Macrocytic anemia: Pathology review
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Macrocytic anemia: Pathology review
Pathology
Anemias
Iron deficiency anemia
Beta-thalassemia
Alpha-thalassemia
Sideroblastic anemia
Anemia of chronic disease
Lead poisoning
Hemolytic disease of the newborn
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Autoimmune hemolytic anemia
Pyruvate kinase deficiency
Paroxysmal nocturnal hemoglobinuria
Sickle cell disease (NORD)
Hereditary spherocytosis
Anemia of chronic disease
Aplastic anemia
Fanconi anemia
Megaloblastic anemia
Folate (Vitamin B9) deficiency
Vitamin B12 deficiency
Fanconi anemia
Diamond-Blackfan anemia
Heme synthesis disorders
Acute intermittent porphyria
Porphyria cutanea tarda
Lead poisoning
Coagulation disorders
Hemophilia
Vitamin K deficiency
Platelet disorders
Bernard-Soulier syndrome
Glanzmann's thrombasthenia
Hemolytic-uremic syndrome
Immune thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Mixed platelet and coagulation disorders
Von Willebrand disease
Disseminated intravascular coagulation
Heparin-induced thrombocytopenia
Thrombosis syndromes (hypercoagulability)
Antithrombin III deficiency
Factor V Leiden
Protein C deficiency
Protein S deficiency
Antiphospholipid syndrome
Lymphomas
Hodgkin lymphoma
Non-Hodgkin lymphoma
Leukemias
Chronic leukemia
Acute leukemia
Leukemoid reaction
Leukemoid reaction
Dysplastic and proliferative disorders
Myelodysplastic syndromes
Polycythemia vera (NORD)
Myelofibrosis (NORD)
Essential thrombocythemia (NORD)
Langerhans cell histiocytosis
Mastocytosis (NORD)
Plasma cell dyscrasias
Multiple myeloma
Monoclonal gammopathy of undetermined significance
Waldenstrom macroglobulinemia
Hematological system pathology review
Microcytic anemia: Pathology review
Non-hemolytic normocytic anemia: Pathology review
Intrinsic hemolytic normocytic anemia: Pathology review
Extrinsic hemolytic normocytic anemia: Pathology review
Macrocytic anemia: Pathology review
Heme synthesis disorders: Pathology review
Coagulation disorders: Pathology review
Platelet disorders: Pathology review
Mixed platelet and coagulation disorders: Pathology review
Thrombosis syndromes (hypercoagulability): Pathology review
Lymphomas: Pathology review
Leukemias: Pathology review
Plasma cell disorders: Pathology review
Myeloproliferative disorders: Pathology review
Assessments
Macrocytic anemia: Pathology review
USMLE® Step 1 questions
0 / 6 complete
Questions
USMLE® Step 1 style questions USMLE
of complete
| Laboratory value | Result |
| Hemoglobin | 8.1 g/dL |
| Leukocyte | 2,300/mm3 |
| Platelet | 65,000/mm3 |
| Mean Corpuscular Volume | 109 mm3 |
Memory Anchors and Partner Content
Transcript
Content Reviewers
Elizabeth Nixon-Shapiro, MSMI, CMI
Marisa Pedron
Antonia Syrnioti, MD
Contributors
Maria Emfietzoglou, MD
Sam Gillespie, BSc
Zachary Kevorkian, MSMI
In the hematology ward, two people came in with the same symptoms: easy fatigability, exertional dyspnea, and weight loss. One of them is a 65 year old caucasian individual named Bobby, and the other one is a 50 year old Hispanic individual named Sara. Bobby complains of frequent falls, while Sara admits she is a chronic user of alcohol. Their lab tests show decreased hemoglobin levels.
Both Bobby and Sara are suffering from anemia, which is defined as lower than average levels of hemoglobin, typically below 13.5 g/dL in adult men and below 12.0 g/dL in adult women. Now, anemias can be broadly grouped into 3 categories based on mean corpuscular volume, or MCV, which reflects the volume of a Red Blood Cell or RBC. So microcytic anemia is where the MCV is lower than 80 fL, normocytic, with an MCV between 80 and 100 fL, and macrocytic, with an MCV larger than 100 fL. Now, let’s focus on the macrocytic anemias. The two most common causes are vitamin B12 deficiency and folate deficiency. Orotic aciduria, Fanconi anemia, Diamond-Blackfan anemia are also macrocytic. Finally, liver diseases and hypothyroidism can also cause this type of anemia, but their mechanisms are not well understood.
Okay! Macrocytic anemias can be classified based on the presence of megaloblasts. These are large, immature red blood cells produced when the cytoplasm develops normally, but the DNA synthesis is impaired and cell division is delayed. So when there’s defective DNA synthesis or defective DNA repair like in folate deficiency, vitamin B12 deficiency, orotic aciduria, and Fanconi anemia there’s megaloblastic macrocytic anemia. Megaloblastic anemia can also affect white blood cell production, so the bone marrow starts releasing large, immature neutrophils, with hypersegmented nuclei, meaning their nucleus has more than 5 lobes. These are called hypersegmented neutrophils and are a key finding on the peripheral blood smear of individuals suffering from megaloblastic anemia.
Sources
- "Robbins Basic Pathology" Elsevier (2017)
- "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
- "Pernicious Anemia" New England Journal of Medicine (1997)
- "Megaloblastic Anemias" Medical Clinics of North America (2017)
- "Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families" Am J Hum Genet (1997)
- "Why does the bone marrow fail in Fanconi anemia?" Blood (2014)
- "Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference" British Journal of Haematology (2008)
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