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Communications to the Editor |

Epoprostenol for Treatment of Pulmonary Hypertension in Patients With Systemic Lupus Erythematosus FREE TO VIEW

Evelyn M. Horn, MD; Robyn J. Barst, MD; Michael Poon, MD
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Columbia University College of Physicians & Surgeons New York, NY Mount Sinai Medical Center New York, NY

Correspondence to: Evelyn M. Horn, MD, Director of Clinical Services, Heart Failure Research Center, New York Presbyterian Hospital, Columbia-Presbyterian Campus, 177 Fort Washington Ave, Milstein 5–435, New York, NY 10032; e-mail: emh3@columbia.edu



Chest. 2000;118(4):1229-1230. doi:10.1378/chest.118.4.1229
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To the Editor:

As reported by Robbins et al (January 2000),1 although IV epoprostenol therapy improves symptoms, exercise tolerance, and hemodynamics in patients with pulmonary hypertension associated with systemic lupus erythematosus (SLE), the overall improvement may not necessarily be as great as that seen with patients who have pulmonary hypertension without associated collagen vascular disorders. In addition, although thrombocytopenia has been reported with long-term epoprostenol therapy, the degree to which this is attributable to the epoprostenol therapy as opposed to other etiologies is unclear. Other causes of thrombocytopenia in pulmonary hypertension patients may include the following: pulmonary vascular sequestration due to the underlying pulmonary vascular disease; hepatosplenomegaly with portal hypertension and splenic sequestration; an autoimmune-mediated “idiopathic thrombocytopenia purpura (ITP)-like” syndrome; and as a consequence of the presence of antiphospholipid antibodies. Furthermore, the degree to which epoprostenol therapy may exacerbate the predisposition for thrombocytopenia in patients with pulmonary hypertension associated with SLE is unknown.

In reviewing our experience with six pulmonary hypertension patients with a history of SLE who were treated with long-term epoprostenol, four of the six patients (who all subsequently died receiving long-term epoprostenol treatment) also had life-threatening thrombocytopenia despite other aspects of their lupus considered quiescent (Table 1 ). Three of these four patients required long-term aggressive steroid therapy as well as repeated administration of IV γ-globulin in an attempt to improve their thrombocytopenia. Despite a previously documented “ITP-like” syndrome requiring treatment prior to institution of long-term epoprostenol complicating the picture in two of these patients, with treatment for the ITP-like syndrome their platelet counts were maintained > 75,000 109/L prior to starting long-term epoprostenol therapy.

The most recent death occurred in patient 4 following splenectomy performed for refractory thrombocytopenia (platelet count, 10,000 to 20,000/mm2) despite prednisone, 60 mg qd, repeated pulse-dose IV steroids, and IV γ-globulin. Because she had no manifestations of active lupus, she was not treated with cyclophosphamide; consideration had also been given to vincristine for refractory thrombocytopenia. Although she had clinically improved from a pulmonary hypertension standpoint with long-term epoprostenol use, she had not improved hemodynamically (by repeat cardiac catheterization at 12 months and 19 months). In addition, she unfortunately was not a candidate for lung transplantation due to her progressive thrombocytopenia. Splenectomy was therefore performed. She was treated perioperatively with inotropic support, low-dose vasopressin, and inhaled nitric oxide. She had no surgical bleeding complications, although her platelet count only responded to perioperative platelet transfusions. She died 6 days postoperatively with an acute pulmonary hypertensive crisis. At autopsy, there was evidence of diffuse microemboli in her lungs only, without an inflammatory component (Fig 1 ). The surgically removed spleen was unremarkable and without evidence of platelet sequestration.

This case (patient 4) raises the possibility that the localization of platelet destruction in SLE patients with pulmonary hypertension is the pulmonary vascular bed, suggesting the need to strongly consider lung transplantation despite its high risk in patients with thrombocytopenia, as opposed to consideration of palliative splenectomy. We remain concerned that long-term epoprostenol use may exacerbate thrombocytopenia in this high-risk patient population, which may prove fatal. Overall, this adverse effect of epoprostenol therapy (eg, thrombocytopenia), may outweigh the potential benefits of epoprostenol treatment in some pulmonary hypertension patients with a history of SLE. Serial reevaluations of risk/benefit considerations for therapeutic options are needed for all pulmonary hypertension patients treated with long-term epoprostenol therapy. However, SLE patients (with significant concomitant medical problems) may even need more frequent reassessments to optimize medical and/or surgical therapeutic options including lung transplantation before it is precluded due to progressive life-threatening thrombocytopenia.

Table Graphic Jump Location
Table 1. Demographic Characteristics, Hemodynamic Parameters, and Outcome in Patients Treated With Epoprostenol*
* 

Pt = patient; F = female; ACL = anticardiolipin; ANA = antinuclear antibody; ENA = extractable nuclear antigen; U, RNP = extractable nuclear antigen subset; vW Ag = vonWillebrand antigen; vWF = vonWillebrand factor; CH50 = CH 50 complement levels; C4 = complement; ADP = adenosine diphosphate; RF = rheumatoid factor.

 

Mean right atrial pressure (RA) and pulmonary artery systolic/diastolic pressure (PA) are expressed as mm Hg; cardiac index (CI) is adenosine expressed as L/min/m2. Mixed venous oxygen saturation (PA sat) is expressed as %.

Figure Jump LinkFigure 1. Organized pulmonary thrombus (top; original × 100) and high-power magnification of small vessel thrombus with platelet consumption (bottom; original × 200).Grahic Jump Location

References

Robbins, IM, Gaine, SP, Schilz, R, et al (2000) Epoprostenol for treatment of pulmonary hypertension in patients with systemic lupus erythematosus.Chest117,14-18. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Organized pulmonary thrombus (top; original × 100) and high-power magnification of small vessel thrombus with platelet consumption (bottom; original × 200).Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Demographic Characteristics, Hemodynamic Parameters, and Outcome in Patients Treated With Epoprostenol*
* 

Pt = patient; F = female; ACL = anticardiolipin; ANA = antinuclear antibody; ENA = extractable nuclear antigen; U, RNP = extractable nuclear antigen subset; vW Ag = vonWillebrand antigen; vWF = vonWillebrand factor; CH50 = CH 50 complement levels; C4 = complement; ADP = adenosine diphosphate; RF = rheumatoid factor.

 

Mean right atrial pressure (RA) and pulmonary artery systolic/diastolic pressure (PA) are expressed as mm Hg; cardiac index (CI) is adenosine expressed as L/min/m2. Mixed venous oxygen saturation (PA sat) is expressed as %.

References

Robbins, IM, Gaine, SP, Schilz, R, et al (2000) Epoprostenol for treatment of pulmonary hypertension in patients with systemic lupus erythematosus.Chest117,14-18. [CrossRef] [PubMed]
 
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