Fibrinolytic activity in patients with idiopathic and secondary deep venous thrombosis.

Decreased fibrinolytic activity (FA) is considered a risk factor in the development of deep venous thrombosis (DVT). The purpose of this study was to test the hypothesis that an abnormally low FA is more likely in idiopathic DVT as opposed to DVT in the presence of other predisposing risk factors. 156 patients were studied three months after an acute DVT confirmed by venography. In 82 patients a predisposing factor such as trauma, surgery or malignancy was present. In 74, DVT was idiopathic. Fibrinolytic activity was measured in all patients using the following tests: 1. Euglobulin Lysis Time (ELT, in minutes). 2. Global Fibrinolytic activity (FA in mg fibrin lysed per hour). ELT measures plasminogen activator activity (PAA) while FA which is a more global test measures the net effect of the PAA, the plasminogen activator inhibitor (PAI) and the clot structure. PAI was measured in 67 patients from both groups using an Enzyme-Linked immunosorbent assay (ELISA). The results obtained show a significant increase in the incidence of abnormal FA and ELT in the idiopathic group. This supports the hypothesis that low FA is an aetiological factor in the development of idiopathic DVT. The results also demonstrate the importance of associating the FA test to the classical tests such as ELT, PA and PAI for the detection of hypofibrinolysis.

Reduced human peritoneal plasminogen activating activity: possible mechanism of adhesion formation.

A unifying pathophysiological hypothesis states that the plasminogen activating activity (PAA) of the peritoneal mesothelium determines whether the fibrin which forms after peritoneal injury is either lysed or organized into permanent fibrous adhesions. The PAA of human peritoneal biopsies was measured using a fibrin plate lysis technique to assess the changes that occur in inflammation and ischaemia, conditions which both produce fibrous adhesions. Activity was found in all biopsies from normal parietal and visceral (appendix, bowel and omentum) peritoneum with no significant site-to-site variation. Inflamed peritoneum (parietal, appendicular and mesenteric) had significantly less PAA compared with normal peritoneum; visceral ischaemia also resulted in a significant decrease of PAA. These reductions in human peritoneal PAA observed in inflammation and ischaemia support the view that mesothelial PAA plays a key part in the prevention of events leading to the production of fibrous adhesions.

Heparin neutralising activity of whole blood in patients undergoing vascular surgery.

A test for measuring the heparin neutralizing activity in whole blood is described. This test was used in 13 patients having peripheral vascular surgery. The heparin neutralising activity (HNA) and fibrinogen concentration in the blood were measured on the day before operation. During operation, blood was withdrawn before and five minutes after administration of 10,000 units of heparin for the measurements of activated clotting time (ACT) and partial thromboplastin time (PTT). There was considerable variation in the ACT and the PTT values at five minutes after heparin administration which showed no correlation to the patients' weight. However, there was a significant linear correlation between the increase in ACT values and the HNA measured on the day before operation and a significant linear correlation between the HNA and the fibrinogen concentration. The results indicate that the ACT and PTT after giving heparin depended on HNA rather than the patients' weight, and are related to the fibrinogen concentration.

The effect of operation and subcutaneous heparin on plasma levels of antithrombin-III.

Plasma antithrombin III (AT-III) levels were measured in 61 patients undergoing general surgery. The patients were randomly allocated to a test or a control group. The test group received 5000iu of subcutaneous heparin two hours before operation and then twelve hourly for seven days. The control group received subcutaneous saline. Plasma levels of AT-III and of heparin were estimated before operation, at two, four and six hours after heparin injection on the day of operation and thereafter before the morning injection on the first, third and sixth postoperative days. Antithrombin III decreased progressively during and after operation in both groups. The decrease was greater in the test group at six hours after the first injection. These findings support the hypothesis that AT-III is consumed during coagulation and its utilization is increased in the presence of heparin.

Estimation of fibrinolytic activity of whole blood in patients with recurrent idiopathic deep venous thrombosis.

The fibrinolytic activity of blood was measured in control subjects and patients with idiopathic deep venous thrombosis by a new method, which was based on the rate of release of radioactivity in vitro from clotted blood to which 125I-fibrinogen was previously added. Blood was obtained without application of a venous tourniquet. The results are expressed as the amount of fibrin lysed per unit of time and are not affected by the fibrinogen concentration, a drawback inherent in previous techniques. The mean value (+/- standard deviation) of fibrinolytic activity was 0.464 +/- 0.158 mg of fibrin lysed per hour in the control subjects and 0.194 +/- 0.089 mg of fibrin lysed per hour in the patients. This difference is significant (p less than 0.01) and indicates a considerable reduction in fibrinolytic activity in patients with idiopathic deep venous thrombosis. This has been demonstrated without the need to stimulate the release of plasminogen activator by applying a venous tourniquet as done in previous studies.

Subcutaneous heparin, plasma heparin levels and postoperative wound haematoma.

Ninety-five patients, over the age of 40, having general surgical operations, were randomly allocated to a control and test group. The test group received 5000 units of subcutaneous heparin two hours before operation and then 12-hourly for seven days. The patients in the control group received the same regimen of isotonic saline. There was a marked variation in the plasma heparin levels from patient to patient, and from day to day in the same patient. There was a significant increase in the incidence of wound haematoma in patients with a plasma heparin level greater than 0.2 units/ml. The results suggest that the increased incidence of wound haematoma previously reported is due to the increase of incidence in patients who have plasma heparin levels greater than 0.2 units/ml.

Prostaglandin E1 in severe Raynaud's phenomenon.

Twenty-one patients with severe Raynaud's phenomenon were treated on 29 occasions with prostaglandin E1 (PGE1), a potent vasodilator and pyrogen. A history of finger sepsis or necrosis was absent in 8 (group I) and present in 13 (group II). Three group I and eight group II patients had an associated connective tissue disease, and previously eight upper limbs had been sympathectomized in six group I patients and 14 upper limbs in eight group II patients. A total of 12 fingers had been amputated in six group II patients. Treatment comprised antibiotics for sepsis, PGE1 intravenously for 72 hours, and subsequent surgical debridement of septic and necrotic tissue in 30 fingers of eight group II patients under general anesthesia. Finger skin temperature measured half-hourly in a temperature-controlled ward cubicle (23.7 degrees +/- 0.7 degrees C), Doppler-detectable digital arterial flow, and finger/brachial systolic pressure index with local finger cooling to 10 degrees C were not improved by the administration of 0.9% saline for 72 hours, but were all significantly improved after PGE1 administration. Finger skin temperature was significantly elevated 11 weeks after treatment. The symptoms did not improve after PGE1 administration in group I patients but did improve in 12 of 13 group II patients. No finger deteriorated, and all debrided fingers healed after surgery. Nail bed removal in 11 fingers met with patient approval and prevented recurrent sepsis and necrosis. PGE1 provides a means of increasing finger blood flow during acute exacerbations of finger sepsis and necrosis; unlike sympathectomy, it is a minor procedure without prolonged side effects and is repeatable.