fibrinopeptide-a and Ischemia

Patients suffering from atherosclerosis may have a hypercoagulable state which is further aggravated by surgery. Thrombin, a central enzyme in the coagulation process, cleaves fibrinogen to fibrin. Therefore, inhibition of thrombin is an important anticoagulant mechanism. This is accomplished by heparin in concert with antithrombin III (AT), but vessel wall glycosaminoglycans may act as substitutes for heparin and catalyse thrombin inhibition. The present study examines whether administration of AT or heparin is effective as an anticoagulant during infrainguinal bypass surgery. Preoperatively and during surgery the patients had elevated levels of fibrinogen, fibrinopeptide A (FPA) and thrombin-antithrombin (T-AT) complexes. There were higher levels of FPA in the venous outflow from the ischemic leg than in the arterial inflow. Taken together these measurements indicate ongoing coagulation in the operated leg. Administration of heparin decreased FPA levels and prevented intraoperative graft thrombosis, whereas in patients receiving AT, T-AT levels increased but FPA levels were unchanged. In the latter group, intraoperative graft thrombosis occurred in a high proportion. Based on additional case histories in these patients with hypercoagulability, it is suggested that fibrinogen is a risk factor for thromboembolic complications and that a combination of low dose of heparin and AT might be an effective regimen to prevent intraoperative thrombosis with a low risk of haemorrhage.

Topics: Adult; Aged; Aged, 80 and over; Antithrombins; Arteriosclerosis; Diabetic Angiopathies; Female; Fibrinopeptide A; Graft Occlusion, Vascular; Heparin; Humans; Intermittent Claudication; Ischemia; Leg; Leg Ulcer; Male; Middle Aged; Postoperative Complications; Premedication

We investigated soluble, thrombin-related material in arterial thrombi and venous plasma during catheter-directed thrombolysis with alteplase. Arteriography was performed before thrombolysis and 0.5, 3, 10 and 24 h after the onset of treatment in six patients with (sub)acute lower extremity ischaemia caused by native artery or bypass occlusion. Samples were collected simultaneously from the thrombus and venous blood. After adding inhibitors of thrombin and plasmin, the centrifuged samples were assayed for prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and fibrinopeptide A (FPA). Levels of F1+2, TAT and FPA were extremely elevated in the thrombus-related samples before the blood flow was re-established (at 0 and 0.5 h) in all five successfully treated patients. In comparison, venous plasma levels of F1+2, TAT and FPA were moderately elevated, and reached a maximum at 3 h. In conclusion, material aspirated from lysing human thrombi formed in vivo contains large amounts of F1+2, TAT and FPA, but our methods prevented us from detecting enzymatically active thrombin.

Topics: Aged; Angiography; Antithrombin III; Blood Coagulation Factors; Catheterization; Female; Fibrinolytic Agents; Fibrinopeptide A; Humans; Ischemia; Leg; Male; Middle Aged; Peptide Fragments; Peptide Hydrolases; Protein Precursors; Prothrombin; Solubility; Thrombolytic Therapy; Thrombosis; Time Factors; Tissue Plasminogen Activator; Treatment Outcome

While vascular patency and overall viability of the gut can be evaluated perioperatively, damage to the mucosal barrier can hardly be judged in the perioperative setting and, moreover, will probably determine the clinical course.. In 19 consecutive cases with intestinal ischemia, the clinical course was correlated to the severity of the disease (APACHE II; Septic Severity Score, SSS), the intraabdominal and systemic inflammatory response, and the translocation of bacteria and endotoxin.. The comparison of the 10 survivors with the nonsurviving group revealed no differences as to the length of history, serum lactate levels, white blood cell counts, body temperature, markers of the inflammatory response, or quantity and macroscopic quality of the exudate. Differences were found in intraperitoneal bacteriology (prevalence 0.37, negative predictive value for lethal outcome 0.8), endotoxin concentrations in the exudate (P = 0.02) and in the plasma (P = 0.015), fibrinopeptide A levels (exudate P = 0.036; plasma P = 0.015), PGE2 plasma concentration (P = 0.0357), and APACHE II (P = 0.0034) and SSS (P = 0.0027) values.. The clinical course of ischemic bowel wall necrosis seems to depend on the severity of the disease at admission and on the integrity of the mucosal barrier rather than on inflammatory response, therapeutic measures, or supportive treatment.

Topics: Aged; APACHE; Body Temperature; Dinoprostone; Endotoxins; Female; Fibrinopeptide A; Humans; Intestines; Ischemia; Lactates; Leukocyte Count; Male; Middle Aged; Severity of Illness Index

In 11 men undergoing infrainguinal bypass surgery, simultaneous blood samples were analyzed by use of sensitive markers of thrombin activity (fibrinopeptide A, FPA) and platelet behavior (beta-thromboglobulin, beta-TG), as well as conventional clotting times. FPA levels were consistently higher in the venous outflow from the ischemic limb compared with the arterial inflow (p less than .01), while no venoarterial difference was noted for beta-TG. This suggests that there is increased thrombin generation, but not platelet activation localized to the ischemic limb. After a mean dose of 6800 units of heparin given during surgery, FPA levels fell significantly (p less than .03), and the activated clotting time (ACT) was prolonged to 230 to 260 sec, but beta-TG levels did not change. Anticoagulation during lower extremity vascular surgery may be usefully monitored by the activated clotting time because an ACT longer than 250 sec is correlated with lower FPA levels (less than 10 ng/ml), reflecting significant inhibition of coagulation.

Topics: beta-Thromboglobulin; Blood Coagulation; Fibrinopeptide A; Heparin; Humans; Intraoperative Care; Ischemia; Leg; Male; Middle Aged; Monitoring, Physiologic; Platelet Aggregation; Thrombin

The role played by coagulation and platelet activation in the pathogenesis of retinal vein occlusions (RVO) has been evaluated by measuring beta-thromboglobulin (B-TG), circulating platelet aggregates (CPA), thromboxane B2 (TxB2) and fibrinopeptide A (FPA) in 25 patients less than 40 years old, investigated after the acute phase of RVO. FPA nd B-TG were significantly higher than in healthy subjects; CPA and TxB2 were not different. These abnormalities, found in patients free from apparent generalized vascular disease, suggest that a thrombophilic state characterized by coagulation and platelet activation is present in a high proportion of young patients with RVO.

Topics: Adolescent; Adult; beta-Thromboglobulin; Blood Coagulation; Blood Platelets; Female; Fibrinopeptide A; Humans; Ischemia; Male; Platelet Aggregation; Retina; Retinal Diseases; Retinal Vein; Thromboxane B2