Multiple venous thromboses in a young man with sarcoidosis: is there a relation between sarcoidosis and venous thrombosis?

Abstract: We describe the case of a 33-year-old African-American male who presented with multiple deep venous thromboses of the upper and lower extremities. Hypercoagulable workup was unrevealing. A chest x-ray showed bilateral hilar lymph node enlargement. Mediastinoscopy with hilar lymph node biopsy was performed. Lymph node histopathologic examination showed noncaseating granulomas. Lymph node tissue culture and special stains were negative for mycobacterial or fungal infection. This is an unusual case of multiple deep venous thromboses and sarcoidosis. The subject of sarcoidosis and venous thrombosis is discussed.

Key Words: sarcoidosis, venous thrombosis

Case Report

A 33-year-old African-American man was admitted to our hospital with swelling of the lower extremities. The patient was otherwise asymptomatic. He denied any history of trauma to his legs. Grayscale ultrasound and spectral Doppler examination of the lower extremities revealed acute deep venous thrombosis of the right distal femoral and popliteal veins and left posterior tibial vein. Subsequently, grayscale ultrasound and spectral Doppler examination of the upper extremities were also done which showed thrombi of the right external jugular vein, left subclavian vein, and left brochiocephalic vein. The patient was started on continuous anticoagulation. His past medical history was significant for diabetes mellitus Type 2 that was diagnosed 3 years before presentation. The patient was a nonsmoker and denied IV drug use. Family history was negative for frequent abortionsor vascular thromboses. His medications included metformin and aspirin. Physical examination showed a temperature of 98[degrees]F, blood pressure of 110/60 mm Hg, heart rate of 70/min, respiratory rate of 16/min, and an oxygen saturation of 99% on room air. Small, mobile, and nontender lymph nodes were palpable in the posterior cervical, axillary, and inguinal areas. Skin, chest, cardiac, and abdominal examinations were all unremarkable. Laboratory findings included a white blood cell count of 3.4 X [l0.sup.3]/mL, hemoglobin of 9.4 g/dL, creatinine of 0.9 mg/dL, serum angiotensin converting enzyme level of 27 U/L (normal 9-67 U/L), negative antinuclear antibody, negative anticardiolipin antibodies (IgG, IgA, IgM), normal levels of serum [beta]2 glucoprotein antibody, negative human immunodeficiency virus antibody, microalbuminuria, and normal hepatic aminotransferases. Protein S, protein C, and antithrombin III serum levels were normal before initiation of anticoagulation. A chest x-ray and computed tomography scan of the chest showed bilateral hilar lymphadenopathy. Although the chest imaging suggested a diagnosis of sarcoidosis, mediastinoscopy with lymph node biopsy was performed to exclude malignancy. Pathology showed noncaseating granulomas involving the mediastinal and hilar lymph nodes. Tissue cultures and special staining for mycobacterial and fungal pathogens were negative.

Discussion

Sarcoidosis is a systemic disease characterized by noncaseating granulomas of unknown origin that involve the lungs, skin, eye, liver, nervous system, and other organs. Sarcoidosis can present with a variety of clinical manifestations that may include asymptomatic mediastinal lymphadenopathy, skin lesions, uveitis, neurosarcoidosis, hepatitis, and pulmonary parenchymal disease as well as other systemic manifestations.

There is only one reported case of deep venous thrombosis (right brachiocephalic vein) in the literature that has been related to sarcoidosis. Venous compression by enlarged lymph nodes, oral contraceptive pill use, cigarette smoking, and obesity were suspected to contribute to the development of DVT. (1) Widespread and recurrent thrombophlebitis has also been described in sarcoidosis. (2) Although DVT of the extremities has rarely been reported in sarcoidosis, thrombus formation has been described in a variety of organs. It is interesting to note that the venous thromboses in these cases were in close anatomic relation with active sarcoidosis, ie, mural thrombus in myocardial sarcoidosis, dural vein thrombosis in neurosarcoidosis, and right brochiocephalic vein in mediastinal disease. A local tissue thrombophilic state may explain this observation. Abnormalities of local tissue procoagulation and fibrinolysis have been described in sarcoidosis; namely, enhanced tissue factor pathway activity, increased tissue thromboplastin activity, diminished plasminogen activator activity, increased factor VII activity, decreased protein C activation, and increased thrombin-activatable fibrinolysis inhibitor. (4) These local tissue alterations may favor thrombus formation in susceptible patients. Increased D-dimer levels in the blood and lungs of sarcoidosis patients also support the concept of coagulation activation and increased deposition of fibrin in tissues. (5)

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In conclusion, we describe a case of multiple venous thrombi in a patient with sarcoidosis. DVT has been rarely reported in association with sarcoidosis. Although the exact mechanism of thrombus formation in sarcoidosis is not yet known, venous stasis secondary to lymph node compression, local tissue thrombophilia in involved organs, and granulomatous phlebitis are potential mechanisms.

References

1. McLaughlin AM, McNicholas Sarcoidosis presenting as upper extremity venous thrombosis. Thorax 2003;58:552.

2. Rowland Payne CM, McGibbon DH. Sarcoidosis presenting as widespread thrombophlebitis. Clin Exp Dermatol 1985;10:592-594.

3. Kinney EL, Murthy R, Ascunce G, et al. Sarcoidosis: rare cause of superior vena caval obstruction. Pa Med 1980;83:31.

4. Hasday JD, Bachwich PR, Lynch JP et al. Procoagulant and plasminogen activator activities of bronchoalveolar fluid in patients with pulmonary sarcoidosis. Exp Lung Res 1988;14:261-278.

5. Shorr AF, Hnatiuk OW. Circulating D dimer in patients with sarcoidosis. Chest 2000;117:1012-1016.

Bobbak Vahid, MD, Bernadette Wildemore, MD, and Paul E. Marik, MD

From the Department of Pulmonary and Critical Care Medicine, and the Department of Pathology, Thomas Jefferson University, Philadelphia, PA.

Reprint requests to Bobbak Vahid, MD, 1015 Chestnut Street Suite M-100, Philadelphia, PA 19107. Email: [e-mail]

Accepted April 11.2006.

RELATED ARTICLE: Key Points

* Deep venous thrombosis has been rarely reported in association with sarcoidosis.

* Although the exact mechanism of thrombus formation in sarcoidosis is not yet known, venous stasis secondary to lymph node compression, local tissue thrombophilia in involved organs, and granulomatous phlebitis are potential mechanisms.

* Superior vena cava syndrome, Budd-Chiari syndrome, retinal vein thrombosis, dural sinus thrombosis, and mural thrombosis in myocardial sarcoidosis are other examples of venous thrombosis associated with sarcoidosis.