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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alveolar macrophages are thought to participate in the clearance of fibrin from the injured lung, but their ability to facilitate the conversion of fibrinogen to fibrin (procoagulant activity) has not been described. In order to characterize their procoagulant properties, unstimulated alveolar macrophages obtained from normal rabbits were tested for their ability to accelerate the coagulation of plasma in a one-stage clotting assay. Compared with control assays containing no macrophages (coagulation times greater than 500 s), intact cells (10(6)/ml) were shown to display procoagulant activity (coagulation time, 153.6 +/- 11.3 s mean +/- SEM). Cell lysis caused further procoagulant activity to be expressed (125.6 +/- 11.8 s). Alveolar macrophages that were stimulated in vitro with bacterial lipopolysaccharide (LPS) or the purified complement fragments C5a and C5a des Arg caused further significant (p less than 0.002) reductions in coagulation times (intact cells, 71 to 76 s; lysed cells, 27 to 32 s), representing 5- to 6-fold and 30- to 40-fold increases in the procoagulant activity of intact and lysed cells, respectively. The generation of this material was independent of the presence of lymphocytes. The procoagulant material was identified as a cell-associated tissue thromboplastin, acting via the extrinsic coagulation pathway. These findings show that alveolar macrophages have procoagulant activity that is markedly augmented by LPS and complement fragments. This suggests that alveolar macrophages may contribute to intra-alveolar fibrin deposition in vivo.
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PMID:Procoagulant activity of rabbit alveolar macrophages. 634 42

Hemorrhage was prospectively identified in 26 of 116 consecutive patients (23%) who were receiving intracoronary streptokinase for occlusive coronary thrombi producing infarction. Bleeding was not influenced by the dose of streptokinase or the method of cardiac catheterization. Before treatment, prothrombin time and partial thromboplastin time were normal in both bleeders and nonbleeders. Fibrinogen levels measured by bioassay after streptokinase (mean +/- SEM) were 62 +/- 29 mg/dl in patients with major bleeding, 111 +/- 26 mg/dl in patients with minor bleeding, and 109 +/- 13 mg/dl in nonbleeders (p = NS). The regression slope b calculated from poststreptokinase fibrinogen time-concentration data in 71 patients was 4.7 mg/dl/hr. However, mean fibrinogen concentrations calculated at sequential 5 hr intervals revealed no net regeneration for the first 20 hr after thrombolysis. The apparent fibrinogen regeneration rate was less than normal (31 mg/kg/day) for more than 10 hr but subsequently increased to 94 +/- 10 mg/kg/day by the second day. The initial apparent latency of fibrinogen regeneration paralleled the sharp rise in fibrinogen degradation products, which began to decline after 20 hr of treatment but remained elevated well into the second day. Because of their anticoagulant effects, these products may interfere with the fibrinogen assay, causing spuriously low results. Thus, whether the early delay in fibrinogen regeneration is real or simply a reflection of the effects of fibrinogen degradation products on the bioassay, it signals the time for caution in initiating systemic heparin therapy.
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PMID:Hemorrhage and the products of fibrinogen digestion after intracoronary administration of streptokinase. 671 16

To elucidate the relationship between estrogen and thrombosis, we studied blood coagulation parameters in women whose ovaries were stimulated with human menopausal gonadotropins (hMG). Daily hMG administration over 1 to 2 weeks in seven anovulatory women increased plasma 17 beta-estradiol levels fivefold over the pretreatment value. Of the coagulation parameters, the fibrinogen level increased significantly from an initial value of 248 +/- 11.7 mg/dl (mean +/- SEM) to 353 +/- 32.2 mg/dl after hMG treatment (P less than 0.05), with a significant positive correlation between estrogen and fibrinogen levels (r = +0.762). In addition, a thrombokinetics study showed that the maximal rate of change in optical density of the prothrombin time and activated partial thromboplastin time was significantly increased, suggesting that the coagulation factors involved in extrinsic, intrinsic, and common pathways could be increased by estrogen. Antithrombin III levels decreased gradually during hMG administration. Thus, increased endogenous estrogen levels appear to induce the so-called "hypercoagulable state" through both an increase in coagulation factors in the coagulation cascade system and a decrease in antithrombin III, a potent natural inhibitor of activated coagulation factors. Patients on a regimen of hMG treatment for induction of ovulation serve as excellent models for the study of alteration of "natural" estrogen-mediated coagulation parameters.
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PMID:Response of blood coagulation parameters to elevated endogenous 17 beta-estradiol levels induced by human menopausal gonadotropins. 678 79

Immune complexes induced the synthesis of apoprotein III, the protein component of tissue thromboplastin (tissue factor), in human monocytes cultured in vitro. The response was maximal (11.1 +/- 1.7 fold increase (mean +/- SEM) when immune complexes were formed at antigen/antibody equivalence. Immune complexes formed with the antigen-binding fragments (F(ab')2) of immunoglobulins induced a 4.7 +/- 1.4 fold activity increase, suggesting that another signal mechanism in addition to the Fc-receptor may be involved.
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PMID:Thromboplastin (factor III) activity in human monocytes induced by immune complexes. 680 71

The thromboplastin synthesis of the human monocytoid cell line U-937 and its two subclones designated U-937-3 and U-937-4 has been studied. U-937-4 seems by several functional criteria to represent a more advanced stage of monocyte differentiation than the original U-937. U-937-3 appears to be arrested at an even more immature stage than the original population. The basal thromboplastin activity was higher in U-937-4 than in U-937-3 or U-937 cells (7.0 +/- 1.9 (SEM), 1.0 +/- 0.2 and 1.6 +/- 0.6 units/mg protein, respectively) although not as high as in human normal monocytes (14.1 +/- 2.4). The thromboplastic expression of the two clones was maximal when cells were in logarithmic growth. Both clones responded with a weak to moderate thromboplastin synthesis upon addition of stimulants like phytohaemagglutinin (PHA), immune complexes or endotoxin. Thromboplastin production was also potentiated in the presence of lymphocytes. The supporting effect of lymphocytes was strong in the case of U-937-3 as well as in U-937 cells, but less pronounced in U-937-4 cells as it also is in human monocytes. The thromboplastin response after PHA stimulation was more rapid in U-937-4 cells (maximal after 4-8 h) than in U-937 or U-937-3 cells (12-16 h). Human monocytes also responds quickly to PHA (maximally 4 h). Total phospholipid content and the relative distribution of individual phospholipids were essentially similar in U-937-3, U-937-4 and U-937. With regard to thromboplastin production, U-937-4 cells seem to be more monocyte-like than the more immature cells U-937-3 and U-937. It is concluded that thromboplastin seems to be a useful marker for monocyte differentiation.
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PMID:Thromboplastin as a marker for monocyte differentiation. 682 57

The effects of sequential prostacyclin infusions at 2, 4, and 8 ng/kg/min for 1 hr were determined in six patients with chronic renal failure. Diastolic blood pressure decreased in a dose-dependent fashion from 74 +/- 4 mm Hg (mean +/- SEM) to 70 +/- 4, 66 +/- 5, and 55 +/- 5 during the 2, 4, and 8 ng/kg/min infusions, respectively; systolic blood pressure was not affected by prostacyclin. The fall in diastolic blood pressure was associated with a progressive rise in heart rate from 77 +/- 3 to 91 +/- 4 bpm and lowering of body temperature from 36.7 +/- 0.1 to 36 +/- 0.2 degrees. The threshold concentration of adenosine diphosphate that evoked reversible and irreversible platelet aggregation increased progressively from 1.2 to 2.8 and from 2.8 to 6 microM, respectively, during the prostacyclin infusions. Prostacyclin infusions had no effect on prothrombin time, activated partial thromboplastin time, or platelet count, but template bleeding time increased (not statistically significantly) from 5.8 to 12.3 min. In three of six patients, the 8 ng/kg/min infusion was terminated prematurely due to nausea, vomiting, and/or hypotension. We conclude that platelet aggregability can be inhibited in patients with chronic uremia by infusing 4 ng/kg/min prostacyclin without causing untoward side effects. When infused at hemodynamically tolerable doses, prostacyclin might serve as an in vivo inhibitor of platelet aggregation during hemodialysis or cardiopulmonary bypass.
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PMID:Effects of prostacyclin infusion in uremic patients: hematologic and hemodynamic responses. 701 91

Prolonged extracorporeal circulation (ECC) using heparin as anticoagulant may be associated with pronounced thrombocytopenia and excessive bleeding. We, therefore, tested the hypothesis that reversible inhibition of platelet function, in lieu of heparinization, might preserve platelets and prevent coagulation in a perfusion circuit. When 500 ml of fresh heparinized (one U/ml) human blood was recirculated in a perfusion circuit constructed of standard silicone rubber components and a membrane oxygenator (0.95 M2), platelet counts declined to 9 +/- 2 (SEM) % of initial levels within 15 mins; plasma levels of the platelet specific protein LA-PF4 rose to 15 +/- 2 micrograms/ml within one hour indicating extensive release of platelet granule contents, and leukocyte counts declined to 91 +/- 4% within 15 mins. Prostacyclin (PGI2, greater than or equal to 25 eta M) or prostaglandin E1 (20 microM) and theophylline (12 mM) prevented platelet loss and release of granule contents. When heparin was reversed with protamine, however, immediate coagulation ensured. This occurred despite the absence of detectable activation of Hageman factor as evidenced by stability of plasma concentrations of prekallikrein in systems anticoagulated with heparin or citrate and despite our inability to detect thromboplastin-like properties in isolated leukocytes. Thus, coagulation in the presence of platelet inhibition suggests that alternative pathways, independent of platelet activation may exist. Platelet inhibition does preserve platelets preventing contact initiated release, but cannot serve by itself for anticoagulation.
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PMID:Prostacyclin in lieu of anticoagulation with heparin for extracorporeal circulation. 703

Chronic hypoxia produces pulmonary artery hypertension through vasoconstriction and structural remodeling of the pulmonary vascular bed. The present study was designed to test the effect of heparin administered via aerosol on the development of hypoxic pulmonary hypertension. Anesthetized, intubated, and mechanically ventilated guinea pigs received an aerosol of either 2 ml normal saline (hypoxic control, HC) or 4,500 units of heparin diluted in 2 ml normal saline via an ultrasonic nebulizer (hypoxic heparin, HH). After 24 h of recovery, the animals were placed in a hypoxic chamber (10% O2) for 10 days. Animals kept in room air served as normoxic controls (NC). Hypoxia increased mean pulmonary artery pressure from 11 +/- 1 (SEM) mm Hg in NC to 24 +/- 1 mm Hg in HC (p < 0.05). Pulmonary artery pressure was significantly lower in HH-treated animals (20 +/- 1 mm Hg, p < 0.05 versus HC) as was the total pulmonary vascular resistance (0.15 +/- 0.01 in HH versus 0.20 +/- 0.01 mm Hg/ml/min in HC, p < 0.05). There was no difference in cardiac output (146 +/- 12 in HH versus 126 +/- 7 ml/min in HC), hematocrit (57 +/- 2 in HH versus 56 +/- 2% in HC), partial thromboplastin time (30 +/- 2 in HH versus 32 +/- 3 s in HC), prothrombin time (46 +/- 1 in HH versus 48 +/- 4 s in HC) or room air arterial blood gas values after 10 days of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of aerosol heparin on the development of hypoxic pulmonary hypertension in the guinea pig. 831 7

Citrate and nadroparin calcium, a low molecular weight heparin (LMWH), were compared in a randomized cross-over trial in 21 chronic hemodialysis patients regarding anticoagulation, calcium and magnesium kinetics, biocompatibility, dialysis efficiency, and aluminum contamination. Citrate was infused into the arterial line at a minimum rate of 0.68 mmol/min, combined with a calcium and magnesium-free dialysate and intravenous supplementation of calcium and magnesium at rates of 0.22 and 0.10 mmol/min, respectively. Seven patients with a dialysis session of six hours, received 2/3 of the nadroparin dose predialysis, and 1/3 after 2.5 hours (divided dose (DD) group). A single predialysis bolus injection of nadroparin was administered to eight patients not on coumarins [single dose (SD) group] and to six patients on coumarins [single dose + coumarins (SD + C) group], all with a dialysis session of four hours. Nineteen patients received a nadroparin dose of 200 ICU/kg. Two patients with a single dose, one of them on coumarins, received a dose of 150 ICU/kg because of a hematocrit < 0.30. With citrate systemic whole blood activated clotting time (ACT) remained unchanged, indicating efficient regional anticoagulation. After two hours of dialysis with nadroparin, systemic ACT increments, that is, the increase compared to predialysis, of the DD, SD, and SD + C groups were 8.8 +/- 1.5, 18.7 +/- 4.7, and 33.3 +/- 6.1 seconds, respectively (mean +/- SEM). Postdialysis ACT increments in these groups were 1.5 +/- 3.4, 17.7 +/- 6.8, and 30.3 +/- 8.0 seconds. Two hour increments of systemic activated partial thromboplastin time (APTT) of the DD, SD, and SD + C groups during nadroparin were 5.0 +/- 1.2, 15.1 +/- 2.7, and 32.2 +/- 5.5 seconds, respectively, and the corresponding postdialysis APTT increments were 2.9 +/- 1.4, 7.8 +/- 2.4, and 15.8 +/- 2.6 seconds. Two-hour anti-Xa increments of the DD, SD, and SD + C groups amounted to 0.34 +/- 0.07, 0.67 +/- 0.07, and 0.80 +/- 0.08 IU/ml. The respective postdialysis anti-Xa increments were 0.21 +/- 0.06, 0.58 +/- 0.06, and 0.71 +/- 0.08 IU/ml (All ACT, APTT and anti-Xa increments were significant; P < 0.05), except for the ACT increments and the postdialysis APTT increment of the DD group). These increments, together with unchanged prothrombin fragments 1 and 2 (PTF1 + 2), indicate systemic anticoagulation with nadroparin. The increments of serum calcium and magnesium during citrate were comparable to the increments observed with a dialysate containing 1.5 mmol/liter calcium and 0.75 mmol/liter magnesium used in combination with nadroparin. Ionized calcium increments during citrate were significant after the end of dialysis, while the dialysate containing 1.5 mmol/liter calcium induced significant increments during and postdialysis. No differences were observed between citrate and nadroparin regarding biocompatibility), (expressed as dialysis-induced leukopenia and thrombocytopenia), and dialysis efficiency [measured as dialyzer urea and creatinine clearance, normalized weekly whole body urea clearance (Kt/Vurea) and time averaged urea concentration (TACurea)]. The citrate solution, if sterilized in glass bottles, contained 2 to 3 micrograms aluminum per mmol citrate, the nadroparin solution 0.009 microgram per 1,000 ICU. Aluminum contamination of the citrate solution was prevented by sterilizing the solution in polypropylene bottles. In conclusion, citrate anticoagulation is regional and is indicated for hemodialysis patients with an active or recently active bleeding focus. However, the citrate solution should be sterilized in polypropylene containers to prevent aluminum contamination. LMWHs induce systemic anticoagulation during hemodialysis, and this effect is enhanced by concomitant coumarin use and mitigated by a divided LMWH dose regimen. For hemodialysis patients not at risk of bleeding, LMWHs provide a simple anticoagulation regimen.
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PMID:Citrate compared to low molecular weight heparin anticoagulation in chronic hemodialysis patients. 864 24

Increases in thrombin activity occur in patients treated with streptokinase, but conjunctive therapy with intravenous heparin does not appear to improve either the rate of early infarct artery patency or survival in patients with acute myocardial infarction. In a recent study we found that concentrations of fibrinopeptide A, a marker of thrombin-mediated fibrin formation, were lower in the first 3 h in patients treated with intravenous heparin (5000 U bolus followed by a fixed-dose 1000 U/h infusion, n = 14) compared with subcutaneous (12,500 U every 12 h, started 4 h after streptokinse, n = 14) administration, but were increased in both groups of patients, consistent with persistent thrombin activity. To determine whether the differential effects of the intensity of heparinization on thrombin formation were reflected in differences in fibrin degradation, we measured cross-linked fibrin degradation products (XL-FDP) before and 1, 2, 3, 8, 12, and 24 h after streptokinase in the same cohort of patients, with a new ELISA with a D-dimer-specific capture antibody (MAb 3B6) and a fibrin-specific tag antibody (MAb 1D2, Agen, Brisbane, Australia). The incidence of early coronary recanalization assessed by creatine-kinase MM isoforms (increase in activity > or = 0.18%/min), was similar in both groups (79 vs 86%). Concentrations of XL-FDP were similar in patients with and without recanalization, but were lower in patients treated with intravenous compared with subcutaneous heparin at 8 h, but the results did not reach statistical significance (627 +/- 151 ng/ml versus 1007 +/- 157 ng/ ml, p = 0.06), and were significantly lower at 12 h (327 +/- 72 versus 781 +/- 162 ng/ml, p = 0.03 at 12 h) (mean +/- SEM). Concentrations of cross-linked fibrin degradation products were also lower in patients in whom the activated partial thromboplastin time was greater than two times the control, compared with those with inadequate anticoagulation (498 +/- 105 versus 1084 +/- 179 ng/ml; p = 0.02) (mean +/- SEM). Thus, more effective inhibition of thrombin with conjunctive intravenous heparin therapy results in less cross-linked fibrin turnover in the first 12 h after thrombolysis with streptokinase. This probably reflects decreased fibrin formation with therapeutic anticoagulation.
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PMID:Conjunctive administration of intravenous heparin attenuates cross-linked fibrin degradation in patients treated with streptokinase. 888 67


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