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Hyperfibrinolysis is observed during and immediately after major orthopedic surgery. The kinetics and duration of this phase should be defined to adjust the duration of antifibrinolytic treatment with tranexamic acid (TXA).We aimed to quantify the duration of postoperative fibrinolysis and to assess the biological impact of TXA administration.Fourteen patients undergoing total hip replacement (THR) and 10 patients undergoing total knee replacement (TKR) with tourniquet were included in an observational, prospective, single-center study. Among these patients, 7 THR patients and 5 TKR patients received TXA (15mg/kg IV intraoperatively, followed by continuous infusion of 15mg/kg/h until end of surgery, then every 4hours until 16±2hours after surgery). D-dimers, euglobulin lysis time (ELT), and thrombin generation time (TGT) were measured prior to surgery as well as 6, 18 and 24hours (H) after.No significant difference in ELT was observed between the groups. In contrast, D-dimers significantly increased postoperatively in patients not treated with TXA (p0.001), while such an increase was prevented in patients receiving TXA, as measured at H0, H6, H18 and H24 after THR, and at H6 and H18 after TKR (p0.001). No significant between-group change in TGT, was observed (peak thrombin and endogenous thrombin potential) all along the study.This study shows that fibrinolysis peaked 6hours after end of surgery and maintained about 18hours after surgery, as evidenced by an increase in D-dimers. When administered for up to 16±2hours after surgery, TXA reduced postoperative fibrinolysis.

The thienopyridine drugs, ticlopidine, and clopidogrel are used extensively as antiplatelet agents. Clopidogrel is used in the treatment of myocardial infarction, stroke, and peripheral vascular disease [1--3]. Clopidogrel’s beneficial effects are derived from its antiplatelet effect, mediated by the inhibition of adenosine diphosphate (ADP) receptors on platelets [4]. Recent studies have suggested that thienopyridines have fibrinolytic properties and propose that a thrombolytic role may be an important mechanism in their efficacy [5]. Oral ticlopidine reduced the euglobulin lysis time (ELT) in human subjects, and experimental infusions of clopidogrel and ticlopidine were shown to reduce the thrombus burden in rats [6]. An associated increase in prostacyclin (PGI 2) was considered as a possible initiator for tissue plasminogen activator (tPA) release.

The measurement of D-dimer in serum samples (s-DD) after standardized coagulation has been reported as a possible single global test for fibrinolysis in unstimulated conditions in healthy subjects and in patients with ischemic heart disease and with different metabolic disorders. No study has been performed on the use of this test in pregnancy, a condition characterized by physiological changes both in coagulation and in fibrinolysis. In this preliminary study, we have evaluated in 28 women with physiological pregnancy and in 23 comparable controls s-DD and a number of markers of coagulation and fibrinolysis. In nonpregnant women s-DD showed a good correlation with fibrinolytic parameters [euglobulin lysis time (ELT) and type 1 inhibitor of tissue plasminogen activator (PAI-1) act: P

The daytime fluctuation of the fibrinolytic activity and the antigen levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) in plasma were analyzed in normal male and female volunteers. Samples were obtained at 8:30, 10:30, 12:30, 14:30 and 16:30 h. Euglobulin clot lysis time (ECLT) showed the longest time at 8:30 to 10:30 h and the shortest time at 16:30 h. The highest level of tPA was obtained at 8:30 h and the lowest at 14:30 h in men, whereas the highest value was at 8:30 h and the lowest was at 16:30 h in females. Active free PAI-1 showed highest value at 10:30 h in men and at 8:30 h in women. The lowest values obtained at 16:30 h in both men and women and were about one third of the highest values. ECLT was always shorter in females than in males and parameter such as tPA and PAI-1 were also lower in females than in males. The phase of the circadian rhythm of the fibrinolytic parameters may be advanced in females than in males.

The behavior of hemostatic system activation during protracted physical exercise is well known, but the duration of its modification is not yet defined. In order to evaluate the time of hemostatic system activation after prolonged strenuous endurance physical exercise (typical marathon race: 42.195 km, v=15.35 km/h; mean length of time run 2.45± 0.15 hours) 12 well-trained long-distance male runners (mean age: 35±7, range 25–47 years) were investigated. Blood samples were drawn in the morning on the day before the performance, immediately after the race, and 24 hours and 48 hours after the end of run. With respect of baseline, immediately after the race, a significant decrease of fibrinogen (−25%) and significant increases of prothrombin fragment 1+2 (+633%) and thrombin-antithrombin complex (+848%) were observed. A significant acceleration of euglobulin lysis time (−41%), and rises of plasma levels of tissue plasminogen activator antigen (+361%), plasminogen activator inhibitor type 1 antigen (+235%), d-dimer (+215%), and plasma fibrinogen degradation products (+1200%) were also found. Only a slight, yet not significant, decrease in plasminogen activator inhibitor type 1 activity was observed. One day after the end of marathon different parameters were still unchanged. Forty-eight hours after the competition all parameters investigated returned to baseline values. These results indicate a persistence of clotting as well as fibrinolysis activation up to 24 hours after the end of the race.

With a view to investigating whether in circadian variations of platelet aggregation (PA) and fibrinolytic activity there is an elevated risk period for incidence and development of ischemic stroke, 25 healthy subjects (5 females and 20 males), their age ranging from 29 to 51, were exposed to the analysis of PA, euglobulin lysis time (ELT), fibrinogen degradation products (FDP), antithrombin III (AT III) and heparin tolerance test (HTT) in blood samples drawn by venepuncture at 08.00, 11.00, 13.00, 15.00, 17.00 and 18.00h; beside these intervals in the case of 10 healthy males, whose age ranged from 32 to 45, blood samples were taken at midnight as vell. The group of 25 subjects comprised those who usually worked daily and nightly shifts, as well as those who were either at bed rest or doing their duties during daytime. The findings of this investigation have demonstrated that all the parameters studied exhibited circadian variations irrespective of sex, age or daily/nightly activities of the subjects. The most pronounced PA interval, which was not accompanied by corresponding increase of fibrinolytic activity, was that around 11.00h and it is marked as the highest risk period for onset of ischemic stroke.

Because fibrinolysis is now recognized as an important factor in hypercoagulable states, we have developed and characterized an easily performed, rapid, and quantitative screening test that assesses a patient's fibrinolytic activity. This modification of the dilute whole blood clotting time (DWBCT) counts the number of intact erythrocytes released from the clot formed in samples obtained before and after the application of a venous occlusion cuff. Samples were corrected for the plasma volume changes that occurred during venous occlusion. This test was performed on nine healthy volunteers. Specimens were diluted 1:1 with PBS, rapidly clotted with thrombin and incubated at 37 C. Starting thirty minutes after the thrombin was added and then at twenty minute intervals until 110 minutes, the number of RBCs released from the clot were counted using a Coulter S Plus counter. There were consistently more RBCs released at each time period after venous occlusion (p less than 0.001). Aliquots were also obtained for measuring PAI activity and TPA levels. PAI activity was lower post-cuff at every point (p less than 0.001). TPA level was higher at every point (p less than 0.001) post-cuff. The addition of exogenous TPA, activated protein C, or anti-PAI antibodies increased the amount of clot lysis; while the addition of anti-TPA antibodies and EACA each prevented the post-cuff increase. Unlike the euglobulin lysis time (ELT) this modified DWBCT (mDWBCT) measures the patients intact fibrinolytic system, including PAI and erythrocytes, in a quantitative fashion. Unlike either the ELT or the DWBCT the mDWBCT can be performed within two hours, so results are rapidly available for clinical decisions. These studies have demonstrated an easily performed, inexpensive, quantitative screening test of a patient's overall fibrinolytic system that reacts appropriately to pharmacologic manipulations.

Twenty-nine patients with acute myocardial infarction were given recombinant tissue plasminogen activator (tPA) within 6 hr after onset of chest pain (mean: 3.2 hr) with a total dose of 100mg iv drip given within 3hr for thrombolytic therapy. Serial determinations of total FDP, FDP D-Dimer (specific for FbDP), fibrinogen (Fg), PT, APTT, reptilase time (RT), plasminogen, alpha 2-antiplasmin (AAP), euglobulin lysis time (ELT) and antithrombin III (ATIII) were performed before and 1, 2, 4, 6, 12, 24, 48 hr after initiation of tPA injection in the 29 patients in order to evaluate the hemostatic changes after thrombolytic therapy. Decreases of plasminogen, Fg, AAP & ELT were found from 1 hr after therapy and persisted to 24, 12, 24 & 12 hr, respectively, with the maximum decrease usually between 1-4 hr. Increases of FDP, FDP D-dimer, PT, APTT & RT were found from 1, 1, 2, 1 & 1 hr after therapy, respectively, and sustained to 24, 12, 12, 24 & 12 hr, respectively, with maximum increases between 1-4 hr. No significant changes of ATIII were noted during the 48-hr study-period. 4 of these 29 patients (13.79%) had the complication of localized bleeding, 1 of them needed 1 unit of packed red blood cell transfusion. All thrombolysis-related changes recovered within 24 hr after tPA therapy. No parameter we have studied so far could be used for the prediction of the possibility of coronary patency after tPA therapy. But markedly elevated FDP was found to be associated with high risk of bleeding complication. As the coagulation changes persist for 24 hr or longer, careful monitoring of the coagulation tests and close observation of clinical bleeding signs up to 48 hr are necessary in patients treated with tPA.

Blood was taken from healthy 15 males and 10 females at 9:30 h, 10:00 h and 12:30 h. The euglobulin fraction was prepared and clotted by the addition of human thrombin. The clot lysis time shortened significantly from 9:30 h to 10:00 h (p less than 0.01) and further to 12:30 h (p less than 0.01). Plasma levels of tissue plasminogen activator (t-PA) antigens did not change from 9:30 h to 10:00 h, but slightly and significantly to 12:30 h (p less than 0.01). Plasma levels of free plasminogen activator inhibitor-1 (PAI-1) and complex of t-PA-PAI-1 decreased from 9:30 h to 10:00 h (p less than 0.02) and to 12:30 h (p less than 0.01). Plasma levels of total PAI-1 (free plus complex) decreased from 9:30 h to 10:00 h (p less than 0.01) and to 12:30 h (p less than 0.01). These results suggest that a major factor contributing to the enhanced fibrinolytic activity of the euglobulin fraction may be a level of PAI-1 (free and total).

Fitzgerald trait, a deficiency of high molecular weight (HMW) kininogen, is characterized by a prolongation of both the activated partial thromboplastin time (aPTT) and of the kaolin-activated euglobulin lysis time. To study the role of HMW kininogen in coagulation and fibrinolysis, highly purified bovine HMW kininogen, kinin-free HMW kininogen, a histidine-rich fragment of HMW kininogen, and low molecular weight (LMW) kininogen were obtained. The effects of these proteins on the aPTT and kaolin-activated euglobulin lysis time of Fitzgerald trait plasma were studied. It was found that whole bovine plasma and HMW kininogen had identical capacities to partially correct the prolonged aPTT. Kinin-free HMW kininogen had only 30% of the correcting capacity of intact HMW kininogen. LMW kininogen had no effect on the aPTT of Fitzgerald plasma. The histidine-rich fragment prolonged the aPTT of Fitzgerald plasma and of normal human plasma without affecting the one-stage prothrombin time. HMW kininogen also corrected the kaolin-activated euglobulin lysis time of Fitzgerald plasma. Kinin-free HMW kininogen and LMW kininogen had weak capacities to correct the Fitzgerald kaolin-activated euglobulin lysis time. The histidine-rich fragment significantly prolonged the kaolin-activated euglobulin lysis time of Fitzgerald and normal plasmas. The histidine-rich fragment appears to inhibit the activation of Hageman factor (Factor XII) by kaolin or ellagic acid. Our data suggest that intact bovine HMW kininogen corrects the deficiency of Fitzgerald trait plasma; but the hydrolysis of HMW kininogen by plasma kallikrein yields peptides with decreased correcting activity, and at least one with inhibitory activity in contact-mediated coagulation and fibrinolysis.

Serial determinations of beta-thromboglobulin (BTG), platelet factor 4 (PF4), fibrinopeptide A (FPA), anti-thrombin III (ATIII), protein C (PC), fibrin(ogen) degradation product (FDP), FDP D-dimer, activated partial thromboplastin time (APTT), prothrombin time (PT), and euglobulin lysis time (ELT) were performed in 18 patients with non-progressing stroke and 14 patients with progressing stroke in order to predict the development of progressing stroke. Increasing levels of BTG, PF4 and FDP with frequent fluctuation were noted in both kinds of stroke. Fluctuation of FPA levels was also noted but was less pronounced. PC levels were found to be slightly decreased with fluctuation but the mean was still in the lower normal limit. BTG, PF4 and PC all elevated at the time of deterioration of physical condition in patients with progressing stroke, whereas FPA had no definite change at that time. From out study, we conclude that both platelet activation and coagulation process do occur in both kinds of stroke. But the latter plays a minor role in the formation of thrombosis. The hemostasis change, especially concerning the thrombosis formation, probably plays a role in the development of progressing stroke, but we cannot predict their development even by the detections of the newly known molecular substances appearing in various steps of the hemostatic mechanism. Developtment of new tests for understanding the whole dynamic change of the thrombosis process is necessary for accurate prediction of the progressing stroke in the future.

The influence of different heparin fractions and of a synthetic polysulfated polysaccharide (SP54) on the fibrinolytic mechanism was examined. In vitro,a significant shortening of the euglobulin lysis time (ELT) was found after addition of standard mucosa heparin, of high MW heparin and of SP 54 respectively. Low MW heparin fractions had no influence on the ELT. Simultaneously with the shortening of the ELT an activation of factor XII and of kallikrein was observed. A similar effect was found in groups of volunteers after i.v. or s.c. injections and even after oral administration of SP 54. The effect of venous occlusion on the ELT and on the activation of factor XII was considerably increased when heparin or SP 54 was injected 2 h prior to the test. When a comparable concentration of the test substances was added to plasma samples before and after venous occlusion,the effect on the ELT was much less pronounced than after injection whilst the effect on factor XII was comparable in both tests. From these results the conclusion was drawn that activation of fibrinolysis by polysulfated polysaccharides is achieved by an endogenous pathway as well as by an increased availability of the vascular activator. The magnitude of the activation of fibrinolysis partly depends on the MW of the substance but apparently also on the degree of sulfatation since a low MW substance with a high number of sulfate bonds such as SP 54 was considerably more active than the low MW fraction of standard heparin.

To diagnose hemorrhagic, thrombotic, and hemorrhagic-thrombotic tendencies respectively, the Hemorrhagogram, Thrombogram, and Hemorrhago-thrombogram were devised. In the Hemorrhagogram, the tests on platelets and the vessel wall, namely, platelet count, bleeding time, clot retraction, and capillary fragility, the tests on coagulation, namely, clotting time, activated partial thromboplastin time (PTT), prothrombin time, and r and k values of thrombelastogram (TEG), and the tests on fibrinolysis, namely, fibrinogen and euglobulin lysis time (ELT) were performed. We prepared the Thrombogram taking fibrinogen and heparin resistance as indicators for coagulation, platelet adhesiveness or platelet aggregation for platelets, plasma clot lysis time (PLT) and ELT for fibrinolysis, and blood viscosity and the TEG-ma value as overall indications. In the Hemorrhago-thrombogram, a series of fifteen tests on blood platelets, coagulation and fibrinolysis, namely, blood viscosity, platelet count, bleeding time, clot retraction, prothrombin consumption, platelet factor 3, platelet adhesiveness, platelet aggregation induced by ADP, TEG, heparin resistance, prothrombin time, PTT, fibrinogen, PLT and ELT, was performed on each blood sample. These diagrams not only gave us an immediate picture of the condition of the disease, but also confirmed the need to make an overall judgment of the essential factors involved in hemorrhagic and/or thrombotic diseases. This kind of integrated analysis is thought to provide a useful indicator for the diagnosis and treatment of these diseases.

By means of a microscopic fluorescence method the dependence of the time course of the euglobulin lysis on the total calcium concentration of the reaction mixture was studied. By the use of various thrombin preparations with different calcium ion concentrations significant differences in the euglobulin lysis time (ELT) were observed. Consequently, equal calcium ion concentrations of various thrombin preparations or of the total reaction mixture respectively are required to obtain comparable results of the euglobulin lysis time.

The depolymerized heparin fragment PK 10169 was compared with unfractioned mucosal sodium heparin. The inhibition of factors Xa and IXa by heparin and by PK 10169 was comparable on a weight base, whilst the inhibition of thrombin by PK 10169 was at least 5 times weaker than by heparin. Subcutaneous injection of PK 10169 was not followed by an increase of the thrombin time. The activated partial thromboplastin time was considerably less prolonged after PK 10169 than after heparin. Platelet count and platelet functions were not influenced by PK 10169. In vitro, the euglobulin lysis time (ELT) was shortened after addition of heparin to plasma but not after addition of PK 10169. After injection however, there was an equal shortening of the ELT by both substances. The half-life in circulation of PK 10169 was longer than the half-life of heparin. The advantages of PK 10169 over heparin are therefore the weaker influence on overall coagulation, the missing influence on platelet functions and the longer half-life in circulation.

Anticoagulant, fibrinolytic and thrombolytic effects of galactan polysulfate (DH 6322), a new semi-synthetic polysaccharide sulfate of bacterial origin, were studied in the rat in vitro , ex vivo and in vivo . Addition of DH 6322 to citrated plasma gave a 50% reduction in euglobulin lysis time at around 50 μg/ml and a 2-fold prolongation in plasma recalcification time at 40 μg/ml. Intravenous injection of DH 6322 caused significant acceleration of euglobulin clot lysis and urokinase-induced plasma clot lysis at doses as low as 2 mg/kg, and also significant prolongation of plasma recalcification time. Oral application of the compound gave similar effects only at an extremely high dose of 3 g/kg. When injected intravenously before induction of pulmonary thrombosis by lactic acid infusion, DH 6322 was found to be effective in preventing thrombus formation. In progressive venous thrombosis induced by insertion of a steel coil into the inferior vena cava, DH 6322 treatment also caused a significant reduction of thrombus size together with increase in the serum levels of fibrin degradation products. The findings indicate that the antithrombotic effects of DH 6322 result from its enhancement of the fibrinolytic potential as well as its anticoagulative action.

This study evaluates how plasminogen activator (PA) behaves in response to intravenous (i. v. ) and intranasal (i. n. ) DDAVP in healthy subjects. Five volunteers received in random order four i.v. DDAVP doses (0.1–0.4 μg/Kg) and saline. Changes in PA (euglobulin lysis time) were measured from baseline after 30, 120 and 360 min. PA increased significantly with dose and reached a seven-fold mean rise at 0.4 μg/Kg. Five other subjects, similarly treated with i. n. DDAVP (1–4μg/Kg), showed a significant increase (two-fold over baseline values) but no clear dose-response relationship. To evaluate the rate of PA return to baseline values, seven subjects received a single i.v. DDAVP dose (0.4 μg/Kg) and PA changes were measured at various post-infusion intervals. The pattern of PA clearance from the circulation was clearly bimodal. The mean half-disappearance time of the rapid component was 62 min, that of the slower component, 457 min. Finally, to assess the consistency of PA response following repeated treatment, five healthy subjects were given five daily i.v. doses of DDAVP (0.4 μg/Kg). Even though there was a progressive reduction in the response, a significant increase over baseline was still observed after the last dose.

In 38 patients subjected to mitral commissurotomy the following changes indicated activation of intravascular coagulation and fibrinolysis: early decrease in fibrinogen level, platelet count, euglobulin lysis time, increase of SFMC in plasma and of FDP in serum. Subsequent hyperfibrinogenemia was associated with a prolongation of euglobulin lysis. In 10 patients operated for abdominal hernia or varicose veins changes in the above mentioned tests, although similar in direction were much less pronounced and non significant.

Patients with Retinal Vein Occlusion (RVO, n = 62) studied within a week after the event showed significant increase of Factor VIII (AHF and RAg), slight decrease of Antithrombin III, and prolongation of Euglobulin Lysis Time, vs. controls (n = 48). The prevalence of “poor responders” after venous occlusion was 23% in RVO vs. 12.5% in controls. Assessment of recanalization of the occluded vein was performed after 3 months in 17 selected cases with retinal branch vein occlusion, by means of dromofluorography (i.e. quantitation of fluorescein dilution curves). Patients who showed poorer recanalization were found to belong to the group of “non responders” and had significantly lower fibrinolytic activity after venous occlusion when compared with those who recanalized. Fibrinolytic response to venous occlusion provides therefore a prognostic indication in regard to spontaneous recanalization of the occluded vein in RVO patients.

Fibrinolysis may be impaired in coronary heart disease patients. 20 coronary heart disease patients and 10 control subjects were examined for tissue-plasminogen activator activity, tissue-plasminogen activator antigen, fast tissue-plasminogen activator inhibitor and other fibrinolytic and haemostatic parameters including antigenic and functional protein C. Both patient and control groups were similar in age and smoking habits. All of these patients had a myocardial infarction between 1-3 months before this study. Assays were evaluated before and after an exercise test. Prothrombin time, activated partial thromboplastin time, protein C, plasminogen, alpha 2-antiplasmin, fibrinogen/fibrin degradation products and contact-activated fibrinolysis were similar before and after exercise in both groups. Fibrinolytic activity assayed by the euglobulin lysis time and fibrin-plate lysis methods was decreased in the patient group as compared with the control group but the difference was not significant. In basal conditions, tissue-plasminogen activator activity was defective in 50% of the coronary heart disease patients (p less than 0.01) and after exercise this percentage rose to 77% (p less than 0.01). However, tissue-plasminogen activator antigen in the coronary heart disease group was similar to that of the control group, both before and after exercise. The activity of the tissue-plasminogen activator inhibitor was persistently increased in coronary heart disease though this increase was not statistically significant. It is concluded that in coronary heart disease patients there is a defective fibrinolytic activity probably due to an increase in tissue-plasminogen activator inhibitor.

The administration of the anabolic steroid stanazolol during 7,8 days as pretreatment before thrombolytic therapy of acute or subacute arterial occlusions enhances the fibrinolytic potential significantly.On average the plasminogen increased from 101% to 133%, the euglobulin lysis time after venous stasis was shortened and the α2-antiplasmin remained constant. This effect could be favourable to prepare patients undergoing thrombolytic treatment.

The present report describes the use of crude Malayan Pit Viper (MPV) venom in the ELT test in an effort to reduce the length of monitoring time during the low-dose infusions of thrombolytic agents

Sodium salt of prostacyclin in 0.1 M Tris buffer pH 9.0 was infused intravenously at doses of 2, 5, 10, 20 and 50 ng/kg/min into six healthy men, aged 26–46 years. Begining with a dose of 5 ng/kg/min prostacyclin caused a dose-dependent inhibition of ADP-induced platelet aggregation in plasma and dissipation of circulating platelet aggregates in blood. At a dose of 20 ng/kg/min template bleeding time and concomitant blood loss were doubled. Prostacyclin did not influence partial thromboplastin time, prothrombin time and euglobulin lysis time. The anti-platelet action of prostacyclin was accompanied by a moderate fall in diastolic blood pressure, increase in heart rate, vasodilation in the regions of face, neck and palms, as well as by arterialization of venous blood. All of the pharmacological effects of prostacyclin disappeared briefly after termination of the infusion. This is the first report on antiplatelet action of prostacyclin in man and it is concluded that prostacyclin may be a valuble drug in the treatment of thromboembolic diseases.

The presence of cryoglobulin in plasma was found to interfere with the assessment of euglobulin fibrinolytic activity. Cryoglobulins co-precipitate with the isoelectrically precipitated euglobulins thereby giving rise to erroneous determinations of components of the extrinsic and intrinsic fibrinolytic systems. Cold-promoted activation of the F XII-dependent part of the intrinsic proactivator system was related to the presence of cryoglobulins. Strictly optimized procedures for the preparation of euglobulin solutions are essential in the accurate determination of euglobulin fibrinolytic activity. Resuspended euglobulins should be kept for at least 30 min at 0 degree C followed by at least 2 min at 37 degrees C in order to secure conditions yielding accurate and reproducible assays of activity in samples of patient plasma.

In an effort to evaluate some laboratory procedures and therapeutic modalities commonly employed in patients suspected of suffering from disseminated intravascular coagulation (DIC), such a state was induced in dogs by means of intravascular infusion of Thrombin. The laboratory procedures included the protamine sulfate and ethanol gelation tests, platelet count, prothrombin time, partial thromboplastin time, thrombin time, fibrinogen concentration and euglobulin lysis time. Heparin, e-aminocaproic acid, and a combination of both drugs represented the therapeutic measures used. Of the laboratory tests mentioned, the protamine sulfate test was both sensitive and specific and was therefore considered the most useful procedure in recognizing intravascular fibrin formation. As regards the other tests, a marked drop in the fibrinogen level and in the platelet count were the most consistent findings. The thrombin time tended to be markedly prolonged, whereas the euglobulin lysis time was found to undergo the least change. The effect of treatment was gauged by the extent to which the drugs employed appeared to minimize the change in results of the various tests caused by thrombin infusion. The combination of Heparin with e-aminocaproic acid seemed to be most effective in this respect, particularly with regard to the platelet count and the fibrinogen level. The Reptilase time which replaced the thrombin time in the testing of Heparin-containing blood specimens was very useful in monitoring the effect of Heparin in the prevention or treatment of thrombin-induced changes in the laboratory tests.