Is Hypocoagulability Associated with Pulmonary Hypertension in Dogs?

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December 2024

In today’s VETgirl online veterinary CE podcast, we discuss hypocoagulability in dogs with pulmonary hypertension. For quick review, pulmonary hypertension, which we will refer to as “PH”, is an abnormal increase in pulmonary pressure and can be caused from cardiac, respiratory, or systemic conditions. In human medicine, both hyper- and hypocoagulability have been associated with PH, but no veterinary studies have been performed on this topic… until now! So today we will be reviewing the AJVR retrospective study by Min et al entitled “Pulmonary Hypertension is Associated with Hypocoagulability in Dogs: A Retrospective Analysis of 66 Cases (2013-2021).”

Now, pulmonary hypertension is pretty tricky to diagnose for all but our trained cardiologists because a definitive diagnosis is only made with the help of measurements from a right heart catheter. As you may imagine, this is technically challenging and typically cost prohibitive. So in veterinary medicine, we instead can make a “presumed” or “highly suspected” PH diagnosis and assign PH severity by identifying echocardiographic changes secondary to PH and indirectly estimating pulmonary arterial pressures (This typically requires evaluating  the severity of tricuspid regurgitation, calculating LaPlace’s law, and a bunch of other fancy cardiology toolbox tricks). With increasing severity of PH, dogs may find their way to us clinicians in various states of mild to severe respiratory distress, they may have syncopal episodes, or they may even present in right-sided heart failure.1 So do we now also have to worry about these patients developing a coagulopathy? Let’s find out!

In this retrospective evaluation of cases, the authors looked at coagulation profiles of dogs performed within 7 days of echocardiographic assessment of PH. Dogs were excluded if they were on antithrombotic medications, diagnosed with a coagulopathy, or diagnosed with severe systemic disease (like DIC or heat stroke) that we would expect to markedly affect coagulation. Thorough details about the patient, diagnostics, treatment, and outcome were extracted from the medical records. Dogs with evidence of PH were classified as low probability, intermediate probability, or high probability according to the 2020 ACVIM consensus guidelines using echocardiographic assessment of peak tricuspid regurgitation velocities and number of sites exhibiting signs of PH.(2) Cases that fell into the intermediate or high categories were included in this study and further classified based on etiology of their PH as 1) pulmonary arterial hypertension 2) left-sided cardiac disease 3) respiratory disease 4) pulmonary embolic disease 5) parasitic disease (like heart or lungworm) and 6) multifactorial or unclear mechanism.

A total of 152 dogs were enrolled in the study, 86 without PH and 66 with PH. Of the 66 dogs with PH, 17/66 (25.8%) had intermediate probability of PH and 49/66 (74.2%) had high probability of PH. Most of these dogs were categorized as type 4 PH which we can recall means secondary to pulmonary embolic or thromboembolic disease. Dogs with PH had significantly higher PT (P = 0.02), PTT (P < 0.0001), and fibrinogen (P = 0.045), but yet lower antithrombin levels (P = 0.005) than dogs without PH. The most common coagulation abnormality found here was a prolonged PTT. The authors also make note that dogs with PH were almost 12X more likely to be hypocoagulable!

These results suggest that dogs with PH may develop the hypocoagulable phenotype regardless of their underlying cause for PH and regardless of whether they are classified as intermediate or severe. Authors theorize that dogs with PH become hypocoagulable after exhausting their coagulation factors from activation by chronic pulmonary endothelial damage. But this theory would also then imply that dogs may first go through a phase of being HYPERcoagulable before becoming HYPOcoagulable. Since many PH dogs in this study suffered from pulmonary embolism or thromboembolism, it stands to reason that these NOW hypocoagulable dogs were potentially once hypercoagulable.

Some limitations of this study include its retrospective nature and small sample size which is fairly common in veterinary studies. The authors also mention that they couldn’t directly compare PT or PTT absolute values because their hospital’s reference intervals changed throughout the span of the study making direct value comparison no longer meaningful. Instead they compared percent prolongation above the test’s maximum reference interval (RI) value which would look like this: [100 x (Patient PTT– maximum RI PTT) / maximum RI PTT], and does still provide meaningful information.

So, what can we take away from this VETgirl podcast? Well, we know that more studies are needed to help us understand the global coagulation states in patients with PH. Remember that the more commonly accessible in-hospital coagulation tests like PT, PTT, ACT, and BMBT only specifically test for HYPOcoagulation. In order to determine HYPERcoagulability, we need access to viscoelastic testing such as rotational thromboelastometry (ROTEM) or thromboelastography (TEG) which are not as widespread available in hospitals other than perhaps larger ER/trauma hospitals and referral specialty practices, or these tests are also accessible through veterinary diagnostic laboratories. But as this study demonstrates, dogs with moderate to high probability of PH are prone to becoming hypocoagulable. So now when faced with a dog with PH and a potentially HYPERcoagulable co-morbidity (i.e. PTE), before starting chronic anti-thrombotic therapies such as aspirin or clopidogrel, perhaps we should first consider submitting full panel coagulation testing to help us better understand our individual patient’s PRESENT state of coagulability.

Reference:
1. Min S, Wesselowski SR, Nabity MB, et al. Pulmonary hypertension is associated with hypocoagulability in dogs: a retrospective analysis of 66 cases (2013-2021). Am J Vet Res. 2024 Feb 12;85(4):ajvr.23.11.0252. doi: 10.2460/ajvr.23.11.0252.
2. Reinero C, Visser LC, Kellihan HB, et al. ACVIM consensus statement guidelines for the diagnosis, classification, treatment, and monitoring of pulmonary hypertension in dogs. J Vet Intern Med. 2020; 34: 549–573.

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