eMedicine Specialties > Vascular Surgery > Medical Topics

Paradoxical Embolism

Author: Igor A Laskowski, MD, Assistant Professor of Surgery, Section of Vascular Surgery, New York Medical College, Westchester Medical Center
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; 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
Contributor Information and Disclosures

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).

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

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