RBC DISORDER 3 Flashcards
Diseases in Normocytic Normochromic RBC
- Acute Blood Loss
- Hemolytic Anemia
- LOW MCV
- Low MCH
- low MCHC
- found in Iron Deficiency Anemia and Thalassemias
Microcytic Hypochromic
- high MCV
- high or normal MCH
- normal MCHC
- Found in megalosblastic anemia
Macrocytic Normochromic
- low MCV
- low MCH
- normal MCHC
- found in anemia of chronic inflammation
Microcytic Normochromic
- defect in spectrin, ankyrin, protein 4.2
- defect spectrin α and β chain, protein4.1
- Spectrin deficiency
Hereditary Spherocytosis- defect in spectrin, ankyrin, protein 4.2
Hereditary Elliptocytosis-defect spectrin α and β chain, protein4.1
Hereditary Poikilocytosis- Spectrin deficiency
- CBC- red cell mass hematocrit
- Bone marrow
- Normoblastic hyperplasia
- Peripheral blood smear
- Normocytic and normochromic
- Reticulocytes- usually after 7 days
- Polychromatophilia
- macrocytes
- Serum
- increased Erythropoietin
Acute Blood Loss
»Anemia =
»Neutropenia = < 500 cells/cumm
»Thrombocytopenia = < 20,000/cumm
» Reticulocyte count = < 1 %
APLASTIC ANEMIA: Pancytopenia
Bone Marrow – hypocellular – “dry tap” – Iron stores decreased • Serum iron concentration increased • LAP score increased • Very high plasma and urine erythropoietin • Normal RDW
Aplastic Anemia
- Pancytopenia becomes obvious after infancy and usually significant by eight year
- increased levels of fetal hemoglobin (HB F) and i Antigen
- Congenital anomalies present:
Hyperpigmentation. malformations of extremities
Short stature microcephaly
Hypogonadism malformations of other organs
Heart and kidneys
Fanconi Anemia
- Congenital red cell aplasia
- 1 year to 6 year old
- Laboratory:
1. Severe normocytic and normochromic anemia (Sometimes slightly macrocytic)
2. WBC – normal or slightly decreased
3. Bone marrow – Red cell aplasia
– Normal granulocytic and megakaryocytic cell line
4. Hemoglobin F increased (5 to 25%)
5. Increased red cell adenosine deaminase (ADA)
Diamond-Blackfan Anemia
- low serum iron
- high TIBC
- low % sat
- low ferritin
- low bone marrow iron
Iron deficiency anemia
- low serum iron
- normal or TIBC
- normal or low % sat
- normal or high ferritin
- normal or high bone marrow iron
Anemia of hronic Disease
- high serum iron
- low TIBC
- high % sat
- high ferritin
- high bone marrow iron
Sideroblastic anemia
- normal or low serum iron
- normal or high TIBC
- normal or high % sat
- nromal or high ferritin
- normal or high bone marrow iron
Thalassemia
- Group of disorders characterized by iron loading and its accumulation in the mitochondria in the erythroid precursors due to a defect in heme synthesis
- May occur as a result of decreased activity of the enzyme ALA synthetase
Sideroblastic Anemia
Sideroblastic Anemia Classification
- Clinical Picture: X –linked recessive trait; Males
- Iron Parameters: Marked increased in serum Iron; Increased transferrin% sat
- Red Cells: Severe anemia: Normocytic, normpchromic or Microcytic, hypochromic
- WBCs & Platelets: Normal count and morphology
- BOne Marrow: Marked increased Iron;10 – 40% Ringed sideroblasts
Hereditary
Sideroblastic Anemia Classification
- Clinical Picture: More common; Adults > 50yo
- Red Cells: Moderate anemia; normocytic to slightly microcytic
- WBCs & Platelets: Normal count and morphology
- BOne Marrow: Increased ringed sideroblasts
Primary Idiopathic
Sideroblastic Anemia Classification
- Clinical Picture: In association with other diseases
Secondary
- accumulation of iron in the macrophages, with less parenchymal injury
- accumulation of iron in the parenchymal cells, with tissue injury
- Hemosiderosis
- Hemochromatosis
- Rare autosomal recessive trait; caused by certain variants in the HFE gene
- In middle aged men
- Laboratory:
- Iron derangement:
- Increased serum iron
- Slightly decreased transferring
- Increased transferring saturation
- Hemoglobin, Hematocrit and peripheral smear are normal
- Bone marrow:
- Macrophages with stainable iron particles
- Absorption of iron is increased
Hereditary Hemochromatosis
• Impaired DNA synthesis
• Types
1. Vitamin B12 deficiency
* Pernicious Anemia
* Imerslund’s Syndrome
2. Folic acid deficiencyMEGALOBLASTIC ANEMIA
Mechanisms:
I. Inadequate Intake
- Extremely rare
- Seen in persons who completely abstain from animal food, milk and eggs.
2. Defective Production of Intrinsic factor
- Most common cause
- PERNICIOUS ANEMIA
Cobalamin (Vitamin B12) Deficiency
- Pathological lesions of the fundus and body of the stomach
- gastric mucosal atrophy
- selective loss of parietal and chief cells from the gastric mucosa
- submucosal lymphocytic infiltrates.
- Autoantibodies are directed against the a- & b-subunit of the gastric H+/K+-
ATPase, a hydrogen transporting enzyme, responsible for the acidification of the stomach lumen. - Gastrectomy
Pernicious Anemia
Pernicious Anemia
Clinical Features:
- Equally common in males and females
- Symptoms: Pallor, Jaundice, Glossitis
- Gastrointestinal - diarrhea, constipation and episodic pain
- Central nervous system - pains, numbness peripheral neuropathies, irritability etc.
- Inherited autosomal recessive trait
- Mainfest during the first 2 years of life
- Deficiency inreceptor site in the terminal ileum.
Imerslund’s Syndrome
Other Causes of Vitamin B12 Deficiency
- affects the terminal ileum
- lodges in the ileum
• Zollinger Ellison syndrome
Other Causes of Vitamin B12 Deficiency • Crohn’s Disease - affects the terminal ileum • Diphyllobotrium latum infection - lodges in the ileum • Zollinger Ellison syndrome - hypersecretion of gastric juice, results to low pH with interference in the binding og VitB12 to the intrinsic factor
– CBC- anemia, usually macrocytic and normochromic – Indices * MCV and RDW high * MCH – Normal to high * MCHC - Normal
Pancytopenia
Therapeutic trial
- Give parenteral physiologic dose of ____(10 ug/d) physiologic dose of ___ (50 to 200 ug/d)
- Optimal hematologic response means deficiency
i. ___ - Reticulocytosis starting 3rd and 4th day peaks on the 7th day
ii. ___ - Erythropoiesis becomes normoblastic by 2 days- Leukopoiesis becomes normal by 12 to 14 days
- WBC and platelet counts become normal in a week
- cobalamin
- folic acid
- PBS
- BM
- Measures ability of the marrow cells in vitro to utilize deoxyuridine for DNA synthesis
- Sensitive, produces abnormal result before anemia or macrocytosis is observed
Deoxyuridine suppression test
Folic acid coenzymes required for the conversion of FIGLU to glutamic acid in the
catabolism of histidine
- If oral histidine, FIGLU will appear in increased amount in urine
Urinary formiminoglutamic acid
Red Blood Cell Destruction
- Takes place in the reticulo-endothelial system - Liver, bone marrow, lymph nodes and circulating monocytes. Account for 90% of red cell destruction
- Destruction of severely damaged blood cells normally occurs intravascularly. Account for 10% of RBC destruction
- Extravascular
- Intravascular
Those anemia which result from premature and excessive destruction of red cells either within the blood vessels or outside it.
Hemolytic Anemia
Classification of Hemolytic Anemia
ACUTE VS CHRONIC
- Rapid onset
- Isolated, episodic or paroxysmic
- Hemolysis either disappears or subsides between episodes
- Examples
> Paroxysmal cold hemoglobinuria
> Paroxysmal nocturnal hemoglobinuria
> Hemolytic Transfusion reactionAcute
Classification of Hemolytic Anemia
ACUTE VS CHRONIC
- RBC life span is chronically shortened
- Categories:
1. Bone Marrow maybe able to compensate -> anemia may not be evident.
2. Bone Marrow cannot generate RBC fast enough -> anemia
- Examples
> Thalassemia
> Hemoglobinopathies
> Glucose 6-Phosphate DehydrogenaseChronic
Classification of Hemolytic Anemia
INHERITED VS ACQUIRED
- Develop in individuals who were previously hematologically normal but acquired condition that lyses RBCs
- Examples
> Infectious disease (Malaria)
> PNHACQUIRED
Classification of Hemolytic Anemia
INHERITED VS ACQUIRED
- Passed of to offspring by mutant genes from parents
- Examples
> Thalassemias
> HemoglobinopathiesINHERITED
Classification of Hemolytic Anemia
EXTRINSIC (Extracorpuscular) vs INTRINSIC (Intracorposcular)
- Develop in individuals who were previously hematologically normal but acquired condition that lyses RBCs
1. Membrane defect
> Hereditary Spherocytosis
> Hereditary Elliptocytosis
> Hereditary Poikilocytosis
2. Enzyme deficiency
> Glucsoe-6-Phosphate Dehydrogenase (Hexose Monophosphate Shunt)
> Pyruvate Kinase (Embden Myerhof)
3. Globin Abnormalities
> Hemoglobinopathies -
4. Acquired Membrane Abnormality
> PNHEXTRINSIC (Extracorpuscular)
Classification of Hemolytic Anemia
EXTRINSIC (Extracorpuscular) vs INTRINSIC (Intracorposcular)
- Conditions that arise from outside the RBCs
- substances in the plasma
ex. Infectious agents – Malarial, sepsis
Chemical agents – Toxins & Drugs
Circulating antibodies
- conditions affecting the anatomy of the vascular system
ex. Mechanical
- Microangiopathic
- Traumatic uremic syndrome
- Prosthetic valves
Physical agents - Burns
Blood lossEXTRINSIC (Extracorpuscular)
Classification of Hemolytic Anemia
EXTRAVASCULAR VS INTRAVASCULAR
- RBCs are engulfed by the macrophage and lyzed by their digestive system
EXTRAVASCULAR
Classification of Hemolytic Anemia
EXTRAVASCULAR VS INTRAVASCULAR
- Destruction of severely damaged blood cell occurs in the blood stream
and can Lyze by fragmentation in the spleen and bone marrow
1. Inherited:
> Membrane abnormalities
> Enzyme deficiencies
> Globin abnormalities
2. Acquired Membrane
> Abnormality – PNHINTRAVASCULAR
- acquired clonal stem cell disorder
-characterized by production of abnormal erythrocytes, granulocytes and megakaryocytes
-Red cell defect render them more susceptible to complement-mediated chronic intravascular hemolysis - Bout of hemolysis could be initiated by
> Infection
> surgery
> Whole blood transfusion
> injection of contrast dyes
> severe exercise
Paroxysmal Nocturnal Hemoglobinuria (Marchiafava-Micheli Syndrome)
Paroxysmal Nocturnal Hemoglobinuria (Marchiafava-Micheli Syndrome)
Laboratory:
- hemoglobinuria
- Hemosidinuria
- Blood: Pancytopenia
> Normocytic anemia
> Neutropenia (3/5ths of cases)
> Thrombocytopenia (2/3rds of cases)- With or without
- always present
- is common
Detects deficiencies in the pentose phosphate pathway: Glucose-6-Phosphate
Dehydrogenase deficiency
> Glutathione reductase
> Glutathione peroxidase
Ascorbate Cyanide Screening Test
• Result from RBC destruction due to RBC autoantibodies: Ig G, M,
E, A
• Most commonly-idiopathic
• Classification
– Warm Autoimmune haemolysis:Ab binds at 37degree Celsius
– Cold Autoimmune haemolysis: Ab binds at 4 degree Celsius
Autoimmune Hemolytic Anemia
- Usually IgG
- Idiopathic
- Secondary causes
- SLE, CLL,lymphomas,Drugs(e.g.Methyldopa)
INVESTIGATION
– Hemolysis, MCV
– P Smear: Microspherocytosis, n-RBC
– Confirmation: Coomb’s Test / Antiglobulin test
Warm Autoimmune hemolysis
• Usually IgM
• Infections
Mycoplasm pneumonia,infectiousmononucleosis lymphoma
proxysmal cold haemoglobinuria
INVESTIGATION
• Periphral Smear:
- Microspherocytosis
- Ig M with specificity to I or I Ag
Cold Autoimmune Hemolysis
- Induced by red cell antigens
- Haemolytic transfusion reactions
- haemolytic disease of the new born
- post stem cell grafts
- Drug induced
- Drug-red cell membrane complex
- immune complex
Alloimmune
