[Antithrombotic therapy in patients with mechanical valve prostheses]. / Traitement antithrombotique chez le porteur de prothèse valvulaire mécanique.

Mechanical valvular prostheses have the advantage of longevity but carry a risk of thrombosis which is itself dependent on many haemodynamic, haemostatic and parietal factors. Antithrombotic therapy in patients with mechanical valvular prostheses is based on vitamin-K antagonists, the optimal dosage of which should reflect the type and location of the prosthesis and the underlying pathology. The patient with a mechanical valvular prosthesis treated by oral anticoagulation must be fully informed and regularly followed up. Special situations: extracardiac surgery, dental extraction, gastrointestinal endoscopy, require specific, well established management.

Mechanical cardiac valve thrombosis. Is fibrinolysis justified?

BACKGROUND: Thrombosis is a serious complication of heart valve replacement, and management is often difficult. In recent years, thrombolytic therapy has been used as the primary technique by some investigators. METHODS AND RESULTS: Sixty-four consecutive patients presenting with 75 instances of prosthetic heart valve thrombosis (41 mitral, 33 aortic, one tricuspid) were treated with fibrinolytic agents. Obstructed prosthetic valves comprised 39 tilting disc and 36 bileaflet valves. The time interval between valve replacement and obstruction ranged from 15 days to 192 months (mean, 38 months). Fibrinolytic agents used were streptokinase (42 patients), urokinase (27 patients), or recombinant tissue-type plasminogen activator (six patients). Immediate results of fibrinolytic treatment were 1) full success after one or several consecutive fibrinolytic regimens in 55 cases (73%), 2) incomplete improvement in two cases, and 3) failure in 18 cases, leading to an emergency surgery in nine cases. Nine patients died (four strokes, four cardiac arrests, one hemorrhage). Only one severe hemorrhagic complication was observed, but 11 cases of embolism occurred during fibrinolytic treatment (14.6%) (four major cerebral embolisms with death). The immediate efficacy was better for thrombosed aortic prosthesis than with the mitral prosthesis (85% versus 63%). CONCLUSIONS: Fibrinolytic treatment appears to be an attractive nonsurgical alternative for prosthetic heart valve thrombosis, but because of the risk of cerebral embolism, its use should be reserved for tricuspid valve thrombosis or critically ill patients with mitral or aortic valve thrombosis. The use of a fibrinolytic agent in cases of small, nonobstructive paravalvular thrombosis demonstrated with transesophageal echocardiography needs further studies.

[Recurrent thrombosis of an aortic valve prosthesis in a pregnant woman. Treatment with urokinase]. / Thrombose récidivante d'une prothèse valvulaire aortique chez une femme enceinte. Traitement par urokinase.

A 36 year old woman developed two thromboses on aortic valve prosthesis. The first thrombus at the 14th week of pregnancy was treated with urokinase (2,000 U/kg/h) plus heparin (700-1,000 U/h) over 24 hours and normal wing kinetics were obtained. The second thrombus developed at the 36 th week of pregnancy when the patient was receiving calciparin, and only transient improvement was obtained with similar doses of urokinase hourly over 72 hours. Progressive worsening resulted in higher doses (4,000 U/kg/h) being given without heparin and the thrombus then resolved. The use of urokinase for the first time in this indication allowed therefore, on two occasions and without hemorrhagic complications the cure of this recurrent thrombosis on aortic prosthesis, and the birth, by caesarean, of a healthy baby.

Hemorheological changes in elderly subjects--effect of pentosan polysulfate and possible role of leucocyte arachidonic acid metabolism.

The effects of pentosan polysulfate (PPS) on various hemorheological parameters were studied in a group of very elderly subjects in good general health. Alterations in blood viscosity and filterability were detected in these patients, without any concomitant changes in factors which are known to affect these parameters: notably hematocrit, fibrinogen and plasma lipid levels. The hemorheological abnormalities were considerably improved by twice daily treatment with 50 mg of PPS (i.m.). Apart from its anticoagulant activity, PPS has been shown to have an anti-inflammatory action. We were interested to investigate its effects on metabolism of exogenous arachidonic acid (AA) by both platelets and leucocytes. It is becoming increasingly recognized that metabolites of AA via the 5 LO pathway appear to play a role in inflammatory processes. In this study, PPS was found to inhibit leucocyte 5 LO activity. Reduction in the levels of these metabolites may therefore have an effect on whole blood rheology.

[Hemorheologic study of different forms of vasomotor acrosyndromes]. / Etude hémorhéologique au cours des différentes formes d'acrosyndromes vasomoteurs.

Hemorheologic disorders are a frequent finding in circulating blood during vascular diseases (arterial disease of lower limb, cerebrovascular accidents). They participate in thrombogenesis and tissue ischemia production, and also in microcirculatory disturbances as shown by behavior in microvessels of red cells with decreased hereditary deformability (sickle cell anemia). Active alterations in erythrocyte rheology have also been demonstrated during vascular diseases in relation to inflammation: cell-protein inflammatory reaction, action of leukocytes. Therapy should be adapted for these microcirculatory disorders by suitable specific clinical trials.

[Microcirculatory consequences of hemorheologic disorders]. / Conséquences microcirculatoires des perturbations hémorhéologiques.

Pronounced and direct relations exist between hemorheologic blood disease and microcirculation in disorders of red blood cells. Within this framework, sickle cell anemia appears as the typical hemorheologic disease clearly illustrating the hemorheology-microcirculation-thrombosis relation. In acquired diseases, particularly those vascular disorders most concerned, the relation is indirect: the hemorheologic disorder predisposes to plasma and cell occlusion of the vascular lumen, probably labile and pre-thrombotic but influencing microcirculation blood flow. The role of endothelial cells and vascular wall in the appearance and localization of this phenomenon is unknown at present. Pharmacologic interest is considerable in both cases, with emphasis on the use of drugs of both cellular but also intercellular and parietal activity.

Factors influencing in vitro sieving of blood in cerebrovascular accidents. Clinical significance and therapeutic strategy.

A haemorheological analysis with measured blood filterability was carried out on 179 patients with cerebrovascular accidents. Reduced blood filterability appeared to be related to the clinical condition: time variation (two phase course), influence of complications and of fatal prognosis. The underlying mechanism of the haemorheological disorders involved three groups of factors: quantitative and qualitative abnormalities of plasma proteins, red cells disturbances and white cells activation, leading to both local and general hyperviscosity, producing a prothrombotic state and a defective microcirculation. The haemorheological treatments are of value to the patients although the relationship between hemodilution and the filterability remains to be exactly defined, as well as a better understanding of the action of the drugs.

[Hemodynamic course during fibrinolysis in severe pulmonary embolism]. / Evolution hémodynamique au cours des fibrinolyses de l'embolie pulmonaire grave.

Seventy seven cases of severe pulmonary embolism (Miller index greater than 13 points) including 61 acute (under 5 days) and 16 subacute episodes, underwent continuous haemodynamic monitoring during treatment with either urokinase 2 000 U/kg/h for 24 hours with heparin (Group I: 18 patients), or urokinase 4 500 U/kg/h for 12 hours without heparin (Group II: 47 patients), or with streptokinase 2 00 000 U over 10 hours (Group III: 12 patients). Efficacy was defined as greater than 20% improvement of Miller index at control angiography after 48 hours (Group I: 10 patients, Group II: 31 patients, Group III: 8 patients). In the 49 patients (63%) with good results, the Miller index fell by about 50% with a significant increase in cardiac index (20%) from the 12th hour. There was a concomitant fall in pulmonary systolic arterial pressure (35%). In the 28 patients (37%) with partial improvement a 20% increase in cardiac index and an 18% fall in pulmonary systolic arterial pressure were observed only in the high dose urokinase group, despite incomplete pulmonary revascularisation demonstrating the vasodilator effect of this protocol. Fibrinolysis was repeated in the patients with incomplete results or a Miller index of over 13 points, leading to improvement in 78% of patients. Accelerated lysis of pulmonary embolism leads to rapid normalisation of haemodynamic parameters and improves the prognosis of massive pulmonary embolism by reducing the number of recurrences and the mortality rate (4%).

Changes in blood filterability in cerebrovascular accidents.

Patients with acute cerebrovascular accidents (CVA) exhibit pathological changes of various hemorheological factors in dependence of severity of the clinical condition. Increase in hematocrit, rise in blood viscosity and impairment of red cell deformability together with increase in plasma proteins, especially of fibrinogen and inflammatory proteins, leukocytosis, hemoconcentration and presence of various risk factors affect cerebral blood flow on microcirculatory level and produce a prethrombotic situation. Deteriorated blood filterability may be regarded as an indicator of severity and prognosis of CVA. Studies of red cell filterability in 100 patients with severe recent CVA and 52 patients with moderate CVA showed in comparison to matching controls a progressing deterioration of filtration up to day 8 whereafter an improvement started in recovering patients. Febrile patients presented clearly more filterability deterioration than non-febrile subjects. Hyperviscosity states seem to respond best to normovolemic hemodilution, whereas red cell deformability and aggregation can be approached by various drugs such as pentoxifylline, piracetam etc. Follow up of blood filtration in CVA patients is of significant prognostic value.

[Fibrinolytic treatment of 28 thromboses of valve prostheses. A biological study]. / Traitement fibrinolytique de 28 thromboses de prothèses valvulaires. Etude biologique.

We carried out a series of laboratory investigation in 28 patients with prosthetic valve thrombosis (17 mitral and 11 aortic). The diagnosis was confirmed by TM and bidimensional echocardiograms and by cineradiography. The treatment consisted of UK (4,500 IU/kg/hour for 12 hours) and/or SK (initial loading dose of 500,000 IU, then 150,000 IU/hour for 10 hours). We measured fibrinogen, degradation products of fibrinogen-fibrin, plasminogen and antiplasmin. Two dimensional electrophoresis against anti-fibrinogen, anti-fragment-D and anti-fragment-E were employed for some samples. After thrombolytic therapy (SK: 18; UK: 7; SK-UK: 2; UK-SK: 1) complete clot removal was obtained in 21 cases (successful: group S), partial removal in 4 cases (improvement: group A) and failure in 3 cases (failure: group E). 3 patients died. Biochemical effects can be seen in group S and in group A. There were no changes in group E.

[Thrombophlebitis and pulmonary embolism in congenital factor XII deficiency]. / Thrombophlébites et embolies pulmonaires lors d'un déficit congénital en facteur XII.

The case of a young man hospitalised for bilateral lower limb deep vein thrombosis is reported. None of the usual causes were found after systematic wide-ranging investigation. The only abnormality on admission was a spontaneous increase in the cephalin-kaolin time to 65 seconds compared to a control time of 40 seconds. Measurements of the clotting factors showed a moderate and isolated deficiency in factor XII (30 p. 100), also present in a brother (50 p. 100) and a sister (42.5 p. 100). Fibrinolytic therapy was administered : an initial course of Streptokinase was followed by extension of a left femoral vein thrombosis and pulmonary embolism. Two courses of Urokinase were given with an eight day interval without significantly improving the venous circulation. This case is an example of thrombogenic disease due to a deficiency of a clotting factor resulting in non-activation of physiological fibrinolysis.

[Efficacy and value of fibrinolytic agents in chronic proximal venous thrombosis of the lower limbs]. / Efficacité et intérêt des fibrinolytiques dans les thromboses veineuses anciennes proximales des membres inférieurs.

Forty patients (mean age = 56 +/- 17 years) hospitalized for proximal venous thrombosis of the lower limbs of over 7 days duration were treated with fibrinolytic drugs: streptokinase (SK) 28 cases, urokinase (UK) 12 cases. The efficacy of fibrinolytic therapy was assessed by phlebography before and 4.5 +/- 2 days after onset of treatment. A phlebographic score based on Marder's method was used to quantify the thrombosis. The repermeabilisation of venous branches was also noted. The results show an overall efficacy of fibrinolytic drugs: total lysis was observed in 6 patients and partial thrombolysis in 18 patients. The overall reduction of the phlebographic score was -2.8 +/- 3.9, and the rate of repermeabilisation of the femoral veins was over 50%. Streptokinase seemed to be the most effective drug. Better results were obtained when the thrombosis was treated early and was proximally situated, but good results were also observed in cases of total thrombosis with a floating thrombus. Effective fibrinolysis was observed in thromboses of up to 3 months duration. There was no correlation between biological efficacy and clinical symptoms. In conclusion, fibrinolytic drugs are partially effective in semi-recent or chronic venous thrombosis and their usefulness should not be overlooked, especially in cases of persistent thrombosis of the femoral veins.

[Fibrinolytic treatment of valve thrombosis. Apropos of 16 cases]. / Traitement fibrinolytique des thromboses valvulaires. A propos de 16 cas.

Sixteen cases of prosthetic valve thrombosis (9 mitral, 5 aortic), occurring in 14 patients, were treated by fibrinolysis. All were disc prostheses. The clinical state of the patients was very poor in 11 of the 16 cases with pulmonary oedema, low output and arrhythmias, but less dramatic in the 5 others who presented with thromboembolism and left ventricular failure. The diagnosis was made by echocardiography (9 cases), radio-cinema of the valve (9 cases) and/or angiography (4 cases). The therapy comprised Urokinase (UK) 4,500 U/kg/hour (6 cases) of Streptokinase (SK) 2,000,000 U in 10 hours (7 cases) or SK and UK at equal doses (3 cases). The outcome was assessed clinically, echocardiographically and radiologically. There were 11 definite successes, 2 partial improvements requiring surgical revision, 2 apparent successes but with massive recurrence at the 7th and 10th days, and 1 failure. Although the biological activity of SK is greater than that of UK, the clinical results were comparable with both fibrinolytic agents. Four patients had regressive embolic episodes during lysis of the valvular thrombosis. As fibrinolytic therapy was effective in 70 p. 100 of patients in this series, it could provide an acceptable alternative to surgery, especially in patients who would be poor operative risks. The management of patients after successful fibrinolysis remains divided between intensive medical follow-up or prosthetic valve replacement.

Filterability and cerebro-vascular thrombosis. Study on the mechanism.

The filterability of red cells was altered in 100 patients with CVA. This disorder appeared to be correlated with risk factors and haemostatic disturbances. The mechanism which links thrombosis with the filterability disorder, mainly depended upon a plasmatic factor. This factor disappeared after the red cells were carefully washed. The hypothesis of products originating from the thrombotic areas amd vasculo-endothelial lesions (mainly fibrin-related products) was supported.