Technical and biological conditions influencing the functional APC resistance test.

Poor anticoagulant response to APC is conveniently screened by a commercially available functional test (Coatest APC Resistance) allowing identification of APC-resistant patients. These patients may then be genotyped with respect to factor V, the Arg -> Gln mutation being the principle cause of APC resistance. However, determination of phenotype generally precedes that of genotype, and the need for an "abnormality threshold" prompted a study of inter-batch variations and the clinical conditions associated with an altered APC response. The response to APC was assessed twice in plasma from 111 patients using two of four successive kit batches. A modest but significant inter-batch variability was observed. At the same time, we also tested 130 patients with retinal venous occlusion (RVO), 28 patients with glaucoma and 24 normal volunteers. The APCaPTT/aPTT ratio was found to be lower in the presence of elevated thrombin-antithrombin complexes (r = 0.167, p < 0.02) and low blood viscosity (at high shear rate: r = 0.305, p < 0.0001) independently of any alteration in genotype.

[Increased activated partial thrombin time: analysis of 250 cases discovered at laboratory]. / Les allongements de temps de céphaline activée: analyse de 250 cas découverts au laboratoire.

This study evaluates and discusses the potential utility (clinical value) of complementary coagulation tests performed in cases with a prolonged aPTT of no obvious etiology from a total of 85,500 routine coagulation tests carried out in our general hospital. aPTT was measured using Actin F.S.L. (Dade, plant-derived and rabbit phospholipids complex with ellagic acid as activator) and Diagen (Biotrol, rabbit phospholipids with kaolin). Tests for acquired anticoagulants and endogenous pathway factors (XII, XI, IX, VIII) were assayed if the aPTT was prolonged by 7 sec or more. 250 abnormal aPTT of previously unknown etiology were found over a 14 months period. 46% of them were without any obvious cause, and were considered "spontaneous" increases: 2/3 of these spontaneous increases were 7-9 (group A), and 1/3 were 10-19 (group B). The diagnoses found in group A were mostly deficits in the contact system, while group B contained mostly cases with acquired anticoagulants and deficits in the contact system. In group C (increases over 20"), an etiology could be established in all cases, with a predominance of acquired anticoagulants and some deficits in factors VIII and XII.

Fibrinolytic and hemorheologic alterations during and after elective aortic graft surgery: implications for postoperative management.

The hemorheologic and fibrinolytic variables of 15 patients undergoing elective aortic graft surgery were investigated before, during, and after surgery. During the operation, a relative hemodilution was induced intentionally by an infusion of crystalloids and albumin. This led to a decrease in hematocrit (35.5 +/- 6.3-->31.8 +/- 5.6%, P < 0.01), fibrinogen, and platelets, as well as a decrease in fibrinolysis (Euglobulin Clot Lysis Time increases 246 +/- 52-->300 +/- 46 min and fast-acting plasminogen activator inhibitor 1 [PAI-1] activity increases 10.5 +/- 6.9-->15.1 +/- 9 IU/mL, P < 0.01). There was also specific rheologic impairment with a dissociation of erythro-aggregates (primary aggregation time 3.37 +/- 2.63-->7.18 +/- 7.2 s). Tissue-type plasminogen activator (t-PA) antigen was only increased just after surgery (8.3-->14.5 ng/mL, P < 0.01). During the first postoperative week, the acute-phase response subsided. This was accompanied by an increase in fibrinogen, von Willebrand factor antigen, and plasma viscosity (1.33 +/- 0.13-->1.49 +/- 0.13 mPa x s, P < 0.01). Hematocrit and the extrinsic fibrinolytic system (t-PA/PAI) returned to baseline values, whereas intrinsic fibrinolysis remained altered (the Euglobulin Clot Lysis Time, reflecting total activity of plasminogen activators, was still increased). Postoperative management may benefit from a recognition of these two distinct phases induced by surgery. The acute-phase reaction of the first postoperative week is an added vascular risk factor and requires a specific therapeutic approach.