Heparin-associated thrombocytopenia treatment with low molecular weight heparin.

Eight patients with heparin associated thrombocytopenia (HAT) were treated by a low molecular weight heparin derivative (LMW). Biological and clinical improvement occurred in all patients. This efficiency confirms the antithrombotic activity of LMW and allows its use in patients with HAT.

Adjusted versus fixed doses of the low-molecular-weight heparin fragmin in the treatment of deep vein thrombosis. Fragmin-Study Group.

Treatment monitoring based on a laboratory parameter increases the efficacy and safety of standard heparin therapy, but it is not known if this also applies to low-molecular-weight heparin (LMWH) therapy of acute deep vein thrombosis (DVT). In a prospective randomized trial involving 122 consecutive patients, group A (58 patients) received a weight adjusted dose of Fragmin (100 IU/kg) subcutaneously twice a day throughout the treatment period (10 days +/- 1), while in group B (64 patients) the dosage was based on the results of an anti factor Xa (anti Xa) amidolytic assay to obtain a target concentration from 0.5 to 1 IU/ml. AntiXa and antithrombin activities were also measured retrospectively on frozen plasma from all patients. The two regimens were comparable in terms of hemorrhagic complications (4 in group A and 3 in group B). Bilateral ascending phlebography was performed before inclusion and at the end of LMWH treatment. Treatment efficacy, based on Marder's score, did not differ between the two groups (p = 0.3). Dosage adjustment to between 0.5 to 1 IU anti-Xa/ml does not therefore appear to improve the efficacy or safety of LMWH treatment. However, correlations between the change in Marder's score and both anti-Xa (p < 0.001) and antithrombin activity (p < 0.001) were observed, suggesting a relationship between the degree of FXa or thrombin inhibition and antithrombotic activity.

Circulating activities during constant infusion of heparin or a low molecular weight derivative (enoxaparine): failure to demonstrate any circadian variations.

We compared in six patients successively treated with an unfractionated heparin (UFH) and a low molecular weight heparin (LMWH) the variations in plasma anti-Xa activity, measured in a chromogenic assay, during a 36 h constant infusion. The values varied in a wider range during UHF infusion, but remained in the therapeutic range except once in one patient. No circadian rhythm could be demonstrated in our six patients. LMWH infusion yielded very constant anti-Xa circulating activities. In both cases, there were no significant modifications of three proteins with high heparin affinity (antithrombin III, heparin cofactor II, histidine-rich glycoprotein). Our results suggest that the circadian rhythm of the biological activities previously observed in patients treated with constant heparin infusion using clotting method is due to other factors than heparin itself.

Heparin cofactor II: an acute phase reactant in patients with deep vein thrombosis.

In human plasma, heparin cofactor II (HCII) is a thrombin inhibitor which displays similarities with antithrombin III (ATIII). As previously reported for hereditary ATIII deficiency, cases of recurrent thrombosis were reported in patients with hereditary HCII deficiency. Here, plasma HCII activity was studied in 372 patients with a history of thrombosis, classified according to their anticoagulant therapy. The mean plasma HCII level was significantly higher in patients with acute deep vein thrombosis (DVT) under heparin therapy than in patients with a history of thrombosis, who were studied more than 3 months after the acute event, and were either on, or had been on, oral anticoagulant therapy. HCII and fibrinogen were significantly correlated in all three groups of patients. These results were strengthened by those of a follow-up study in 23 patients with acute DVT. Changes in plasma HCII activity paralleled those of fibrinogen. This suggests that HCII might behave like an acute phase reactant in patients with thrombosis and that the measurement of its plasma level as a risk factor for thrombosis should be performed some time after the acute episode. In conclusion, the prevalence of HCII deficiency in patients with a history of thrombosis might have been underestimated in series which included patients with acute thrombosis.

Peripheral artery thrombolysis with urokinase-lys-plasminogen. A disappointing experience.

Thirty-five patients with peripheral arterial occlusion were treated by intra-arterial infusion of low dose urokinase associated with bolus of lys-plasminogen. Systemic fibrinolysis was moderate, thrombolysis was achieved in 26 patients (74%). Only one patient required blood transfusion, five patients (14%) had distal emboli. Infection at the catheter entry site occurred in 2 patients, 3 patients experienced proximal embolism. Six patients required leg amputation, 4 died, in 2 of them deaths were related to arterial catheterization. Local thrombolysis with limited systemic fibrinolysis is associated to a high rate of catheter-related complications.

[Left ventricular thrombus revealed by electron bean computed tomography, in a patient with antiphospholipid syndrome]. / Thrombus de la pointe du ventricule gauche révélé par le scanner à faisceau d'électrons, chez une patiente atteinte d'un syndrome des antiphospholipides.

The authors report a case of a 48 year old woman admitted to hospital because of digital ischemia, in a context of antiphospholipid syndrome. The electrocardiogram-triggered electron beam computed tomography revealed an apical thrombus associated with a thinning left ventricular wall, suggesting painless myocardial infarction. The diagnosis was secondary confirmed by coronarography.

[Acute polymyositis with spontaneously regressive subcutaneous edema. Apropos of a case]. / Polymyosite aiguë avec oedème sous-cutané spontanément régressive. A propos d'un cas.

A 65 year-old man with an oesophageal carcinoma had an acute polymyositis with an extensive oedema of shoulders and arms which improved spontaneously. The significance of these disorders is discussed.

[Biological profile of the 1st 4 hours of a thrombolytic treatment combining urokinase with lysyl-plasminogen]. / Profil biologique dans les 4 premières heures d'un traitement thrombolytique associant l'urokinase et du lysyl-plasminogène.

The authors study the biological variations which accompany an oral, thrombolytic treatment in which urokinase and lysyl-plasminogen are combined. Fibrinogen, the products of degradation of fibrinogen or fibrin, plasminogen and rapid alpha 2 antiplasmin are studied as a function of time. Two dimensional electrophoreses were carried out at precisely determined times. The combination of the two therapeutic agents causes the appearance of plasmin in the circulation, but it is neutralised by its rapid inhibitor. This therapeutic protocol entails moderate circulating fibrinolysis and may easily be monitored by determination of the circulating fibrinogen.

[Intra-arterial thrombolysis with the combination of urokinase and lysyl-plasminogen. 27 cases of acute arterial obliteration of the lower limbs]. / Thrombolyse intra-artérielle par l'association urokinase-lysyl-plasminogène.

Twenty-five in situ thrombolysis using Lysyl Plasminogen and low doses of urokinase were performed on 25 acute, recent and severe arterial occlusion of lower limbs. Early success were 56% and 44% with a follow up of 5 months. Complications were very limited. Thus the thrombolytic treatment used in this study appears as effective as locally administered streptokinase but higher tolerated. It seems to be able to win one of the best places in the treatment of the arterial disease of the lower limbs.

[Treatment of deep venous thrombosis. Comparative study of a low molecular weight heparin fragment (Fragmin) by the subcutaneous route and standard heparin by the continuous intravenous route. A multicenter study]. / Traitement des thromboses veineuses profondes constituées. Etude comparative d'un fragment d'héparine de bas poids moléculaire (Fragmine) administrée par voie sous-cutanée et de l'héparine standard administrée par voie intraveineuse continue. Etude multicentrique.

This open, randomised multicenter trial compares the efficacy and safety of Fragmin administered subcutaneously twice daily with standard heparin administered by continuous infusion in the treatment of deep vein thrombosis (DVT). The initial dose of Fragmin is 100 U anti-Xa/kg/12 h and the further doses are adjusted according to the anti-Xa activity between 0.5 and 0.8 U/ml, 3 hours after the morning injection. The initial dose of standard heparin is 240 UI/kg/12 h. The dose adjustments are based on the daily results of APTT (1.5 - 3 times the control). Treatments efficacy are appreciated when comparing the venography performed before and after 10 days of treatment. The safety is evaluated on clinical parameters and iterative biological tests. Sixty-six patients have been included in this study. Efficacy of the two treatments is equivalent with a phlebographic improvement in respectively 79.3 p. 100 (Heparin Group) and 71.0 p. 100 (Fragmin Group) of the cases and an aggravation in 3.4 p. 100 and 6.4 p. 100 (NS) respectively. The frequency of dosage adjustments is lower and the stability of biological tests is better in the Fragmin group. In conclusion, the administration of Fragmin twice daily by subcutaneous route seems to be equivalent at least to standard heparin continuous infusion in the treatment of recent DVT. The better convenience and safety of Fragmin have to be verified on a larger panel of patients.

[Results of in situ arterial thrombolysis by the combination of urokinase and lysyl plasminogen in acute arterial occlusive diseases of the lower limbs]. / Résultats de la thrombolyse artérielle in situ par association urokinase-lysyl plasminogéne dans les oblitérátions artérielles aiguës des membres inférieurs.

35 patients with acute arterial occlusions [27] and graft thromboses [8], responsible for severe and recent ischemia, were treated by fibrinolytic therapy (Urokinase: 1 000 units/kg/hour, and Lys Plasminogen). These drugs were delivered at the site of occlusions using a 5 French catheter. Angiographically, initial success was obtained in 30 patients (85%) and a significant clinical benefit persisted 5 months later, in 20 patients (57%). 4 distal embolisms during the treatment were noted, and one woman died a few hours after the withdrawal of an axillary catheter of a cerebellar infarction. Only two minor (6%) and one severe (3%) groin hematoma were encountered. No patient had at any moment a fibrinogen concentration lower than 1 g/l. Thus, the thrombolytic treatment used in the study appears as effective as locally administered Streptokinase but better tolerated.

[Role of myocardium scintigraphy with thallium dipyridamole in the evaluation of arterial disease of the legs]. / La place de la scintigraphie myocardique au thallium dipyridamole dans le bilan de l'artériopathie des membres inférieurs.

Thirty-eight consecutive patients with severe arterial disease of the lower extremities benefited from an exploration of the coronary reserve by myocardial scintigraphy with thallium dipyridamole. With this examination, it has been possible to screen 20 p. cent of asymptomatic patients and at least modify the perioperative treatment or even the very indication for surgery.

[Role of computerized pulmonary angiography by peripheral venous approach in the study of deep venous thromboses of the legs]. / Place de l'angiographie pulmonaire numérisée par voie veineuse périphérique dans l'exploration des thromboses veineuses profondes des membres inférieurs.

A pulmonary angiography through peripheral venous approach was systematically performed in 40 consecutive patients presenting a recent deep venous thrombosis. None of these patients had been sent for a suspected pulmonary embolus. The analysis of the images that were obtained, enabled to confirm the diagnosis of pulmonary migration in 9 of these patients (22.5%). The retrospective study of the files confirms the fact that these pulmonary emboli present few symptoms or are asymptomatic in 17.5 p. cent of the cases. The quality of the images, the good acceptability and the moderate cost of pulmonary angiography through peripheral venous approach allow the performance of this examination during the initial work-up of a deep venous thrombosis. The demonstration of a latent pulmonary embolus must enable to separate high risk patients and thus guide subsequent therapy.

[Thrombosis of the gastrocnemic veins. A clinical entity]. / La thrombose des veines jumelles. Une entité clinique.

Among deep venous thromboses of the calf, isolated gastrocnemic vein thrombosis is a rare condition. Its main characteristics could be extracted from 5 cases. Following a positional or mechanical triggering factor, the diagnosis is suggested by pain localized to the calf. Ultrasonography shows the intraluminal thrombus better than phlebography, since the gastrocnemic veins, which bypass the larger deep veins, can be opacified only after a garrot is placed above the knee. The thrombus may extend to the popliteal vein, with a risk of pulmonary embolism and post-phlebitis disease. Treatment consists of anticoagulants and elastic bandage.