Diagnostic Approach and Overview of Pancytopenias

Diagnostic Approach and Overview of Pancytopenias

Diagnostic Approach and Overview of Pancytopenias Andrew J Seier, MD PGY-1 Types Bone marrow infiltration/destruction Infections: tuberculosis, fungi (e.g. disseminated histoplasmosis, visceral leishmaniasis) Bone marrow aplasia B12/folate deficiency, medications (e.g. methotrexate, cyclophosphamide,

colchicine, azathioprine, ganciclovir, etc.), immune destruction, aplastic anemia, infection (HIV, viral hepatitis, parvovirus B19) Alcohol consumption, benzene exposure Blood cell sequestration/destruction Hypersplenism (e.g. from cirrhosis, lymphoma, autoimmune disease), DIC, TTP, myelodysplastic syndrome The Importance of Physical Exam Lymphadenopathy

Hepatomegaly, splenomegaly, stigmata of liver disease Liver disease as a cause of hypersplenism/sequestration Infectious causes Rashes Associated with hematologic malignancies, autoimmune and infectious diseases related to drug reactions, rheumatologic disorders, infections, and malignancies

Oral lesions Thrush suggests immune compromise Oral ulcers may be seen in SLE, Crohns Initial Evaluation CBC with diff Peripheral smear Reticulocyte count (absolute < 20,000 suggests hypoproliferation)

PT/INR, aPTT CMP, LDH, uric acid Type & screen Bone Marrow Biopsy Helpful Acute Not leukemias Aplastic anemia

Multiple myeloma helpful Medication-induced Recent use of hematopoietic growth factors Peripheral destruction, sequestration Pancytopenic Emergencies ANC < 1000, newly-diagnosed or with evidence of infection

Symptomatic anemia (e.g. myocardial ischemia, hypotension) Thrombocytopenia < 10,000 (or < 50,000 with active bleeding) DIC, TTP, HUS, or other MAHA with schistocytes and elevated LDH Acute leukemia (e.g. with DIC or tumor lysis syndrome) Associated metabolic abnormalities

Delirium, dehydration, abdominal pain: hypercalcemia (multiple myeloma, adult T-cell leukemia/lymphoma) Acute renal failure (e.g. with elevated uric acid in tumor lysis syndrome If none of the above are present, CBC is stable and near normal, and the patient is asymptomatic, referral is non-urgent Autoimmune Causes RA, Feltys syndrome SLE

Sarcoidosis Associated conditions Pernicious anemia Thyroid disease (severe hypothyroid, thyrotoxicosis) Hypoproliferative Causes Aplastic anemia B12, folate, or copper deficiency

Suppression from alcohol or viral infections Myelodysplastic syndrome Certain malignancies Hairy cell leukemia T-cell large granular lymphocyte leukemia Neoplastic Causes Acute leukemias

Myelodysplastic syndrome Often see circulating blasts Often see dysplastic leukocytes Myelofibrosis Tear drop cells (dacrocytes), nucleated RBCs, early WBCs Overview and Treatment of Myelodysplastic Syndromes Description A group of hematopoietic stem cell disorders

characterized by Ineffective, dysplastic hematopoiesis Risk of transformation to acute leukemia Quantitative and qualitative defects in production of red blood cells, platelets, and granulocytes Develops like other cancers, from stepwise acquisition of oncogenic mutations Epidemiology 10,000-30,0000 cases per year in the United States

Most common in older adults, median age at diagnosis 65 years or older Associated with certain exposures: benzene, radiation, tobacco, chemotherapy drugs Certain connective tissue disorders associated Behets, Sjgrens, IBD, polymyalgia rheumatica, relapsing polychondritis No causal link established

Presentation Hepatomegaly, splenomegaly, lymphadenopathy uncommon Infection Usually bacterial, often skin infections Non-infectious cutaneous manifestations Sweet syndrome (acute febrile neutrophilic dermatosis: uncommon, but much greater frequency than in general population)

Myeloid sarcoma (extra-medullary AML) Pancytopenia with inappropriately low reticulocyte response Peripheral Smear Findings RBCs Normocytic or macrocytic Ovalomacrocytes most common, can also see dacrocytes, stomatocytes, or acanthocytes

Basophilic stippling, Howell-Jolly bodies, and megaloblastoid nucleated red cells Peripheral Smear Findings (cont.) WBCs: most commonly seen finding are the pseudoPelger-Huet abnormality and reduced granulation Pre-treatment Evaluation: Scoring Treatment Modalities High-intensity Allogeneic hematopoietic cell transplant

Combination chemotherapy, such as daunorubicin and cytarabine Low-intensity (improves symptoms, not curative) Hematopoietic growth factors (epoetin alfa, eltrombopag, GM-CSF) Azacitidine/decitabine (hypomethylating agents) Immunosuppresive therapy Lenalidomide Supportive care

Antibiotics PRN RBC and platelet transfusions PRN Prognosis Highly dependent on underlying cytogenetics Intermediate-, high-, or very high-risk patients can receive high-intensity therapy, which can be curative With older age, other medical comorbidities, often supportive care is the best option

High- to very-high risk groups have survival measured in months with supportive care End

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