Paradoxical Embolism Workup

Laboratory studies in paradoxical embolism (PDE) are performed to evaluate for hypercoagulable states that increase the risk of deep vein thrombosis (DVT). Younger patients (eg, < 50 years) have a higher percentage of congenital abnormalities, and testing may be warranted after the first DVT episode. As a general rule and recommendation, order blood tests after a recurrent DVT episode.

Determine the prothrombin time (PT), the international normalized ratio (INR), and the activated partial thromboplastin time (aPTT) before anticoagulation commences. Perform a complete blood count (CBC); the platelet count affects the decision as to whether heparin use is plausible in the presence of thrombocytopenia.

Factor V Leiden assay determines the level of hypercoagulability. Protein C and S antigen levels may still be obtainable. Measuring protein C, protein S, and antithrombin deficiencies helps assess hypercoagulability states. Protein C and S are affected by warfarin, and antithrombin III is affected by heparin. The labs now can run a hypercoagulation panel on patients taking warfarin, but the clinician must tell the lab about the warfarin.

Prothrombin gene mutation, homocysteine levels, and antiphospholipid antibodies may not be affected by anticoagulation. A prothrombin gene mutation assay evaluates genetic risk factors for thrombus formation. Obtain homocysteine levels to exclude elevation. Lupus anticoagulant, anticardiolipin antibodies, and syphilis serology should be evaluated in patients in a prothrombotic state.

Pulmonary embolism (PE) is present in most reported cases of PDE; acute PE generally is considered a prerequisite for PDE. The quantitative plasma D-dimer enzyme-linked immunosorbent assay (ELISA) is elevated (>500 ng/mL) in more than 90% of patients with PE.

Arterial blood gas determinations evaluate the partial pressures of oxygen and carbon dioxide. This also indicates the metabolic state of the patient and provides an estimation of the alveolar-arterial oxygen gradient.

DVT as an initial source of PDE must be excluded clinically and investigated with noninvasive studies such as duplex venous ultrasonography (B-mode [2-dimensional] imaging and pulse-wave Doppler interrogation) with compression studies to evaluate thrombus either through direct visualization or through inference when the vein does not collapse. Flow abnormalities occur when DVT is present. Impedance plethysmography is less sensitive for diagnosing DVT of the calves.

Magnetic resonance imaging (MRI) is another noninvasive means of detecting DVT. It is an accurate method in patients with suspected thrombosis of the superior and inferior venae cavae or pelvic veins.

Patients who present with unilateral limb swelling whose duplex scan findings are negative for femoral or popliteal vein DVT should undergo computed tomography (CT) with intravenous (IV) contrast or magnetic resonance venography to rule out iliac vein thrombosis. DVT can be diagnosed by means of venography using contrast medium to highlight filling defects in the deep venous system.

PE imaging studies are important in PDE because of the association between PE and PDE. Findings from chest roentgenography are normal or near normal. Abnormalities may include focal oligemia, a peripheral wedge-shaped density above the diaphragm, and an enlarged right descending pulmonary artery.

Ventilation-perfusion lung scanning is the main test for the diagnosis of PE. A high-probability scan for PE is defined as one that shows 2 or more perfusion defects despite normal ventilation.

Spiral CT with IV contrast is used commonly to help diagnose PE. Its sensitivity is close to that of pulmonary angiography, which is the most specific test available for the diagnosis of PE and is capable of detecting emboli as small as 1 mm. The drawback of pulmonary angiography is that it is an invasive study and therefore poses a greater risk to the patient.

Contrast echocardiography has evolved as the diagnostic method of choice for the assessment of patent foramen ovale (PFO) because of its ability to visualize the atria, the interatrial septum, and the site of contrast passage. Two approaches are employed: transthoracic echocardiography (TTE) and contrast transesophageal echocardiography (TEE).

Contrast TEE is minimally invasive, involving the use of a modified gastroscope that is passed blindly into the esophagus. The nearness of the esophagus to the posterior heart and the use of higher-frequency imaging transducers allow enhanced spatial resolution and detection of intracardiac thrombi, PFO, and spontaneous left atrial echo contrast, which is the most common TEE finding among patients being evaluated for intracardiac thrombus as a source of embolism.

TEE is superior to TTE for detecting intracardiac masses and PFO. On echocardiography, an intracardiac thrombus appears as a mobile mass of irregular, serpentine, or lobulated shape, the configuration of which changes with each cardiac cycle. TTE is limited in its capability to differentiate between an intracardiac thrombus and a myxoma. Contrast TEE is more sensitive in detecting PFO (100% vs 63%) and has similar specificity at approximately 78%. Contrast TEE has 100% sensitivity and 99% specificity for diagnosis of intracardiac thrombus.

The cough test is superior to the Valsalva maneuver in the diagnosis of PFO during contrast TEE or contrast TTE. Valsalva maneuvers cause the right atrial pressure to exceed the left atrial pressure transiently, thereby reversing the normal left-to-right gradient that keeps the flap closed. By increasing the right atrial pressure, a Valsalva maneuver or cough could potentially dislodge an entrapped thrombus. Impending PDE may result in a false-negative result on contrast echocardiography because of thrombotic occlusion of the PFO.

Bubble-contrast studies can help assess and exclude the diagnosis of PDE. A positive result from the contrast study for a PFO occurs when 2-5 microbubbles measuring 3-5 µm pass the interatrial septum within 3 cycles of complete opacification of the right atrium.

Second harmonic imaging (SHI) is a newer modality based on the system of receiving double the emitted ultrasound frequency. It improves visualization of the left-heart echocardiographic contrast agents and enhances transthoracic 2-dimensional image quality. TEE and TTE with SHI in combination with IV contrast have comparable yields for the detection of atrial right-to-right shunting. In young stroke patients without clinical evidence of cardiac disease or arrhythmia in whom TEE is indicated, noninvasive TTE with SHI is a reasonable diagnostic alternative.

Transcranial Doppler ultrasonography (TCD) employs monitoring of right middle cerebral artery blood flow using a microbubble contrast medium. Perform TCD with the Doppler probe placed against the side of the skull just above the zygomatic arch. The sensitivity and specificity of TCD are close to 100%. This test is an alternative to TEE in the detection of right-to-left shunting.

PDE can often be classified as proven if a venothrombus is found within an intracardiac defect, usually a PFO, at autopsy. Impending PDE has been described before death and at autopsy.

In PE, electrocardiography (ECG) may demonstrate classic findings, which include sinus tachycardia, right axis deviation, and T-wave inversion in leads V₁ through V₃, reflecting right ventricular strain. In PE, especially impending PDE, ECG changes may involve ventricular tachycardia or fibrillation, leading to cardiac arrest.

Noncontrast CT scans of the head are important in the evaluation of any intracranial bleeding, space-occupying lesions, midline shifts, or herniation, all of which are contraindications for treatment with thrombolytics and anticoagulation.

Intracardiac shunts can be demonstrated with right-heart catheterization by using atrial pressure gradients, typical oxygen saturation (oxygen step-up), and visual evidence of contrast medium traversing the abnormal communication with cough or Valsalva enhancement.

Evaluation of peripheral arterial embolism depends on the site that is involved (eg, the mesenteric, splenic, or renal artery). Tests employed may include mesenteric, renal, and peripheral studies or magnetic resonance angiography.