Definition

Develops when a thrombus lodges in the pulmonary arterial tree and occludes blood flow to the portion of lung supplied by that artery.

Pathophysiology

• Pulmonary thromboemboli associated with heartworm disease occur in situ in the pulmonary vessels; in most other instances, the origin of the thrombus is unclear.
• Potential sites of origin include the right atrium, vena cavae, jugular veins, and femoral or mesenteric veins; these venous thrombi are carried in the venous circulation to the lungs, where they lodge in the pulmonary arteries.
• Abnormal blood flow (stasis), vascular endothelial damage, and altered coagulability (hypercoagulable state) are believed to predispose to thrombus formation.
• In most patients, PTE is a complicating feature of another primary disease process.

Systems Affected

• Cardiovascular-pulmonary hypertension may result, leading to right ventricular enlargement, right ventricular failure (cor pulmonale), and reduced cardiac output.
• Respiratory-diminished pulmonary blood flow leads to arterial hypoxemia and dyspnea.

Incidence/Prevalence

• Not known-likelihood of pulmonary thromboembolism increases in animals with abnormal coagulation or severe systemic disease.
• Uncommon diagnosis in the dog and cat; likely under-diagnosed due to nonspecific clinical signs, lack of clinical suspicion, and paucity of non-invasive, definitive diagnostic tests.

Signalment

Signs

Causes

• Heartworm disease
• Neoplasia
• Hyperadrenocorticism (Cushing's disease) or corticosteroid administration
• Protein-losing nephropathy (renal loss of antithrombin) or enteropathy
• Immune-mediated hemolytic anemia
• Pancreatitis
• Pulmonary hypertension (primary or secondary)
• Orthopedic trauma or surgery
• Sepsis
• Disseminated intravascular coagulopathy
• Liver disease

Risk Factors

• Coagulopathy, especially any hypercoagulable state.
• Diseases listed under “Causes” are associated.
• Estrogen administration and air travel may be causative in humans.

Differential Diagnosis

• Other diseases that cause clinically important dyspnea and hypoxemia without profound radiographic findings include upper airway obstruction, laryngeal paralysis, and diffuse airway disease processes (e.g., toxin inhalation and interstitial lung disease).
• Upper airway obstruction often manifests as inspiratory dyspnea; breath sounds often loudest over the trachea or larynx.
• Should be a leading diagnostic consideration in a patient with acute onset of dyspnea or collapse and a disease known to be associated with pulmonary thromboembolism.

CBC/Biochemistry/Urinalysis

CBC-may be normal; thrombocytopenia may be seen in up to 50% of dogs with PTE; leukocytosis may develop. Chemistry profile-results often reflect the underlying disease. Urinalysis-results often reflect the underlying disease; evaluate for proteinuria.

Other Laboratory Tests

• Arterial blood gases often show arterial hypoxemia (PaO₂ often <65 mmHg) and low PaCO₂ with respiratory alkalosis.
• Metabolic and respiratory acidosis may develop in severely affected patients.
• D-dimers result from the breakdown of cross-linked fibrin and are indicators of physiologic or pathologic thrombosis. D-dimer testing plays a pivotal role in diagnostic algorithms for PTE in humans; however, their utility for diagnosis of PTE in veterinary patients is uncertain. Plasma D-dimer levels may be inconsistently elevated in dogs with PTE and a low D-dimer level does not exclude the possibility of PTE.
• Thromboelastography is a technique that provides a global assessment of coagulation and thrombolysis; may be useful in diagnosing systemic hypercoagulability but not widely available.
• Coagulation profile may show high fibrin degradation products, abnormal fibrinogen, or alterations in one-stage PT and activated PTT.
• Heartworm serology (antigen testing in dogs; both antigen and antibody testing in cats) should be performed in any animal with suspected PTE.
• Cardiac biomarkers-cardiac troponin I and NT-proBNP levels may be elevated.

Imaging

Diagnostic Procedures

Pathologic Findings

• Thrombi in the major branches of the pulmonary arteries.
• Some patients exhibit multiple smaller thrombi in small vessels of the pulmonary arteries, eventually leading to marked respiratory dysfunction and death.
• Concurrent pulmonary pathology such as pneumonia, pulmonary edema, pulmonary neoplasia or interstitial fibrosis is common.

Appropriate Health Care

Treat patients documented to have pulmonary thromboembolism as inpatients until hypoxemia is resolved.

Nursing Care

• Administer IV fluids cautiously unless pre-existing volume depletion exists; they may contribute to the development of right-sided congestive heart failure.
• Administer oxygen if dyspnea exists and/or PaO₂ <65 mmHg; response to oxygen therapy is variable.

Client Education

• Alert client that disease is often fatal; further episodes are likely unless an underlying cause is identified and corrected; sudden death is not unusual.
• Treatment with traditional anticoagulant medications can lead to bleeding complications necessitating frequent re-evaluation of clotting times (e.g., PT and PTT) for successful management; LMWHs are safer and require less monitoring but are associated with greater expense; anticoagulant administration may be required for several months, even after resolution of the causative disease.

Drug(s) Of Choice

• Always identify and treat the underlying disease; if this is unlikely to be successful, aggressive efforts to treat pulmonary thromboembolism will probably be in vain.
• Unfractionated heparin may help to prevent further thrombi from developing; low dosages are probably inadequate for initial management; a dosage of 200–300 units/kg SC q8h or alternatively a bolus of 200 units/kg IV followed by a CRI at 15–30 units/kg/h adjusted to maintain the PTT at 1.5–2 times the baseline value.
• Thrombolytic drug administration (e.g., urokinase, streptokinase or tissue plasminogen activator) may also be useful in hemodynamically unstable cases; these drugs are expensive and carry a higher risk of bleeding complications.
• Warfarin-may be considered for long-term treatment (0.1 mg/kg q24h), with dosage adjustments to maintain a PT 1.5–2 times the baseline value; animals must be heparinized prior to warfarin therapy to avoid initial hypercoagulable phase.
• The low molecular weight heparins are likely associated with fewer bleeding complications than UFH or warfarin, require less intensive monitoring, and are more suitable for long-term management; however, the expense of these drugs may be a limiting factor in their use.
• Thromboprophylactic effects have been demonstrated for dalteparin (150 units/kg SC q12h) in the absence of prolonged bleeding times or adverse effects; enoxaparin has been used at 1 mg/kg SC q12h.
• Sildenafil (1–2 mg/kg PO q 8–12 h) may be helpful in selected animals with PTE and concomitant pulmonary hypertension.

Precautions

Warfarin-interacts with many other drugs; degree of anticoagulation may change after giving these drugs; or with diet alterations. Dose titration may be difficult in patients with diseases that result in coagulopathy. Review the mechanism of action and pharmacology of the antithrombotic drugs before use.

Patient Monitoring

• Serial arterial blood gases and/or pulse oximetry-may help determine improvement in respiratory function.
• Check PT every 3 days initially for adjusting warfarin dosage to achieve a PT 1.5–2 times the baseline value. International normalization ratios (INR) are recommended to minimize the effects of variability in thromboplastin preparations on PT results. Check weekly after an effective dosage is achieved (typically no sooner than 2 weeks).

Prevention/Avoidance

• Activity or physical therapy may improve venous blood flow and prevent development of venous thrombi in immobile patients with severe systemic disease.
• Aspirin (0.5–5 mg/kg PO q12–24h) may have some preventive role but is inadequate as treatment.
• Clopidogrel (1–2 mg/kg PO q24h) is an alternative antiplatelet drug that may have some role in prevention. A single loading dose, up to 10 mg/kg, can be administered for rapid platelet inactivation in cases with active thrombosis.
• Heparin may be administered to animals predisposed to the development of pulmonary thromboembolism (200 units/kg IV initially and 75–200 units/kg SC q8h).
• Alternatively, dalteparin (150 units/kg SC q12h) may be used for thromboprophylaxis.
• Newer oral anticoagulants such as rivaroxaban, apixaban, or dabigatrin may be as effective as warfarin for prevention of recurrent thrombosis in people and require less monitoring; these drugs may play a future role in longer-term anticoagulation of veterinary patients but further study on dosing and safety in animals is needed.

Possible Complications

Clinically important bleeding complications may arise in patients treated with anticoagulant drugs. Bleeding may occur from any organ system. Anticipate active bleeding or anemia necessitating blood or plasma transfusion and have blood products readily available.

Expected Course and Prognosis

Generally guarded to poor; depends on resolution of the precipitating cause. For irreversible diseases (e.g., some neoplasias and advanced protein-losing nephropathy), prognosis is poor long-term; it is somewhat better for patients with thromboembolism due to trauma or sepsis.

Synonym

Pulmonary embolism

See Also

• Anemia, Immune-Mediated
• Disseminated Intravascular Coagulation
• Heartworm Disease-Cats
• Heartworm Disease-Dogs
• Hyperadrenocorticism (Cushing's Syndrome)-Cats
• Hyperadrenocorticism (Cushing's Syndrome)-Dogs
• Nephrotic Syndrome
• Sepsis and Bacteremia

Abbreviations

• CT = computed tomography
• LMWH = low molecular weight heparin
• PT = prothrombin time
• PTE = pulmonary thromboembolism
• PTT = partial thromboplastin time
• UFH = unfractionated heparin

Client Education Handout Available Online