Red Blood Cell Disorders Flashcards
Anemia
Classic presentation?
- Reduction in circulating red blood cell (RBC) mass
- Presents with signs and symptoms of hypoxia
1. Weakness, fatigue, and dyspnea
2. Pale conjunctiva and skin
3. Headache and lightheadedness
4. Angina, especially with preexisting coronary artery disease
Surrogates for RBC mass? Official definition of Anemia?
- Hemoglobin (Hb), hematocrit (Hct), and RBC count are used as surrogates for RBC mass, which is difficult to measure
- Anemia is defined as Hb < 13.5 g/dL in males and < 12.5 g/dL in females (normal
Hb is 13.5-17.5 g/dL in males and 12.5-16.0 g/dL in females).
- Anemia is defined as Hb < 13.5 g/dL in males and < 12.5 g/dL in females (normal
How are anemias classified?
- Based on mean corpuscular volume (MCV), anemia can be classified as
- microcytic (MCV < 80 cubic micrometers)
- normocytic (MCV = 80- 100)
- macrocytic (MCV > 100 um3
MICROCYTIC ANEMIAS
Cause?
Anemia with MCV < 80um3
Microcytic anemias are due to decreased production of hemoglobin.
- RBC progenitor cells in the bone marrow are large and normally divide multiple times to produce smaller mature cells (MCV = 80- 100)
- Microcytosis is due to an “extra” division which occurs to maintain hemoglobin concentration.
Hemoglobin is made of heme and globin; heme is composed of iron and protoporphyrin. A decrease in any of these components leads to microcytic anemia.
Types of microcytic anemias?
- Thalassemia
- Anemia of CD
- Iron deficiency anemia
- Lead
- Sideroblastic
What is the most common type of anemia? What causes this type?
IRON DEFICIENCY ANEMIA
A. Due to decreased levels of iron -> decreased heme -> decreased Hb -> microcytic anemia
Lack of iron is the most common nutritional deficiency in the world, affecting roughly 1/3 of world’s population.
How is iron obtained?
Describe absorption and transport of Fe.
Iron is consumed in heme (meat-derived) and non-heme (vegetable-derived) forms.
$ 1. Absorption occurs in the duodenum. Enterocytes have heme and non-heme (DMT1) transporters; the heme form is more readily absorbed.
2. Enterocytes transport iron across the cell membrane into blood via ferroportin.
3. Transferrin transports iron in the blood and delivers it to liver and bone marrow
macrophages for storage.
4. Stored intraccllular iron is bound to ferritin, which prevents iron from forming free radicals via the Fenton reaction.
Serum iron
measure of iron in the blood
Total iron-binding capacity (TIBC)
measure of transferrin molecules in the blood
%saturation
percentage of transferrin molecules that are bound by iron (normal is 33%)
Serum ferritin
reflects iron stores in macrophages and the liver
What causes iron deficiency?
Iron deficiency is usually caused by dietary lack or blood loss.
- Infants-breast-feeding (human milk is low in iron)
- Children- poor diet
- Adults (20-50 years)-peplic ulcer disease in males and menorrhagia or pregnancy in females
- Elderly- colon polyps/carcinoma in the Western world; hookworm (Ancylostoma duodenale and Necator americanus) in the developing world
- Other causes include malnutrition, malabsorption, and gastrectomy (acid aids iron absorption by maintaining the Fe2+ state, which is more readily absorbed than Fe3’+).
Stages of iron deficiency
- Storage iron is depleted- ↓ ferritin; ↑TIBC
- Serum iron is depleted- ↓ serum iron; ↓ %saturation
- Normocytic anemia-Bone marrow makes fewer, but normal-sized, RBCs.
- Microcytic, hypochromic anemia-Bone marrow makes smaller and fewer RBCs.
Clinical features of iron deficiency
anemia, koilonychia, and pica.
Laboratory findings in IDA
- Microcytic, hypochromic RBCs with ↑ red cell distribution width
- ↓ ferritin; ↑ TIBC; ↓ serum iron; ↓ % saturation
$ 3. ↑ Free erythrocyte protoporphyrin (FEP)
Plummer~Vinson syndrome
iron deficiency anemia with esophageal web and
atrophic glossitis; presents with anemia, dysphagia, and beefy-red tongue
ACD
Anemia associated with chronic inflammation (e.g., endocarditis or autoimmune conditions) or cancer; most common type of anemia in hospitalized patients
Mechanism of ACD?
Chronic disease results in production of acute phase reactants from the liver,
including hepcidin.
l. Hepcidin sequesters iron in storage sites by (1) limiting iron transfer from macrophages to erythroid precursors and (2) suppressing erythropoietin (EPO) production; aim is to prevent bacteria from accessing iron, which is necessary for their survival.
Reduced available iron = reduced heme = reduced Hb = microcytic anemia
Lab findings in ACD
- ↑ ferritin, ↓ TlBC, ↓ serum iron, and ↓% saturation
- ↑ Free erythrocyte protoporphyrin (EEP)
SIDEROBLASTlC ANEMIA
Anemia due to defective protoporphyrin synthesis
Low protoporphoryn, can’t make heme, can’t make Hb, microcytic anemia
Lab findings in sideroblastic anemia?
- ↑ ferritin
- ↓ TIBC
- ↑ serum iron
- ↑ % saturation
- (iron-overloaded state) Same labs as in hemochromatosis
How is protoporphyrin synthesized?
I. Aminolevulinic acid synthetase (ALAS) converts succinyl CoA to levulinic acid (ALA) using vitamin B6 as a cofactor (rate-limiting step).
- Aminolevulinic acid dehydrogenase (ALAD) converts ALA to porphobilinogen.
- Additional reactions convert porphobilinogen to protoporphyrin.
- Ferrochelatase attaches protoporphyrin to iron to make heme (final reaction; occurs in the mitochondria).
What is the consequence of deficient protoporphyrin?
Iron is transferred to erythroid precursors and enters the mitochondria to form heme. If protoporphyrin is deficient, iron remains trapped in mitochondria.
- Iron-laden mitochondria form a ring around the nucleus of erythroid precursors; these cells are called ringed sideroblasts (hence, the term sideroblastic anemia,
What are the 2 types of sieroblastic anemia?
Congenital or acquired
$ Most common congenital defect leading to a sideroblastic anemia?
$ Congenital defect most commonly involves ALAS (rate-limiting enzyme).
Acquired causes of sideroblastic anemia?
- Alcoholism-mitochondrial poison
- Lead poisoning-inhibits ALAD (can’ make protoporphyrin) and ferrochelatase (can’t link protoporphyrin)
- Vitamin B6 deficiency-required cofactor for ALAS; most commonly seen as a side effect of isoniazid treatment for tuberculosis
THALASSEMIA
Why did this evolve over time?
How are thalassemias divided?
Anemia due to decreased synthesis of the globin chains of hemoglobin
low globin = low Hb = microcytic
Inherited mutation; carriers are protected against Plasmodium Falciparum malaria.
Divided into a- and beta-thalassemia based on decreased production of alpha or beta globin chains.
What is the usual cause of alpha thalassemia?
$ a-Thalassemia is usually due to gene deletion; normally, 4 alpha genes are present on chromosome 16.
- One gene deleted-asymptomatic
- Two genes deleted- mild anemia with increased RBC count; cis deletion is associated with an increased risk of severe thalassemia in offspring.
i. Cis deletion is when both deletions occur on the same chromosome; seen in Asians
ii. Trans deletion is when one deletion occurs on each chromosome; seen in Africans, including African Americans - Three genes deleted- severe anemia; ~chains form tetramers (HbH) that
damage RBCs; HbH is seen on electrophoresis. - Four genes deleted- lethal in utero (hydrops fetalis); y chains form tetramers
(Hb Barts) that damage RBCs; Hb Barts is seen on electrophoresis.
Usual cause of beta thalassemia?
gene mutations (point mutations in promoter or
splicing sites); seen in individuals of African and Mediterranean descent
Two beta genes are present on chromosome 11; mutations result in absent (beta-0 ) or diminished (beta+) production of thebeta-globin chain.
Beta-thal minor
- Mild form, asymptomatic usually with increased RBC count
- Microcytic hypochromic RBCs and target cells
- Hb electrophoresis shows increased Hb2 about 5% instead of 2.5%, slight increase in HbF
Beta-thal major
- Severe Massive erythroid hyperplasia with expansion of hematopoiesis into skull - crewcut appearance, facial bones,
- extramedullary heatopoiesis with hepatosplenomegaly,
- risk of aplastic crisis with parvovirus B19 infection
- Little or NO HbA!
MACROCYTIC ANEMIA
- Anemia with MCV > 100
- most commonly due to folate or vitamin B12
- deficiency (megaloblastic anemia)
- Folate and vitamin 812 are necessary for synthesis of DNA precursors.
- Lack of folate or vitamin Bl2 impairs synthesis of DNA precursors.
- Other causes of macrocytic anemia (without megaloblastic change) include
alcoholism, liver disease, and drugs (e.g., 5-FU).
Where is dietary folate absorbed?
How long does it take to develop a deficiency?
What causes folate deficiency?
Dietary folate is obtained from green vegetables and some fruits.
Absorbed in the jejunum
B. Folate deficiency develops within months, as body stores are minimal.
C. Causes include poor diet (e.g., alcoholics and elderly), increased demand (e.g., pregnancy, cancer, and hemolytic anemia), and folate antagonists (e.g., methotrexate, which inhibits dihydrofolate reductase).
Clinical findings in folate deficiency?
- 1.. Macrocytic RBCs and hypersegmented neutrophils (> 5 lobes)
- Glossitis
- ↓ serum folate
- ↑ serum homocysteine (increases risk for thrombosis)
- Normal methylmalonic acid
Explain how B12 is obtained
Dietary vitamin Bl2 is complexed to animal-derived proteins.
1. Salivary gland en:qmes (e.g., amylase) liberate vitamin Bl2, which is then bound
by R-binder (also from the salivary gland) and carried through the stomach.
2. Pancreatic proteases in the duodenum detach vitamin Bl2 from R-binder.
3. Vitamin B12 binds intrinsic factor (made by gastric parietal cells) in the small
bowel; the intrinsic factor-vitamin B12 complex is absorbed in the ileum.
Most common cause of B12 deficiency?
- Pernicious anemia is the most common cause of vitamin B12 deficiency.
- Autoimmune destruction of parietal cells (body of stomach) leads to intrinsic factor deficiency
- Other causes of vitamin Bl2 deficiency include pancreatic insufficiency and damage to the terminal ileum (e.g., Crohn disease or Diphyllobothrium latum [fish tapeworm]); dietary deficiency is rare, except in vegans.
Clinical findings in B12 deficiency?
Mechanism?
- Macrocytic RBCs with hypersegmented neutrophils
- Glossitis
* *$ 3. Subacute combined degeneration of the spinal cord**
- i. Vitamin Bl2 is a cofactor for the conversion of methylmalonic acid to succinyl CoA (important in fatty acid metabolism).
- ii. Vitamin Bl2 deficiency results in increased levels of methylmalonic acid, which impairs spinal cord myelinization.
- iii. Damage results in poor proprioception and vibratory sensation (posterior column) and spastic paresis (lateral corticospinal tract).
- ↓ serum vitamin B12
-
↑ serum homocysteine (similar to folate deficiency), which increases risk for thrombosis
* *$ 6. ↑ methylmalonic acid (unlike folate deficiency)**
What causes normocytic anemia?
A. Anemia with normal-sized RBCs (MCV = 80- 100 j.tm3)
B. Due to increased peripheral destruction or underproduction
Reticulocyte count helps to distinguish between these two etiologies.
RETICULOCYTES
Young RBCs released from the bone marrow
- Identified on blood smear as larger cells with bluish cytoplasm (due to residual RNA,
Normal reticulocyte count (RC) is 1-2%.
1. RBC lifespan is 120 days; each day roughly 1-2% of RBCs are removed from circulation and replaced by reticulocytes.
How does a properly functioning marow respond to anemia?
A properly functioning marrow responds to anemia by increasing the RC to >3%.
**$ How do you correct the RC? **
What is a good or bad response?
$ RC is corrected by multiplying reticulocyte count by Hct/45.
- Corrected count > 3% indicates good marrow response and suggests peripheral destruction.
- Corrected count < 3% indicates poor marrow response and suggests underproduction.
PERIPHERAL RBC DESTRUCTION (HEMOLYSIS)
How do we classify these?
Divided into extravascular and intravascular hemolysis; both result in anemia with a good marrow response.
Extravascular hemolysis involves RBC destruction by the reticuloendothelial system (macrophages of the spleen, liver, and lymph nodes).
Intravascular hemolysis involves destruction of RBCs within vessels.
Describe the mechanism of extravascular hemolysis.
Macrophages consume RBCs and break down hemoglobin.
i. Globin is broken down into amino acids.
ii. Heme is broken down into iron and protoporphyrin; iron is recycled.
iii. Protoporphyrin is broken down into unconjugated bilirubin, which is bound
to serum albumin and delivered to the liver for conjugation and excretion into bile.
Clinical findings in extravascular hemolysis?
- Anemia with splenomegaly, jaundice due to unconjugated bilirubin, and increased risk for bilirubin gallstones
- Marrow hyperplasia with corrected reticulocyte count > 3%
Clinical findings in intravascular hemolysis?
Intravascular hemolysis involves destruction of RBCs within vessels.
1. Clinical and laboratory findings include:
i. Hemoglobinemia -Hb leaks into blood
ii. Hemoglobinuria - Hb leaks into urine
$iii. Hemosiderinuria-**Renal tubular cells pick up some of the hemoglobin that is filtered into the urine and break it down into iron, which accumulates as hemosiderin; tubular cells are eventually shed resulting in hemosiderinuria. **
iv. Decreased serum haptoglobin - FIRST CHANGE that tells us there is intravascular hemolysis (haptoglobin binds free Hb in blood and takes it to the spleen)
NORMOCYTIC ANEMIAS WITH PREDOMINANT
EXTRAVASCULAR HEMOLYSIS
- HEREDITARY SPHEROCYTOSIS
- SICKLE CELL ANEMIA
- HEMOGLOBIN C
HEREDITARY SPHEROCYTOSIS
Inherited defect of RBC cytoskeleton-membrane tethering proteins 1. Most commonly involves spectrin, ankyrin, or band 3.1
Membrane blebs are formed and lost over time.
- Loss of membrane renders cells round (spherocytes) instead of disc-shaped.
- Spherocytes are less able to maneuver through splenic sinusoids and are consumed by splenic macrophages, resulting in anemia.
Clinical findings in Hereditary spherocytosis?
- Spherocytes with loss of central pallor
- ↑ RDW and ↑ mean corpuscular hemoglobin concentration (MCHC)
- Splenomegaly, jaundice with unconjugated bilirubin, and increased risk for bilirubin gallstones (extravascular hemolysis)
$ 4. ↑ risk for aplastic crisis with parvovirus B19 infection of erythroid precursors
SICKLE CELL ANEMIA
Autosomal recessive mutation in p chain of hemoglobin; a single amino acid change replaces normal glutamic acid (hydrophilic) with valine (hydrophobic).
What is the effect of sickling on RBCs in SCA?
Complications related to RBC membrane damage as sickle and de-sickle while passing through microcirculation.
- Extravascular hemolysis-Reticuloendothelial system removes RBCs with damaged membranes, leading to anemia, jaundice with unconjugated hyperbilirubinemia, and increased risk for bilirubin gallstones.
- Intravascular hemolysis-RBCs with damaged membranes dehydrate, leading to hemolysis with decreased haptoglobin and target cells on blood smear.
- Massive erythroid hyperplasia ensues resulting in
i. Expansion of hematopoiesis into the skull (‘crewcut’ appearance on x-ray)
and facial bones (‘chipmunk facies’)
ii. Extramedullary hematopoiesis with hepatomegaly
iii. Risk of aplastic crisis with parvovirus B19 infec tion of erythroid precursors
$$$ What complications does irreversible sickling lead to?
Irreversible sickling leads to complications of vaso-occlusion.
$ 1. Dactylitis- swollen hands and feet due to vase-occlusive infarcts in bones; common presenting sign in infants
2. Autosplenectomy-shrunken, fibrotic spleen. Consequences include
$ i. Increased risk of infection with encapsulated organisms such as Streptococcus
$ pneumoniae and _Haemophilus influenzae (most common cause of death in
children);_ affected children should be vaccinated by 5 years of age.
$ii. Increased risk of Salmonella paratyphi osteomyelitis
iii. Howell-Jolly bodies on blood smear
$ 3. Acute chest syndrome-vaso-occlusion in pulmonary microcirculation
i. Presents with chest pain, shortness of breath, and lung infiltrates
ii. Often precipitated by pneumonia
* *$ iii. Most common cause of death in adult patients**
4. Pain crisis
5. Renal papillary necrosis-results in gross hematuria and proteinuria
Sickle cell trait manifestations?
Sickle cell trait is the presence of one mutated and one normal beta chain; results in < 50% HbS in RBCs (HbA is slightly more efficiently produced than HbS)
l. Generally asymptomatic with no anemia; RBCs with <50% HbS do not sickle in vivo except in the renal medulla.
i. Extreme hypoxia and hypertonicity of the medulla cause sickling, which results in microinfarctions leading to microscopic hematuria and, eventually,
* *$ decreased ability to concentrate urine**.
Lab findings in SCA
Disease vs Trait?
- Sickle cells and target cells are seen on blood smear in sickle cell disease, but not in sickle cell trait.
- Metabisulfite screen causes cells with any amount of HbS to sickle; positive in both disease and trait
- Hb electrophoresis confirms the presence and amount of HbS.
Disease -90% HbS, 8% HbF, 2% HbA2 (no HbA)
Trait- 55% HbA, 43% HbS, 2% HbA2
HEMOGLOBIN C
A. Autosomal recessive mutation in beta chain of hemoglobin
1. Normal glutamic acid is replaced by lysine.
2. Less common than sickle cell disease
B. Presents with mild anemia due to extravascular hemolysis
C. Characteristic HbC crystals are seen in RBCs on blood smear
NORMOCYTIC ANEMIAS WITH PREDOMINANT
INTRAVASCULAR HEMOLYSIS
- PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
- GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY
- IMMUNE HEMOLYTIC ANEMIA (IHA)
- MICROANGIOPATHIC HEMOLYTIC ANEMIA
- MALARIA
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
Acquired defect in myeloid stem cells resulting in absent
glycosylphosphatidylinositol (GPI); renders cells susceptible to destruction by complement
- Blood cells coexist with complement.
2. Decay accelerating factor (DAF) on the surface of blood cells protects against complement-mediated damage by inhibiting C3 convertase.
3. DAF is secured to the cell membrane by GPI (an anchoring protein).
4. Absence of GPI leads to absence of DAF, rendering cells susceptible to complement-mediated damage.*
- Blood cells coexist with complement.
What type of hemolysis occurs in PNH?
Intravascular hemolysis occurs episodically, often at night during sleep.
- Mild respiratory acidosis develops with shallow breathing during sleep and activates complement.
- RBCs, WBCs, and platelets are lysed.
- Intravascular hemolysis leads to hemoglobinemia and hemoglobinuria (especially in the morning); hemosiderinuria is seen days after hemolysis.
What test is used to screen for PNH?
Sucrose test is used to screen for disease; confirmatory test is the acidified serum test or flow cytometry to detect lack of CD55 (DAF) on blood cells.
$ Main cause of death in PNH?
$$$ Main cause of death in PNH is thrombosis of the hepatic, portal, or cerebral veins -* Destroyed platelets release cytoplasmic contents into circulation, inducing
thrombosis.*
$ Complications of PNH?
$$$ Complications include
- iron deficiency anemia (due to chronic loss of hemoglobin in the urine) and
- acute myeloid leukemia (AML), which develops in 10% of patients.
$ Blood count in PNH?
$ RBCs, WBCs, and platelets are lysed b/c all lack the GPI linker molecule
GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY
X-linked recessive disorder resulting in reduced half-life of G6PD; renders cells susceptible to oxidative stress
- REduced G6PD = Reduced NADPH = Reduced glutathione = oxidative injury by hydrogen peroxide = intravascular hemolysis
- African and Mediterranean variant
Which variant of G6PD is worse?
G6PD deficiency has two major variants.
- African variant-mildly reduced half-life ofG6PD leading to mild intravascular hemolysis with oxidative stress
- Mediterranean variant-markedly reduced half-life of G6PD leading to marked intravascular hemolysis with oxidative st ress
- High carrier frequency in both populations is likely due to protective role against falciparum malaria.
What does oxidative stress (in G6PD) do to RBCs?
Oxidative stress precipitates Hb as Heinz bodies.
- Causes of oxidative stress include infections, drugs (e.g., primaquine, sulfa drugs, and dapsone), and fava beans.
- Heinz bodies are removed from RBCs by splenic macrophages, resulting in bite cells
- Leads to predominantly intravascular hemolysis
How does G6PD deficiency present?
Presents with hemoglobinuria and back pain (Hb is nephrotoxic) hours after exposure to oxidative stress
Whatis the test used to screen for G6PD?
Heinz preparation is used to screen for disease (precipitated hemoglobin can only be seen with a special Heinz stain, Fig. 5.12); enzyme studies confirm deficiency (performed weeks after hemolytic episode resolves).
IMMUNE HEMOLYTIC ANEMIA (IHA)
- Antibody-mediated (IgG or IgM) destruction of RBCs
- IgG-mediated disease usually involves extravascular hemolysis.
- IgG binds R BCs in the relatively warm temperature of the central body (warm
agglutinin) ; membrane of antibody-coated RBC is consumed by splenic macrophages, resulting in spherocytes.
Most common cause of IHA?
Rx?
Associated with SLE (most common cause), CLL, and certain drugs (classically, penicillin and cephalosporins)
i. Drug may attach to RBC membrane (e.g., penicillin) with subsequent binding of antibody to drug-membrane complex
ii. Drug may induce production of autoantibodies (e.g., a-methyldopa) that bind self antigens on RBCs
Treatment involves cessation of the offending drug, steroids, IVIG, and, if necessary, splenectomy.
What type of hemolysis is seen in IgM mediated disease causing IHA
$ What are the 2 major associations with IgM mediated IHA?
IgM-mediated disease usually involves intravascular hemolysis.
- IgM binds RBCs and fixes complement in the relatively cold temperature of the extremities (cold agglutinin).
- $ 2. Associated with Mycoplasma pneumoniae and infectious mononucleosis
What test is used to diagnose IHA?
Coombs test is used to diagnose IHA; testing can be direct or indirect.
- Direct Coombs test confirms the presence of antibody-coated RBCs. Anti-IgG is added to patient RBCs; agglutination occurs ifRBCs are already coated with
antibody. This is the most important test for IHA. - Indirect Coombs test confirms the presence of antibodies in patient serum. AntiIgG
and test RBCs are mixed with the patient serum; agglutination occurs if
serum antibodies are present.
MICROANGIOPATHIC HEMOLYTIC ANEMIA
- Intravascular hemolysis that results from vascular pathology; RBCs are destroyed as they pass through the circulation. Iron deficiency anemia occurs with chronic hemolysis.
- Occurs with microthrombi (TTP-HUS, DIC, HELLP), prosthetic heart valves, and
aortic stenosis; microthrombi produce schistocytes on blood smear
MALARIA
A. Infection of RBCs and liver with Plasmodium transmitted by the femaleAnopheles mosquito
B. RBCs rupture as a part of the Plasmodium life cycle, resulting in intravascular
hemolysis and cyclical fever.
1. P falciparum-daily fever
2. P vivax and P ovale-fever every other day
C. Spleen also consumes some infected RBCs; results in mild extravascular hemolysis
with splenomegaly
ANEMIA DUE TO UNDERPRODUCTION
- PARVOVIRUS Bl9
- APLASTIC ANEMIA
- MYELOPHTHISIC PROCESS
Basic principles of ANEMIA DUE TO UNDERPRODUCTION
A. Decreased production of RBCs by bone marrow; characterized by low corrected reticulocyte count
B. Etiologies include
- Causes of microcytic and macrocytic anemia
- Renal failure-decreased production ofEPO by peritubular interstitial cells
- Damage to bone marrow precursor cells (may result in anemia or pancytopenia)
PARVOVIRUS Bl9
A. Infects progenitor red cells and temporarily halts erythropoiesis; leads to significant anemia in the setting of preexisting marrow stress (e.g., sickle cell anemia).
B. Treatment is supportive (infection is self-limited). Usually resolves in 7-10 days
APLASTIC ANEMIA
- Damage to hematopoietic stem cells, resulting in pancytopenia (anemia, thrombocytopenia, and leukopenia) with low reticulocyte count
- Etiologies include drugs or chemicals, viral infections, and autoimmune damage.
- Biopsy reveals an empty, fatty marrow
Treatment of Aplastic anemia?
Treatment includes cessation of any causative drugs and supportive care with transfusions and marrow-stimulating factors (e.g., erythropoietin, GM-CSF, and
G-CSF).
1. Immunosuppression may be helpful as some idiopathic cases are due to
abnormal T-cell activation with release of cytokines.
- May require bone marrow transplantation as a last resort
What is a MYELOPHTHISIC PROCESS?
- Pathologic process (e.g., metastatic cancer) that replaces bone marrow; hematopoiesis is impaired, resulting in pancytopenia.
- Anemia due to underproduction
Where is EPO synthesized?
interstitial cells in
peritubular capillary bed
Polyehromasia
divide original correction by 2
Most common site for EMH
Extramedullary hematopoiesis (EMH)
• RBC WBC, anil platelet production that occurs outside the hone marrow
1. Common sites of EMH are the liver and spleen.
Couiponents of a CBC
- Hemoglobin Hb), Hct, RBC count
- RBC indices, RBC distribution width (RDW)
- WBC count with a differential count, platelet count
- Evaluation of the peripheral blood morphology
Where is ferritin synthesized?
synthesized
in bone marrow
macrophages
most common anemia in malignancy, alcohol excess
Anemia of chronic disease (ACD)
Hepcidin
- antimicrobial peptide synthesized/ released by liver
- Prevents the release of iron to transferrin
Most common cause of a sideroblastic anemia?
- Chronic alcoholism (most common cause)
- occurs in -30% of hospitalized chronic alcoholics
Aplastic anemia symptoms
Lab findings
- Fever due to infection associated with neutropenia
- Bleeding due to thrombocytopenia
- Fatigue due to anemia
- Laboratory findings
a. Pancytopenia
b. Retiulocytopenia
e. Hypocellular bone marrow
black, calcium bilirubinate gallstones
Hereditary spherocytosis
Jaundice due to increased unconjugated bilirubin
Increased incidence of calcium bilirubinate gallstones
Due to increased concentration of conjugated bilirubin in bile
Target cells
excess RBC membrane; sign of hemoglobinopathy or alcohol excess
Drugs that cause G6PD
primaquine, dapsone, sulfonamides
