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PubMed1986

Hemostatic abnormalities in equine colic.

Hemostatic profiles were determined in 30 horses with clinical colic. Blood samples were obtained at the time of the animal's admission, and the following hemostatic tests were done: blood platelet count, plasma fibrinogen, plasma antithrombin, prothrombin time, partial thromboplastin time, thrombin time, protamine sulfate test for soluble fibrin monomer, and fibrin-fibrinogen degradation products. The patients were categorized in retrospect, according to the cause of the colic: group 1--colic associated with colitis and/or severe diarrhea, group 2--colic associated with torsion or obstruction of the intestine, and group 3--colic associated with impaction of the intestine or the presence of enteroliths. Of the 30 horses with colic, 28 had at least 1 abnormality in their coagulogram--the most frequent abnormalities being high plasma fibrinogen concentration, high circulating soluble fibrin monomer, or a long partial thromboplastin time or thrombin time. The horses in group 1 seemed to have the most severe coagulopathies, as indicated by the average number of demonstrable abnormalities. The horses in group 3 showed the fewest abnormalities--usually a high plasma concentrations of fibrinogen and/or soluble fibrin monomer. The results indicated that hemostatic abnormalities are not uncommon in horses with gastrointestinal disease and colic--the degree of severity depending to some extent on the cause of the colic.

Animals↗
PubMed1974

Fibrinogen Cleveland II. An abnormal fibrinogen with defective release of fibrinopeptide A.

An abnormal fibrinogen (fibrinogen Cleveland II) was detected in the plasma of a 23-yr-old white man with a mild bleeding diathesis. The one-stage prothrombin time, thrombin time, and Reptilase time were all prolonged. 16 of 24 tested relatives had the defect, which appeared to be transmitted as an autosomal dominant characteristic. The thrombin time of normal plasma was slightly inhibited by the proband's plasma. The abnormally long thrombin time of fibrinogen Cleveland II was partially corrected by addition of calcium ions. Fibrinogen Cleveland II was indistinguishable from normal fibrinogen by immunoelectrophoresis, DEAE-cellulose column chromatography, or polyacrylamide gel electrophoresis of reduced fibrinogen in sodium dodecyl sulfate. The major defect detected appeared to be impaired release of fibrinopeptide A when fibrinogen Cleveland II was incubated with thrombin. This defect was localized to the NH(2)-terminal disulfide knot portion of the molecule. An abnormality of polymerization of fibrin monomers was also present, but the abnormal fibrin demonstrated relatively normal crosslinking. Despite these defects, fibrinogen Cleveland II achieved a degree of coagulability similar to normal fibrinogen and appeared to incorporate some molecules of fibrin with intact fibrinopeptide A into the clot. The fibrin clot that was formed appeared to be abnormal by electron microscopy. These functional defects and other descriptive characteristics appear to distinguish fibrinogen Cleveland II from other inherited abnormal fibrinogens.

Adult↗
PubMed1986

[Bolus injection of anisoylated plasminogen-streptokinase activator complex (BRL 26921) as an alternative concept of systemic lysis in acute myocardial infarct].

The thrombolytic properties of anisoylated plasminogen streptokinase activator complex (BRL 26921) and clinical results of the treatment were studied in 10 consecutive patients with acute myocardial infarction. Exclusion criteria were general contraindications against thrombolytic therapy and a time interval of more than 4 h between the onset of symptoms and admission to the hospital. All patients received a 250-mg bolus of prednisolone prior to intravenous injection of 30 mg BRL 26921 within 2 min. A continuous infusion of heparin at a dose of 1,000 USPU/h was started 2 h after the injection. Blood pressure was monitored via an arterial line. Arrhythmias and changes in the ST segments were documented by conventional ECG recording and computer-based ECG monitoring. Coronary arteriography and left ventriculography were carried out within 72 h. Besides routine laboratory tests, serial CK and CK-MB activity measurements were carried out. We determined the following hemostaseological parameters before and 15 min, 30 min, 1 h, 4 h, and 12 h after application of BRL 26921: prothrombin time, activated partial thrombosplastin time, thrombin time, thrombin coagulase time, fibrinogen, streptokinaseplasminogen activator activity, plasminogen and alpha-2-antiplasmin. Our results (reperfusion in all patients angiographically and in 7 to 8 of 10 patients from noninvasive criteria) show that BRL 26921 is a highly effective thrombolytic agent in patients with myocardial infarction, when compared with high-dose systemic fibrinolysis. Applied in dosages required for early reperfusion, it does not appear to be selectively thrombolytic and is not free of hypotensive effects in man. The decrease of fibrinolytic activity is biphasic with a half-disappearance time of 112 min.

Adult↗
PubMed1989

Physiological coagulation profile of dairy cattle.

90 clinically healthy cattle with a normal estrus cycle (German Black Pied) were investigated. Normal values for the physiological coagulation profile including prothrombin time, partial thromboplastin time, thrombin time, and fibrinogen concentration were determined. The following ranges of normal values (means +/- 2SD) were calculated: prothrombin time (PT) 20.1-30.1 seconds; partial thromboplastin time (PTT) 25.3-44.5 seconds; thrombin time (TT) 12.4-17.2 seconds, and fibrinogen concentration 125-697 mg/dl. During the day and day to day variations in the individual parameters of the coagulation profile were not observed.

Animals↗
PubMed1979

Hemostatic abnormalities in malignancy, a prospective study of one hundred eight patients. Part I. Coagulation studies.

A prospective study of hemostatic abnormalities in 108 cancer patients was undertken at an oncology clinic in a university teaching hospital. Tests included Quick prothrombin time, activated partial thromboplastin time, thrombin time, platelet count, modified Ivy bleeding time, fibrinogen, fibrin degradation products (FDP), euglobulin lysis time, protamine sulfate test, and factor V, VII, VIII and X assays. Ninety-eight per cent of the patients had one or more abnormal coagulation tests. The commonest abnormalities were elevated fibrin degradation products and prolonged thrombin time. Thrombocytosis occurred in 57% of patients, hyperfibrinogenemia in 46%, thrombocytopenia in 11%, and non had hypofibrinogenmia. It is suggested that platelet count, fibrinogen concentration, and serum FDP assay are the most useful tests in assessing the hemostatic abnormalities in cancer patients, although thrombin time, factor V assay, and bleeding time may also be helpful. The peripheral blood smears of 53 patients were reviewed, and only one showed microangiopathic hemolytic anemia. The data illustrate that subclinical coagulopathy is relatively frequent in patients with malignancy.

Adolescent↗
PubMed1990

Coagulation activation in diabetes mellitus.

One hundred and fourty-eight insulin-dependent diabetic patients were available for this study; 56 males and 92 females. For the investigation of coagulation activation we determined activated partial thromboplastin time, thrombin time, and fibrinogen besides fibrin monomers and thrombin-antithrombin III complexes (TAT-III). We assessed large percentages of increased fibrinogen levels but non-significant increases of the mean values in comparison with the reference group. The values for thrombin time were significantly prolonged, although relatively small percentages were exceeding the reference range. For the activated partial thromboplastin time, the values exceeded the upper reference limit, and the mean values were significantly higher than those of the reference group. Also for the fibrin monomers we obtained often enhanced values, and moreover, the values were significantly higher as compared with the reference subjects. The amount of TAT-III concentrations above the reference range was much smaller than for the fibrin monomers and the TAT-III levels were not significantly enhanced. The results presented here are indicative of coagulation activation in diabetics, as indicated by the fibrin monomers and more or less by the TAT-III levels. Moreover, there could be demonstrated a positive correlation between fibrin monomer levels and HbA1 concentrations.

Adult↗
PubMed1985

Circadian changes in anticoagulant effect of heparin infused at a constant rate.

Six patients with venous thromboembolism were treated with heparin, administered intravenously by a constant infusion pump. The initial daily dose of heparin was adjusted to keep the activated partial thromboplastin time, sampled at 0800, between 1.5 and 2.5 times the control level. Once that level was obtained, this dose was kept constant. Anticoagulation was thereafter measured, every four hours for 48 hours, by activated partial thromboplastin time, thrombin time, and coagulation factor Xa inhibition assay. The results of all three coagulation tests showed a circadian variation in the six patients. Maximum values were achieved at night and minimum values in the morning. These circadian variations were reproduced for two consecutive days. Differences between night and morning values reached almost 50% for activated partial thromboplastin time, 60% for thrombin time, and 40% for factor Xa inhibition assay. This circadian variation resulted from two rhythms, a circadian rhythm lasting 24 hours and an ultradian rhythm lasting 12 hours, which were detected by cosinor analysis for each coagulation test (p less than 0.01). A circadian rhythm was detected individually in most of the patients for each coagulation test (p less than 0.05). All patients had a nocturnal peak in activated partial thromboplastin time on both days. In four patients this peak exceeded the upper desired limit of activated partial thromboplastin time. These rhythms should be taken into account when evaluating the dosage of heparin to be administered.

Aged↗
PubMed1993

Hemostasis in cows with endotoxin-induced mastitis.

Hemostasis was evaluated in cows with experimentally induced endotoxemia and mastitis, caused by intramammary infusion of endotoxin (1 mg) derived from Escherichia coli. Hemostatic tests included prothrombin time; activated partial thromboplastin time; thrombin time; fibrinogen, fibrin(ogen) degradation products, and platelet concentrations; and antithrombin-III and plasminogen activities. Significant alterations were observed in the mean values of most analytes (prothrombin time was increased; thrombin time was increased with subsequent decrease; activated partial thromboplastin time, fibrinogen concentration, plasminogen activity, and platelet concentration were decreased; and antithrombin-III activity and fibrin(ogen) degradation products concentration were unchanged) at 1 or more postchallenge sample collection times (3, 12, or 24 hours) after endotoxin administration, compared with mean values obtained from samples prior to endotoxin administration. These data indicated activation of hemostatic mechanisms, initiated either directly by endotoxin or by inflammatory mediators released or produced in response to endotoxin infusion.

Animals↗
PubMedDate not supplied

Study of haemostatic disorders in experimentally induced leishmaniasis in Beagle dogs.

Haemostatic alterations in dogs experimentally infected with Leishmania infantum were studied before and after therapy with meglumine antimonate. Haemostatic function tests including platelet count, collagen-induced platelet aggregation, prothrombin time, activated partial thromboplastin time, thrombin time, plasma fibrinogen determination, and serum fibrinogen/fibrin degradation products concentration were performed. In the course of infection and before treatment, moderate thrombocytopenia (P<0.00001), decreased collagen induced platelet aggregation (P=0.0003), prolonged thrombin time (P=0.0117) and increased fibrinogen/fibrin degradation products were observed. Statistically significant differences of plasma fibrinogen concentration, prothrombin time, and activated partial thromboplastin time were not encountered. Haemostatic parameters returned to normal values after therapy. The results indicate that Leishmania infection may impair haemostasis suggesting induction of disseminated intravascular coagulation (DIC), and that treating dogs in an early stage of infection may potentially avoid the possibility of developing an uncompensated DIC.

Animals↗
PubMed1999

Evaluation of the automated coagulation analyzer SYSMEX CA 6000.

In the present study the coagulation analyzer SYSMEX CA 6000 (TOA Medical Electronics Co., Kobe, Japan), an analyzer equipped with a photooptical clot detection unit and a cap-piercing system, was evaluated with respect to its technical characteristics in the determination of standard coagulation tests (prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, and antithrombin) and in the determination of coagulation single factor activities. In the normal and in the pathological range the intraassay coefficients of variation (CV) and interassay CV for most parameters were below 5% (exceptions: intraassay CV 5.4% for prolonged thrombin time; intraassay CV 9.26% and interassay CV 10.7% for decreased antithrombin; interassay CV 5.62% for fibrinogen in the normal range, intraassay CV 10.1% for fibrinogen greater than 7.0 g/L; intraassay CV 6.36% and interassay CV 11.7% for decreased fibrinogen; interassay CV 11.6% for prolonged activated partial thromboplastin time; interassay CV 6.12% for decreased factor VII). Interference studies with lipemic, icteric, and hemolytic samples showed just minor influences of these abnormal sample characteristics on prothrombin time, activated partial thromboplastin time, fibrinogen, and antithrombin measurements when compared to the results obtained by using mechanical clot detection (STA, Stago Diagnostica, Asnieres-Sur-Seine, France). No carryover was detected in alternating measurements of heparinized (3 U/mL unfractionated heparin) and normal plasma samples. Measurement of the activities of clotting factors V, VII, VIII, and IX showed a good correlation (r=0.993 to r=0.977) between SYSMEX CA 6000 and STA. Our results demonstrate that using SYSMEX CA 6000 analyzer basal routine coagulation testing as well as specialized tests for single factor activities can be performed with satisfactory precision; in particular, the cap-piercing system has no negative effect on the performance of the analyzer.

Adult↗
PubMed1997

Bioavailability of Desmin, a low molecular weight dermatan sulfate, after subcutaneous administration to healthy volunteers.

The bioavailability of two different s.c. doses of Desmin (a new low molecular weight dermatan sulfate) was evaluated in 12 healthy volunteers (6 men, 6 women aged 22-45 years) who were injected, on 3 separate days and with a wash-out period of at least 21 days between each administration, with 200 and 300 mg of Desmin by the s.c. route and 200 mg by the i.v. route. Immediately before injection and at various times thereafter (after 15 min and 30 min for i.v. only and after 1, 2, 3, 4, 6, 8, 12, and 24 h for both s.c. and i.v. dosing), blood samples were drawn to investigate bioavailability by measuring several coagulation parameters: activated partial thromboplastin time, thrombin time, inhibition of factor Xa, Heptest, and heparin cofactor II. Furthermore the local tolerance of the s.c. and i.v. injections were investigated. The s.c. administration of the two Desmin doses had a negligible effect on the activated partial thromboplastin time and a very small effect on the thrombin time, measured with human thrombin; in contrast, Heptest, heparin cofactor II, and anti-Xa activities increased, with a good drug bioavailability (more than 100%). The plasma effects of Desmin were dose dependent only when measured by Heptest, which also gave a greater response after the s.c. administrations. There were no symptoms of intolerance or pain at the injection site after single i.v. and s.c. Desmin administration.

Adult↗
PubMed2005

[Functional status of haemostasis system in patients with visceral leishmaniasis].

During the last decades in Georgia was observed significant increase of cases of visceral leishmaniasis and fight against this disease became important problem as far as the management of this disease is rather problematic. According to references and our clinical experience patients with visceral leishmaniasis are predisposed to bleeding. The objective of our study was the assessment of functional status of hemostasis related to the degree of clinical severity. We have studied platelet count, activated partial thromboplastin time (APTT), prothrombin time, thrombin time, plasma concentration of fibrinogen, the soluble fibrin-monomeric complexes (SFMC), fibrinogen/fibrin degradation products (D-dimer) and anticoagulant protein C. Haemostatic functional tests were studied in 45 patients with visceral leishmaniasis before and after treatment (with 20-25 day intervals). Before treatment the reduction of platelet count was observed in 95%. Prolonged APTT and prothrombin time was found in severe forms of the disease. Thrombin time prolonged in 45.7%, SFMC level was increased in 80% (p=0.003) and D-dimer level in 95.6% (p=0.023). Protein C was in normal value in 73%. The results indicate that leishmania infection affects primary haemostasis, coagulation and fibrinolysis and these alterations are related to the severity of clinical symptoms. Investigation of SFMC and D-dimer showed that in case of visceral leishmaniasis activation of intravascular coagulation takes place, particularly during the severe forms of the disease, study of these markers is of the diagnostic and prognostic importance and the treatment at an early stage of infection may potentially avoid the possibility of developing an uncompensated DIC.

Adolescent↗
PubMed2000

Pharmacological profile of recombinant, human activated protein C (LY203638) in a canine model of coronary artery thrombosis.

The antithrombotic activity of recombinant, human activated protein C (rh-APC, LY203638) was examined in a model of canine coronary artery thrombosis. Three doses of rh-APC (0.5, 1.0, and 2.0 mg/kg/h) were administered intravenously for 2 h. Whole blood clotting times (thrombin time, activated partial thromboplastin time), ex vivo platelet aggregation, and template bleeding times were determined. Activated partial thromboplastin time significantly increased 2- and 3.7-fold during the 2-h infusion of rh-APC (1.0 and 2.0 mg/kg/h, respectively); thrombin time did not change. Intravenous infusions of rh-APC (1.0 and 2.0 mg/kg/h) produced significant prolongations to occlusion, 186 +/- 21 and 190 +/- 22 min, respectively, compared with the vehicle and the 0.5 mg/kg/h group (86 +/- 12 and 93 +/- 17 min, respectively). Vessel patency was better at the end of the experiment in the intermediate- and high-dose groups (3 of 6 and 3 of 5 vessels, 1.0 and 2.0 mg/kg/h, respectively) compared with the vehicle and 0.5 mg/kg/h groups (0/5 and 0/6, respectively). Only the 1.0 mg/kg/h group was found to have significantly elevated template bleeding times, with peak increases seen 60 min into the drug infusion. All groups had returned to baseline values by the end of the study. There was no observed inhibition of platelet aggregation. These data demonstrate that recombinant, human activated protein C is an effective anticoagulant and antithrombotic agent in the dog.

Animals↗
PubMed2002

Bleeding and coagulation changes during spinal fusion surgery: a comparison of neuromuscular and idiopathic scoliosis patients.

OBJECTIVE: Major blood loss is common during spinal fusion surgery. We have previously demonstrated that patients with neuromuscular scoliosis have more blood loss and greater transfusion requirement than those with idiopathic scoliosis. Our objective is to study the relationships between etiology of scoliosis, blood loss, and coagulation changes in children and adolescents undergoing spinal fusion surgery. DESIGN: Prospective, observational study. SETTING: University teaching hospital. PATIENTS: A total of 25 patients, 11 with neuromuscular and 14 with idiopathic scoliosis, undergoing spinal fusion surgery. INTERVENTIONS: Blood was obtained preoperatively, 2 and 4 hrs intraoperatively, and 2 and 24 hrs postoperatively for prothrombin time, partial thromboplastin time, thrombin time, platelet count, D-dimer, factor VII and VIII activity, thrombin-antithrombin III complex, and protein induced by vitamin K absence. Changes in coagulation over time were analyzed by repeated-measures analysis of variance. Comparisons between groups were made using independent t-tests. RESULTS: Neuromuscular scoliosis patients had significantly greater blood loss than idiopathic scoliosis patients (median blood loss, 78% of total blood volume; range, 25-127% vs. 20%, 2-82%; p < .001). Prothrombin time increased over time in both groups and was higher in the neuromuscular than the idiopathic group both preoperatively and postoperatively (p < .05). Factor VII activity decreased over time in both groups (p < .001) and was lower in the neuromuscular than the idiopathic group during surgery (p < .05). No changes in partial thromboplastin time, thrombin time, or factor VIII activity were observed. D-dimers were present in both groups by 4 hrs intraoperatively. Protein induced by vitamin K absence was not detected in any patient. CONCLUSIONS: Neuromuscular scoliosis patients have more blood loss during spinal fusion surgery than idiopathic scoliosis patients. The prolongation of prothrombin time and decrease in Factor VII activity suggest activation of the extrinsic coagulation pathway. Depletion of clotting factors during scoliosis surgery occurs to a greater extent in patients with underlying neuromuscular disease.

Journal Article↗
PubMed1993

[Changes in coagulation in patients with sepsis].

Aiming to know the coagulation disorders that occur in patients with sepsis, a retrospective study of 75 such patients hospitalized in an Intensive Care Unit was performed. The coagulation profile requested by the attending physician, that included platelet count, prothrombin time, partial thromboplastin time, thrombin time, protamine sulphate test, fibrinogen and euglobin lysis time, was analyzed. Fourteen patients that were receiving prophylactic subcutaneous heparin were excluded from further analysis. Of the 61 remaining patients, 23 had hemorrhagic manifestations and 94.4% of these had multiple alterations in coagulation parameters. Eighty one percent of patients had abnormal prothrombin time and 73% thrombocytopenia. Isolated alterations were infrequent and consisted in thrombocytopenia (3.7%) and fibrinogen elevation (1.9%). Fifty two percent of patients had shock and they had significantly lower platelet counts and higher prothrombin and thrombin times than patients without hemodynamic disturbances. Global mortality was 63.9%. No relation between coagulation disturbances and mortality was observed. Likewise, no differences in mortality between patients with or without shock was observed. It is concluded that coagulation is frequently disturbed in patients with sepsis, even without clinical hemorrhagic symptoms, that these abnormalities are more marked in patients in shock and that 53% of these are consistent with intravascular coagulation.

Adolescent↗
PubMed1993

[Selected parameters of coagulation, fibrinolysis and antibodies to fibrinogen in lung cancer].

Levels of fibrinogen, fibrinogen degradation products, clot lysis time, thrombin time, titer of antifibrinogen antibodies were studied in 40 lung cancer patients and 30 honorary blood donors. Increase of fibrinolytic activity was observed which was related to clinical stage but not to type of cancer. Statistically significant increase in fibrinogen levels (p < 0.01) fibrinogen degradation products levels, antifibrinogen antibodies, prolonged thrombin time and clot lysis time was found in all lung cancer patients.

Adult↗
PubMed1991

Urokinase-mediated thrombolysis: a dose-response relationship in cats. Work in progress.

A cat model was developed to study thrombolytic agents. The infrarenal aorta was surgically exposed, all side branches were ligated, and both ends of the segment were occluded. After preformed clot was injected into the segment, proximal flow was restored and a distal stenosis was created. Urokinase was infused at rates varying from 4,000 to 250,000 U/h. Amount of remaining clot was quantified every 15 minutes with cine angiography. Pre- and postinfusion measurements of prothrombin time, partial thromboplastin time, thrombin time, and levels of fibrinogen and fibrin degradation products were obtained. A graph of thrombolysis rate versus infusion rate was obtained yielding maximal thrombolytic activity at 126,000 U/h and 90% of maximal activity at an infusion rate of 70,000 U/h. Levels of fibrin degradation products did not change. Prothrombin, partial thromboplastin, and thrombin times increased with increasing infusion rates, leveling off at 100,000 U/h, while fibrinogen levels decreased, with a plateau at 50,000 U/h.

Animals↗
PubMed2006

Hypercoagulability: interaction between inflammation and coagulation in familial Mediterranean fever.

Familial Mediterranean fever (FMF) patients in clinical remission are reported to have increased baseline inflammation. Normal function of the natural anticoagulant pathways is particularly needed in diminishing inflammatory responses. In the presence of subclinical inflammation, natural anticoagulant response may be exaggerated. We aimed to observe the anticoagulant-procoagulant status in attack-free FMF patients. Twenty-seven FMF patients diagnosed in accordance with Tel-Hashomer criteria, and 26 healthy controls were included. All patients were attack-free under regular colchicine treatment. Amyloidosis, autoimmunity, accompanying liver and renal disease, and vasculitis were excluded. Predisposing factors for thrombosis were not present. Acute phase reactants (APRs), anticardiolipin antibody positivity, prothrombin time (PT), activated prothrombin time, thrombin time (TT) and d-dimer, protein C activity, activated protein C resistance, free protein S, antithrombin, lupus anticoagulant, human prothrombin fragment F 1 + 2, and human thrombin/antithrombin III complex were analyzed for all subjects. APRs were comparable with controls. Autoimmune markers were negative in all. Anti-streptolysin titers were significantly different than the control group. PT, TT, protein C activity, and F 1 + 2 levels were significantly different from those of healthy controls. Shortened PT and TT, decreased protein C activity vs increased levels of F 1 + 2 suggested a hypercoagulable state in our patients. The hypercoagulable state detected in FMF patients suggests that screening with abnormal coagulation tests may be beneficial for tracing the future consequences of subclinical inflammation in these patients. Studies covering larger groups of patients are needed to verify the currently observed hypercoagulable status in FMF.

Adolescent↗