Megaloblastic anemia

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Megaloblastic anemia Classification and external resources
Image:Megaloblastic anemia.jpg
Megaloblastic anemia blood smear
ICD-10	D51.1, D52.0, D53.1
ICD-9	281
DiseasesDB	29507
eMedicine	med/1420  ped/2575
MeSH	D000749

Megaloblastic anemia is an anemia (of macrocytic classification) which results from inhibition of DNA synthesis in red blood cell production. It is often due to deficiency of vitamin B₁₂ and/or folic acid. It can be the result of a lack of intrinsic factor (which lack interferes with B₁₂ absorption), causing pernicious anemia, or with other antimetabolites which poison DNA production, such as chemotherapeutic agents.

It is characterized by many large immature and dysfunctional red blood cells (megaloblasts) in the bone marrow,^[1] and also by hypersegmented or multisegmented neutrophils.

Contents 1 Causes 2 Hematological findings 3 Analysis 4 References

[edit] Causes

• Vitamin B12 Deficiency:
  • Deficient intake
  • Deficient intrinsic factor (pernicious anaemia or gastrectomy)
  • Biological competition for B12 by diverticulosis, fistula, intestinal anastomosis, achlorhydria and infection by the marine parasite Diphyllobothrium latum
  • Selective B12 malabsorption (congenital and drug-induced)
  • Chronic pancreatitis
  • Ileal resection and bypass

• Folate Deficiency:
  • Deficient intake.
  • Increased needs: pregnancy, infant, rapid cellular proliferation, and cirrhosis
  • Malabsorption (congenital and drug-induced)
  • Intestinal and jujenal resection

• Combined Dieficiency (Tropical Sprue): Vitamin B12 & Folate.

• Inherited DNA Synthesis Disorders: Deficient thiamine and factors (e.g. enzymes) responsible for folate metabolism.

• Toxins and Drugs:
  • Folic acid antagonists (methotrexate)
  • Purine antagonists (6-mercaptopurine)
  • Pyrimidine antagonists (cytosine arabinoside)

• Erythroleukemia

[edit] Hematological findings

The blood film can point towards vitamin deficiency:

• Decreased red blood cell (RBC) count and hemoglobin levels
• Increased mean corpuscular volume (MCV, >95 fl) and mean corpuscular hemoglobin (MCH)
• The reticulocyte count is normal
• The platelet count may be reduced.
• Neutrophil granulocytes may show multisegmented nuclei ("senile neutrophil"). This is thought to be due to decreased production and a compensatory prolonged lifespan for circulating neutrophils.
• Anisocytosis (increased variation in RBC size) and poikilocytosis (abnormally shaped RBCs).
• Macrocytes (larger than normal RBCs) are present.
• Ovalocytes (oval shaped RBCs) are present.
• Bone marrow (not normally checked in a patient suspected of megaloblastic anemia) shows megaloblastic hyperplasia.
• Howell-Jolly bodies (chromosomal remnant) also present.

Blood chemistries will also show:

• Increased homocysteine and methylmalonic acid in B₁₂ deficiency
• Increased homocysteine in folate defiency

Normal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty. ^[2]

[edit] Analysis

The Schilling test was performed in the past to determine the nature of the vitamin B₁₂ deficiency, but due to the lack of available radioactive B₁₂, it is now largely a historical artifact. Vitamin B₁₂ is a necessary prosthetic group to the enzyme methylmalonyl-coenzyme A mutase. B₁₂ deficiency leads to dysfunction of this enzyme and a buildup of its substrate, methylmalonic acid, the elevated level of which can be detected in the urine and blood. Since the level of methylmalonic acid is not elevated in folic acid deficiency, this test provides a one tool in differentiating the two. However, since the test for elevated methylmalonic acid is not specific enough, the gold standard for the diagnosis of B₁₂ deficiency is a low blood level of B₁₂. Unlike the Shilling test, which often included B₁₂ with intrinsic factor, a low level of blood B₁₂ gives no indication as to the etiology of the low B₁₂, which may result from a number of mechanisms.

[edit] References

v • d • e Pathology: hematology, hematologic disease (primarily D50-D77, 280-289) RBCs/anemia/ hemoglobinopathy (Myeloid) nutritional anemia: Iron deficiency anemia, Plummer-Vinson syndrome, Megaloblastic anemia (Pernicious anemia) hereditary hemolytic anemia: enzyme disorders (G6PD Deficiency, Pyruvate kinase deficiency,Triosephosphate isomerase deficiency), Thalassemia, Sickle-cell disease/trait, Hereditary spherocytosis, Hereditary elliptocytosis, Hereditary stomatocytosis acquired hemolytic anemia: Autoimmune (Warm), HUS, MAHA, PNH, PCH aplastic anemia: Acquired PRCA, Diamond-Blackfan anemia, Fanconi anemia • Sideroblastic anemia Polycythemia - Methemoglobinemia Coagulation/platelets (Myeloid) coagulopathy: DIC (Congenital afibrinogenemia, Purpura fulminans) • Hemophilia (A/VII, B/IX, C/XI, XIII) • Von Willebrand disease • Hypoprothrombinemia Purpura: Henoch-Schönlein, ITP (Evans syndrome), TTP primary hypercoagulable state: Protein C deficiency - Protein S deficiency - Antithrombin III deficiency - Factor V Leiden - Activated protein C resistance - Antiphospholipid syndrome other hemorrhagic conditions: Bernard-Soulier syndrome - Glanzmann's thrombasthenia - Grey platelet syndrome - May Hegglin anomaly - Pelger-Huet anomaly Essential thrombocytosis - Thrombocytopenia Monocytes/Macrophages (Myeloid) WHO-I histiocytosis (Langerhans cell histiocytosis) WHO-II/non-Langerhans-cell histiocytosis (Juvenile xanthogranuloma, Hemophagocytic lymphohistiocytosis) WHO-III/malignant histiocytic disorders (Acute monocytic leukemia, Malignant histiocytosis, Erdheim-Chester disease) -cytosis: Monocytosis -penia: Monocytopenia Granulocytes (Myeloid) -cytosis: granulocytosis (Neutrophilia, Eosinophilia, Basophilia) -penia: Granulocytopenia/agranulocytosis (Neutropenia, Kostmann syndrome) Other/general myeloid Chronic granulomatous disease Lymphoid -cytosis: Lymphocytosis -penia: Lymphopenia Other Splenic disease (Asplenia/hyposplenism, Wandering spleen) - Pancytopenia See also hematological malignancy and immune disorders