thromboplastin and Ischemia

The exposure of tissue factor (TF) to blood flow is the initial step in the coagulation process and plays an important role in thrombogenesis. We investigated the role of genetic polymorphisms and haplotypes of the TF gene in the risk of ischemic vascular disease.. Four hundred and twenty-two Italian patients with juvenile myocardial infarction (MI) and 434 controls, 808 US cases with MI and 1005 controls, 267 Italian cases with juvenile ischemic stroke and 209 controls and 148 German cases with juvenile ischemic stroke and 191 controls were studied. rs1361600, rs3917629 (rs3354 in the US population), rs1324214 and rs3917639 Tag single nucleotide polymorphisms were genotyped. Additionally, a meta-analysis of all previous studies on TF loci and the risk of ischemic coronary disease (ICD) was performed.. After multivariable analysis none of the SNPs, major SNP haplotypes or haplotype-pairs showed any consistent association with MI. Pooled meta-analysis of six studies also suggested that TF polymorphisms are not associated with CHD. A significant, independent association between SNP rs1324214 (C/T) and juvenile stroke was found in Italian and German populations (OR for TT homozygotes = 0.47, 95% CI 0.24-0.92, in combined analysis). Pooled analysis also showed a significant association for haplotype H3 (OR = 0.76, 95% CI 0.57-1.00) and haplotype-pair H3-H3 (OR = 0.43, 95% CI 0.20-0.92).. TF genetic variations were associated with the risk of ischemic stroke at young age, but did not affect ischemic coronary disease.

Topics: Adult; Case-Control Studies; Female; Genetic Variation; Haplotypes; Homozygote; Humans; Interleukin-1beta; Ischemia; Italy; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Risk; Stroke; Thromboplastin

Increased numbers of CD146-defined circulating endothelial cells (CECs), as are present in the peripheral blood of patients suffering acute coronary syndromes, imply injury to the endothelium. Endothelial damage can also be assessed by the measurement of plasma levels of von Willebrand factor (vWf). Increased levels of procoagulant plasma tissue factor (TF), arising from monocytes/macrophages and endothelial cells, is present in atherosclerosis. We hypothesised increased CECs in patients with ischaemic rest pain (IRP) of the lower limb due to peripheral atherosclerosis and comparable to that seen in patients with acute myocardial infarction (AMI), when compared to patients with intermittent claudication (IC) or healthy controls that would correlate with vWf and TF.. We recruited 20 patients in each of four groups: (i) IRP of the lower limb; (ii) AMI; (iii) 'stable' IC; and (iv) healthy controls. CD146-expressing CECs were measured by immumomagnetic separation and counting under a fluorescence microscope; plasma vWf and TF by ELISA.. In IRP, median (IQR) CEC levels were 3.5 (2.0-5.8) cells/ml, in IC were 1.1 (0.6-2.9) cells/ml, and in healthy controls were 1.0 (0.5-1.7) cells/ml (p<0.001). The levels of vWf (p=0.034) and TF (p=0.007) were also significantly different between the groups, with the highest levels in patients with IRP. Levels of CECs correlated with vWf (rs=0.4, p=0.002) and TF ( rs=0.296, p=0.021 ). In AMI, CEC levels were higher than those in IRP at 4.9 (3.6-8.4) cells/ml (p=0.0385).. This study demonstrates evidence of direct endothelial cell injury (i.e. raised CECs) in patients with IRP that correlated with vWf and TF, but that this is less severe than in AMI.

Topics: Aged; Analysis of Variance; Antigens, CD; Arteriosclerosis; CD146 Antigen; Endothelial Cells; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intermittent Claudication; Ischemia; Leg; Male; Membrane Glycoproteins; Middle Aged; Myocardial Infarction; Neural Cell Adhesion Molecules; Pain; Thromboplastin; von Willebrand Factor

Ischemic acute kidney injury is common, deadly, and accelerates the progression of chronic kidney disease, yet has no specific therapy. After ischemia, reperfusion is patchy with early and persistent impairment in regional renal blood flow and cellular injury. We tested the hypothesis that intrarenal coagulation results in sustained renal ischemia following reperfusion, using a well-characterized model. Markedly decreased, but heterogeneous, microvascular plasma flow with microthrombi was found postischemia by intravital microscopy. Widespread tissue factor expression and fibrin deposition were also apparent. Clotting was accompanied by complement activation and inflammation. Treatment with exosomes derived from renal tubular cells or with the fibrinolytic urokinase, given 24 h postischemia when renal failure was established, significantly improved microvascular flow, coagulation, serum creatinine, and histological evidence of injury. These data support the hypothesis that intrarenal clotting occurs early and the resultant sustained ischemia is a critical determinant of renal failure following ischemia; they demonstrate that the coagulation abnormalities are amenable to therapy and that therapy results in improvement in both function and postischemic inflammation.

Topics: Acute Kidney Injury; Animals; Creatinine; Disease Models, Animal; Fibrin; Inflammation; Ischemia; Kidney; Reperfusion; Reperfusion Injury; Thromboplastin; Urokinase-Type Plasminogen Activator

Despite increasing evidence that monocytes may acquire endothelial features, it remains unclear how monocytes participate in angiogenesis after ischaemic damage. We investigated whether ischaemic cells can release microvesicles (MVs) and promote neovascularization in a model of peripheral artery disease (PAD).. To model PAD, we used an in vivo experimental model of hind-limb ischaemia (HLI) in mice. MVs were isolated from the ischaemic muscle and from peripheral blood at different times after unilateral femoral artery ligation. MVs were phenotypically characterized to identify cell origin. HLI in mice induced the release of MVs with a much higher content of tissue factor (TF) than non-HLI control mice both in the MVs isolated from the affected limb muscle area and from blood. MVs were mainly released from endothelial cells (ECs) and induced Mo differentiation to endothelial cell-like (ECL) cells. Differentiation to ECL cells encompassed highly strict hierarchical transcription factor activation, initiated by ETS1 activation. MVs secreted by microvascular ECs over-expressing TF (upTF-EMVs), were injected in the ischaemic hind-limb in parallel with control EMVs (from random siRNA-treated cells) or EMVs released by silenced TF ECs. In animals treated with upTF-EMVs in the ischaemic zone, there was a highly significant increase in functional new vessels formation (seen by magnetic resonance angiography), a concomitant increase in the pool of circulating Ly6Clow Mo expressing vascular EC markers, and a significantly higher number of Mo/macrophages surrounding and integrating the newly formed collaterals.. Ischaemia-activated ECs release EMVs rich in TF that induce monocyte differentiation into ECL cells and the formation of new vessels in the ischaemic zone. TF by this mechanism of formation of new blood microvessels can contribute to ischaemic tissue repair.

Topics: Animals; Cell-Derived Microparticles; Endothelial Cells; Ischemia; Mice; Monocytes; Thromboplastin

For the purposes of the present study, the protective effect of prostaglandin E1 (PGE1) on lung injury following renal ischemia-reperfusion (RIR) was investigated. Adult male rats were divided into four groups, namely, (I) control rats given physiological saline; (II) rats given PGE1 (20 μg/kg, intravenously); (III) rats subjected to RIR; and (IV) rats subjected to RIR given PGE1 30 min prior to ischemia and just before reperfusion. The right nephrectomy was performed in the RIR model. The left renal pedicle was occluded for 60 min to induce ischemia and then the left kidney was subjected to reperfusion for 60 min. The lungs of rats were used for microscopic and biochemical analyses. Although rats subjected to RIR did not exhibit heavy degenerative alterations in the lung structure, they possessed pulmonary interstitial edema. Lung glutathione levels and catalase, superoxide dismutase, glutathione peroxidase, and tissue factor (TF) activities were decreased in rats subjected to RIR, while lung lipid peroxidation, myeloperoxidase (MPO), xanthine oxidase and serum lactate dehydrogenase (LDH) activities, and blood urea and serum creatinine levels were increased in these rats when compared with the control group. PGE1 treatments resulted in the regression of oxidative stress via induction of antioxidant system, the decreased MPO and LDH activities, the reduced urea and creatinine levels, and the induced TF activity in rats subjected to RIR, while edema still remained permanent. We conclude that PGE1 may be useful in preventing lung injury with the exception of edema that occurred as a result of RIR in rats.

Topics: Acute Lung Injury; Alprostadil; Animals; Biomarkers; Glutathione; Immunohistochemistry; Infusions, Intravenous; Ischemia; Kidney; Lipid Peroxidation; Lung; Male; Nephrectomy; Oxidative Stress; Oxidoreductases; Protective Agents; Pulmonary Edema; Rats, Sprague-Dawley; Reperfusion Injury; Thromboplastin

Therapeutic angiogenesis is a promising strategy for treating ischemia. Our previous work showed that endogenous endothelial tissue factor (TF) expression induces intracrine signaling and switches-on angiogenesis in microvascular endothelial cells (mECs). We have hypothesized that activated mECs could exert a further paracrine regulation through the release of TF-rich microvascular endothelial microparticles (mEMPs) and induce neovascularization of ischemic tissues.. Here, we describe for the first time that activated mECs are able to induce reparative neovascularization in ischemic zones by releasing TF-rich microparticles. We show in vitro and in vivo that mEMPs released by both wild-type and TF-upregulated-mECs induce angiogenesis and collateral vessel formation, whereas TF-poor mEMPs derived from TF-silenced mECs are not able to trigger angiogenesis. Isolated TF-bearing mEMPs delivered to nonperfused adductor muscles in a murine hindlimb ischemia model enhance collateral flow and capillary formation evidenced by MRI. TF-bearing mEMPs increase angiogenesis operating via paracrine regulation of neighboring endothelial cells, signaling through the β1-integrin pathway Rac1-ERK1/2-ETS1 and triggering CCL2 (chemokine [C-C motif] ligand 2) production to form new and competent mature neovessels.. These findings demonstrate that TF-rich mEMPs released by microvascular endothelial cells can overcome the consequences of arterial occlusion and tissue ischemia by promoting postischemic neovascularization and tissue reperfusion.

Topics: Animals; Cell Line; Cell-Derived Microparticles; Collateral Circulation; Disease Models, Animal; Endothelial Cells; Hindlimb; Humans; Integrin beta1; Ischemia; Magnetic Resonance Angiography; Male; Mice, Nude; Microvessels; Muscle, Skeletal; Neovascularization, Physiologic; Paracrine Communication; RNA Interference; Signal Transduction; Thromboplastin; Time Factors; Tissue Culture Techniques; Transfection

Ischemia is the defined pathway leading to steroid-associated osteonecrosis (ON). Early detection of ischemic condition may help predict later ON occurrence. Bone marrow perfusion function evaluation by perfusion magnetic resonance imaging (MRI) may be a unique modality for this application. Twenty-five adult male New Zealand white rabbits were used in this study. Lipopolysaccharide (LPS) and methylprednisolone (MPS) were administrated for ON induction based on a published protocol. T1-weighted and fat suppression T2-weighted MR imaging (conventional MRI) were performed for ON lesion detection based on the abnormal signal in the proximal femora at week 0 as the baseline (before LPS injection), and week 1 and week 2 after MPS injection. At the same time, the blood perfusion function in the proximal femora was measured by perfusion MRI. Maximum enhancement (ME)--an index of MRI perfusion function was analyzed. After MRI scanning, the proximal femora were prepared histopathologically for ON lesion analysis. The rabbit with bilateral histopathological ON lesions was defined as an ON+ rabbit and included in the ON+ group evaluated at week 1 and week 2, respectively, and the rabbit without ON lesions in bilateral femora was classified into the ON- group. For the underlying mechanism of perfusion change, the extravascular marrow fat cells were measured and the intravascular endothelium inflammation injury indicator of tissue factor (TF) expression and thrombus formation were detected. In ON+ group, ME in perfusion MRI showed a significant decrease at week 1 and week 2 as compared with the baseline (p < 0.01). There was a more than 50% decrease in ME at week 1 in ON+ group; whereas there were no detectable ON lesions by conventional MRI at week 1, though 93% (14/15) rabbits could be detected at week 2 in ON+ group. In ON- group, ME showed a slight decrease at week 1 (less than 30%), and nearly recovered to normal at week 2 as compared with the baseline. Histological results showed a much larger average marrow fat area and more severe marrow blood sinusoids compression from surrounding crowded fat cells, and stronger positive TF expression in marrow endothelium and more thrombus formation in ON+ rabbits than ON- rabbits. This study demonstrated that functional perfusion MRI could predict development of steroid-associated ON. Our experimental data suggested that perfusion MRI might be a sensitive noninvasive modality for monitoring steroid-associated ON in patients

Topics: Adipose Tissue; Animals; Bone Marrow; Disease Models, Animal; Endothelium, Vascular; Glucocorticoids; Ischemia; Lipopolysaccharides; Magnetic Resonance Imaging; Male; Methylprednisolone; Osteonecrosis; Predictive Value of Tests; Rabbits; Sensitivity and Specificity; Thromboplastin

Thrombus formation plays a critical role in pathogenesis of cardiovascular complications in atherosclerotic peripheral arterial occlusive disease (PAOD). Tissue factor (TF) initiates the clotting cascade and is considered an important regulator of hemostasis and thrombosis. TF activity is regulated by TF pathway inhibitor (TFPI). The aim of our study was to evaluate plasma levels of the TF, TFPI and their relation to coagulation system and various other risk factors of atherosclerosis in patients with chronic limbs ischemia.. Plasma TF, total TFPI, truncated TFPI, full-length TFPI were assessed by ELISA using commercially available kits (IMUBIND Tissue Factor; Total TFPI; Truncated TFPI ELISA Kit; American Diagnostica Inc. Stamford) in 62 claudicant patients with PAOD and 20 healthy controls.. We observed statistically higher levels of TF (94+/-52 pg/mL), total TFPI (43+/-8 ng/mL), and truncated TFPI (22+/-7 ng/mL) in patients with PAOD compared to healthy individuals (TF: 66+/-15 pg/mL; total TFPI: 36+/-4 ng/mL; truncated TFPI: 14+/-5 ng/mL). Full-length TFPI (20+/-4 ng/mL) is lower in patients with PAOD than in controls (23+/-5 ng/mL). The study indicated a positive correlation between TF and truncated TFPI (r=0.34), total TFPI and full TFPI (r=0.5), total TFPI and truncated TFPI (r=0.83) in patients with PAOD, and negative correlation between full TFPI and truncated TFPI (r=-0.65) in the control.. Elevated levels of TF, disorders of balance between full-length TFPI and truncated TFPI as well as significantly increased truncated TFPI level in patients with PAOD can be independent risk factors of atherosclerotic complications.

Topics: Arterial Occlusive Diseases; Atherosclerosis; Biomarkers; Blood Coagulation; Case-Control Studies; Female; Humans; Ischemia; Lipoproteins; Lower Extremity; Male; Middle Aged; Peripheral Vascular Diseases; Pilot Projects; Risk Assessment; Risk Factors; Thromboplastin; Up-Regulation

Topics: Apoptosis; Blood Coagulation Disorders; Blood Platelets; Cell Membrane; Endothelium, Vascular; Hemostasis; Humans; Inflammation; Ischemia; Microspheres; Neovascularization, Physiologic; Platelet Activation; Thrombin; Thromboplastin

Previous studies have emphasized the role of ischemia in inducing vascular thrombosis.. Using a skin flap model of acute ischemia in the rat, we studied the effect of active-site inactivated factor VIIa (FVIIai), an inhibitor of tissue factor (TF), on tissue survival during acute ischemia.. Ribonuclease protection analysis revealed an increase in TF in ischemic parts of the flap, and in situ hybridization localized this increase mainly to perivascular cells. A decrease in vascular thrombosis, as determined by fibrin immunostaining, was observed in FVIIai-treated animals. Intravenous administration of FVIIai had a positive impact on survival of the flap. Laser Doppler flowmetry revealed an increase in blood flow in the FVIIai-treated group. In treated animals, prothrombin time (PT) was increased (P < 0.01), whereas partial thromboplastin time (APTT) was unaltered; no significant impairment in systemic hemostasis (peri- and postoperative bleeding) was observed.. These findings demonstrate that TF expression is increased in perivascular cells in ischemic skin flaps and that FVIIai, by inhibiting TF, increases flap survival.

Topics: Acute Disease; Animals; Blood Coagulation; Factor VIIa; Female; Ischemia; Necrosis; Rats; Rats, Wistar; Regional Blood Flow; Skin; Surgical Flaps; Thromboplastin; Thrombosis; Time Factors; Tissue Survival

Localized large vessel thrombosis in acute leukaemia is rare, haemorrhagic complications being more common.. We present a patient with acute promyelocytic leukaemia (APL) presenting with an acutely ischaemic lower limb. Large vessel thrombosis is a rare presentation of APL. We reviewed the literature on the coagulopathy of APL and discuss the pathology and current treatment options.. Disordered haemostasis is typical of acute promyelocytic leukaemia (FAB M3) and relates to the intrinsic properties of the blast cells as well as thrombocytopenia from bone marrow involvement. Expression of procoagulants, stimulation of cytokines and alterations in endothelial cell anticoagulant properties initiate a disseminated intravascular coagulation (DIC) resulting in the typical clinical and laboratory findings in APL. The promyelocytes are characterized by the balanced reciprocal translocation between chromosomes 15 and 17. All-trans-retinoic acid (ATRA) induces differentiation in these cells, revolutionizing the treatment of APL.. Unexpected limb ischaemia in a young, apparently healthy patient might be the presenting symptom of an underlying haematological disorder such as APL. A thorough haematological investigation should be performed prior to contemplating surgery. New treatment strategies based on knowledge of the molecular biology of APL has improved the prognosis of patients suffering from APL.

Topics: Amputation, Surgical; Antineoplastic Combined Chemotherapy Protocols; Arterial Occlusive Diseases; Cysteine Endopeptidases; Cytarabine; Daunorubicin; Female; Gangrene; Humans; Intermittent Claudication; Ischemia; Leg; Leukemia, Promyelocytic, Acute; Middle Aged; Neoplasm Proteins; Neoplastic Stem Cells; Popliteal Artery; Remission Induction; Smoking; Thioguanine; Thrombophilia; Thromboplastin; Thrombosis; Toes; Tretinoin

Topics: Animals; Arteriosclerosis; DNA-Binding Proteins; Early Growth Response Protein 1; Endothelium, Vascular; Humans; Immediate-Early Proteins; Ischemia; Mice; Mice, Knockout; Platelet-Derived Growth Factor; Thromboplastin; Transcription Factors; Zinc Fingers

Topics: Animals; Hepatic Artery; Humans; Ischemia; Liver; Liver Circulation; Male; Portal Vein; Rats; Rats, Inbred Lew; Recombinant Proteins; Reperfusion Injury; Survival Rate; Thromboplastin

Tissue factor (TF) is a membranous protein normally present on the surface of the fibroblasts and smooth muscle cells of vessels. TF is an initiation factor for blood coagulation, and its expression is induced on macrophages and endothelial cells during the inflammatory or immune response. We studied the significance of TF expression in warm ischemic-reperfusion injury of the liver using a rat model.. Following laparotomy of Lewis rats, the branches of the hepatic artery and portal vein leading to the median, left, and caudate lobes of the liver were clamped for 2 hr. The liver was reperfused after 120 min of ischemia. Rats were killed at 0, 1, 3, 5, 8, and 12 hr after reperfusion, and liver tissues were harvested. TF activity was measured by the chromophilic substrate S-2222. TF expression was studied by immunohistochemical staining with the monoclonal antibody HTF-K108.. TF activity in the blood showed a peak at 3 hr after reperfusion (8.9+/-0.5 U/L), then decreased and returned to the normal level by 12 hr (0.9+/-0.3 U/L). TF activity in ischemic liver tissue increased gradually over 12 hr after reperfusion (1223+/-275 U/g dry weight before ischemia and 2545+/-284 U/g weight at 12 hr after reperfusion). Histologically spotty necroses were observed in the liver tissue 5 hr after reperfusion. The necrotic area extended and encompassed almost all of the ischemic liver by 12 hr after reperfusion. Histochemically, TF staining was negative on the hepatocytes and slightly positive on sinusoid cells of the normal liver. On the other hand, TF was strongly stained, especially on the hypertrophic monocytic cells accumulating at the site of the necrosis, but staining was not evident on the necrotic hepatocytes. A slight degree of TF staining was observed on the alveolar epithelium of the lung, irrespective of liver ischemia and reperfusion.. These results demonstrate that TF plays an important role in the development of the hepatic ischemic-reperfusion injury, and the subsequent microcirculatory incompetence might cause the formation of microthrombus and the development of necrosis.

Topics: Alanine Transaminase; Animals; Disease Models, Animal; Hyaluronic Acid; Immunohistochemistry; Ischemia; Liver; Lung; Male; Rats; Rats, Inbred Lew; Reperfusion Injury; Temperature; Thromboplastin; Tumor Necrosis Factor-alpha

Topics: Alanine Transaminase; Animals; Antithrombin III; Hyaluronic Acid; Ischemia; Liver; Male; Peptide Hydrolases; Prothrombin Time; Rats; Rats, Inbred Lew; Reperfusion; Reperfusion Injury; Thromboplastin; Tumor Necrosis Factor-alpha

Topics: Animals; Gene Expression; Ischemia; Kidney; Male; Rats; Rats, Inbred Lew; Renal Artery; Renal Veins; Reperfusion Injury; Thromboplastin

Topics: Animals; Gene Expression; Immunohistochemistry; Ischemia; Liver; Male; Rats; Rats, Inbred Lew; Reperfusion Injury; Thromboplastin; Time Factors

Topics: Animals; Immunohistochemistry; Ischemia; Kidney; Rats; Reperfusion Injury; Thromboplastin

Alveolar and interstitial fibrin deposition is a prominent pathologic feature in many acute lung injury syndromes. Previous studies have suggested that ischemic lung preservation has a stimulatory effect on donor alveolar macrophages (Mphis) during transplantation. An animal model of lung preservation was developed to examine the hypothesis that ischemia enhances Mphi procoagulant activity (PCA) as a potential mechanism contributing to lung reperfusion injury. Histologic examination of ischemic lungs reperfused ex vivo revealed evidence of alveolar fibrin deposition. Mphis lavaged from lungs stored for at least 8 h at 21 degrees C exhibited increased PCA. The use of factor-deficient human plasma characterized this Mphi procoagulant as tissue factor (TF). Since increased PCA correlated with decreased airspace pO2 at the end of preservation, the effect of various O2 concentrations on PCA induction in vivo and in vitro was examined. Lung inflation during ischemia with decreasing O2 concentrations confirmed that hypoxia was associated with a rise in Mphi PCA in situ. However, in vitro exposure of Mphis to hypoxia did not increase Mphi PCA, suggesting that hypoxia alone was not responsible for induction of this procoagulant effect. Northern blot analysis demonstrated an increase in TF mRNA levels from in situ but not in vitro Mphis, thereby confirming transcriptional TF induction in this group. In addition, enhanced PCA was observed when Mphis were suspended in the bronchoalveolar lavage supernatant from the ischemic lungs stored at 21 degrees C. This suggests that in situ lung ischemia and hypoxia may produce soluble factors that either directly or indirectly stimulate Mphi TF expression. These factors may contribute to Mphi-mediated ischemic lung injury.

Topics: Animals; Blotting, Northern; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Fibrin; Hypoxia; Ischemia; Macrophages, Alveolar; Male; Microscopy, Electron, Scanning; Pulmonary Alveoli; Rats; Rats, Wistar; Reperfusion Injury; RNA, Messenger; Thromboplastin; Tubulin

Primary antiphospholipid syndrome (PAPS) is an autoimmune disorder manifested by recurrent thrombosis in the venous and arterial system. We report a group of seven patients with lower limb ischaemia associated with PAPS. Four were male patients and three were females, with a mean age of 37 years. All had a previous deep vein thrombosis and the majority, five out of seven, had a prior cerebrovascular accident (CVA). Prolonged activated thromboplastin time was demonstrated in all our patients and PAPS was established by positive thromboplastin titration index, circulating anticoagulant index and increased anticardiolipin levels. Symptoms included claudication in three, rest pain in four and gangrene in five patients. Angiography demonstrated thrombosis of various segments of the arterial tree including: aorta, iliac, femoral and popliteal arteries. Two patients were treated conservatively and one by percutaneous transluminal angioplasty (PTA) of the distal aorta. A total of eleven vascular surgical procedures were performed in four patients resulting in early postoperative thrombosis (2h-30 days) in 10 cases. Only one graft remained patent, when full heparinisation (1000 units/h) was used perioperatively. We conclude that PAPS patients are at high risk for graft thrombosis and should only be operated upon on full anticoagulation, starting at operation and proceeding indefinitely.

Topics: Adolescent; Adult; Aged; Antiphospholipid Syndrome; Female; Graft Occlusion, Vascular; Humans; Ischemia; Leg; Male; Middle Aged; Partial Thromboplastin Time; Postoperative Complications; Thrombectomy; Thromboembolism; Thromboplastin; Ultrasonography; Whole Blood Coagulation Time

It was shown in experiments on white rats that combined administration of nucleotide antiaggregants NAD+ and AMP, and NAD+ decomposition inhibitor--nicotinamide, decreased the increment of procoagulant (thromboplastic) activity of membrane particles in the ischemized kidneys and reduced thromboplastic activity of membrane particles in intact kidneys. When nucleotide antiaggregants were added to rabbit citrate plasma, the inhibition by membrane activation of recalcified plasma coagulation was more pronounced with the use of tissue thromboplastin of the kidneys and brain--proteophospholipid liposomes, than with the use of phospholipid liposomes obtained from thromboplastin. The data presented have evidenced an indirect anticoagulant effect of nucleotide aggregants at the level of tissue coagulation factors, and their direct anticoagulant action at the level of membrane activation of plasma factors.

Topics: Adenosine Monophosphate; Animals; Blood Coagulation; Disease Models, Animal; Ischemia; Kidney; Male; NAD; Platelet Aggregation Inhibitors; Rabbits; Rats; Thromboplastin

Increasing evidence has demonstrated the importance of monocyte procoagulant activity (PCA) in the pathogenesis of coagulopathies in a variety of diseases. Because endotoxin precipitated coagulopathies are common sequelae to intestinal ischemia/endotoxemia in the equine species, we investigated the ability of equine peripheral blood monocytes to express PCA. Monocytes isolated from five healthy adult horses were incubated in vitro with Escherichia coli endotoxin (10 micrograms), and the PCA was measured by the ability of cellular lysates to accelerate the clotting times of equine plasma in a modified one-stage recalcification assay. Equine monocyte PCA was identified as thromboplastin based on lack of clot formation in factor VII-deficient plasma. The induction of PCA occurred as early as 2 hr after endotoxin exposure, peaked at 6 hr (396% increase), and then gradually declined. The amount of PCA was proportional to the dose of endotoxin (0.01 to 100 micrograms) and the number of monocytes. Neither platelets nor neutrophils produced PCA, either in the absence or presence of endotoxin (1 microgram). Lymphocytes at a concentration of 4 x 10(6)/ml RPMI did produce a significant amount of PCA, compared to the time-matched controls. Co-incubation of neutrophils or lymphocytes with monocytes did not alter the PCA, whereas coincubation of platelets and monocytes significantly enhanced the expression of PCA. This effect was further augmented by the addition of endotoxin (1 microgram).

Topics: Animals; Blood Cells; Blood Coagulation Factors; Endotoxins; Horses; In Vitro Techniques; Intestines; Ischemia; Leukocyte Count; Monocytes; Thromboplastin

Yucatan miniature swine were the experimental model used to examine the effect of ischemia-injury on post-ischemic monocyte (MO) and immune function. Monocyte plasminogen activator (PA) was depressed while MO tissue factor activity was increased. The ability of porcine monocytes to generate a primary in vitro antibody forming cell (AFC) response to sheep red blood cells (SRBC) also was depressed by ischemic injury. The mechanism by which ischemic injury modulated immunosuppression appeared to be through generation of immunosuppressive serum substances.

Topics: Animals; Antibody Formation; Disease Models, Animal; Extremities; Female; Immune Tolerance; Immunity, Cellular; Ischemia; Lymphocytes; Monocytes; Plasminogen Activators; Swine; Swine, Miniature; Thromboplastin; Wounds and Injuries

Topics: Animals; Blood Coagulation; Cat Diseases; Cats; Disseminated Intravascular Coagulation; Diuresis; Dog Diseases; Dogs; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Heparin; Ischemia; Kidney; Platelet Aggregation; Shock; Thromboplastin; Urine

Topics: Animals; Aorta, Thoracic; Autoradiography; Blood Coagulation; Blood Platelet Disorders; Cell Nucleus; Cyanosis; DNA; DNA Repair; Endothelium; Endotoxins; Factor XII; Ischemia; Isotope Labeling; Kidney; Male; Polymers; Rats; Shwartzman Phenomenon; Thromboplastin

Topics: Acute Disease; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Deafness; Dextrans; Ear, Inner; Evaluation Studies as Topic; Female; Hearing Disorders; Humans; Ischemia; Labyrinth Diseases; Male; Nicotinic Acids; Prothrombin Time; Theophylline; Thrombelastography; Thromboplastin; Time Factors

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Blood Coagulation Disorders; Endotoxins; Histamine Release; Humans; Hypotension; Hypoxia; Intestinal Absorption; Ischemia; Mononuclear Phagocyte System; Pulmonary Atelectasis; Shock; Shock, Septic; Thromboplastin

Topics: Acute Kidney Injury; Anemia, Hemolytic; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Coronary Disease; Female; Heart Arrest; Hemorrhagic Disorders; Humans; Hyaline Membrane Disease; Infant, Newborn; Ischemia; Kidney Transplantation; Male; Obstetric Labor Complications; Pregnancy; Shock, Septic; Shwartzman Phenomenon; Thrombocytopenia; Thromboembolism; Thromboplastin; Toxemia; Wounds and Injuries

Topics: Angiography; Blood Platelets; Blood Vessels; Dextrans; Humans; Inflammation; Ischemia; Platelet Adhesiveness; Thrombin; Thromboplastin; Thrombosis; Veins

Topics: Animals; Blood Coagulation; Dogs; Fibrinogen; Hematocrit; Ischemia; Plasminogen; Thromboplastin

Topics: Blood Coagulation; Fibrinolysis; Humans; Ischemia; Niacin; Nicotinic Acids; Thromboplastin