Marc Verstraete

A rapid enzymatic method for assay of fibrinogen fibrin polymerization time (FPT test).

Abstract A quantitative enzymatic fibrinogen assay can be based on kinetic data for the conversion of fibrinogen to fibrin in the presence of thrombin. The 2 essential conditions are: a critically low substrate range and a good quality enzyme source, whose activity should be high enough to reduce the fibrinogen proteolysis time to a constant minimum. The 2 reagents corresponding to these criteria are extensively discussed. The preparation of a standard curve, the reproducibility of results and arguments for expressing in clinical practice the fibrinogen content in terms of whole blood rather than plasma are discussed. The FPT test is also suggested as a capillary blood method for fibrinogen assay.

Outcome of Recent Thromboembolic Occlusions of Limb Arteries Treated with Streptokinase

All our patients with a recent thromboembolic occlusion of limb arteries treated with streptokinase have been reviewed retrospectively. Clearing of the main artery, as judged by arteriography or reappearance of arterial pulsations, occurred more often when treatment was started early. If only patients with an iliac, femoral, or popliteal artery occlusion are considered, those who received a lower initial dose had a significantly higher clearing rate and a significantly lower mortality than those who received a high initial dose (500,000 units of streptokinase or more). Therefore an initial standard dose of 1,200,000 units of streptokinase is no longer recommended in these conditions, and even an individually titrated initial dose of more than half a million units could be hazardous. If no neurological abnormalities were present on admission amputation was never necessary, even if clearing of the main artery did not occur. If there was sensory loss of at least part of a limb, amputation was avoided only if the pulsations returned in at least one artery of hand or foot.

Survival Time of Prothrombin and Factors VII, IX and X after Completely Synthesis Blocking Doses of Coumarin Derivatives

It is widely accepted for publication that, after the administration of coumarin drugs, all affected clotting factors do not decrease in concentration at the same rate. Factor VII is reported to decrease in concentration very rapidly and prothrombin rather slowly (Walker and Hunter, 1954; Verstraete and Vandenbroucke, 1957; Sise, Adamis and Kimball, 1957; Larrieu, 1958; Horder, 1958; Bierstedt, 1959). This concept is very important from the therapeutic point of view. There is still some disagreement as to how rapidly the activities of Factor IX, Factor X and prothrombin are reduced to the therapeutic level. The rapidity of the decrease of activity of each individual clotting factor depends not only on the degree of blocking of synthesis but also on its turnover‐rate. The turnover‐rates of the different clotting factors are still very much debated questions and several reasons may explain the discrepancies between different authors. The subject has been well reviewed by Aggeler (1961) and Hjort and Hassel‐back (1961).

ENZYMATIC CLOT DISSOLUTION IN MAN: A NEW THERAPEUTIC APPROACH.

SummaryThe fibrinolytic system in man is reviewed and the different components enhancing or inhibiting fibrinolysis (proteolysis) are discussed. The difference between fibrinogenolysis and thrombolysis is stressed and two working hypotheses for the enzymatic treatment of intravascular occlusions are formulated.In the second part of this study, the therapeutic approach inducing increased fibrino(geno)lysis in man is given. The experience with a limited group of patients totalising 26 arterial occlusions is reported. After continuous and prolonged treatment with streptokinase, restoration of arterial flow was obtained in 20 instances (77 %). In all instances the arterial occlusion was demonstrated before treatment with serial arteriograms; control arteriography after treatment was performed in 16 instances. No control series without streptokinase was established to compare the results. With a new administration scheme of streptokinase thrombolysis was obtained in all 16 recent arterial occlusions treated.

Diagnostic hints for intravascular coagulation and its treatment with heparin

SummaryThe term intravascular coagulation refers to increased consumption of coagulation factors which often leads to a haemorrhagic condition and not to intravascular thrombus formation.Four examples of intravascular coagulation which belong to four distinct categories of patients are reported. In these bleeding patients anticoagulation bv heparin perfusions was followed by improved or normalized activity of the previously depressed concentration of various components of the coagulation system.The syndrome of intravascular coagulation can be diagnosed if three of the four following criteria are met : a depression of the platelet count, of fibrinogen level and of factor V activity and the presence of activated or serum platelets.

Enhancing Blood Fibrinolytic Activity By A Niacin Compound Activation And Nonactivation

A quantitative study of the activation of the human fibrinolytic system by 3-(methyl-oxyethylamino)-2-oxypropyltheophylline nicotinate, as measured on fibrin film, was performed. A highly significant increase of plasma and euglobulin fibrinolytic activity on heated and unheated fibrin film was observed aftr a first intravenous injection of this product. After repeated injections at a 4-hour interval a fifth intravenous administration of this drug caused no renewed activation of the fibrinolytic system. No decrease of the plasminogen concentration or increase of plasma inhibitory capcity versus nicotinate activated euglobulins could explain this nonactivation. Nevertheless, a highly significant decrease of spontaneous euglobulin activity was observed at the stage of nonactivation. An original hypothesis is formulated to explain these two phenomena.

Practical Method for Thrombolytic Therapy With Streptokinase

In a previous paper we reported our clinical experience with purified streptokinase as a thrombolytic agent in patients with peripheral arterial occlusions (Verstraete et al., 1963). In that study the need of angiographic control in evaluating the success of the thrombolytic treatment was emphasized. More recently we have demonstrated that in 17 recent occlusions treated during at least 48 hours, arteriographic evidence of clot dissolution was obtained in 10 instances (59%) (Amery et al., 1963c). It is considered that a causal relationship with the administered streptokinase is at least a fair assumption. Further research was directed toward the discovery of a satisfactory parameter, whose modifications would have a definite relationship with thrombolytic success. Previous experiments have demonstrated that the fibrinolytic activity of circulating blood on heated or unheated fibrin film, the streptokinase reactivity, and the blood-fibrinogen level fail to be such parameters (Amery et al., 1963 bis). Subsequently our attention was drawn to the plasma-plasminogen level as a possible parameter whose variations could be related to thrombolysis: this molecule is not only the precursor of plasmin activity, but is also closely related to the formation of activator activity. If plasminogen variation is to be studied as a parameter, the thrombolytic effect of various degrees of streptokinase-induced plasminogen depletion should be evaluated. In this paper results obtained with nearly complete plasminogen exhaustion are presented.

Influence of coumarin treatment on plasma thromboplastin formation and heparin tolerance

Summary1.In patients under long-term anticoagulant therapy with coumarin derivatives, there is a good relationship between the results of Quick time and thromboplastin generation test, and between the results of Quick time and heparin tolerance test, under 30% of Quick value.2.Below 20–30% of Quick value, there is a true state of “intravascular” hypocoagulability by depressed “plasma thromboplastin” formation and heparin tolerance. This is in agreement with the clinical observation that the Quick value has to be below 20–30% for an efficient hypocoagulability.Zusammenfassung1.Bei Patienten, welche unter Antikoagulantien-Langzeittherapie mit Cumarinderivaten stehen, besteht eine gute Beziehung zwischen den Ergebnissen der Quick-Zeit und dem Thromboplastin-Generations-Test und zwischen den Ergebnissen der Quick-Zeit und dem Heparin-Toleranz-Test, wenn sie einen Quick-Wert unter 30% haben.2.Bei einem Quick-Wert unter 20–30% findet sich eine tatsächliche intravasculäre Hypokoagulabilität durch erniedrigte Plasma-Thromboplastin-Bildung und Heparin-Toleranz. Dies stimmt mit der klinischen Beobachtung überein, daß der Quick-Wert zur Erzielung einer wirksamen Hypokoagulabilität unter 20–30% liegen muß.

Evaluation Du Traitement Anticoagulant Prolonge Pendant 1302 Mois Chez 107 Malades

Summary107 out patients have been treated for 1302 months with dicoumarol derivatives. Half of these patients were maintained on anticoagulant therapy for more than six months.Disregarding the first month of treatment which is not included in these statistics, 73 % of the 1475 results of the Quick test are included in the therapeutic range of 10 to %.During 43,5 % of the total duration of treatment, the mean dosage of Marcoumar is 15 to 21 mg per week.Some patients are very sensitive to dicoumarol derivatives (3 to 9 mg of Marcoumar per week), others on the contrary develop a progressive resistance (42 - 54 mg Marcoumar per week).During the 1302 months of treatment, there have been 7 relapses of thrombo-embolic phenomena. In 4 of these patients, the Quick test was above the therapeutic range 12 hours after the accident; 27 minor hemorrhages have been observed during the 39.060 days of treatment (125 years) and 3 severe hemorrhages, one of which being fatal (cerebral hemorrhage).