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Baseline coagulation assay values for northern elephant seals (Mirounga angustirostris), and disseminated intravascular coagulation in this species.

Coagulation assays, including platelet counts, antithrombin III, fibrinogen, fibrinogen degradation product levels, prothrombin (PT), activated partial thromboplastin (APTT) and activated clotting times (ACT), were performed on 20 healthy juvenile northern elephant seals (Mirounga angustirostris) stranded along the central California coastline from 15 March to 15 April 1994, to establish baseline parameters for this species. Elephant seals appear to have relatively short ACT, PT, and APTT times, while fibrinogen, platelet and antithrombin III levels are similar to domestic species. Based on these mean values in healthy animals, disseminated intravascular coagulation (DIC) was diagnosed in an elephant seal with low plasma fibrinogen and extended ACT, PT and APTT times; this animal had hemorrhages, mixed bacterial suppurative interstitial pneumonia with verminous arteritis, epicarditis, hepatitis and enterocolitis.

Animals↗

Exchange transfusion activates coagulation and alters the coagulation profile in newborn infants.

Exchange transfusion (ET) with adult blood is a standard procedure for neonates with severe hyperbilirubinemia. How ET affects newborn coagulation system remains, however, largely unknown. Thus, we prospectively evaluated the effect of ET on thrombin formation and coagulation profile in 18 newborns (22 ETs). Prothrombin fragment F1+2 and thrombin-antithrombin complexes increased considerably during ET while platelets were significantly reduced. Protein C increased less (p < 0.001) and factor VIIIc more (p < 0.001) than expected based on their levels in the infused blood. Further, in vitro thrombin generation initiated by 5 pM tissue factor was analysed. Before the first ET, newborn endogenous thrombin potential (ETP) and thrombin peak remained at approximately 60% of adult control plasma levels, but the lag time to thrombin burst in newborn plasma was approximately 45% shorter than the lag time in adult plasma. At the end of the first ET, the thrombin burst still started approximately 35% earlier in newborn than adult plasma, whereas ETP and thrombin peak were increased to > 90% of adult levels. ETP and peak remained elevated at adult levels until the beginning of the second ET. APC-induced reductions in newborn ETP remained unaltered throughout the first ET. The reductions of ETP by APC were less pronounced in newborn than adult plasma (p < 0.0001). We conclude that ET is associated with multiple procoagulant changes and increased in vivo thrombin formation. This ET-induced procoagulant challenge may be of clinical significance in sick newborns already prone to bleeding and thrombotic complications.

Adult↗

Mechanical properties of coagulated albumin and failure mechanisms of liver repaired with the use of an argon-beam coagulator with albumin.

Hemostasis in the traumatized liver has been achieved by thermally denaturing topically applied albumin. In this article, the mechanical properties of liver and denatured albumin (solder) were measured, and the failure methods of liver repaired with albumin were identified. The ultimate tensile strength and Young's modulus were measured for healthy liver (N = 20) and thermally damaged liver (N = 20). The ultimate tensile strength and Young's modulus were measured for three concentrations of coagulated albumin (25, 38, and 53%) in a single layer and for two layers of denatured 38% albumin. Failure under tension of argon-beam coagulator soldered liver on the parenchymal surface (N = 30) with 38% albumin in two layers had a 70% occurrence for tearing at a mean stress of 39 kPa and a 23% occurrence for shearing at a mean stress of 7 kPa. Liver repaired on the interior surface (N = 11) failed in tension by tearing (64%) at a mean stress of 34 kPa and by shearing (36%) at a mean stress of 6 kPa. Argon-beam coagulator soldering with 38% albumin took 6 s/cm(2) for two layers of solder and gave the best balance of usability, strength, and matching of mechanical properties with those of the liver.

Albumins↗

Tissue factor accelerates the activation of coagulation factor VII: the role of a bifunctional coagulation cofactor.

One way in which coagulation may be initiated is via the tissue factor pathway in which a non-proteolytic enzyme activator, tissue factor, complexes with a plasma protein, factor VII. Factor VII is the zymogen of a serine protease, factor VIIa. While factor VII-tissue factor has coagulant activity, upon conversion to factor VIIa the activity increases about 120-fold. We now show that tissue factor markedly accelerates the conversion of factor VII to factor VIIa. Thus, this essential coagulation cofactor is clearly bifunctional.

Animals↗

Hemodialysis and blood coagulation: the effect of hemodialysis on coagulation factor XIII and thrombin-antithrombin III complex.

Blood membrane interaction during hemodialysis (HD) regularly leads to stimulation of leukocyte function and related release of granular enzymes. The present study aimed to investigate the possible influence of an HD-induced release of granulocyte elastase on blood coagulation. Therefore a highly sensitive substrate of polymorphonuclear elastase, the plasma coagulation factor XIII and its subunits A and S were determined in the course of HD. Consumption of both subunit A and S have been previously shown to be due to proteolysis by elastase, whereas a decrease in subunit A will be typical for thrombin activation. Furthermore, the thrombin-antithrombin III complex (TAT) acting as a predisposition parameter for thrombotic events was measured during HD treatment. Apart from a virtual fall in factor XIII total activity simulated by heparin, no significant HD-induced consumption of factor XIII could be observed. There was also no indication of an elastase- or thrombin-related change in subunit concentrations. Predialysis values of the TAT complex were generally elevated in HD patients, but only patients with acute renal failure showed a constant increase of TAT during HD. These findings suggest that HD patients are exposed to a latent activation of coagulation resulting in an elevated thrombogenetic risk mainly due to the underlying disease. An additional coagulatory stimulation by the HD procedure seems to be restricted to cases of acute renal failure.

Acute Kidney Injury↗

Static suppression of tomato bacterial wilt by bacterial coagulation using a new functional polymer that coagulates bacterial cells and is highly biodegradable.

Tomato bacterial wilt by Ralstonia solanacearum was suppressed by coagulation of bacterial cells without disinfection using a copolymer of methyl methacrylate with N-benzyl-4-vinylpyridinium chloride in a molar ratio of 3:1 (PMMA-co-BVP) as a polymeric coagulant for bacterial cells. When 10 mg/kg of PMMA-co-BVP was added to soil before transplanting of tomato seedlings, and 2 mg/kg was supplemented once a week after transplanting, a 51% reduction of appearance and a 54% reduction of index of symptoms were observed. PMMA-co-BVP did not exhibit bactericidal activity against R. solanacearum, and coagulation of the bacterial cells appeared to reduce the opportunity for infectious contact of roots of tomato with cells of R. solanacearum, and resulted in disease suppression. PMMA-co-BVP was shown to be highly biodegradable, and the half-life was 5.1 d when treated with activated sludge in soil.

Biodegradation, Environmental↗

The two-stage coagulation of milk proteins in the minimum of the heat coagulation time-pH profile of milk: effect of casein micelle size.

Milks with casein micelles larger or smaller than control milk were prepared by differential centrifugation. The heat stability of these modified milks increased markedly throughout the pH range 6.4 to 7.1 with decreasing casein micelle size. Within the region of the minimum in the heat coagulation time-pH profile, the control milk coagulated by a two-stage process, but the modified milks, because of their narrower casein micelle size distribution, coagulated by a single-stage process at the pH of minimum stability. The content of kappa-CN and protein hydration increased as the size of the casein micelles decreased, and the level of glycosylation of kappa-CN and protein surface hydrophobicity increased as a function of micelle size. The effect of casein micelle size on the heat stability of milk is likely to be related to changes in the above physico-chemical properties.

Animals↗

[Therapy of recurrent menorrhagia--Cavaterm balloon coagulation versus roller-ball endometrium coagulation--a prospective randomized comparative study].

In a prospective study 20 patients suffering from recurrent, therapy-refractory menorrhagias were pre-treated for endometrial ablation after exclusion of intrauterine abnormalities and histological pathology. Two injections of GnRH-analogues (3.75 mg leuprorelinacetate depot, Enantone Gyn, Takeda Pharma GmbH Aachen, Germany). Two weeks after the last injection a hysteroscopic surgery by roller-ball-techniques was performed in 10 patients and a balloon-thermocoagulation by Cavaterm-technique (Wallsten Medical, Morges, Schweiz) was performed in 10 patients. Both patients groups were comparable according to age and anamnesis. In a follow-up of 9 to 15 months we found about identical results. All 20 patients were satisfied with the treatment. The Cavaterm-coagulation is in comparison to the operative hysteroscopy a simple method for endometrial coagulation, and can also be used by an hysteroscopically inexperienced gynaecologists with simple technical equipment. In strict indication the Cavaterm-coagulation is a simple method of endometrial ablation in many patients.

Catheterization↗

Coagulation patterns of disseminated intravascular coagulation in acute promyelocytic leukemia.

Coagulation patterns of 19 newly-diagnosed acute promyelocytic leukemia (APL) patients with disseminated intravascular coagulation (DIC) at presentation were studied. Seventeen patients had hemorrhagic complications, of which four were fatal. Fatal hemorrhages were related with lower fibrinogen level and lower platelet count. DIC of the APL patients without infection was characterized by low fibrinogen and normal antithrombin III (ATIII) level. Thrombin-ATIII complex level was elevated in all patients examined. Patients with infection had higher fibrinogen levels than those without infection and some patients had reduced ATIII level. Ten remission inductions were tried with multidrug chemotherapy and seven with all-trans retinoic acid (ATRA). Complete remission was achieved in seven of ten inductions with chemotherapy and in all seven inductions with ATRA. Two patients treated with chemotherapy had fatal hemorrhage after starting therapy but none treated with ATRA.

Adolescent↗

In vivo demonstration in humans that large postprandial triglyceride-rich lipoproteins activate coagulation factor VII through the intrinsic coagulation pathway.

In vitro studies in purified plasma systems have suggested that triglyceride-rich lipoproteins such as chylomicrons, very low density lipoproteins, and their remnants promote activation of factor VII through activated factor XII (XIIa) and the intrinsic coagulation pathway. We specifically examined the roles of factors XII, XI, and IX in activation of factor VII during alimentary lipemia in vivo in humans and addressed the issue of whether generation of activated factor VII (VIIa) is accompanied by increased thrombin production. For this purpose XIIa, factor IX activation peptide (IXP), VIIa, prothrombin fragment 1 + 2 (F1 + 2), and thrombin-antithrombin complex (TAT) were determined in plasma samples taken before and 3, 6, and 9 hours after intake of a mixed meal type of oral fat load in 24 healthy men The VIIa response to fat intake was also determined in 7 patients with single coagulation-factor deficiency, of whom 2 were deficient in factor XII, 2 in factor XI, and 3 in factor IX. Postprandial activation of factors IX and VII occurred in the healthy individuals, whereas the plasma levels of XIIa did not change in response to the test meal. Of note, plasma concentrations of F1 + 2 were unaltered during alimentary lipemia, and TAT levels showed a small decrease (P < .05) in the 3-hour sample compared with the fasting level, indicating that thrombin generation is not stimulated in the postprandial state, despite the generation of activated factor IX (IXa) and VIIa. Factor VIIa increased in the postprandial period in the 2 factor XII-deficient patients who underwent the oral fat tolerance test but appeared to remain unchanged in the factor XI- and factor IX-deficient patients. Therefore, the current concept that activation of factor XII plays a pivotal role in initiating the sequence of events linking postprandial lipemia to activation of factor VII is contradicted by the present study. Whether activation of factor XI by triglyceride rich lipoproteins initiates these reactions needs to be demonstrated in future studies.

Adult↗

[Coagulation, inflammation and immune response -- an evolutionary conserved plan as cause for disseminated intravasal coagulation?].

The concomitant activation of the immune response and the coagulation system in response to injury represents a phylogenetic old and adaptive principle already present in the early eukaryotic development. The close connection between coagulation, inflammation, and immune defense has been conserved during evolution and can still be found in humans in a number of physiologic reactions to potentially detrimental effects.

Biological Evolution↗

[Clinical data obtained through coagulation testing suggests that hypothermia exerts influence on a patient's blood coagulation reaction].

It often takes longer to achieve hemostasis when performing an operation on a patient in cerebral hypothermia therapy than in a normal patient, despite the lack of abnormal clinical blood coagulation findings, and this study was conducted to investigate the cause of delays in coagulation in patients with hypothermia. In this study, 93 samples of plasma were collected at our center from 10 patients(7 men and 3 women; mean age, 33.7) who were in cerebral hypothermia therapy with a urinary bladder temperature maintained at 32-34 degrees C. Each sample was divided into two, and PT(prothrombin time) and APTT(activated partial thromboplastin time) were measured at the normal analysis temperature of 37 degrees C in one sample, and at the hypothermia temperature of 32-34 degrees C in the other sample. The results showed that PT and APTT tended to shorter at 37 degrees C, than those measured at 32-34 degrees C. Thus, we suggest that it is necessary to regulate the temperature of patients with accidental hypothermia or in whom hypothermia therapy is performed.

Adult↗

[Coagulation disorders due to burns. Disseminated intravascular coagulation (DIC) and its possible prevention].

Coagulation data were studied in 77 patients with severe burns divided into two groups (A, 45 cases, and B, 32 cases). Increased PDF, platelet deficiency, enhanced fibrinogen turnover, and paracoagulation tests showing disseminated intravascular coagulation were frequent in both groups. Platelet deficiency was significantly more frequent in group A (64.9% of cases) than in group B (37.5%). Patients in the latter group received small subcutaneous doses of heparin from the moment of admission.

Blood Cell Count↗

Transmittance waveform of routine coagulation tests is a sensitive and specific method for diagnosing non-overt disseminated intravascular coagulation.

The transmittance waveform profile on the routine coagulation test of the activated partial thromboplastin time can be characteristically biphasic in patients with disseminated intravascular coagulation (DIC). We have previously shown that there is increasing positive predictive value for DIC with increasing abnormality in this profile, and that waveform changes often preceded those in the more conventional parameters used for diagnosing DIC. We now show that a single analysis of the activated partial thromboplastin time waveform within the first hour of intensive care admission can assign risk of DIC development, and that this is superior to that of D-dimer measurements. Additionally, the analysis can also rapidly monitor progression from non-overt to overt DIC. This offers the potential of improved diagnostic means for targeting therapeutic intervention early in the DIC progress, as can be particularly useful in sepsis.

Blood Coagulation Tests↗

Progestational agents and blood coagulation. VII. Thromboembolic and other complications of oral contraceptive therapy in relationship to pretreatment levels of blood coagulation factors: summary report of a ten-year study.

During a ten-year period, 348 women were studied for a total of 5,877 patient months in four separate studies relating oral contraceptives to changes in hematologic parameters. Significant increases in certain factors of the blood coagulation and fibrinolysin systems (factors I,II,VII,VIII,IX, and X and plasminogen) were observed in the treated groups. Severe complications developed in four patients. All four had an abnormal blood coagulation profile, suggesting "hypercoagulability" before initiation of therapy. Some of these findings represented the most extreme abnormalities seen in the entire group of patients; some increased further during therapy. One of these patients developed a myocardial infarction before receiving any medication, shortly after the base-line values were obtained. One patient developed retinopathy 19 months after she began therapy, and another developed thrombophlebitis after 27 months of therapy. The fourth patient developed thrombophlebitis 14 days after initiation of contraceptive therapy. All four patients were of the A or AB blood group. Previous studies suggested the possiblility of increased propensity for thromboembolic episodes in patients possessing the A antigen. It appears from these data that hematologic work-ups may be useful in women who are about to start long-term oral contraceptive therapy.

Adult↗

[Coagulation and fibrinolysis parameters in disseminated intravascular coagulation (DIC)].

Eighty six plasma samples from 41 patients with suspected disseminated intravascular coagulation (DIC) were divided into 3 groups as follows: Group A, 53 samples from established DIC; Group B, 19 samples from possible DIC; and Group C, 14 samples from probable DIC. The following parameters of coagulation and fibrinolysis were evaluated: thrombin/antithrombin III complex (TAT), plasmin/alpha 2 plasmin inhibitor complex (PIC), D-dimer (D-D) and fibrin monomer (FM). In Group A, TAT and PIC were significantly elevated, being 29.5 +/- 20.7 micrograms/l and 7.2 +/- 6.1 mg/l respectively, suggesting marked hypercoagulability and accelerated fibrinolysis. There were no correlations between antithrombin III (ATIII) and TAT, between alpha 2 plasmin inhibitor (alpha 2PI) and PIC, or between TAT and PIC, showing the clinical diversity of patients with DIC. In all groups abnormal TAT, PIC and D-D findings were observed in many samples (86-100%), and FM was present in 83%, 63%, and 29% of samples in Groups A, B, and C respectively. In Groups B and C, abnormal findings for TAT, PIC, D-D, FM and alpha 2PI apparently indicated hypercoagulability and accelerated fibrinolysis, even though fibrinogen and platelet count were within normal limits.

Antifibrinolytic Agents↗

[Coagulative activity and acid resistance of damaged and intact erythrocytes in various types of intravascular blood coagulation].

Blood assay in patients with DIC-syndrome and thrombosis has shown different changes in red blood cell acid resistance: it is increased in acute noninfectious DIC-syndrome, and significantly decreased in the presence of sepsis, in patients with chronic DIC-syndrome and acute thrombophlebitis it is less lowered, while it is significantly elevated in the development of thromboembolism of the pulmonary artery. At the same time red blood cells damaged due to DIC-syndrome are characterized by increased acid resistance and high coagulation potential. This combination has proved the pathogenetic role of damaged red blood cells and the process of fragmentation in the development of intravascular blood coagulation.

Blood Coagulation↗

Activation of the contact system of coagulation by a monoclonal antibody directed against a neodeterminant in the heavy chain region of human coagulation factor XII (Hageman factor).

We studied the characteristics of two monoclonal antibodies (mAbs), F1 and F3, against human coagulation factor XII (Hageman factor). Experiments with trypsin-digested 125I-factor XII revealed that the epitope for mAb F1 is located in the NH2-terminal Mr 40,100 portion of factor XII, whereas that for mAb F3 resides in the COOH-terminal Mr 30,000 portion of this protein. Factor XII in fresh plasma (single-chain factor XII) bound approximately 190 times less to mAb F1 than factor XII in dextran sulfate-activated plasma (cleaved factor XII). However, no difference in accessibility of the epitope for mAb F1 was observed between cleaved and single-chain factor XII when bound to glass. mAb F3 appeared to bind to both single-chain and cleaved factor XII in plasma as well as when bound to glass. Neither mAb F1, nor F3 affected the amidolytic activity of factor XIIa, whereas both mAb F1 and F3 inhibited factor XII-coagulant activity to about 15 and 70%, respectively, at a molar ratio of mAb to factor XII of 20 to 1. mAb F1, as well as F(ab')2 and F(ab') fragments of this antibody induced activation of the contact system in plasma, as reflected by the generation of factor XIIa. C1 inhibitor and kallikrein. C1 inhibitor complexes. Activation was induced neither upon incubation with mAb F3, nor with that of control mAbs. mAb F1-induced contact activation required the presence of factor XII, prekallikrein, and high molecular weight kininogen and, in contrast to activation by negatively charged surfaces, was not inhibited by the presence of Polybrene. Based on these results we propose that a conformational change in factor XII is a key event in the activation process of this molecule. This conformational change can be induced by binding of factor XII to a surface as well as by proteolytic cleavage. As mAb F1 can also induce this conformational change, this antibody may provide a unique tool in studies of the activation of factor XII.

Animals↗