MDS Flashcards
A 72-year-old man is brought to the emergency department from his assisted living facility after an unwitnessed fall two hours ago. He reports feeling dizzy while getting out of bed and falling onto his left side. He did not hit his head or lose consciousness. He continues to feel lightheaded after receiving one liter of intravenous fluids by EMS. He has had fatigue and weakness for the past eight months. He does not drink alcohol or take any medications. Temperature is 36.1°C (97°F), pulse is 91/min, respiratory rate is 16/min, blood pressure is 103/74 mmHg, and oxygen saturation is 97% on room air. On physical examination, he appears thin and pale. He is alert and oriented to time, person, place, and situation. His skin is dry, with an area of ecchymosis overlying his left elbow. Strength is 5/5 in all extremities. Cardiopulmonary and abdominal examinations are unremarkable. He has no blood in the stool. Results of initial complete blood count are shown below. What is the best next step in management?
This elderly patient presents after a fall due to dizziness in the context of chronic fatigue and weakness. Bloodwork reveals pancytopenia (i.e. macrocytic anemia, leukopenia, and thrombocytopenia) consistent with myelodysplastic syndrome (MDS). In the acute setting, packed red blood transfusion should be considered for significant anemia (hemoglobin levels < 7 to 8 g/dL) as well as for persistent symptoms following fluid resuscitation and for patients with underlying cardiovascular disease.
The most common medical condition that causes non-megaloblastic macrocytic anemia is MDS. If laboratory findings show low white blood cells and platelets, then a bone marrow aspirate should be performed for definitive diagnosis. If there is hypocellularity with myelodysplastic morphology, MDS can be diagnosed. MDS refers to an acquired clonal disorder of the bone marrow that is a common cause of unexplained anemia in adults older than 65 years. Patients with MDS typically present with symptomatic anemia. Some patients may have symptoms of thrombocytopenia, such as bruising or bleeding, or findings from neutropenia, such as recurrent infections. Without treatment, most patients with MDS will eventually require red blood cell (RBC) transfusions. Whenever possible, use of erythropoiesis-stimulating agents (ESAs) should be utilized to prevent repeated transfusions.
What is the pathophysiology of myelodysplastic syndrome (MDS)?
MDS is a clonal disorder of hematopoietic stem cells in the bone marrow, leading to ineffective hematopoiesis. Bone marrow produces dysplastic and dysfunctional red cells, white cells, and platelets, resulting in pancytopenia. MDS can progress to acute myeloid leukemia (AML) in some cases.
What are the common clinical manifestations of MDS?
1) Anemia (most common): Fatigue, weakness, pallor, lightheadedness.
2) Thrombocytopenia: Easy bruising, petechiae, mucosal bleeding.
3) Leukopenia: Recurrent infections due to neutropenia.
4) Unexplained pancytopenia in an older adult (>65 years old) should raise suspicion for MDS.
Why is packed red blood cell (RBC) transfusion prioritized over diagnostic tests in symptomatic MDS?
Transfusion is needed first because the patient has symptomatic anemia (Hb <7-8 g/dL), which requires immediate correction to prevent complications like dizziness, falls, and cardiac strain. Diagnostic steps (peripheral smear, bone marrow biopsy) can be pursued later, but initial stabilization takes precedence.
What are the key laboratory findings in MDS?
1) Macrocytic anemia (MCV >100 fL), often without folate or B12 deficiency.
2) Pancytopenia (low WBCs, RBCs, platelets) due to ineffective hematopoiesis.
3) Dysplastic bone marrow morphology on bone marrow biopsy (megaloblastoid RBC precursors, nuclear abnormalities).
4) Cytogenetic abnormalities (e.g., del(5q), monosomy 7, trisomy 8) in some cases.
How is MDS distinguished from megaloblastic anemia?
MDS shows macrocytic anemia with normal folate and B12 levels. Bone marrow biopsy in MDS reveals dysplastic cells with abnormal nuclei, whereas megaloblastic anemia shows hypersegmented neutrophils due to folate/B12 deficiency.
How does MDS differ from aplastic anemia?
Both conditions cause pancytopenia, but MDS has dysplastic cells in the bone marrow, while aplastic anemia shows severely hypocellular marrow without dysplasia.
What are the treatment options for MDS?
1) Supportive care: RBC transfusions for symptomatic anemia, platelet transfusions if thrombocytopenic bleeding.
2) Erythropoiesis-stimulating agents (ESAs) (e.g., erythropoietin) to reduce transfusion dependence.
3) Lenalidomide for del(5q) MDS subtype.
4) Hypomethylating agents (azacitidine, decitabine) for higher-risk MDS.
5) Allogeneic stem cell transplant (curative but reserved for younger, high-risk patients).
When should erythropoiesis-stimulating agents (ESAs) be used in MDS?
ESAs (e.g., epoetin alfa, darbepoetin) are used when patients have low erythropoietin levels (<500 mU/mL) and require frequent transfusions. They reduce transfusion dependence but are ineffective in high-risk MDS cases.
What is the most common complication of MDS?
Progression to acute myeloid leukemia (AML). Up to 30% of MDS cases transform into AML, particularly in high-risk cytogenetic subtypes.
Which chromosomal abnormality in MDS is associated with a good prognosis?
Deletion of chromosome 5q [del(5q)]. This subtype responds well to lenalidomide therapy and has a lower risk of AML progression.
Which patients with MDS should receive allogeneic stem cell transplantation?
Stem cell transplant is curative but reserved for younger patients (<60 years) with high-risk disease who have a suitable donor. Older patients typically receive supportive care or hypomethylating agents instead.
