A retrospective study of canine D‐dimer concentrations measured using an immunometric “Point‐of‐Care” test

Dewhurst, E; Cue, SM; Crawford, EM; Papasouliotis, Kostas

doi:10.1111/j.1748-5827.2008.00583.x

Cited by 31 publications

(41 citation statements)

References 12 publications

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“…In both dogs expressing FIX in the range of mild hemophilia (Wick and Trex), TAT complex and D-dimer levels at multiple time points remained in the normal range, 26,32 consistent with a lack of clinically recognized thrombosis (supplemental Figure 3). Notably, data from the dog Wiley showed continuous expression of supraphysiologic levels of FIX-Padua after inhibitor eradication for .400 days and yet presented no clinical evidence of peripheral thrombosis.…”

Section: Canine Studiesmentioning

confidence: 89%

“…24 Canine FIX antigen, activity, and antibody assays Whole blood clotting time (WBCT), cFIX antigen and activity, and thromboelastography (TEG) were assayed as previously described. 25,26 Neutralizing antibodies to cFIX were determined by the Bethesda assay. Antibodies against cFIX were measured by enzyme-linked immunosorbent assay (ELISA) against immunoglobulin (Ig)G1, IgG2, and total IgG (Bethyl Laboratories, Montgomery, TX).…”

Section: Systemic and Local Toxicitymentioning

confidence: 99%

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AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice

Crudele

Finn

Siner

et al. 2015

Blood

138

178

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• Liver-restricted expression of FIX-Padua induces immune tolerance to the transgene in hemophilia B inhibitor dog models.• Long-term toxicity studies show no increased risk of thrombogenicity of FIX-Padua in mice and dogs.Emerging successful clinical data on gene therapy using adeno-associated viral (AAV) vector for hemophilia B (HB) showed that the risk of cellular immune response to vector capsid is clearly dose dependent. To decrease the vector dose, we explored AAV-8 (1-3 3 10 12 vg/kg) encoding a hyperfunctional factor IX (FIX-Padua, arginine 338 to leucine)in FIX inhibitor-prone HB dogs. Two naïve HB dogs showed sustained expression of FIX-Padua with an 8-to 12-fold increased specific activity reaching 25% to 40% activity without antibody formation to FIX. A third dog with preexisting FIX inhibitors exhibited a transient anamnestic response (5 Bethesda units) at 2 weeks after vector delivery following by spontaneous eradication of the antibody to FIX by day 70. In this dog, sustained FIX expression reached ∼200% and 30% of activity and antigen levels, respectively. Immune tolerance was confirmed in all dogs after challenges with plasma-derived FIX concentrate. Shortening of the clotting times and lack of bleeding episodes support the phenotypic correction of the severe phenotype, with no clinical or laboratory evidence of risk of thrombosis. Provocative studies in mice showed that FIX-Padua exhibits similar immunogenicity and thrombogenicity compared with FIX wild type. Collectively, these data support the potential translation of gene-based strategies using FIX-Padua for HB. (Blood. 2015;125(10):1553-1561

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Section: Canine Studiesmentioning

confidence: 89%

Section: Systemic and Local Toxicitymentioning

confidence: 99%

AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice

Crudele

Finn

Siner

et al. 2015

Blood

138

178

View full text Add to dashboard Cite

show abstract

“…Platelet counts were within the normal range throughout the study ( Figure 3A). Because mice continuously expressing mFVIIa at levels more than 2 g/mL exhibited premature mortality, 10 to further address the safety of this gene transfer approach, we used 3 different assays: levels of TAT complex, D-dimer levels (elevated levels of which are indicators of thromboembolic disease and disseminated intravascular coagulation [DIC] in dogs 29,30 ), and fibrinogen levels, elevated levels of which are associated with cardiovascular disease. 31 We did not detect any significant changes in TAT or D-dimer levels relative to pre-AAV administration (P Ͼ .2) in any of the vector doses used in AAV-treated dogs throughout the observation period ( Figure 3B and C, respectively).…”

Section: Safety Of Long-term Cfviia Expression In the Aav-treated Hemmentioning

confidence: 99%

Successful treatment of canine hemophilia by continuous expression of canine FVIIa

Margaritis

Roy

Aljamali

et al. 2009

Blood

103

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“…A sensitivity of 100% with a specificity of 97% has been reported (Stokol et al 2000). An immunometric "Pointof-Care" test has been used in healthy dogs (Wiinberg et al 2007), dogs with chronic congestive heart failure (Tarnow et al 2007) and in clinically ill dogs with and without TE/DIC (Dewhurst et al 2008). In the latter study, D-dimer test was found to be an easy to use test, which could aid in a first opinion practice.…”

Section: Methods For D-dimer Determinationmentioning

confidence: 99%

D-dimer as a diagnostic tool for canine thromboembolic disorders

Giannoulopoulos

Athanasiou

Polizopoulou

2017

J Hellenic Vet Med Soc

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D-dimers are small protein fragments present in the blood after a blood clot is degraded by plasmin. During the fibrin(ogen) degradation, a number of products are produced called fibrin(ogen) degradation products (FDPs). D-dimers are part of the FDPs, formed as a result of plasmin activity on cross-linked fibrin. Thus, D-dimers indicate the activity of both thrombin and plasmin and are specific markers for fibrinolysis. D-dimer measurement is widely used in the diagnostic work-up of human patients as the most sensitive test to diagnose pulmonary thromboembolism (PTE) and disseminated intravascular coagulation (DIC) and it is, also, considered essential in the evaluation of antithrombotic therapy. During the last decade, there was considerable research regarding the potential utility of D-dimer in veterinary medicine, particularly in canine and equine species. In dogs, D-dimer plasma concentrations can be used to rapidly detect the thrombotic complications and DIC associated with many systemic diseases (high quantitative D-dimer levels). The symptoms of PTE are subtle and the confirmation of diagnosis with routine hematological tests can be difficult, thus jeopardizing the patient's survival. Several techniques have been employed for the detection of D-dimer; the immunoenzymatic assay (ELISA), the immuno-turbidimetric assay and several latex agglutination assays are more commonly used.

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A retrospective study of canine D‐dimer concentrations measured using an immunometric “Point‐of‐Care” test

Cited by 31 publications

References 12 publications

AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice

AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice

Successful treatment of canine hemophilia by continuous expression of canine FVIIa

D-dimer as a diagnostic tool for canine thromboembolic disorders

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