L3 Anemia II Flashcards
(35 cards)
Morphological Class of Hemolytic Anemias?
Mostly NORMOCYTIC
Can be associated with MACROCYTOSIS (in cases of elevated reticulocyte count)
MICROCYTIC –Thalassemia
____________: Premature destruction of erythrocytes
Haemolysis: Premature destruction of erythrocytes
Intrinsic vs. Extrinsic Causes of Hemolytic Anemia
Intrinsic RBC Defect : Due to a defect within RBCs
➢ Red cell membrane disorders
o Hereditary spherocytosis
o Hereditary elliptocytosis
➢ Disorders of haemoglobin synthesis
o Thalassemia
o Sickle cell anaemia (HbSS)
o Haemoglobin C disease
➢ RBC enzyme deficiencies
Extrinsic RBC Defect: Healthy RBCs are produced but later destroyed
➢ Immune-mediated
o Incompatible blood transfusions
o Haemolytic disease of the newborn
o Drug-induced
➢ Non-immune
o Mechanical trauma
o Infections (e.g., malaria)
Increase in the rate of destruction of RBD => more ________produced => _________
Increase in the rate of destruction of RBD => more bilirubin produced => jaundice
Differenced between Extravascular and Intravascular Hemolysis
Extravascular
Causes: Autoimmune Hemolytic Anemia (AIHI), hereditary disorders
Spherocytes (round w/ palor at center)
Normal or low serum haptoglobin
Direct antiglobulin test (DAT) ++++ (AIHA)
No haemoglobinaemia/-uria
No methemoglobin formation
+/-Splenomegaly, +/-Hepatomegaly
Extramedullary hematopoiesis
Intravascular
CAUSES: Shear stress/mechanical damage, Autoimmune diseases, Toxins, Tumour lysis syndrome
Schistocytes (helmet shaped)
Very low/absent serum haptoglobin (RBCS damaged in vessels => haptoglobin binds free hemoglobin)
DAT usually negative
Hemoglobinemia(excess of hemoglobin in the blood plasma)
Hemoglobinuria (hemoglobin found in abnormally high concentrations in the urine)
Haemosiderinuria,methaemoglobinaemia/-uria
NO splenomegaly
+/-Acute renal tubular necrosis
Examples of Hyperproliferative and Hypoproliferative aAnemia?
HYPERproliferative Anemia:
Anemia due to Hemolysis
Anemia due to hypersplenism
Thalesmina (Microcytic)
HYPOproliferative Anemia:
Aplastic anemia (normocytic)
Iron deficiency anemia (microcytic)
Megaloblastic anemia (Folate and vitamin B12 deficiency) (macrocytic)
Pathogenesis/Manifestation/Treatment of Heredity Spherocytosis
Pathogenesis:
- Defect in ankyrin, spectrin→ spherocytes
- Extravascular haemolysis (macrophages in spleen destroy RBCs)
Manifestation
- Haemolysis→ increased bilirubin →Jaundice
- Splenomegaly
- Pigment gallstones
- Increased risk for aplastic crisis (due to parvovirus B19 infection)
- Increased red cell osmotic fragility
Treatment:
- Splenectomy
- Folic acid
Fetal vs. Adult Hemoglobin?
Foetal: Hb F (2α:2γ) → ~80% at birth is Hb F
Adult: Hb A (2α:2β) → >95% of adult Hb is Hb A
Hb A2 (2α:2δ)
Disorders of Hemoglobin synthesis involving gene defect(s) resulting in reduced production of globin chains?
α-thalassaemia (reduced α chain synthesis)
ß-thalassaemia(reduced ß chain synthesis)
α-thalassaemia is ____________ disease and can be expressed both ____________ and ____________
α-thalassaemia is ‘Dose-dependent’ disease and can be expressed both prenatally and postnatally
depending how many globin chains effected by mutaion: varies from mild to very severe disease
Globulin chains precipitated in those with Thalasseimia?
Heinz Bodies
Varies forms of α-thalassaemia?
Silent carrier: 1 gene lost (-α/αα). No symptoms, normal lab
α-thalassaemia trait: 2 genes lost (–/ααor -α/-α). Similar to β-thalassaemia minor
Hb H disease: 3 genes lost. Severe as β-thalassemia intermedia
- Increased Hb H (β4) →Heinz bodies
- Hb H has high O2affinity →tissue hypoxia
Hydrops fetalis:
- Hemoglobin composed entirely of Gamma chains, No α-chains
- HbBarts(γ4) high O2 affinity →tissue hypoxia
- Lethal in utero without intrauterine transfusions
Various Forms of β-thalassaemia
Minor
- Heterozygosity
- Asymptomatic
- Mild anaemia, microcytosis
- Increased HbA2 (2α2δ) and HbF(2α2γ)
Intermedia: varying degrees of anemia, but no transfusions are needed
Major (Cooley’s anaemia): Most severe form
- Homozygosity
- No symptoms at birth
- Symptoms develop at 6-9 months
- Severe anaemia, requires lifelong transfusion
- Increased HbF(2α2γ): >90%
- Normal or increased HbA2 and Increased HbA
β-thalassaemia major (aka_________) Pathologenesis?
β-thalassaemia major (aka Cooley’s Anemia) Pathologenesis?
Reduced β- Globin synthesis => lack of beta-globin chains
=> insoluble alpha aggregates => abnormal Erythroblasts
=> most RBCs destroyed in bone marrow
=> surviving destroyed by macrophages in spleen
=> Because of ineffective erythropoiesis:
INCREASED RBC production in Liver, Spleen, Heart
INCREASED Iron absorption
β-thalassaemia major (aka. ________) Clinical features?
β-thalassaemia major (aka. Cooley’s Anemia)
Hepatosplenomegaly
Haemolysis → jaundice and bilirubin gallstones
Secondary hemochromatosis (frequent transfusions) and increased dietary iron absorption
Facial bone abnormalities, “chipmunk face” (increased size of maxilla)
“Crewcut” skull on X-ray (due to maxillary overgrowth caused by erythroid hyperplasia in Bone Marrow)
Transfusion-associated infections; infections due to asplenia
Heart failure (due to iron overload) –most common cause of death
The most common cause of death from Cooley’s Anemia?
➢Heart failure (due to iron overload)
How to diagnose Hereditary Spherocytosis?
Test for RBC fragility to diagnose => place in solution to see point at which breakup occurs (RBC osmatic fragility increased)
_______________________ is done to identify normal and abnormal haemoglobins and assess their quantity
Haemoglobin electrophoresis is done to identify normal and abnormal haemoglobins and assess their quantity
Mutation leading to Sickle Cell DIsease
β-globin gene point mutation: Glu for Val at 6thcodon
Homozygous vs. Heterozygous for sickle cell mutation
Homozygous (SS) -Sickle cell anemia: Severe haemolytic anaemia
Chronic haemolysis
intermittent microvascular occlusions
tissue damage
Heterozygous (AS) -Sickle cell trait: Asymptomatic (or mild symptoms) -Resistance against malaria
In sickle cell Anemia under __________ conditions Hb S forms polymers →sickling →_________
Under low oxygen conditions, Hb S forms polymers →sickling→occlusion of small vessels
Factors that influence sickling?
Increased HbF makes symptoms better (infants are asymptomatic until 5-6 months of age)
Increased HbF makes symptoms better (infants are asymptomatic until 5-6 months of age)
Increased concentration of HbS (dehydration of RBC) makes symptoms worse
Increased HbF makes symptoms better (infants are asymptomatic until 5-6 months of age)
Decreased pH decreases oxygen affinity to Hb → fraction of deoxygenated HbS increased => symptoms worse
Inflamed microvascular beds →slower transit time of RBCs →prone to sickling and occlusion worse
Clinical Features of Sickle Cell Anemia
- Dactylitis: Swollen hands and legs
-
Acute chest syndrome -Pleuritic chest pain, hypoxaemia, fever, tachypnoea, and infiltrate(s) on CXR
- Vasoocclusion in the lung tissue
- Pulmonary inflammation (e.g., due to infection) may trigger it
- Asthma is a contributing factor
-
Cerebral infarct
- Stroke by age of 40 (peak incidence in late childhood and early teenage years) in 25% of patients
- Another third of patients: silent cerebral infarcts (→cognitive deficits)
-
Priapism -45% of males after puberty
- Autosplenectomy: Chronic stasis and trapping of sickled RBC’s leads to infarctions, fibrosis and eventually shrinkageof the spleen by adolescence.
Sickle Cell Disease Treatments?
PROPHYLAXIS:
- Penicillin daily
- Vaccination against Pneumococcus
- Folic acid supplementation
TREATMENT:
- Transfusions (complications: iron overload, alloimmunization, infection)
- Red cell exchange (for example, if acute stroke or acute chest syndrome)
- Hydroxyurea (to increase HbF→makes symptoms better because of decreasing cc of HbS)
