Microangiopathic hemolytic Anemia & Hemolytic Uremic Syndrome
Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia ....
Transcript of Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia ....
![Page 1: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/1.jpg)
Hemolytic Anemias
![Page 2: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/2.jpg)
• Hemolytic anemias share the following features:
- A shortened red cell life < 120 days
- Elevated erythropoietin levels (compensatory increase in erythropoiesis)
- Accumulation of hemoglobin degradation products (red cell hemolysis)
![Page 3: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/3.jpg)
Extravascular hemolysis (within phagocytes): m.C Cause: RBCs deformability sequestration/phagocytosis
Splenomegaly (hyperplasia of phagocytes) Anemia Jaundice (unconjugated bilirubin) Tx: splenectomy
![Page 4: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/4.jpg)
Intravascular hemolysis:
Less common
Cause:
mechanical injury (cardiac valves, thrombotic narrowing of the Microcirculation, repetitive physical trauma ) complement fixation
intracellular parasites
exogenous toxic factors (clostridial sepsis/release ofenzymes that digest the red cell membrane)
Anemia hemoglobinemia hemoglobinuria hemosiderinuria jaundice (unconjugated bilirubin)
Lysed RBCs---- free hemoglobin------haptoglobin------phagocytes
If haptoglobin ------free hemoglobin/ methemoglobin------ Red-brown urine
No splenomegaly
![Page 5: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/5.jpg)
MORPHOLOGY:
erythroid precursors (normoblasts) in BM
prominent reticulocytosis in the p. blood
Erythropoietin
Hemosiderosis (accumulation of the iron containing pigment hemosiderin, particularly
in the spleen, liver, and bone marrow)
Extramedullary hematopoiesis (liver, spleen, and lymph nodes)----- Anemia
pigment gallstones (cholelithiasis)----- biliary excretion of bilirubin
![Page 6: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/6.jpg)
![Page 7: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/7.jpg)
![Page 8: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/8.jpg)
![Page 9: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/9.jpg)
Hereditary Spherocytosis
autosomal dominant
defects in RBC membrane skeleton---spheroid RBCs---- less deformable ----splenic sequestration/destruction
HS is caused by diverse mutations that lead to an
insufficiency of membrane skeletal components.
![Page 10: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/10.jpg)
• Young HS red cells are normal in shape, but the destabilized lipid bilayer sheds membrane fragments as red cells age in the circulation.
• the life span of the affected red cells is decreased on average to 10 to 20 days from the normal 120 days.
![Page 11: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/11.jpg)
![Page 12: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/12.jpg)
![Page 13: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/13.jpg)
• MORPHOLOGY:
Spherocytosis ----------- destinctive but not pathognomonic
Other features of hemolytic anemias
Moderate splenic enlargement (500-1000 gm)
![Page 14: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/14.jpg)
![Page 15: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/15.jpg)
• Clinical Features:
family history
RBCs---hypotonic salt solutions---osmotic lysis (influx of water) mean cell hemoglobin concentration (dehydration loss of K+ H2O)
If compensated by erythropoiesis----------- asymptomatic
If decompensated-----hemolytic anemia--- Splenomegaly Anemia Jaundice
![Page 16: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/16.jpg)
• aplastic crises ---- acute parvovirus infection.
• Hemolytic crises----intercurrent events leading to increased splenic destruction of red cells (e.g., infectious mononucleosis)
• Gallstones
![Page 17: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/17.jpg)
• Splenectomy treats the anemia and its complications
![Page 18: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/18.jpg)
Glucose-6-Phosphate Dehydrogenase Deficiency
• X-linked trait
• Hemolytic disease due to red cell enzyme defect (G6PD)----- antioxidant enzyme
• hemolysis result in misfolding of the protein, making it more susceptible to proteolytic degradation
![Page 19: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/19.jpg)
![Page 20: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/20.jpg)
Several hundred G6PD genetic variants are known, but most are harmless.
clinically significant variants:
• G6PD− : 10% of American blacks
• G6PD Mediterranean: in the Middle East
Reduced half-life of G6PD
G6PD activities fall quickly to levels inadequate to protect against oxidant stress as red cells age.
![Page 21: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/21.jpg)
Episodic hemolysis is characteristic
Intravascular and extravascular hemolysis
exposures that generate oxidant stress. The most common triggers ar: infections ---- oxygen-derived free radicals/activated leukocytes
Drugs ---- antimalarials , sulfonamides, nitrofurantoins
certain foods ---- fava bean “Favism”
![Page 22: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/22.jpg)
Morphology:
Heinz bodies (denatured globin forming membrane bound
Precipitates/inclusions)
Bite cells ( when macrophages pluck out the Heinz bodies in spleen)
spherocytes
![Page 23: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/23.jpg)
![Page 24: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/24.jpg)
• Clinical features: Acute intravascular hemolysis Anemia --- hemoglobinemia ---- hemoglobinuria begins 2 to 3 days following exposure of G6PD-deficient individuals to oxidants. greater G6PD Mediterranean variant. Because only older red cells are at risk for lysis, the episode is self-limited Intermittent hemolysis (not chronic) --- No splenomegaly No cholelithiasis
![Page 25: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/25.jpg)
Sickle Cell Disease
common hereditary hemoglobinopathy
Mainly in individual of African descent
point mutation in the sixth codon of β-globin--- replacement of a glutamate residue with a
valine residue.
![Page 26: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/26.jpg)
![Page 27: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/27.jpg)
• Normal adult red cells:
contain mainly HbA (α2β2)
small amounts of HbA2 (α2δ2)
fetal hemoglobin (HbF; α2γ2)
![Page 28: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/28.jpg)
![Page 29: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/29.jpg)
• sickle cell trait: heterozygous for HbS (HbS:40%, HbA:60%)
Asymptomatic
do not sickle except under profound hypoxia
• sickle cell disease: homozygous for HbS
Symptomatic
![Page 30: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/30.jpg)
• Pathogenesis:
HbS molecules undergo polymerization when deoxygenated.
Chronic hemolysis
Microvascular occlusions
Tissue damage
![Page 31: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/31.jpg)
• Several variables affect the rate and degree of sickling:
- Interaction of HbS with the other types of hemoglobin in the cell:
HbA ---- HbS polymerization ---- heterozygous
HbF ---- HbS polymerization---- infants >5 or 6 months of age
HbC ---- Lysine/ Glutamate ------- milder, HbSC (50%, 50%)
- Mean cell hemoglobin concentration (MCHC):
MCHC ---- intracellular dehydration ---- sickling/polymerization
MCHC ---- α-thalassemia ----- sickling/polymerization
- Intracellular Ph:
Ph ----- O2 affinity ---- sickling
- Transit time of red cells through microvascular beds
If slow --- sickling ---- spleen, BM, inflamed tissue
![Page 32: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/32.jpg)
![Page 33: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/33.jpg)
extravascular hemolysis (mainly)
intravascular hemolysis
Microvascular occlusion
sickle cells express adhesion molecule so sticky
![Page 34: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/34.jpg)
• MORPHOLOGY:
sickled cells
reticulocytosis
target cells (red cell dehydration)
Howell-Jolly bodies (small nuclear DNA remnants)/asplenia
BM is hyperplastic as a result of a compensatory erythroid hyperplasia.
bone resorption and secondary new bone formation, resulting in prominent cheekbones
![Page 35: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/35.jpg)
• Childhood----spleen is enlarged up to 500 gm • Adolescence/early adulthood ---- splenic
infarction, fibrosis (autosplenectomy).
• Infarctions caused by vascular occlusions can occur in many other tissues as well, including the bones, brain, kidney
• In adult patients, vascular stagnation in
subcutaneous tissues often leads to leg ulcers
![Page 36: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/36.jpg)
![Page 37: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/37.jpg)
![Page 38: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/38.jpg)
![Page 39: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/39.jpg)
• Clinical Features: Vaso-occlusive crises/ pain crises: Infection/dehydration/acidosis---in most instances no predisposing cause is identified. bones, lungs, liver, brain, spleen, and penis. hand-foot syndrome or dactylitis of the bones of the hands or feet, Acute chest syndrome (fever, cough, chest pain, and pulmonary infiltrates)– fatal Priapism loss of visual
In children, painful bone crises are extremely common and often difficult to distinguish from acute osteomyelitis The most common cause of patient morbidity and mortality
![Page 40: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/40.jpg)
![Page 41: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/41.jpg)
Sequestration crises:
Massive entrapment of sickle red cells---rapid splenic enlargement----hypovolemia---shock----fatal-----treatment with exchange transfusions.
Aplastic crises:
parvovirus B19--- -erythropoiesis----anemia.
![Page 42: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/42.jpg)
• Chronic hypoxia is responsible for a generalized impairment of growth and development, as well as organ damage affecting the spleen, heart, kidneys, and lungs.
• Increased susceptibility to infection with encapsulated organisms
• Pneumococcus pneumoniae and Haemophilus influenzae septicemia and meningitis are common, particularly in children, but can be reduced by vaccination and prophylactic antibiotics
![Page 43: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/43.jpg)
• Diagnosis:
mixing a blood sample with an oxygen-consuming reagent, which induces sickling of red cells.
Hemoglobin electrophoresis.
Prenatal diagnosis is possible by analysis of fetal DNA obtained by amniocentesis or chorionic biopsy.
![Page 44: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/44.jpg)
• About 90% of patients survive to age 20, and close to 50% survive beyond the fifth decade
• Treatment:
Blood transfusion
Antibiotics
Bone marrow transplant
Hydroxyurea (DNA inhibitor) : + HbF
![Page 45: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/45.jpg)
Thalassemia Syndromes
• inherited mutations that decrease the synthesis of either the α-globin or β-globin chains that compose adult hemoglobin, HbA (α2β2)
• endemic in the Mediterranean basin, the Middle East, tropical Africa, the Indian subcontinent,
![Page 46: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/46.jpg)
β-Thalassemias
• mutations that diminish the synthesis of β-globin chains.
• more than 100 different causative mutations, mostly consisting of point mutations
• two β chains are encoded by a single β-globin gene on chromosome 11
• β0 mutations: absent β-globin synthesis
• β+ mutations: reduced β-globin synthesis
![Page 47: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/47.jpg)
• Impaired β-globin synthesis results in anemia by two mechanisms:
1- The deficit in HbA synthesis produces underhemoglobinized hypochromic, microcytic red cells with subnormal oxygen transport capacity.
2- diminished survival of red cells and their precursors. α chains precipitate within red cell precursors, forming insoluble inclusions----membrane damage----- apoptosis ---- ineffective erythropoiesis
insoluble inclusions----membrane damage----- sequestration---- extravascular hemolysis
![Page 48: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/48.jpg)
• erythroid hyperplasia in the marrow
• Extensive extramedullary hematopoiesis
• skeletal abnormalities
• extraosseous masses in the thorax, abdomen, and pelvis.
• excessive absorption of dietary iron/due to -hepcidin
• secondary hemochromatosis
![Page 49: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/49.jpg)
![Page 50: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/50.jpg)
• β-Thalassemia Major:
Anemia---6 /9 m after birth---switches HbF-HbA
Hb: 3 to 6 gm/dL
RBCs: lack HbA (β0/β0) or small amounts (β+/β+ or β0/β+)
HbF: The major RBCs Hb
HbA2: normal, low, high
![Page 51: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/51.jpg)
• MORPHOLOGY: Anisocytosis poikilocytosis Microcytosis Hypochromia Target cells Basophilic stippling fragmented red cells enlargement of the spleen The liver and the lymph nodes can also be enlarged by extramedullary hematopoiesis. new bone formation
![Page 52: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/52.jpg)
![Page 53: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/53.jpg)
![Page 54: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/54.jpg)
• clinical course:
Untreated children suffer from growth retardation and die at an early age from the effects of anemia.
cheekbones and other bony prominences are enlarged and distorted.
![Page 55: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/55.jpg)
![Page 56: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/56.jpg)
• With transfusions and iron chelation, survival into the third decade is possible
• BM transplantation is the only therapy offering a cure
• Cardiac disease resulting from progressive iron overload and secondary hemochromatosis
![Page 57: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/57.jpg)
• β-Thalassemia Minor:
More common
Asymptomatic or mild anemia
HbA2 (4-8%)
HbF : normal or slightly increased
![Page 58: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/58.jpg)
α-Thalassemias
• inherited deletions that result in reduced or absent synthesis of α-globin chains
• The two α chains in HbA are encoded by an identical pair of α-globin genes on chromosome 16,
![Page 59: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/59.jpg)
• Newborns----γ4 tetramers--hemoglobin Barts • older children/adults---β4 tetramers---HbH---
more in Asian high affinity for O2 so not useful for O2 delivery
• hemolysis and ineffective erythropoiesis are less severe than in β-thalassemias because free β and γ chains are more soluble than free α chains and form fairly stable homotetramers
• HbA2: normal or low
![Page 60: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/60.jpg)
![Page 61: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/61.jpg)
Paroxysmal Nocturnal Hemoglobinuria
• acquired mutations in the phosphatidylinositol glycan complementation group A gene (PIGA), an enzyme that is essential for the synthesis of certain membrane-associated complement regulatory proteins (GBI=glycosylphosphatidylinositol)
• PNH blood cells are deficient in three GPI-linked
proteins that regulate complement activity: (1) CD55 (2) CD59 (3) C8 binding protein. Of these
![Page 62: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/62.jpg)
• Red cells deficient in these GPI-linked factors are abnormally susceptible to lysis or injury by complement.
intravascular hemolysis: paroxysmal and nocturnal (–PH/+complement) in only 25% of cases; chronic hemolysis without dramatic hemoglobinuria is more typical.
Anemia
Venous thrombosis (platelet dysfunction)
Acute leukemia/MDS (Hematopoietic stem cells)
![Page 63: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/63.jpg)
• diagnosed by flow cytometry (CD59, CD55)
• Tx:
C5 inhibitor therapy
Immunosuppressive drugs
BM transplantation
![Page 64: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/64.jpg)
Immunohemolytic/autoimmune hemolytic Anemias
• caused by antibodies that bind to red cells, leading to their premature destruction.
• direct Coombs antiglobulin test
Patient’s RBCs with sera AB
• indirect Coombs antiglobulin test
Patient’s serum with RBCs/Ag
![Page 65: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/65.jpg)
• Warm Antibody Type:
M.C
Extravascular hemolysis,
Tx: removal of initiating cause, immunosuppressive therapy, splenectomy
![Page 66: Hemolytic Anemias Done by :Aseel Twaijer & Laith Sorour · mot common pathway in hemolytic anemia . ... If patient have Alpha-thalasemia and sickle cell the sickling will be milder](https://reader030.fdocuments.net/reader030/viewer/2022040717/5e24ce8c729e7f66c9346fc1/html5/thumbnails/66.jpg)
• Cold Agglutinin Type:
Finger, nose, ears---- vascular occlusion---pallor, cyanosis, Raynaud phenomenon
Hemolysis