RBC Disorders (Part 2) Flashcards
This is a macrocytic anemia in which DNA synthesis is unimpaired.
Macrocytic nonmegaloblastic anemia
Macrocytosis tends to be mild; the MCV usually ranges from100 to 110 fL and rarely exceeds 120 fL
Macrocytic nonmegaloblastic anemia
This macrocytic anemia lacks hypersegmented neutrophils and oval macrocytes in the peripheral blood and megaloblasts in the bone marrow
Macrocytic nonmegaloblastic anemia
Pathologic result of nonmegaloblastic macocytic anemia
liver disease, chronic alcoholism, or bone marrow failure
What are the characteristics of a macrocytic anemia? Cite atleast three. (HIPA)
- Hypercellular Bone Marrow
- Presence of megaloblast
- Ineffective erythropoiesis
- Active intramedullary hemolysis
It is where there is an impaired DNA synthesis and many of the cells never undergo mitosis & rather they breakdown and
die in the bone marrow
Ineffective erythropoiesis
Cite at least three consequences of ineffective erythropoiesis.
- Bone marrow destructions of erythroid presursors
- Lack of regeneration of bone marrow elements during anemic stress
-Lack of nucleated red blood cells in peripheral smear
-Lack of polychromasia in peripheral smear - Reticulocytopenia
- Intramedullary hemolysis
- Increased bilirubin and LDH
- Decreased haptoglobin
What are the two major divisions of megaloblastic anemia?
Vitamin b12 (cobalamin, Cbl) deficiency
Folic acid deficiency
It manifests macro-ovalocytes and giant hypersegmented neutrophils
Megaloblastic anemia
What causes an impaired DNA synthesis?
Vitamin B12 or folate deficiency
If DNA synthesis is impaired what happens?
Nuclear replication slows down and each step of maturation will be delayed
If this is prolonged it would results in a large nucleus. Resulting to a megaloblast, large nucleus, increase cytoplasmic RNA, and early synthesis of hemoglobin
premitotic interval
Cite the megalocyte maturation sequence
Promegaloblast (Megaloblastic rubriblast) >
Basophilic megaloblast (Megaloblastic prorubricyte) >
Polychromatophilic megaloblast (Megaloblastic rubricyte) >
Orthochromic megaloblast (Megaloblastic metarubricyte) >
Polychromatophilic megalocyte (Megaloblastic reticulocyte) >
Megalocyte (Oval macrocyte)
A decrease amount of cells in all cell lines
(WBC, RBC, platelets)
Pancytopenia
Megaloblastic macrocytic anemia results to?
- Pancytopenia
- Increased MCV and MCHC
- Hypersegmented neutrophils (five lobes or
more in segmented neutrophils) - Increased bilirubin
- Increased LDH
- Hyperplasia in the bone marrow
- Decreased M:E ratio (usually 10:1)
- Reticulocytopenia
These are cells found in the bone marrow of a patient
with megaloblastic anemia
Megaloblasts
It is characterized by a more open chromatin
pattern, karyorrhexis, & multiple Howell Jolly
bodies
Megaloblasts
It is a product of maturation arrest or nuclear cytoplasmic asynchrony
Megaloblast
This causes the nucleus
and then cytoplasm to not mature together
nuclear-cytoplasmic asynchrony
Where does cobalamin absorption takes place?
Ileum of the small intestine
It is the only vitamin exclusively synthesized by microorganisms
Cobalamin
Form of stored cobalamin in the liver
adenosylcobalamin
In order to absorb cobalamin, it requires?
Castle’s factor or Intrinsic factor
Cobalamin is transported in the plasma in the form of?
methylcobalamin
Transporter of methylcobalamin
transcobalamin
Vitamin B12 is otherwise known as?
cyanocobalamin
What are the causes of Vitamin B12 deficiency?
- Fish tapeworm Diphyllobothrium latum infection
- Pernicious anemia
- Malabsorption syndrome caused by gastric resection, gastric carcinoma, and some forms of celiac disease or screw
- Nutritional deficiency
- Hypochlorhydria
It refers to the decrease production of hydrochloric acid in the stomach
hypochlorhydria
Hypochlorhydria is associated with?
pernicious anemia
It is caused by failure of the gastric mucosa to secrete intrinsic factor
Pernicious Anemia
Other term for Pernicious Anemia
Addison’s anemia or Atrophy gastritis
Pernicious anemia is an autoimmune disease caused by two antibodies called?
Anti-parietal cell antibodies and Anti-intrinsic factor antibodies.
It produces a yellow lemon color of the skin
Pernicious anemia
Because pernicious anemia has neurologic symptoms, it has been called as?
Megaloblastic madness
It is an autosomally recessive inherited defect in the
intestinal absorption of cobalamin
Imerslund-Grasbeck Syndrome
There is a problem in the absorption of cobalamin but the intrinsic factor is normal
Imerslund-Grasbeck Syndrome
What are the diagnosis used for cobalamin deficiency?
Schilling test
Serum Cobalamin Assay
Methylmalonic Acid and Homocysteine
Assays
Deoxyuridine Suppression Test
It tests the ability of the patient to absorb an oral dose of
radioactive cobalamin
Schilling test
It is a microbiological assay which utilizes the organism
called Euglena gracilis
Serum Cobalamin Assay
It measures the ability of the marrow cells in vitro
Deoxyuridine Suppression Test
These both increase in megaloblastic anemia
Methylmalonic Acid and Homocysteine
Assays
It is considered as the reference procedure for
the determination of pernicious anemia
Schilling test
In Schilling test, If the abnormal result of stage 1 improves with administration of intrinsic factor, it means that a patient has?
Intrinsic factor
deficiency
Folate is absorbed where?
Jejunum
It cannot be
corrected by having vitamin b12 supplementation
folate deficiency
This can be partially corrected by folate even in the absence
of cobalamin supplementation
Anemia of cobalamin
deficiency
What are the causes of folate/folate acid deficiency? (CPPS)
- Chronic alcoholics
- Poor dietary habits
- Pregnancy
- Steatorrhea - tropical sprue, nontropical sprue, celiac disease
Diagnosis of folate deficiency
- Microbiological assay (definitive)
- Serum folate (<3 ug/L)
- Red cell folate
This test for folate deficiency utilizes the organism Lactobacillus casei
Microbiological assay
If the patients has low Vit. B12, normal or high serum folate and low red cell folate the patient has?
Vitamin B12 deficiency
If the patient has normal Vit. B12, but low serum folate and red cell folate, the patient has?
Folic Acid deficiency
If the patient has low Vit. B12, low serum folate, and low red cell folate, the patient has?
Both Vitamin B12 and Folate acid deficiency
How can you spot a megaloblastic anemia?
By looking at the MCV. One of the signs of a megaloblastic anemia is the presence of a high MCV .
Aside from a high MCV result what are the other indicators that would confirm that a patient has megaloblastic anemia?
hypersegmented neutrophil plus the presence of macroovalocytes in the peripheral blood smear
Termed as “shift reticulocytes”, especially in response to acute blood loss, hemolysis, and bone marrow infiltration
Non-megaloblastic anemia
Results in high levels of EPO
Non-megaloblastic anemia
Seen in a plastic anemia, refractory anemia, and Diamond-Blackfan anemia
High levels of EPO
This macrocyte is seen in folic acid deficiency, vitamin b12 deficiency, and pernicious anemia
Oval macrocyte
This macrocyte is seen in alcoholism, hypothyroidism, and liver disease
Round hypochromic macrocyte
This macrocyte is seen in neonate response to anemic stress and response to anemic stress
Blue- tinged macrocyte
This macrocyte is seen in non-megaloblastic anemia
Round hypochromic
macrocyte
Reticulocyte stain with
supravital stain
Blue-tinged macrocyte
This macrocyte is seen in megaloblastic anemia
Oval macrocyte
Characterized by
Normochromic and normocytic
Myelophthisic anemia
Associated with marrow replacement by involvement with abnormal cells or tissue
Myelophthisic anemia
Characterized by increased NRBC
Myelophthisic anemia
A condition in which bone marrow is replaced by abnormal cells but still the peripheral smear would present a normochromic and normocytic RBCs but there is an increase in the presence of
your nucleated RBC
Myelophthisic anemia
A condition in which bone marrow does not produce any blood
cells
Aplastic anemia
Seen in pancytopenia, macrocytosis, increase RDW, and chloramphenicol
Aplastic anemia
It is a medication that can commonly cause aplastic anemia
Chloramphenicol
An inherited Aplastic Anemia
Fanconi’s Anemia
Presence of scattered giant pronormoblasts in the bone marrow
Transient Aplastic Crises
Caused by increased levels of Hb F and i antigen
Fanconi’s Anemia
Caused by parvovirus B19 infection
Transient Aplastic Crises
It is often preceeded by an infection.
Transient Aplastic Crises
Not an aplastic anemia but just pure red cell aplasia
Transient Aplastic Crises
A condition where there is pancytopenia. Wherein all of the cell lines are affected.
Fanconi anemia
An anemia wherein only the red cells are affected
Diamond Blackfan anemia
Characterized by congenital Red Cell Aplasia, Macrocytic, low reticulocyte level, elevated Hb F, and the frequent presence of antigen i
Diamond Blackfan Anemia
Blood is lost in small amounts over an
extended period
Chronic Posthemorrhagic Anemia
Transient fall in the platelet count which made
the platelet count may rise to elevated levels
within 1 hour
Acute Posthemorrhagic Anemia
Blood is lost over a short time in amounts
sufficient to cause anemia. Reticulocyte increases 3-5 days after blood loss
Acute Posthemorrhagic Anemia
Increase red blood cell destruction
Hemolytic anemia
(Membrane disorders)
The lifespan of normal RBC would decrease if they were transfused into the patient but patient’s red cells survive normally if given to a
normal patient
Extrinsic hemolytic anemia
Increased hemolysis also results in?
increased LDH
This test is to determine whether it (anemia) is immune- mediated or not
Antiglobulin test
Patient’s RBC would not survive when
transfused to a normal recipient. Defect of RBC itself, and membrane, metabolic, and hemoglobin
defects
Intrinsic hemolytic anemia
IDENTIFY: hemoglobinemia, hemoglobinuria, or hemosideriuria is absent. Increase in urine or fecal urobilinogen, increase blood carboxyhemoglobin level, and increase indirect- reacting serum bilirubin
Extravascular or Extrinsic hemolytic anemia
IDENTIFY: hemoglobinemia, methemalbuminemia, hemoglobinuria, or hemosideriuria is present, there is also an increase in LDH
Intravascular or Intrinsic hemolytic anemia
Reversal of the LD isoenzyme pattern is seen with LD1 exceeding LD2
Intravascular or Intrinsic hemolytic anemia
Most red cell destruction about 80-90%is presumed to be
________ within macrophages of the mononuclear phagocytic system of the liver and the spleen.
extravascular
Identify: MCHC > 36%, decreased surface-area-to-volume ratio, hyperpermeable to sodium thus increase osmotic fragility
Spherocytes
IDENTIFY: hemoglobinemia, methemalbuminemia, hemoglobinuria, or hemosideriuria is present. Increase in LDH is also observed
Intravascular or Intrinsic hemolytic anemia
IDENTIFY: MCHC > 36%, decreased surface-area-to-volume ratio, hyperpermeable to sodium thus increase osmotic fragility
Spherocytes
Most common prevalent hereditary hemolytic anemia among people of Northern European descent
Hereditary Spherocytosis
Hereditary Spherocytosis is caused by deficiency of the key membrane protein called?
spectrin
Characterized by increase osmotic fragility. An extravascular hemolysis within creased pigment catabolism, erythroid hyperplasia, and reticulocytosis but is DAT (Direct Anti-Globulin Test) negative because its not immune-mediated–it’s a membrane defect
Hereditary Spherocytosis
Refers to the weakening of the membrane skeleton and defective association of proteins that hold the skeleton together.
Hereditary Elliptocytosis
Deficiency of spectrin is again present but there is also a
deficiency in the proteins commonly associated with the
ALPHA & BETA-spectrin regions.
Hereditary Elliptocytosis
RBCs may
even fragment at 37°C, body
temperature with prolonged heating
Hereditary pyropoikilocytosis
In normal RBC budding and fragmentation show when heated at?
49°C
Red cell fragments at 45°C to 46 °C
Hereditary pyropoikilocytosis
Characterized by a well-defined band 3 molecular deletion and increased resistance to malaria
Southeast Asian Ovalocytes
It is a severe congenital hemolytic anemia, which is
characterized by microcytosis, striking micropoikilocytosis
and fragmentatin
Hereditary pyropoikilocytosis
Appears to have two bars across the center
Stomatocytic Ovalocyte
A thinner variant of elliptocytes or ovalocytes
Pencil cells/oat cells
Where the red cell is dehydrated due to loss of
cations, predominantly K+ and water
Hereditary stomatocytosis
MCV is normal or slightly increased and increased MCHC
Hereditary stomatocytosis
Opposite of hereditary spherocytosis because there is a decrease in osmotic fragility. MCHC is high
Hereditary xerocytosis
Stomatocytes seen on blood smears
Hereditary stomatocytosis
Increased surface-to-volume ratio leading to moderate to severe anemia
Hereditary xerocytosis
Gene suppression or the present of a silent Rh gene
Rh null Disease
This form of acanthocyte-associated hemolytic anemia is seen in patients with established alcoholic cirrhosis
Spur Cell Hemolytic Anemia
Increase OFT and autohemolysis
Rh null Disease
Marked dehydration and irreversible potassium
loss, peculiar red cell morphology where the hemoglobin of
red cells seem paddled at one end of the red cell
Hereditary xerocytosis
In a peripheral smear you can see stomatocytes and spherocytes
Rh null Disease
Caused by autoantibodies that are usually directed at Rh antigens
Warm Autoimmune Hemolytic Anemia
Can also be anti-U, anti-LW, and anti-Kell, and JKa or Fya
Warm Autoimmune Hemolytic Anemia
Usually anti-I. Complement factors occurs frequently due to M. pneumonia, respiratory infarctions, IMDAT+
Cold Autoimmune Hemolytic Anemia
It is the more common autoimmune hemolytic anemia
Warm Autoimmune Hemolytic Anemia
Exhibits spherocytosis, schistocytes, polychromasia, and nucleated erythrocytes
Warm Autoimmune Hemolytic Anemia
Involves coating of IgG of erythrocytes with or without complement taxation
Warm Autoimmune Hemolytic Anemia
Presence agglutination of the patient’s RBC in the capillaries
Cold Autoimmune Hemolytic Anemia
Most common medication associated with Cold Autoimmune Hemolytic Anemia
Aldomet
Optimal temperature of reactivity of Warm AIHM
37°C
Immunoglobulin class of cold AIHM
IgM
Site of hemolysis of cold AIHA
Intravascular
Optimal temperature of reactivity of Cold AIHM
4°C
Immunoglobulin class of warm AIHM
IgG
Site of hemolysis of warm AIHA
Extravascular
Complement activation of cold AIHA
+ (positive)
Complement activation of warm AIHA
positive (+) & negative (-)
In Cold Hemagglutinin Disease, Complement is fixed on the red cells during cold temperatures ________ and then red cells agglutinate and hemolyze as body temperature rises, ________
0 to 5 °C and 20 to 25 °C, respectively
Decay Accelerating Factor deficiency
Paroxysmal Nocturnal Hemoglobinuria
Intermittent (paroxysmal) sleep associated
(nocturnal) blood in the urine (hemoglobinuria)
Paroxysmal Nocturnal Hemoglobinuria
Also called Donath Landsteiner antibody with anti-P specificity
Paroxysmal Cold Hemoglobinuria
A rare hemolytic anemia caused by anti-P
Paroxysmal Cold Hemoglobinuria
Positive sucrose hemolysis and Ham’s tests
Paroxysmal Nocturnal Hemoglobinuria
Screening test for Paroxysmal Cold Hemoglobinuria
Donath- Landsteiner test
It attaches to the RBC at lower temperature, it
activates complement at a warmer temperature. It’s a cold reacting IgG autoantibody termed as auto hemolysin
Anti-P
It attaches to the RBC at lower temperature, it
activates complement at a warmer temperature. It’s a cold reacting IgG autoantibody termed as auto hemolysin
Anti-P
This usually
happens in soldiers after intense marches
March Anemia
These are consumptive coagulopatis that involves deposition of microthrombi and conditions in the blood vessels
Microangiopathic Red Cell Destruction/ Disseminated Intravascular Coagulation
Most common human enzyme deficiency in
the world; sex linked; highest in young RBCs
G6PD-Dehydrogenase Deficiency
Presents with lots of Heinz bodies inclusions
G6PD-Dehydrogenase Deficiency
For blacks, G6PD-Dehydrogenase Deficiency is triggered by?
primaquine
For non blacks, G6PD-Dehydrogenase Deficiency is triggered by?
ingestion of chloramphenicol, quinine, and
quinidine and the legume fava beans (Favism)
In G6PD-Dehydrogenase Deficiency, ingestion of this will cause hemolytic crisis
Legume fava beans (Favism)
Characterized by increase serum bilirubin and reticulocytes count
G6PD-Dehydrogenase Deficiency
In this condition, mature erythrocytes lack mitochondria and are exclusively dependent on anaerobic glycolysis for generation of ATP
Pyruvate Kinase Deficiency
Result is a rigid inflexible cells that are sequestered by the spleen
Pyruvate Kinase Deficiency
Shown to be resistant to malaria
Pyruvate Kinase Deficiency
Auto hemolysis is normal in this condition
Pyruvate Kinase Deficiency
In this condition, ferrous iron is converted into ferric iron instead of a normal hemoglobin, methemoglobin is present
Methemoglobin Reductase Deficiency
Methemoglobin Reductase Deficiency is also known as?
Hemoglobin M disease
A deficiency in this enzyme can result from the inheritance of an autosomal recessive traitor in conjunction with hemoglobin M disease, or as a result of exposure to toxic substances or various drugs
NADH diaphorase or Methemoglobin Reductase Deficiency
There is an impaired nucleotide metabolism, accumulation of
pyridmidine; impairs degradation of RNA;
Pyrimidine 5 nucleotide deficiency
Third most common enzyme deficiency
Glucose phosphate isomerase deficiency
In this deficiency, auto hemolysis is increased and is poorly corrected by glucose
Pyrimidine 5 nucleotide deficiency
In this deficiency, Auto hemolysis is increase and is partially corrected by glucose
Glucose phosphate isomerase deficiency
Heterozygous state for Hb S
Sickle Cell Trait (Hb AS)
This is the most common hemoglobinopathy in the United States
Sickle Cell Trait (Hb AS)
A benign condition without clinical symptoms or hematologic abnormalities
Sickle Cell Trait (Hb AS)
Glutamic acid in the sixth position on the β- chain is replaced by valine
Sickle Cell Disease
Confers protection against P. falcifarum
Sickle Cell Trait (Hb AS)
Infectious crisis is commonly due to?
streptococcus
pneumonia
It is freely soluble when fully oxygenated; when O2 is
removed, this polymerizes, with formation of tactoids (fluid
crystals) that are rigid and deforms the cell into the shape
that gave the disease its name
Hb S or Sickle Cell Disease
Primary cause of death of sickle cell disease
Infectious crisis
The complications involve in infectious crisis are?
- Vaso-occlusive crises
- Bone and joint crises
- Aplastic crises
- No Hb A
Common in African Americans
Hemoglobin SC Disease
In this disease, Patients have only Hb S and C with an
absence of Hb A and normal increased levels
of Hb F
Hemoglobin SC Disease
Anicytosis and poikilocytosis are mild to severe in?
Hemoglobin SC Disease
IDENTIFY: No Hemoglobin A present, microcytic hypochromic and splenomegaly is usually present
Hemoglobin S-Beta Thalassemia
Substitution of lysine for glutamic acid (a2 β2- glu –> lys) in the sixth position of the N- terminal end of the beta chain
Hemoglobin C
There is a presence of crystalline structures in the red cells
that appears as blocks or bars of gold
Hemoglobin C
Second most common Hemoglobin variant
worldwide
Hemoglobin E
Extremely high occurrence in individuals from
Southeast Asian countries. It resembles a thalassemia trait; there’s microcytosis, erythrocytosis but normal MCHC
& only a slight anemia
Hemoglobin E
This constitutes the most common D variant in African Americans
Hb D Los Angeles (Punjab) (B121 glu–> gln)
Most common alpha chain variant in black
people
Hb G Philadelphia ( a 68asn–> lys)
Two major types of Hereditary Persistence of Fetal Hemoglobin
(1) Pancellular and (2) heterocellular (or Swiss) HPFH
A hemoglobin analogous to the Lepore hemoglobin, which is associated with HPFH phenotype
Hb Kenya
Has less Hb F ranging from 2% to 5%
Heterocellular or Swiss Type HPFH
The Hb F is homogeneously or evenly distributed among the red cells
Pancellular HPFH
The distribution of HbF is uneven: Both F cells and erythrocytes lacking Hb F are present
Heterocellular or Swiss Type HPFH
Diagnosed based on elevated hematocrit level above the normal range
Polycythemia (Erythrocytosis)
According to WHO, what is the male and female Hgb range for polycythemia?
> 18.5 g/dL for men
16.5g/dL for women
Increase in the total red cell mass in the body
Absolute Polycythemia
The total red cell mass is normal, but the Hct is elevated because the plasma volume is decreased (usually seen in dehydration)
Relative Polycythemia
Known as apparent polycythemia or Gaisbock syndrome.
Spurious Polycythemia
The red cell mass is often high normal and the plasma volume is low normal
Spurious Polycythemia
Characterized by an increase panmyelosis, erythrocytosis, leukocytosis, and
thrombocytosis of varing degrees
Polycythemia Vera
Where all cell lines are increased
panmyelosis
A condition where there is an excessive proliferation of erythrocytes as well as other
cells lines
Polycythemia Vera
Cite the polycythemias classified under absolute polycythemia
- Secondary polycythemia with appropriately increased EPO production
- Secondary polycythemia with inappropriately increased EPO production
- Genetic polycythemia
- Primary marrow disorders (Polycythemia vera)
Cite the polycythemias classified under relative polycythemia
- Diminished plasma volume: dehydration; shock
- Spurious polycythemia (stress polycythemia; Gaisbock syndrome)
