Prothrombotic mechanisms and anticoagulant therapy in dogs with immune‐mediated hemolytic anemia

Kidd, Linda; Mackman, Nigel

doi:10.1111/j.1476-4431.2012.00824.x

Cited by 46 publications

(53 citation statements)

References 111 publications

(241 reference statements)

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“…VTE is also recognized as a major cause of death in dogs with AIHA[12,33].Post-mortem examinations in 25 dogs with AIHA showed thromboembolism in 80% of cases[33]. In this study on 72 dogs with AIHA, severe thrombocytopenia, serum bilirubin concentration of N 5 mg/dL and hypoalbuminemia were risk factors for thromboembolism.…”

mentioning

confidence: 77%

Venous thromboembolism related to warm autoimmune hemolytic anemia: A case–control study

Lecouffe-Desprets

Néel

Graveleau

et al. 2015

Autoimmunity Reviews

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mentioning

confidence: 77%

Venous thromboembolism related to warm autoimmune hemolytic anemia: A case–control study

Lecouffe-Desprets

Néel

Graveleau

et al. 2015

Autoimmunity Reviews

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“…Previous data from various animal models and studies in humans also support the potential role of C1‐INH in decreasing coagulation activation, clotting, and fibrinolysis in dogs . This is clinically relevant in IMHA dogs because coagulation abnormalities are common and have been associated with an overall worse prognosis …”

Section: Discussionmentioning

confidence: 78%

In vitro Inhibition of Canine Complement‐Mediated Hemolysis

Hernández¹,

Goggs

Behling‐Kelly³

2017

Veterinary Internal Medicne

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BackgroundImmune‐mediated hemolytic anemia (IMHA) is the most common hematologic immune‐mediated disease in dogs. Complement fixation on erythrocytes causes hemolysis. Complement inhibition decreases hemolysis in people with the hemolytic disease and also may prove effective in treating IMHA in dogs.Hypothesis/ObjectivesEvaluate the in vitro efficacy of 2 complement inhibitors used in humans against canine complement.MethodsThe inhibitory activity of the C3‐inhibitor compstatin and recombinant human C1‐esterase inhibitor (C1‐INH) was evaluated using an in vitro hemolytic assay and spectrophotometric measurement of released hemoglobin. Dose‐response curves for each inhibitor were generated.ResultsCompstatin decreased approximately 50% of canine complement‐mediated hemolysis in initial experiments. This inhibition largely was lost when a new lot of drug was purchased. C1‐INH showed a dose‐dependent inhibition. The highest concentration of C1‐INH tested (500 μg/mL) decreased >80% of canine complement‐mediated hemolysis, and the lowest concentration tested (31.25 μg/mL) decreased hemolysis >60%.Conclusions and Clinical ImportanceHuman C1‐INH is a robust inhibitor of canine complement‐mediated hemolysis, whereas compstatin was minimally and variably effective. Human C1‐INH may substantially decrease complement‐mediated hemolysis in dogs with IMHA and warrants further investigation.

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“…Although it is widely accepted that thrombosis (or thromboembolism) is an important feature of the clinical presentation of IMHA in dogs, the exact mechanisms predisposing these patients to thrombosis are not clear. A relationship between systemic inflammation and increased risk for thrombosis is well described.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Extracellular Traps in Plasma from Dogs with Immune‐mediated Hemolytic Anemia

Lawson

Smith

O'Brien

et al. 2017

Veterinary Internal Medicne

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BackgroundNeutrophil extracellular traps (NETs) are part of the innate immune response and are essential in local pathogen control, but are associated with pathological inflammation, organ damage, autoimmunity, and thrombosis. Immune‐mediated hemolytic anemia (IMHA) is a pro‐inflammatory, prothrombotic disease associated with high mortality.Hypothesis/ObjectivesNeutrophil extracellular traps (NETs) are a feature of the inflammatory process in dogs with IMHA. The objective of the study was to evaluate plasma from dogs with IMHA for the presence of 2 indirect markers and 1 direct marker of NETs.AnimalsHealthy client‐owned dogs (56) and hospitalized dogs with IMHA (n = 35).MethodsProspective study. Plasma samples for all dogs were evaluated for cell‐free DNA using a fluorescence assay, histone‐DNA (hisDNA) complex using an ELISA, and citrullinated histone H3 (specific for NETosis) using Western blot. Reference intervals were generated using plasma from healthy dogs.ResultsIn dogs with IMHA, cell‐free DNA concentration was above the reference interval in 17% of samples with a median (range) of 1.0 μg/mL (0.1–17.3), and hisDNA concentration was above the reference interval in 94% of samples with a median (range) of 30.7 × pooled normal plasma (PNP; 0.6–372.1). Western blot for citrullinated histone H3 identified detectable bands in 84% samples from dogs with IMHA.Conclusions and Clinical ImportanceThe assay for cell‐free DNA detected evidence of NETs in fewer dogs than did the other approaches. Excessive NETs appears to be a feature of IMHA in dogs and contributions to the prothrombotic state deserve further study.

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Prothrombotic mechanisms and anticoagulant therapy in dogs with immune‐mediated hemolytic anemia

Abstract: Prospective clinical trials comparing individually adjusted heparin or other anti-coagulant drugs to anti-platelet drugs are needed to make evidence-based recommendations for thromboprophylaxis in dogs with IMHA.

Cited by 46 publications

References 111 publications

Venous thromboembolism related to warm autoimmune hemolytic anemia: A case–control study

Venous thromboembolism related to warm autoimmune hemolytic anemia: A case–control study

In vitro Inhibition of Canine Complement‐Mediated Hemolysis

Neutrophil Extracellular Traps in Plasma from Dogs with Immune‐mediated Hemolytic Anemia

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