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Phlegmasia Cerulea Dolens

Phlebitis Blue of Gregoire

Phlegmasia cerulea dolens describes clot formation in the venous system over a large area. Patients usually present with edema, pain, blanching and it may progress to gangrene and systemic shock in severe cases.


Presentation

Common symptoms include pain, edema and blanching [6]. Patients may also sometimes exhibit different degrees of shock in severe cases. The pain characteristic of phlegmasia cerulea dolens is severe,constant, begins at the femoral triangle and subsequently radiates to the whole extremity. Arterial constriction is not responsible for the blanching, but rather congestion of the venous system as well as subcutaneous edema. Another characteristic finding of phlegmasia cerulea dolens is bluish discoloration, which starts in the distal areas before moving to proximal ones. In addition, extensive fluid extravasation can result in bullae and bleb formation.

Gangrene can sometimes accompany the disease and follows a similar pattern to the cyanosis. Arterial pulses depend on the severity of the gangrene. They may still be detected if the gangrene is superficial, although a pulse deficit results when the muscle comportment is involved. On the other hand, significant swelling may prevent the detection of any pulses.

Pain
  • We present a clinical image of a 55-year-old man with newly diagnosed cholangiocarcinoma who presented with worsening left lower extremity pain. We found painful swelling with purple discoloration extending up to the ankle joint.[ncbi.nlm.nih.gov]
  • Phlegmasia cerulea dolens (blue, painful leg) is an uncommon manifestation of deep-vein thrombosis and results from massive thrombosis compromising venous outflow, which causes ischemia.[dx.doi.org]
  • The patient will present with a swollen, cyanotic, painful leg that may or may not show signs of venous gangrene.[ncbi.nlm.nih.gov]
Fever
  • If fever ceased, swelling and discoloration progressed upward to mid-thigh. The patient was transferred to a vascular surgery center where an amputation was made. Discussion Phlegmasia dolens (PD) is a rare complication of VTE.[panafrican-med-journal.com]
  • She was admitted at the emergency unit on the third postpartum month, complaining of fever and intense fatigue for 10 days.[scielo.br]
  • He had no fever and he could still move his leg, but his pain could not be evaluated since he was delirious.[ncbi.nlm.nih.gov]
Leg Edema
  • In nine patients with venous gangrene that underwent iliofemoral thrombectomy below knee had transmetatarsal amputation done after decreasing leg edema. All patients underwent caval filter insertion before venous thrombectomy.[ncbi.nlm.nih.gov]
  • On the next day at the surgical intensive care unit (ICU), he developed progressive left leg edema with cyanosis. He had no fever and he could still move his leg, but his pain could not be evaluated since he was delirious.[ncbi.nlm.nih.gov]
Lower Extremity Pain
  • Phlegmasia cerulea dolens is a rare form of massive proximal venous thrombosis of the lower extremities associated with a high degree of morbidity, presenting with sudden severe lower extremity pain with edema and cyanosis.[ncbi.nlm.nih.gov]
  • Subsequently, her left lower extremity pain subsided and she was discharged home. ACCEPTED MANUSCRIPT Discussion: Phlegmasia cerulea dolens is a rare syndrome defined as a clinical triad of acute limb swelling, ischemic pain and cyanosis.[docksci.com]
  • He had been admitted to the hospital three days prior to transfer after presenting with progressive bilateral lower extremity pain and decreased sensation in his gluteal region.[onlinelibrary.wiley.com]
Pulse Deficit
  • 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.[thehealthscience.com]
  • They may still be detected if the gangrene is superficial, although a pulse deficit results when the muscle comportment is involved. On the other hand, significant swelling may prevent the detection of any pulses.[symptoma.com]
Delayed Wound Healing
  • Nonetheless, fasciotomy has significant disadvantages because it delays wound healing and a increases the risk of infection.[symptoma.com]
Discoloration of the Lower Extremity
  • After five days of therapeutic heparin, the patient's clinical response was inadequate due to progressive pain and discoloration of bilateral lower extremities; therefore, decision was made to provide catheter directed thrombolytic therapy.[ijcasereportsandimages.com]
Knee Pain
  • We review a case report of a 66-year-old woman that presented to small community army hospital after a 26-hour bus drive with knee pain and leg swelling.[ncbi.nlm.nih.gov]
Discoloration of the Lower Extremity
  • After five days of therapeutic heparin, the patient's clinical response was inadequate due to progressive pain and discoloration of bilateral lower extremities; therefore, decision was made to provide catheter directed thrombolytic therapy.[ijcasereportsandimages.com]
Suggestibility
  • This report also suggests the utility of serial ultrasound examinations to define clinically nonapparent thrombosis as an early indicator of a potentially catastrophic complication.[ncbi.nlm.nih.gov]
  • Computed tomographic scan suggested a hematoma in the paraspinal and latissimus dorsi muscles. Warfarin was discontinued, and an IVC filter was placed.[ncbi.nlm.nih.gov]
  • These data suggest that nongangrenous forms of PCD respond well to systemic anticoagulation.[ncbi.nlm.nih.gov]
  • Evidence suggests that the second method works more effectively in cases of gangrene. Many clinicians suggest placement of a vena cava filter before starting therapy with thrombolytics.[symptoma.com]
  • In this volume it is suggested that these variants (which are characterized by extensive thrombosis, limited to the venous circulation and often in association with shock) are commoner than is generally believed.[annals.org]
Enlarged Uterus
  • It is also strongly associated with the third trimester of pregnancy, where the enlarged uterus can compress veins in the pelvis and lead to similar manifestations.[symptoma.com]

Workup

Overall clinical picture is critical to the diagnosis of phlegmasia cerulea dolens and phlegmasia alba dolens, although duplex ultrasonography and contrast venography are usually used [7]. Technical improvements have increased reliability and have made it easier to assess for proximal deep thrombi with significantly less morbidity. Ultrasonography can now be used to diagnose deep vein thrombosis and monitor patients for the propagation of thrombi. It is also frequently employed when performing diagnostic venography during the initial venipuncture and administration of thrombolytic therapy.

Approximately a quarter of all patients may not be adequately tested with contrast venography because of technical difficulties. This is especially true when severe deep vein thrombosis is simultaneously present, making visualization of the venous system extremely difficult. This problem can be circumvented with descending venography administered through the contralateral femoral vein or through the upper extremity veins.

On the other hand, magnetic resonance venography is a new potential diagnostic modality. It allows the visualization of both the distal and the proximal parts of the thrombus with only one study. However, it also has its disadvantages. It cannot be employed with acutely ill patients, unstable patients and in those who are in extreme pain because of motion artifacts.

Treatment

Treatment for both phlegmasia and venous gangrene is developing gradually. Current treatment strategies have only resulted in partial success, so new treatments need to be formulated to improve overall outcomes.

Conservative medical treatment is recommended for phlegmasia alba dolens and phlegmasia cerulea dolens not associated with gangrene. These consist of elevation of the extremity, resuscitation with fluids and anticoagulation through heparin infused via the intravenous route. In fact, leg elevation is the optimal nonsurgical method to decrease swelling in the affected extremity.

Heparin is critical in the management of these patients. It can prevent clot formation and embolization, although it does not resolve edema. It is usually administered at a continuous rate of 15 to 18 units per kgs, preceded by an intravenous bolus of 80 to 100 units kg. The activated partial thromboplastin time should be frequently monitored, and treatment should target values 2 to 2.5 times greater than the reference range. In addition, the platelet count should be closely monitored so as not to miss heparin-induced thrombocytopenia. Although low molecular weight heparin has been shown to be effective in the management of pulmonary embolism and deep vein thrombosis, no studies have validated its use in phlegmasia [8]. In case of heparin-induced thrombocytopenia, heparin should be immediately stopped and substituted with a different anticoagulant, such as Danaparoid and lepirudin. Risk of thrombocytopenia with danaparoid is not completely eliminated given its cross reactivity with antibodies to heparin in 10 to 19 % cases. After heparin administration, oral therapy with warfarin should be continued for at least six months. Some patients in a hypercoagulable state may require lifelong treatment with anticoagulants.

Thrombolysis is another potential treatment modality. It was first introduced in 1970 by Paquet for the treatment of phlegmasia cerulea dolens [9]. There are different ways to perform thrombolysis. One method involves the insertion of a catheter into the vein, and the administration of urokinase or tissue plasminogen activator through the catheter. The second method proposes the administration of thrombolytic drugs via the arterial route through the common femoral artery. It is hypothesized that the agent will be delivered into the venous system after passing through the capillaries. Evidence suggests that the second method works more effectively in cases of gangrene. Many clinicians suggest placement of a vena cava filter before starting therapy with thrombolytics. A combination of anticoagulation, thrombolysis and heparin infusion is usually the standard of treatment [10].

A wide range of surgical approaches is also available. Urgent decompression of elevated pressure in the venous system can be achieved with surgical thrombectomy. The operation is usually conducted while the patient is in the Trendelenburg position, thus decreasing the risk of a pulmonary embolism. Other methods are also available to decrease the risk of pulmonary embolism such as thrombectomy in combination with transabdominal cavotomy. In addition, to decrease the risk of recurrence, an arteriovenous fistula is created between the greater saphenous vein and the femoral artery. Polytetrafluoroethylene may also be used to reconstruct the veins of the pelvis. These procedures are helpful in cases where there is compression from external structures, damage, or constriction of the proximal iliofemoral vein.

Increased pressure in the fascial compartment can be best treated with fasciotomy alone or in combination with thrombectomy and thrombolysis. Nonetheless, fasciotomy has significant disadvantages because it delays wound healing and a increases the risk of infection.

Prognosis

Phlegmasia cerulea dolens (PCD) and venous gangrene have a bad prognosis with very high mortality rates of up to 20 and 40%, despite the improvement in the treatment options. The most common cause of death in phlegmasia cerulea dolens is pulmonary embolism, which is responsible for 30% for all mortalities. 

In addition, patients are at a very high risk of losing an extremity, with rates ranging from 12 to 50%. Postphlebitic sequelae can also take place in 60 to 94% of all patients who survive the disease. 

Etiology

Phlegmasia is most commonly caused by thrombus formation and blockage in venous blood flow. Several factors may ultimately lead to the disease [4]. Malignancy is responsible for around 20 to 40% of all cases of phlegmasia cerulea dolens. In addition, the condition has been especially associated with pregnancy, particularly in the third trimester. The enlarged ureters can compress the left common iliac vein against the pelvis, leading to venous obstruction. Some patients, nonetheless, have no identifiable risk factors.

A number of other causative factors are also involved, and these include trauma, surgery, gastroenteritis, heart failure, mitral valve stenosis, May-Thurner syndrome, insertion of a vena caval filter, ulcerative colitis and hypercoagulable syndrome. May-Thurner syndrome occurs when the right iliac artery compresses the left iliac vein.

Epidemiology

The exact incidence of phlegmasia cerulea dolens is still unknown. The disease was first described in the 16th century by Fabricius Hildanus and was subsequently differentiated from phlegmasia alba dolens in 1938 by Gregoire [5]. Unlike phlegmasia cerulea dolens, phlegmasia alba dolens involves massive thrombosis but in the absence of ischemia.

In the United States, 600,000 cases of venous thromboembolism are thought to occur every year. Phlegmasia cerulea dolens has been described in every age group but occurs more frequently in the fifth and sixth decades. It is also more common in women than in men.

Sex distribution
Age distribution

Pathophysiology

Phlegmasia cerulea dolens targets both superficial collateral veins and deep veins, leading to severe congestion, fluid extravasation and swelling. In contrast, phlegmasia alba dolens spares collateral veins and thrombosis only occurs in the deep veins of the extremities. 

40% to 60% of cases of phlegmasia cerulea dolens also involve the capillaries. This ultimately leads to irreversible changes that affect the muscle, the subcutaneous tissue as well as the skin. The mechanisms underlying arterial collapse remain controversial but it is thought that the increased interstitial pressure can exert pressure over small arteries, increase resistance to venous outflow and result in shock. Furthermore, some suggest that the mechanisms involve vascular constriction of the resistance vessels.

The increase in hydrostatic pressure within the capillaries leads to fluid extravasation in the amount of 6 to 10 Liters. This occurs within a short duration due to the drastic increase in hydrostatic pressure of about 16 to 17 times in the space of 6 hours. The loss of fluid in the interstitial space can result in circulatory shock in approximately one third of all patients.

Prevention

Changes in lifestyle play an important role in the prevention of phlegmasia cerulea dolens. Smoking cessation and a regular exercise regimen to lose weight as well as a close monitoring of blood pressure are all considered effective preventive measures. In addition, it is important for the patient to stay active and avoid sitting continuously in the same position. In case the patient is scheduled for surgery, anticoagulation medication should be administered to decrease the postoperative risk of developing blood clots.

Summary

Phlegmasia cerulea dolens is a rare disease that manifests with extensive thrombosis and clot formation in the venous system. The nomenclature was introduced in 1938 by Gregoire who was able to differentiate it from similar conditions that are also associated with venous thrombosis, but in the absence of ischemia. There are many causes responsible for the disease. One of the most common causative factors is malignancy, accounting for 40% of all cases, although there is a range of disorders that can ultimately lead to the development of phlegmasia cerulea dolens. It is also strongly associated with the third trimester of pregnancy, where the enlarged uterus can compress veins in the pelvis and lead to similar manifestations. Patients usually present with severe pain, blanching and swelling and can progress to life threatening complications [1]. Diagnosis is established clinically but interventional as well as imaging studies can be performed. Treatment is with anticoagulation medication such as heparin and warfarin, in addition to thrombectomy or administration of thrombolytics. Prognosis of phlegmasia cerulea dolens is poor with mortality rates of up to 40% and a risk of amputation in up to 50% of surviving patients [2] [3].

Patient Information

Phlegmasia cerulea dolens is a medical condition in which clots can form in the venous system, resulting in the blockage of circulation and in the development of tissue death in severe cases. Causative factors are various, but malignancy accounts for up to 40% of all cases. It is also associated with pregnancy, in which the enlarged uterus can compress veins in the pelvis and result in the formation of clots. Patients usually present with edema of the extremity, continuous pain and blanching of the skin. They may also exhibit various skin manifestations such as blebs or bullae, which signal gangrene, a process that eventually leads to death of the tissue. Diagnosis is established clinically, although interventional as well as imaging modalities can also be used. In particular, the physician may utilize ultrasound, MRI or a procedure in which a contrast agent is injected into the veins, allowing the visualization of the venous structures. Treatment is with medication that prevents clot formation such as heparin and warfarin as well as drugs that dissolve the primary clot. In addition, surgical intervention may be necessary in unstable cases. Prognosis of phlegmasia cerulea dolens is poor with mortality rates reaching 40%. Up to 50% of all surviving patients will require limb amputation.

References

Article

  1. Collins DN, Barnes CL, McCowan TC, et al. Vena caval filter use in orthopaedic trauma patients with recognized preoperative venous thromboembolic disease. J Ort/iop Trauma. 1992; 6:135-138.
  2. Burke PE, Michna BA, Harve CF,et al. Experimental comparison of percutaneous vena caval devices titanium Greenfield filter versus bird’s nest filter. J Vasc Surg. 1987; 6:66-70.
  3. Bertelsen S, Anker N. Phlegmasia coerulea dolens, Pathophysiology, clinical features, treatment, and prognosis. Acta Chir Scan. 1968; 134:107- 114.
  4. Wilson B, Hakins ML, Mansberger AR. Posttraumatic phlegmasia cerulea dolens: an indication for the Greenfield filter. South Med J. 1989; 82:780–782.
  5. Gregoire R. La Phlebite bleue (Phlegmasia Cerulea Dolens). 1938; 48:1313-15.
  6. Sarwar S, Narra S, Munir A. Phlegmasia cerulea dolens. Tex Heart Inst J. 2009; 36:76–77.
  7. Green D. Diagnosis, prevalence, and management of thromboembolism in patients with spinal cord injury. J Spinal Cord Med. 2003; 26:329–234.
  8. 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. 1992 Apr 9; 326(15):975-82.
  9. Paquet KJ, Popov S, Egli H. [Guidelines and results of consequent fibrinolytic therapy in phlegmasia cerulea dolens]. Dtsch Med Wochenschr. 1970 Apr 17; 95(16):903-4.
  10. Rokni Yazdi H, Rostami N, Hakimian H, et al. Successful catheter-directed venous thrombolysis in an ankylosing spondylitis patient with phlegmasia cerulea dolens. Iran J Radiol. 2013 Jun; 10(2):81-5.

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Last updated: 2019-07-11 20:29