RBC disorders part 2 Flashcards
*Hypercellular Bone Marrow
*Presence of megaloblast
*Ineffective erythropoiesis
*Active intramedullary hemolysis
Macrocytic anemia
Unimpaired DNA synthesis
Non-megaloblastic (macrocytic) anemia
How do you examine patients with non-megaloblastic, macrocytic anemia from those with megaloblastic anemia?
- Patients with non-megaloblastic, macrocytic anemia lack hypersegmented neutrophils and;
- oval macrocytes in the peripheral blood and;
- megaloblasts in the bone marrow
characteristics of a megaloblast
- Progenitor cell
- finely stippled lacey nuclear chromatin pattern
Megaloblastic anemia has two (2) major division:
- Vitamin b12 (cobalamin, Cbl) deficiency
- Folic acid deficiency
key features of Megaloblastic Anemia
- Diminished capacity of DNA synthesis
- Manifest macro-ovalocytes and giant hypersegmented neutrophils - - Increase MCV
How does megaloblastic anemia develops?
Deficiency of vitamin B12 or folates —> Impaired DNA synthesis —> Slows down nuclear replication —> prolonged premitotic interval —> resulting large nucleus for megaloblasts
This refers to decrease amount of cells in all cell lines i.e. WBC, RBC, platelets)
- Pancytopenia
M:E ratio for MA?
M:E ratio - 10:1
Cells found in the bone marrow of a patient with megaloblastic anemia
megaloblasts
Illeum: _____________
_____________: Liver, storage
Castle’s factor : ____________
_____________: Plasma
Transcobalamin : __________
Absorption
Adenosylcobalamin
Intrinsic factor
Methylcobalamin
Transporter
VItamin B12 is otherwise known as?
cyanocobalamin
Causes for Vitamin B12 deficiency
- D. latum infection
- Pernicious anemia
- Malabsorption syndrome
- Nutritional deficiency
- Hypochlorhydria
What condition is associated decrease production of hydrochloric acid in the stomach
Hypochlorhydria
(often seen in pernicious anemia)
*Addison’s anemia
*Caused by failure of the gastric mucosa to secrete intrinsic factor
Pernicious Anemia
other term for pernicious anemia
atrophy gastritis
which condition is an autoimmune disease caused by two antibodies— anti- parietal cell antibodies
- anti-intrinsic factor antibodies.
Pernicious anemia
An autosomally recessive inherited defect in the intestinal absorption of cobalamin that occurs in the presence of normal intrinsic factor
Immerslund-Grasbeck Syndrome
*Ability of the patient to absorb an oral dose of radioactive cobalamin
*Considered as the reference procedure for the determination of pernicious anemia
Schilling’s Test
Microbiological assay which utilizes the organism called Euglena gracilis
Serum Cobalamin Assay
Both increase in megaloblastic anemia
Methylmalonic Acid & Homocysteine Assays
Measures the ability of the marrow cells in vitro to utilize the deoxyuridine in DNA synthesis
Deoxyuridine suppression test
if Vitamin B12 is absorbed within the ileum, where does Folate being absorbed?
Jejunum
Causes for Folate deficiency
- Chronic alcoholics
- Poor dietary habits
- Pregnancy
- Steatorrhea
Name the three (3) diagnostic tests for folate deficiency
- Microbiological assays
- Serum folate (<3 ug/L)
- Red cell folate
“shift reticulocytes” especiallly in response to acute blood loss, hemolysis, and bone marrow infiltration
Non-megaloblastic anemia
what cell is seen in folic acid deficiency, Vitamin B12 deficiency, and pernicious anemia
Oval macrocyte
Seen in alcoholism, hypothyroidism and liver disease
Round hypochromic macrocyte
*Seen in neonate response to anemic stress, response to anemic stress
*Reticulocyte stain with supravital stain
Blue-tinged macrocyte
Associated with marrow replacement by involvement with abnormal cells or tissue components
Myelophthisic anemia
*Bone marrow does not produce any blood cells
*Pancytopenia
*Macrocytosis
*Increase RDW
*Chloramphenicol
Aplastic anemia
is a medication that is commonly can cause aplastic anemia
Chloramphenicol
*Inherited Aplastic Anemia
*Autosomal recessive *Normochromatic and may be macrocytic
* ncreased levels of Hb F and i antigen
*Pancytopenia
Fanconi’s syndrome
*Parvovirus B19 infection
*Presence of scattered giant pronormoblasts in the bone marrow
Transient Aplastic Crises
*Congenital Red Cell Aplasia
*Macrocytic, reticulocyte level is low
*Hb F is elevated, antigen i is often present
Diamond’s Blackfan Aplasia
Blood is lost over a short time in amounts sufficient to cause anemia
Acute Posthemorrhagic Anemia
*Blood is lost in small amounts over an extended period
*Iron deficiency anemia
Chronic Posthemorrhagic Anemia
*Defect of RBC itself
*Membrane, metabolic, and hemoglobin defects
Intrinsic hemolytic anemia
*Due to a factor of the RBC and acting upon it
*Acquired
Extrinsic hemolytic anemia
*Increased hemolysis is also an increased in ________?
LDH
This test is used to determine whether it is immune- mediated or not
Antiglobulin test
Most red cell destruction about 80-90% is presumed to be ____________
Extravascular
Intravascular : __________
Liver & spleen : _________
Activation of igG & IgM : _________
Cell mediated phagocytosis (IgM and IgG coated cells) : _________
- Blood
- Extravascular
- Intravascular
- Extravascular
*Most common prevalent hereditary hemolytic anemia among people of Northern European descent
*Deficiency of the key membrane protein: spectrin
Hereditary Spherocytosis
increased osmotic fragility
Hereditary Spherocytosis
Spherocytes are hyperpermeable to ________ which causes osmotic fragility
Sodium
*Horizontal defect
*deficiency in the proteins commonly associated with the ALPHA & BETA-spectrin regions.
Hereditary Elliptocytosis
*Red cell fragments at 45°C to 46 °C
*50 to 75 fL MCV
Hereditary Pyropoikilocytosis
*Melanesian and Malaysian populations
*Well-defined band 3 molecular deletion
*Increased resistance to malaria
South Asian Ovalocytes
There is red cell dehydration due to loss of cations, predominantly K+ and water
Hereditary Stomatocytosis
*Increased surface-to-volume ratio leading to moderate to severe anemia
*Decrease osmotic fragility, and high MCHC
Hereditary Xerocytosis
Gene suppression or the present of a silent Rh gene
Rh null disease
What RBC membrane defects can be associated with Rh null disease?
stomatocytes and spherocytes
This form of acanthocyte-associated hemolytic anemia is seen in patients with established alcoholic cirrhosis
Spur Cell Hemolytic Anemia
*Decay Accelerating Factor deficiency
*Intravascular hemolysis
*Intermittent (paroxysmal) sleep associated (nocturnal) blood in the urine (hemoglobinuria)
Paroxysmal Nocturnal Hemoglobinuria
*A rare hemolytic anemia caused by anti-P
*Also called Donath Landsteiner antibody with anti-P specificity
Paroxysmal COld Hemoglobinuria
*Disseminated Intravascular Coagulation
*March Anemia
Microangiopathic Hemolytic Anemia
*Most common human enzyme deficiency in the world; sex linked; highest in young RBCs
*Presents with lots of Heinz bodies inclusions
Glucose-6-phosphate-dehydrogenase (G6PD)
*Mature erythrocytes lack mitochondria and are exclusively dependent on anaerobic glycolysis for generation of ATP
*has been shown to be resistant to malaria
Pyruvate kinase deficiency
medication that only blacks are affected
primaquine
Most common human enzyme deficiency in the world; sex linked; highest in young RBCs
G6PD
*Increase methemoglobin
*Hemoglobin M disease
*Cyanosis because the methemoglobin cannot carry oxygen to the tissues
Methemoglobin reductase deficiency
*There is an impaired nucleotide metabolism, accumulation of pyrimidine; impairs degradation of RNA;
Pyrimidine 5 nucleotide deficiency
*Third most common enzyme deficiency
*Autohemolysis is increase and is partially corrected by glucose
Glucose phosphate isomerase deficiency
*Heterozygous state for Hb S
*most common hemoglobinopathy in the United States
*a benign condition without clinical symptoms or hematologic abnormalities
Sickle Cell trait (Hemoglobin AS)
Confers protection against P. falcifarum
Sickle Cell trait (Hemoglobin AS)
*glutamic acid in the sixth position on the β- chain is replaced by valine
*Hb S
Sickle Cell disease
*Common in African Americans
* Anicytosis and poikilocytosis are mild to severe
*Target cells (85% of the erythrocytes)
Hemoglobin SC disease
*No Hemoglobin A present
*Microcytic hypochromic
*Splenomegaly is usually present
Hemoglobin S-Beta thalassemia
Presence of crystalline factors in the red cells that appears as blocks or bars of gold
Hemoglobin C disease
*Second most common Hemoglobin variant worldwide
*Extremely high occurrence in individuals from southeast Asian countries
Hemoglobin E disease
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)
which hemoglobin is analogous to the Lepore hemoglobin which is associated with HPFH phenotype?
Hb Kenya
The distribution of Hb F is uneven (heterocellular): Both F cells and erythrocytes lacking Hb F are present
Heterocellular or Swiss type HPFH
Hb F is homogeneously or evenly distributed among the red cells
Pancellular
*Diagnosed based on elevated hematocrit level above the normal range
*Hgb > 18.5 g/dL for men, > 16.5 g/dL for women (WHO)
Polycythemia (Erythrocytosis)
*Apparent polycythemia, Gaisbock syndrome
*The red cell mass is often high normal and the plasma volume is low normal
Spurious Polycythemia
increase in the total red cell mass in the body
Absolute
the total red cell mass is normal, but the Hct is elevated because the plasma volume is decreased usually seen in dehydration
Relative
Condition where there is an excessive proliferation of erythrocytes as well as other cells lines (panmyelosis)
Polycythemia Vera
