Hematology 13: Anemia Part 1 (Microcytic-Hypochromic)

Morphologic Classification Chart

Microcytic-Hypochromic Anemia

circulating RBCs are smaller than the usual size of RBCs (microcytic) and have decreased red color (hypochromic), most common anemia, result from impaired hemoglobin synthesis

Hgb < 12 g/dL (F) or < 13 g/dL (M) with mean cell volume (MCV) < 80 fL

common causes of Microcytic-Hypochromic Anemia

Blood loss

Iron-deficiency anemia (IDA)

Thalassemia

Anemia of chronic disease (ACD)

Sideroblastic anemia

Lead poisoning

Etiology: Blood loss

Acute

: temporary anemia caused by a rapid hemorrhage due to trauma (e.g., car accident, surgery, or childbirth).

The body quickly replaces plasma but usually needs several weeks to replace RBCs

Etiology: Blood loss

chronic

Chronic: anemia develops due to lack of sufficient functional iron and hemoglobin-deficient RBCs (e.g., GI bleeding, heavy menstruation)

pathophysiology for iron deficiency anemia

Iron loss exceeds iron intake

clinical presentation of blood loss leading to ida

Fatigue, pallor, shortness of breath

Laboratory Evaluation of Blood Loss

Peripheral blood smear

MCV 55-74 fL – microcytic

MCHC 22-31 g/dL – hypochromic

Reticulocyte count

High

Iron deficiency anemia (IDA)

is a common form of anemia that occurs when the body has insufficient iron to produce hemoglobin.

Iron deficiency is the most common nutritional deficiency in the world

Affects 8-10% of children in the US

Prevalent in countries where:

Grain major part of the diet, and meat is scarce

Parasitic infections are endemic (i.e., hookworm)

Defective Hgb production can be due to disturbances in:

Heme synthesis

Iron deficiency

Defective iron metabolism

Defective porphyrin synthesis

Globin synthesis

Result of defective Hgb production

Microcytic hypochromic anemia

does iron need to be bound to protein to do function?

yes

enterocytes

digestive cells that absorb iron

hepatocytes

liver cells store iron

macrophages

remove senescent rbc from spleen, bone marrow and liver

iron is primarily found in (5):

circulating rbc, enterocytes, hepatocytes, splenic macrophages and rbc precursors

where is most of iron found

hb

iron distribution

Hgb is the major fraction of body iron

Iron in Hgb remains in RBC until cell is removed from circulation.

Splenic macrophages degrade and release Hgb

Iron, bound to transferrin, is recycled for heme synthesis in BM

absorption - Iron in the enterocyte can be:

stored as ferritin, then transported via ferroportin

when does intestinal iron absorption increase?

when erythropoietin increases

when absorbed in the blood, what is iron bound to?

transferrin

iron cycle diagram

Iron homeostasis depends on:

Interaction of iron with proteins involved in iron absorption, transport, retention, export

Liver

Major storage site for iron storage

“Command central” of iron homeostasis

hepcidin

Master iron-regulating hormone

Controls the release of iron from enterocytes and macrophages into the circulation

Iron-Deficiency Anemia (IDA)- pathophysiology and clinical presentation

Insufficient iron for hemoglobin synthesis

•Koilonychia

•Dry mouth, glossitis

•Muscle dysfunction

•Inability to regulate body temp

•Pica

peripheral blood smear of IDA: size, color and morphology of cells

•MCV 55-74 fL – microcytic

•MCHC 22-31 g/dL – hypochromic

•RDW will be increased – anisocytosis

•Poikilocytes - •Target cells •Elliptocytes •Teardrop cells

reticulocyte count of IDA

low - not enough iron to make hb → less cells

iron studies of ida

Low serum iron <30 ug/dL

Low serum ferritin <12 ug/dL

High TIBC (total iron binding capacity - not enough iron = more room to bind)

iron deficiency anemia - look for color and size first - microcytic, hypochromic

iron deficiency anemia

list causes of IDA

Blood loss

Lack of dietary iron (strict vegetarianism or poor diet)

Malabsorption

Defective iron utilization. Characterized by ineffective RBC formation and the presence of ferritin in developing RBCs. (Sideroblastic anemia)

Defective iron reutilization. This is the second most common form of anemia and is related to a variety of chronic diseases, infections, and cancers

Obesity

Thalassemia

genetic blood disorder caused by mutations in one or more globin genes (alpha or beta) responsible for hemoglobin production.

These mutations result in decreased or absent synthesis of globin chain(s)

different kinds of thalassemia

•> 400 unique mutations

•α-thalassemia

•β-thalassemia

thalassemia pathophysiology

The imbalance in globin chain production leads to ineffective erythropoiesis and hemolysis. The excess unpaired globin chains precipitate in red blood cell precursors, causing their premature destruction in the bone marrow (ineffective erythropoiesis) or spleen (hemolysis).

thalassemia Clinical Presentation:

Symptoms: Fatigue, weakness, pallor, and jaundice

Severe Cases: Growth retardation, bone deformities, and splenomegaly

Complications: Heart failure, liver disease, and endocrine dysfunction due to iron overload from frequent blood transfusions

Peripheral blood smear of thalassemia: size, color, morphology, and inclusion bodies

•MCV 55-74 fL – microcytic

•MCHC 22-31 g/dL – hypochromic

•RDW will be increased

•Target cells, basophilic stippling - telltale sign, NRBCs

Reticulocyte count of thalassemia

high

Hgb electrophoresis of thalassemia

Abnormal hemoglobin patterns, reduced or absent specific globin chains.

thalassemia

thalassemia

thalassemia, fetal hb is up, hbA decreases, hb origin decreased

normal vs thallasemia hb electrophoresis

why do thalassemic patients have high levels of hbF?

To compensate, the body increases the production of gamma chains,

thalassemia

thalassemia

Anemia of Chronic Disease (acd) etiology

underlying chronic conditions such as infections, autoimmune diseases, chronic kidney disease, and malignancies lead to altered iron metabolism and impaired erythropoiesis.

Pathophysiology: ACD is characterized by

Increased hepcidin levels, which inhibit iron absorption and release from macrophages.

Shortened red blood cell lifespan due to increased phagocytosis.

Impaired response to erythropoietin, reducing red blood cell production.

Inflammatory cytokines, like IL-6, further suppressing erythropoiesis and iron availability.

How do cytokines/inflammation cause ACD?

In response to inflammatory signals, monocytes and T cells become activated and release cytokines

A. IL-6 increase hepcidin levels, which in turn bind and degrade ferroportin, trapping Fe³⁺ within the M𝞅 decrease, erythropoiesis.

B. IL-1 inhibits EPO release from kidneys, decreasing erythropoiesis.

C.TNF and IFN inhibit RBC progenitor proliferation

D.TNF increase erythrophagocytosis by M𝞅

clinical presentation of ACD

Mild to moderate anemia symptoms: fatigue, weakness, and pallor.

Symptoms of the underlying chronic condition (e.g., joint pain in rheumatoid arthritis, fever in chronic infections).

Complete Blood Count (CBC) of acd: cell size

Mild to moderate anemia, normocytic or microcytic

Serum Ferritin of acd lab eval

Normal or increased (reflecting adequate iron stores)

Serum Iron, Transferrin, and TIBC:

Low or decreased, tbic low because stores are filled with iron, so not being used

Bone marrow evaulation of acd

↑ M:E ratio

Poor hemoglobin production in erythroblasts

Sideroblasts < 30% - holding onto iron

Increased hemosiderin in macrophages - macrophages holding onto iron

Sideroblastic Anemias

anemias result from a mutation that affects the first enzymatic step of heme synthesis (formation of ALA).

heme synthesis accumulates in mitochondria, but in this anemia, you don’t get heme so iron deposits in these cells

Sideroblastic Anemias etiology

can be caused by a variety of factors, including genetic mutations (congenital sideroblastic anemia), acquired conditions (such as myelodysplastic syndromes), chronic alcoholism, lead poisoning, and certain medications (e.g., isoniazid, chloramphenicol).

Sideroblastic Anemias Pathophysiology

defective heme synthesis within the erythroid precursors in the bone marrow. This defect leads to

the accumulation of iron in the mitochondria surrounding the nucleus of the developing red blood cells → ring sideroblasts.

Disruption in normal RBC production

Sideroblastic Anemias clinical presentation

•Symptoms of anemia: fatigue, weakness, pallor, and shortness of breath.

•Hepatosplenomegaly (enlarged liver and spleen)

•Iron overload

•Symptoms related to hemosiderosis such as joint pain and diabetes mellitus

Complete Blood Count (CBC): sideroblastic anemia - color and size

•Normochromic and hypochromic

•Anisocytosis w/microcytes, macrocytes, and normocytes

type of abnormal cell and inclusion body of sideroblastic anemia

•Target cells

•Inclusion bodies w/Pappenheimer bodies (iron deposits)

sideroblastic anemia

Bone Marrow Examination of Sideroblastic anemia

Ring sideroblasts > 40% of erythroblasts

sideroblastic bone marrow