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Phlegmasia Alba and Cerulea Dolens

Author: Alan Dardik, MD, PhD, FACS, Associate Professor, Department of Surgery, Section of Vascular Surgery, Yale University School of Medicine
Coauthor(s): Dina Rahhal, MD, Postdoctoral Fellow in Transplant Immunology, Institute for Cellular Therapeutics, University of Louisville
Contributor Information and Disclosures

Updated: Sep 10, 2009

Introduction

More than 600,000 cases of venous thromboembolism are estimated to occur each year in the United States. Pulmonary embolism (PE) complicates approximately 50% of cases of untreated proximal deep venous thrombosis (DVT) and contributes to 10-15% of all hospital deaths. Less frequent manifestations of venous thrombosis include phlegmasia alba dolens, phlegmasia cerulea dolens (PCD), and venous gangrene. These form a clinical spectrum of the same disorder. All 3 manifestations result from acute massive venous thrombosis and obstruction of the venous drainage of an extremity.

Principal deep veins of the lower extremity.

Principal deep veins of the lower extremity.

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Principal deep veins of the lower extremity.

Principal deep veins of the lower extremity.

History of the Procedure

In the 16th century, Fabricius Hildanus first described the clinical syndrome of what is currently called PCD. In 1938, Gregoire made an outstanding description of the condition and used the term PCD to differentiate ischemia-associated massive venous thrombosis from phlegmasia alba dolens, which describes fulminant venous thrombosis without ischemia.1 The exact incidence of these disorders is not well reported.

In 1939, Leriche and Geissendorfer performed the first thrombectomy for cases of PCD.2 Historically, surgical thrombectomy has been the procedure of choice for PCD refractory to medical therapy and in patients with established or impeding gangrene.

Frequency

More than 600,000 cases of venous thromboembolism are estimated to occur annually in the United States. Phlegmasia alba dolens, PCD, and venous gangrene occur at any age but are more common during the fifth and sixth decades of life. Incidence is higher in females than in males.

Etiology

The main causative factor in phlegmasia is massive thrombosis and occlusion of major venous channels with significantly compromised venous outflow. Multiple triggering factors exist. Malignancy is the most common triggering factor and is present in approximately 20-40% of patients with PCD. Other associated risk factors include hypercoagulable syndrome, surgery, trauma, ulcerative colitis, gastroenteritis, heart failure, mitral valve stenosis, vena caval filter insertion, and May-Thurner syndrome (compression of the left iliac vein by the right iliac artery). Pregnancy has often been associated with phlegmasia alba dolens, especially during the third trimester when the uterus is large enough to compress the left common iliac vein against the pelvic rim (ie, milk leg syndrome). Finally, 10% of patients with phlegmasia have no apparent risk factors.

Pathophysiology

In phlegmasia alba dolens, the thrombosis involves only major deep venous channels of the extremity, therefore sparing collateral veins. The venous drainage is decreased but still present; the lack of venous congestion differentiates this entity from PCD.

In PCD, the thrombosis extends to collateral veins, resulting in venous congestions with massive fluid sequestration and more significant edema. Without established gangrene, these phases are reversible if proper measures are taken.

Of PCD cases, 40-60% also have capillary involvement, which results in irreversible venous gangrene that involves the skin, subcutaneous tissue, or muscle. Under these conditions, the hydrostatic pressure in arterial and venous capillaries exceeds the oncotic pressure, causing fluid sequestration in the interstitium. Venous pressure may increase rapidly, as much as 16- to 17-fold within 6 hours. Fluid sequestration may reach 6-10 L in the affected extremity within days. Circulatory shock, which is present in about one third of patients, and arterial insufficiency may ensue.

The exact mechanism for the compromised arterial circulation is debatable but may involve shock, increased venous outflow resistance, and collapse of arterioles due to increased interstitial pressure. Vasospasm of the resistance vessels has also been hypothesized but has never been observed experimentally or radiographically.

Presentation

In the lower extremities, left-sided involvement is more common by a 3:1 or 4:1 ratio. Involvement of upper extremities occurs in less than 5% of patients with PCD. Manifestations may be gradual or fulminant. Of PCD cases, 50-60% are preceded by phlegmasia alba dolens, with symptoms of edema, pain, and blanching (alba) without cyanosis. The blanching, which previously was thought to be caused by arterial vasospasm, is caused by subcutaneous edema, without venous congestion.

Patients with PCD present with the clinical triad of edema, agonizing pain, and cyanosis. Massive fluid sequestration may lead to bleb and bullae formation. The pain is constant, usually starting at the femoral triangle and then progressing to the entire extremity. Cyanosis is the pathognomonic finding of PCD, progressing from distal to proximal areas.

When venous gangrene occurs, it has a similar distribution with the cyanosis. Arterial pulses may be present when the venous gangrene is superficial; however, gangrene that involves the muscular compartment may result in increased compartment pressures and a pulse deficit. In addition, the pulses may be difficult to appreciate because of the significant edema. Various degrees of shock may be present because of significant fluid loss.

Indications

Historically, surgical thrombectomy has been the procedure of choice for phlegmasia cerulea dolens (PCD) refractory to medical therapy and for patients with established or impeding gangrene. The standard treatment of phlegmasia and venous gangrene is evolving, but most clinicians attempt endovascular approaches to thrombolysis, if possible.

Relevant Anatomy

The main causative factor in phlegmasia is massive deep venous thrombosis (DVT) and occlusion of major venous channels with significantly compromised venous outflow. In phlegmasia alba dolens, the thrombosis involves only major deep venous channels of the extremity, therefore sparing collateral veins and preserving some venous outflow from the limb. In phlegmasia cerulea dolens (PCD), the thrombosis extends to collateral veins, with complete obstruction of venous outflow, resulting in massive venous congestion and fluid sequestration and more significant edema.

Contraindications

For phlegmasia alba dolens and mild nongangrenous forms of phlegmasia cerulea dolens (PCD), conservative medical treatment, rather than surgical thrombectomy, should be the initial course of therapy. Thrombolysis may be initiated if conservative management does not elicit a response and if the patient has no contraindication to lytic therapy.

Surgical thrombectomy cannot open the small venules that are affected in venous gangrene, and it does not prevent valvular incompetence or postphlebitic syndrome. For these reasons, thrombolysis seems to be an attractive alternative in the management of PCD and venous gangrene.

More on Phlegmasia Alba and Cerulea Dolens

Overview: Phlegmasia Alba and Cerulea Dolens
Workup: Phlegmasia Alba and Cerulea Dolens
Treatment: Phlegmasia Alba and Cerulea Dolens
Follow-up: Phlegmasia Alba and Cerulea Dolens
Multimedia: Phlegmasia Alba and Cerulea Dolens
References
Further Reading
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References

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  2. Leriche R, Geisendorf W. Resultats d'une thrombectomie precose avec resction veineuse dans une phlebite grave des deux membres inferieurs. Presse Med. 1939;47:1239.

  3. Hull RD, Raskob GE, Pineo GF. Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med. Apr 9 1992;326(15):975-82. [Medline].

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  5. Snow V, Qaseem A, Barry P, Hornbake ER, Rodnick JE, Tobolic T, et al. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. Feb 6 2007;146(3):204-10. [Medline].

  6. Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. Jun 2008;133(6 Suppl):454S-545S. [Medline].

  7. Anderson FA Jr, Wheeler HB, Goldberg RJ. A population-based perspective of the hospital incidence and case- fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med. May 1991;151(5):933-8. [Medline].

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  12. Haimovici H. The ischemic forms of venous thrombosis. 1. Phlegmasia cerulea dolens. 2. Venous gangrene. J Cardiovasc Surg (Torino). Sep 5-18 1965;Suppl:164-73. [Medline].

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Further Reading

Clinical guidelines

Snow V, Qaseem A, Barry P, Hornbake ER, Rodnick JE, Tobolic T, Ireland B, Segal JB, Bass EB, Weiss KB, Green L, Owens DK, American College of Physicians, American Academy of Family Physicians Panel on Deep Venous. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med 2007 Feb 6;146(3):204-10. 5

Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008 Jun;133(6 Suppl):454S-545S. 6

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Keywords

phlegmasia alba dolens, phlegmasia cerulea dolens, PCD, venous gangrene, surgical thrombectomy, thrombolysis, pulmonary embolism, PE, deep venous thrombosis, DVT, thromboembolism, venous thromboembolism, thrombosis, hypercoagulable syndrome, gastroenteritis, mitral valve stenosis, heart failure, vena caval filter insertion, May-Thurner syndrome, massive thrombosis, ulcerative colitis

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Contributor Information and Disclosures

Author

Alan Dardik, MD, PhD, FACS, Associate Professor, Department of Surgery, Section of Vascular Surgery, Yale University School of Medicine
Alan Dardik, MD, PhD, FACS is a member of the following medical societies: American College of Surgeons, American Society for Cell Biology, Association for Academic Surgery, Association of VA Surgeons, Eastern Vascular Society, Peripheral Vascular Surgery Society, Phi Beta Kappa, Society for Clinical Vascular Surgery, Society for Vascular Medicine and Biology, and Society for Vascular Surgery
Disclosure: Nothing to disclose.

Coauthor(s)

Dina Rahhal, MD, Postdoctoral Fellow in Transplant Immunology, Institute for Cellular Therapeutics, University of Louisville
Disclosure: Nothing to disclose.

Medical 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.

Pharmacy Editor

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

Managing Editor

Vincent Lopez Rowe, MD, Assistant Professor of Surgery, Department of Surgery, Division of Vascular Surgery, University of Southern California Medical Center
Vincent Lopez Rowe, MD is a member of the following medical societies: American College of Surgeons, Association for Academic Surgery, Peripheral Vascular Surgery Society, Society for Clinical Vascular Surgery, and Society for Vascular Surgery
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.

 
 
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