have values for haemoglobin, haematocrit and fibrinogen similar to the human ones. On the contrary, factors V, X and XIII, along with plasminogen, are in higher concentration, especially the former. Factor II is present at about half the human concentration. No fibrinolytic activity could be demonstrated with the methods used here.

Animals↗
PubMed2003

The effect of hydroxyurea on the coagulation system in sickle cell anemia and beta-thalassemia intermedia patients: a preliminary study.

Hydroxyurea (HU) has been shown to reduce the frequency of vaso-occlusive manifestations in both adults and children with sickle cell disease (SCD), and the induction of hemoglobin F (HbF) is thought to be the underlying mechanism responsible for clinical improvement in some patients. However, there exists no good correlation between the amount of HbF increase and clinical response. Recent studies suggest that increased activity of the coagulation system may be important in the pathogenesis of vascular occlusion in sickle cell disease. To analyze the effect of HU on the coagulation system in children, the authors studied the levels of some coagulation factors and natural inhibitors. Eleven children who had been treated with HU because of SCD (5 patients), sickle-beta-thalassemia (3 patients), and beta-thalassemia intermedia (3 patients) were enrolled in the study. Levels of the coagulation factors II, V, VII, VIII, IX, X, XI, and XII, and of protein C and protein S, prothrombin times, activated partial thromboplastine times, thrombin times, and reptilase times were measured before the treatment and at the 5th or 6th months of HU therapy when the patients were in a steady-state condition. There was a decrease in all of the coagulation factors except for FIX and FXII and in inhibitors such as protein C and protein S. However, statistically significant decreases were observed only in factor VIII and protein C levels. The rates of decrease were 54.8 and 12.5% (p = .015 and p = .018) in FVIII and protein C, respectively. This result shows that HC has significant effects on the coagulation and natural inhibitory systems.

Adolescent↗
PubMed2004

The coagulation system in horses with colic.

Colic in horses very often induces changes in the coagulation system causing the development of disseminated intravascular clotting. It is promoted by blood concentration and an increase in exposition of coagulation activators with a simultaneous decrease in coagulation inhibitors activity, mainly antithrombin III. Progressing blood platelets aggregation supports production of microthromboses and plugging capillary vessels. The progression of this processes causes complications in basic disease and becomes the reason for therapeutic failure. Determination of coagulation system indexes such as the number of platelets, prothrombin time, activated partial thromboplastin time, thrombin time, concentration of fibrinogen and fibrinogen degradation products, and D-dimmer and antithrombin III contents enables diagnosis and facilitates appropriate therapy of colic in horses.

Animals↗
PubMed2005

Platelet dysfunction-eosinophilia syndrome in parasitized Venezuelan children.

Platelet dysfunction was detected in six children with purpura and eosinophilia. We conducted clinical evaluations, hematologic and platelet function tests, clotting studies (bleeding time, prothrombin time, partial thromboplastin time, thrombin time, factor XIII, factor VIII, and von Willebrand factor), assays for IgG and IgM antibodies to platelets, and a search for stool parasites. Mild bleeding phenomena (ecchymoses, petechiae, epistaxis, and gingival) were transient. All children showed intestinal parasites and marked eosinophilia (mean count = 2,615.2 cells/muL, 95% confidence interval = 1,259.6-5,429.8). Main abnormalities included prolonged bleeding times (50%) and defective aggregation with collagen (100%) adrenaline (66%), or ADP (66%). Antibodies to platelets were not detected. Anti-parasite therapy reversed the hemorrhagic manifestations and normalized eosinophil counts and platelet alterations. No relationship could be established between excess eosinophils, intensity of bleeding, or type and degree of platelet abnormalities. Thrombocytopathic features mimicked the intrinsic defect of storage pool disease. The possible pathogenic roles of eosinophilia and parasitism are reviewed. This is the first report of this pathologic combination in Latin American children.

Blood Coagulation Tests↗
PubMedDate not supplied

[Haemostatic and fibrinolytic variables in women with anorexia nervosa].

AIM: The aim of this study was to evaluate haemostatic variables in women with anorexia nervosa --AN. MATERIAL AND METHODS: 23 obese female patients, and 39 female anorexic patients diagnosed acc. to DSM-IV and ICD-10 criteria were recruited. The studied group was compared to a control group--37 healthy female volunteers. BMI was calculated for AN, obese, and the control group. The following measurements were taken: prothrombin index, prothrombin time, thrombin time, fibrinogen, factor VII, ATIII, D-dimers, INR, APTT, protein C and PAI-1 activity, t-PA activity, PAI-1 antigen, t-PA antigen, glucose level, insulin level, E2 and total fat. RESULTS: In the AN group the INR, prothrombin time, PAI-1 activity, t-PA activity, protein C level were increased, whereas PAI-1 antigen, t-PA antigen, prothrombin index, fasting insulin level and fasting glucose level were decreased. CONCLUSIONS: We conclude that, in the AN group, an impaired fibrinolysis and coagulation are observed and there is a correlation between fibrinolytic and coagulation parameters and carbohydrate metabolism.

Adult↗
PubMedDate not supplied

[Preoperative hypervolemic hemodilution with 6% hydroxyethyl starch 130/0,4 (HES 130/ 0.4) solution as a way of reducing needs for donor blood transfusion].

UNLABELLED: The efficacy of hypervolemic hemodilution (HHD) in reducing the rate of donor blood transfusion is controversely discussed. The present prospective, randomized, clinical study analyzes the impact of HHD with 6% hydroxyethyl starch (HES) 130/0.4 solution on the rate transfusion, laboratory parameters, and the incidence of complications as compared with those in the control group receiving no preoperative HHD. MATERIAL AND METHODS: 80 patients who had undergone total prostatectomy or cystectomy were randomized into 2 groups. Before anesthesia, the HHD group (n=40) received 15 ml/kg of 6% HES 130/0.4 solution. In the HHD and control (n=40) groups, 6% HES 130/0.4 was intraintraoperatively infused in its maximum dose of 33 ml/kg according to the patients' needs. Indicationsf or blood transfusion trigger were Hb <5 g/dl or packed cell volume < 0.24. Laboratory parameters (Hb, PCV, platelets, prothrombin index, prothrombin time, thrombin time, fibrinogen, antithrombin III were measured before surgery, after HHD and 2, 24, and 48 hours after surgery. The mean blood pressure (MBP), heart rate (HR), and central venous pressure (CVP) were determined before surgery, after HHD, and 2 hours postsurgery. Statistical measurements were made in all patients from the HHD and control groups, as well as in a subgroup, in which intraoperative blood loss was greater than 30% of the total blood volume (70 ml/kg body weight). RESULTS: Demographic data and surgical techniques were similar in both groups. After HHD, CVP rose significantly. The changes in MBP and HR were statistically insignificant. There were no complications after HHD. Of the 40 HHD-group patents, 5 needed donor blood transfusion while in the control group blood was transfused to 10 of the 40 patients in the control group. Comparing both groups showed a lower need for blood transfusion in the HHD-group patients than in the controls (10 versus 24 packed red cells). The postoperative Hb values showed no difference between both groups. CONCLUSIONS: Preoperative HHD in patients undergoing surgery with expected >30% blood loss leads to decreased needs for blood transfusion. The method is safe and easy-to-use.

Blood Loss, Surgical↗
PubMed1990

[Effect of acute aprotinin (Gordox) therapy on hemostasis in heart surgery patients, with special reference to hyperfibrinolysis].

Authors have studied the effect of Gordox-therapy on haemostasis after open heart surgery in a prospective clinical trial. Thirty seven patients (pts) undergoing cardiac surgery due to their valve disease were randomly assigned either to control-group (20 pts) or to Gordox-group (17 pts). The patients in the Gordox group were given Gordox according the following scheme: 2 M IU within 20 min. after induction of anaesthesia followed by 0.5 M IU/hour infusion until the end of the operation. One M IU also was given into the oxygenator before starting the extracorporeal circulation. The postoperative chest tube drainage was less in Gordox-group (534 +/- 260 ml vs. 987 +/- 583 ml, p less than 0.005), and donor blood and fresh frozen plasma requirement was also lower in this group (534 +/- 633 ml vs. 935 +/- 718 ml p less than 0.05; 70 +/- 153 ml vs. 211 +/- 245 ml p less than 0.05, respectively). There was no significant difference between the two groups concerning the postoperative activated partial thromboplastin time, prothrombin time, thrombin time values. The authors could document significantly higher fibrinogen concentration and significantly lower fibrinolytic activity postoperatively in the Gordox-group (p less than 0.05). Gordox therapy has advantageous effect on haemostasis after open heart surgery which can be documented both by clinical and laboratory examination.

Aprotinin↗
PubMed1990

Effects of soman poisoning on hematology and coagulation parameters and serum biochemistry in rabbits.

The effects of soman poisoning on hematological (counts of red blood cells (RBC), white blood cells (WBC), and platelets and measurement of hematocrit) and coagulation parameters (prothrombin time, activated partial thromboplastin time, thrombin time and concentrations of fibrinogen, factor V, factor VII, and factor XI) and serum biochemistry (concentration of albumin, protein, calcium, cholesterol, triglycerides, blood urea nitrogen (BUN), magnesium, and creatinine and activities of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, cholinesterase, creatinine phosphokinase (CPK), hydroxybutyrate dehydrogenase, and amylase) were determined at 1, 2, 4, 24, and 48 hours after poisoning of rabbits. There were significant (p less than 0.05) decreases in the RBC counts in all treatment groups that were measured initially at 4 hours and were reflected by parallel decreases in the hematocrit values. These changes were probably due to an increase in the hemolysis of the RBC rather than a decrease in the production of RBC. There were minor changes in the coagulation parameters. Generally, the fibrinogen content increased. The activated partial thromboplastin time decreased significantly (p less than 0.05) 24 and 48 hours after soman (50 micrograms/kg) poisoning. Blood cholinesterase values were significantly reduced in all treatment groups at all time periods. The CPK activity was increased after 4 and 24 hours in the 20 and 50 micrograms/kg soman groups. There were minor changes in the other biochemistry values, but none that showed a dose-response relationship; thus, they were considered to be of limited significance with regard to the toxic manifestations of soman exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

A study of 31 patients with easy bruising from University Hospital, Kuala Lumpur.

Thirty one patients were investigated for the main complaint of easy bruising. These patients had normal platelet count with no past history of immune thrombocytopenia or systemic disorders known to predispose to bruising and a negative drug history. The evaluation of these patients included clinical review (history and physical examination) plus coagulation tests consisting of bleeding time, prothrombin time, partial thromboplastin time, thrombin time, fibrinogen level, FXIII screen and platelet functions test. Seven of the paediatric patients had acquired platelet dysfunction with eosinophilia (APDE). In 17 (94.4%) of the 18 adult patients no abnormality was demonstrated. Hence APDE was the commonest cause of easy bruising in children while the haemostatic defect contributing to easy bruising in adults remained unknown.

Adolescent↗