The effects of prostacyclin on the coagulation of whole blood.

The effects of prostacyclin (PGI2) on mechanical properties of forming clots were investigated by testing human blood samples on a Thrombelastograph. Concentrations greater than 50 ng/ml (blood) caused a biphasic development of clot stiffness. During the first phase, PGI2 partially inhibited the platelet involvement in coagulation causing initial clot formation at a normal time but with reduced clot stiffness. The second phase occurred after neutralization of PGI2 activity and was characterized by recovery of platelet activity to produce a final clot with normal shear modulus. The duration of the inhibitory effects depended on PGI2 concentration and hematocrit. With a normal hematocrit, a PGI2 concentration of 60 ng/ml caused an inhibition for about 40 min whereas a concentration of 100 ng/ml caused inhibition for about 75 min.

Decreased platelet number and function and increased fibrinolysis contribute to postoperative bleeding in cardiopulmonary bypass patients.

We simultaneously evaluated platelet and fibrinolytic parameters to assess their individual and combined contributions to postoperative blood loss in cardiopulmonary (CP) bypass patients. Platelet count, platelet aggregability, hematocrit, plasminogen (PLG) concentration, alpha 2-antiplasmin (AP) concentration, free protease activity (fPA), and antithrombin-III (AT-III) were measured in nine patients undergoing surgery using cardiopulmonary bypass. Chest tube drainage was used as the measure of postoperative blood loss. Hematocrit, platelet count, PLG, AP, and AT-III all decreased during CP bypass, with PLG and AT-III decreasing much more than dilution. During CP bypass, platelet aggregability to ADP did not change significantly from pre-bypass, but aggregability to arachidonic acid (AA) decreased significantly. Following protamine administration there was a large increase (83%) in fPA, the platelet count showed a further drop (from 61% to 50% of pre-bypass levels), and platelet aggregability decreased significantly (from 95% to 34% of pre-bypass levels for ADP, and from 55% to 11.9% for AA). Chest tube drainage during the first four postoperative hours correlated positively (p less than 0.05) with the combination of increase in free protease activity and decrease in platelet count. The total chest tube drainage correlated significantly with the combination of decrease in platelet count and the decrease in platelet aggregability. These combinations of changes correlated significantly with postoperative blood loss whereas the individual changes did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of thrombelastography with common coagulation tests.

Thrombelastography, although proven as a useful research tool has not been evaluated for its clinical utility against common coagulation laboratory tests. In this study we compare the thrombelastographic measurements with six common tests (the hematocrit, platelet count, fibrinogen, prothrombin time, activated thromboplastin time and fibrin split products). For such comparisons, two samples of subjects were selected, 141 normal volunteers and 121 patients with cancer. The data was subjected to various statistical techniques such as correlation, ANOVA, canonical and discriminant analysis to measure the extent of the correlations between the two sets of variables and their relative strength to detect blood clotting abnormalities. The results indicate that, although there is a strong relationship between the thrombelastographic variables and these common laboratory tests, the thrombelastographic variables contain additional information on the hemostatic process.

In vitro comparison of fibrinolytic activity of plasminogen activators using a thrombelastographic method: in vivo evaluation of the B-chain-streptokinase complex in the dog model using pre-titered doses.

Thrombelastography was used to quantitatively compare the clot-lysing efficiency of 6 different plasminogen activators, using human whole blood, pooled normal plasma, and platelet rich plasma. The activators compared were the B-chain-streptokinase complex, the plasmin-streptokinase complex, the mini-plasminogen-streptokinase complex, tissue plasminogen activator, streptokinase, and urokinase. The most efficient activator found was the B-chain-streptokinase complex. This complex was 4.0 times more effective than streptokinase, 3.0 times more effective than the plasmin-streptokinase complex, 1.3 times more effective than the mini-plasminogen-streptokinase complex, 2.3 times more effective than tissue plasminogen activator, and 16.0 times more effective than urokinase. Although there were differences in both the coagulation and fibrinolysis thrombelastographic patterns between plasma and whole blood, the comparative efficiencies of each activator were the same with either plasma or blood. The B-chain-streptokinase complex was evaluated as a thrombolytic agent in clot-lysis experiments in the jugular vein in the dog model, using a thrombelastographic method to determine the minimum dose of activator necessary for clot-lysis. With 6 dogs infused locally with 0.25 mg (8000 I.U.) of the plasmin-streptokinase complex, the cumulative clot-lysis was 18.0 +/- 3.0% with the first dose, 33.0 +/- 2.1% with the second dose, and 55.2 +/- 8.6% with the third dose. With 6 dogs infused locally with 0.03 mg (2000 I.U.) of the B-chain-streptokinase complex, the cumulative clot-lysis was 30.6 +/- 6.4% with the first dose, 54.4 +/- 9.6% with the second dose, and 80.2 +/- 9.0% with the third dose.

Thrombelastography of blood from subjects with chronic renal failure.

Blood samples from 23 subjects with chronic renal failure and 19 controls were tested using thrombelastography and other hematologic tests. The uremic subjects were divided into two groups, those who had not yet begun maintenance hemodialysis treatments (12 subjects) and those who had (11 subjects). Compared to those from control subjects, the thrombelastograms from the uremic subjects consistently indicate normal clotting times but significantly elevated amplitudes. The increased amplitudes correlate positively in the dialyzed uremic group with both platelet count and fibrinogen concentration and correlate negatively in both uremic groups with hematocrit. Thrombelastography demonstrates a hypercoagulability in these samples in vitro, despite the prolonged bleeding time that commonly occurs in uremic subjects.

Relationship between postsurgical fibrinolytic parameters and deep vein thrombosis in surgical patients treated with compression devices.

This study consisted of 52 patients admitted for orthopedic surgery and 28 patients admitted for general surgery, who were treated with Sequential Compression Devices (SCD) and Thromboembolic Deterrent Stockings (TEDS) and monitored for the development of deep vein thrombosis (DVT). Coagulation and fibrinolytic profiles were carried out on these patients preoperatively, and on days one, three, and six postoperatively. All patients were followed by I-125-Fibrinogen scanning, Venous Doppler, and Impedance Plethysmography studies for clot detection. In the orthopedic surgery group, six (11.5%) developed DVT, and in the general surgery group, one (3.6%) developed DVT. No patients developed pulmonary embolism. The combined incidence of DVT was 8.8 per cent. A variety of parameters was measured in order to determine whether compression devices prevent a fibrinolytic shut-down commonly seen in the postsurgical patient. A combination of three assays was found to be significant in demonstrating a fibrinolytic response. These parameters were a post-surgical decrease in the plasminogen level, an increase in the level of free protease activity postoperatively, and an increase in the level of tissue plasminogen activator after surgery. 56.3 per cent of all patients treated with SCD and TEDS showed a fibrinolytic response on postoperative day one by a combination of all three of these parameters. In the group of patients that developed DVT none showed an increase in free protease activity, and five of seven showed no significant decrease in plasminogen and no increase in tissue plasminogen activator. Patients who developed thrombosis had measurable differences in their fibrinolytic system compared to those without postoperative thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)