Anemia

Decreased hemoglobin and/or circulating RBCs; decreased oxygen-carrying capacity of blood

Anemia

Three mechanisms include inadequate RBC production, RBC maturation defect, and blood loss or increased RBC destruction/hemolysis

Anemia

Consequences are increased morbidity in ESRD, CKD, and heart failure; independent mortality risk in dialysis-dependent CKD and heart failure; cognitive dysfunction in renal failure, cancer, and older adults; older adults have increased falls and dementia risk; pregnancy increases low birth weight, preterm delivery, and perinatal mortality; maternal IDA may increase postpartum depression

Anemia

Risk factors include preschool age, pregnancy, advanced age, poor nutrition/nutrient deficiencies, gastric bypass surgery, and chronic inflammatory disease

Anemia

Adult RBCs are primarily produced in ____ _____ _____ of vertebrae, ribs, sternum, clavicle, pelvic crest, and proximal epiphyses of long bones

Red bone marrow

What is the mature RBC lifespan?

120 days

Old RBCs undergo phagocytic breakdown in the _____ and ____, components are recycled

Spleen and liver

____ binding promotes erythroid precursor proliferation and differentiation

EPO

These three nutrients are required for functional RBC development

Iron, vitamin B12, folic acid

_______ enter peripheral blood and mature within several days

Reticulocytes

These are nonnucleated, non-dividing, and hemoglobin constitutes >90% of protein content

Red blood cells

Approximately 90% produced by kidneys; tissue hypoxia leads to kidney detecting decreased O2 and increased production of this hormone

Erythropoietin

Prevents erythroid precursor apoptosis, promotes proliferation and maturation, and feedback-regulated to maintain a stable RBC mass

Erythropoietin

In CKD, there is decreased __________ production leading to hypoproliferative anemia

Erythropoietin

Essential component of heme and hemoglobin

Iron

Delivers circulating iron to bone marrow

Transferrin

Excess iron is stored in liver, marrow, and spleen macrophages as _______

Ferritin

Iron deficiency leads to inadequate hemoglobin production leading to ____, hypochromic RBCs

Small

These nutrients are both required for DNA synthesis, cell division, and RBC nuclear maturation

Vitamin B12 and folate

Deficiency in vitamin B12 or folate leads to _____, dysfunctional RBCs

Large

Indicated by high homocysteine and normal MMA

Folate deficiency

Indicated by high homocysteine and high MMA

B12 deficiency

The specific marker for B12 deficiency

MMA

Caused by inadequate RBC production; examples are bone marrow damage, iron deficiency, CKD, inflammation, and metabolic disease

Hypoproliferative anemia

Caused by cytoplasmic or nuclear maturation defect; examples are IDA, thalassemia, folate deficiency, B12 deficiency

Maturation disorder anemia

Caused by blood loss or increased RBC destruction; examples are acute blood loss, intravascular hemolysis, autoimmune disease, and membrane/metabolic defects

Hemolytic anemia

Symptoms are tachycardia, palpitations, chest pain, hypotension, lightheadedness, shortness of breath, all due to less time for physiologic compensation

Acute anemia

Symptoms are headache, orthopnea/dyspnea on exertion, vertigo, cold sensitiity, pallor, loss of skin tone, all due to better compensation despite low hemoglobin

Chronic anemia

These two symptoms occur with either acute or chronic anemia

Fatigue and weakness

What is the anemia threshold for nonpregnant women >15 years?

<12 g/dL

What is the anemia threshold for men >15 years?

<13 g/dL

What is the threshold for severe anemia?

<8 g/dL

What is the threshold for moderate anemia?

<10.9 g/dL

Includes RBC count, Hb, HCT, MCV, MCH, MCHC, RDW

CBC

Includes serum iron, TIBC, TSat, and ferritin

Iron studies

Percentage of whole blood occupied by RBCs

HCT

Hb amount per volume of blood; estimates oxygen-carrying capacity

Hb

Average RBC size

MCV

Average Hb amount per RBC; generally changes with MCG

MCH

Hb concentration independent of RBC size

MCHC

Having a low MCHC indicates ___________ which is common in IDA

Hypochromia

Variation in RBC size

RDW

What is the MCV threshold for microcytic anemia?

<80 fL

Examples of this type of anemia are IDA, thalassemia, and sickle cell disease

Microcytic

What is the MCV range for normocytic anemia?

80-100 fL

What is the MCG threshold for macrocytic anemia?

>100 fL

Examples or this type of anemia are AI/CKD, hemolysis, blood loss, and marrow failure

Normocytic

Examples of this type of anemia are B12 deficiency and folate deficiency

Macrocytic

Normal MCV with elevated RDW suggests _________ anemia; attain both iron studies and macrocytic anemia tests

Mixed

This is an indirect marker of marrow RBC production

Reticulocyte count

A _____ reticulocyte count means marrow is responding to RBC loss, indicating acute blood loss or hemolysis

High

A _________ reticulocyte count indicates inadequate RBC production due to AI, CKD, nutrient deficiency, and bone marrow failure

Low

This is expected to increase after effective replacement within 3-7 days

Reticulocyte count

A normal MCV with high RDW indicates _______ anemia

Mixed

A normal MCV with _____ reticulocytes indicates blood loss or hemolysis

High

A normal MCV with ____ reticulocytes means you should also assess WBC/platelets

Low

A normal MCV with low reticulocytes and low WBC/platelets suggests this

Bone marrow failure

Normal MCV with normal RDW and high WBC/platelets could mean anemia of __________

Inflammation

Goals are to relieve signs/symptoms, correct underlying cause, achieve target Hb, normalize related parameters such as MCV, ferritin, or B12, and prevent recurrence

Anemia treatment

Anemia can be caused by inadequate _________ intake

Dietary

Anemia can be caused by impaired _________ of nutrients as seen in gastric bypass or intestinal resection, IBD, celiac disease, and chronic alcohol use

Absorption

Anemia can be caused by increased nutrient ________ as seen in pregnancy, blood loss, malignancy, and ESA initiation for iron

Requirements

Causes include pernicious anemia/lack of intrinsic factor and H. pylori

Vitamin B12 deficiency

What two medications can cause iron deficiency?

PPIs and calcium antacids

What two medications can cause folate deficiency?

Methotrexate and phenytoin

What two medications can cause vitamin B12 deficiency?

Metformin and PPIs

Sources include red meat, poultry, eggs, seafood, fortified cereals/oatmeal/pasta/grains, leafy greens, beans, lentils, peas, broccoli, asparagus, Brussel sprouts, tofu

Iron

Sources include beef liver, fortified grains/cereals, leafy greens, legumes, broccoli, asparagus, Brussel sprouts, and citrus fruit

Folate

Sources include beef liver, red meat, trout, salmon, clams, oysters, tuna, fortified cereal/nutritional yeast, dairy

Vitamin B12

Develops from prolonged negative balance; commonly associated with chronic blood loss, inadequate intake, malabsorption, or increased requirements

Iron-deficiency anemia

Iron-deficiency is a _________ hypochromic anemia

Microcytic

Unique symptoms include glossitis/glossal pain, smooth tongue, reduced salivary flow, pica, and pagaphagia

Iron-deficiency anemia

Iron-deficiency anemia symptom; eating nonfood materials

Pica

Iron-deficiency anemia symptom; compulsive ice eating

Pagophagia

What are the key labs for diagnosing iron-deficiency anemia (3)?

Low MCV, low ferritin, low TSat

Low serum iron alone is insufficient in diagnosing iron-deficiency anemia because it may also occur in _________ ___ _______

Anemia of inflammation

First step in treating iron-deficiency anemia is t identify bleeding, malabsorption, medication contributors, or inadequate intake and increase _____-____ rich foods when appropriate

Heme-iron

Iron-deficiency anemia; recommended elemental iron is _____-_____ mg every other day or Monday/Wednesday/Friday

60-120

This administration of iron improves absorption, reduces hepicidin-related absorption limitation, and may reduce adverse effects

Every-other-day

Oral iron for iron-deficiency anemia should be continued for ___ to ____ months after anemia resolves to replenish stores

3 to 6

What are the two preferred formulations of oral iron?

Ferrous sulfate and ferrous fumarate

Adverse effects include nausea, abdominal cramping/discomfort, constipation, dark stools

Oral iron

What is the dosing for ferrous sulfate and ferrous fumarate?

1 tablet every other day

Counseling is prefer empty stomach and acidic environment; may take with food if GI intolerance occurs, but absorption decreases; avoid delayed-release and enteric-coated products; dark stools are expected; keep away from children and pets; for GI intolerance begin lower and titrate

Oral iron

Vitamin C, citrus juice, tomato products, and other acidic foods may improve absorption of this

Oral iron

Coffee, tea, dairy, and fiber inhibit absorption of this

Oral iron

What drugs reduce iron absorption (7)?

Antacids, H2-receptor antagonists, PPIs, fluoroquinolones, tetracycline, doxyccyline, cholestyramine

What drugs have absorption reduced by iron (7)?

Levodopa, Methyldopa, Levothyroxine, Fluoroquinolones, Tetracycline, Doxycycline, Mycophenolate

This is preferred for patients with CKD on hemodialysis, ESA therapy in CKD or cancer, severe oral-iron intolerance, malabsorption due to short-gut syndrome, Crohn disease, ulceratve colitis; persistent nonadherence, need for faster/more reliable replacement

IV iron

These three conditions lead to malabsorption of oral iron, leading to IV being preferred

Short-gut syndrome, Crohn disease, Ulcerative colitis

IV iron with highest hypersensitivity concern; 25 mg test dose required

Iron dextran

IV iron involving repeated smaller doses

Iron sucrose

IV iron with repeated doses

Sodium ferric gluconate

IV iron with two-dose regimen; also has high hypersensitivity risk

Ferumoxytol

IV iron that has highest hypophoshatemia risk

Ferric carboxymaltose

IV iron that can be given as a single 1g dose

Ferric derisomaltose

Adverse effects include myalgias, flushing, hypotension or hypertension, tachycardia, chest pain, peripheral edema, hypophosphatemia, and hypersensitivity/anaphylaxis

IV iron

Risk factors include multiple drug allergies, severe asthma, atopic dermatitis, systemic inflammatory disease (such as RA or lupus), previous IV-iron reaction, and rapid infusion rate

IV iron hypersensitivity

When giving IV iron, it is very important to verify the ________ _____

Infusion rate

This form of IV iron requires test dose

Iron dextran