causes of anemias

IRON-DEFICIENCY

Smear shows anisocytosis (increased RDW) & poikilocytosis. If severe: cigar-shaped RBC & elliptocytes. Low reticulocytes.

Merck Manual Professional.

Iron-deficiency

• Usually results from blood loss (e.g. heavy menstruation), but can also be d/t malabsorption
• Most frequent causes:
• Premenopausal women: menstrual blood loss
• Postmenopasual women + men: chronic occult bleeding, often from GI tract
• In developing countries (...or the tropics), you may see GI bleeding d/t hookworm infection
• RBCs often microcytic and hypochromic, with low iron stores (low serum ferritin & serum iron, high TIBC)
• Rule out occult blood loss!
• Supplement with iron; treat cause of blood loss

IRON-TRANSPORT DEFICIENCY

Iron-transport deficiency

• Rare!!
• Iron-refractory deficiency anemia: IRIDA: germline mutations in TMPRSS6 gene -- regulates production of hepcidin --> inappropriately elevated
• Presents with microcytic anemia w/ low transferrin saturation refractory to oral iron
• Treat with IV iron or oral iron + vitamin C
• What does vitamin C do?

• Related: myelodysplastic syndrome -- ineffective and dysplastic hemtopoiesis

IRON-UTILIZATION ANEMIAS

Ring sideroblasts (erythroid precursors with iron-engorged mitochondria around nucleus) in bone marrow. Merck.

Iron-utilization

• Inadequate bone marrow use of Fe for heme synthesis
• Includes some sideroblastic anemias, lead poisoning
• Sideroblastic anemias:
• Increased serum iron, ferritin, and transferrin saturation with ringed sideroblasts (erythroblasts + iron-engorged mitochondria around the nucleus)
• Acquired/macrocytic (myelodysplastic syndrome, drugs, or toxins) or congential/microcytic (genetic)
• Polychromatophilia and stippled RBCs (siderocytes) with iron-laden granules (Pappenheimer bodies)
• Lead poisoning:
• Inhibits ferro chelatase and ALA dehydratase in heme pathway --> no heme synthesis despite adequate iron
• Causes minimal symptoms at first --> acute encphalopathy + organ damage. In children --> cognitive defects.
• Risks: homes painted before 1978, ceramics, occupational
• Diagnosis: whole blood lead level (any level is BAD)
• Treatment: Reduce lead exposure; chelation therapy
• Succimer or dimercaprol (+/- CaNa2 EDTA)

ANEMIA OF

CHRONIC DISEASE

https://www.researchgate.net/figure/Anemia-in-CKD-Accumulation-of-uremic-toxins-induces-a-decrease-of-EPO-production-in-the_fig2_344152672

https://www.researchgate.net/figure/Progression-of-rheumatoid-arthritis-RA-and-osteoarthritis-OA-In-contrast-to-the_fig2_349892267

Anemia of chronic disease

• AKA anemia of chronic inflammation
• Normocytic initially, then microcytic if severe, + low retics.
• Low-normal serum iron & transferrin; normal-high ferritin
• Causes: chronic infection, autoimmune dz (esp. rheumatoid arthritis),
• Pathophysiology
• Shortened RBC survival (↑ Macrophage activity)
• Decrease EPO production & marrow responsiveness
• Increased hepcidin --> increase iron sequestration
• Treatment: treat underlying disorder, give EPO

THALASSEMIA

http://www.pathophys.org/thalassemia/

Thalassemia

• Thalassemia is a microcytic, hemolytic

anemia with different subtypes of varying severity

• Common in SE Asians, Africans & Mediterraneans
• Decreased production of >/= 1 globin polypeptide
• Alpha, Beta, Gamma, Delta
• Alpha-thalassema: +, 0
• Beta-thalassemia: Minor, intermedia, major
• Diagnosis:
• Hemolytic or microcytic anemia on peripheral smear, Hgb electrophoresis, DNA testing
• Thalassemia trait may have ↑ RBCs
• Elevated serum bilirubin, iron, & ferritin
• Beta-thalassemia major: severe-- Hgb < 6 g/dL
• Blood smear: nucleated erythroblasts,

target cells, small pale RBCs, punctate & diffuse basophilia

https://thalassaemia.org.cy/education/learn-about-thalassaemia/haemoglobin-disorders/beta-thalassaemia/

https://askhematologist.com/thalassemias/

NONMEGALOBLASTIC MACROCYTIC ANEMIAS

NON-MEGALO- BLASTIC

• Suspected when patients have macrocytic anemias without folate or B12 deficiency
• Mechanisms not completely understood
• Causes
• Chronic alcohol intake (independent of vitamin deficiency)
• Drugs (eg, zidovudine, azathioprine, methotrexate, hydroxyurea, imatinib)
• Hemolysis with reticulocytosis
• Liver disease
• Myelodysplastic syndromes (MDS)
• Aplastic anemia recovery
• Hypothyroidism
• Hereditary spherocytosis (maybe)
• Peripheral blood smear may or may NOT have macro-ovalocytes, increased RBC distribution width
• Can do bone marrow & cytogenic analysis to narrow down cause

MEGALOBLASTIC MACROCYTIC ANEMIA

Oval macrocytes & hypersegmented neutrophils in vit B12 deficiency (via Merck)

MEGALO-BLASTIC

• Ineffective hematopoises
• Often linked to B12 or Folate deficiencies
• Homocysteine is increased in B12 deficiency & folate deficiency
• Methylmalonic acid increased in B12 deficiency only
• Peripheral blood smear: anisocytosis, poikilocytosis, macro-ovalocytes, Howell-Jolly bodies (residual fragments of nucleus), hypersegmented neutrophils, reticulocytopenia
• B12 stores last 2-6 years
• Risk factor: vegan diet, gastrectomy, ileal resection
• Levels may be in the "normal" range, but pt still has anemia!
• Folate stores last 4 weeks
• Risk factor: increased need (sporiasis, hemolysis, pregnancy) or malabsorption
• On an exam, if not sure if B12 or folate--folate is more likely! d/t less stores in body
• SXS: diarrhea, anorexia, glossitis
• B12: peripheral neuropathy, gait instability

Homocysteine & methylmalonyl-coA pathway