Refractory Thrombocytopenia Associated with Dengue Hemorrhagic Fever Responds to Romiplostim
Authors: Rodriguez-Mejorada Margarita S. , Rosel-Gomez Gonzalo C , Rosado-Castro Rilke A , Ruiz-Argüelles Guillermo J. 
Published: October 2019

Abstract 4668

Second-generation thrombopoiesis-stimulating molecules are now available, which have unique pharmacological properties and no sequence homology to endogenous TPO. Dengue is the most prevalent arthropod-borne virus affecting humans today. The virus group consists of 4 serotypes that manifest with similar symptoms and cause a spectrum of disease, ranging from a mild febrile illness to a life-threatening dengue hemorrhagic fever (DHF). Breeding sites for the mosquitoes that transmit dengue virus have proliferated, partly because of population growth and uncontrolled urbanization in tropical and subtropical countries. Dengue viruses have evolved rapidly as they have spread worldwide, and genotypes associated with increased virulence have spread across Asia and the Americas. DHF is endemic in México. We report the case of a female patient diagnosed 36 months before admission as multiple myeloma and autografted. She was admitted with a febrile syndrome diagnosed as Dengue hemorrhagic fever with severe and persistent thrombocytopenia, refractory to steroids and platelet transfusions.

56 year old lady, previosly diagnosed as multiple myeloma, treated with thalidomide, dexametasone and bortezomib until partial response. In march 2007 she was autografted using high dose melphalan (6). After autotransplant she continued using thalidomide 100 mg per day.

In february 2010, 24 hours before admission to our Institution she developed nausea, vomiting, headache, fever and myalgia, no evidence of hemorrhage at physical exam. Laboratory reported positive Ag and IgM anti-Dengue virus (Platelia Dengue NS1 AG BioRad), anemia (8.3 g/dl), leukopenia (0.7 × 109/L), thrombocytopenia (17×109/L). Bone marrow aspirate and biopsy was hipocellular with mild diseritropoyesis, megaloblastic erythroid precursor cells and no evidence of myeloma.

The patient was treated with intravenous hidrocortisone (300 mg/day), subcutaneous filgrastim (300 mcg/day) and antibiotics. Neutropenia resolved 4 days after starting G-CSF. Thrombocytopenia had a transient improvement and sudden fall even daily transfusions. Was treated with oprelvekin with mínimum response and serious side effects.

She became refractory to allogeneic platelets ten days after first transfusion, with platelet counts between 3–10 × 109/L and severe cutaneous bleeding. Romiplostim was started (4 ug/kg/week) 55 days after severe thrombocytopenia, platelet count increased 100% in the next 48 hours with continuous elevation and no side effects. At third week of Romiplostim there was a 7 fold increase in the initial platelet count. The platelet count remains above 100 × 109/L after six dose administration with no decline in biweekly measurements. The figure shows the evolution of the platelet count before and after starting romiplostim.

Steroids have been shown to be useful when DHF complicates with septic shock and even though thrombocytopenia resolves spontaneously frequently, it has been shown to be prolonged in certain circumstances. An immune mechanism of thrombocytopenia due to increased platelet destruction appears to be operative in patients with DHF; however, in the case that we are here reporting, the previous stem cell transplant and the use of thalidomide led into a hypoplastic marrow which most likely was unable to compensate the peripheral platelet destruction. The usefulness of romiplostim in this case may stem from the fact that the patients had a combined origin of the refractory thrombocytopenia, on one hand the platelet destruction induced by the dengue virus and on the other a hypoplastic marrow derived not only from the viral infection, but also from the previous stem cell allograft and the chronic use of thalidomide.

Disclosures:

No relevant conflicts of interest to declare.