Chronic myeloproliferative disorders (CMD) are characterized by clonal expansion of a multipotent hematopoietic progenitor cell with the overproduction of one or more of the formed elements of the blood. Pulmonary complications are usually infectious or thromboembolic. Pulmonary hypertension (PH) is higher than expected in patients with CMD (1). The contributing role of chemotherapy, mainly Anagrelide and Busulfan may be underestimated. We are reporting a case of PH in a patient with idiopathic myelofibrosis.
78 year-old man, former smoker (20 pack years, quit 40 years prior) with CMD (diagnosed 1 ½ years PTA), presented with a history of increasing fatigue and dyspnea on exertion for 6 months. He denied chest pain, cough or palpitations. He denied any other constitutional symptoms or toxic habits. His past medical history was also significant for bleeding gastric ulcers treated with partial gastrectomy (1960), HTN and hypercholesterolemia. He had been on lisinopril, Simvastatin and Aspirin. On physical exam he was afebrile, P=90, BP=150/62, RR=18. The remainder of his physical exam was normal except for a grade II/VI systolic murmur that radiated to the left sternal border, and hepatosplenomegaly. Laboratory data: WBC= 21 K, Hct= 26 %, platelet count (plt)= 521 K, LDH=2557 U/L, normal liver function tests. Chest roentgenogram showed blunting of the of the right costophrenic angle. The remainder of the lung fields appeared well aerated. The cardiac silhouette was unremarkable. Transthoracic echocardiography revealed peak RVSP= 55-63 mmHg, mild MR and mild TR. The LV and RV functions were normal. Pulmonary function tests (PFTs) showed an FEV1=3.29 liters (157% of predicted), a TLC=7.94 (133%of predicted) and DLCO=16.6(74% of predicted). A perfusion lung scan in the presence of a normal chest roentgenogram, and a helical chest CT were negative for pulmonary embolism.DISCUSSION: The etiology of the pulmonary hypertension was unclear in this patient who denied using any anorectic drugs and was never treated with any chemotherapeutic agents with direct effect on pulmonary vasculature or parenchyma. Thromboemblic disorders were extremely unlikely given the results of the lung scan and the helical chest CT. The TTE failed to demonstrate any evidence of congenital heart disease. Other etiologies for secondary pulmonary hypertension, such as connective tissue disorders, HIV infection, carcinoid syndrome, or chronic liver disease were unlikely (serologies were negative- ANA, RH factor, anti-cardiolipin Ab).The exact mechanism for PH in patients with CMD is still unknown. Infiltration of the lung parenchyma by hematopoietic cells, thromboembolic disorders and Left ventricular failure have all been incriminated (2). Plts and plts derived growth factors have been advocated to play a central role (12). Lowering plt counts may improve symptoms or delays the onset of PH. Plt count was persistently elevated in this patient. Anagrelide, a medication usually used to control plt count, is occasionally associated with many cardiovascular and pulmonary side effects including PH. Its use may be attempted mainly in patients with thrombocytosis, considering the potential benefit in this serious condition. Anticoagulation and antiplatelet therapy should be tried in the absence of bleeding diathesis and could be beneficial.
PH associated with CMD is a serious condition, associated with considerable morbidity and mortality and without proven effective therapy. It should be suspected in patients with MDS presenting with dyspnea. An attempt to lower platelets count could be helpful.
J.G. Zein, None.