Cardiac tamponade in myelofibrosis: A Mayo clinic series of nine consecutive cases
Authors: Sravanthi Lavu, Ayalew Tefferi
Journal: American Journal of Hematology (2017)

Myelofibrosis (MF) is a BCR-ABL1 negative myeloproliferative neoplasm (MPN) and arises de novo (primary myelofibrosis; PMF) or as sequelae to polycythemia vera (PV) or essential thrombocythemia (ET).1, 2 One of the complications of MF is extramedullary hematopoiesis (EMH) in sites other than the bone marrow.2, 3 The most common sites of EMH are the liver and spleen; other sites include mediastinum, pericardium, pleura, peritoneum, gastrointestinal tract, central nervous system, skin, and lymph nodes. Pericardial EMH might result in pericardial effusion and cardiac tamponade and such occurrences have rarely been reported, mostly as single case reports.1-4 The current case series represents the largest of its kind and describes the characteristics of MF-associated cardiac tamponade, its treatment, and outcome. The current study was performed as part of institutional review board approved projects. The Mayo Clinic Advanced Cohort Explorer query tool was used to identify the patients; between 1975 and now, 3821 cases of MF were reported to be seen at our institution and 31 possible cases of pericardial effusion or tamponade were considered. All 31 cases were reviewed to confirm the diagnosis of MF and identify the cases with signs of cardiac tamponade at presentation. Diagnosis of myelofibrosis was made based on conventional criteria available at the time of diagnosis. Cardiac tamponade was diagnosed by echocardiogram in eight patients while one patient was diagnosed at the time of autopsy. Statistical analyses considered clinical and laboratory parameters obtained both at the time of initial diagnosis of MF and the time of diagnosis of cardiac tamponade. Median age, at the time of cardiac tamponade, of the nine study patients was 69 years (range: 47–80) and the gender distribution was three females and six males. At the time of MF diagnosis, median values for hemoglobin, platelet count and leukocyte count were 9 g/dL (range: 5.2–12.5), 151 × 109/L (range: 1.3–526), and 11.9 (range: 1.5–1144), respectively; the percentage of circulating blasts ranged from 1 to 5%. Constitutional symptoms were present in three patients and one patient was red cell transfusion dependent. Abnormal karyotype was reported in three patients and JAK2 driver mutation in 1 patient. The median time interval from diagnosis of MF to the manifestation of cardiac tamponade was 1 year (range: 0.2–17.4). At the time of diagnosis of cardiac tamponade, median values were 94,000 × 109/L (range: 28,000–714,000) for platelet count, 9.7 × 109/L (range: 0.2–82.4) for leukocyte count, 2% (range: 1–12%) for circulating blasts and 9 g/dL (range: 5.8–10.7) for hemoglobin; seven of the nine patients were red cell transfusion dependent and four reported constitutional symptoms (Table 1). Karyotype information was available in three patients; normal in two patients and abnormal in one patient. Driver mutations were known in three patients; two had JAK2 mutations and one had type 1 CALR mutation. The risk distribution at the time of cardiac tamponade, according to the dynamic international prognostic scoring system (DIPSS),1 was high in four patients, intermediate-2 in four patients and intermediate-1 in one patient. Treatment history at time of cardiac tamponade included two patients who were not on any specific therapy, two patients who were status post allogeneic stem cell transplantation, one patient had participated in an imetelstat clinical trial, two patients were treated with hydroxyurea only, one patient was treated with subcutaneous heparin to prevent thrombotic complications and one patient was treated with thalidomide, prednisolone, and erythropoietin; the latter patient had progressed to acute myeloid leukemia (AML) and was receiving induction chemotherapy when he developed cardiac tamponade. At the time of diagnosis of cardiac tamponade, the appearance of the diagnostic pericardial fluid was bloody in four patients, serous in three patients and serosanguinous in one patient. The amount of fluid drained ranged from 200 to 1900 ml. One patient had Staphylococcus aureus cultured from the pericardial fluid while the rest had sterile fluid. The typical pericardial fluid content included nucleated red blood cells and atypical cells, along with other myeloid cells. Comparison of pericardial fluid and peripheral blood at the time of cardiac tamponade, in informative cases, revealed higher lactate dehydrogenase (LDH) in the pericardial fluid in two cases but similar levels in one other case; glucose levels were mostly similar in the two fluid compartments although it was markedly decreased in one case. Monocyte and macrophage percentages were usually higher in the pericardial fluid. Eight of the nine study patients received treatment for their cardiac tamponade, while a diagnosis of tamponade was made following an autopsy in one patient. Pericardiocentesis alone was the primary intervention in six patients. One patient received, in addition to pericardiocentesis, involved field radiotherapy and chemotherapy with hydroxyurea. The eighth patient was receiving induction chemotherapy for AML at the time of cardiac tamponade diagnosis and appeared to respond transiently to the particular treatment. Durable complete resolution was seen in seven patients and recurrent pericardial effusion was documented in only one patient; recurrence occurred during consolidation therapy for AML in the latter patient (Table 1). At the time of this writing, post-tamponade follow-up was median 2.1 months (range: 0.6–76.4 months) and leukemic transformation was documented in only one patient, 1.3 years after diagnosis of cardiac tamponade. Nine case reports of MF-associated cardiac tamponade in the literature were reviewed.4 Treatment was reported for seven patients and pericardial fenestration in two patients, pericardial fenestration and pericardiocentesis in one patient, pericardiocentesis and radiotherapy in two patients and combined pericardial fenestration, pericardiocentesis and radiotherapy in one patient. Complete resolution was seen in patients who had pericardial fenestration. One patient who had pericardial fenestration and pericardiocentesis was reported to have died. Two patients who underwent pericardial fenestration, pericardiocentesis and radiotherapy had complete resolution while one patient had a partial resolution. The current series confirms the rarity of cardiac tamponade as a complication of MF, with less than a dozen cases diagnosed at the Mayo Clinic over the last 4 decades and with close to 4000 MF cases seen during the same time period. We show that the particular complication does not spare early stage or molecularly good-risk patients and can occur in patients who have not required treatment for their MF. The limited data from the current study also underscores the nonspecific nature of pericardial fluid analysis in terms of specific diagnosis. The most important take-home message is that cardiac tamponade in MF is often self-limited and easily and durably managed by pericardiocentesis only, without the need for additional chemotherapy or radiotherapy. The authors have no conflict of interest to declare.