HEMA Flashcards
1
Q
normochromic ,normocytic ,or macrocytic and are characterized by a low reticulocytecount
A
Hypoproliferative anemia
2
Q
Pancytopenia with Hypocellular Bone Marrow
A
– Acquired aplastic anemia
– Constitutional aplastic anemia Some myelodysplasia
– Rare aleukemic leukemia
– Some lymphomas of bone marrow
3
Q
Pancytopenia with Cellular Bone Marrow
PRIMARY BONE DISEASE
A
Myelodysplasia PNH Myelofibrosis Myelophthisis Bone Marrow Lymphoma Hairy Cell Leukemia
4
Q
Pancytopenia with Cellular Bone Marrow
SECONDARY CAUSES
A
SLE Alcohol intake Cobalamin deficiency Hypersplenism Overwhelming Infection
5
Q
Acquired o Chemical Exposure, Radiation, Viral Infection, Immune Mediated Disorders, Paroxysmal Nocturnal hemoglobinuria, Pregnancy – Idiopathic – Hereditary o Fanconi’s Anemia o Dyskeratosis Congenita o Shwachman-Diamond syndrome
A
APLASTIC ANEMIA
6
Q
notorious cause of bone marrow failure
A
Chemicals- Benzene
7
Q
is the most common preceding infection, and posthepatitis marrow failure accounts for approximately 5% of etiologies in most series
A
Hepatitis infection
8
Q
A major consequence and the inevitable cause of death in transfusion-associated graft-versus-host disease (GVHD)
A
Immunologic
9
Q
Symptomatic anemia and Hemorrhage.
– Presence of infection
– Discovered serendipitously at preoperative evaluation, blood donation, or from screening tests
A
APLASTIC ANEMIA
10
Q
Acquired Aplastic Anemia MECHANISMS
A
- Direct toxicity to hematopoietic multipotential cells (HSCs)
- A defect in the stromal microenvironment of the marrow required for hematopoietic cell development
- Impaired production or release of essential multilineage hematopoietic growth factors
- Cellular or humoral immune suppression of the marrow multipotential cells
- Progressive erosion of chromosome telomeres.
11
Q
DIAGNOSTICS FOR APLASTIC ANEMIA
A
– Findings of Pancytopenia – An elevated mean corpuscular volume is frequent in aplastic anemia at presentation. – Bone Marrow Biopsy o The “empty” marrow on histology o Erythroid islands
12
Q
Fever or documented infection occuring in the presence of severe neutropenia (<500/uL IS TREATED WITH
A
Broad spectrum parenteral antibiotic.
13
Q
__________is preferred when feasible as it is curative.
_________ is most commonly used as first therapy in the United States and worldwide
A
Hematopoietic Stem Cell Transplantation (HSCT)
Immunosupressive Treatment (IST)
14
Q
Immunossuppressive therapy (IST) COMPONENTS
A
Standard initial IST is horse Anti Thymocyte Globulin (ATG) and Cycolsporine (CsA),
15
Q
APLASTIC ANEMIA DUE TO CONSTITUTIONAL DISORDERS
A
- FANCONIS ANEMIA
- DYSKERATOSIS CONGENITA
- SHWACHMAN-DIAMOND SYNDROME
16
Q
an autosomal recessive disorder, progressive pancytopenia, and an increased risk of malignancy.
– Typically have short stature, cafe au lait spots, and anomalies involving the thumb, radius, and genitourinary tract.
A
FANCONIS ANEMIA
17
Q
An aplastic anemia of childhood due to mutations in genes of the telomere repair complex due to mutations in the DKC1 (dyskerin) gene; – Triad of : o Mucous membrane leukoplasia o Dystrophic nails o Reticular hyperpigmentation
A
DYSKERATOSIS CONGENITA
18
Q
Presents early in life with neutropenia, pancreatic insufficiency and malabsorption.
– Most patients have compound heterozygous mutations in SBDS that may affect both ribosomal biogenesis and marrow stroma function
A
SHWACHMAN-DIAMOND SYNDROME
19
Q
characterized by anemia, reticulocytopenia, and absent or rare erythroid precursor cells in the bone marrow, associated with immune system diseases.
A
PURE RED CELL APLASIA
20
Q
ETIOLOGY OF PURE RED CELL APLASIA
A
ETIOLOGY
– Thymoma.
– Large Granular Lymphocytosis (LGL) or complicate chronic lymphocytic leukemia (CLL).
– Strongly associated with the 5th disease caused by B19 Parvovirus Infection.
– Subcutaneous administration of erythropoietin (EPO) has provoked PRCA mediated by neutralizing antibodies.
21
Q
TX OF PRCA
A
Intravenous Immunoglobulin (IVIg) – Corticosteroids – Cyclosporine with ATG – Azathioprine – Cyclophosphamide
22
Q
Cytopenias due to bone marrow failure
o High risk of development of acute myeloid leukemia
o is a disease of the elderly; the mean age at onset is older than 70 years with a slight male preponderance
A
MYELODYSPLASIA (MDS)
23
Q
A group of clonal bone marrow stem cell disorders, presenting with hypercellular marrow, peripheral cytopenias, and cell functional abnormalities due to Ineffective Hematopoiesis
A
MYELODYSPLASIA (MDS)
24
Q
Dysplasia in ≥10% of cells from a single myeloid lineage <5% marrow blasts, <1% blood blasts, and noAuer rods , <15% of erythroid precursors are ring sideroblasts.
A
Refractory cytopenia with unilineage dysplasia (RCUD)
25
o Isolated erythroid dysplasia <5% marrow blasts, <1% blood blasts, and no Auer rods, ≥15% of erythroid precursors are ring sideroblasts
Refractory anemia with ring sideroblasts (RARS)
26
5Q31 deletion as the sole chromosomal abnormality and is associated with increased megakaryocytes
Myelodysplastic syndromes (MDS) associated with isolated del (5Q)
27
Dysplasia in ≥10% of cells from two or more myeloid lineages <5% marrow blasts, <1% blood blasts, and no Auer rods, Blood monocyte count <1 × 109/L
Refractory cytopenia with multilineage dysplasia (RCMD)
28
Type 1: 5–9% marrow blasts, <5% blood blasts, and no Auer rods
o Type 2: 10–19% marrow blasts, 5–19% blood blasts, or Auer rods Blood monocyte count <1 × 109/L
Refractory anemia with excess blasts (RAEB
29
Minimal dysplasia the presence of a clonal cytogenetic lesion considered presumptive evidence of MDS
Unclassifiable MDS (MDS-U)
30
ETIOLOGY OF MDS
```
Acquired:
o Senescence
o Mutagen/Genotoxic Stress
Therapeutic
alkylators, Topo-II agents,
B-emitters (32P), autoSCT
Environmental/occupational (benzene)
Tobacco
o Aplastic anemia
o PNH
– Heritable:
o Constitutional genetic disorders
Trisomy 8 mosaicism
Familial monosomy 7
o Neurofibromatosis 1
o Embryonal dysgenesis (dEL12p)
o Congenital Neutropenia
Kostmann, Schwachman-Diamond DNA repair deficiencies
Fanconi anemia, AT, Bloom syndrome
o Pharmacogenomic polymorphisms (GSTq1-null)
```
31
DIAGNOSTIC CRITERIA OF MDS
Presence of one or more otherwise unexplained cytopenias
o Hemoglobin <11 g/dL
o Absolute neutrophil count <1500/μL
o Platelet count <100,000/μL
– >10% dysplastic cells in erythroid, myeloid, and/or megakaryocyte lineages
– 5 to 19% marrow blasts
– Evidence of a cytogenetic abnormality typical for MDS
– Presence of one or more myelodysplastic syndrome (MDS) decisive criteria
32
TX OF MDS
```
CHEMOTHERAPEUTIC AGENTS
– Azacitadine
– Decitabine
– Lenalidomide (del 5Q)
– Cytarabine
– Immunosuppressive Agents
– EPO
– Supportive transfusion with iron Chelation
```
33
Fibrosis of the bone marrow usually accompanied by a characteristic blood smear picture called ____________, can occur as a primary hematologic disease, called ____________
MYELOPHTHISIC MARROW
leukoerythroblastosis
myelofibrosis or myeloid metaplasia
34
ETIOLOGY OF..
Fibrosis can be a response to invading tumor cells, usually an epithelial cancer of breast, lung, or prostate origin or neuroblastoma.
– Infection of mycobacteria, fungi, or HIV and in sarcoidosis.
MYELOPHTHISIC MARROW
35
The pathophysiology has three distinct features
– Proliferation of fibroblasts in the marrow space (myelofibrosis)
– Extension of hematopoiesis into the long bones and into extramedullary sites, usually the spleen, liver, and lymph nodes (myeloid metaplasia)
– Ineffective erythropoiesis.
MYELOPHTHISIC MARROW
36
CHRONIC INFLAMMATION
– Inflammatory cytokine
release (IL-6) triggers
release of _____
Hepcidin regulates iron
absorption and release
depriving effective
37
Progressive CKD is usually associated with a moderate to severe hypoproliferative anemia
– The level of the anemia correlates with the stage of CKD.
– The anemia is primarily due to a failure of EPO production by the diseased kidney and a reduction in red cell survival
– Patients with the anemia of CKD usually present with normal serum iron, TIBC, and ferritin levels.
– However, those maintained on chronic hemodialysis may develop iron deficiency from blood loss through the dialysis procedure.
ANEMIA OF RENAL DISEASE
38
The heme moiety binds O2, providing the means to circulate O2 from the lungs to tissues.
– The active site of electron transport in cytochromes and cytochrome oxygenase, essential coenzymes in the Krebs cycle.
HYPOCHROMIC, MICROCYTIC ANEMIA
39
It is the most prevalent form of malnutrition globally
IRON DEFICIENCY ANEMIA (IDA)
40
SX OF IDA
Cheilosis
| – Koilonychia
41
LAB FREATURE OF IDA
```
Red cell indices:
o Low Hb conc.
o MCV, MCH, MCHC ↓
– Blood film:
Hypochromic microcytic
o Pencil shaped poikilocytes
o Occasional Target cells.
o Reactive Thromocytosis
```
42
most convenient test to estimate Iron Stores
Serum Ferritin:
43
indirect measurement of
| bound/unbound transferrin
– Total iron binding capacity:
44
STAGES OF IDA
Demands for( or losses of) Iron exceed the body’s ability to
absorb Iron from the diet
– Blood loss in excess of 10-20mL exceeds the absorbed from diet
Negative Iron Balance
45
Hemoglobin synthesis becomes decreased once the transferrin
saturations falls to 15 to 20%
– Microcytes
Iron Deficient Erythropoiesis
46
Hemoglobin and Hematocrit begin to fall
– The transferrin saturation at his point is 10-15%
o Hypoproliferation
Iron Deficiency Anemia
47
DIFFERENTIALS
| OF IDA
INFLAMMATION
THALASSEMIA
SIDEROBLASTIC ANEMIA
48
TX OF IDA
```
Oral Iron preparations
– Parenteral Iron preparation
– Transfusion
Diet
– 3 ounce of serving of steak provides only about 3 mg of iron.
– 10 pounds of steak
Correct the Anemia
o Replenish Stores (0.5g to 1g)
o 6 to 12 months
```
Reticulocyte count increases by 4th to 7th day
– Hgb should increase halfway to a point between starting and
normal levels in an average of 18 days
– At 3 weeks, Hgb should have risen 5.9 +/- 17% toward Normal
– Iron tolerance test: Serum Iron determination done after 2
hours from intake of two Iron Tablets
49
Absence of Response TO IDA
```
Incorrect diagnosis of iron deficiency
– Blood loss greater than Hgb regeneration (in which case retics
should rise even if hgb does not)
– Inadequate prescription
– Noncompliance with therapy
– Iron malabsorption
– Superimposed infection, inflammation, malignancy or uremia
(Epo deficiency)
– Lead poisoning
– Concomitant folate or B12 deficiency
```
50
Indications for Parenteral TherapY OF IDA
Unable to tolerate iron compounds orally
– Poor compliance
– Persistent loss of blood or iron at a rate too rapid for oral
intake to compensate for the loss
– Disorder of GI tract e.g. ulcerative colitis
– Malabsorption of iron
– Inability of maintain iron balance during treatment with
hemodialysis
– Donating large amounts of blood for auto transfusion
51
Amount of Iron needed formula
– Body weight x 2.3 x (1.5 – Patients Hgb g/dL)
| – + (500 or 1000mg)
52
is reserved for individuals who have
symptoms of anemia, cardiovascular instability, continued and
excessive blood loss from whatever source, and require
immediate intervention
transfusion
53
Inherited disorders of global biosynthesis causing ABNORMAL
supply of global
– Diminishes production of hemoglobin tetramers, causing
hypochromia and microcytosis
THALASSEMIA
54
pathogenesis of thalassemia
Thalassemia most common genetic disorder in the world
– Inherited Autosomal Codominant Trait
– Deranged splicing of the mRNA precursor
– Premature termination of mRNA translation
55
```
sx of what disease
Jaundice
– Skull and other bones may be deformed
– Cortical bone thinning
– Hepatomegaly
– Bilirubin stones
– Splenomegaly
– Endocrine dysfunction
```
thalassemia
56
Laboratory Features of thalassemia
| –
CBC
– Peripheral blood smear
– Hgb Electrophoresis and column chromatography
57
Peripheral Blood Smear of Thalassemia
Marked anisopoikilocytosis
– Hypochroomia
– Target cell formation (codocytes)
– Basophilic Stippling
58
– A test to evaluate for and identify variant and abnormal
hemoglobins.
– Alkaline and/or citrate agar electrophoresis is the commonly
used method.
– Separation of hemoglobins is based on variable rates of
migration of charged hemoglobin molecules in an electrical
field
Hgb Electrophoresis
59
Abnormal accumulation alpha chains causing formation of toxic
inclusions (Hemolytic Anemia).
o Erythroid Hyperplasia
o Extramedullary Hematopoietic Tissues
B THALASSEMIA
60
```
– Severe Homozygous
– Childhood, growth delay
– Severe anemia,Hepatosplenomegaly
– Requires transfusion
– Iron Overload
Hgb Electrophoresis
o Absent Hb A
o Increased Hb F
o Increased Hb A
```
Beta thalassemia major
61
```
Similar stigmata like major
– Survive without transfusion
– Moderate anemia, microcytosis, hypochromia
– Hb Electrophoresis
o HbF- 20-100%
o HbA2- 3.5%-5.5%
o HbA- 0.30%
```
Beta thalassemia intermedia
62
```
Profound microcytosis, target cells
– Minimal anemia
– Similar bld picture of iron def anemia
– Lab inv:
o MCV<75,Hct <30-33%
o Hb electr: HbA2-3.5-7.5%, HbA-80-95%, HbF-1-5%
```
Beta thalassemia minor
63
Thalassemia Syndromes
o Deletion of one a globin loci
o Asymptomatic Carrier
a thal 2 trait (- a / a a)
64
```
Thalassemia Syndromes
o Cis (-a/-a)
o Trans (--/aa)
```
a thal 1 trait
65
```
Thalassemia Syndromes
o Offspring of a thal 1 and 2 trait
o Decrease of Hgb A 25-30%
o Increase in Hgb B chain
o Mod to severe hemolytic anemia
```
HbH (--/-a)
66
```
Thalassemia Syndromes
o Hgb Bart’s
o Accumulation of Gamma Globin
o High O2 Affinity deprives the fetus with Oxygen
o Hydrops Fetalis
```
Homozygous State a thal cis deletion (--/--)
67
The primary goal of _____ is to
prevent the accumulation of iron reaching harmful
levels
o Commences by the time the serum ferritin level
reaches approximately 1000 mcg/dL.
o Careful monitoring of the degree of iron
accumulation during chelation therapy is absolutely
vital.
o a regular estimation of the serum ferritin level, which
should be maintained at less than 1500 mcg/L
Iron Chelation
68
SC administration: 1-2g (20-40mg/kg/day) SC over 8-24 hours
– IV administration in patients with IV access: 40-50mg/kg/day
over 8-12 hours for 5-7 days/ week (maximum of <
60mg/kg/day and an IV infusion rate of <15mg/kg/hr)
– IM administration: 0.5-1g QD (Maximum of 1g QD)
Deferoxamine
69
25-33 mg/kg PO TID (ie, total daily dosage range 75-99
mg/kg/day)
– Monitor serum ferritin concentration every 2-3 months to
assess the effects on body iron stores
– If the serum ferritin falls consistently <500 mcg/L, consider
temporarily interrupting therapy
Deferipone
70
20-30 mg/kg taken orally by dissolving in water
– Metabolized in the liver
– Iron is excreted via the gut
Deferasirox
71
Point mutation of 17th nucleotide in on chromosome 11 (β-globin gene) thymine to adenine
– 6th amino acid on the B-chains to glutamic acid → Valine
– Point mutation responsible for the distortion of normal RBCs
into sickle-shaped RBCs.
SICKLE CELL ANEMIA (SCA)
72
Most Common Presentation SCA
Acute Painful Crisis
73
The onset of chest pain, a temperature higher than 38.5°C,
tachypnea, wheezing, or cough.
– New or progressive pulmonary infiltrate in a patient with sickle
cell disease.
o Admit and treat
Acute Chest Syndrome
74
Clinical Consequences of Sickle Disease
```
Vaso-occlusion (pain)
– Stroke
– Proliferative retinopathy
– Acute Chest Syndrome/Pulmonary Hypertension
– Gallstones
– Splenic sequestration/infarcts/hyposplenism
– Renal insufficiency
– Avascularnecrosis
– Spontaneous pregnancy loss
– Priapism
– Osteonecrosis
– Non-healing skin ulcer
```
75
dx of sca
```
Clinical Presentation
– Hemoglobin electrophoresis
o HbS >80%
o HbF -1-20%
o HbA2 -2- 4.5%
– Hemolysis
– Sickle Cells (Drepanocytes)
```
76
tx of sca
```
Supportive care
o Hydration
o O2 supplementation
o Transfusion (especially for Acute Chest Syndrome)
o Pain Control (Aggressive Analgesia)
o Treat the underlying cause
– HYDROXYUREA
o 10-30 mg/kg
o Increases HbF
o Decrease Reticulocyte Count and Granulocytes.
– Azacytidine
– Bone Marrow Transplant
```
77
Transfusion in Sickle Cell
– Simple transfusion – give blood
– Partial exchange transfusion - remove blood and give blood
– Erythrocytapheresis – use apheresis to maximize blood exchange
78
```
Symptoms associated with anemia
– Jaundice
– Hemoglobinuria (Tea Colored Urine)
– Organomegaly
o Splenomegaly
o Hepatomegaly
```
HEMOLYTIC ANEMIA
79
```
LABORATORY FEATURES
– CBC
o Hgb → Normal to Reduced
o MCV and MCH → Increased
– Reticulocyte Count → Increased
– Bilirubin levels → Increased
– LDH level → Increased
– Haptoglobulin level → decreased
```
hemolytic anemia
80
– Predominantly warm type IgG
– May be part of an underlying condition
– Direct Antiblobulin Test (DAT)→ Coombs test
– May also present with thrombocytopenia (Evan’s) Syndrome
– Prednisone 1mg/kg
– Rituximab, Cyclosporine
AUTOIMMUNE HEMOLYTIC ANEMIA
81
o Occurs after a viral infection
| o Donath Landsteiner Anitbody
Paroxysmal Cold Hemoglobinuria
82
o Antibodies that are active in Temp less than 370C
o Mostly IgM antibodies
o Associated with lymphoproliferative disorders or monoclonal B cell expansion
o Immunosuppresives not very effective as in AIHA
Cold Agglutinin Disease
83
is a rare, clonal hematopoietic stem cell disorder that manifests with a hemolytic anemia from uncontrolled complement activation, propensity for thrombosis formation and the is associated syndrome of bone marrow failure.
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
84
TREATMENT OF PNH
– Bone Marrow Transplant
o the only curative therapy
o associated with significant morbidity and mortality
85
```
Hypercellular Marrow
– Ineffective Erythropoiesis
– Macrocytosis (Increase in MCV)
– Cobalamin and Folate Deficencies
– DNA synthesis abnormalities
```
MEGALOBLASTIC ANEMIA
86
Parent compound of a large family of natural folate compounds that are water soluble.
o They are partly or completely reduced to di- or tetrahydrofolate (THF) derivatives.
o They usually contain a single carbon unit.
o 70–90% of natural folates are folatepolyglutamates.
folates
87
```
CLINICAL FEATURES
– Symptoms related to anemia.
– Anorexia and Weight Loss.
– Diarrhea or Constipation.
– Glossitis or Angular Cheilosis.
– Mild fever in more severely anemic patients.
– Jaundice (unconjugated).
– Reversible Melanin skin hyperpigmentation.
– Increase susceptibility to infection
```
megaloblastic anemia
88
OTHER TISSUES AFFECTED
– Epithelial Surface
o the next most frequently affected tissues
o Mouth, Stomach, Small Intestine
o Respiratory, Urinary, and Female Genital Tracts
o Macrocytosis and Multinucleated dying cells
– Pregnancy
o Prematurity
o Neural Tube Defects
– Cardiovascular
o Increase Homocysteine level
o Cerebrovascular, Peripheral vascular, Coronary Heart Disease and Deep Vein Thrombosis.
– Malignancy
o Increases Risk for malignancy in newborn
– Neurologic Manifestations
o Peripheral neuropathy and Cerebral symptoms.
o Optic Atrophy or Visual Impairment.
o Paresthesias, muscle weakness, or difficulty in walking
o Psychotic Disturbances, sometimes dementia
megaloblastic anemia
89
CAUSES OF COBALAMIN DEFICIENCY
```
– Diet → Vegan
– Pernicious Anemia
o Decrease in Intrinsfic Factor
– Gastrectomy
– Ileal Resection
– Tropical Spure
– Fish Tapeworm Manifestation
– Zollinger Ellison Syndrome
```
90
CAUSES OF FOLATE DEFICIENCY
```
– Nutritional
– Malabsoprtion
– Excess utilization
o Pregnancy
o Prematurity
o Hematologic Disorders
o Inflammation
– Antifolate Drugs
o Methotrexate
```
91
LABORATORY FINDINGS of MA
```
– Blood cell count
o macrocytic anemia ( MCV>100fl )
o thrombocytopenia (<40x109/L)
o Leucopenia (>1.5 × 109/L)
o low reticulocyte count
– Blood smear
o Macroovalocytosis
o Hypersegmentation
```
