The introduction of the activated partial thromboplastin time (APTT) as a screening test has resulted in increased recognition of circulating anticoagulants. The most frequently encountered inhibitor is the lupus-type anticoagulant. However, criteria for differentiation of this inhibitor are not well-established. We evaluated the ability of two procedures, tissue thromboplastin inhibition (TTI) and a new platelet neutralization procedure (PNP), to differentiate between various types of coagulation inhibitors. The TTI, widely used for the diagnosis of lupus anticoagulants, proved to be nonspecific. The PNP specifically separated lupus-type inhibitors from Factor VIII, X, and V inhibitors. The PNP may be a useful test for the diagnosis of lupus anticoagulants.
Factor VII (FVII) deficiency is a rare inheritable bleeding disorder affecting 1/500 000 individuals. Clinical manifestations are heterogeneous, from asymptomatic to severe and potentially fatal bleeding. These clinical manifestations do not correlate well with FVII plasma levels. For this reason, FVII-deficient patient management during surgery or for long-term prophylaxis remains challenging. Laboratory testing for FVII activity is, however, the first-line method for FVII deficiency diagnosis and is helpful for managing patients in combination with clinical history. Additional testing consists of FVII immunoassay and genetic testing. Genetic abnormalities on the FVII gene are heterogeneous and can translate into quantitative or qualitative defects. Some of the latter can react differently with different thromboplastins; this can be misleading for the laboratory as no consensus exists at present on an FVII deficiency diagnosis methodology. Indeed, no single test is able to predict accurately the bleeding risk. This review provides a broad picture of inherited and acquired FVII deficiency with a particular focus on laboratory diagnosis.
Until recently, the laboratory identification of lupus anticoagulants (LA) was not considered important. Often LA were regarded as a nuisance, resulting in factor assays and other coagulation tests with inconclusive results. However, the recognition of important clinical complications associated with the presence of LA has resulted in an emphasis on the detection of this phospholipid-dependent inhibitor. Most studies have evaluated the sensitivity of various screening or confirmatory procedures used in establishing the diagnosis of LA. The authors have focused on the variables involved in the mixing studies used to identify the presence of a circulating inhibitor. To detect the latter, attention to the ratio of patient plasma to normal plasma is important, particularly in the case of a minimally prolonged APTT. Also the source of "normal" plasma must be platelet poor to maximize sensitivity in the case of a weak LA.
The purpose of this study was to determine whether the anti-activated factor X (anti-FXa) assay is less affected by pre-analytical variables in monitoring patients on unfractionated heparin (UFH) and low molecular weight heparin (LMWH) than the activated partial thromboplastin time (aPTT). Forty-six subjects receiving either enoxaparin (LMWH) or UFH were randomly selected. Each study subject had six vacutainer tubes (3.8% sodium citrate, 3.2% sodium citrate) drawn by an atraumatic venipuncture. One tube from each set had a blood to anticoagulant ratio of 9: 1. The other tube had an intentional "short-draw" of approximately 6: 1 blood to anticoagulant ratio. All specimens had an aPTT and a chromogenic anti-FXa assay performed on each specimen regardless of heparin type. The aPTT assay mean with the 3.8% sodium citrate tube short-draw tube was statistically different from the other aPTT assays (P = 0.06). However, all six of the mean anti-FXa assays for the UFH and LMWH heparin subjects were not statistically or clinically different (analysis of variance, P = 0.9878 for UFH and P = 0.9060 for LMWH). The intentional short-draw tube did not affect the anti-FXa assay regardless of the anticoagulant. The anti-FXa assay appears to be a better method for monitoring heparin subjects than the aPTT due to the lack of effect of pre-analytical variables.
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