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Emmanuel J Favaloro

Publications and source records attributed to Emmanuel J Favaloro.

36 records · Page 2Linked to original sources
PubMed2005

An international survey of current practice in the laboratory assessment of anticoagulant therapy with heparin.

AIMS: We conducted a survey of laboratory practice for assessment of heparin anticoagulant therapy by participants of the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA QAP). METHODS: A questionnaire was sent to 646 laboratories enrolled in the Haematology component of the QAP, requesting details of tests used for monitoring heparin therapy. RESULTS: Seventy laboratories (10.8%) returned results that indicated that they performed laboratory monitoring of heparin therapy. Most laboratories (69/70 = 98.6%) use the activated partial thromboplastin time (APTT) to monitor unfractionated heparin, with eight (11.4%) also using the APTT for monitoring low molecular weight (LMW) heparin. Five (7.1%) laboratories use the thrombin time (TT) test to help monitor heparin therapy and 37 (52.9%) laboratories use an anti-Xa assay to monitor heparin (either LMW or unfractionated). Normal reference ranges (NRR) for APTT differed considerably between laboratories, even those using the same reagent. Therapeutic ranges (TR) also differed considerably between laboratories, for both APTT and the anti-Xa assay. Laboratory differences in NRR and TR using the same reagents could only be partly explained by the use of different instrumentation. CONCLUSIONS: There is a large variation in current laboratory practice relating to monitoring of heparin anticoagulant therapy. This finding is similar to that of a similar survey conducted by the RCPA QAP almost a decade ago. This study suggests that better standardisation is still required for laboratory monitoring of heparin therapy.

Anticoagulants↗
PubMed2005

Cross-laboratory audit of normal reference ranges and assessment of ABO blood group, gender and age on detected levels of plasma coagulation factors.

We have assessed the influence of the ABO blood group, gender and age on plasma levels of the coagulation factors II, V, VII, VIII, IX, X, XI and XII as part of a quality audit of laboratory activities. There was no statistically significant difference in gender donor age (total normal donors: n = 406, mean/median age = 46.0/47.0 years, range = 16-77 years; females: n = 177, mean/median age = 44.7/46.0 years, range = 16-75 years; males: n = 229, mean/median age = 47.0/48.0 years, range = 17-77 years). With increasing age, we observed small but statistically significant rises (linear correlation; P < 0.01 for all parameters) in factors V, VII, VIII, IX and XI. With gender, we observed higher levels (P < 0.05) in females for factors II, VII, X, IX, XI and XII. With the ABO group, we observed lower levels in the O group (versus non-O group; P < 0.05) for factors VIII, IX and XII. We could therefore define differing normal reference ranges based on the differing study data. Study findings are compared with previously published literature, and this has identified a wide diversity in normal reference ranges both between different factors and between different studies. Finally, we also performed a cross-laboratory audit of peer laboratory practice and similarly show a wide diversity in normal reference ranges used between different laboratories.

ABO Blood-Group System↗
PubMed2005

Laboratory diagnosis of von Willebrand disorder: use of multiple functional assays reduces diagnostic error rates.

Regular multilaboratory surveys of laboratories primarily in Australia, New Zealand, and Southeast Asia have been conducted over the past 8 years to evaluate testing proficiency in the diagnosis of von Willebrand disorder (VWD). We have reassessed the findings of these surveys with a particular emphasis on the diagnostic errors and error rates associated with particular tests or test panel limitations. The 37 plasma samples dispatched to survey participants include 9 normal samples, 4 type 1 VWD samples, 8 type 2 VWD samples (2A x 3, 2B x 3, 2M x 1, and 2N x 1), and 4 type 3 VWD samples. In addition to providing numerical test results, participant laboratories (average, n = 35) were asked to provide diagnostic interpretations of their test results regarding whether VWD was evident and, if so, the probable subtype. Although laboratories usually provided correct interpretative responses, diagnostic errors occurred in a substantial number of cases. On average, type 1 VWD plasma was misidentified as type 2 VWD plasma in 11% of cases, and laboratories that performed the ristocetin cofactor assay for von Willebrand factor (VWF:RCo) without performing the collagen-binding activity assay for VWF (VWF:CB) were 6 times more likely to make such an error than those that did perform the VWF:CB. Similarly, type 2 VWD plasma samples were misidentified as type 1 or type 3 VWD in an average of 20% of cases, and laboratories that performed the VWF:RCo without the VWF:CB were 3 times more likely to make such an error than those that performed the VWF:CB. Finally, normal plasma was misidentified as VWD plasma in an average of 5% of cases, and laboratories that performed the VWF:RCo without the VWF:CB were 10 times more likely to make such an error than those that performed the VWF:CB. We conclude that laboratories are generally proficient in their testing for VWD and that diagnostic error rates are substantially reduced when test panels are more comprehensive and include the VWF:CB.

Asia, Southeastern↗
PubMed2005

How useful is the monitoring of (low molecular weight) heparin therapy by anti-Xa assay? A laboratory perspective.

We have conducted a series of laboratory-based surveys to assess variability in assay results utilized to monitor heparin anticoagulant therapy. These surveys involved laboratories participating in the Haematology component of the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA QAP). Thirty five of 646 laboratories that were sent a preliminary questionnaire indicated that they performed anti-Xa assays and these laboratories were sent a panel of four plasma samples. These plasma samples contained respectively: (i) no added heparin, (ii) low molecular weight heparin (LMWH), enoxaparin, added to a level of approximately .5 U/mL, (iii) unfractionated heparin added to a level of approximately .5 U/mL, and (iv) LMWH added to a level of approximately 1.0 U/mL. Tests to be performed were the activated partial thromboplastin time (APTT), the thrombin time (TT), fibrinogen, and anti-Xa. As expected, returned results for APTT and TT showed some elevation in heparinized samples while fibrinogen assays were not affected. Anti-Xa assays yielded the following results (median [range]): (i) .01 [0-.11], (ii) .43 [.33-.80], (iii) .23 [.10-.49], and (iv) .90 [.60-1.30]. Thus, although median values were close to those anticipated, there was a wide variation in returned results. In a repeat exercise a few months later laboratories were also asked about their therapeutic ranges (TRs) and provided with an additional vial of LMWH-spiked (1.0 U/mL) plasma labeled as 'heparin-standard' to be used as an assay calibrant. TRs varied substantially between laboratories, from low ranges of .2-.4 to high ranges of .8-1.2. Anti-Xa assay results were similar to those of the first survey: (median [range]): (a) repeat testing: (i) .02 [0-.28], (ii) .47 [.34-.80], (iii) .25 [.14-.58], (iv) .95 [.65-1.31]; (b) repeat testing using survey provided 'heparin-standard': (i) .02 [0-.24], (ii) .55 [.4-.83], (iii) .28 [.10-.63], (iv) 1.00 [.9-1.16]. Thus using the provided 'heparin-standard' yielded lower variability in results for LMWH. In conclusion, the high variability of anti-Xa assay results coupled with the widely variable TRs suggests that therapeutic heparin monitoring is poorly standardized, and this raises some concerns over the clinical value of such monitoring.

Drug Monitoring↗
PubMed2005

Laboratory identification of familial thrombophilia: do the pitfalls exceed the benefits? A reassessment of ABO-blood group, gender, age, and other laboratory parameters on the potential influence on a diagnosis of protein C, protein S, and antithrombin deficiency and the potential high risk of a false positive diagnosis.

Laboratory testing for familial thrombophilia defines a large proportion of the modern hemostasis laboratory workload. As part of an ongoing assessment of our activities, we have re-evaluated our laboratory procedures for antithrombin (AT), Protein C (PC), and Protein S (PS), inclusive of normal reference ranges (NRR), the potential influence of ABO-blood group, gender and age, as well as other laboratory parameters, in order to help assess the effectiveness of testing as an aid to clinical diagnosis. We did not observe a significant influence of ABO-blood group on AT, PC, or PS. However, there were gender-related effects for PS (lower in females) and AT (higher in females), but not for PC. There were also age-related effects for AT, PC, and PS. Data is compared with literature findings. We also audited the positive detection rate for PC and/or PS deficiencies. In a 6-month period of testing, we identified that 18.9% of tested samples yielded low or near-low PC and/or PS levels. However, 33.3% of such samples were potentially derived from patients on oral anticoagulant therapy (ie, potential false positives). Additional pre-analytical variables, intra-assay, inter-assay, and inter-laboratory variability also contribute to the possibility of false positive detection. Thus, whilst NRR can be developed for test parameters, the likelihood of a false-positive test result can still be shown to exceed the likelihood of a true positive result, and this casts a shadow over the clinical value of such testing in some cases. In conclusion, laboratory testing for these markers of familial thrombophilia may or may not assist in the clinical diagnosis of this condition and clinical specialists should be made aware of laboratory test limitations, and consult with laboratories prior to making a definitive diagnosis of AT, PC, or PS deficiency.

ABO Blood-Group System↗
PubMed2005

Reassessment of ABO blood group, sex, and age on laboratory parameters used to diagnose von Willebrand disorder: potential influence on the diagnosis vs the potential association with risk of thrombosis.

We reassessed the influence of ABO blood group, sex, and age on plasma levels of von Willebrand factor (vWF) antigen, vWF:ristocetin cofactor, vWF:collagen binding assay, and factor VIII coagulant (FVIII:C). Data show that levels of vWF and FVIII:C increase with increasing age (P < .001 for all parameters) and that the ABO blood group influences plasma levels such that O group levels are significantly less than non-O group levels. There was no significant association with sex and Rh status. The selection of normal ranges based on ABO blood groups may influence the clinical diagnosis of von Willebrand disease (vWD) but might not be clinically relevant or help identify people at increased risk of bleeding. Differences in ABO-related ranges were more extensive at the high end of the ranges. This is of particular interest because high levels of vWF and FVIII are associated with thrombosis risk, and an ABO relationship also has been described. O group individuals may or may not be at greater risk for bleeding (they have lower levels of vWF and FVIII:C) and are more likely to be diagnosed with vWD. It also is possible that O group status may be protective for thrombosis.

ABO Blood-Group System↗
PubMed2004

Consensus guidelines on anti-cardiolipin antibody testing and reporting.

UNLABELLED: Consensus guidelines on anti-cardiolipin antibody (aCL) testing have been developed to help minimise laboratory variation in the performance and reporting of aCL assays. These guidelines include minimum, optimum and optional recommendations for the following aspects of aCL testing and reporting: (1) isotype of aCL tested; (2) specimen type; (3) controls and assay precision; (4) calibrators; (5) patient samples; (6) rheumatoid factors and IgM aCL testing; (7) reporting of results; (8) cut-off values; and (9) interpretative comments. ABBREVIATIONS: aCL, anti-cardiolipin antibodies; APS, anti-phospholipid antibody syndrome; ASCIA, Australasian Society of Clinical Immunology and Allergy; ASTH, Australasian Society of Thrombosis and Haemostasis; beta2-GPI=beta2-glycoprotein I; ELISA, enzyme-linked immunosorbent assay; NCCLS, National Committee for Clinical Laboratory Standards; HSANZ, Haematology Society of Australia and New Zealand; QAP, Quality Assurance Program; RCPA, Royal College of Pathologists of Australasia; %CV, inter-assay inter-run coefficient of variation.

Antibodies, Anticardiolipin↗
PubMed2004

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

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.

Adult↗
PubMed2004

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

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.

ABO Blood-Group System↗
PubMed2003

Laboratory diagnosis of von Willebrand disorder. Current practice in the southern hemisphere.

A survey of 44 laboratories was conducted to evaluate current testing proficiency in the diagnosis of von Willebrand disorder (vWD) and to assess recent changes in test practices. Laboratories performed their usual panel of tests for vWD and interpreted results for the likelihood of vWD and potential subtype. Samples were as follows: normal plasma; borderline normal or abnormal levels of von Willebrand factor (vWF) and factor VIII; type 3 vWD; type 2A vWD; and 2 samples from a healthy person, processed after handling at 22 degrees C and 4 degrees C, respectively. Interassay and within-method coefficients of variation were similar for all assays (approximately 15%-25%). Most laboratories reported test values consistent with expected findings and made correct interpretations, although discrepant results for 5% to 10% of responses are of concern. For the sample stored at 4 degrees C, all laboratories detected low or borderline levels of vWF and factor VIII coagulant, and no laboratory identified this sample as from a healthy person. In contrast, for the sample stored at 22 degrees C, most laboratories reported normal results. Compared with previous results, performance of some assays has declined while that of others has increased. Laboratories generally are proficient in tests for vWD, and transport of samples at 4 degrees C before processing may lead to false identification of vWD, suggesting that NCCLS guidelines should be reviewed.

Antigens↗
PubMed2002

Von Willebrand factor collagen-binding (activity) assay in the diagnosis of von Willebrand disease: a 15-year journey.

The correct diagnosis and classification of von Willebrand disease (vWD) is crucial because the presenting biological activity of von Willebrand factor (vWF) determines both the hemorrhagic risk and the subsequent clinical management. A variety of laboratory assays may be employed, not necessarily restricted to assessments of vWF. This article discusses the relative strengths and limitations of various functional or discriminatory vWF assays with a special focus on the vWF:collagen-binding activity (vWF:CBA) assay. This is a functional vWF assay that relies on the property of vWF adhesion to collagen. The vWF:CBA was first described approximately 15 years ago. The journey from that time point has been an interesting one, and the vWF:CBA is now gaining more widespread acceptance. There are now many published studies confirming the superiority of the vWF:CBA over the vWF ristocetin cofactor (vWF:RCof) activity as a functional screening diagnostic test process for vWD. However, both tests may be required in order to appropriately diagnose all forms of vWD. The relationship of these assays with multimer analysis is also discussed. In summary, an optimized vWF:CBA detects primarily high-molecular-weight (HMW) vWF forms and probably only about 30% of the total plasma vWF pool detected by vWF antigen (vWF:Ag). Because these HMW vWF forms are missing in types 2A and 2B vWD, the vWF:CBA is extremely useful in the detection of these qualitative vWD subtypes. In addition, however, concordance of vWF:CBA with vWF:Ag in unison with low vWF levels may alternatively suggest a type 1 vWD, and an absence of both vWF:Ag and vWF:CBA will suggest type 3 vWD. The vWF:CBA is also being investigated in various disease states, as is its usefulness as an effective marker of functional HMW vWF in both desmopressin (DDAVP) and factor-concentrate therapy in vWD.

Agglutination Tests↗
PubMed2002

A 9-year retrospective assessment of laboratory testing for activated protein C resistance: evolution of a novel approach to thrombophilia investigations.

AIMS: To assess international and local trends in laboratory testing for activated protein C (APC) resistance (APCR) and factor V Leiden (FVL). Also, to compare local results of FVL testing with a variety of different clot-based APCR assays to assess utility for detection of APCR both related and unrelated to FVL. METHODS: Local test statistics and test result patterns were evaluated and international literature was reviewed over the past 9 years. Direct comparisons of FVL testing by DNA analysis against (a) the standard APTT-based APCR assay, with and without pre-dilution with factor V deficient (FVD) plasma, or with and without normalisation, and (b) three alternative RVVT-based procedures (most recently using a commercial RVVT-based procedure called GradiLeiden V; GLV). In total, data obtained over the past 7 years, using referred samples from over 1,000 patients, have been assessed. RESULTS: The 9-year retrospective assessment has seen many changes in test-based processes. Locally, test requests for both APCR and FVL have consistently increased. We suspect this has been fuelled in part by media reports of 'economy class syndrome' (ECS) and associated general public and clinical concern. Current request patterns number around 800 APCR and 1,600 FVL per year. Interestingly, most requests are for one or either test, with joint requests comprising less than 20% of those overall. Although test requests are increasing, detection of the FVL defect as a proportion of test requests is actually falling (from a high of over 25% in 1996 to around 14% currently). Whether this suggests an increasing tendency for clinical ordering in the absence of appropriate clinical histories is a matter of concern. Consistent with previous findings, the original and commonly used APTT-based procedure was found to show the least correlation with DNA findings, with a large overlap between FVL and non-FVL individuals. The alternate-RVVT-based procedures showed much better differentiation. Thus, for the APTT-based method, in order to ensure 100% sensitivity, an APC ratio cut-off value of 3.1 was required, and this yielded only 49.1% specificity. In contrast, for the GLV RVVT-based method, in order to ensure 100% sensitivity, an APC ratio cut-off value of 1.65 was required, and this yielded 96.6% specificity. CONCLUSIONS: It is important to recognise the limitation of APTT-based assays to discriminate FVL. However, a combination of RVVT- and APTT-based testing is still recommended, as this will provide excellent discriminatory power for the FVL defect, particularly negative prediction, in addition to detection of potential APCR unrelated to FVL, as well as detection of other potential haemostatic disturbances. Accordingly, we detail strategies, including a test algorithm that we are currently using to improve our detection of APCR and prediction of FVL, and use of clotting-based procedures as the first-line approach.

Activated Protein C Resistance↗
PubMed2002

Clinical application of the PFA-100.

The PFA-100 (platelet function analyzer) is a relatively new tool for the investigation of primary hemostasis. Recent studies have shown its utility as a screening tool for investigating possible von Willebrand disorder (VWD) and various platelet disorders. More recently, the PFA-100 has been shown to be valuable in monitoring desmopressin acetate (DDAVP) therapy in both VWD and platelet disorders. The PFA-100 has also been evaluated in many other studies for its utility in assessing drug effects, for potential monitoring of antiplatelet medication (including aspirin), or for evaluation of overall primary hemostasis in various clinical disorders or during surgical procedures. This article reviews current findings and highlights the benefits and limitations of the clinical utility of the PFA-100. Ultimately, the greatest strengths of the PFA-100 are its simplicity of use and excellent sensitivity to particular hemostatic disturbances such as VWD, platelet disorders, and platelet-affecting medication. However, because it is thus a global test system, this also creates a significant limitation because the PFA-100 is not specific for, nor predictive of, any particular disorder. However, used appropriately, the PFA-100 can be considered a worthwhile addition to any hemostasis laboratory involved in the diagnosis or therapeutic monitoring of bleeding disorders and potentially of antiplatelet medication. This review should be valuable to both hemostasis scientists and clinical specialists.

Blood Coagulation Disorders↗
PubMed2002

Identification of von Willebrand disease type 2N (Normandy) in Australia: a cross-laboratory investigation using different methods.

We report on a cross-laboratory study of type 2N von Willebrand disease (vWD). We tested 101 selected plasma samples for factor VIII and factor VIII binding activity of von Willebrand factor (vWF). Of these plasma samples, 31 were cotested by 2 specialist centers using different detection procedures for vWF-factor VIII binding: there was good agreement between results obtained by chromogenic assay and enzyme-linked immunosorbent assay. In total, 8 patients with type 2N vWD were identified. The 2-stage factor VIII assay detected a deficiency of factor VIII relative to vWF antigen in all 8 patients; the 1-stage factor VIII assay detected a relative deficiency in only 3 patients. Four patients were homozygous for the most common type 2N mutation (R854Q), 3 patients were presumed to be compound heterozygotes, and in 1 patient no type 2N mutations were identified. In this study of patients from 5 specialist centers in Australia, type 2N vWD was found in 5 families. The 2-stage factor VIII assay was more useful as a screening test than the 1-stage assay, and both vWF-factor VIII binding assays were equally effective.

Adult↗
PubMed2002

Assessing the usefulness of anticardiolipin antibody assays: a cautious approach is suggested by high variation and limited consensus in multilaboratory testing.

An anticardiolipin antibody (ACA) assay has become a laboratory standard for the detection of antiphospholipid antibodies. We evaluated data from a quality assurance program to assess ACA assay usefulness. Cross-laboratory (n = 56) testing of 12 serum samples yielded interlaboratory coefficients of variation (CVs) for lgG ACA and IgM ACA that were higher than 50% in 17 (71%) of 24 cases. The situation for testing consensus was of equal concern. Total consensus occurred in 6 (25%) of 24 cases. General consensus (interlaboratory agreement, 90% or more) was obtained in 10 (42%) of 24 cases. In the majority of test cases, laboratories could not agree on whether a serum sample tested was ACA-positive or ACA-negative. Differing method-related issues also were evident; some methods tended toward higher or lower ACA values. Method-based majority consensus differed from participant majority consensus on many test occasions. Exceedingly high interlaboratory result variation, combined with a general lack of test result grading consensus and method-based variation, indicate that a cautious clinical approach toward laboratory findings is prudent. Laboratory tests should be repeated at least once before making a clinical diagnosis of any anti-phospholipid syndrome-like disorder.

Antibodies, Anticardiolipin↗
PubMed2002

A comparative multi-laboratory assessment of three factor VIII/von Willebrand factor concentrates.

Five expert laboratories have participated in a cross-laboratory study to co-evaluate and compare three commercial Factor VIII/von Willebrand factor (VWF) concentrates. A total of nine factor concentrate lots were evaluated, comprising AHF (High Purity) (AHF HP; x3), Biostate (x3) and Humate/Haemate (x3). All laboratories blind tested for FVIII: C, VWF: Ag and VWF: CB, four tested for VWF: RCo, and one performed VWF: Multimers. The study yielded inter-laboratory CVs for VWF: Ag and FVIII:C around 10-15%, and for VWF:CB and VWF:RCo around 20%, significantly lower than those of previous multi-laboratory surveys. All three lots of AHF HP contained in the vicinity of 25 U/ml FVIII:C, around 60-75 U/ml of VWF:Ag, but only 30-45 U/ml of VWF:CB and 40-50 U/ml of VWF:RCo (thus, CB/Ag ratio around 0.5-0.6 and RCo/Ag ratio around 0.6-0.7). Study determined that FVIII: C and VWF: RCo levels were similar to manufacturer assigned levels. Some loss of the high molecular weight (HMW) multimers was observed, together with an intense low molecular weight (LMW) VWF band consistent with some reduction or proteolysis of HMW VWF. All three lots of Humate/Haemate contained in the vicinity of 23-32 U/ml of FVIII:C, 70-105 U/ml of VWF: Ag, 50-90 U/ml of VWF: CB and VWF: RCo (i.e. CB/Ag ratio around 0.6-0.9 and RCo/Ag ratio around 0.6-1.1). Study-determined FVIII: C and VWF: RCo levels were similar to manufacturer-assigned levels. The LMW multimer band seen with AHF HP was also observed with Humate/Haemate. All three lots of Biostate contained in the vicinity of 40-55 U/ml of FVIII:C, 105-170 U/ml of VWF:Ag, 90-150 U/ml of VWF:CB, and 90-135 U/ml of VWF:RCo (i.e. CB/Ag and RCo/Ag ratios around 0.7-1.0). Study-determined FVIII:C levels were similar to manufacturer-assigned levels. The LMW multimer band seen with AHF HP was not observed with Biostate. The defined pattern of increasing CB/ Ag from AHF HP to Humate/Haemate and Biostate was consistently observed in study data from each of the five laboratories. In conclusion, study findings indicate some differences in the retention of functional/ HMW VWF between factor concentrates, and this is expected to have significant implications in terms of clinical efficacy for therapy in VWD.

Dimerization↗