RBC 1 Flashcards
Size and color: generally disorders of hemoglobin synthesis, often iron deficiency
Microcytic normochromic
Size: generally from impaired maturation of red cell precursors in BM. B12 and folate deficiency. pernicious anemia
Macrocytic
size and color: anemia of chronic disease
normocytic normochromic
normocytic value
80-100
What measurements are useful for color of RBCs
- mean cell hemoglobin
- mean cell hemoglobin concentration
what is normal red cell distribution width
12-15
Older male above 60 with iron deficiency anemia. what is the workup?
if it’s a female?
colon cancer
-may be perimenopausal or gynecological bleeding but could also be colon cancer
is the HCT clinically useful in evaluating acute blood loss?
No, you are losing both red cells and plasma
How quickly are reticulocytes produced
5 days
What are the features of hemolytic anemias?
- shortened red cell life span below the typical 120 days
- Elevated erythropoietin levels and a compensatory increase in erythropoiesis
- Hemoglobin degradation products tend to accumulate during red cell hemolysis
Predominant features of extravascular hemolytic anemia
- anemia
- SPLENOMEGALY
- and jaundice
features of intravascular hemolytic anemia?
- anemia
- hemoglobinemia
- hemoglobinuria
- hemosidinuria
- Jaundice
- NO SPLENOMEGALY
Role of haptoglobin in hemolytic anemia
it binds degradation product so it goes down
in all types of uncomplicated hemolytic anemias, the excess serum bilirubin is _____
unconjugated
an inherited disorder caused by intrinsic defects in the red cell membrane skeleton that render red cells spheroid, less deformable, and vulnerable to splenic sequestration and destruction
Hereditary spherocytosis (HS)
what is the inheritance pattern of 75% of hereditary spherocytosis
autosomal dominant
in 2/3 of HS, the red cells are abnormally sensitive to what?
osmotic lysis when incubated in hypotonic salt solutions which causes the influx of water into sperocytes with little margin for expansion
what is the Mean cell hemoglobin concentration (MCHC) in HS
increased due to dehydration caused by loss of K+ and water
What are the characteristic clinical features of HS?
- anemia
- splenomegaly
- Jaundice
The generally stable course of HS is sometimes puncuated by aplastic crises, usually triggered by what?
an acute parvovirus infection
describe the hemolytic crisis that can occur in HS?
produced by intercurrent events leading to increased splenic destruction of red cells (infectious mononucleosis)
What stones are found in many HS pts?
gallstones
What treats the anemia of HS?
splenectomy but brings with it an increased risk of sepsis
The episodic hemolysis that is characteristic of G6PD deficiency is caused by exposures that generate oxidant stress . . what are most common causes?
- infections
- Antimalarial drugs (like quinidine)
- Tonic water from gin and tonics
Heinz bodies
G6PD deficiency
Bite cells
G6PD deficiency
A common hereditary hemoglobinopathy caused by a point mutation in b-globin that promotes the polymerization of deoxygenated hemoglobin, leading to red cell distortion, hemolytic anemia, microvascular obstruction, and ischemic tissue damage
Sickle cell Disease
what is common in children with sickle cell disease
painful bone crisis that is difficult to distinguish from acute osteomyelitis
What is a particularly dangerous type of vaso-occlusive crisis involving the lungs in sickle cell disease
Acute chest syndrome which typically present with fever, cough, chest pain, and pulmonary infiltrates
In sickle cell disease, what affects up to 45% of males after puberty and may lead to hypoxic damage and erectile dysfunction
Priapism
other disorders related to vascular obstruction in sickle cell disease
-stroke and retinopathy leading to loss of visual acuity
What are the factors proposed to contribute to stroke in sickle cell disease
adhesion of sickled red cells to arterial vascular endothelium and vasocontriction caused by the depletion of NO by free hemoglobin
Aplastic crisis in sickle cell disease stem from infection of red cell progrenitors by what?
parvovirus B19
A heterogeneous group of disorders caused by inherited mutations that decrease the synthesis of either the alpha or beta globin chains that compose adult hemoglobin
Thalassemias
Beta thallasemias are mainly what type of genetic abnormality?
Alpha?
point mutations
gene deletions
What beta thalassemia requires blood transfusions?
Which is severe but doesn’t require blood transfusions?
Which is Asymptomatic with mild or absent anemia; Target cells
Major
intermedia
minor
genotype for an alpha thalassemia silent carrier?
trait?
HBH disease?
Hydrops fetalis?
- /a a/a
- /- a/a (asian) or -/a -/a (Black african, asian)
- /- -/a
- /- -/-
size and color anemia for B-Thalassemia
hypochromic, microcytic
Where is B-Thalassemia Major most common
Mediterranean countries, parts of Africa, Southeast Asia
When does B-Thalassemia Major manifest?
6 to 9 months after birth as hemoglobin synthesis switches from HbF to HbA
What is the Major red cell hemoglobin in B-thalassemia Major?
What are the levels of HbA2?
HbF is markedly elevated
sometimes high but more often are normal or low
describe the cheek bones in B-Thalassemia Major pts if they survive long enough?
other clinical findings?
enlarged and distorted . . crew cut appearance on X ray
Hepatosplenomegaly due to extramedullary hematopoiesis
Describe the complications of blood transfusions in a B-Thalassemia major patient
Cardiac disease resulting from progressive iron overload and secondary hemochromatosis is an important cause of death, . . must be treated with iron chelators like EDTA
What is the only therapy offering a cure for B-Thalassemia Major
Hematopoietic stem cell transplantation
Hemoglobin elecrophoresis in B-Thalassemia minor shows what?
- an increase in HbA2
- HbF levels are generally normal or occasionally slightly increased
Recognition of B-Thalassemia minor is important for what 2 reasons?
- it superficially resembles the hypochromic microcytic anemia of iron deficiency
- it has implications for genetic counseling
There are women who are pregnant and have b thalassemia minor undiagnosed and present with microcytic hypochromic anemia and it’s immediately thought that they have iron deficiency anemia . . . Hb electrophoresis is called for . . .THE INCREASE IN HbA2 is DIAGNOSTICALLY USEFUL
in newborns with alpha-Thalassemia, excess unpaired gamma-globin chains form gamma4 tetramers known as what?
Which alpha thalassemias is this found in?
hemoglobin barts
Silent carrier and trait
A disease that result from acquired mutations in the phosphatidylinositol glycan complementation group A gene (PIGA), an enzyme that is essential for the synthesis of certain membrane associated complement regulatory proteins
Paroxysmal nocturnal hemoglobinuria (PNH)
what is the only hemolytic anemia caused by an acquired genetic defect?
PNH
what is the leading cause of disease related death in individuals with PNH
Thrombosis: about 40% of patients suffer from venous thrombosis
About 5 -10% of PNH pts eventually develop what?
AML or a myelodysplastic syndrome
How is PNH diagnosed?
by flow cytometry . . red cells deficient in CD59
hemolytic anemias in this category are caused by antibodies that bind to red cells, leading to their premature destruction
immunohemolytic anemia . . commonly called autoimmune hemolytic anemia
What ig is the culprit in warm antibody type immunohymolytic anemia?
What are the causes?
IgG
- Primary
- Secondary (SLE), drugs,
What ig is the culprit in cold agglutinin type immunohymolytic anemia?
What are the causes?
IgM
- Acute: mycoplasm infection, infectious mononucleosis)
- Chronic: lymphoid neoplasms
What ig is the culprit in cold hemolysin type immunohymolytic anemia?
What are the causes?
- IgG
- mainly in children following viral infections
Patients red cells are mixed with sera containing antibodies that are specific for human Ig or complement
DIRECT Coombs tests
Patients serum is tested for its ability to agglutinate commercially availble red cells bearing particular defined antigens
INDIRECT coombs test
The most significant hemolysis caused by trauma to red cells is seen in what individuals?
those with cardiac valve prosthesis and microangiopathic disorders
Microangiopathic hemolytic anemia is most commonly seen with what?
DIC
microvascular lesion that results in luminal narrowing often due to the deposition of fibrin and platelets
microangiopathic hemolytic anemia
Red cell fragments (schistocytes), burr cells, helmet cells, triangle cells
Traumatic damage
The most common and important anemias associated with red cell underproduction are those caused by what?
nutritional deficiencies
What dietary deficiencies cause megaloblastic anemia
Vitamin B12 and folic acid
What is one of the major white cell effects of megaloblastic anemia?
-multi lobated PMNs or nutrophils with five or more nuclear lobules
Neurologic complications of B12 deficiency
-spastic paraparesis, sensory ataxia and severe parathesias of the lower limbs
a specific form of megaloblastic anemia caused by autoimmune gastritis that impairs production of IF, required for vitamin B12 uptake from GI
Pernicious anemia
Age for pernicious anemia
median of 60. rare under 30
A diagnosis of pernicious anemia is based on what?
- moderate to severe megaloblastic anemia
- Leukopenia with hypersegmented granulocytes
- Low serum B12
- Elevated serum levels of homocysteine and methymalonic acid
in a true case of pernicious anemia, what happens about 5 days after parenteral administration of B12
reticulocytosis and a rising HCT
What is often found in B12 deficiency that is NOT related to pernicious anemia
-Achlorhydria and loss of pepsin secretion, vitamin B12 is not readily released from protein in food
list the things that can cause B12 deficiency that are NOT pernicious anemia
- Gastrectomy
- loss of exocrine pancreas function
- Illeal resection
- tapeworms from raw fish
- increased demand (pregnancy, hyperthyroidism, disseminated cancer, chronic infection)
What are the manifestations of folic acid deficiency?
exactly the same as B12 deficiency
What foods are the source of folic acid?
B vitamins?
green veggies
Meats
Why is it essential to exclude B12 deficiency in megaloblastic anemia before initiating folate therapy?
folate does not prevent and may even exacerbate the neurologic deficits seen in B12 deficiency states
What is the Schilling test
its a way to tell the difference b/t pure B12 deficiency and pernicious anemia but uses radioactive substances
pigments involved in the formation of heme?
porphyrins
Clinical effects of chronic Porphyria?
- seen in skin (abnormal reactions to sunlight, blistering, abnormal hair growth)
- teeth (staining)
clinical effects of acute Porphyria?
-nervous system (referred pain thorax and abdomen), seizures, hallucinations, general psychosis
What is the most common nutritional disorder in the world
Iron deficiency anemia
plasma ferritin levels in Iron deficiency anemia
<12
High iron in med is considered a risk factor for what?
Atherosclerosis because it is related to chronic inflammation
What molecule is used for iron absorption
hepcidin
hepcidin level in anemia of chronic disease
Increased
What is the most common cause of iron deficiency in the Western world
Chronic blood loss
Iron deficiency anemia in men and post menopausal women in the western world should be ascribed to what until proven otherwise
Occult blood loss. . . GI
Describe the size and color of RBCs at first with IDA
normocytic normochromic
describe RBCs in well established IDA
microcytic hypochromic anemia with modest poikilocytosis
- Microcytic hypochromic anemia
- Esophageal Webs
- Atrophic glossitis
Plummer-Vinson syndrome
Diagnosis of IDA
- HCT, Hgb decreased
- serum iron: low
- serum ferritin: low
- TIBC; Total Iron binding capacity: high
- Serum hepcidin: low
what is considered the most common type of anemia in hospitalized patients in the US?
3 major categories in this setting?
impaired red cell production associated with chronic diseases that produde systemic inflammation
- Chronic infection
- Chronic autoimmune disorders
- Neoplasms; bronchogenic carcinoma, HL
Erythropoietin level in anemia of chronic disease?
Serum ferritin?
TIBC?
low
high
low
size and color of RBCs in anemia of chronic disease
Normocytic normochromic
What type of anemia exhibits pancytopenia
aplastic anemia
What is necessary for diagnosis of aplastic anemia
bone marrow biopsy: HYPOcellular, contains mainly fat
Prognosis of Aplastic anemia
Bone marrow transplantation is treatment of choice and 5 year survival more than 75%
A primary marrow disorder in which only red cell precursors are affected
Pure red cell aplasia
Etiology of Pure red cell aplasia
- thymoma: resection leads to improvement in half
- Large, granular lymphocytic leukemia
- certain drugs
- autoimmune disorders
- Parvovirus B19
Abnormally high red cell count, increased Hgb
Polycythemia
What is relative polycythemia
reduced plasma volume (hemoconcentration)
erythropoietin in Primary absolute polycythemia?
Secondary
Low
high
What is the most common cause of Primary absolute polycythemia?
polycythemia vera
