Evidence-based information & thrombosis awareness
What Causes Blood Clots in IMHA?
Clinical Focus: Mechanisms contributing to hypercoagulability and thrombosis in IMHA.
Why Thrombosis Matters in IMHA
Immune-mediated haemolytic anaemia is associated with substantial morbidity and mortality, particularly in dogs. Thrombotic disease is a recognised and important complication and is considered a leading contributor to poor outcome, alongside the effects of severe anaemia, haemolysis, inflammation and concurrent disease.
Pulmonary thromboembolism and thrombosis at other sites have been documented in affected dogs, but the precise frequency and distribution of clinically important thrombi are difficult to determine because many events are not diagnosed before death.
Understanding the mechanisms that favour thrombosis helps explain why the 2019 ACVIM consensus strongly recommends thromboprophylaxis for dogs with IMHA unless severe thrombocytopenia or another important contraindication makes treatment inappropriate [Swann et al., 2019].
Applying Virchow's Triad
Virchow's triad is a classical framework for understanding thrombosis, grouping contributing factors into changes affecting the vessel wall, blood flow and the coagulation system.
Inflammation and endothelial activation can favour expression of procoagulant signals and reduce normal antithrombotic properties of the vascular surface.
Anaemia, altered blood viscosity, cardiovascular compensation, immobility and critical illness can contribute to disturbed blood flow and haemostatic imbalance.
Multiple procoagulant, platelet and fibrinolytic changes can shift haemostasis towards thrombosis.
Mechanisms That May Contribute to Hypercoagulability
Research in canine IMHA suggests that several overlapping mechanisms may contribute to a prothrombotic state. The importance of each mechanism in an individual patient is not fully established, and feline evidence is more limited.
1. Haemolysis and Procoagulant Signalling
Intravascular haemolysis releases cell-free haemoglobin and erythrocyte-derived material into the circulation. Haemolysis, inflammation and monocyte or endothelial activation may promote tissue-factor expression and other procoagulant signalling.
2. Platelet Activation
Platelet activation has been documented in canine IMHA and may contribute to thrombus formation. Platelets interact with coagulation proteins, inflammatory mediators and the vascular endothelium, creating several routes by which inflammation and coagulation can amplify one another.
3. Inflammation and Endothelial Activation
Systemic inflammation can alter endothelial function and promote procoagulant activity. Inflammatory mediators may also affect platelet activation, coagulation-factor expression and natural anticoagulant pathways.
4. Neutrophil Extracellular Traps (NETs)
Neutrophil extracellular traps are DNA- and protein-rich structures released during neutrophil activation. In a prospective study of 35 dogs with IMHA, histone-DNA complexes were above the reference interval in 94% of samples and citrullinated histone H3, a more specific marker of NETosis, was detected in 84%. These findings support NET formation as a feature of canine IMHA, but they do not establish how much NETosis contributes to clinical thrombosis in an individual dog [Lawson et al., 2018].
5. Reduced Fibrinolytic Capacity
A 2025 study of 20 dogs with non-associative IMHA found hypercoagulable thromboelastography tracings, frequent resistance to tissue-plasminogen-activator-induced clot lysis, increased TAFI activity and higher active PAI-1 concentrations than in healthy controls. These results support hypofibrinolysis — impaired clot breakdown — as another component of the prothrombotic state, while the clinical importance of individual fibrinolytic abnormalities and their treatment implications remain under investigation [Goggs et al., 2025].
A 2026 retrospective study of 35 dogs with IMHA found clot-waveform abnormalities consistent with a hypercoagulable haemostatic profile in nearly all dogs assessed, while D-dimer was increased in 17 of 18 dogs in which it was measured. These findings add laboratory evidence of disturbed coagulation in canine IMHA, but clot-waveform analysis is not yet a validated stand-alone predictor of which individual dogs will develop clinical thrombosis [Richter et al., 2026].
Interactive Pathway Model
This schematic illustrates some of the cellular and coagulation components that can participate in thrombus formation. It is conceptual rather than a literal sequence of events.
Antithrombotic Treatment Context
Because canine IMHA is associated with clinically important thrombotic risk, the 2019 ACVIM consensus recommends thromboprophylaxis for dogs with IMHA except where severe thrombocytopenia or another important contraindication makes treatment inappropriate [Swann et al., 2019]. The consensus suggests that a regimen incorporating an anticoagulant may be preferred, particularly during the first two weeks after diagnosis, while antiplatelet drugs and combination regimens may also be selected according to the individual patient.
Rivaroxaban inhibits factor Xa, while clopidogrel inhibits platelet P2Y12 signalling. They act at different points in haemostasis and are not simply interchangeable alternatives. A 2026 retrospective IMHA cohort also reported gastrointestinal bleeding in 5 of 34 rivaroxaban-treated dogs, including two major bleeds and one fatal event, although the study could not establish that rivaroxaban caused those events [Conway et al., 2026]. Selection, combination, monitoring and duration should therefore be determined by the attending veterinary surgeon using current guidance and the individual patient’s thrombotic and bleeding risks.