Pulmonary thromboembolism (Proceedings)
Pulmonary thromboembolism (PTE) is the occlusion of the pulmonary vasculature by products of the coagulation cascade. Thrombosis of pulmonary vasculature results in an ischemic condition. This commonly results in tachypnea, dyspnea, and potentially, cyanosis. PTE occurs through 3 major mechanisms; damage to vascular endothelium, altered pulmonary blood flow, and hypercoagulability. Diseases commonly associated with damage to vascular endothelium include dirofilariasis, neoplasia, valvular heart disease, endotoxemia, and any cause of vasculitis including pancreatitis and immune mediated disease. Altered pulmonary blood flow occurs most commonly with cardiomyopathy, partial venous occlusion by granulomatous disease or neoplasia, valvular heart disease, vascular tumors, any form of shock, polycythemia, and hyperviscosity syndromes. Syndromes of hypercoagulability can be either primary or secondary. People develop primary antithrombin III (ATIII), protein C, plasminogen, and plasminogen activator deficiencies as well as dysfibrinogenemia that predisposes to thrombus formation. Acquired hypercoagulability occurs with many diseases resulting in decreased production of ATIII, lost of ATIII, increased concentration of some coagulation factors, platelet hypersensitivity, or thrombocytosis.
Following the development of pulmonary thromboembolism, ventilation perfusion mismatch occurs leading to hypoxemia and hypocapnia. Pulmonary arterial hypertension occurs due to massive embolism and reflex vasoconstriction that leads ultimately to cor pulmonale. Regional bronchial constriction and resultant increased airway resistance occurs secondary to increased vagal stimulation or factors associated with thrombus formation. The combination of these pathologic mechanisms leads to clinical signs of disease.The most common clinical signs associated with PTE include acute onset dyspnea or tachypnea with or without cough and hemoptysis. Auscultation generally reveals increased bronchial sounds; crackles are rare. Split second heart sound may occur due to pulmonary arterial hypertension.
Diagnosis can be difficult. Thoracic radiographic findings are dependent on the primary disease but can include increased interstitial densities, increased size of the pulmonary arteries, mild right heart enlargement, alveolar lung disease, and pleural effusion. Occasionally, thoracic radiographs are normal acutely. Central venous pressure is often greater than 3 cm of H2O due to occlusion of pulmonary arteries and resultant increased backpressure into the right heart. Hypoxemia and hypocapnia are common abnormalities noted by assessing arterial blood gases. There is often a dramatic increase in PO2 when arterial blood gas assessment is repeated with the animal breathing oxygen from a tight fitting facemask. This finding is supportive of PTE. Definitive diagnosis requires angiography, nuclear scintigraphy (ventilation/perfusion scan) or necropsy.
PTE in dogs and cats occurs most commonly with cardiac diseases, protein-losing nephropathy, hyperadrenocorticism, immune-mediated hemolytic anemia, dirofilariasis, disseminated intravascular coagulation, neoplasia and sepsis. The combination of clinical evidence of a primary etiology with appropriate clinical signs, thoracic radiographic findings, increased central venous pressure and blood gas abnormalities leads to a clinical presumptive diagnosis of PTE.
Nephrotic syndrome is the combination of proteinuria, hypercholesterolemia, hypoalbuminemia and clinical evidence of edema. The primary disease is either glomerulonephritis or amyloidosis that leads to urinary protein loss. Small proteins like albumin and ATIII are lost. Thromboembolism is thought to result from the loss of ATIII, increased serum fibrinogen and some coagulation factors, vascular irritation and platelet hypersensitivity, and concurrent hyperlipidemia. Diagnosis and treatment is aimed at finding and eliminating the cause of the glomerulonephritis.
Pituitary dependent, adrenal dependent or iatrogenic hyperadrenocorticism can lead to PTE. Pathogenesis is thought to be due to increased concentration of some coagulation factors and platelet hypersensitivity. Treatment of PTE is directed at the primary disease. Pituitary dependent hyperadrenocorticism is generally managed medically; adrenal dependent hyperadrenocorticism can be managed medically or surgically. Since PTE is a potentially fatal complication or hyperadrenocorticism it is recommended that all dogs should be treated regardless of the severity of other clinical signs.
PTE due to dirofilariasis is thought to be due to pulmonary arterial vessel endothelial damage, potentiation of coagulation due to blood stasis, and platelet hypersensitivity. Pulmonary thromboembolic disease is most common following adulticide therapy and is most severe 7-21 days post-therapy in dogs that do not get enforced rest.
Immune mediated hemolytic anemia has been noted to lead to deterioration and sudden death due to PTE. Pathogenesis is thought to be pulmonary artery endothelial damage and inflammatory cytokine amplification of coagulation reactions. The disease is more common in middle-aged, female dogs. Diagnosis is based on the presence of macrocytic, hypochromic regenerative anemia with positive Coomb's testing, autoagglutination, and the presence of spherocytes. Glucocorticoid therapy may exacerbate pulmonary thromboembolic complications as discussed for hyperadrenocorticism. If possible, intravenous catheters should be avoided as they act as a nidus for platelet aggregation.
Neoplasia can cause PTE due to tumor compression of pulmonary vasculature with venous stasis, increased concentrations of some coagulation factors, decreased ATIII due to renal loss and consumptive coagulopathies, accelerated fibrinolysis, and increased production of procoagulants.
Sepsis and the systemic inflammatory response syndrome (SIRS) can cause thromboembolic disease via several mechanisms; endotoxin release and inflammatory cytokines trigger the coagulation cascade. Pancreatitis induces endothelial damage and inflammatory cytokine release triggering the coagulation cascade. Hyperlipidemia induces vasculitis and platelet hypersensitivity. Thrombocytosis and hyperviscosity syndromes can cause abnormal platelet function, blood stasis and possible endothelial damage.