La Ricerca in clinica e in laboratorio最新文献

In order to determine a scheme for the screening of inherited thrombotic disorders, abnormalities considered as predisposing to thrombosis have been reviewed. Owing to the low prevalence of biological alterations, a selection of patients is required: documented venous thromboses, possibly at unusual sites (mesenteric vein, portal, cerebral veins), occurring before the age of 40 in patients with a positive family history of thromboses are relatively frequently associated with coagulation abnormalities. In addition, patients with skin necrosis at the initiation of oral anticoagulants, or with repeated superficial vein thrombosis or unexplained arterial occlusions at a young age might be included for screening. Tests have also to be selected. Some abnormalities, such as congenital deficiencies in antithrombin III, protein C and protein S, are recognized risk factors and have to be searched. Some others cannot be at present considered as definite risk factors (e.g., dysfibrinogenemias or deficiencies in factor XII), but their detection is easy by routine tests: prothrombin time, fibrinogen assay. Other abnormalities are recognized risk factors (or not) and need specific uncommon tests (e.g., study of fibrinolysis). Each time a biological abnormality is found, it is important to verify it is isolated since combined deficiencies have been observed and we should be able to answer the question whether the abnormality is the cause or the consequence of thrombosis, or a coincidence. Finally, in our experience, even in well selected patients, a coagulation disorder is detected in less than 30% of patients, so that new tests are needed to improve our knowledge in this field.

There is considerable variation in available methods for the activated partial thromboplastin time (APTT), giving widely differing results with patients on heparin treatment. The study is primarily concerned with the assessment of five of the widest used APTT reagents. The heparin response of these reagents has been related to their lipid composition and physical properties. Of the various correlations between lipid composition of the reagents and clotting performance only electrophoretic mobility was associated with the APTT response to heparin. There was a highly significant negative correlation between the APTT prolongation with heparin and electrophoretic mobility. When plasma is heparinized in vitro a differing order of ranking for APTT reagents is obtained than when heparinized patients are tested. The APTT response in patients with recent thrombosis must therefore be the best guide to the clinical dose of heparin. The therapeutic range of conventional heparin therapy is generally regarded as 1.5-2.5 times the control. External quality assessment programmes in the UK and USA have shown considerable differences between heparin dosage according to the APTT test systems. The definition of the therapeutic range must be derived from randomized clinical studies. The need for progress in standardization of the APTT monitoring of heparin is demonstrated.

Autoisodiasostasis of the liver, i.e., its self-maintenance without change over the course of time, is characterized by a bistable equilibrium between two extreme phases called homopoiesis, during which the liver system repairs its worn structures and replicates its cells, and homeorhesis, during which it satisfies the body's needs. Albumin traffic through the hepatocyte, rendered visible by means of an immunohistological method, has been used as a prototype model to study the dynamics of autoisodiasostasis. An account is given of the oscillation of autoisodiasostasis between homopoiesis and homeorhesis through two intermediate phases. The phase cycle of autoisodiasostasis is illustrated in the form of atemporal bidimensional and tridimensional diagrams. The temporal behavior of the system is represented as a helix trajectory obtained by the projections of homopoiesis-homeorhesis phase cycle on time series.

Thromboembolic events play a major pathogenetic role in the final occlusion of atherosclerotic vessels. May such a catastrophic event be predicted or an increased risk be indicated by analyzing the hemostatic system in plasma? A hugh literature exists about disturbances of the platelet, coagulation and fibrinolytic systems after atherosclerotic events such as myocardial infarction or stroke. This data, however, has no predictive significance. In contrast, the epidemiological studies in healthy persons have shown fibrinogen to be a potent risk predictor which is independent from other risk factors such as age, cholesterol or cigarette smoking. Results on factor VII:C are still controversial. Ongoing studies have included further factors of the hemostatic system. A second approach to elaborate the predictive power of hemostatic factors is to follow up patients with overt atherosclerotic disease and to correlate baseline hemostatic tests with event recurrences. The ECAT Angina Pectoris Study performed in 19 European clinical centers will present its prospective results by 1990. Some correlations of risk factors at baseline point to the many interrelationships among each other and to the need of careful statistical management of such data. It is reasonable to include fibrinogen in the recently developed coronary risk scores. So far, thrombin clotting time procedures, such as the Clauss method, appear to be appropriate for the purposes of risk prediction.

A thorough screening procedure to diagnose congenital coagulation disorders must start from a careful collection of the personal and family clinical history, followed by a two-step laboratory screening. The first step is aimed at detecting the most frequent and well established causes of hemorrhage by a simple battery of laboratory tests such as bleeding time, platelet count, prothrombin time and activated partial thromboplastin time. The second step is to be performed in case of a past history of bleeding, but normal first-step laboratory screening and is aimed at detecting the less frequent abnormalities of hemostasis such as factor XIII, antiplasmin, platelet factor 3, von Willebrand factor, tissue plasminogen activator and dysfibrinogenemia, to which the first-step screening tests are not sensitive.

The partial thromboplastin time (PTT) test is widely used as a screening test for the detection of hemophilia. It is also used to monitor patients on heparin anticoagulation. These proposed guidelines for the performance of this test, including comparable reference ranges, precision and sensitivity requirements are felt to be reasonable and attainable. Whether further progress will occur depends upon a perceived need by laboratorians, instrument and reagent manufacturers and government regulators that standardization of the PTT is desirable.

In the context of the system theoretic theory of the liver, a new categorical approach is introduced, by which autoisodiasostasis is characterized in terms of the splitting of certain idempotents. Equifinal behaviors are then described in this setting.

The lupus anticoagulant may be defined as an immunoglobulin (IgG, IgM or both) which interferes with one or more of the in vitro phospholipid-dependent tests of coagulation. For many years, lupus anticoagulants were regarded as a laboratory nuisance; consequently, reagents were often selected on the basis of insensitivity to lupus anticoagulants. Recently, lupus anticoagulants have been associated with a variety of clinical conditions including recurrent thromboembolic events (both arterial and venous), obstetrical complications including fetal death and spontaneous abortion, and a variety of hematologic and neurologic complications. As a result, many laboratories are now being asked to identify the presence of lupus anticoagulants in selected patient populations. In addition to assays for lupus anticoagulants, there are immunologic assays designed to detect phospholipid antibodies using solid phase systems (RIA or ELISA). A variety of screening tests have been designed to enhance sensitivity to lupus anticoagulants. Test systems with decreased amounts of phospholipid (phosphatidylserine) appear to be most sensitive to lupus anticoagulants. Of the various tests used, the activated partial thromboplastin time (APTT) appears to be most sensitive. The sensitivity of any screening test system is inversely proportional to the residual platelets in the patient sample. APTT reagents differ widely in their sensitivity to lupus anticoagulants. The dilute Russell viper venom time is also highly dependent on the choice and concentration of phospholipid with respect to its sensitivity. Once an abnormality of a screening test has been identified, it is necessary to prove the abnormal result is due to the presence of an inhibitor. This step in the diagnosis may utilize either mixing studies or plasma agarose gels. The final step in the diagnosis of lupus anticoagulants is the demonstration of phospholipid specificity of the inhibitor. Two approaches have been utilized: 1. test systems designed to enhance anticoagulant effect (phospholipid-depleted), and 2. test systems with increased or altered phospholipids which will bypass or neutralize the anticoagulant.

The liver is described as a composite system consisting of a set of operative creodic microunits open to a continuous flow of matter, energy and informations. Its dynamics depend on two interactive and interrelated subsystems with actions described as homopoiesis and homeorhesis, making it an autoisodiasostic system. The system's emergent (equifinal) or emergence states, operative potential, diffusion and reaction phenomena and compensation states are also formally described. For readers not familiar with the language of general system theory, of system dynamics and of categorical analysis, a glossary of some terms is provided.