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Biomedical subjects

Ross Baker

Publications and source records attributed to Ross Baker.

11 recordsLinked to original sources
PubMed2006

Reducing errors in identification of von Willebrand disease: the experience of the royal college of pathologists of australasia quality assurance program.

Regular multilaboratory surveys of laboratories derived primarily from Australia, New Zealand, and Southeast Asia have been conducted during the last 8 years to evaluate testing proficiency in the diagnosis of von Willebrand disease (vWD). We summarize and update the findings of these surveys with a particular emphasis on diagnostic errors and error rates associated with particular tests or test panel limitations. A total of 43 plasma samples have been dispatched to survey participants. These have included 13 normal samples, five type 1 vWD samples, eight type 2 vWD samples (three 2A, three 2B, one 2M, and one 2N), and four type 3 vWD samples. In addition to numerical test results, participant laboratories (currently, n = 49) were asked to provide diagnostic interpretations regarding results, and whether or not vWD was suggested, and if so, a 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 in 13.3% of cases, and laboratories performing von Willebrand factor (vWF):ristocetin cofactor activity (RCo) without vWF:collagen-binding activity (CB) were seven times more likely to make such an error compared with those performing vWF:CB. Similarly, type 2 vWD plasma was misidentified as type 1 or type 3 vWD in an average of 20.1% of cases, and laboratories performing vWF:RCo without vWF:CB were three times more likely to make such an error compared with those performing vWF:CB. Finally, normal plasma was misidentified as vWD in an average of 6.7% of cases, and laboratories performing vWF:RCo without vWF:CB were four times more likely to make such an error compared with those performing vWF:CB. We conclude that although laboratories are generally proficient in tests for vWD, diagnostic errors do occur and error rates are substantially reduced when test panels are more comprehensive and include the vWF:CB.

Australasia↗
PubMed2006

The tissue factor pathway in ischemic stroke.

To explore the role of the the tissue factor (TF) pathway in ischemic stroke. We measured blood concentrations of markers of the TF pathway [TF antigen, free tissue factor pathway inhibitor antigen (TFPIf) and activity (TFPIac), and activated factor VII (FVIIa)] within 7 days (acute phase) and after 3-6 months (convalescence) in 150 patients with first-ever ischemic stroke and 150 community controls. During the acute phase, TF antigen and TFPIf were not significantly altered but TFPIac was increased (mean 1.27 versus 1.13 U/ml, P = 0.04) and FVIIa was decreased in cases compared with controls (mean 43.3 versus 57.9 mU/ml, P = 0.0004). After adjusting for baseline differences between cases and controls, increasing quartiles of TFPIf were independently associated with reduced odds of stroke, and reducing quartiles of FVIIa and increasing quartiles of TFPIac with increased odds of stroke. During the convalescent phase, FVIIa and TFPIac returned to normal but TF antigen and TFPIf were significantly decreased compared with controls [median TF antigen, 110 (follow-up) versus 155 pg/ml (controls), P = 0.0008; median TFPIf, 15.5 (follow-up) versus 23.3 ng/ml (controls), P = 0.002]. Alterations of blood concentrations of TF pathway markers are common in patients with acute ischemic stroke. The mechanisms are unclear but may relate to enhanced formation of TF-FVIIa complexes and upregulation and release of TFPI during the acute phase, and ongoing consumption of TF antigen and TFPIf during the chronic phase as the atherosclerotic plaque heals.

Aged↗
PubMed2006

The effects of tissue factor pathway inhibitor and anti-beta-2-glycoprotein-I IgG on thrombin generation.

BACKGROUND AND OBJECTIVES: Recent evidence suggests that autoantibodies to tissue factor pathway inhibitor (TFPI) and/or antiphospholipid antibodies (aPL) may contribute to upregulation of the tissue factor (TF) pathway of blood coagulation and the development of thrombotic complications in the antiphospholipid syndrome (aPS). The aim of this study was to determine the influence of aPL e.g. anti-beta-2-glycoprotein-I (anti-beta2GPI) and anti-prothrombin, on in vitro TF-induced thrombin generation in the presence and absence of TFPI. DESIGN AND METHODS: IgG fractions were collected from subjects with aPL (n=21) and normal controls (n=36). Anti-TFPI activity was determined after incubation of IgG isolated from control or subject plasma with pooled normal plasma using an amidolytic assay for TFPI. The influence of IgG fractions and purified aPL (anti-beta2GPI and anti-prothrombin) on TF-induced in vitro thrombin generation was determined using a chromogenic assay of thrombin activity. RESULTS: Patients with aPL had significantly elevated thrombin generation (median [interquartile range]) compared to normal controls (112.0 [104.0-124.0]% vs 89.9 [85.7-100.9]%, respectively; p<0.001). Thrombin generation was significantly correlated with anti-TFPI activity in patients with aPL (r(s)=0.452; p=0.039). It was also demonstrated that anti-beta2GPI, but not anti-prothrombin IgG antibodies, significantly enhanced TF-induced thrombin generation in the presence of TFPI, using both purified and patients' samples. INTERPRETATION AND CONCLUSIONS: Our findings support the hypothesis that anti-beta2GPI IgG antibodies accelerate thrombin generation in the presence of TFPI and may contribute to hypercoagulability in patients with aPS.

Adult↗
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↗
PubMed2004

Anti-tissue factor pathway inhibitor activity in subjects with antiphospholipid syndrome is associated with increased thrombin generation.

BACKGROUND AND OBJECTIVES: Immunoglobulin G (IgG) fractions from subjects with antiphospholipid syndrome (aPS) have previously been demonstrated to have inhibitory activity against tissue factor pathway inhibitor (TFPI). This may contribute to the development of a prothrombotic state by impaired regulation of the tissue factor (TF) pathway. This study investigated the effect that IgG fractions from aPS subjects containing anti-TFPI activity have on in vitro TF-induced thrombin generation. DESIGN AND METHODS: TFPI and anti-TFPI activities were determined in normal controls (n=29) and aPS subjects (n=57). TFPI activity was determined using an amidolytic assay based on the generation of factor Xa. Anti-TFPI activity was determined after incubating IgG isolated from a control or subject plasma with pooled normal plasma, using the TFPI activity assay. The influence of IgG fractions from controls (n=10) and subjects (n=23) on TF-induced in vitro thrombin generation was determined using a chromogenic assay of thrombin activity. RESULTS: TFPI activity in controls (1.13+/-0.25 U/mL) was significantly lower than in subjects (1.30+/-0.42 U/mL) (p < 0.05). Anti-TFPI activity was significantly higher in subjects than controls (p = 0.0001). TF-induced thrombin generation was positively associated with anti-TFPI activity (r = 0.356; p > 0.05), with increased levels of each demonstrated in 5 subjects. INTERPRETATION AND CONCLUSIONS: Anti-TFPI activity was confirmed in 65% of aPS subjects. IgG fractions demonstrated a variable ability to interfere with TFPI function and TF-induced thrombin generation. Cross-reacting antiphospholipid antibodies and/or other entities may interfere with TFPI function, resulting in a net increase in thrombin generation and an increased thrombotic risk.

Adult↗
PubMed2003

Protein Z in ischemic stroke and its etiologic subtypes.

BACKGROUND AND PURPOSE: Protein Z is a vitamin K-dependent plasma protein whose significance in arterial thrombosis remains uncertain. The objectives of this study were to determine the association between protein Z, ischemic stroke, and etiologic subtypes of ischemic stroke. METHODS: We conducted a case-control study of 173 hospital cases of first-ever ischemic stroke and 186 randomly selected community controls. Using established criteria, we classified cases of stroke by etiologic subtype. Protein Z concentrations were measured during the first 7 days and at 3 to 6 months after the acute stroke event. RESULTS: Blood levels of protein Z measured within 7 days of acute stroke were significantly higher in cases than in controls (geometric mean, 1.46 versus 1.16 microg/mL; P<0.0001). Compared with the lowest tertile, the upper 2 tertiles of protein Z were associated with an adjusted odds ratio (OR) of ischemic stroke of 1.75 (95% CI, 1.00 to 3.07) for the second tertile and 3.07 (95% CI, 1.73 to 5.45) for the upper tertile. The adjusted odds of ischemic stroke caused by large-artery atherothrombosis was nearly 8-fold greater for those with protein Z concentrations in the upper tertile compared with the lower tertile (OR, 7.91; 95% CI, 3.11 to 20.14). The adjusted odds of ischemic stroke due to small-artery disease (OR, 1.79; 95% CI, 0.83 to 3.87) and cardioembolism (OR, 1.80; 95% CI, 0.58 to 5.64) was also increased among individuals with protein Z concentrations in the upper tertile compared with the lower tertile, but not significantly so. There was no significant difference between mean protein Z concentrations among cases in the convalescent phase (3 months) after stroke and age- and sex-matched controls. CONCLUSIONS: There is a strong, independent relationship between elevated blood levels of protein Z and ischemic stroke during the acute phase, particularly ischemic stroke due to large-artery atherothromboembolism, which is no longer evident during the convalescent phase. These results are consistent with the notion that protein Z is either an important factor in the pathogenesis of ischemic stroke due to large-artery atherothromboembolism or an acute phase reactant. Further studies are required to elucidate whether protein Z has a causative or prognostic role in acute arterial thrombosis.

Age Distribution↗
PubMed2002

Pre-operative hemostatic assessment and management.

Excessive surgical bleeding can be predicted and then prevented in most patients with a recognised hereditary bleeding tendency or in those on anti-thrombotic therapy. However the clinical consultation of an individual patient can be challenging because the diagnosis can be unclear or a balance needs to be achieved between minimising bleeding without precipitating thrombosis. Laboratory testing does provide assistance in assessment of a bleeding tendency but it is not uncommon for the results to be inconclusive. Investigations such as the level of von Willebrand factor assays should be regarded as a continuous risk factor for surgical bleeding rather than defining a disease category. Appropriate replacement therapy prior to surgery is effective in preventing surgical bleeding. Aggressive anti coagulant therapy around the time of surgery in patients who usually are on warfarin more often lead to unnecessary haemorrhage rather than preventing further thrombosis. A risk assessment of both bleeding versus thrombosis for the particular operation is necessary to ensure the best outcome.

Blood Loss, Surgical↗
PubMed2002

Investigation of coagulopathy in three cases of tiger snake (Notechis ater occidentalis) envenomation.

AIMS: To investigate the severe coagulopathy (fibrinogen < 1.0 g/l) that occurs in some cases of tiger snake envenomation. Specifically, to determine the concentration of clotting factors on presentation and during resolution of the coagulopathy. METHODS: Clotting factors II, V, VII, VIII, IX, XI were assayed on all coagulation samples received from three successive cases of severe tiger snake envenomations. Assays were performed at dilutions of 1:5 and 1:10 using an MLA 1600c automated coagulation analyser and Dade Behring factor-deficient plasmas, controls and standards. D-dimers were assayed using Agen Dimertest latex kit, fibrinogen was determined using the Clauss method and platelet counts were performed using Abbott Cell-Dyn 4000 analysers. RESULTS: The activity of the coagulation factors of the intrinsic pathway was reduced (factor VIII < 44% in all cases, factor IX < 33%, factor XI < 52% in Cases 1 and 2) but the results for the two dilutions were not parallel. In one case, factor VIII and factor IX activity increased 2-fold prior to the administration of blood products. Treatment with blood products corrected the coagulation indices in two out of the three cases but factor V remained low in one case (25%). CONCLUSIONS: The non-parallel results and the apparent increase in factor levels prior to treatment may result from the transient presence of an inhibitor to factors VIII, IX and XI in cases of tiger snake envenomation. Insight into the effects of snake venom on individual coagulation factors could be beneficial when considering new treatments for the coagulopathy induced by snake envenomation.

Adult↗