bluuebunny/crossref_metadata_2025 huggingface dataset:
THROMBIN BINDING FRAGMENT E GENERATED DURING FIBRINOGENOLYSIS
Authors: Goodwin C A , Scully M F , Ellis V , Kakkar V V
Published: August 2018

Binding of fibrinogen by thrombin was measured by inhibition of amidolysis of S2238 and found to be 12 μM. Upon digestion of fibrinogen with plasmin (0.16ugs/mg fibrinogen) for 4 hours at 37°C, thrombin binding activity remained in the supernatants upon heat treatment. The thrombin binding activity in the dialyzed supernatant reached a maximum after two hours coinciding with maximal release of B 1-42 and 45-39 KDa chain fragments. Measured immunologically, levels of fragment E at this time were 45% of the maximum generated after 4 hours digestion. FPA levels in the dialyzed supernatant (measured by RIA and HPLC) after thrombin treatment, were zero and did not increase until 1½ hours after the beginning of digestion, reaching a maximum at 4 hours. The thrombin binding activity generated was stable to further plasmin action. Upon gel chromatography of 2 and 4 hour supernatants, thrombin binding activity coincided closely with fragment E, measured immunologically. Further purification showed the fragment to have Ki for thrombin amidolytic activity of 0.5μM. The fragment also inhibited the thrombin clotting time of plasma but did not affect fibrin monomer polymerization.The fragment was susceptible to very slow inactivation by thrombin but not arvin (though it did inhibit arvin amidolytic activity). A thrombin binding (thrombin inhibitory) fragment is therefore generated during the early stages of f ibrinogenolysis and may be the result of protection by 45 and 39 KDa A α carboxy terminus fragments since E fragments generated in later stages (in the presence of 29 and 25 KDa fragments) do not have this property. These findings may give interesting new insight into thrombin/fibrinogen interaction.
REDUCED TISSUE PLASMINOGEN ACTIVATOR RELEASE AND NORMAL PLASMINOGEN ACTIVATOR INHIBITOR LEVEL IN A FAMILY WITH RECURRENT VENOUS THROMBOSES
Authors: Petäjä J , Myllylä G , Rasi V , Vahtera E
Published: August 2018

We have studied the fibrinolytic system in one asymptomatic and six symptomatic members of a family with recurrent DVTs in three generations. Tissue plasminogen activator activity (TPA) and fast acting inhibitor of TPA (PAI) were determined using chromogenic substrate and TPA antigen with ELISA. Measurements were made at rest and after 10 and 20 minutes of venous occlusion (VO). 17 healthy subjects served as controls. The mean TPA in the seven family members was significantly lower than in controls at 10 and 20 min VO (p< 0.01).TPA was below the lowest value of controls (<1.7 U/ml) in five of the six patients with DVT at 10 min VO and remained below the range of controls in three at 20 min VO (<3.3 U/ml). The lowered TPA activity was associated with impaired release of TPA antigen (mean level at 10 min VO 12.A ng/ml, controls 19.5 ng/ml, p<0.05; at 20 min VO 18.2 ng/ml, controls 43.2 ng/ml, p<0.01). Four .patients with and one without DVT had TPA antigen below the lowest level of controls at 10 and/or 20 min VO. The level of'PAI at rest was normal in all cases (from 0.6 to 1.7 U/ml, controls from 0 to 3.7 U/ml). In accordance with low release of TPA antigen PAI was consumed less during VO in patients than in controls (mean level at 20 min VO 0.9 U/ml, controls 0.4 U/ml, p<0.05). The levels of antithrombin III, protein C, protein S, plasminogen, fibrinogen, F V, F VIII:C, vWf:Ag, fibrinopeptide A and beta-thromboglobulin were normal . Circulating anticoagulant was not found. It is concluded that impaired release of TPA, independent of PAI, is associated with DVT in this family. The pattern of inheritance suggested autosomal dominant trait.
PREGNANCY AND CONGENITAL DEFICIENCY IN ANTITHROMBIN III OR PROTEIN C
Authors: Conard J , Horellou M H , Van Dreden P , Samama M
Published: August 2018

Pregnancy as well as congenital deficiency in coagulation inhibitors are recognized as predisposing conditions to thrombosis. Thus, in women with a congenital deficiency, the risk of thrombosis associated to pregnancy is expected to be higher than in normal women (incidence of approximately 1°/..). We have investigated this risk in 16 women with congenital Antithrombin III (AT III) deficiency and in 31 with Protein C (PC) deficiency.

In the 16 women with AT III deficiency, 30 pregnancies occured 3 of them were interrupted by provoked abortions and a deep vein thrombosis (DVT) or pulmonary embolism were observed in 2 patients after abortion. Of the 27 other pregnancies, in the absence of any anticoagulant treatment, 17 were complicated by thrombosis (62 %), either during pregnancy (n = 8) or in the post-partun period (n = 9).

In the group of 31 women with PC deficiency, 82 pregnancies occured : 16 ended with a provoked abortion, followed by a DVT in one case. Out of the 66 other pregnancies, 17 (25 %) were associated with thrombosis, during pregnancy (n = 5) or in the post-partum (n = 12).

Thus, pregnancy is a situation at high risk of thrombosis in PC deficient women, and even higher in AT III deficient ones. No standardized anticoagulant prophylaxis being available, various anticoagulant treatments (mainly SC heparin) were given at various doses, started at different moments of pregnancy to 6 AT III and 3 PC deficient women : 3 and O thrombosis occured respectively.

In the post-partum, a thrombosis was observed in 1 of 4 AT III and 2 of 4 PC deficient women who received a treatment. Consequently, an efficient treatment remains to be determined.

If a pregnancy is unwanted, estroprogestogens are contra-indicated but progestogen only treatments with chlormadinone acetate, levonorgestrel or low dose of norethisterone were given to 4 AT III and 6 PC deficient women who were simultaneously receiving AVK : no recurrence of thrombosis was observed afer 1 to 3 years of treatment.
LONG-TERM MORBIDITY AFTER DEEP VEIN THROMBOSIS (DVT)
Authors: Widmer L K , Widmer M Th , Zemp E , Duckert F , Marbet G , Schmitt H E , Brandenberg E , Voëlin R
Published: August 2018

5 yr follow-up of 341 patients with special consideration of post-thrombotic syndrome (PTS) and methodolo-cigal difficulties.

INTRODUCTION

Methodological difficulties responsable for lacking unité de doctrine: (a) Acute phase: random allocation taking into account DVT of different extent; assessment of effect of treatment (b) Follow-up: drop out definition of parameters of success esp. PTS, comparison of truely comparable groups, limited information about economic aspects.

5 yr FOLLOW-UP PTS-INCIDENCE after ANTICOAGULATION (AC) or THROMBOLYSIS (TL)

Method: 341 non-randomized, consecutive patients; unilateral DVT documented by initial and control-phlebo-gramm (<14 d) , treated by AC or thrombolytic agents. 226 men, 115 women, 51.9 ± 16 yr at entry. DVT: left 193, right 148; limited 35 %, extended 65 %. Treatment effect by analysis “vein per vein”. Re-examination: “blind technique” by 2 observers; definition of PTS considering corona phlebectatica, cyanosis, edema, cirumference difference, trophic changes; Score > 10= PTS

Results:

1. Group with unchanged initial and control phlebogramm

Correlation between DVT-extent at entry and PTS-incidence (table). Consequently comparison of AC and TL must be made between subgroups with similar DVT-extent at entry.

2. Subgroups with clearance ( + ) vs. non-clearance ( - ):

Figures white PTS without ulcera, black leg ulcer
CYCLES OF REOCCLUSION-REPERFUSION DURING RT-PA TREATMENT IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION (AMI)
Authors: Barbash G I , Hod H , Rath S , Har-Zahav Y , Rabinovitz B , Seligsohn U
Published: August 2018

Early reocclusion of reperfused coronary arteries is observed in 20%-45% of AMI patients. Our protocol included: 10 mg rt-PA in bolus and continuous infusion of 50 mg in the 1st hr., 20 mg in the 2nd hr., and 10 mg during each of the following 4 hrs. Concomitantly, heparin 5,000 iu in bolus and continous infusion of 25,000 iu/24hr., and aspirin 250 mg/24hr were given. Five our of 49 patients who had clinical and electrocardiographic signs of reperfusion redeveloped severe chest pain and ST elevation while on 6 hr rt-PA and heparin. Increase of rt-PA infusion rate resulted, within 1-2 min., in resolution of chest pain and normalization of the ST elevation. 2-4 such cycles of reocclusion-reperfusion were observed in each case. In 2 out of these 5 patients stable reperfusion was achieved by administration of the 120 mg rt-PA infusion during 3.5 hr in one, and by repeated full dose protocol in the other. 2 underwent emergency percutaneous transluminal coronary angioplasty (PTCA), but kept reoccluding following several dilatations, and were eventually referred to an emergency bypass operation. 1 patient received the full protocol, but an infarction of the anterior wall was not prevented. Conceivably, there is a subset of patients with AMI in whom the present rt-PA regimen is insufficient, and higher total dose of rt-PA may be more effective.
BLEEDING RISK IN INTRAVENOUS THROMBOLYTIC TREATMENT FOR ACUTE MYOCARDIAL INFARCTION
Authors: Acar J , Vahanian A , Conard J , Michel P L , Verdy E , Bouton S , Dorent R
Published: August 2018

To evaluate the risk of bleeding (B) related to intravenous (IV) thrombolysis (TL) in acute myocardial infarction (AMI), we retrospectively studied 110 patients (pts), age<70. All were treated within 6 hours of onset of pain by streptokinase (SK) : 1.5 M IU IV in 1 hour (n = 54) ; APSAC : 30 mg IV in 5 min (n = 16) ; rt-PA IV:.75 mg/kg in 90 min (n = 30), or rt-PA plus intracoronary (IC) SK (n = 10). Pre TL, heparin (H) was administered to all pts : a 5.000 IU bolus followed by continuous infusion . In 40, aspirin (ASA) : 250 or 500 mg IV, followed by 100 mg/day orally was associated with SK (n = 9), APSAC (n = 5) or rt-PA (n =26). At the end of TL, coronary angiography was performed in 73 pts followed by PTCA in 38.

No fatal or neurological B occurred. Blood transfusion (BT) was required in 5 pts (4.5 %) : 4 on day 1 (2 hematomas at catheter site, 1 prolonged B at venous puncture site, and 1 hematemesis) and 1 on day 3 (pericardial haemorrhage needing surgery). Significant B, not requiring BT, occurred in 7 pts (6.3 %). B was often related to catheterization as 4 out 12 severe or significant B were located at the femoral puncture site. Minor ecchymo-sis and hematoma were not taken into account.

Severe B only occurred in pts treated with SK either IV (3/ 54) or IC following rt-PA (2/10), but differences with other groups were not statistically significant. The responsability of associated H is difficult to assess since all pts were similarly anticoagulated. The frequency ofB was the same in pts with (3/40) as without ASA (9/70). Fibrinogen (F) (Clauss method) was undetectable at 1-4, 6, 12, 16 hours in respectively 75%, 67%, 45%, 5% of pts with SK, which was never the case with rt-PA. Intensity of defibrination was similar with APSAC or SK.In SK pts the mean duration of severe defibrination (F<.5g/1) was 13.3 t 5.5 hrs in pts without B and 10.3 ± 5.4 hrs in pts with B. It is conceivable, that severe defibrination may contribute to the risk of B, but no relationship was found between the intensity of defibrination or its duration and B.

We conclude : 1) TL in AMI is relatively safe if contra-indications are respected 2) B is often located at the catheterization site
THROMBOLYTIC THERAPY IN ACUTE MYOCARDIAL INFARCTION: THE SCOPE IN A DISTRICT GENERAL HOSPITAL
Authors: Murray R G , Jagger J , Davies M K , Littler W A
Published: August 2018

Despite the interest in thrombolytic therapy in acute’ myocardial infarction, it has been reported.that only a small minority of patients considered for thrombloysis would be suitable. .To determine the demand for such therapy in a District General Hospital, data were collected for patients admitted with chest pain to our Coronary Care Unit over a six month period. Of 197 patients admitted with chest pain 131 patients (67%) were proven to have acute myocardial infarction. Criteria for thrombolytic therapy included presentation within six hours of the onset of symptoms, ST elevation ≥ 0.2 mV in 2 or more ECG leads and age ≤ 70 years. Sixty-seven (51%) of the 131 patients with subsequently proven acute myocardial infarction were eligible for thrombolysis. Criteria for thrombolysis were not fulfilled in 41 patients with acute myocardial infarction; 17 (13%) presented later than six hours, 15 (12%) failed to meet the ECG criteria and 9 (7%) were over 70 years. A further 12 (9%) patients were excluded for cardiogenic shock, patients had peptic ulcers, one patient sustained a recent acute myocardial infarction 2 weeks previously and data from 8 patients were lost.

These results suggest that around 50% of patients with acute myocardial infarction and 34% of all patients presenting with chest pain would be suitable for thrombolytic therapy. These data do not support the view that such treatment may only be applicable to a small number of patients with acute myocardial infarction.
REPERFUSION VENTRICULAR FIBRILLATION, CORONARY FLOW AND PHARMACOLOGIC PREVENTION
Authors: Cosin J , Hernándiz A , Caffarena T , Andrés F , Cabadés A , Diago J L
Published: August 2018

Reperfusion ventricular fibrillation (RVF) might be involved in sudden death. A reliable model for the evaluation of the prevention of RVF does not exist and published results vary greatly. To investigate: a) the relationship between coronary flow and RVF and b) pharmacologic prevention of RVF, two experimental series have been performed.

a) Ultrasonic flow-meters were implanted in the circumflex coronary artery (cca) of 19 anaesthatised open chest dogs. In each dogs several occlusion/reperfusion procedures on the cca, were performed. b) Two occlusion/reperfusion procedures of 10' on the cca were performed. In each experience the first reperfusion acted as a control of the drug's effects on the second reperfusion. The procedure was followed in 54 dogs with controls of epicardium and surface ECG, cca blood flow (n = 24) and right and left intraventricular pressures. Phentolamine (0.30 mg/kg), Quinidine (8 mg/kg), Nifedipine (0.16 mg/kg), Verapamil (0.25 mg/kg), Dipyridamole (0.40 mg/kg), were injected intravenously.

After removing the obstruction, increases in coronary flow were produced, reaching a mean maximum of 218.1% over the basal flow (p < 0.001). The RVF's appeared between 2 and 16 seconds (9.4 ± 6.8 secs) after the beginning of reperfusion, when coronary perfusion had reached 73% above the basal flow (pt 0.001) and had not reached the theoretical maximum flow. The speed of the reperfusion was no a determinating factor of the arrythmia.

Only Dipyridamole significantly prevented the incidence of RVF in the second reperfusion in regards to the first (p <. 0.01). Dipyridamole produced a greater increase in basal flow (128.4% ± 70.7) and reperfusion flow (360.5% ± 131).

Dipyridamole had a preventive effect of experimental RVF. This action may be a consequence of its effects on coronary flow.
THE ROLE OF VARIOUS HAEMOSTASIS PARAMETERS IN MONITORING FIBRINOLYSIS WITH PRO-UROKINASE/STREPTOKINASE IN TREATMENT OF MYOCARDIAL INFARCTION
Authors: Keller F , Schanzenbächer P , Dati F , Huber J , kochsiek K
Published: August 2018

The new drug pro-urokinase, a proenzyme of urokinase (scu-PA), seems to have advantages in comparison with other fibrinolytic agents. Properties like higher fibrin specifity, non-systemic activity and lower antigenity may lead to a lower rate of complications. In a pilot study 10 patients with acute myocardial infarction have been treated under angiographical control with pro-urokinase (3-9 millions IU) by i.v. application. In case of no perfusion a further administration of streptokinase was carried on. The blood samples were obtained at therapy begin and after 5, 10, 30, 60 and 120 minutes. The therapy monitoring was performed by determination of established haemostasis parameters, like fibrinogen, fibrin(ogen)-split products (FSP), a2-antiplasmin. Plasminogen and batroxobin-time. Furthermore, the diagnostic relevance of new laboratory tests for fibrinolysis, D-Dimer and thrombin-anti thrombin Ill-complex (TAT) has been investigated considering some typical follow-ups. D-Dimer were determined by latex agglutination test and TAT by enzyme immunoassay.

Generally the application of pro-urokinase in contrast to streptokinase results in minimal changes of the classic fibrinolysis parameters like fibrinogen, FSP, batroxobin-time etc. demonstrating no systemic lysis. The appearance of plasmic degradation products of cross-linked fibrin (D-Dimer) is a specific indi-cater of the release of thrombotic material. Other non-specific degradation products (fibrinogenolysis) were detected by the measurement of FSP. In some cases in which perfusion ocurred an increase of TAT followed by a rapid decrease was observed. This indicates a higher thromboplastic activity which may originate from the infarcted area producing TAT complex formation.
REDUCTION OF EARLY MORTALITY AND OF CARDIAC RUPTURE IN ACUTE TRANSMURAL MYOCARDIAL INFARCTION BY INTRAVENOUS STREPTOKINASE
Authors: Figueras J , Cortadellas J , Monasterio Y
Published: August 2018

Patients (Pts)≤ 70 years old with a first transmural AMI of ≤ 4h (164±55 min) were randomized to receive (Group I,GI n=105) or not (GII, n=102) i.v. streptokinase (SK, 840.000U in lh).Contrc ST segment elevation and at lh and 24h after admission were comparable in both groups. Coronary arteriography performed within 15 days showed a recanalization rate of 64% in GI and of 27% in GII (p<0.001)but an incidence of severe stenosis (≥90<100%) higher in GI (46 vs 22%, p<0.01).Recanalized Pts presented an earlier peak of MB creatin kinase in GI (12 vs 16h p<0.01) as well as in GII (15 vs 21h, p<0.002). The incidence of pericarditis was lower in GI (14 vs 35%, p<0.001). Although hospital mortality was comparable in the 2 groups (GI,8% vs GII,11%), early mortality, <5 days, was lower in GI (2 vs 10%, p<0.02). Sudden electromechanical dissociation was the mechanism of death in 12% of patients from GI and in 77% of those from GII and it was associated with left ventricular free wall rupture in each of the 5 autopsied cases but in none of the 5 autopsied cases who died without electromechanical dissociation During a follow-up of 20±11 months (1-36) , mortality an incidence of angina was similar in both groups but reinfarction rate was higher in GI (16 vs 1%, p<0.05).

It is concluded that: 1) In contrast with the changes in ST .segment, an early MB creatin kinase peak is a reliable marker of reperfusion; 2) i.v. SK lowers the incidence of pericarditis and of early mortality reducing the incidence of cardiac rupture; and 3) It is conceivable that early treatment of critical residual stenosis will reduce in hospital mortality and reinfarction in these Pts.
EVALUATION OF OPTIMUM STREPTOKINASE DOSAGE IN SYSTEMIC THROMBOLYTIC THERAPY FOR ACUTE MYOCARDIAL INFARCTION: A RANDOMIZED TRIAL
Authors: Balnave K , Moriarty A J , Nelson S D
Published: August 2018

The aim of this ongoing study is to determine whether or not there is a difference in terms of efficacy between lower dose and higher dose streptokinase (STK) regimens used in the systemic thrombolytic therapy of acute myocardial infarction. Acute infarction patients are randomized to low dose (600,000 I.U.) or high dose (1,500,000 I.U.) STK delivered over 30 minutes. To date 52 cases have been serially paired and analysed statistically by the method of sequential analysis. One response taken to be of primary importance as an indirect indicator of clot lysis in assessment of treatment is the time to onset of recession of the ST segment towards the isoelectric baseline on the ECG.

Another response is the ratio of fibrinogen/fibrin degradation products formed per unit of plasma fibrinogen. This is a direct measurement of plasmin activity. Treatment preference per low dose/high dose pairing is plotted in Figures 1 and 2 respectively for each response. No chart entry is made where there is no marked preference. In both instances, though statistical significance (p < 0.05) has not yet been reached, the trend is strongly in favour of low dose STK or, at a minimum, no difference between the doses. Not least, this has economic implications also.
EFFICACY OF INTRAVENOUS STREPTOKINASE IN ACUTE MYOCARDIAL INFARCTION: ACUTE AND FOLLOW UP STUDY
Authors: Lochan R , Tyagi S , Yadav B S , Rao D K M , Bhat A , Khalilullah M
Published: August 2018

The efficacy of intravenous streptokinase on recanalization of the 'infarct vessel' and its effect on left ventricular function was assessed in two groups of patients. Group I consisted of 90 consecutive patients (age 32-75 years, mean 56 years) received 500,000 units of intravenous streptokinase (STK) over 30 minutes within 6 hours of onset of acute myocardial infarction (MI). Forty-eight patients had anterior MI and forty-two had inferior MI. The control group consisted of forty survivors of acute MI comparable in age and site of infarction. In Group I, ten patients were administered STK after baseline coronary angiogram demonstrated total occlusion of infarct related coronary artery. In these patients, serial coronary angiogram were done at intervals of 30 minutes after STK infusion upto a period of 3 hours. Recanalization was seen in all cases within 75-135 minutes (average 120 minutes). Seventy-nine of STK group and all of the control group underwent selective coronary arteriography and contrast left ventriculography within 48 to 72 hours of acute MI. Recanalization of infarct related artery was demonstrated in 72 out of 79 patients (91%) in STK group while 8 (20%) in control group had spontaneous recanalization. Left ventricular ejection fraction (LVEF) was higher in STK group (58%) as compared to control group (49%). Among patients with anterior MI, LVEF was significantly better in STK compared to control group (59% Vs. 44%, p > 0.01)while in inferior MI the difference was not significant (63% Vs. 59.4%, p > 0.05) in the two groups. Follow up study in 20 STK patients at 6 months revealed a decrease in residual stenosis from 75 ± 8% to 60 ± 6% and improvement in LVEF from 59 ± 8% to 68 ± 12% (p > 0.01). In conclusion, intravenous STK in acute MI results in high rate of infarct vessel patency and improved global left ventricular function during both early and late follow up period.
COMPARATIVE FIBRINOLYTIC ACTIVITY AND THROMBOLYTIC EFFICACY OF APSAC WITH VARIOUS REGIMENS OF STREPTOKINASE IN ACUTE MYOCARDIAL INFARCTION
Authors: Col J , Col-De Beys Ch , Lavenne-Pardonge E , Moriau M , Renkin J
Published: August 2018

Fibrinolytic activity of APSAC (anisoylated plasminogen-strep-tokinase activator complex) 30 U intravenous bolus (n = 10) was compared with intravenous (IV) streptokinase (SK). 1.500.000 IU (n = 14), SK 500.000 IU (n = 6), and intracoronary SK 250.000 IU (n = 20) given for acute myocardial infarction ≤; 4 hours) and following pretreatment with heparin (10.000 IU bolus).

Plasminogen activator levels (fibrin plate) were highest for ASPAC group and correlated with the dosages of SK*. Levels also directly correlated to the duration of the activity (> 10 mm2), from 3 hours for SK 250.000 IU up to 18 hours for APSAC*.

Plasmin activity (fibrin plate) raised acutely with all regimens and was maintained (> 5 mm2) during 3 hours (SK 250.000 IU), 12 hours (SK 500.000 IU), 16 hours (SK 1.500.000 IU) and 18 hours (APSAC). Reductions of plasminogen, α2 antiplasmin and fibrinogen (Clauss) were found accordingly most depressed after APSAC and significantly less after SK 250.000 IU (p < 0.05).

The thrombolytic efficacy was judged on the patency rate assessed from post interventional (4 hours) angiogram in larger groups treated with intracoronary SK 250.000 IU : 28/35 (80 %), IV SK 500.000 IU : 29/41 (72 %), IV SK 1.500.000 : 18/25 (72 %), APSAC : 8/10 (80 %).

To conclude, fibrinolytic activity of APSAC was best compared to the intensity and duration of IV SK 1.500.000 IU. Its thrombolytic efficacy appears to be in the range of the other regimens.

* p < 0.01 rank test
INTRA-ARTERIAL UROKINASE INFUSION IN ACUTE ARTERIAL OCCLUSION OF THE LIMBS
Authors: Martínez-Brotóns F , Calderón A , Cairols M A , Reynaldo C , Capdevila J M
Published: August 2018

20 patients with acute arterial occlusion of the limbs have been treated with a continuous urokinase (UK) infusion through an intra-arterial catheter placed as close as possible to the occlusion. A loading dose of 4400 IU/Kg was given over a period of 15 minutes. Subsequently an infusion of 4400 IU/Kg per hour was administered during the following 12 hours. Blood samples were drawn pre- and post-therapy to see the state of coagulation and fibrinolysis, including α2-antiplasmin (α2-AP), plasminogen (PLG) (chromogenic methods) and fibrinogen degradation products (FDP) (Merskey) determinations.

RESULTS: There was a mild decrease of the plasma fibrinogen level from 306 ± 75 mg/lOOml previous to treatment to 195 ± 64 mg/lOOml post UK infusion and the FDP raised up to 330 ± 274 μg/ml. After terminating the UK infusion, Thrombin time ratio was 1.8 ± 0.5 and Reptilase time ratio was 2.0 ± 0.9. α2-AP activity was near 0 % in all cases and PLG fell to 33.7 ± 14.4 % of its initial concentration. Factor V activity was 63.6±19.9 %. In two out of three patients with severe ischaemia amputation was avoided. 17 patients suffered a less severe limb ischaemia. When the estimated occlusion time was less than 7 days a 60 % of complete lysis and a 20 % of partial lysis was obtained. In occlusions of more than a week the figures were 14 % and 28 % respectively. Bleeding around the insertion site of the catheter or local hematoma occurred in 5 cases.

We conclude that intra-arterial infusion of UK in acute arterial ischaemia of the limbs is an effective treatment in occlusions of less than 7 days. According to our previous experience the bleeding risk seems to be less than during systemic or local streptokinase therapy.

(All data are expressed as mean ± SD.)
FIBRINOLYTIC THERAPY WITH STREPTOKINASE AND UROKINASE IN DEEP VEIN THROMBOSIS
Authors: Trübestein G , Ludwig M , Wilgalis M , Trübestein R , Popov S
Published: August 2018

336 patients with acute 1-6 day old, and subacute, 1-3 week old deep vein thrombosis were treated with streptokinase (SK) or urokinase (UK) up to April 1, 1985. 175 patients were included in the SK group, 161 patients in the UK group. A standardized SK-heparin and the standardized UK-heparin dosage scheme with 100.000 IU SK/h or 100.000 IU UK/ h were used. In patients with acute deep vein thrombosis a complete recanalisation could be achieved in 67% and a partial recanalisation in 25% with the standardized SK scheme; a complete recanalisation could be achieved in 46%, and a partial recanalisation in 30% with the standardized UK scheme.

Since April 1, 1985 we use the ultra high SK dosage scheme, with an initial dose of 250.000 IU SK/h and a maintenance dose of 1.500.000 IU SK/h over.6 hours. So far 28 patients were treated in this way. The results show, that with an ultra high SK-dosage scheme a complete recanalisation could be achieved in 46% and a partial recanalisation in 25% in 1-6 day old deep vein thromboses. The results of both the SK schemes and the UK scheme are discussed in accordance with the haemostaseologica1 parameters.
IS IT POSSIBLE TO PREDICT THE EFFICIENCY OF THE FIBRINOLYTIC AND SURGICAL TREATMENT OF DEEP VEIN THROMBOSIS BY ULTRASOUND IMAGING AND DOPPLER ?
Authors: Elias A , Bouvier J L , Le Corff G , Serradimigni A
Published: August 2018

The sucess of the fibrinolytic or surgical treatment of venous thrombosis depends largely on how old the thrombosis is.To study the therapeutic predictibility of the ultrasonographic signs,their pretherapeutic aspects were compared to the results of the fibrinolytic treatment during 3 days or to the anatomic aspects intra-operatively. This prospective study was carried out on 21 patients presenting an isolated venous thrombosis confirmed by venography. 65 involved venous segments from the popliteal to the inferior vena cava were studied.

The following are analyzed : 1) The C.W. Doppler signal when there is a complete obstruction of the femoral iliac junction : absence or presence of flow (MEDAS0NICS BF4A 5.3MHZ).2)The morphological and dynamic aspects of the vein, the thrombus and the flow using echographic test (DIASONICS DRF 400. 10-7.5-5MHZ) were retained as predictible signs of sucessfull treatment a hypodens^homogeneous thrombus with major venous dilation (about twice the controlateral vein) where there is a total obstruction, and a free floating thrombus or even “elastic”,soft,compressible when there is a partial obstruction.The opposite signs were interpreted as predicting a therapeutic failure : a dense heterogeneous adherent and hard thrombus.

The criteria for thrombolysis efficiency is the total disappearance of the thrombus when there was a partial obstruction,or a recanalization (>50%)where there was a complete occlusion.

The ultrasonographic predictible signs compared with the effective results are indicated in the following tables.

Ultrasonography enables most cases tne recognition or a “recent” thrombus from an “old” one and allows talcing thus a cal-lated risk. If the evaluation of the echotexture of the thrombus is subjective and technique dependant, and if an objective measurement of the density distribution insight the clot as reported is preferable, a combined study of the other ultrasonographic parameters seems to be essential.
THE EFFECT OF HEPARIN ON THERAPEUTIC SUCCESS OF LOCAL STREPTOKINASE TREATMENT OF PERIPHERAL ARTERIAL OCCLUSIONS
Authors: Poredoš P , Videčnik V
Published: August 2018

In some cases the thrombolytic treatment is not successfull inspite the fact, that lysis of the thrombus occured. This could be the consequence of ascending thrombosis and early reocclusion due to prevailing thrombogenic potential (decreased floow endothelial damage, presence of intraarterial catheter). The aim of the present study was to established if simultaneous heparin administration improves local thrombolytic treatment of arterial occlusions. The study encompassed three groups of patients with acute and subacute arterial occlusions of the lower limbs. In the first group there were 31 patients treated with streptokinase only (SK group). The second group (33 patients) received heparin (450 IU/hour) simultaneously with SK through the proximal opening of the coaxial catheter. Heparin so poured over the distal part of the catheter (SK-H group). In patients of the third group (22 patients) treated as SK-H group, thrombi were before treatment enriched with 7,5 ug of plasminogen (SK-H-Plg group). Patients of all three groups received SK as continuous intraarterial infusion (3750 IU/hour) until recanalisation occured but at most for 3 days. The results of the treatment are shown in the table.

Heparin significantly reduced the number of ascending thrombosis along the intraarterial catheter (p<0,05). Although the difference between the number of successfully and unsuccessfully treated patients of the three groups was not statistically significant (the reason for this were probably too small groups) the results suggested that heparin contributed to greater therapeutic success.
HEPARIN AND ACETYLSALICYLIC ACID (ASA) 75 MG/DAY IN UNSTABLE CORONARY ARTERY DISEASE - EFFECTS ON PLATELET REACTIVITY
Authors: Wallentin Lars , Nyman Ingyar , Berglund ULF , Swahn Eva
Published: August 2018

In unstable coronary artery disease (UCAD), i.e. unstable angina pectoris (UAP) or non-Q-myocardial infarction (NMI), treatment with heparin or ASA have given encouraging results. The present study attempts to verify the effects of i.v. heparin (5 days) and to evaluate the utility of ASA 75 mg/day (one year). Patients, admitted because of chest pain, who either develops NMI or signs of ischemia in resting or exercise ECG.s are included. Within 72 hours patients are randomized to obtain Heparin+ASA, Heparin+Placebo, Placebo + ASA or Placebo+Placebo . Platelet reactivity is studied in vitro in platelet rich plasma (PRP) in a subgroup of patients.

The aggregation response is studied after addition of collagen and ADP and after preincubation with prostacyclin before aggregation with ADP. The figures present results from 85 randomized patients tested before, 5 days, one month and one year after start of therapy.

Conclusion: In patients with unstable CAD long term treatment with ASA 75 mg/day inhibits collagen induced platelet aggregation and hampers the ADP response. I.v. heparin tends to raise platelet reactivity and reduce the inhibitory effect of prostacyclin. Heparin induced platelet activation is reduced by simultaneous ASA therapy.
THROMBOLYTIC THERAPY IN UNSTABLE ANGINA: EFFECTS OF SHORT TERM HIGH DOSE INTRAVENOUS UROKINASE
Authors: Foresti A , Ambrosini F , Gentile G , Repetto S , Lotto A
Published: August 2018

20 Pts with U.A. admitted to CCU within 3 hours from onset of pain and ECG evidence of acute ischemia were studied. In 10 of them (UK Group) a bolus of high dose i.v. Urokinase (1500000 U) was added to conventional therapy -nitrates, ca-antagonist, heparin i.v.-. In the control group (C) no fibrinolytic drug was administered. Remission of pain was observed in 5/10 pts in UK and in 3/10 in C group in the first 3 hours. In the same time ECG markers of ischemia were virtually suppressed in 9/10 in UK and in 5/10 pts in C group. IIo pts in both groups had patological Q waves or CK elevation greater than twice normal, but in the first week 4/10 in UK and 5/10 in C group experienced one or more new acute ische mic attacks. Coronary angiography was performed:

During follow-up (3 months) revascularization procedures (PTCA or CABPS) were performed in 5/10 pts in UK and in 5/10 pts in C groups.

This study enphasizes the lack of difference from the anatomic point of view and the clinical course between the two groups of pts; nevertheless systemic fibrinoly sis performed in pts with U.A. may lead to an improvement of “very short term morbidity” and might be consi dered (as in acute myocardial infarction) a useful and safe treatment to offer these patients, often with impending M.I. to further and rapid revascularization procedures.
CHANGES IN t-PA ACTIVITY AND INHIBITION AS PART OF THE ACUTE PHASE REACTION IN ACUTE MYOCARDIAL INFARCTION
Authors: Gram J , Kluft C , Jespersen J
Published: August 2018

Acute myocardial infarction (AMI) is accompanied by sequential fluctuations in several plasma proteins indicative of an acute phase reaction. Global screening tests (ECLT and WBCLT) have revealed temporary depression of systemic fibrinolysis. However, such tests do not allow definite conclusions regarding the specific variables involved.

In a prospective study of 34 patients with AMI we determined selected variables involved in fibrinolysis, and in addition we investigated whether any fluctuation was related to the development of leg vein thrombosis (isotope-technique) or due to AMI. Blood samples were collected on days 1,2,4,6,8 after admission and eight weeks (recovery) after discharge. Euglobulin fibrinolytic activity was determined on fibrin plates. The measured activity was lower in the initial acute period (≤ 48 h after AMI) than in the recovery period (p<0.05). The intrinsic fibrinolytic proactivators (representing more than 95% of the total activator potential of plasma) did not change during the period of study. Levels in the euglobulins of C1-inactivator (the main inhibitor of the intrinsic system) were constant during the first 48 hours. This suggests that the observed reduction represents t-PA activity and this was verified by specific assay of t-PA. The t-PA inhibition capacity in plasma was elevated in the initial acute period compared to the recovery period (week 8; p<0.05). C-reactive protein and fibrinogen followed another pattern with the highest plasma level at day 4 and day 6, respectively. Plasma levels of C1-inactivator increased slowly with a peak at day 8. There was no difference of the determined variables between the DVT negative and positive group, suggesting that the observed changes were due to myocardial injury. Our findings show that components of the fibrinolytic system take part in the acute phase reaction following AMI, and that this involves a brief, initial period of reduced fibrinolytic potential (<48h). The initial, high levels of t-PA inhibition deserve consideration in regard to the institution of thrombolytic therapy with t-PA. (Undertaken within the frame of ECAT).
INVERSE CORRELATIONS BETWEEN PLASMA BETA-THROMBOGLOBULIN LEVEL AND: (1) TIME FROM ONSET OF ACUTE MYOCARDIAL INFARCTION (2) MEAN TIME TO CLOT LYSIS FOLLOWING SYSTEMIC STREPTOKINASE
Authors: Nelson S D , Moriarty A J , McLoughlin M , Balnave K
Published: August 2018

The platelet specific protein, beta-thromboglobulin (²-TG) is released into the circulation when blood platelets undergo the release reaction as in platelet aggregation and clotting. This paper describes a study of a cohort of patients (N = 40) in which ²-TG was serially assayed by a radioimmunassay technique at various times from the onset of acute myocardial infarction.

It shows a negative correlation (R = -0.76, p = 0.01) between initial ²-TG level and time elapsed since the onset of symptoms. Furthermore, patients fell into two groups - those with high initial or rising levels, and those in whom the levels were not elevated and did not rise. Both groups underwent thrombolytic therapy with intravenous streptokinase, the former manifesting significantly earlier ECG evidence of re-perfusion. Respective mean lysis times and standard errors of the mean (hours) were 0.798 (0.139) and 3.490 (0.498) with p = 0.001 on t-testing. Clearly when the clotting process is well established it is much more difficult to lyse the clot. ²-TG is a marker for the age of the clot in that it reflects the platelet secretion in vivo that accompanies the early stages of clot formation.

We conclude that ²-TG assay is not purely an esoteric research technique but has everyday clinical application in differentiating between early streptokinase-induces lysis, when some at-risk myocardium is still viable, and later spontaneous recanalization. Angiography cannot make this distinction.
NEUTROPHIL ELASTASE IS A MARKER OF NEUTROPHIL ACTIVATION IN ACUTE MYOCARDIAL INFARCTION
Authors: Bell D , Jackson M , MacRae C , Muir A L , Dawes J
Published: August 2018

Elastase is released from human neutrophils as a result of active secretion, phagocytosis or cell lysis. It is a broad-spectrum protease which not only hydrolyses the major components of tissue matrix, but can also affect platelet aggregation, coagulation and fibrinolysis. Neutrophils localise at the site of myocardial infarction and have been implicated in subsequent cell damage. A radioimmunoassay was developed which detects elastase complexed to its inhibitors α2- antitrypsin and α2-macroglobulin as wen as the free enzyme. Plasma concentrations of elastase in 31 healthy controls were 21.3 ± 13.8 ng/ml, and did not differ significantly from those in 22 patients with stable angina (23.6 ± 8.6 ng/nl). In 19 patients with myocardial infarction, however, plasma elastase levels rose to a peak within 48 hours of infarct which was significantly higher than normal levels (95.1 < 83.7; P < 0.001), and then declined. Correction of the data for neutrophil count did not affect the significance of the observed differences. Measurement of whole blood elastase reflected the neutrophil count and was not otherwise informative. Thus, neutrophils are activated after myocardial infarction and release sufficient elastase for it to be detected systemically. This may extend tissue damage and affect coagulation and fibrinolysis at the site of infarction.
PREACTIVATION AND INHIBITION OF EXTRINSIC COAGULATION PATHWAY IN ACUTE CORONARY DISEASE
Authors: Sandset P M , Sirnes P A , Abildgaard U , Petterson M
Published: August 2018

It has recently been shown that plasma from individuals with a high risk score for developing AMI shows an abnormal depression of factor VII (EVII) coagulant activity after treatment with phospholipase C (PLC), (Dalaker, K.& Prydz, H., Br . J . Haematol. 61,315, 1985) revealing the presence of “preactivated” FVII in complex with lipid. We have studied this phenomenon in patients in a coronary unit, by serial determinations of Normotest (NT) + PLC pretreatment (which correlates with FVII clotting) assay ± PLC) and EVII amidolytic assay (EVIIram) (OswaldsBn et al., Tromb.Haemostas. 54,26,1985). The newly described inhibitor of FVII-Tissue thromboplastin (EPI) was also measured. Mean patient values day 2 are listed:

More than 20% depression of NT by PLC treatment was found in 2/14 controls, 9/19 AMI patients, 3/17 angina patients and 2/15 patients with other heart disease. The EVII:am values correlated better with NT (r = 0.81) than with PLC+NT (r=0.62). It has been suggested that FVII:am correlates with the molar concentration of FVII. If correct, our data precludes two chain FVII as contributing much to preactivation. EPI values were in the high normal range for all three groups of heart patients. The individual variation in EPI values was great, particularly in AMI patients. Apparently, EPI did not correlate to any of the FVII assays. Three patients with more then 50% reduced NT after PLC had EPI values 67, 149, and 130%. In conclusion, lipid activation was frequent in AMI patients, and was not related to EPI activity.
RELEVANCE OF FREE PLATELET COUNT RATIO (PCR) TO CIRCULATING PLATELET AGGREGATES (CPA) AND TO THE RELEASE OF B-THROMBOGLOBULIN(β-tg) INDUCED BY EXERCICE IN PATIENTS WITH CORONARY HEART DISEASE (CHD). EFFECTS OF TICLOPIDINE (T) TREATMENT
Authors: David J L , Legrand V , Kulbertus H E
Published: August 2018

CPA are considered as a possible cause of blood flow impairment and as a risk factor of sudden death in patients with CHD. The relevance of a low PCR to the presence of CPA is still debated. Indeed in a critical and well designed evaluation of this index, Sanibaldi et al.(1986) have shown that PCR obtained by counting free platelets in diluted whole blood was not lowered in patients with “thrombotic tendency”. They suggested that low CPA reported in other clinical studies may result from an artifact of blood sampling or from ex-vivo procedures.

In order to reevalute the meaning of a low PCR, selected patients with CHD have been submitted to an exercice resulting in platelet stimulation. Free platelets were counted, whole blood and plasma β-tg were simultaneously determined by RIA after careful blood sampling performed before the exercice, at its end and 30 min later. Patients were previously treated by Placebo (P)or by T 500 mg per day given in a cross-over double blind manner.

It was shown that : 1) after P treatment, PCR was lowered and β-tg was increased, both significantly, at the end of exercice; 30 min later, PCR was normalized whereas β-tg remained high presumably because β-tg is not cleared from plasma within 30 min. 2) T treatment significantly inhibited both platelet responses.

In conclusion, when platelets are submitted to systemic and sustained stimuli occurring during exercice stress, lowered PCR reflects the presence of circulating platelet aggregates which can be dispersed ex-vivo by EDTA. In these conditions, the meaning of this index is strongly confirmed by the simultaneous release of βtg. T treatment significantly reduces platelet reactivity to exer cice stress and may reduce the effects of platelet aggregation and release on compromised microcirculation.
EPIDEMIOLOGICAL ASPECTS OF ANTITHROMBIN-III, SELENIUM AND LIPOPROTEIN COMPONENTS IN CORONARY DISEASE
Authors: Aursnes I , Smith P , Arnesen H
Published: August 2018

The known risk factors for coronary disease can only “explain” a proportion of the incidence of the disease. Looking for supplementary risk factors we thus selected for detailed study both a group of patients with normal levels of risk factors (normo-tensives, non-smokers with normal serum cholesterol) and a group with high conventional risk factors, comparing both groups with an age and sex matched control group. Subgroups were formed by individuals aged below (young) and above (old) 60 years.

Total- and HDL-cholesterol, apo-lipoproteins A-I and B and triglycerides showed co-variation with each others and with fatty acids in serum. With "factor analysis" seven "factors" were extracted and the factor scores for sub-groups were calculated. Two factors discriminated between young, high risk patients and controls. One was a positive risk factor and the other a negative one. The factors may be dependent on the existence of two unknown sub-groups of serum lipoproteins which were characterized by high concentrations of certain fatty acids.

Coronary patients were found to have 9.1% higher antithrombin-III (AT-III) activity in their plasma than controls (p=0.037). Plasma selenium levels were slightly less in patients than in controls. There was a slight, but significant (r = 0.29 , p = 0.01 5) positive correlation between selenium and AT-III concentrations. Multivariate statistical anlysis indicated that selenium was significantly negatively correlated with disease.

It is concluded that antithrombin-III tend to be high and that plasma selenium levels are relatively sub-normal in some coronary patients. It is also suggested that fatty acid analysis may be useful in the characterization of lipoproteins that are involved in the development of atherosclerosis.
THE EFFECT OF HEPARIN AND FIBRIN ON THE ENZYMATIC EFFICIENCIES OF THROMBOLYTICS IN_ VITRO
Authors: Fears R
Published: August 2018

Selective fibrinolysis may be achieved physiologically by the binding of both endogenous plasminogen activator (t-PA) and plasminogen to fibrin. It has been suggested that t-PA may also exhibit fibrin-selectivity when used at therapeutic doses for acute myocardial infarction whereas the other principal thrombo-lytics, urokinase (UK) and streptokinase (SK).plasminogen, are not bound. However, in the present kinetic studies it was found that plasminogen activation by SK.lys-plasminogen was enhanced by soluble fibrin (the effect mainly on Km), the affinity of binding to fibrin was similar to t-PA (dissociation constant approx. 100 nM) and the reaction mechanism appeared similar (Rapid Equilibrium Ordered Bireactant). When evaluating the in vivo significance of fibrin-enhancement, variation in the form of the substrate (i.e., glu1- or lys77-forms) and the contribution of heparin must also be considered. Both t-PA and UK activities were potentiated by heparin (the effect mainly on Km) but in the presence of fibrin the effect of heparin on t-PA was attenuated; SK.plasminogen enzymatic activity was unaffected by heparin. Thus, in the presence of heparin, in vivo, there may be an exacerbation of the systemic action of t-PA. As differences in fibrin binding and enhancement between t-PA and intact SK.plasminogen - the activator that is produced from APSAC (Eminase) - are relative rather than absolute, therapeutic activity will be influenced more by the dosage regimen and the clearance rate.