thromboplastin and Arterial-Occlusive-Diseases

Thrombosis, or complications from thrombosis, currently occupies the top three positions in the cardiovascular causes of morbidity and mortality in the developed world. There are a limited number of safe and effective drugs to prevent and treat thrombosis. Animal models of thrombosis are necessary to better understand the complex components and interactions involved in the formation of a clot. Tissue factor (TF) is required for the initiation of blood coagulation and likely plays a key role in both arterial and venous thrombosis. Understanding the role of TF in thrombosis may permit the development of new antithrombotic drugs. This review will focus on the role of TF in in vivo models of thrombosis.

Topics: Animals; Arterial Occlusive Diseases; Blood Coagulation; Disease Models, Animal; Disseminated Intravascular Coagulation; Fibrinolytic Agents; Humans; Microcirculation; Thromboplastin; Thrombosis; Venous Thrombosis

When the continuity of the vascular endothelium is disrupted, platelets and fibrin seal off the defect. Haemostatic processes are classified as primary (mainly involving platelets) and secondary (mainly related to fibrin formation or blood coagulation). When the blood clot is no longer required for haemostasis, the fibrinolytic system will dissolve it. The pivotal ligand for initial platelet recruitment to injured vessel wall components is von Willebrand factor (vWF), a multimeric protein present in the subendothelium and in plasma, where it is conformationally activated by shear forces. Adhering activated platelets recruit additional platelets, which are in turn activated and form a platelet aggregate. Coagulation is initiated by a reaction, activating factors IX and X. Once critical amounts of factor Xa are generated, thrombin generation is initiated and soluble fibrinogen is converted into insoluble fibrin. Excessive thrombin generation is prevented via inhibition by antithrombin and also via downregulation of its further generation by activation of the protein C pathway. Activation of the fibrinolytic system results from conversion of the proenzyme plasminogen into the active serine proteinase plasmin by tissue-type or urokinase-type plasminogen activators. Plasmin digests the fibrin component of a blood clot. Inhibition of the fibrinolytic system occurs at the level of the plasminogen activator (by plasminogen activator inhibitors) or at the level of plasmin (by alpha2-antiplasmin). Together, these physiological processes act to maintain normal functioning blood vessels and a non-thrombotic state.

Topics: Animals; Arterial Occlusive Diseases; Blood Coagulation; Blood Platelets; Endothelium, Vascular; Fibrinolysis; Hemostasis; Humans; Plasminogen; Plasminogen Activators; Platelet Aggregation; Platelet Membrane Glycoproteins; Receptors, Collagen; Thromboplastin

Topics: Arterial Occlusive Diseases; Blood Coagulation; Factor VIIa; Humans; Thromboplastin

Among 100 consecutive patients receiving heparin in therapeutic dosage, major bleeding occurred in 21, and minor bleeding in 16. Two patients died from bleeding, and two had recurrent pulmonary embolism. Major bleeding occurred in 21% when therapy was regulated with whole-blood clotting time and in 20% when heparin was given without clotting tests. In a subsequent prospective trial patients received heparin by intermittent intravenous injection with or without laboratory control according to the partial thromboplastin time or continuously by intravenous infusion. Recurrent thromboembolism occurred once in each group. Major bleeding was seven times more frequent with intermittent injection than with continuous infusion. Control with the partial thromboplastin time did not prevent major bleeding in patients receiving intermittent injections. With continuous infusion, one-fourth less heparin was required than with intermittent injections. Administration of heparin by continuous infusion appears safer than intermittent injection with or without laboratory control and is no less effective for prevention of thromboembolism.

Topics: Administration, Oral; Adolescent; Adult; Aged; Arterial Occlusive Diseases; Blood Coagulation Tests; Cerebrovascular Disorders; Clinical Trials as Topic; Hemorrhage; Heparin; Humans; Infusions, Parenteral; Injections, Intravenous; Middle Aged; Myocardial Infarction; Prospective Studies; Prothrombin Time; Pulmonary Embolism; Recurrence; Thromboembolism; Thromboplastin; Thrombosis; Time Factors

Despite public awareness of its deleterious effects, smoking remains a major cause of death. Indeed, it is a risk factor for atherothrombotic complications and in line with this, the introduction of smoking ban in public areas reduced smoking-associated cardiovascular complications. Nonetheless, smoking remains a major concern, and molecular mechanisms by which it causes cardiovascular disease are not known. Peripheral blood monocytes from healthy smokers displayed increased JNK2 and tissue factor (TF) gene expression compared to non-smokers (n=15, p<0.05). Similarly, human aortic endothelial cells exposed to cigarette smoke total particulate matter (CS-TPM) revealed increased TF expression mediated by JNK2 (n=4; p<0.05). Wild-type and JNK2

Topics: Animals; Arterial Occlusive Diseases; Blood Coagulation; Carotid Artery Injuries; Cells, Cultured; Endothelial Cells; Female; Genetic Predisposition to Disease; Humans; Male; Mice, Inbred C57BL; Mice, Knockout; Mitogen-Activated Protein Kinase 9; Phenotype; Reactive Oxygen Species; Signal Transduction; Smoke; Smoking; Thromboplastin; Thrombosis

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

The importance of prothrombotic activity in cardiovascular disease has been well established. However, limited data exist on the relationship between prothrombotic activity and the severity of peripheral arterial occlusive disease (PAD). The objective of the present study was to investigate the relationship between markers of haemostasis and the diagnostic measures of PAD: ankle-brachial-index (ABI), maximum treadmill walking distance and angiographic score. In a cross-sectional study of 127 patients (mean age 66 years; 64% males) with angiographically verified PAD, fasting blood samples were drawn, and citrated plasma was obtained for determination of selected haemostatic variables: von Willebrand factor (vWF), thrombomodulin (sTM), thrombin-antithrombin complex (TAT), soluble tissue factor (sTF), tPA antigen (tPAag) and D-dimer were all significantly correlated with the angiographic score (p < 0.05 for all). D-dimer, tPAag and fibrinogen were inversely correlated with the maximum treadmill walking distance, (p < 0.0001, p < 0.04 and p < 0.05, respectively), whereas fibrinogen was the only variable correlating to ABI (r = -0.223, p < 0.05). After adjustment for relevant covariates, D-dimer and TAT remained statistically significantly associated with the angiographic score (p < 0.001), and fibrinogen was, independent of other risk factors, inversely related with both the maximum treadmill walking distance and the ABI (p < 0.01 for both). This rather large study in patients with PAD showed that plasma levels of D-dimer, TAT and fibrinogen significantly predicted the extent of atherosclerosis, evaluated by angiographic score, maximum treadmill walking distance and ABI, respectively. These findings demonstrate a prothrombotic state in PAD patients, which might be of importance in future diagnosis and treatment of the disease.

Topics: Aged; Angiography; Antithrombins; Arterial Occlusive Diseases; Female; Humans; Male; Middle Aged; Thrombin; Thrombomodulin; Thromboplastin; Thrombosis; von Willebrand Factor; Walking

Plaque disruption does not always result in complete thrombotic occlusion. The mechanism of arterial thrombus propagation remains unclear.. We studied how vascular wall thrombogenicity and blood flow reduction affect thrombus propagation using a rabbit model of single and repeated balloon injury. After balloon injury of the normal femoral artery, the blood flow was reduced to 50%, 25%, or 10% (n=5). Small mural thrombi composed of aggregated platelets were produced, but no occlusive thrombi developed in any flow reduction. Three weeks after the first balloon injury, neointima with tissue factor expression and increased procoagulant activity was developed. Balloon injury of the neointima with the same blood flow reduction (n=5) induced fibrin-rich thrombus formation. Additionally, injury with flow reduced to 25% and 10% promoted thrombus propagation resulting in vessel occlusion within 160+/-18 and 71+/-17 seconds, respectively. An injection of anti-von Willebrand factor (vWF) monoclonal antibody (AJW200; 1.0 mg/kg) prevented occlusive thrombus formation.. Increased vascular wall thrombogenicity together with a substantial blood flow reduction is crucial for occlusive thrombus formation, and vWF plays an important role in thrombus propagation. Reduced blood flow at plaque disruption sites might contribute to thrombus propagation leading to acute coronary syndromes.

Topics: Animals; Arterial Occlusive Diseases; Catheterization; Connective Tissue; Constriction, Pathologic; Disease Models, Animal; Femoral Artery; Male; Microscopy, Electron, Transmission; Neovascularization, Pathologic; Rabbits; Regional Blood Flow; Thromboplastin; Thrombosis; Tunica Intima

Men and women with lower extremity peripheral arterial disease (PAD) have reduced physical activity levels compared with persons without PAD. We describe associations between physical activity levels with D-dimer, pro-coagulant factors, and inflammatory markers in patients with PAD. Participants were 188 patients with PAD identified from non-invasive vascular laboratories. Physical activity was measured over 7 days with a vertical accelerometer. We measured the ankle-brachial index (ABI) and levels of D-dimer, C-reactive protein (CRP), fibrinogen, serum amyloid A (SAA), prothrombin 1.2, t-PA antigen, PAI-1, and the t-PA antigen/PAI-1 ratio. Adjusting for age, sex, race, body mass index, ABI, comorbidities, smoking, total cholesterol/HDL ratio and statin use (for CRP only), we found significant inverse linear associations between physical activity levels and log D-dimer (p = 0.002), log CRP (p < 0.001), fibrinogen (p = 0.014), and log SAA (p = 0.012). There were no significant associations between physical activity levels and other blood factors. In an analysis adjusting for all blood factors simultaneously along with known and potential confounders, log D-dimer was the only blood factor associated significantly with physical activity levels (p = 0.036). Based on these findings, future studies should assess whether interventions to increase physical activity in patients with PAD reduce levels of D-dimer and inflammatory markers.

Topics: Arterial Occlusive Diseases; Biomarkers; C-Reactive Protein; Female; Fibrin Fibrinogen Degradation Products; Humans; Lower Extremity; Male; Middle Aged; Motor Activity; Peripheral Vascular Diseases; Thromboplastin

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

Hemorrhage and thrombosis are associated with major vascular and trauma surgery. Release of heparinoids and thrombotic mediators may contribute to these complications and have been described in rabbits after aortic occlusion-reperfusion. We hypothesized that the resuscitative fluid used could reduce heparinoid and thrombotic mediator release after aortic occlusion-reperfusion in rabbits as assessed by thromboelastographic variables (R, reaction time; alpha, angle; and G, a measure of clot strength). Anesthetized rabbits were administered lactated Ringer's solution (n = 8) or PentaLyte (n = 8) at reperfusion after 30 min of ischemia. Blood was obtained before ischemia and after 30 min of reperfusion for thromboelastography under four conditions: 1) unmodified sample, 2) platelet inhibition, 3) heparinase, and 4) platelet inhibition and heparinase. During reperfusion, unmodified samples demonstrated a significant increase in R and decrease in alpha and G that was not affected by PentaLyte. In the presence of heparinase, no significant fluid-specific thromboelastographic differences were noted. However, thrombotic mediator release (discerned by a decrease in R and an increase in alpha) during reperfusion in samples with platelet inhibition and heparinase was significantly attenuated by PentaLyte. PentaLyte administration does not decrease heparinoid release but does decrease thrombotic mediator release after aortic occlusion-reperfusion.

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Arterial Occlusive Diseases; Electrolytes; Glucose; Hematocrit; Hemodynamics; Heparinoids; Hydroxyethyl Starch Derivatives; Rabbits; Reperfusion; Resuscitation; Thromboplastin; Thrombosis

The substrate recognition region of tissue factor contains two residues, Lys165 and Lys166, which are important for macromolecular substrate activation by the tissue factor:factor VIIa complex. Replacement of these two residues with alanine in a soluble version of human tissue factor resulted in a mutant, hTFAA, which can bind factor VIIa but forms an enzymatically inactive complex. We found that hTFAA inhibits the activity of guinea pig factor VIIa, allowing us to evaluate hTFAA's effects on thrombosis and hemostasis in a guinea pig model of recurrent arterial thrombosis. In addition to heparin, the effects of hTFAA were compared to active site inhibited factor IXa (F.IXai) and factor Xa (F.Xai). We found that hTFAA, F.IXai and F.Xai were potent antithrombotics and may possess a decreased risk of hemorrhage when compared to unfractionated heparin. When administered at a dose that inhibited thrombosis by about 90%, hTFAA neither affected cuticle bleeding nor the activated partial thromboplastin time, and had only a modest effect on the prothrombin time. At equi-efficacious doses, F.IXai, F.Xai and heparin prolonged bleeding times by 20% (p >0.5), 50% (p <0.05) and 100% (p <0.01), respectively. In summary, our study demonstrates that, unlike heparin, specific inhibitors of factors VIIa, IXa and Xa can produce antithrombotic effects without or with only minimally disturbing normal hemostasis. The results further suggest that factor VIIa and factor IXa are especially promising targets for antithrombotic drug development.

Topics: Amino Acid Substitution; Animals; Arterial Occlusive Diseases; Bleeding Time; Carotid Artery Thrombosis; Catalytic Domain; Disease Models, Animal; Factor IXa; Factor VIIa; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents; Guinea Pigs; Heparin; Humans; Solubility; Thromboplastin; Thrombosis

Tissue factor (TF), the initiator of coagulation, has been implicated as a critical mediator of arterial thrombosis. Previous studies have demonstrated that TF is rapidly induced in the normal rodent arterial wall by balloon injury, but is not associated with fibrin deposition. A second injury, however, performed 10-14 days after the first, is followed by small platelet-fibrin microthrombi. This study was undertaken to better localize active TF in balloon-injured rat arteries and to explore possible mechanisms underlying the apparent discrepancy between injury-induced TF expression and the lack of large platelet-fibrin thrombi. By immunohistochemistry, TF antigen was first detected in the media 24 h after injury to rat aortas, and subsequently accumulated in the neointima. Using an ex vivo flow chamber, no TF activity (Factor Xa generation) was found on the luminal surface of normal or injured aortas. Wiping the luminal surface with a cotton swab exposed TF activity in all vessels; levels were increased approximately 3-fold in arteries containing a neointima. The exposed TF activity was rapidly washed into the perfusate, rendering the luminal surface inactive. The loss of luminal TF into the circulation may attenuate thrombosis at sites of arterial injury.

Topics: Angioplasty, Balloon, Coronary; Animals; Aorta, Abdominal; Aorta, Thoracic; Arterial Occlusive Diseases; Fibrin; Male; Microscopy, Electron, Scanning; Rats; Rats, Sprague-Dawley; Recurrence; Thromboplastin; Thrombosis; Tunica Intima

Polyethylene glycol (PEG)-hirudin is a derivative of hirudin with a long plasma half-life. We have compared the efficacy of PEG-hirudin with unfractionated heparin (UH) in preventing arterial thrombosis. Arterial thrombus formation was induced ex vivo in 12 healthy human volunteers by exposing a tissue factor-coated coverslip positioned in a parallel-plate perfusion chamber to flowing nonanticoagulated human blood drawn directly from an antecubital vein at an arterial wall shear rate of 2600 s-1 for 3.5 minutes. PEG-hirudin, UH, or saline (as control) were administered ex vivo through a heparin-coated mixing device positioned proximal to the perfusion chamber. Platelet and fibrin deposition was quantified by immunoenzymatic measure of the P-selectin and D-dimer content of dissolved plasmin-digested thrombi, respectively. UH was administered to a plasma concentration of 0.35 IU/mL. This concentration prolonged the activated partial thromboplastin time from 32+/-1 seconds to 79+/-4 seconds (P<0.01). UH did not significantly prevent platelet deposition. However, fibrin deposition was reduced by 39% (P<0.05). PEG-hirudin in plasma concentrations of 0.5, 2.5, and 5 microg/mL prolonged the activated partial thromboplastin time to 48+/-2, 87+/-4, and 118+/-4 seconds, respectively. In contrast to UH, PEG-hirudin prevented both platelet and fibrin deposition in a dose-dependent manner with a >80% reduction at 5 microg/mL (P<0.01). Furthermore, the plasma level of PEG-hirudin required to significantly prevent fibrin deposition (0.5 microg/mL) corresponded to a much shorter prolongation of activated partial thromboplastin time (48+/-2 seconds) than that needed for UH (79+/-4 seconds). Thus, our results are compatible with the view that thrombin is greatly involved in recruitment of platelets in evolving thrombi, and that PEG-hirudin is an effective agent for preventing arterial thrombosis in a human ex vivo experimental model.

Topics: Antithrombin III; Arterial Occlusive Diseases; beta-Thromboglobulin; Blood Coagulation; Blood Coagulation Tests; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Glass; Half-Life; Heparin; Hirudins; Humans; P-Selectin; Peptide Hydrolases; Platelet Activation; Sodium Chloride; Thromboplastin; Thrombosis

We have previously shown that humic acid (well-water humic acid, HA, and synthetic humic acid, SHA) enhances cell surface expression of tissue factor (TF). Here we report that incubation of human umbilical vein endothelial cells (HUVEC) for 2 hr with HA or SHA cause a rapid rise in TF mRNA levels, as shown by Northern blot analysis. To understand the cytotoxic and fibrinolytic effects of HA and SHA on cultured HUVEC, the cells treated with varying concentrations of HA and SHA for various periods of time. Both HA and SHA (10-200 micrograms/ml) inhibited the viability of subconfluent HUVEC, cultured in the presence or absence of 20% FBS (Fetal Bovine serum) in the culture medium, in a dose-dependent manner. Both HA and SHA induced surface changes in the HUVEC as revealed by scanning electron micrography (SEM). However, protocatechuic acid, the monomer of SHA, did not significantly inhibit cell growth, and showed a cytotoxic effect only at 200 micrograms/ml. Furthermore both HA and SHA stimulated HUVEC to produce plasminogen activator inhibitor (PAI-1) and tissue plasminogen activator (t-PA) in a dose and time dependent fashion; the amount of PAI-1 produced was found to exceed that of t-PA. The monomer of SHA did not have this stimulatory effect. These results distinctly suggest that in addition to the inhibition of viability HA is involved in TF induction and PAI-1 synthesis in HUVEC and these may be some of the plausible mechanisms underlying the thrombotic disorders in Blackfoot disease.

Topics: Arterial Occlusive Diseases; Blood Coagulation; Cell Division; Cell Survival; Cells, Cultured; Endothelium, Vascular; Humans; Humic Substances; Microscopy, Electron, Scanning; Plasminogen Activator Inhibitor 1; RNA, Messenger; Taiwan; Thromboplastin; Tissue Plasminogen Activator; Umbilical Veins

This study was designed to determine whether arterial reocclusion after thrombolysis can be prevented by lipoprotein-associated coagulation inhibitor (LACI), a physiological inhibitor of tissue factor-induced coagulation mediated by the extrinsic pathway.. Thrombosis was induced in femoral arteries of anesthetized dogs with the use of anodal current to elicit extensive vascular injury and formation of platelet-rich thrombi in one artery and with thrombogenic copper wire to elicit fibrin-rich thrombi without appreciable vascular injury in the contralateral artery. Recanalization of both vessels was induced with t-PA (1.7 mg/kg i.v. over 1 hour) and verified with Doppler flow probes. Reocclusion occurred within 2 hours in seven of seven arteries with electrical injury-induced thrombosis and in four of seven arteries with copper wire-induced thrombosis in the absence of LACI. In dogs given infusions of recombinant DNA-produced LACI (225 micrograms/kg over 15 minutes, followed by 4 micrograms/kg/min i.v.) after completion of the infusion of t-PA, no reocclusion occurred during the 2-hour interval of observation in any of the five arteries subjected to electrical injury (p less than 0.001), and cyclic partial occlusions were nearly abolished (0.4 +/- 0.4/hr in LACI-treated dogs compared with 13.7 +/- 5.5/hr in saline-treated dogs, p less than 0.0001). In contrast, reocclusion occurred in two of five arteries with indwelling copper wires, and cyclic partial occlusions were unaffected despite LACI. LACI prolonged the partial thromboplastin time modestly (1.7 +/- 0.2 x baseline) but did not affect platelet counts or aggregation assessed ex vivo.. Inhibition of the extrinsic pathway of coagulation with LACI prevents thrombotic arterial reocclusion after thrombolysis in vessels subjected to extensive vascular injury. Our results demonstrate that activation of the extrinsic pathway plays a critical role in thrombotic reocclusion and that LACI provides a highly targeted approach to facilitate sustained recanalization without directly inhibiting platelets.

Topics: Animals; Arterial Occlusive Diseases; Copper; Dogs; Electric Injuries; Factor VII; Fibrinolytic Agents; Lipoproteins; Osmolar Concentration; Prostheses and Implants; Recurrence; Thromboplastin; Thrombosis

Topics: Animals; Anticoagulants; Arterial Occlusive Diseases; Drug Therapy, Combination; Factor VII; Fibrinolytic Agents; Humans; Lipoproteins; Recurrence; Thromboplastin; Thrombosis

Isolated human monocytes generate tissue factor when stimulated with endotoxin. Tissue factor generation provides a marker for activation of the monocyte and of the clotting system. Determination of the recalcification time of blood after incubation with endotoxin detects minute changes in coagulability. This clotting assay was utilized to assess the presence of a hypercoagulable state in patients with peripheral arterial occlusive disease when compared with healthy volunteers. Citrated blood was incubated with endotoxin for two hours, CaCl2 was added, and the recalcification time determined. Hypercoagulability was indicated by shortened recalcification time. The recalcification time +/- standard deviation for saline (control) and endotoxin-activated samples from 19 healthy volunteers was 6.55 +/- 0.8 and 5.69 +/- 0.7 minutes, respectively, whereas it was 4.93 +/- 1.2 and 4.55 +/- 0.9 minutes for 31 patients with peripheral arterial occlusive disease (p less than .001 for each). This hypercoagulable state can accentuate the arterial occlusive process in patients with peripheral vascular disease and may prove to be of diagnostic, therapeutic, and prognostic significance.

Topics: Arterial Occlusive Diseases; Blood Coagulation; Blood Coagulation Tests; Humans; Male; Middle Aged; Monocytes; Thromboplastin

A prospective study was performed on 32 consecutive patients undergoing elective operations on the abdominal aorta. Dacron prosthetic grafts were used to replace resected abdominal aortic aneurysms or to bypass aorta-iliac occlusive disease. Complete coagulation studies were performed preoperatively, immediately postoperatively and 24 hours postoperatively. Twenty to 30 per cent of the patients had significant postoperative alterations in prothrombin time, partial thromboplastin time and platelet count. Fibrin monomer, fibrin split products and plasminogen were abnormal in 40 to 80 per cent of the patients postoperatively. Results of preoperative studies showed no significant abnormalities. One of the 32 patients had mild clinical evidence of disseminated intravascular coagulation postoperatively, which was treated with 5 units of heparin per kilogram per hour. Results of the study indicate that aortic grafting procedures frequently produce intravascular coagulation, either local or disseminated. In most patients, this is offset by activation of the fibrinolytic system. However, clinically significant sequelae may result, requiring prompt recognition and treatment.

Topics: Aged; Aorta, Abdominal; Aortic Aneurysm; Aortic Diseases; Arterial Occlusive Diseases; Blood Cell Count; Blood Coagulation Tests; Blood Platelets; Blood Vessel Prosthesis; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Prothrombin Time; Thromboplastin

Topics: Arterial Occlusive Diseases; Blood Coagulation; Humans; Peripheral Vascular Diseases; Thromboplastin; Thrombosis