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Pulmonary Veno-Occlusive Disease Medication

  • Author: Hakim Azfar Ali, MD; Chief Editor: Ryland P Byrd, Jr, MD  more...
Updated: Apr 01, 2016

Medication Summary

As previously stated, the prostaglandin epoprostenol, a vasodilator, has been reported to have some hemodynamic benefits in patients with pulmonary veno-occlusive disease (PVOD) and has been shown to reverse the increase in pulmonary venule vasomotor tone that occurs in this condition.[51] Nonetheless, the development of acute fulminant pulmonary edema and death have been reported with the infusion of intravenous epoprostenol, even at a very low dose. Therefore, this drug should be used with great caution in patients with suspected PVOD.



Class Summary

These agents have vasodilatory effects.

Epoprostenol (Flolan, Veletri)


Epoprostenol, an analogue of prostacyclin (PGI2), has potent vasodilatory properties, an immediate onset of action, and a half-life of approximately 5 minutes. In addition to its action as a vasodilator, epoprostenol also contributes to the inhibition of platelet aggregation and plays a role in the inhibition of smooth muscle proliferation.[46]

Long-term infusion of this drug improves the outcome in patients with primary pulmonary hypertension and in selected patients with secondary pulmonary hypertension. A short-term vasodilatory response appears to be unrelated because favorable impact on disease progression occurs with long-term therapy.

The dose is determined during a dose/effect study performed in the catheterization laboratory or the intensive care unit (ICU). The selected dose should produce maximum vasodilation with minimal systemic hypotension.



Class Summary

These agents prevent thromboembolic disorders.

Warfarin (Coumadin)


Warfarin interferes with the hepatic synthesis of vitamin K–dependent coagulation factors. It is used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders.

Tailor the dose to maintain an INR in the range of 2-3. The recurrence rate of deep venous thrombosis (DVT) and pulmonary embolism increases dramatically when the INR drops to below 2 and decreases when the INR is kept at 2-3. Serious bleeding risk (including hemorrhagic stroke) is approximately constant when the INR is 2.5-4.5 but rises dramatically when INR is over 5.

Procoagulant vitamin K–dependent proteins are responsible for a transient hypercoagulable state when warfarin is first started and when it is stopped. This phenomenon occasionally causes warfarin-induced necrosis of large areas of skin or of distal appendages. Heparin is always used to protect against this hypercoagulability when warfarin is started; however, when warfarin is stopped, the problem resurfaces, causing an abrupt, temporary rise in the rate of recurrent venous thromboembolism.

At least 186 different foods and drugs have been reported to interact with warfarin. Clinically significant interactions have been verified for a total of 26 common drugs and foods, including 6 antibiotics and 5 cardiac drugs. Every effort should be made to keep the patient adequately anticoagulated at all times because procoagulant factors recover first when warfarin therapy is inadequate.

Patients who have difficulty maintaining adequate anticoagulation while taking warfarin may be asked to limit their intake of foods that contain vitamin K. Foods that have moderate to high amounts of this vitamin include Brussels sprouts, kale, green tea, asparagus, avocado, broccoli, cabbage, cauliflower, collard greens, liver, certain beans, soybean oil, soybeans, mustard greens, peas (black-eyed peas, split peas, chick peas), turnip greens, parsley, green onions, spinach, and lettuce.



Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.



Prednisone is an immunosuppressant used for autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) leukocyte activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocytes and antibody production. It has some role in the treatment of pulmonary veno-occlusive disease (PVOD), particularly when autoimmune features coexist with it.



Class Summary

These agents have immunosuppressive properties.

Azathioprine (Imuran, Azasan)


Azathioprine is an imidazolyl derivative of 6-mercaptopurine, and many of its biologic effects are similar to those of its parent compound. Both compounds are eliminated rapidly from blood and are oxidized or methylated in erythrocytes and the liver. No azathioprine or mercaptopurine is detectable in urine 8 hours after administration.

Azathioprine antagonizes purine metabolism and inhibits the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteins. The mechanism through which azathioprine affects autoimmune diseases is unknown. The drug works primarily on T cells. It suppresses hypersensitivities of the cell-mediated type and causes variable alterations in antibody production. Immunosuppressive, delayed hypersensitivity, and cellular cytotoxicity test results are suppressed to a greater degree than are antibody responses.

Azathioprine works very slowly; it may require 3-6 months of trial prior to effect. Up to 10% of patients may have an idiosyncratic reaction to the drug, disallowing use. The white blood cell (WBC) count must not be allowed to drop below 3000/µL or the lymphocyte count be allowed to drop below 1000/µL. Azathioprine is available in tablet form for oral administration or in 100mg vials for intravenous injection.

Contributor Information and Disclosures

Hakim Azfar Ali, MD Consultant in Pulmonary and Critical Care Medicine, Christiana Care Hospital

Hakim Azfar Ali, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Nothing to disclose.


Shoaib Alam, MD Staff Clinician, Pulmonary and Vascular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health

Shoaib Alam, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, Society of Critical Care Medicine, International Society for Magnetic Resonance in Medicine, European Respiratory Society, Pennsylvania Thoracic Society

Disclosure: Nothing to disclose.

Chief Editor

Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.


Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP Professor of Genomics and Personalized Medicine Research, Internal Medicine, and Pediatrics, Associate Director, Center for Genomics and Personalized Medicine Research, Director of Research, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society, and Sigma Xi

Disclosure: See below for list of all activities None None

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

  1. Rounds S, Cutaia MV. Pulmonary hypertension: Pathophysiology and clinical disorders. Baum GL, Crapo JD, Celli BR, Karlinsky JB, eds. Textbook of Pulmonary Diseases. Philadelphia, Pa: Lippincott-Raven; 1998. 1273-95.

  2. Wagenvoort CA. Lung biopsy specimens in the evaluation of pulmonary vascular disease. Chest. 1980 May. 77(5):614-25. [Medline].

  3. Thadani U, Burrow C, Whitaker W, et al. Pulmonary veno-occlusive disease. Q J Med. 1975 Jan. 44(173):133-59. [Medline].

  4. Wagenvoort CA. Pulmonary veno-occlusive disease. Entity or syndrome?. Chest. 1976 Jan. 69(1):82-6. [Medline].

  5. Hora J. Zur Histologie der klinischen "primaren Pulmonalsklerose". Frankfurt Z Pathol. 1934. 47:100-08.

  6. Shackelford GD, Sacks EJ, Mullins JD, et al. Pulmonary venoocclusive disease: case report and review of the literature. AJR Am J Roentgenol. 1977 Apr. 128(4):643-8. [Medline].

  7. De Vries TW, Weening JJ, Roorda RJ. Pulmonary veno-occlusive disease: a case report and a review of therapeutic possibilities. Eur Respir J. 1991 Sep. 4(8):1029-32. [Medline].

  8. Chazova I, Robbins I, Loyd J, et al. Venous and arterial changes in pulmonary veno-occlusive disease, mitral stenosis and fibrosing mediastinitis. Eur Respir J. 2000 Jan. 15(1):116-22. [Medline].

  9. Wagenvoort CA, Wagenvoort N, Takahashi T. Pulmonary veno-occlusive disease: involvement of pulmonary arteries and review of the literature. Hum Pathol. 1985 Oct. 16(10):1033-41. [Medline].

  10. Lathen C, Zhang Y, Chow J, Singh M, Lin G, Nigam V, et al. ERG-APLNR axis controls pulmonary venule endothelial proliferation in pulmonary veno-occlusive disease. Circulation. 2014 Sep 30. 130(14):1179-91. [Medline]. [Full Text].

  11. Dai Z, Matsui Y. Pulmonary veno-occlusive disease: an 80-year-old mystery. Respiration. 2014. 88(2):148-57. [Medline].

  12. Sanderson JE, Spiro SG, Hendry AT, et al. A case of pulmonary veno-occlusive disease respondong to treatment with azathioprine. Thorax. 1977 Apr. 32(2):140-8. [Medline].

  13. Kishida Y, Kanai Y, Kuramochi S, et al. Pulmonary venoocclusive disease in a patient with systemic lupus erythematosus. J Rheumatol. 1993 Dec. 20(12):2161-2. [Medline].

  14. Zhang L, Visscher D, Rihal C, et al. Pulmonary veno-occlusive disease as a primary cause of pulmonary hypertension in a patient with mixed connective tissue disease. Rheumatol Int. 2007 Oct. 27(12):1163-5. [Medline].

  15. Morassut PA, Walley VM, Smith CD. Pulmonary veno-occlusive disease and the CREST variant of scleroderma. Can J Cardiol. 1992 Dec. 8(10):1055-8. [Medline].

  16. Johnson SR, Patsios D, Hwang DM, et al. Pulmonary veno-occlusive disease and scleroderma associated pulmonary hypertension. J Rheumatol. 2006 Nov. 33(11):2347-50. [Medline].

  17. McDonnell PJ, Summer WR, Hutchins GM. Pulmonary veno-occlusive disease. Morphological changes suggesting a viral cause. JAMA. 1981 Aug 7. 246(6):667-71. [Medline].

  18. Escamilla R, Hermant C, Berjaud J, et al. Pulmonary veno-occlusive disease in a HIV-infected intravenous drug abuser. Eur Respir J. 1995 Nov. 8(11):1982-4. [Medline].

  19. Davies P, Reid L. Pulmonary veno-occlusive disease in siblings: case reports and morphometric study. Hum Pathol. 1982 Oct. 13(10):911-5. [Medline].

  20. Voordes CG, Kuipers JR, Elema JD. Familial pulmonary veno-occlusive disease: a case report. Thorax. 1977 Dec. 32(6):763-6. [Medline].

  21. Runo JR, Vnencak-Jones CL, Prince M, et al. Pulmonary veno-occlusive disease caused by an inherited mutation in bone morphogenetic protein receptor II. Am J Respir Crit Care Med. 2003 Mar 15. 167(6):889-94. [Medline].

  22. Joselson R, Warnock M. Pulmonary veno-occlusive disease after chemotherapy. Hum Pathol. 1983 Jan. 14(1):88-91. [Medline].

  23. Knight BK, Rose AG. Pulmonary veno-occlusive disease after chemotherapy. Thorax. 1985 Nov. 40(11):874-5. [Medline].

  24. Liu L, Sackler JP. A case of pulmonary veno-occlusive disease: Etiological and therapeutic appraisal. Angiology. 1973. 23:299-304.

  25. Williams LM, Fussell S, Veith RW, et al. Pulmonary veno-occlusive disease in an adult following bone marrow transplantation. Case report and review of the literature. Chest. 1996 May. 109(5):1388-91. [Medline].

  26. Hosokawa K, Yamazaki H, Nishitsuji M, Kobayashi S, Takami A, Fujimura M, et al. Pulmonary Veno-occlusive Disease Following Reduced-intensity Allogeneic Bone Marrow Transplantation for Acute Myeloid Leukemia. Intern Med. 2012. 51(2):195-8. [Medline].

  27. Kramer MR, Estenne M, Berkman N, et al. Radiation-induced pulmonary veno-occlusive disease. Chest. 1993 Oct. 104(4):1282-4. [Medline].

  28. Cassart M, Gevenois PA, Kramer M, et al. Pulmonary venoocclusive disease: CT findings before and after single-lung transplantation. AJR Am J Roentgenol. 1993 Apr. 160(4):759-60. [Medline].

  29. Mandel J, Mark EJ, Hales CA. Pulmonary veno-occlusive disease. Am J Respir Crit Care Med. 2000 Nov. 162(5):1964-73. [Medline].

  30. Wagenvoort CA, Losekoot G, Mulder E. Pulmonary veno-occlusive disease of presumably intrauterine origin. Thorax. 1971 Jul. 26(4):429-34. [Medline].

  31. Cohn RC, Wong R, Spohn WA, et al. Death due to diffuse alveolar hemorrhage in a child with pulmonary veno-occlusive disease. Chest. 1991 Nov. 100(5):1456-8. [Medline].

  32. Rabiller A, Jais X, Hamid A, et al. Occult alveolar haemorrhage in pulmonary veno-occlusive disease. Eur Respir J. 2006 Jan. 27(1):108-13. [Medline].

  33. Rosenthal A, Vawter G, Wagenvoort CA. Intrapulmonary veno-occlusive disease. Am J Cardiol. 1973 Jan. 31(1):78-83. [Medline].

  34. Glassroth J, Woodford DW, Carrington CB, et al. Pulmonary veno-occlusive disease in the middle-aged. Respiration. 1985. 47(4):309-21. [Medline].

  35. Bolster MA, Hogan J, Bredin CP. Pulmonary vascular occlusive disease presenting as sudden death. Med Sci Law. 1990 Jan. 30(1):26-8. [Medline].

  36. Swensen SJ, Tashjian JH, Myers JL, et al. Pulmonary venoocclusive disease: CT findings in eight patients. AJR Am J Roentgenol. 1996 Oct. 167(4):937-40. [Medline].

  37. Laveneziana P, Montani D, Dorfmuller P, Girerd B, Sitbon O, Jais X, et al. Mechanisms of exertional dyspnoea in pulmonary veno-occlusive disease with EIF2AK4 mutations. Eur Respir J. 2014 Oct. 44(4):1069-72. [Medline].

  38. Holcomb BW Jr, Loyd JE, Ely EW, et al. Pulmonary veno-occlusive disease: a case series and new observations. Chest. 2000 Dec. 118(6):1671-9. [Medline].

  39. Maltby JD, Gouverne ML. CT findings in pulmonary venoocclusive disease. J Comput Assist Tomogr. 1984 Aug. 8(4):758-61. [Medline].

  40. Resten A, Maitre S, Capron F, et al. [Pulmonary hypertension: CT findings in pulmonary veno-occlusive disease]. J Radiol. 2003 Nov. 84(11 Pt 1):1739-45. [Medline].

  41. Gunther S, Jais X, Maitre S, Berezne A, Dorfmuller P, Seferian A, et al. Computed tomography findings of pulmonary veno-occlusive disease in scleroderma patients presenting with precapillary pulmonary hypertension. Arthritis Rheum. 2012 May 1. [Medline].

  42. Dufour B, Maitre S, Humbert M, et al. High-resolution CT of the chest in four patients with pulmonary capillary hemangiomatosis or pulmonary venoocclusive disease. AJR Am J Roentgenol. 1998 Nov. 171(5):1321-4. [Medline].

  43. Seferian A, Helal B, Jais X, Girerd B, Price LC, Gunther S, et al. Ventilation perfusion lung scan in pulmonary veno-occlusive disease. Eur Respir J. 2011 Nov 16. [Medline].

  44. Bailey CL, Channick RN, Auger WR, et al. "High probability" perfusion lung scans in pulmonary venoocclusive disease. Am J Respir Crit Care Med. 2000 Nov. 162(5):1974-8. [Medline].

  45. Rubin LJ. Primary pulmonary hypertension. N Engl J Med. 1997 Jan 9. 336(2):111-7. [Medline].

  46. Ogawa A, Miyaji K, Yamadori I, Shinno Y, Miura A, Kusano KF, et al. Safety and Efficacy of Epoprostenol Therapy in Pulmonary Veno-Occlusive Disease and Pulmonary Capillary Hemangiomatosis. Circ J. 2012 Apr 5. [Medline].

  47. Nicod P, Moser KM. Primary pulmonary hypertension. The risk and benefit of lung biopsy. Circulation. 1989 Nov. 80(5):1486-8. [Medline].

  48. Izbicki G, Shitrit D, Schechtman I, et al. Recurrence of pulmonary veno-occlusive disease after heart-lung transplantation. J Heart Lung Transplant. 2005 May. 24(5):635-7. [Medline].

  49. Palmer SM, Robinson LJ, Wang A, et al. Massive pulmonary edema and death after prostacyclin infusion in a patient with pulmonary veno-occlusive disease. Chest. 1998 Jan. 113(1):237-40. [Medline].

  50. Montani D, Achouh L, Dorfmuller P, et al. Pulmonary veno-occlusive disease: clinical, functional, radiologic, and hemodynamic characteristics and outcome of 24 cases confirmed by histology. Medicine (Baltimore). 2008 Jul. 87(4):220-33. [Medline].

  51. Davis LL, deBoisblanc BP, Glynn CE, et al. Effect of prostacyclin on microvascular pressures in a patient with pulmonary veno-occlusive disease. Chest. 1995 Dec. 108(6):1754-6. [Medline].

  52. Badesch DB, Abman SH, Ahearn GS, Barst RJ, McCrory DC, Simonneau G, et al. Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004 Jul. 126(1 Suppl):35S-62S. [Medline].

  53. Gilroy RJ Jr, Teague MW, Loyd JE. Pulmonary veno-occlusive disease. Fatal progression of pulmonary hypertension despite steroid-induced remission of interstitial pneumonitis. Am Rev Respir Dis. 1991 May. 143(5 Pt 1):1130-3. [Medline].

Medium-power photomicrograph (original magnification, X10; hematoxylin and eosin stain) demonstrates a fibrotic interlobular septum containing a vein with an occluded lumen (arrowhead). The occlusion is composed of dense, collagen-rich, fibrous tissue. Image courtesy of Thoracic Imaging Section, Department of Radiologic Pathology, Armed Forces Institute of Pathology.
Pulmonary veno-occlusive disease in a 43-year-old man. An axial computed tomography (CT) scan (lung window level) shows multiple septal lines (arrowhead) and a dilated central pulmonary artery (arrow). Image courtesy of Thoracic Imaging Section, Department of Radiologic Pathology, Armed Forces Institute of Pathology.
Table 1. Distinguishing Pulmonary Edema From PVOD Based on Radiographic, Echocardiographic, and Heart Catheterization Data
Features Pulmonary Edema PVOD
Chest radiograph    
Kerley B lines Present Present
Pleural effusion Usually present May be present
Enlarged cardiac silhouette Present Less prominent
Enlarged pulmonary artery Present Present
Chest CT scan    
Thickened septae Present Present
Pleural effusion Usually present May be present
Enlarged heart Present Less prominent
Enlarged pulmonary artery Present Present
Septal concavity into left ventricle Absent Present
Pulmonary artery systolic pressure Elevated (usually not >80 mm Hg) Elevated (may be >80 mm Hg)
Left atrial enlargement Present Absent
Right atrial enlargement Present Present
Right ventricular hypertrophy Absent Present
Paradoxical septal motion Absent Present
Large pericardial effusion Absent May be present
Right-sided heart catheterization    
Pulmonary vascular resistance Below 3.0 Wood units Above 3.0 Wood units
Pulmonary capillary wedge pressure Above 18 mm Hg Usually below 15 mm Hg

(if catheter is properly wedged)

Mean pulmonary artery pressure Elevated (almost never >50 mm Hg) Elevated (may be >50 mm Hg)
Cardiac output May be normal, low, or high Mostly decreased, may be low normal
Oxyhemoglobin step-up Absent Absent
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