eMedicine Specialties > Vascular Surgery > Medical Topics

Paradoxical Embolism

Igor A Laskowski, MD, Assistant Professor of Surgery, Section of Vascular Surgery, New York Medical College, Westchester Medical Center
Sateesh C Babu, MD, Professor of Clinical Surgery, New York Medical College; Associate Director, Vascular Surgery, Co-chief Endovascular Surgery, Westchester Medical Center, Valhalla NY; Oladayo Osinuga, MD, Attending Physician, Department of Internal Medicine, Atlanta Medical Center; Maurice Rachko, MD, FACC, FACP, Director of Coronary Care Unit, Brooklyn Hospital Center; Clinical Assistant Professor, Department of Medicine, Weill Medical College of Cornell University; Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital; Nelson Menezes, MD, RVT, Chief of Vascular Surgery, Assistant Professor, Department of Surgery, Division of Vascular Surgery, The Brooklyn Hospital Center and Cornell University

Updated: Sep 17, 2009

Introduction

Background

In 1877, Cohnheim initially described the term paradoxical embolism (PDE).¹ It illustrates a condition in which emboli from the venous system reach the systemic arterial circulation by passing through an abnormal communication between the chambers of the heart, leading to a systemic manifestation such as stroke, kidney infarction, or acute limb infarction.

Zahn reported a case in 1885 in which autopsy revealed thrombosis in the pelvic veins, multiple systemic emboli, and a thrombus passing through a patent foramen ovale (PFO).

The clinical manifestations of paradoxical embolism (PDE) are nonspecific, and the diagnosis is difficult to establish. Patients with paradoxical embolism (PDE) may present with neurological abnormalities or features suggesting arterial embolism. The disease starts with the formation of emboli within the venous system, which traverse a PFO into the systemic circulation.² PFOs have been found on autopsy in up to 35% of the healthy population.

Paradoxical embolism (PDE) originates in the veins of the lower extremities and, occasionally, in the pelvic veins. Emboli may be of various types, such as clots, air, tumor, fat, and amniotic fluid.³ Septic emboli have led to brain abscesses. Projectile embolization is rare (eg, from a shotgun pellet).

Paradoxical embolism.

The management of paradoxical embolism (PDE) is both medical and surgical in nature. Paradoxical embolism (PDE) is considered the major cause of cerebral ischemic events in young patients. Paradoxical embolism (PDE) may rarely occlude the pelvic aortic bifurcation. The largest documented thrombus in a PFO (impending PDE) was 25 cm in length.

Paradoxical embolism (PDE) is confirmed by the presence of thrombus within an intracardiac defect on contrast echocardiography or at autopsy. Paradoxical embolism (PDE) can be presumed in the presence of arterial embolism with no evidence of left-sided circulation thrombus, deep venous thrombosis (DVT) with or without pulmonary embolism (PE), and right-to-left shunting through an intracardiac communication, commonly the PFO.⁴

Pathophysiology

Paradoxical embolism (PDE) originates from a venous thrombosis. In most cases, the source is in the deep veins of the lower extremities; thrombosis occurs less frequently in the upper extremities than in the lower extremities.

Many conditions predispose individuals to increased risk for development of venous thrombosis, including hypercoagulable states, such as factor V Leiden (resistance to activated protein C); antithrombin III, protein C, or protein S deficiencies; antiphospholipid antibody syndrome; prothrombin mutation; and dysfibrinogenemia.

Immobilization, pregnancy, estrogen use, previous DVT, trauma, and neoplasms (ie, breast, pelvic malignancy, stomach, pancreas, lung) are risk factors. Surgery is also a common risk factor for DVT, especially orthopedic, abdominal, and genitourinary procedures. Thromboangiitis obliterans and homocystinuria, 2 types of venulitis, are among the least common risk factors. The thrombus is composed of platelets, fibrin, and, eventually, red blood cells. The thrombus tends to propagate in the direction of the blood flow.

The intracardiac communication between the venous and arterial circulations can be in the form of a PFO, atrial septal defect (ASD), pulmonary arteriovenous malformation, ventricular septal defect, Ebstein anomaly, and patent ductus arteriosus.

A PFO is defined as a valvelike opening between the septum primum and the septum secundum without evidence of an anatomic defect in the septa. PFO is significant in the etiology of paradoxical embolism (PDE) if associated right-to-left shunting is present. Some causes of right-to-left shunting are right atrial hypertension; right ventricular hypertension; right ventricular failure with increased end-diastolic pressure; positive-pressure ventilation; positive end-expiratory pressure; pulmonary hypertension from hypoxemia; myocardial infarction of the right side of the heart; and Valsalva-type maneuvers (forced expiration against a closed glottis), including urination, defecation, and sneezing.

The clinical manifestations are based on complications of embolism and depend on the site of the embolus; multiorgan ischemia and infarction can occur. PE is a prerequisite for paradoxical embolism (PDE). If the left pulmonary artery is occluded suddenly, the mean pulmonary artery pressure increases by 30% from the baseline. According to estimates, PE may lead to paradoxical embolism (PDE) only if it produces a rise in mean pulmonary artery pressure greater than 30 mm Hg, facilitating an increase in right atrial pressure above left atrial pressure, resulting in right-to-left shunting.

The PFO increases in size with advancing age, from a mean of 3 mm in the first decade to 6 mm in the 10th decade.

Frequency

United States

The actual frequency of paradoxical embolism (PDE) is unknown because most cases are presumed rather than proved and most cryptogenic strokes are not investigated.

Paradoxical embolism (PDE) may be common. The incidence of stroke in the United States is approximately 500,000 per year. Of all strokes, 35-40% are cryptogenic (ie, without an identifiable source). PFO prevalence is approximately 20-30% in cryptogenic strokes. Autopsy data suggest that PFO may be present in 25-35% of the normal population. Right-to-left atrial shunts in paradoxical embolism (PDE) are associated with an underlying PFO in approximately 70% of case series and autopsy reports.

DVT may escape clinical detection in more than 50% of cases. Venous thrombosis may occur in more than 50% of orthopedic surgical procedures and in more than 20% of patients who undergo abdominal or thoracic surgical procedures.
The clinical findings of paradoxical embolism (PDE) are arterial embolic manifestations that include cerebral (40%), peripheral (50%), coronary (8%), renal (1%), and splenic (1%) ischemia or infarction. PE has been demonstrated in as many as 85% of diagnosed cases of paradoxical embolism (PDE). Chronically elevated pressures of the right side of the heart are associated with 5% of paradoxical embolism (PDE) cases.

Mortality/Morbidity

Morbidity and mortality are increased in patients with paradoxical embolism (PDE) and PE, depending on the size of the embolus and end-organ lodgment.
Patients with paradoxical embolism (PDE) can have permanent neurological damage with residual physical incapability.

Race

No established differences exist across racial or ethnic groups.

Sex

Both sexes are equally represented in the demographics of the disease because no sex difference exists in the incidence of PFO in the normal population.

Age

Elderly patients are commonly affected. Risk of DVT is increased in the elderly population. This correlates to the increased incidence of paradoxical embolism (PDE) in patients older than 55 years. Elderly patients may be at increased risk for the passage of thrombus through a PFO. The size of the PFO in this age group is usually larger when compared with younger populations. The average size of a PFO is 3 mm in the first decade of life versus 6 mm in the 10th decade of life.
Paradoxical embolisms (PDEs) do occur in individuals younger than 55 years when an intracardiac communication is present with risk of DVT and right-to-left atrial shunting. PFO with atrial right-to-left shunt is the most frequent cardiac finding in patients younger than 55 years with an otherwise unexplained ischemic cerebral insult or cryptogenic stroke.

Clinical

History

The clinical findings of paradoxical embolism (PDE) are nonspecific and are related to other disease entities such as PE, neurological deficits associated with transient ischemic attack (TIA)/embolic stroke, and systemic arterial embolism.

The clinical triad of paradoxical embolism (PDE) is DVT with or without PE, intracardiac communication with a right-to-left shunt, and arterial embolism. Patients with normal hemodynamics and a PFO show no detectable abnormality in their medical history or on their physical examination findings, chest roentgenogram, or ECGs; however, patients with right atrial pressure elevated above the left atrial pressure tend to have right-to-left shunts and a predisposition to paradoxical embolism (PDE). PFO is the most frequent conduit for right-to-left shunts in more than 70% of cases.

Patient symptoms can be exacerbated with Valsalva-type maneuvers, such as defecation, urination, and cough. Despite provocative maneuvers (eg, Valsalva or cough), left atrial pressure may remain higher than right atrial pressure, thereby preventing right-to-left shunting.

Paradoxical embolism (PDE) has been recognized increasingly as a cause of embolic stroke. It is often a diagnosis of exclusion. DVT as an initial source of paradoxical embolism (PDE) must be ruled out clinically. A causative relationship exists among DVT, PFO, and ischemic neurologic events. Neurological deficits in patients with cardiovascular events or DVT, PE, or any unexplained arterial embolism, such as in the retinal artery, mesenteric artery, splenic artery, and renal artery, should be regarded with a high level of clinical suspicion for paradoxical embolism (PDE).

Symptoms associated with DVT may include the following:
- Unilateral leg pain
- Leg swelling (Swelling of one lower extremity is the most important clinical manifestation of lower extremity DVT. Generally, the swelling is painless. On palpation, the calf muscle is tender, and the Homan sign is present in less than half the cases of DVT.)
- Unilateral leg redness (Redness is not seen in most cases of DVT. It is almost always seen in superficial thrombophlebitis.)
- A positive history of previous DVT (indicative because one third of all DVTs are recurrent)
Symptoms associated with PE include the following:
- Dyspnea
- Chest pain
- Hemoptysis
- Syncope
Symptoms associated with embolic stroke include the following:
- Unilateral weakness
- Speech abnormality
- Visual abnormality
- Swallowing abnormality
- Seizures
Symptoms associated with arterial embolism depend on the affected artery, which can supply any of the extremities or any of the major organs. Symptoms include the following:
- Acute severe extremity pain
- In the classic case of embolic occlusion of lower extremity artery (eg, femoral or popliteal artery), the clinical picture can be described as 5 Ps: pain, pallor, pulselessness, paresthesia, and paralysis.
- Paresthesia
- Numbness
- Skin discoloration
- Inability to use the extremity
Clinical symptomatology associated with multiorgan arterial embolism depends on the location of the embolism (eg, retinal artery, mesenteric artery, splenic artery).

Physical

Physical manifestations of paradoxical embolism (PDE) are related to DVT, PE, and manifestations of peripheral/central arterial embolism.

DVT can present physically with the following:
- Unilateral leg swelling, tenderness, warmth, and erythema
- Palpable cord along the course of the affected veins (possible)
- Appearance of prominent venous collaterals (may be noted)
PE may present physically with following:
- Tachypnea
- Hypotension
- Central cyanosis
- Tachycardia
- Low-grade fever
- Jugular venous distension
- Accentuated pulmonic component of the second heart sound
- Newly onset atrial fibrillation (sometimes a subtle sign of PE)
Physical manifestations of cerebral embolism include the following:
- Focal neurologic deficits that correspond to the areas of the cerebral cortex that the affected artery supplies
- Facial weakness and visual neglect
- Broca or Wernicke aphasia
Physical manifestations of acute arterial occlusion depend on the site, duration, and severity of the obstruction. Manifestations include the following:
- Pain
- Coldness
- Paralysis/motor weakness
- Peripheral cyanosis or pallor
- Loss of sensation
Intracardiac clot can lead to a new murmur, depending on the size and the location.

Causes

Many conditions predispose individuals to increased risk for DVT. These can include the following:
- Hypercoagulable states, such as factor V Leiden (resistance to activated protein C); antithrombin III, protein C, and protein S deficiencies; antiphospholipid antibody syndrome; prothrombin mutation; and dysfibrinogenemia
- Previous DVT
- Immobilization
- Pregnancy and estrogen use
- Neoplasms (ie, breast, pelvic malignancy, stomach)
- Surgery and/or procedures such as pancreas and lung surgeries
- Orthopedic, abdominal, and genitourinary procedures
- Trauma
- Venulitis such as thromboangiitis obliterans and homocystinuria
Intracardiac communication of the venous and arterial circulations can lead to paradoxical embolism (PDE), and this communication can occur via the following:
- PFO
- ASD
- Pulmonary arteriovenous malformation
- Ventricular septal defect
- Ebstein anomaly
- Patent ductus arteriosus

Differential Diagnoses

Deep Venous Thrombosis

Workup

Laboratory Studies

Current diagnosis of paradoxical embolism (PDE) requires the following criteria:
- DVT with or without PE
- Abnormal communication between right (venous) and left (systemic) circulation
- Clinical, angiographic, or pathologic evidence for systemic embolism
- Presence of a favorable pressure gradient, promoting right-to-left shunting
When a PFO is detected in a patient with embolism, leg DVT is present in approximately 90%. DVT may be occult upon physical examination.
The laboratory studies in paradoxical embolism (PDE) are performed to evaluate for hypercoagulability that increases the risk of DVT. Younger patients (eg, <50 y) 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. For more information, see the eMedicine topic Deep Venous Thrombosis.
Perform measurements of prothrombin time, International Normalized Ratio (INR), and activated partial thromboplastin time before anticoagulation commences.
CBC count assesses the platelet count to decide whether heparin use is plausible in the presence of thrombocytopenia.
Factor V Leiden assay determines the level of hypercoagulability.
Protein C and S activity are affected by warfarin (Coumadin). Protein C and S antigen levels may still be obtainable.
Obtain homocysteine levels to exclude elevation.
Lupus anticoagulant, anticardiolipin antibodies, and syphilis serology should be evaluated in patients in a prothrombotic state.
Measuring protein C, protein S, and antithrombin deficiencies helps assess hypercoagulability states.
A prothrombin gene mutation assay evaluates genetic risk factors for thrombus formation.
PE is present in most reported cases of paradoxical embolism (PDE); acute PE generally is considered a prerequisite for paradoxical embolism (PDE). The quantitative plasma D-dimer enzyme-linked immunosorbent assay is elevated (>500 ng/mL) in more than 90% of patients with PE.
Protein C and S are affected by warfarin (Coumadin), and antithrombin III is affected by heparin. The labs now can run a hypercoagulation panel on patients taking warfarin (Coumadin), but the clinician must tell the lab about the warfarin (Coumadin).
Prothrombin gene mutation, homocysteine levels, and antiphospholipid antibodies may not be affected by anticoagulation.

Imaging Studies

DVT as an initial source of paradoxical embolism (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 by direct visualization or by 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.
- MRI is another noninvasive means to detect DVT. It is used accurately 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 CT scan with intravenous contrast or MR venogram to rule out iliac vein thrombosis.
Contrast echocardiography has evolved as the diagnostic method of choice for the assessment of PFO in view of direct visualization of the atria, atrial septum, and the site of contrast passage. PFO can be detected using contrast echocardiography that includes contrast transthoracic echocardiogram (TTE) and contrast transesophageal echocardiogram (TEE).
- TEE is minimally invasive, involving 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 allows 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 in detecting intracardiac masses and PFO. The echocardiographic characteristics of an intracardiac thrombus are those of 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 than contrast TTE 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 be greater than the left atrial pressure transiently, thereby reversing the normal left-to-right gradient that keeps the flap closed. Valsalva or cough could potentially dislodge an entrapped thrombus because of increased right atrial pressure. Impending paradoxical embolism (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 paradoxical embolism (PDE) qualitatively. A positive result from the contrast study for a PFO occurs when 2-5 microbubbles measuring 3-5 micrometer pass the interatrial septum within 3 cycles of complete opacification of the right atrium.
Second harmonic imaging (SHI) is a new imaging modality that is based on the system of receiving double the emitted ultrasound frequency. It has been demonstrated to improve the visualization of the left heart echo-contrast agents and to improve transthoracic 2-dimensional image quality. TEE and TTE with SHI in combination with intravenous contrast have a comparable yield for the detection of atrial right-to-right shunt. In young patients with stroke without clinical evidence of cardiac disease or arrhythmia in whom TEE is indicated, the noninvasive TTE with SHI is a reasonable diagnostic alternative.
Transcranial Doppler ultrasonography (TCD) employs monitoring of right-middle cerebral artery blood flow using microbubble contrast medium. Perform TCD with the Doppler probe placed against the side of the skull just above the zygomatic arch. Sensitivity and specificity are close to 100%. This is an alternative to TEE in the detection of right-to-left shunting.
PE imaging studies are important in paradoxical embolism (PDE) because of the association between PE and paradoxical embolism (PDE).
- Chest roentgenogram findings are normal or near normal. Abnormalities include focal oligemia, a peripheral wedge-shaped density above the diaphragm, or an enlarged right descending pulmonary artery.
- Ventilation and perfusion lung scanning is the main test for the diagnosis of PE. A high-probability scan for PE is defined as having 2 or more perfusion defects despite normal ventilation.
- Spiral computed tomography (CT) scan with intravenous contrast is used commonly to help diagnose PE. It has sensitivity close to that of pulmonary angiography, which has been the criterion standard for PE.
Noncontrast CT scans of the head are important in evaluating any intracranial bleeding, space-occupying lesions, midline shifts, or herniation, which are contraindications to treatment with thrombolytics and anticoagulation.

Other Tests

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.
Paradoxical embolism (PDE) can often be classified as proven if a venothrombus is found within an intracardiac defect, usually a PFO, at autopsy. Impending paradoxical embolism (PDE) has been described prior to death and at autopsy.
ECG may demonstrate classic findings in PE, which include sinus tachycardia, right axis deviation, and T-wave inversion in leads V₁ through V₃, reflecting right ventricular strain.
ECG changes in paradoxical embolism (PDE) may involve ventricular tachycardia or fibrillation, leading to cardiac arrest, especially in impending paradoxical embolism (PDE).

Procedures

Venography: DVT can be diagnosed using venography, using contrast medium to highlight filling defects in the deep venous system.
Cardiac catheterization: Intracardiac shunts can be demonstrated by 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.
Pulmonary angiography: This is the most specific test available for the diagnosis of PE, and it can detect emboli as small as 1 mm. The drawback is that it is an invasive study, therefore conferring a greater risk to the patient.
Peripheral arterial embolisms are evaluated depending on the site that is involved (ie, mesenteric, splenic, renal). Angiographic/arteriographic studies include mesenteric, renal, and peripheral studies or magnetic resonance angiography.

Treatment

Medical Care

Paradoxical embolism (PDE) treatment involves medical intervention, surgical intervention, or both. The initial treatment is anticoagulation to prevent propagation of an intracardiac clot. The presence of paradoxical embolism (PDE) with PE or atrial clots increases mortality. No difference in survival exists whether patients are treated medically or surgically.

Anticoagulation can be in the form of heparin, low molecular-weight heparin (LMWH; eg, enoxaparin, tinzaparin), or the new direct thrombin inhibitors (eg, hirudin) in the presence of heparin-induced thrombocytopenia (HIT). The main goal is to prevent the progression of embolic phenomena while awaiting emergent intracardiac embolectomy with PFO closure.
Thrombolytics are another alternative available therapy when acute cor pulmonale or hemodynamic instability is present because of acute PE. Anticoagulation and thrombolytics can be used in conjunction or separately, depending on the absence of contraindications and as an alternative to surgical intervention if the patient refuses. Thrombolytics include the recombinant tissue-type plasminogen activator (tPA), reteplase, and TNKase.
- Contraindications include intracranial disease, recent surgery, or trauma. An approximate 1% risk of intracranial hemorrhage exists with the use of tPA.
- It has the additional advantage of treating associated PE and acute arterial occlusion of the extremities. This can lead to immediate decrease in pulmonary artery pressure and can reduce the incidence of recurrent paradoxical embolism (PDE).
- Treatment of the underlying cause of increased right atrial pressure is intended to reverse the right-to-left shunt, restoring the hemodynamic homeostasis.
DVT and PE in conjunction with paradoxical embolism (PDE) can be treated with long-term anticoagulation in the form of warfarin when surgical intervention is not an option. Inferior vena cava interruption with caval filters, such as a Greenfield filter, can be used. However, they are not protective against emboli smaller than 3 mm.
Antiplatelet therapy may be beneficial if anticoagulants are contraindicated. Options include dipyridamole/aspirin (Aggrenox), clopidogrel (Plavix), dipyridamole (Persantine), and ticlopidine (Ticlid). They also are beneficial in the treatment of TIA, which can be a presentation of paradoxical embolism (PDE).
Oxygen therapy is indicated for hypoxia.

Surgical Care

Surgical therapies that include embolectomy and intracardiac communication closure (commonly PFO) are the treatments of choice and are used widely in patients with presumed paradoxical embolism (PDE).⁵

Surgical embolectomy with closure of a PFO or ASD appears to be the best treatment option for patients with an impending paradoxical embolism (PDE), except in fixed pulmonary hypertension, where indefinite anticoagulation is an acceptable option.
Transcatheter closure of intracardiac communication is an alternative option to surgical closure.⁶
- Both surgical closure and long-term anticoagulation therapy have significant associated morbidity and mortality, making transcatheter closure of PFO or ASD a promising alternative to surgical closure and a promising treatment for patients who are unable to tolerate long-term anticoagulation or who are poor surgical candidates.
- Transcatheter closure can be employed using a Bard ClamShell septal occluder device, the buttoned device, or the CardioSEAL septal occluder device. These all are available for transcatheter closure.
- Complications of nonsurgical closure of PFO or ASD for paradoxical embolism (PDE) are intermediate-term risks of recurrent neurologic events due to suboptimal device performance due to malalignment of the device, with significant residual shunting and the development of a displaced fractured device-arm friction lesion. The rate of recurrent stroke or a transient neurological event following the device placement is 3.2% per year.
Monitoring of patients is achieved with postclosure TEE or TTE using Doppler color mapping or agitated saline solution contrast injection. Residual shunting may eventually lead to surgical closure when recurrent neurologic deficit or stroke complicates transcatheter PFO or ASD closure.

Consultations

Radiology interventionists can help in the diagnostic evaluation (which may include angiographic/arteriographic studies) of patients with paradoxical embolism (PDE); they can also help in the treatment of these patients with transcatheter device placement for PFO closure.
A cardiothoracic surgeon should be consulted to remove an intracardiac thrombus to correct impending paradoxical embolism (PDE). Open-heart surgery is an alternative to close the intracardiac communication.
A vascular surgeon should be consulted for peripheral embolectomy.
All emboli removed from the peripheral arterial system should be sent to pathology for histological examination because cardiac myxoma is an important differential diagnosis of paradoxical embolism (PDE), and the clinical manifestations (peripheral, visceral, cerebral embolism) are identical.
Consultation with a pulmonologist and/or intensivist may be useful for patients with paradoxical embolism (PDE) and PE with hemodynamic compromise for positive-pressure ventilation and intensive care monitoring.
Early (<1 h) evaluation by a neurologist is very important for thrombolysis in acute stroke.

Diet

Diet depends on the comorbid state of the patient, such as hypertension or diabetes mellitus, and whether the patient is stable enough to tolerate oral feeding or assisted feeding.
Nasogastric/nasoenteral feeding is appropriate when patients cannot protect their airway.

Activity

Bedrest: Patients with paradoxical embolism (PDE) should remain in bed until the threat of dislodgement of the thrombus is minimal.
Restraints: Elderly patients with increased risk of falls or patients who are confused should be protected with restraints or one-on-one monitoring to prevent falls that can lead to bleeding in the presence of anticoagulation.
Early mobilization is possible in patients who are hemodynamically stable, without risk of falls and without risk of further embolism.

Medication

Paradoxical embolism (PDE) treatment is based on anticoagulation to prevent clot propagation. Anticoagulants, such as heparin and LMWHs (ie, enoxaparin, tinzaparin), are used for acute cases. Lepirudin (direct thrombin inhibitor) is used in HIT. All medications described previously are adjusted in those with compromised renal states.

Warfarin is used for long-term anticoagulation over a period of months.

Thrombolytics are used commonly to lyse a clot in acute arterial occlusion, preventing permanent damage as occurs in ischemic stroke, PE, and arterial occlusion. Dosages for thrombolytics vary depending on the site involved.

Anticoagulants

These agents are used for the treatment of thromboembolic disorders.

Heparin

Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.

Dosing

Adult

Initial: 40-170 IU/kg IV
Maintenance infusion: 18 IU/kg/h IV; alternatively, 50 IU/kg/h IV initially, followed by continuous infusion of 15-25 IU/kg/h; increase dose by 5 IU/kg/h q4h prn using aPTT results

Pediatric

Initial: 50 IU/kg IV
Maintenance infusion: 15-25 IU/kg/h IV, increase dose by 2-4 IU/kg/h q6-8h prn using aPTT results

Interactions

Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, ASA, dextran, dipyridamole, and hydroxychloroquine may increase heparin toxicity

Contraindications

Documented hypersensitivity; subacute bacterial endocarditis; active bleeding; history of HIT

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In neonates, preservative-free heparin is recommended to avoid possible toxicity (gasping syndrome) by benzyl alcohol, which is used as preservative; caution in severe hypotension and shock; monitor for bleeding in peptic ulcer disease, menstruation, increased capillary permeability, and when administering IM injections

Enoxaparin (Lovenox)

Enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, preferentially increases inhibition of factor Xa. Average duration of treatment is 7-14 d.

Dosing

Adult

1 mg/kg SC q12h; alternatively, 1.5 mg/kg SC qd

Pediatric

Not established; suggested dose is as follows:
<2 months: 0.75 mg/kg/dose SC bid
>2 months: 0.5 mg/kg/dose SC bid

Interactions

Platelet inhibitors or oral anticoagulants, such as dipyridamole, salicylates, aspirin, NSAIDs, sulfinpyrazone, and ticlopidine, may increase risk of bleeding

Contraindications

Documented hypersensitivity; major bleeding; thrombocytopenia

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

If thromboembolic event occurs despite LMWH prophylaxis, discontinue drug and initiate alternate therapy; elevation of hepatic transaminases may occur but is reversible; heparin-associated thrombocytopenia may occur with fractionated LMWHs; 1 mg of protamine sulfate reverses effect of approximately 1 mg of enoxaparin if significant bleeding complications develop

Tinzaparin (Innohep)

LMWH with antithrombotic effect. It inhibits factors Xa and IIa (thrombin). The primary inhibitory activity is mediated through antithrombin.

Dosing

Adult

175 IU/kg SC qd at same time each day

Pediatric

Not established

Interactions

Platelet inhibitors or oral anticoagulants, such as dipyridamole, salicylates, aspirin, NSAIDs, sulfinpyrazone, and ticlopidine, may increase risk of bleeding

Contraindications

Documented hypersensitivity; active major bleeding; thrombocytopenia

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Bleeding diathesis; uncontrolled arterial hypertension; history of recent GI ulceration, diabetic retinopathy, and hemorrhage

Warfarin (Coumadin)

Interferes with hepatic synthesis of vitamin K–dependent coagulation factors.
Used for prophylaxis and treatment of venous thrombosis, PE, and thromboembolic disorders. Tailor dose to maintain an INR in the range of 2-3 with an overlap of 3-5 days of therapeutic aPTT using heparin regimen as previously described.

Dosing

Adult

5-15 mg/d PO qd for 2-5 d; adjust dose according to desired INR

Pediatric

Administer weight-based dose of 0.05-0.34 mg/kg/d PO; adjust dose according to desired INR

Interactions

Drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, oral contraceptives, and sucralfate
Medications that may increase anticoagulant effects of warfarin include oral antibiotics, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen, and sulindac

Contraindications

Documented hypersensitivity; severe liver or kidney disease; open wounds or GI ulcers

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Do not switch brands after achieving therapeutic response; caution in active tuberculosis or diabetes; patients with protein C or S deficiency are at risk of developing skin necrosis

Lepirudin (Refludan)

Highly specific direct thrombin inhibitor. Recombinant hirudin derived from yeast cells. Indicated for anticoagulation in HIT and associated thromboembolic disease.
Action is independent of antithrombin III.
It blocks thrombogenic activity of thrombin. Affects all thrombin-dependent coagulation assays (ie, aPTT values increase in dose-dependent manner). Adjust dose based on aPTT ratios (target 1.5-2.5 normal) determined q4h and then qd.

Dosing

Adult

0.4 mg/kg (not to exceed 44 mg) slow IV bolus over 15-20 sec, then 0.15 mg/kg/h (not to exceed 16.5 mg/h) continuous IV for 2-10 d or longer as indicated

Pediatric

Not established

Interactions

Thrombolytics, oral anticoagulants (ie, warfarin), antiplatelet agents, penicillin, and cephalosporins may increase risk of bleeding

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Recent puncture of large vessels or organ biopsy, anomaly of vessels or organs, recent CVA, intracerebral surgery; severe uncontrolled hypertension; bacterial endocarditis; advanced renal impairment; recent major bleeding (ie, intracranial, GI, intraocular, pulmonary)

Thrombolytics

These agents are used to restore circulation through a previously occluded vessel by the rapid and complete removal of a pathologic intraluminal thrombus or embolus that has not been dissolved by the endogenous fibrinolytic system.

Alteplase (Activase)

A tPA used in management of AMI, acute ischemic stroke, and PE. Safety and efficacy with concomitant administration of heparin or aspirin during first 24 h after symptom onset have not been investigated.

Dosing

Adult

PE: 100 mg IV infusion over 2 h, then restart heparin when aPTT £ twice normal
Cerebral embolism: Infuse 0.9 mg/kg (not to exceed 90 mg) 10% as IV bolus, then remainder infused over 60 min

Pediatric

Not established

Interactions

Drugs that alter platelet function (aspirin, dipyridamole, abciximab) may increase risk of bleeding prior to, during, or after therapy; may administer heparin with and after alteplase infusions to reduce risk of repeat thrombosis; either heparin or alteplase may cause bleeding complications

Contraindications

Documented hypersensitivity; active internal bleeding; cerebrovascular accident or stroke within last 2 mo; intracranial or intraspinal surgery or trauma; intracranial hemorrhage on pretreatment evaluation; suspicion of subarachnoid hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm; bleeding diathesis; severe uncontrolled hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor for bleeding, especially at arterial puncture sites, with coadministration of vitamin K antagonists; control and monitor blood pressure frequently during and following administration (when managing acute ischemic stroke); do not use >0.9 mg/kg to manage acute ischemic stroke; doses >0.9 mg/kg may cause ICH

Streptokinase (Streptase)

Acts with plasminogen to convert plasminogen to plasmin. Plasmin degrades fibrin clots, fibrinogen, and other plasma proteins. Increase in fibrinolytic activity that degrades fibrinogen levels for 24-36 h takes place with IV infusion of streptokinase.

Dosing

Adult

PE
Loading dose: 250,000 IU IV over 30 min
Maintenance: 100,000 IU/h IV for 24 h (if concurrent DVT suspected, administer for 72 h)
DVT
Loading dose: 250,000 IU IV over 30 min
Maintenance: 100,000 IU/h IV for 72 h
Arterial thrombosis or embolism
Loading dose: 250,000 IU IV over 30 min
Maintenance: 100,000 IU/h IV for 24-72 h

Pediatric

Administer as in adults

Interactions

Antifibrinolytic agents may decrease effects; heparin, warfarin, and aspirin may increase risk of bleeding

Contraindications

Documented hypersensitivity; active internal bleeding; intracranial neoplasm; aneurysm; diathesis; severe uncontrolled arterial hypertension

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in severe hypertension, IM administration of medications, trauma, or surgery in the previous 10 days; measure hematocrit, platelet count, aPTT, TT, PT, or fibrinogen levels before therapy is implemented; either TT or aPTT should be less than twice the normal control value following infusion of streptokinase and before (re) instituting heparin; do not take blood pressure in the lower extremities because it may dislodge possible deep vein thrombi; monitor PT, aPTT, TT, or fibrinogen 4 h after the initiation of therapy

Reteplase (Retavase)

A recombinant tPA that forms plasmin after facilitating cleavage of endogenous plasminogen.
In clinical trials, has been shown to be comparable with tPA in achieving TIMI 2 or 3 patency at 90 min. Heparin and aspirin are usually given concomitantly and after.

Dosing

Adult

10 U IV over 2 min, followed 30 min later by a second dose at 10 U IV

Pediatric

Not established

Interactions

Anticoagulants and antiplatelets may increase risk of bleeding

Contraindications

Documented hypersensitivity; uncontrolled hypertension; recent intracranial surgery; malformation of aneurysm; bleeding diathesis

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular arrhythmias, hypotension, and perfusion arrhythmias

Tenecteplase (TNKase)

Modified version of alteplase (tPA) made by substituting 3 amino acids of alteplase. Has longer half-life and, thus, can be given as single bolus over 5-s infusion instead of 90 min with alteplase.
Appears to cause less non–intracranial bleeding but has similar risk of intracranial bleeding and stroke as alteplase. Base dose using patient weight. Initiate treatment as soon as possible after onset of AMI symptoms. Because tenecteplase contains no antibacterial preservatives, reconstitute immediately before use.

Dosing

Adult

Give IV bolus over 5 s using body weight, not to exceed 50 mg
<60 kg: 30 mg (6 mL)
60-70 kg: 35 mg (7 mL)
70-80 kg: 40 mg (8 mL)
80-90 kg: 45 mg (9 mL)
>90 kg: 50 mg (10 mL)

Pediatric

Not established

Interactions

Heparin and vitamin K antagonists, acetylsalicylic acid, dipyridamole, and GP IIb/IIIa inhibitors may increase risk of bleeding if coadministered

Contraindications

Documented hypersensitivity; active internal bleeding; intracranial neoplasm, arteriovenous malformation, or aneurysm; history of cerebrovascular accident; intracranial or intraspinal surgery or trauma within 2 months; known bleeding diathesis; severe uncontrolled hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution if readministering to patients who have received prior plasminogen activator therapy (may develop immunity); coronary thrombolysis may result in arrhythmias associated with reperfusion but not different from those often seen in ordinary course of AMI (may be managed with standard antiarrhythmic measures); in elderly, weigh benefits of tenecteplase on mortality against risk of increased adverse events, including bleeding; cholesterol embolism is associated with all types of thrombolytic agents, but true incidence is unknown

Antiplatelets

These agents inhibit platelet aggregation and reduce thrombotic stroke in transient ischemia of the brain.

Clopidogrel (Plavix)

Selectively inhibits adenosine diphosphate (ADP) binding to platelet receptor and subsequent ADP-mediated activation of glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation.

Dosing

Adult

75 mg PO qd

Pediatric

Not established

Interactions

Coadministration with naproxen is associated with increased occult GI blood loss; prolongs bleeding time; safety of coadministration with warfarin not established

Contraindications

Documented hypersensitivity; active pathological bleeding, such as peptic ulcer or intracranial hemorrhage

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients at increased risk of bleeding from trauma, surgery, or other pathological conditions; caution in patients with lesions with propensity to bleed (such as ulcers)

Ticlopidine (Ticlid)

Second-line antiplatelet therapy for patients who cannot tolerate or fail ASA therapy.

Dosing

Adult

250 mg PO bid

Pediatric

Not established

Interactions

Effects may decrease with coadministration of corticosteroids and antacids; toxicity increases when taken concurrently with theophylline, cimetidine, aspirin, and NSAIDS

Contraindications

Documented hypersensitivity; neutropenia or thrombocytopenia; liver damage; active bleeding disorders

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Discontinue if absolute neutrophil count decreases to <1200/mm³ or if platelet count falls to <80,000/mm³

Dipyridamole 200 mg/aspirin 25 mg (Aggrenox)

Combination antiplatelet agent using additive antiplatelet effects of dipyridamole and aspirin.
Dipyridamole acts via adenosine-platelet A2-receptor system, while aspirin inhibits platelet aggregation by irreversible inhibition of cyclooxygenase system and thus inhibits generation of thromboxane A2, a powerful enhancer of platelet aggregation and vasoconstriction.

Dosing

Adult

1 cap PO bid

Pediatric

Not established

Interactions

Diminishes effects of beta-blockers, ACE inhibitors, cholinesterase inhibitors, and diuretics; increased risk of bleeding with anticoagulants, antineoplastic agents, and NSAIDs; increases effect of antidiabetic agents; increased aspirin toxicity with corticosteroids; increases toxicity of methotrexate; aspirin added to treatment regimen that includes valproic acid increases valproic acid toxicity; aspirin discontinued from treatment regimen that includes valproic acid decreases effectiveness of valproic acid

Contraindications

Documented hypersensitivity; NSAIDS allergy; asthma; rhinitis; nasal polyps;
Reye syndrome; coagulation abnormalities; pregnancy (especially third trimester)

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Pregnancy category D (aspirin) and B (dipyridamole); caution in coronary artery disease, hepatic insufficiency, hypotension, renal failure, recent MI, unstable angina, GI ulcers, or bleeding peptic ulcers; discontinue if dizziness or tinnitus occur

Follow-up

Further Inpatient Care

Inpatient care for people with paradoxical embolism (PDE) depends on their hemodynamic stability and associated presenting clinical manifestations, such as PE, TIA, acute arterial embolism, or debilitating neurological deficits, that may warrant intensive care or regular monitoring.
- Safety precautions and fall prevention when the risk for falls and safety concerns are present, especially in elderly patients.
- Aspiration prophylaxis is paramount in patients who are bedridden with minimal or no cough reflex.
- Neurologic watch is needed to monitor any further neurologic deficit to intervene before further deterioration.
- Intensive care monitoring is needed in the presence of hypotension and when the patient needs vasopressors, intubation, and mechanical ventilation.
- Pain management is needed in patients with acute arterial limb occlusion that commonly presents with severe pain and pain associated with DVT.
- Gastrointestinal prophylaxis is needed to prevent stress ulcers in the presence of cerebral insult.
- Skin care may involve frequent turning and protective skin devices to prevent skin breakdown and eventual decubitus ulcer.

Further Outpatient Care

Outpatient care for paradoxical embolism (PDE) is based on evidence of idiopathic venous thrombosis, hypercoagulable states, PE, the risk-determined DVT, and the sequelae of the clinical manifestation.
- Chronic anticoagulation therapy with warfarin may be used for 6 months in DVT/PE or as lifelong therapy with monitoring of the INR in the presence of hypercoagulable states.
- Chronic antithrombotic therapy with antiplatelet drugs is needed for patients with history of TIA.
- Physical therapy is needed for patients who will benefit from physical rehabilitation.
- Visiting nurse may be highly beneficial for monitoring INR at home and helping patients in the administration of subcutaneous injection of LMWH when used for long-term anticoagulation for eventual self-administration.

Inpatient & Outpatient Medications

Anticoagulation
- Warfarin
- Enoxaparin
- Tinzaparin
Antiplatelet therapy
- Dipyridamole/aspirin (Aggrenox)
- Clopidogrel (Plavix)
- Ticlopidine (Ticlid)
Thrombolytics, eg, alteplase (tPA)

Transfer

Intensive care unit: Patients with paradoxical embolism (PDE) can be transferred to medical or surgical intensive care units in the presence of hemodynamic compromise.
Subacute rehabilitation facility: This may be beneficial in patients with significant neurological deficits and with no further risk of emboli.

Deterrence/Prevention

Prevention remains controversial. Whether or not prophylaxis of persons with a recognized predisposition for paradoxical embolism (PDE) is beneficial and whether patients with hypercoagulable states should be screened routinely using contrast echocardiography for PFO or ASD are not established.

Complications

Neurologic deficit as a manifestation of stroke
Hemiplegia
Amaurosis fugax with eventual blindness
Motor aphasia
Seizure disorder complicating a cerebral insult
Arrhythmia such as ventricular tachycardia/fibrillation in cases of impending paradoxical embolism (PDE)
Acute myocardial infarction
Loss of limb function with amputation
Organ damage, eg, renal infarction
Death

Prognosis

Prognosis of paradoxical embolism (PDE) is good when it is not complicated.
Prognosis of paradoxical embolism (PDE) is poor when it is complicated by PE. When impending paradoxical embolism (PDE) occurs, the choice of treatment involves open-heart surgery.

Patient Education

Patients on long-term anticoagulant therapy should be compliant with their medications to prevent recurrent thrombolic events; emphasize compliance.
Avoid vitamin K–containing foods such as green leafy vegetables, including spinach, broccoli, and cauliflower.
Varicose veins coexist commonly with cyanotic congenital heart disease, and these may predispose to thromboembolic phenomena. These patients should avoid passive standing, should avoid crossing their legs when sitting, and should not allow their legs to be dependent.
Avoid Valsalva maneuvers to prevent elevation of the right atrial pressure above the left atrial pressure, which can lead to transient right-to-left shunting in patients with risk factors for paradoxical embolism (PDE).
For excellent patient education resources, visit eMedicine's Circulatory Problems Center. Also, see eMedicine's patient education article Blood Clot in the Legs.

Miscellaneous

Medicolegal Pitfalls

The clinical presentation of paradoxical embolism (PDE) is nonspecific. Therefore, paradoxical embolism (PDE) is a diagnostic challenge that is prone to misdiagnosis, which may result in medicolegal action by the patient and family. Paradoxical embolism (PDE) mimics other diseases, and suspicion should be high in order to avoid medicolegal implications.
Outcome may be devastating with complications such as neurological deficits, blindness, gangrene of extremities, and amputation, depending on whether the limb is salvageable or not. Organ damage may include renal infarction with eventual renal insufficiency.
Adverse reactions from intravenous contrast agents may occur in studies such as venography, arteriography, angiography, and cardiac catheterization. Obtaining an informed consent with full explanation about the indications, implications, and complications of the procedure and the possibility of contrast-associated adverse reactions is important.
Appropriate treatment can lead to morbidity and mortality. Thrombolytic treatment can lead to intracranial hemorrhage with extensive neurologic deficits. Transcatheter closure of PFO may lead to residual shunting due to malalignment of the occluder device; this can cause recurrent strokes.
Surgical intervention, in the form of embolectomy and closure of PFO, in the presence of intracardiac embolus and PFO has a survival rate of 75% and death rate close to 25%. In view of all the complications of treatment, the benefits should be weighed against the risks. To avoid medicolegal pitfalls, patients and their families should be provided with a thorough explanation about the outcome of the intervention.

Special Concerns

Paradoxical embolism (PDE) is not common in pediatric age groups.
Paradoxical embolism (PDE) in pregnancy is rare but possible because of increased risk of DVT. Noninvasive modalities should be chosen over an invasive workup, and the treatment is mainly conservative in nature. Heparin is the anticoagulant of choice; the other anticoagulants and thrombolytics are contraindicated. The eventual treatment of choice depends on the trimester of the pregnancy and the assessment of risks versus benefits of treatment.
Paradoxical embolism (PDE) in elderly patients is significant because of the associated morbidity and mortality in this age group. Noninvasive and less invasive procedures may be preferable. The risk of falls in elderly persons may make inferior vena cava interruption a better choice than warfarin for long-term anticoagulation when DVT and PE are present in paradoxical embolism (PDE).

Multimedia

Media file 1: Paradoxical embolism.

References

Cohnheim J. Thrombose und Embolie. Vorlesung ueber allgemeine Pathologie. Berlin, Hirschwald. 1877;1:134.
Eichhorn V, Bender A, Reuter DA. Paradoxical air embolism from a central venous catheter. Br J Anaesth. May 2009;102(5):717-8. [Medline].
Vellayappan U, Attias MD, Shulman MS. Paradoxical embolization by amniotic fluid seen on the transesophageal echocardiography. Anesth Analg. Apr 2009;108(4):1110-2. [Medline].
Mascarenhas V, Kalyanasundaram A, Nassef LA, Lico S, Qureshi A. Simultaneous massive pulmonary embolism and impending paradoxical embolism through a patent foramen ovale. J Am Coll Cardiol. Apr 14 2009;53(15):1338. [Medline].
Kuppuswamy M, Kourliouros A, Sutherland G, Sarsam M. Complete surgical correction for impending paradoxical embolism with pulmonary embolism, tricuspid regurgitation, and atrial flutter. Heart Surg Forum. Dec 2008;11(6):E378-9. [Medline].
Cifarelli A, Musto C, Parma A, Pandolfi C, Pucci E, Fiorilli R, et al. Long-term outcome of transcatheter patent foramen ovale closure in patients with paradoxical embolism. Int J Cardiol. Jan 28 2009;[Medline].
Allie DE, Lirtzman MD, Wyatt CH, et al. Septic paradoxical embolus through a patent foramen ovale after pacemaker implantation. Ann Thorac Surg. Mar 2000;69(3):946-8. [Medline].
Bridges ND, Hellenbrand W, Latson L, et al. Transcatheter closure of patent foramen ovale after presumed paradoxical embolism. Circulation. Dec 1992;86(6):1902-8. [Medline].
Cheng TO. Paradoxical embolism. Circulation. Jun 29 1999;99(25):3323. [Medline].
Corrin C. Paradoxical embolism. Br Heart J. 1991;26:549.
Dearani JA, Ugurlu BS, Danielson GK, et al. Surgical patent foramen ovale closure for prevention of paradoxical embolism-related cerebrovascular ischemic events. Circulation. Nov 9 1999;100(19 Suppl):II171-5. [Medline].
Devuyst G, Bogousslavsky J, Ruchat P, et al. Prognosis after stroke followed by surgical closure of patent foramen ovale: a prospective follow-up study with brain MRI and simultaneous transesophageal and transcranial Doppler ultrasound. Neurology. Nov 1996;47(5):1162-6. [Medline].
Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc. Jan 1984;59(1):17-20. [Medline].
Hung J, Landzberg MJ, Jenkins KJ, et al. Closure of patent foramen ovale for paradoxical emboli: intermediate-term risk of recurrent neurological events following transcatheter device placement. J Am Coll Cardiol. Apr 2000;35(5):1311-6. [Medline].
Ikonomidis JS, Nisco SJ, Liang DH, et al. Paradoxical embolism of a shotgun pellet. Ann Thorac Surg. Aug 1998;66(2):562-4. [Medline].
Johnson BI. Paradoxical embolism. J Clin Pathol. 1951;4:316-32.
Kuhl HP, Hoffmann R, Merx MW, et al. Transthoracic echocardiography using second harmonic imaging: diagnostic alternative to transesophageal echocardiography for the detection of atrial right to left shunt in patients with cerebral embolic events. J Am Coll Cardiol. Nov 15 1999;34(6):1823-30. [Medline].
Loscalzo J. Paradoxical embolism: clinical presentation, diagnostic strategies, and therapeutic options. Am Heart J. Jul 1986;112(1):141-5. [Medline].
Lynch JJ, Schuchard GH, Gross CM, et al. Prevalence of right-to-left atrial shunting in a healthy population: detection by Valsalva maneuver contrast echocardiography. Am J Cardiol. May 15 1984;53(10):1478-80. [Medline].
Mas JL. Diagnosis and management of paradoxical embolism and patent formen ovale. Curr Opin Cardiol. Sep 1996;11(5):519-24. [Medline].
Mas JL, Zuber M. Recurrent cerebrovascular events in patients with patent foramen ovale, atrial septal aneurysm, or both and cryptogenic stroke or transient ischemic attack. French Study Group on Patent Foramen Ovale and Atrial Septal Aneurysm. Am Heart J. Nov 1995;130(5):1083-8. [Medline].
Meacham RR 3rd, Headley AS, Bronze MS, et al. Impending paradoxical embolism. Arch Intern Med. Mar 9 1998;158(5):438-48. [Medline].
Nemec JJ, Marwick TH, Lorig RJ, et al. Comparison of transcranial Doppler ultrasound and transesophageal contrast echocardiography in the detection of interatrial right-to-left shunts. Am J Cardiol. Dec 1 1991;68(15):1498-502. [Medline].
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Keywords

paradoxical embolism, PDE, deep vein thrombosis, DVT, deep venous thrombosis, PFO, patent foramen ovale, thromboembolic disease, embolism

Contributor Information and Disclosures

Author

Igor A Laskowski, MD, Assistant Professor of Surgery, Section of Vascular Surgery, New York Medical College, Westchester Medical Center
Igor A Laskowski, MD is a member of the following medical societies: American College of Surgeons, American Hepato-Pancreato-Biliary Association, Peripheral Vascular Surgery Society, Society for Vascular Surgery, and Transplantation Society
Disclosure: Nothing to disclose.

Coauthor(s)

Sateesh C Babu, MD, Professor of Clinical Surgery, New York Medical College; Associate Director, Vascular Surgery, Co-chief Endovascular Surgery, Westchester Medical Center, Valhalla NY
Sateesh C Babu, MD is a member of the following medical societies: American College of Surgeons, American Heart Association, American Institute of Ultrasound in Medicine, American Medical Association, Eastern Vascular Society, International Society of Endovascular Specialists, New York Academy of Sciences, Royal Society of Medicine, Society for Vascular Surgery, and Stroke Council of the American Heart Association
Disclosure: Nothing to disclose.

Oladayo Osinuga, MD, Attending Physician, Department of Internal Medicine, Atlanta Medical Center
Oladayo Osinuga, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and American Medical Association
Disclosure: Nothing to disclose.

Maurice Rachko, MD, FACC, FACP, Director of Coronary Care Unit, Brooklyn Hospital Center; Clinical Assistant Professor, Department of Medicine, Weill Medical College of Cornell University
Maurice Rachko, MD, FACC, FACP is a member of the following medical societies: American College of Cardiology and American College of Physicians
Disclosure: Nothing to disclose.

Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital
Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Artificial Internal Organs, American Thoracic Society, Physicians for Social Responsibility, and Society of Critical Care Medicine
Disclosure: sepracor Ownership interest None

Nelson Menezes, MD, RVT, Chief of Vascular Surgery, Assistant Professor, Department of Surgery, Division of Vascular Surgery, The Brooklyn Hospital Center and Cornell University
Nelson Menezes, MD, RVT is a member of the following medical societies: American College of Surgeons, International Society of Endovascular Specialists, Medical Society of the State of New York, and Society for Vascular Surgery
Disclosure: Nothing to disclose.

Medical Editor

Alan D Forker, MD, Professor of Medicine, Program Director of Cardiovascular Fellowship, University of Missouri at Kansas City School of Medicine; Director, Outpatient Lipid Diabetes Research Center, MidAmerica Heart Institute of St Luke's Hospital
Alan D Forker, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American College of Physicians, American Heart Association, American Medical Association, American Society of Hypertension, and Phi Beta Kappa
Disclosure: Research Grant Grant/research funds Hospital contracts to do research; I am a hospital employee with no personal profit; Speakers Bureau Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Steven J Compton, MD, FACC, FACP, Director of Cardiac Electrophysiology, Alaska Heart Institute, Providence and Alaska Regional Hospitals
Steven J Compton, MD, FACC, FACP is a member of the following medical societies: Alaska State Medical Association, American College of Cardiology, and American College of Physicians
Disclosure: Nothing to disclose.

CME Editor

Paolo Zamboni, MD, Professor of Surgery, Chief of Day Surgery Unit, Chair of Vascular Diseases Center, University of Ferrara, Italy
Paolo Zamboni, MD is a member of the following medical societies: American Venous Forum and New York Academy of Sciences
Disclosure: Nothing to disclose.

Chief Editor

William H Pearce, MD, Chief, Division of Vascular Surgery, Violet and Charles Baldwin Professor of Vascular Surgery, Department of Surgery, Northwestern University School of Medicine
William H Pearce, MD is a member of the following medical societies: American College of Surgeons, American Heart Association, American Surgical Association, Association for Academic Surgery, Association of VA Surgeons, Central Surgical Association, New York Academy of Sciences, Society for Vascular Surgery, Society of Critical Care Medicine, Society of University Surgeons, and Western Surgical Association
Disclosure: Nothing to disclose.

Further Reading

Clinical guidelines

Deep venous thrombosis.
Finnish Medical Society Duodecim - Professional Association. 2001 Apr 30 (revised 2006 Apr 27). Various pagings. NGC:004983

Guidelines on the diagnosis and management of pericardial diseases. The task force on the diagnosis and management of pericardial diseases of the European Society of Cardiology.
European Society of Cardiology - Medical Specialty Society. 2004 Jan. 28 pages. NGC:003524

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease.
Global Initiative for Chronic Obstructive Lung Disease - Disease Specific Society
National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]
World Health Organization - International Agency. 2006 (revised 2007). 109 pages. [NGC Update Pending] NGC:006275

Clinical trials

PC-Trial: Patent Foramen Ovale and Cryptogenic Embolism

Risk of Stroke in Pulmonary Embolism With a Patent Foramen Ovale (PFO)

Related eMedicine topics

Patent Foramen Ovale

Atrial Septal Defect, Patent Foramen Ovale

Venous Air Embolism

Pulmonary Embolism

Deep Vein Thrombosis, Lower Extremity

eMedicine Specialties > Vascular Surgery > Medical Topics

Paradoxical Embolism

Introduction

Background

Paradoxical embolism.

Pathophysiology

Frequency

United States

Mortality/Morbidity

Race

Sex

Age

Clinical

History

Physical

Causes

Differential Diagnoses

Other Problems to Be Considered

Workup

Laboratory Studies

Imaging Studies

Other Tests

Procedures

Treatment

Medical Care

Surgical Care

Consultations

Diet

Activity

Medication

Anticoagulants

Heparin

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Enoxaparin (Lovenox)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Tinzaparin (Innohep)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Warfarin (Coumadin)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Lepirudin (Refludan)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Thrombolytics

Alteplase (Activase)

Dosing

Adult