Pulmonary Thrombotic Microangiopathy

Posted by • January 6th, 2012

In our latest Clinical Problem-Solving article, a 50-year-old woman presented with fatigue and shortness of breath. Dyspnea after moderate exertion had developed gradually, along with profound malaise and a nonproductive cough. In the 48 hours before admission, her shortness of breath had worsened.    

The clinicopathological syndrome of subacute cor pulmonale caused by tumor microemboli to the pulmonary vasculature is exceedingly rare, and details of its pathophysiology are sparse. Microscopically, tumor cells can be found in isolation or small clumps. Emboli are often mixed with fibrin thrombi. Intimal proliferation of small pulmonary arteries and arterioles leads to luminal stenosis and occlusion. The spread of tumor cells is believed to occur by means of direct hematogenous metastasis or through the lymphatics, with entrance into the venous system through the thoracic duct. In one autopsy series, right ventricular enlargement and hypertrophy were found in 40 to 45% of cases, although the mechanism by which tumor emboli cause pulmonary hypertension is unclear.   

Clinical Pearls

 How should one approach the differential diagnosis of dyspnea? 

Although one usually thinks first of pulmonary disease, the chief symptom of dyspnea should evoke a broad differential diagnosis that includes extrapulmonary processes. Intrinsic lung disease can be divided into three categories: disease of the vessels, disease of the airways, and disease of the parenchyma (i.e., the alveoli and iterstitium). Pleural effusions that cause sufficient compressive atelectasis may lead to a mismatch between ventilation and perfusion that can be manifested as dyspnea. Cardiac causes of dyspnea include coronary ischemia and congestive heart failure. Dyspnea is rarely the initial manifestation of neuromuscular conditions, but they should be considered, especially in patients who have a primary ventilatory defect on blood gas analysis. Exertional dyspnea can occur in patients with anemia when the oxygen-carrying capacity of the blood fails to meet the body’s metabolic demands. Patients with metabolic acidosis often experience shortness of breath because alveolar ventilation increases to compensate for decreased blood pH values. Anxiety should be considered as the cause of dyspnea only after organic causes have been ruled out.

 What are classic physical exam findings in the presentation of a patient with a pulmonary embolism? 

The combination of hypoxemia and normal breath sounds should always make pulmonary embolism a consideration. The presence of jugular venous distention and an increased intensity of the pulmonic component of the second heart sound, findings that are consistent with pulmonary hypertension and right heart failure may be seen as well, particularly in the presence of a large pulmonary embolus. Sinus tachycardia is seen in approximately 30% of patients with pulmonary embolism and somewhat more frequently in those with right ventricular strain. The specificity of this finding is limited because most patients with dyspnea due to other causes also present with tachycardia because of impaired oxygen delivery, distress, or both. Asymmetric lower extremity swelling may point to the etiology of a pulmonary embolus, but may often be absent. 

Morning Report Questions

Q: How might one differentiate a diagnosis of pulmonary embolism from pulmonary thrombotic microangiopathy?    

A: Typically, patients with both pulmonary embolism and pulmonary thrombotic microangiopathy present with hypoxemia and have normal findings on chest radiography and nonspecific findings on chest CT. A good-quality CT angiogram of the pulmonary arteries obtained after a well-timed bolus injection of contrast material is highly sensitive for the detection of pulmonary emboli out to the third-order or even fourth-order vessel. Pulmonary angiography has very poor sensitivity and specificity for the detection of tumor microemboli. Ventilation-perfusion scanning often reveals multiple peripheral, subsegmental, symmetrically distributed perfusion defects. This finding, together with a CT pulmonary angiogram that shows no filling defects, particularly in a patient with a history of malignancy, is suggestive of tumor microemboli. PET-CT performed after the administration of 18F-fluorodeoxyglucose may be useful in diagnosing pulmonary tumor thrombotic microangiopathy, but more data are needed to assess the role of this test in cases in which the diagnosis is suspected.

Q: Which laboratory findings may be seen with pulmonary tumor thrombotic microangiopathy? 

A: Laboratory findings consistent with a consumptive coagulopathy, including thrombocytopenia, elevated levels of lactate dehydrogenase, and an increased INR, have been described in cases of pulmonary tumor thrombotic microangiopathy.

One Response to “Pulmonary Thrombotic Microangiopathy”

  1. chaminda says:

    what sort of tumors are more prone to cause pulmonary thrombotic microangiopathy?
    Isn’t it important, the onset of dyspnea to differntiate PTA & large pulmonary embolism?