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PubMed1977

[Factor XIII deficiency in burns].

In 34 patients with severe burn injuries platelets, fibrinogen, prothrombin time, partial thromboplastin time, thrombin time and factor XIII were measured daily. Half of the patients were administered 15 000 IE of heparin per 24 hours. In the first 4 days there was a rapid fall of factor XIII to a value of approximately 30%. Values remained very low during the whole observation period of up to 20 days. However, in patients treated with heparin, values tended to be 10--15% higher. After an initial decline on the tenth day, the platelets had risen to the lowest normal level. Platelets were identical in both groups. The causes for the changes in these haemostasis parameters, their significance, and possible consequences of therapy are discussed.

Blood Coagulation Tests↗
PubMedDate not supplied

Apgar score and blood coagulation factors.

Blood coagulation tests were performed in 93 newborn infants with different Apgar score at the 1st and 5th minutes of life. The laboratorial determinations were periodically performed at 0, 24 and 48 hours of life. The following tests were performed: bleeding time, whole blood clotting time, prothrombin time, kaolin-cephalin clotting time, thrombin time, dosage of factors I, V, VIII and X, clot retraction, platelet count, englobulin lysis time and the tourniquet test. Immediately after birth, the mean values of the blood coagulation factors were significantly different among the groups, with the exception of the whole blood clotting time and the platelet count. Those differences were due to the presence of the more depressed neonates. Although these results could indicate some degree of hepatic damage, it was apparent that an activation of the blood coagulation mechanisms took place, leading to a consumption coagulopathy. The infants who died (10) presented clinical and laboratorial data suggestive of disseminated intravascular coagulation (DIC). Necroscopic findings of microthrombosis in the liver and in the central nervous system were diagnosed in two infants.

Apgar Score↗
PubMed1976

Platelet aggregation as a sign of septicemia in thermal injury. A prospective study.

Serial measurements of coagulation activity, platelet counts, and platelet aggregation were done in patients with full-thickness burns involving 25% or more of body surface area to detect specific changes that might correlate with the onset of septicemia. Mean and maximal values for prothrombin time, partial thromboplastin time, thrombin time, activities of factor V and factor VIII, and concentrations of fibrinogen and fibrinogen-related antigens observed in the presence of bacterial septicemia did not differ significantly from those observed in the absence of septicemia. Mean platelet counts were significantly less with sepsis, but values in individual subjects were not indicative of the presence of septicemia. By contrast, platelet aggregation in response to adenosine diphosphate, epinephrine, and collagen always became severely abnormal with the onset of septicemia but not in the absence of sepsis.

Anti-Bacterial Agents↗
PubMed1998

Effect of estrogen-progestin hormonal replacement therapy on plasma antithrombin III of postmenopausal women.

BACKGROUND: This study was performed to evaluate antithrombin III levels in postmenopausal women receiving hormonal replacement treatment. METHODS: It is a prospective randomized study concerning 19 postmenopausal patients, aged 40 to 65 years, who received either continuous daily oral equine conjugated estrogen 0.625 mg (group A, N=10) or daily transdermal 17beta-estradiol 50 microg (group B, N=9). Medroxyprogesterone acetate (5 mg/day, 14 days monthly) was given to all patients. Blood samples were obtained before and after 3, 6, 9 and 12 months of treatment. Coagulation tests included Antithrombin III (functional method), prothrombin time, partial activated prothrombin time, thrombin time, factor V, fibrinogen, platelet count and euglobulin lysis time. Friedman analysis of variance and Mann-Whitney test were used for statistical analysis. RESULTS: Antithrombin III level was reduced (p<0.05) in group A but not in group B, although it remained within normal range. No changes were detected in the other coagulation tests. CONCLUSIONS: These data suggest that oral conjugated estrogen replacement reduces functional ATIII, whereas transdermal estradiol replacement therapy does not modify it.

Administration, Cutaneous↗
PubMed1998

[Recurrent epistaxis in children as an indicator of hemostatic disorders].

OBJECTIVE: To distinguish which nosebleeds in children hide an underlying coagulation disorder, characteristics of recurrent epistaxis were evaluated correlating the severity with a battery of specific tests on primary and secondary hemostasis. PATIENTS AND METHODS: Epistaxis of fifty-eight children were classified as mild or severe according to frequency, duration, amount of blood lost, proportion of life that nosebleeds have been recurrent and uni- or bilateral bleeding. Epidemiological characteristics were evaluated, as well as hemostatic tests including: platelet count, mean platelet volume, plasmatic fibrinogen level, prothrombine time, activated partial thromboplastin time, thrombin time, bleeding time, von Willebrand factor antigen and ristocetin cofactor, factor VIII coagulant, and platelet aggregation to different agents. The effect of drugs or the presence of tumors was discarded. RESULTS: In the group of children with mild epistaxis (n = 39) there were three cases with laboratory abnormalities (10.3%). In severe epistaxis (n = 19) abnormalities were found in eleven cases (57.9%) and specific entities were detected in six of them (three children with von Willebrand's disease, one Bernard-Soulier syndrome, one autoimmune thrombocytopenic purpura and one Rendü-Osler-Weber disease). Epistaxis labeled as mild needed less cauterizations and packings, were more related to seasonal prevalence and self-handling, and poorly influenced iron metabolism. CONCLUSIONS: The five qualities pointed out on recurrent epistaxis in children allow the identification of who must be thoroughly studied by means of specific tests to rule out any kind of hemostatic disorder.

Adolescent↗
PubMed1990

Absence of drug interaction between heparin and nitroglycerin. Randomized placebo-controlled crossover study.

The purpose of this randomized crossover study was to determine whether nitroglycerin interacts with heparin in terms of its anticoagulative properties as determined by activated partial thromboplastin time and thrombin time. Eight healthy adults were given either a 60-minute intravenous infusion of 5 mg of nitroglycerin or a 0.9% sodium chloride solution subsequent to the administration of an intravenous injection of 5000 U of heparin. No nitroglycerin-related drug interference with heparin was observed as measured by the activated partial thromboplastin time and the thrombin time.

Adult↗
PubMed1988

Plasma heparin values and hemostasis in equids after subcutaneous administration of low-dose calcium heparin.

Different doses of heparin were given to equids SC to establish 0.05 to 0.20 U of heparin/ml of plasma. Plasma heparin values and antithrombin III activities were assayed, using chromogenic substrate methods. Activated partial thromboplastin and thrombin times were determined, using conventional coagulation assays. Tests were run every hour (or every 2 hours for antithrombin III) for 12 hours from 5 groups of 5 equids each after single injection of 40, 60, 80, 100, or 125 U of calcium heparin/kg of body weight and from 11 equids after injection of 150 U of calcium heparin/kg. The smaller dose (40 U/kg) did not or only insufficiently increase plasma heparin values. After 150 U of heparin/kg, plasma heparin concentrations were increased for 11 hours and were significantly (P = 0.05) increased between postadministration hours 2 and 7. The desired range beyond 0.05 U of heparin/ml was achieved between postadministration hours 2 and 6. Antithrombin III, activated partial thromboplastin time, and thrombin time were not significantly affected by any heparin dose. In cumulative studies, 2 equids were given 150 U of heparin/kg 7 times at 12-hour intervals. After the 3rd injection, a mean plasma concentration of 0.20 U of heparin/ml was achieved; after the 7th injection, the mean concentration was 0.22 U of heparin/ml. Four equids were given 150 U of heparin/kg initially, followed by 125 U of heparin/kg 6 times at 12-hour intervals. After the 3rd injection, a maximal plasma heparin concentration of 0.12 U of heparin/ml was achieved; after the 7th injection, the mean concentration was 0.18 U of heparin/ml. Repeated SC heparin injections caused moderate swelling at the injection sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Anticoagulant effects of repeated subcutaneous injections of high doses of unfractionated heparin in healthy dogs.

OBJECTIVE: To evaluate s.c. administration of unfractionated heparin (UFH) in accordance with a dosing regimen for high-dose treatment in dogs. ANIMALS: 10 healthy adult Beagles. PROCEDURES: Two groups of dogs (5 dogs/group) were given 6 injections of heparin (500 units of UFH/kg of body weight, s.c.) at intervals of 8 (experiment 1) and 12 (experiment 2) hours. Blood samples were collected before and 4 hours after heparin injections to determine amidolytic heparin activity, activated partial thromboplastin time (APTT), thrombin time, antithrombin activity, platelet count, and Hct. RESULTS: For experiments 1 and 2, mean +/- SD heparin activities before (experiment 1, 1.32 +/- 0.20 U/ml; experiment 2, 0.69 +/- 0.174 U/ml) and 4 hours after the last heparin injection (experiment 1, 1.71 +/- 0.30 U/ml; experiment 2, 1.10 +/- 0.30 U/ml) were higher than values calculated for the regimen used in experiment 1. Results of the investigated thrombin time test system with low thrombin activity were frequently beyond the measurement range, even with UFH activities > or = 0.6 U/ml. Moreover, a severe decrease of antithrombin activity became evident during both experiments (eg, in experiment 2 from 95.6 +/- 4.8 to 59.2 +/- 6.6%). In each treatment group, 2 dogs developed hematomas. CONCLUSIONS AND CLINICAL RELEVANCE: Calculations of the course of heparin activity after a single injection do not result in a reliable dosing regimen for high-dose heparin treatment in dogs. High-dose treatment must be monitored for each dog. Thrombin time measured with low thrombin activity is unsuitable for this purpose.

Animals↗
PubMedDate not supplied

Effects of a supersulfated low molecular weight heparin (IK-SSH) on different hemostatic parameters.

In a phase I trial effects of a new supersulfated low molecular weight heparin (IK-SSH) on different hemostatic parameters were investigated in healthy volunteers. Parameters studied were activated partial thromboplastin time (aPTT), thrombin time, Heptest, anti-activated factor II (anti-FIIa) and anti-activated factor X (anti-FXa) activity, platelet adhesion, platelet count, platelet-induced thrombin generation time (PITT), bleeding time, antithrombin III, fibrinogen and several safety parameters. After single intravenous (i.v.) injections of IK-SSH (0.14, 0.33 and 0.66 mg/kg) aPTT, Heptest and PITT were strongly and dose-dependently prolonged. After ascending subcutaneous (s.c.) doses of IK-SSH (0.33, 0.66 and 1 mg/kg) aPTT, Heptest and PITT were prolonged in a dose-dependent manner. Repeat s.c. injections of 1 mg/kg IK-SSH for 5 days markedly prolonged aPTT, Heptest and PITT. No cumulative effects were observed. Anti-FIIa and anti-FXa activity were not or only slightly increased. Bleeding time, thrombin time and platelet adhesion were not significantly changed after i.v. and s.c. injections of IK-SSH. However, tissue factor pathway inhibitor (TFPI) concentration was markedly increased after each injection of IK-SSH and returned to the preinjection value 24 h later. IK-SSH prolongs aPTT, Heptest and PITT in a similar manner as other low molecular weight heparins but without significantly affecting thrombin time, FIIa and FXa activity. The release of TFPI may well be responsible for the prolongation of aPTT, Heptest and PITT. IK-SSH may be further developed as an antithrombotic agent.

Adult↗
PubMed1983

Thrombin clotting time and fibrinogen concentration in patients treated with coumadin.

Thrombin clotting times and fibrinogen levels were measured in plasma from patients on chronic coumadin therapy who had prolonged prothrombin times. Thrombin clotting times were usually prolonged. Fibrinogen concentrations were generally elevated, but some were normal or even low. There was no evidence for disseminated intravascular coagulation. Comparison of thrombin clotting times and fibrinogen levels in normal plasma demonstrates that as fibrinogen concentration increases the thrombin clotting time lengthens. A similar correlation was found in many of the patients tested.

Blood Coagulation↗
PubMed1993

Comparison of bedside coagulation monitoring tests with standard laboratory tests in patients after cardiac surgery.

We compared portable bedside tests of whole blood coagulation with standard laboratory plasma coagulation tests to assess the accuracy and precision of the bedside tests in a clinical setting (postcardiac surgery). The Ciba Corning 512 Coagulation Monitor (Ciba Corning Diagnostics Corp., Medfield, MA) and the Hemochron 801 (International Technidyne Corp., Edison, NJ) were tested. One hundred forty-one patients who underwent cardiac surgery requiring cardiopulmonary bypass were evaluated upon arrival in the intensive care unit. Nine milliliters of fresh whole blood were used to obtain the prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and the heparin-neutralized thrombin time (HNTT) that were measured by bedside coagulation monitors. TT and HNTT were only measured by the Hemochron method. Blood from the same sample was also sent to the Hospital Stat Laboratory for simultaneous comparison of bedside results and standard coagulation tests. For PT and aPTT testing, an accuracy of +/- 10% and a precision of +/- 25% were considered clinically acceptable. Both of the PT tests met the dual criteria for clinical acceptability, but the aPTT tests did not meet either criterion. The difference between Hemochron TT and Hemochron HNTT correlated weakly, but significantly, with laboratory aPTT ratio (r = 0.52, P < 0.001). The slope of the regression line indicated that a TT-HNTT difference > 30 s correlated with an aPTT > 1.5 x control. We conclude that, in the postoperative cardiac surgical patient, PT was both accurate and precise in two commercially available tests, but aPTT was not.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗
PubMed1999

Evaluation of secondary haemostasis in canine leishmaniasis.

Secondary haemostasis was evaluated in 26 dogs with leishmaniasis and 10 normal dogs by measurements of modified one-stage prothrombin time (m-OSPT), activated partial thromboplastin time (APTT), thrombin time, fibrinogen concentration and fibrin degradation products. There were no significant differences between the groups in the m-OSPT, fibrinogen concentration, or levels of fibrin degradation products. The APTT was significantly (P = 0.006) longer in the infected dogs than in the control group, and in infected dogs with alanine aminotransferase (ALT) activities > 50 U/litre. There was a significant linear regression between ALT and APTT. Thrombin time was significantly (P = 0.003) longer in the infected dogs than in the normal dogs. There were no significant differences between the thrombin times of sick dogs with different levels of creatinine or activities of ALT, or between male and female dogs, whether diseased or normal.

Alanine Transaminase↗
PubMed1985

Heparin assays and bleeding complications in treatment of deep venous thrombosis with particular reference to retroperitoneal bleeding.

Bleeding complications occurred in 30 (11%) out of 280 patients who received continuous heparin infusion for deep venous thrombosis (DVT). 22 (8%) had minor while 8 patients (3%) had major bleeding complications (1 intrathoracic [fatal], 2 gastrointestinal and 5 retroperitoneal). Heparin activity, in daily drawn blood samples, was determined by four assays (chromogenic substrate [CS] assay, activated partial thromboplastin time [APTT], thrombin time with citrated plasma [CiTT] and thrombin time with recalcified plasma [CaTT]). The differences in median heparin activity between patients with minor bleeding and patients with no bleeding did not reach significance for any of the tests. In patients with major bleeding, the differences were significant with the CS (p = .011) and the CaTT (p = .030) assays. Patients with retroperitoneal bleeding had significantly increased median activity judged by all four assays: CS (p = .002), CaTT (p = .003), APTT (p = .010), CiTT (p = .029). The difference was most pronounced after four days of heparin treatment, but there was a considerable overlap with patients without bleeding.

Adult↗
PubMed1983

Thrombokinetic studies in normal and factor VIII-deficient canine plasmas.

Thrombokinetograms are graphic depictions of the optical changes occurring in plasma during the clotting process and provide information, not only on the time required for clotting to begin, but also on the way in which the clot forms. We studied thrombokinetic profiles in plasmas from normal dogs, and dogs with varying degrees of factor VIII deficiency. Clotting was induced through intrinsic, extrinsic and common coagulation pathways [activated partial thromboplastin time, prothrombin time and thrombin time, respectively]. The thrombokinetograms for the various clotting tests were qualitatively similar in normal canine plasmas. After activation of the clotting system there was a period in which no change in optical density occurred. This period was represented by the left base line and corresponded to the duration of the clotting time. When fibrin production commenced there was a rapid increase in the rate of optical density change (DeltaOD) to a maximum (V(max)DeltaOD) in time t(1). This was followed by a more gradual reduction in DeltaOD in time t(2). The activated partial thromboplastin time thrombokinetograms for von Willebrand's disease plasmas were characterized by a reduced V(max)DeltaOD and prolonged t(1). In severe hemophilic plasma [factor VIII coagulant (F VIII:C)<1% of normal] there was a very slow increase in DeltaOD following a prolonged left baseline. The V(max)DeltaOD, t(1) and t(2) could not be determined since a peak was not attained in one minute. The prothrombin and thrombin time thrombokinetograms for von Willebrand's disease plasmas were normal. The prothrombin time thrombokinetogram for hemophilic plasma had a 2X normal V(max)DeltaOD possibly related to the relatively high fibrinogen concentration of this plasma compared to the normal. Changes in thrombokinetogram profiles may be of value in studying mild to moderate clotting factor deficiencies particularly where the clotting times are not markedly prolonged.

Animals↗
PubMed1991

Partial in vivo neutralisation of plasma anticoagulant effects of Lomoparan (Org 10172) by protamine chloride.

In a cross-over study increasing doses of protamine hydrochloride (20-100 mg) or placebo were administered to six groups of four healthy male volunteers each, following a single intravenous dose of 3200 anti-Xa units of Org 10172. No neutralising effects were observed on the Org 10172 induced changes in the bleeding time, prothrombin time and thrombin time. A small and statistically not significant temporary decrease in anti-Xa activity was observed after doses of 80 and 100 mg protamine chloride. The anti-thrombin activity was dose-dependently and partly irreversibly neutralised by protamine chloride to a maximum of approximately 60%. This neutralisation correlated with the observed shorter prolongation of the thrombin time. The thrombin-generation inhibition activity was for approximately 35% neutralised by protamine chloride doses of 60-100 mg.

Adolescent↗
PubMed1988

The thrombin clotting time. Evaluation of Thromboquik, a commercial thrombin reagent, and observations on sensitivity and on centrifugation.

The thrombin clotting time (TCT) is an important screening test of coagulation, but thrombin can be a troublesome reagent to use, and in general the TCT has not been well standardized, even with respect to the ideal normal range. Thromboquik is a thrombin reagent that is convenient in its day-to-day use and that exhibits prolonged stability after reconstitution. As an extension of an evaluation of this commercial thrombin reagent, the authors have made several observations about the TCT itself. In a comparison between multiple pairs of TCT reagents, the relative extent of departure of clotting times from normal, for any given abnormal plasma sample, was not predictably related to the mean normal clotting times of the two reagents. The authors also concluded that centrifugation of blood at 1,500 X g is inadequate to prepare plasma for the TCT.

Blood Coagulation Tests↗
PubMed2002

Investigations on blood coagulation in the green iguana (Iguana iguana).

The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, kaolin clotting time (KCT), dilute Russell's viper venom time (DRVVT) and reptilase time, as well as five different plasma fibrinogen assays [gravimetry, Jacobsson method (extinction at 280 nm), Millar method (heat precipitation), kinetic turbidometry, Clauss method] and resonance thrombography were performed in 26 clinically healthy green iguanas. All assays were carried out in comparison with pooled normal canine plasma. In iguana plasma, the PT [median (x0.50) = 453-831 s, dependent on the reagent], APTT (x0.50 = 170-242 s, dependent on the reagent), thrombin time (x0.50 = 118 - > 1000 s, dependent on thrombin activity), KCT (x0.50 = 274 s), DRVVT (x0.50 = 349 s) and reptilase time (all samples > 1000 s) were widely scattered at the limit of measurability. Only fibrinogen concentrations measured using the Jacobsson method (x0.50 = 4.40 g/l) correlated well (r = 0.91) with gravimetry (x0.50 = 4.22 g/l). The results of this study indicate a limited suitability and a confined diagnostic significance of the selected methods in the green iguana. This may be caused by the species specificity of certain components of the reagents used, as well as a less optimal test system, i.e. relationship of test reagent to clotting factor concentrations in iguana plasma.

Animals↗
PubMed2006

High density fermentation and activity of a recombinant lumbrokinase (PI239) from Pichia pastoris.

A system for the expression of recombinant lumbrokinase (rPI239) was developed in the yeast Pichia pastoris. A total supernatant protein content of 0.174 g/L of high density fermentation broth was obtained. The rPI239 exhibited in vitro fibrinolytic activity. The in vivo activity of rPI239 was measured by prothrombin time, kaolin part thrombin time, thrombin time, and fibrinolytic activity. This work presents the high-density fermentation of rPI239 from P. pastoris and shows that the recombinant protein has similar fibrinolytic activity both in vivo and in vitro.

DNA Primers↗