Showing papers by "Emmanuel J. Favaloro published in 2004"

Factor V inhibitors: rare or not so uncommon? A multi-laboratory investigation.

Abstract: Acquired deficiencies of, or inhibitors to, factor V are considered rare events. We report a series of 14 acquired factor V deficiencies, 10 of which were confirmed to have inhibitors to factor V, as identified within Australia in the past 5 years following a multi-laboratory investigation. The initial index case seen by one laboratory was followed within 4 months by a separate similar case. This prompted local contact with colleagues (n = 20) working in other haemostasis referral laboratories to identify the current case series. In total, nearly one-half of all haemostasis referral laboratories contacted had seen a case within the past 5 years. Clinical features and the apparent associated risk of bleeding complications generally varied, as did laboratory findings and the likely causal event. There were three females and 11 males. Age ranged from 44 to 95 years (median, 81 years). The level of inhibitor ranged from undetectable to over 250 Bethesda units. The probable cause leading to development of the inhibitors ranged from exposure to bovine thrombin, exposure to antibiotics, surgery and malignancy. Of additional interest was the apparent association of anti-phospholipid antibodies in many of the cases. For example, in the two similar index cases, with factor V inhibitor titres > 200 Bethesda units, high levels of anti-cardiolipin antibodies (> 70 GPL units) were also detected. Although less clear because of inhibitor interference, many of the cases also showed evident co-associated lupus anticoagulant activity. In conclusion, we report a series of factor V inhibitors recently identified within our geographic region that would represent an annual incidence of around 0.29 cases per million Australians. Although considered a rare finding, there is a high likelihood that most haemostasis referral laboratories will see a case every five or so years.

Potential laboratory misdiagnosis of hemophilia and von Willebrand disorder owing to cold activation of blood samples for testing.

Abstract: To assess the potential for misdiagnosis of von Willebrand disorder (vWD) and hemophilia A while following current National Committee for Clinical Laboratory Standards (NCCLS) guidelines and consequent to a poorly recognized cold-activation phenomenon, we processed 39 normal citrate-anticoagulated samples by standard procedures (reference) or stored at low (approximately 4 degrees C) or ambient (approximately 22 degrees C) temperature for 3.5 hours before centrifugation and processing. Samples were tested in parallel for several hemostasis factors, including von Willebrand factor (vWF). Similar results were obtained for all samples for factors II, V, VII, IX, X, XI, and XII. For factor VIII (FVIII) and vWF, only samples stored at ambient temperature had results comparable to reference sample results. In most cases, low temperature storage led to much lower results. Taking the lower reference limit as 50%, most would have been defined as "abnormal," and a misdiagnosis of vWD or hemophilia A could easily arise. ABO classification and age were associated with FVIII and vWF levels, but neither was associated conclusively with relative loss of plasma FVIII coagulant and vWF caused by the cold-activation phenomenon. We advise laboratories following current NCCLS guidelines not to store or transport whole blood samples for FVIII and vWF testing at 2 degrees C to 4 degrees C because of the risk of misdiagnosing vWD or hemophilia A. Storage and transport at ambient temperature seem acceptable and provide results comparable to freshly centrifuged samples.

von Willebrand disease: laboratory aspects of diagnosis and treatment

Abstract: von Willebrand disease is the most common inherited bleeding disorder in humans. VWD can be classified into three major types, designated Types 1, 2 and 3; Type 2 can be further separated into subtypes 2A, 2B, 2M and 2N. The diagnosis of VWD requires a personal and family history of bleeding and confirmation by laboratory analysis. Although Types 2 and 3 are relatively straightforward to diagnose, there may be a risk of overdiagnosis of Type 1 because of an overlap within the normal range. We also report on the clinical profile and diagnosis of VWD in a South American cohort of patients and on the in vitro characteristics of some factor concentrates available for treatment of VWD.

Laboratory diagnosis of von Willebrand's disorder: quality and diagnostic improvements driven by peer review in a multilaboratory test process

Abstract: Regular multilaboratory surveys of laboratories derived primarily from Australia, New Zealand and Southeast Asia have been conducted over the past 7 years to evaluate testing proficiency in the diagnosis of von Willebrand's disorder (VWD) and to assess changes to test practice. Participating laboratories (currently 45) are asked to perform their usual panel of tests for VWD, and then to self-interpret test results as to the likelihood (or not) of VWD, as well as to the potential subtype identified. Samples provided in the past two survey distributions (both conducted in 2003) were as follows. Survey part A/distribution 1: Normal donor plasma, plasma with borderline normal/reduced levels of VWF (×2) and plasma from an individual with type 2 A VWD. Survey part B/distribution 2 (family VWD study): Plasma from a father, mother and son with borderline normal/reduced von Willebrand factor (VWF), and a daughter with type 3 VWD. In line with previously published survey results, the interassay and within method coefficients of variation (CV) were similar for all assays (around 15-25%), although tending to be slightly higher for VWF:RCo and VWF:CB than VWF:Ag and FVIII:C. Most laboratories reported test values consistent with expected findings, and made correct interpretations or predictions regarding the nature of the samples, although discrepant assay results or interpretations are still seen in approximately 5-10% of responses (typically from laboratories using a more limited test panel or not performing the VWF:CB). Overall, problems with the non-identification of functional VWF discordance in type 2 VWD, the misidentification of functional VWF discordance in type 1 VWD, and difficulties in discriminating types 1 and 3 VWD appear to predominate. In comparison with previous surveys, performance of electro-immuno diffusion (EID) (or Laurel gel) procedures has now ceased, and a reduction in VWF:RCo and VWF:Multimer testing and an increase in latex immunoassay (LIA) testing is sustained. We conclude that laboratories are generally proficient in tests for VWD, and that diagnostic error rates are reduced when test panels are more comprehensive and include the VWF:CB. © 2004 Blackwell Publishing Ltd.

Basic Immunology: Functions and Disorders of the Immune System - 2nd Edition [Book Review]

Abstract: Publishers details for: Basic Immunology: Functions and Disorders of the Immune System - 2nd Edition, edited by Abul K Abbas and Andrew H Lichtman, Saunders, 322 pages, 156 figures, ISBN: 072160241X, A$77.00.

Evaluation of primary haemostasis in people with neurofibromatosis type 1

Abstract: Assessment of haemostasis in people with neurofibromatosis type 1 (NF-1) is essentially lacking, despite case reports of an association with von Willebrand disorder (VWD) and reported excessive bleeding post-surgery. We assessed routine blood haematology, routine coagulation parameters [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen], coagulation factors II, V, VII, VIII, IX, X, XI and XII, von Willebrand (VWF) factor antigen and activity, and platelet function [using the platelet function analyser (PFA-100)] in a group of individuals with NF-1 (n = 30). Their perceived haemorrhagic bleeding risk was also graded by means of a structured clinical assessment and physical examination. Routine blood assessments including platelet counts were generally normal, as were the routine coagulation tests PT, TT and fibrinogen, and most coagulation factors. Elevated APTTs were detected in 11 individuals, reduced factor XII levels in three, reduced VWF levels in four, and elevated PFA closure times (CTs) in 13. Laboratory results correlated with each other in some but not all cases. For example, elevated APTTs were identified in two of three individuals with a reduced factor XII level and prolonged CTs were identified in three individuals who also showed reduced aggregation responses in classical platelet function studies. Moreover, all individuals with VWF results below the normal reference range showed elevated CTs with both PFA test cartridges, and those with VWF results identified as borderline normal (i.e. 50-65%) also showed elevated CTs with both PFA test cartridges in three of five cases. The relationship between VWF and CTs was also identified by linear regression analysis (P-values of <0.05, for all comparisons). However, as clinically perceived bleeding risk did not appear to be correlated with laboratory test results in most cases, blanket screening of NF-1 individuals for evaluation of laboratory haemostasis may not be warranted.