Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Pulmonary Veno-Occlusive Disease Treatment & Management

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

Approach Considerations

Specific PAH therapies may be associated with a risk of pulmonary edema at any time during the therapy. Extreme caution should be used while administering intravenous or subcutaneous prostanoids and dose escalation should be relatively slow.

No well-structured, prospective clinical trials have been performed to evaluate the effect of various nonsurgical interventions on the outcome of pulmonary veno-occlusive disease (PVOD). Currently, the information gained from clinical trials involving other forms of pulmonary arterial hypertension (PAH) is extrapolated from clinical experience, case reports, and case series in order to choose various therapies. Patients with PVOD are best served at a pulmonary hypertension specialty center.

No general consensus has been reached on the choice of first-line therapy for persons with PVOD. However, because PAH therapies (eg, continuous intravenous prostacyclin) are poorly tolerated and are perceived to have only a marginal effect on outcome, patients are offered the option of lung transplantation whenever possible. In the absence of this surgery, most patients do not survive beyond 2-3 years after diagnosis.

Lung transplantation

Currently, lung transplantation is the only therapeutic option capable of significantly prolonging and improving the lives of patients with PVOD. Single- and double-lung transplantation procedures have both been used. Recurrence after heart-lung transplantation was reported in one patient.[48]

Next

Specific PAH Therapies

The use of specific pulmonary arterial hypertension (PAH) therapies—eg, prostacyclin analogues, endothelin receptor antagonists, phosphodiesterase-5 inhibitors—in patients with pulmonary veno-occlusive disease (PVOD) is controversial.

Initial reports described the development of acute fulminant pulmonary edema and death[49] in association with infusions of intravenous epoprostenol. A 2008 report comparing PVOD patients with or without PCH to idiopathic patients reported pulmonary edema in 7 of 16 PVOD patients with vasodilator therapy.[50] However, in patients who do not have the option of lung transplantation, PVOD results in death within a few months to years after diagnosis. Consequently, continuous intravenous epoprostenol has been tried in PVOD patients, very cautiously and with relatively slow-dose up-titration. This treatment was met with some success.[46]

Epoprostenol has been reported to have some beneficial effects on hemodynamics in patients with pulmonary veno-occlusive disease (PVOD) and it has been demonstrated to reverse the increased vasomotor tone in pulmonary venules.[51] However, no structured clinical trials are available to support the use of any specific PAH therapies in PVOD patients.

Presently, treatment must be individualized to the patient after discussing the risks and benefits from the sparse data available. Pulmonary edema may occur, acutely or months after initiation of therapy, with the use of vasodilators.[38]

In the absence of an obvious or potential contraindication, the American College of Chest Physicians recommends anticoagulation in patients with PAH.[52] It is not unreasonable to consider anticoagulation with warfarin (Coumadin) in PVOD patients if they have no contraindications (eg, history of significant hemoptysis). The target international normalized ratio (INR) is 1.5-2.5.

Long-term oxygen supplementation therapy should be used for hypoxemic patients with PVOD to keep their oxyhemoglobin saturation at greater than 90% at all times. This may result in symptomatic and subjective improvement. No direct good-quality evidence exists for speculation about the magnitude of benefit in terms of survival or exercise capacity in patients with PVOD.

Previous
Next

Immunosuppressants, Steroids, and Antithrombotic Agents

Other therapies have been reported to have some role in pulmonary veno-occlusive disease (PVOD) management. However, their use is not widespread.

The role of immunosuppressive medications in the treatment of PVOD remains undefined but these agents may help a subset of patients with PVOD, particularly those with autoimmune features.[7]

A trial of corticosteroids may be considered following a chest radiograph and oxygen therapy. Although it does not change the course of the disease, corticosteroid treatment may provide symptomatic improvement.[53]

Most experimental interventions involve antithrombotic treatment with agents such as heparin, thrombolytic agents such as recombinant tissue plasminogen activator, antithrombin III concentrate in patients with a documented antithrombin III deficienc. Another drug, defibrotide, which is a polydeoxyribonucleotide derived from mammalian cells, is now approved in the United States for hepatic VOD in adults and children with renal or pulmonary dysfunction following HSCT. Currently, none of these therapies has any role in the treatment of patients with PVOD.

Previous
 
 
Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

Acknowledgements

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

References
  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].

 
Previous
Next
 
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
Echocardiogram    
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
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.