QUANTITATIVE RED CELL DISORDERS PART II Flashcards
- are macrocytic anemias in which DNA is unimpaired
- lack hypersegmented neutrophils and oval macrocytes in the peripheral blood and megaloblasts in the bone marrow
Macrocytic nonmegaloblastic anemias
Normocytic normochromic anemia
Bone marrow failure
cells have increased expression of Fas receptors that mediate apoptosis and increased expression of apoptosis- related genes
CD34+ aplastic anemia
-elevated blood and bone marrow cytotoxic T cells with an oligoclonal expansion of specific T-cell clones
- increased T cell production of such cytokines as interferon-Ξ³ and tumor necrosis factor-Ξ±
- upregulation of T-bet
- increased TNF-Ξ± receptors on CD34+ cells
- improvement in cytopenias after immunosuppressive therapy
Autoimmune pathophysiology: Acquired Aplastic Anemia
Symptoms:
- insidious-onset anemia with pallor, fatigue, and weakness
- tachycardia, hypotension, cardiac failure, death
- petechiae, bruising, epistaxis, mucosal bleeding, menorrhagia, retinal hemorrhages, intestinal bleeding, intracranial hemorrhage
- fever and bacterial/fungal infections
APLASTIC ANEMIA
decreased neutrophils, monocytes, and platelets
APLASTIC ANEMIA
RBCs are macrocytic or normocytic
APLASTIC ANEMIA
- toxic granulation in neutrophils may be observed
- serum iron level and percent transferrin saturation are increased
- erythroid, granulocytic, and megakaryocytic cells are decreased/ab
APLASTIC ANEMIA
present at an earlier age and may have characteristic physical stigmata
Inherited Aplastic Anemia
- is a chromosome instability disorder characterized by aplastic anemia, physical abnormalities, and cancer susceptibility
Fanconi Anemia
skeletal abnormalities (thumb malformations, radila hypoplasia, microcephaly, hip dislocation, scoliosis)
Fanconi Anemia
- skin pigmentation (hyper-/hypopigmentation, cafe-au-lait lesions)
- short stature, abnormalities of the eyes, kidneys, and genitals
- low birth weight and developmental delay
Fanconi Anemia
-characterized by mucocutaneous abnormalities, bone marrow failure, and pancytopenia
- triad of abnormal skin pigmentation, dystrophic nails, and oral leukoplakia
Dyskeratosis Congenita
Multisystem abnormalities: pulmonary fibrosis, liver disease, developmental delay, short stature, microcephaly, prematurely gray hair or hair loss, immunodeficiency dental carries, periodontal disease
Dyskeratosis Congenita
an inherited multisystem disorder characterized by pancreatic insufficiency, cytopenia, skeletal abnormalities, and a predisposition for hematologic malignancies
Shwachman-Bodian-Diamond Syndrome
3 types of Inherited Aplastic Anemia
- Fanconi Anemia
- Dyskeratosis Congenita
- Shwachman-Bodian-Diamond Syndrome
- a rare disorder of erythropoiesis characterized by a selective decrease in erythrocyte precursors in an otherwise normal bone marrow
PURE RED CELL APLASIA
Acquired Pure Red Cell Aplasia:
Transient Erythroblastopenia of Childhood
Take note
the acquired form of PRCA in young children
Transient Erythroblastopenia of Childhood
Diamond-Blackfan Anemia
Congenital Pure Red Cell Aplasia:
- a congenital erythroid hypoplastic disorder of early infancy
- approximately half of patients have: physical anomalies (craniofacial dysmorphisms, short stature, neck and thumb malformations)
Diamond-Blackfan Anemia
- are a heterogeneous group of rare disorders characterized by refractory anemia, reticulocytopenia, hypercellular bone marrow with markedly ineffective erythropoiesis, distinctive dysplastic changes in bone marrow erythroblasts
CONGENITAL DYSERYTHROPOIETIC ANEMIA
is due to the infiltration of abnormal cells into the bone marrow and subsequent destruction and replacement of
normal hematopoietic cells
MYELOPHTHISIC ANEMIA
- common complication of CKD is anemia
- burr cells are common peripheral blood film findings
1ANEMIA OF CHRONIC KIDNEY DISEASE
- Inadequate renal production of EPO
- Uremia
- Hemodialysis and frequent blood draws
- Chronic inflammation and a restricted diet
ANEMIA OF CHRONIC KIDNEY DISEASE
results when the rate of RBC destruction exceeds the increased rate of RBC production
HEMOLYTIC ANEMIA
has a rapid onset and is isolated (sudden), episodic, or paroxysmal
Acute hemolysis
may not be evident if the bone marrow is able to compensate, but it may be punctuated over
time with hemolytic crises that cause the anemia
Chronic hemolysis HEMOLYTIC ANEMIA
are passed to offspring by mutant genes from the parents
Inherited HEMOLYTIC ANEMIA
develop in individuals who were previously hematologically normal but acquire an agent of condition that lyses RBCs
Acquired HEMOLYTIC ANEMIA
destruction of the RBCs due to a defect within the RBCs themselves
Intrinsic hemolytic conditions
- arise from outside the RBC, typically substances in the plasma or conditions affecting the anatomy of the circulatory system
Extrinsic hemolytic conditions
takes place most often within the bloodstream; occurs by fragmentation
Intravascular hemolysis -
can refer either to lysis within the macrophage and not in the bloodstream or to the fact
that most of the macrophages are in tissues
Extravascular hemolysis
occurs when RBCs are engulfed by macrophages and lysed by their digestive enzymes
Macrophage-mediated
Mechanisms to salvage hemoglobin iron and prevent oxidation reactions during fragmentation hemolysis:
- Haptoglobin
- Hemopexin
- Albumin
Clinical features:
- fatigue, dyspnea, dizziness
- signs of pallor and tachycardia
- jaundice
- splenomegaly, gallstones
- bone deformities in children
HEMOLYTIC ANEMIA
IN SERUM π©Έ
Total bilirubin = INCREASED
Indirect bilirubin = INCREASED
Direct bilirubin = WRI
LDH = INCREASED
Haptoglobin = DECREASED
Free hemoglobin = INCREASED
Hemopexin = DECREASED
Fragmentation hemolysis and Macrophage- mediated hemolysis
Plasma Color. Coffee-brown
Fragmentation hemolysis
Urine
Urobilinogen = INCREASED
Free hemoglobin (+)
Methemoglobin (+)
Prussian blue staining of urine sediment (+)
Urine color = Root beer/beer-colored
Fragmentation hemolysis
Urine
Urobilinogen = INCREASED
Free hemoglobin (-)
Methemoglobin (-)
Prussian blue staining of urine sediment (-)
Urine color
Macrophage- mediated hemolysis
Anticoagulated whole blood
Hgb,Hct,RBC count DECREASED
Schistocytes POSITIVE
Spherocytes NEGATIVE
Glycated hemoglobin DECREASED
Fragmentation hemolysis
Anticoagulated whole blood
Hgb,Hct,RBC count DECREASED
Schistocytes NEGATIVE
Spherocytes POSITIVE
Glycated hemoglobin DECREASED
Macrophage- mediated hemolysis
SPECIAL TESTSπ§ͺ
Endogenous carbon monoxide INCREASED
Erythrocyte llife span DECREASED
Fragmentation hemolysis
Macrophage- mediated hemolysis
- caused by the defects in proteins that disrupt the vertical interactions between transmembrane proteins and the underlying protein cytoskeleton
- results from gene mutation
HEREDITARY SPHEROCYTOSIS
the defects in vertical membrane protein interactions cause RBCs to lose unsupported lipid membrane over time because of local disconnections of the lipid bilayer and underlying cytoskeleton
HEREDITARY SPHEROCYTOSIS
Symptoms:
Three key clinical manifestations:
anemia, jaundice, splenomegaly
HEREDITARY SPHEROCYTOSIS
Laboratory findings:
Hallmark: spherocytes on the peripheral blood film
- increased MCHC hyperchromia
- decreased serum haptoglobin
- increased serum indirect bilirubin and lactate dehydrogenase
HEREDITARY SPHEROCYTOSIS
- demonstrates increased RBC fragility in blood specimens in which the RBCs have decreased surface area-to-volume ratios
- cells with decreased surface area:volume ratio have limited capacity to expand in hypotonic solutions, hence undergo lysis
Osmotic fragility HEREDITARY SPHEROCYTOSIS
Anticoagulant: Osmotic fragility
Heparin
EMA is a fluorescent dye that binds to transmembrane proteins band 3, Rh, RhAg, and CD47 in the RBC membrane
Eosin-5β-maleimide (EMA) binding test
