test 2 - anemias

a condition where the bone marrow doesn’t produce enough red blood cells that results in anemia

hypoproliferative anemia

• decrease in ferritin (storage iron)

• no anemia

• rbc morphology normal

• rdw can be elevated

stage 1 of IDA

• decrease in iron for erythropoiesis

• no anemia or hypochromia

• rbc slightly microcytic

stage 2 of IDA

• decrease in blood hgb

• decrease in peripheral tissue oxygen delivery

• all lab tests are abnormal

• microcytic, hypochromic anemia

stage 3 of IDA

sideroblastic anemia is a type of ________.

porphyria

primary function of iron in the body

oxygen transport

what are 4 conditions that influence iron absorption and storage

excessive loss, nutritional deficiency, increased physiological demand, and faulty/incomplete absorption

examples of pathological excessive loss

• GI bleeding

• urogenital bleeding

• pulmonary hemosiderosis

• intravascular hemolysis

• malignancy (colon cancer)

examples of physiological excessive loss

menstruation and pregnancy

examples of increased physiological demand

• postnatal growth spurt

• adolescent growth spurt

examples of faulty or incomplete absoprtion

• autoimmune gastritis

• celiac disease

• H. pylori infection

signs and symptoms of IDA

• pallor (paleness), fatigue and/or weakness

• papilledema

• bulging of fontanelles in infants

• psychomotor and mental impairment in first 2 years of life

• PICA

• shortness of breath

• lethargy

• gastritis

• koilonychia

spoon nails

koilonychia

swelling of optic discs

papilledema

blood smear findings of IDA

• microcytic, hypochromic

• anisocytoses

• microcytes

• poik

• teardrops

• targets

• elliptocytes

• polychromasia

heme results of IDA

• MCV < 80 fL

• MCH <27 pg

• MCHC < 32%

• decreased hgb

• decreased hct

• normal to increased retic

• decreased rbc

• increased RDW

bone marrow results of IDA

erythroid hyperplasia with a decrease in stainable iron

non-heme results of IDA

• transferrin saturation < 16%

• serum ferritin < 12 ug/L

• low serum iron

• increase TIBC

results from illness, chronic infection, malignancy, or various systemic diseases

anemia of chronic disease

anemia of chronic disease

iron is unavailable, it gets deposited into macrophages in storage form → release is blocked

hypoproliferative anemia resulting from underproduction of rbc

ACD

list causes for ACD

• critical illness, obesity, aging, kidney failure

• ½ cases are subacute or chronic infections

  • tb, lung abscess, bacterial endocarditis

• neoplasms, rheumatoid arthritis, rheumatic fever, SLE, uremia, chronic liver disease

lab findings of ACD

• decreased rbc, hgb, hct, MCV, MCH, serum iron

• normal to decreased MCHC

• wbc/plt might be high

• retic variable (normal to low)

• decreased iron

• normal to low TIBC

• increased stainable iron in BM with decreased sideroblasts’

• normocytic, normochromic

• targets, elliptocytes, teardrops

disease of heme metabolism in which a primary abnormality in porphyrin biosynthesis leads to excessive accumulation and excretion of porphyrins or their precursors by the biliary and/or renal route

porphyria

porphyrias

disorders in the synthesis of porphyrin

clinical significance of hemochromatosis

too much iron accumulates causing hemochromatosis, which can lead to a toxic buildup of iron in the organs

treatment of hemochromatosis

iron removal by therapeutic phlebotomy or iron chelation therapy

safest way of treatment for hemochromatosis

• one unit (450 mL) of whole blood 1-2 times weekly until a change is seen in transferrin and ferritin

• then, 2-6 therapeutic phlebotomy sessions yearly for long term maintenance

list causes for sideroblastic anemia

• genetic (sex-linked autosomal, males)

• idiopathic

• uremia, thyrotoxicosis, porphyria

• secondary to drugs

• after chemo

• toxins (alcohol, chronic lead poisoning)

lab features of sideroblastic anemia

• iron granules seen on bone marrow

• sideroblasts

• increased erythropoietic activity in BM

• microcytic hypochromic

• target cells

• basophilic stippling

• increased serum iron and serum ferritin

• normal to increased iron

• normal to decreased TIBC, UIBC

treatment of sideroblastic anemia

• pyridoxine trial in pharmalogical doses (ineffective in acquired forms)

• remove offending drugs or toxins and providing supporting care

• chemo if condition evolves into acute myelogenous leukemia

clinical signs and symptoms of megaloblastic anemias

• lemon yellow skin

• hyperpigmented nail beds, skin creases, and area around eyes

• cracking at corners of mouth

• dyspepsia

• diarrhea

• glossitis/painful tongue

• early graying of hair

• tiredness

• vertigo

• tinnitus secondary to anemia

• congestive heart failure

• SOB on exertion

genetic predisposition to bone marrow failure

faconi’s anemia

faconi’s anemia

• 5-10 years old

• low birth weight

• hyperpigmentation

• short stature

• dyspnea

• bleeding

• infections

• skeletal disorders

uncoordinated malnutrition of nucleus and cytoplasm

megaloblastic

classify megaloblastic anemia by size, shape, and color of rbc’s.

• nrbc’s

• multiple Ho-Jos

• microcytes and dacrocytes

• hypercellular bone marrow

• large, abnormal hematopoietic progenitor cells

• finely stippled, lacy nuclear chromatin pattern

• less condensed chromatin pattern

• basophilic stippling

2 major causes of megaloblastic anemia

vitamin B12 deficiency and folic acid deficiency

4 causes of vitamin B12 deficiency

• increased utilization of vitamin B12

  • parasitic infections

  • diverticulitis

• malabsorption syndrome

  • gastric resection

  • gastric carcinoma

• nutritional deficiency

• pernicious anemia

4 causes of folic acid deficiency

• inadequate dietary intake

• malabsorption

• increased requirement

• drugs

epidemiology of pernicious anemia

• vitamin B12 deficiency because of lack of intrinsic factor is limited to older patients of european descent

• median age for diagnosis is 70

• gastric autoantibodies (genetic predisposition)

phase 1 of aplastic anemia - onset of disease

after initiating event, the hematopoietic compartment is destroyed by immune system

phase 2 of aplastic anemia - recovery

partial or complete response can occur initially, won’t last (no real increase in stem cells)

phase 3 of aplastic anemia - late disease

pancytopenia, will evolve into PNH, AML, MDS

Howell jolly bodies seen in which anemias (residual DNA)

megaloblastic and hemolytic

Heinz bodies seen in which anemia (denatured hemoglobin)

G6PD, hemolytic anemia, hemoglobinopathies

stomatocytes are seen in which anemias

hereditary stomatocytotosis (also in alcoholism)

Hb C crystal seen with hemoglobins

Hb SC, Hb CC

target cells are in which anemias

iDA, ACD, megaloblastic anemias, hemolytic anemia

microcytic hypochromic anemias

IDA, sideroblastic anemia, ACD, thalassemia

sickle cells in which forms of anemia?

• Hb SS (sickle cell disease)

• Hb AS (sickle cell trait)

• Hb SC disease

spherocytes seen in which anemias

hereditary spherocytosis and hemolytic anemia (extravascular)

basophilic stippling (residual RNA) seen in what anemias

IDA, sideroblastic (lead toxicity), megaloblastic, thalassemia

prevention/treatment of thalassemia’s

• genetic counseling, newborn screening

• hyper transfusion, with iron chelation

• bone marrow or hematopoietic stem cell transplant

beta thalassemia major/ Cooley’s anemia

severe microcytic hypochromic anemia

• marked bone changes due to expansion of bone marrow space for increased erythropoiesis

• detected in early childhood (failure to thrive, fever, pallor, hepatosplenomegaly, cardiac failure

• bossing of skull, long bones, facial deformities, hair on end appearance of skull

• bronze pigment

• Hb A production is reduced

• Hb A2 and Hg F production increased

beta thalassemia minor

• common, 200 point mutations

• mild asymptomatic hemolytic anemia unless pt. is under stress (pregnancy, infection, folic acid deficiency)

• one normal beta gene and one mutated beta gene

clinical findings associated with thalassemia

• anemia/hypoxia

• increased extravascular hemolysis

• splenomegaly

• gallstones

• iron overload/toxicity

lab findings of thalassemia

• microcytic hypochromic

• targets, aniso, nRBCs, basophilic stippling

• decreased/normal rbc

• decreased hgb and hct

• increased retic

• increased RDW

• increased bilirubin

• increased haptoglobin

• increased LDH

• decreased TIBC

bone marrow of thalassemia

erythroid hyperplasia, increased iron (Prussian blue)

alpha thalassemia (beta chain excess)

• unstable

• high oxygen affinity, poor oxygen transporter

• combines to form hgb molecules with absence of 3 out of 4 alpha chains

• infants: excess gamma chains combine with hgb molecules

• deletion of one or both alpha globulin genes

4 types of alpha thalassemia

• silent carrier state (one inactive alpha gene)

• alpha thalassemia trait (2 inactive alpha genes)

• Hb H disease (3 inactive alpha genes)

• hydrops fetalis with Hb Bart (4 inactive alpha genes) → incompatible with life

beta thalassemia (excess alpha chain)

• unstable (usually from point mutation)

• precipitates within the cell, causing damage

• macrophages destroy the damaged RBCs in BM → ineffective erythropoiesis

• spleen also removes damaged RBCs, leads to chronic extravascular hemolysis

the mildest form of beta thalassemia

beta thalassemia minima/silent carrier state

heterozygous disorder resulting in mild hypochromic microcytic hemolytic anemia

beta thalassemia minor

severity lies between minor and major

beta thalassemia intermedia

homozygous disorder resulting in severe transfusion dependent hemolytic anemia

beta thalassemia major

globin chain is abnormal

hemoglobinopathies

results in overall decrease amount of hemoglobin produced and may induce hemolysis

thalassemia

2 major types of thalassemia

• alpha - caused by defect in rate of synthesis of alpha chains

• beta - caused by defect in synthesis of beta chain

in thalassemia, what does the decreased globin production cause

• imbalanced globin chain synthesis

• defective hgb production

• damage to rbc

may contribute protection against malaria

thalassemia

disorder results from the inheritance of one gene for Hb S from one parent and one gene for Hb C from the other parent. the course of this disease is generally milder than SCD, although Hb C tends to aggregate and potentiate the sickling of Hb S

hemoglobin SC disease

this hemoglobinopathy is prevalent in the same geographic area as SCD

hemoglobin C disease

how does Hb C differ from Hb A?

substitution of a single amino acid residual, lysine for glutamic acid, in the 6th position from the amino terminal end of the beta chain (exact point of substitution of Hb S)

• 2 alpha and 2 beta chains

• 95-98% adult hgb

hemoglobin A

• 2 alpha, 2 delta

• 1-3% normal adult hemoglobin

hemoglobin A2

• 2 alpha and 2 gamma

• <2% in adults

• primary hgb of fetus

hemoglobin F

sickle cell trait

• heterozygous AS with more Hb A than Hb S, so condition is compensated for

• normal life span

• asymptomatic with occasional hematuria

• if oxygen is reduced, sickling can occur

lab findings of sickle cell trait

• normal CBC

• few targets or sickle cells

• positive sickle solubility test

• both A and S present on electrophoresis

sickle cell anemia treatment

• children: exams, vaccines, avoid dehydration

• prevention of infection

• reduce organ damage

  • hydroxyurea using chemotherapeutic agents

  • avoidance of situations that could cause a crisis

• minimize pain

  • BM transplant

  • blood transfusion

median age of death for sickle cell anemia

females - 48

males - 42

lab findings in sickle cell anemia

• normocytic normochromic

• hgb 6-10 g/dL

• aniso and poik

• drepanocytes

• targets

• decreased rbc

• ovalocytes and schistocytes

• nRBCs with polychromasia

• increased retic

• basophilic stippling

• Ho-Joes

• pappenheimer bodies

• leukocytosis with left shift

• thrombocytosis

chemistry tests for sickle cell anemia

• increased LDH and bili

• decreased haptoglobin

organs affected by sickle cell anemia

liver - enlarges, malfunctions, jaundice, hyperbilirubinemia
heart - cardiomegaly, iron deposits

spleen - enlarges, leads to infarction and fibrosis, eventually shrivels and becomes nonfunctional

skin - ulcers, jaundice

kidney - hematuria, eventual renal failure

lungs - obstruction of blood flow

brain - strokes

blood - hemolytic anemia

pathophysiology of sickle cell anemia

• 1st stage starts with small amounts, but with prolonged deoxygenation, large amounts of polymerized cells get stuck in small vessels (vaso-occlusion)

• causes severe pain from blood not flowing with decreased oxygen, intense pain in crisis

• if/when they receive oxygen, cells can return to normal shape → with repeated cycles of sickling, hemolysis occurs (necrosis to tissues)

most common hemoglobinopathy

sickle cell anemia

SS

sickle cell disease

AS

sickle cell trait

how is Hb S different from Hb A

a single nucleotide change (GAT to GTT) that results in substitution of valine for glutamic acid at the 6th position on the beta chain on hgb molecule

hemoglobinopathies (qualitative) demographic

malarial belt, heterozygotes have a selective advantage against infection with plasmodium falciparum