Comparison of quantification methods of 111In-labelled platelet deposition in peripheral bypass grafts.

The action of antithrombotic drugs can be evaluated by measuring the deposition of 111In-labelled platelets on peripheral bypass grafts several days after injection. This evaluation can be performed qualitatively (visual interpretation on the daily images) or quantitatively. Four different methods which calculate the ratio of platelet uptake with a reference region are compared: two methods use a gamma camera and two a detector.

Sodium fluoride mimics effects of both agonists and antagonists on intact human platelets by simultaneous modulation of phospholipase C and adenylate cyclase activity.

Using intact human platelets, we studied the effect of sodium fluoride (NaF) on platelet aggregation and release reaction and correlated the functional changes to intracellular events specific for either agonist-induced or antagonist-induced platelet responses. At lower concentrations, with a peak activity between 30 and 40 mmol/L, NaF induced aggregation and release of adenosine 5'-triphosphate (ATP) that was associated with increased formation of inositol phosphates, a rise in cytosolic free Ca2+, and phosphorylation of 20-kd and 40-kd proteins. At NaF concentrations greater than 40 mmol/L, aggregation and ATP release decreased dose-dependently in parallel with a decrease in Ca2+ mobilization, whereas neither inositol phosphate formation nor 40-kd protein phosphorylation was reduced.

Intraarterial low-dose streptokinase infusion in the treatment of acute renal thromboembolism.

A case of acute renal thromboembolism treated by intraarterial low dose streptokinase infusion is reported. The treatment appears effective, safe and less-invasive then surgery, with quick relief of pain and normalisation of blood pressure and renal function. It is concluded that intraarterial infusion of thrombolytic agents should be attempted first in the treatment of renal arterial thrombo-embolism.

[Molecular defects of coagulation factors and of the fibrinolytic system associated with thromboembolism].

Some molecular defects of components of the coagulation or fibrinolytic system are associated with thromboembolism. One possibility is that physiologic inhibitors of the coagulation system have an abnormal function e.g.

Continuous inhibition of serotonin-induced platelet aggregation during chronic ketanserin administration to man can be detected after plasma pH control.

Ketanserin is a well-known serotonin S2 receptor antagonist but its capacity to inhibit serotonin-induced aggregation ex vivo during chronic administration has been a matter of debate. In vitro evidence is presented that the inhibitory capacity of ketanserin is lowered by increasing plasma pH. Since the pH of plasma kept at the open air increases with time, we studied the effect of chronic administered ketanserin on serotonin-induced platelet aggregation in plasma kept at a lowered pH of 7.

Increased release of prostacyclin-like activity from rat aorta by plasma from patients with hepatic or renal failure.

Exhausted rat aorta slices were incubated for 20 minutes at room temperature with plasma from 6 uremic patients undergoing maintenance hemodialysis, from 23 patients with hepatic disorders and with plasma from healthy volunteers. We observed that plasma from uremic as well as from patients with liver dysfunction stimulated prostacyclin release more than the simultaneously studied normal plasmas. Enhanced prostacyclin release may play a role in the pathogenesis of the hemorrhagic diathesis of patients with renal or hepatic failure.

Local thrombolysis in femoropopliteal occlusion: early and late results.

The early and late results of local thrombolysis with low-dose streptokinase followed by balloon dilatation in 64 patients with an occluded femoropopliteal artery are reviewed. The primary success rate was 77% for the native arteries; it was higher (80%) for short (less than 10 cm) as compared with long occlusion (40%) and for patients with claudication as compared with those with advanced ischemia (89% versus 48%). Eleven complications were observed in 10 patients, most frequently a local hematoma at the puncture site.

Percutaneous transluminal angioplasty of the subclavian artery: early and late results.

Percutaneous transluminal angioplasty of 23 subclavian arteries was attempted in 22 patients. Dilatation was successful in 3 of 4 right subclavian artery stenoses and 18 of 19 left subclavian artery stenoses. The primary clinical indication was posterior fossa ischemia in 11 patients, upper limb ischemia in 14 and both symptoms in 6.

Role of platelet activation and fibrin formation in thrombogenesis.

Further progress in the search for more effective but safe antithrombotic agents is coupled to an improved understanding of the factors involved in arterial and venous thrombogenesis. Although arterial thrombosis is initiated by formation of a layer of platelets on modified endothelium or subendothelial constituents and subsequent recruitment of passing-by platelets, this phenomenon is not sufficient to lead to a full thrombus. Further growth of such a platelet mass depends, to a large extent, on the presence of free thrombin.

Venous thromboses in particular organs.

Although venous thrombosis most often occurs in the return circulation of the legs and pelvis, it may also occur in the veins of several organs and compromise venous return. Thus, the clinician, in any field will regularly be confronted with manifestations of venous thrombosis in particular organs. This review summarizes the pathogenesis and the main clinical features of venous thrombosis in the central retinal vein, the cerebral veins and sinuses of the skull, the renal and the portal veins and the hepatic and mesenteric veins as well as priapism.

Evaluation of three methods of platelet labelling.

The study of the kinetics of labelled platelets makes sense only when the platelets preserve their viability after separation and labelling. The separation and labelling procedures described in the manual of two producers of 111In-oxinate (Amersham, Mallinckrodt) have been evaluated by in vitro aggregation tests. The method of Mallinckrodt diminished the aggregation capacities of the thrombocytes.

Current issues in thrombosis prevention with antiplatelet drugs.

In this review, the major current problems related to the pharmacology and clinical use of antiplatelet drugs are discussed in relation to the physiopathology of the platelet-vessel wall interaction and arterial thrombus formation. Although platelet adhesion to injured vessels is a crucial step in thrombogenesis, none of the currently used antiaggregating drugs prevents this phenomenon. Why the normal endothelium does not react with platelets is not known.

Leukotriene B4 production by stimulated whole blood: comparative studies with isolated polymorphonuclear cells.

A new method was developed to study leukotriene B4 (LTB4) production by stimulated whole blood. The calcium ionophore A23187 and serum-treated zymosan induced LTB4 production, measured by radioimmunoassay, in a dose- and time-dependent manner. The pattern of LTB4 production by whole blood differed markedly from that observed with isolated, purified polymorphonuclear leukocytes.

Thrombosis and immune disorders.

The purpose of this review has been to draw the attention of clinicians towards the possibility that some of the patients they are treating for thrombosis may have an underlying immune disturbance. This could involve functional abnormalities of the complement system (as in acquired angioneurotic oedema or in paroxysmal nocturnal haemoglobinuria), or cell-mediated immunological damage to the vessel wall (as in Behcet's syndrome or Buerger's disease), or the presence of circulating antibodies (the lupus anticoagulant or antibodies to heparin). While obviously our knowledge on most aspects is still very incomplete, the awareness of the association of thrombosis with certain immune disorders should encourage further detailed studies of mechanisms and enhance our understanding of the role of blood constituents and the vessel wall in thrombogenesis.

Mechanism of the antiplatelet action of dipyridamole in whole blood: modulation of adenosine concentration and activity.

Dipyridamole inhibits platelet aggregation in whole blood at lower concentrations than in plasma. The blood cells responsible for increased effectiveness in blood are the erythrocytes. Using the impedance aggregometer we have carried out a series of pharmacological studies in vitro to elucidate the mechanism of action of dipyridamole in whole blood.

Heparin-induced thrombocytopenia platelet aggregation studies in the presence of heparin fractions or semi-synthetic analogues of various molecular weights and anticoagulant activities.

One case of heparin-induced thrombocytopenia is reported. Aggregation was observed in the platelet-rich plasma of this patient in the presence of two commercial standard heparin preparations (from a final concentration of 0.025 IU/ml upwards), of two semi-synthetic heparin analogues (0.

'Lupus' anticoagulant and thrombosis of the hepatic veins (Budd-Chiari syndrome). Report of three patients and review of the literature.

Three patients with Budd-Chiari syndrome in association with the 'lupus' anticoagulant are described. This anticoagulant was looked for in our patients with an otherwise idiopathic hepatic venous thrombosis because of the presence of a pronounced thrombocytopenia, a prolonged activated partial thromboplastin time or a history of repeated abortions and deep leg vein thrombosis, respectively. An active search for the 'lupus' anticoagulant should be performed to lower the percentage of apparently idiopathic cases of Budd-Chiari syndrome.

Intravenous ionic contrast media cause local prostacyclin release in man.

The effect of intravenous administration of ionic contrast media on local release of prostacyclin (PGI2) was investigated in man. Iodamide and ioxaglate, high- and low-osmolality contrast media, respectively, both significantly increased PGI2 levels at the site of injection. Iodamide was the most active, whereas an identical volume of isotonic saline had no effect.

Thromboxane A2 and prostacyclin do not modulate the systemic hemodynamic response to cold in humans.

The immersion of a limb in a mixture of water and ice induces in normal humans an initial vasoconstriction mediated mainly by catecholamine release. In some studies the cold pressor test was associated with an increase in vasoconstrictor thromboxane A2 and in vasodilating prostacyclin. Dazoxiben hydrochloride, a thromboxane synthase inhibitor, has been reported to suppress cold-induced vasoconstriction.