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92 Cards in this Set
- Front
- Back
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what are the two broad classifications of hemolytic anemias?
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intracorpuscular = intrinsic
extracorpuscular = extrinsic |
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what are the principal sites where hemolytic anemias take place?
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intravascular and extravascular
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what are the principal types of intracorpuscular anemias?
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membrane defects
enyzme deficiency hemoglobinopathies |
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what are differentiating features of intrinsic and extrinsic hemolytic anemias?
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most intrinsic hemolytic anemias are hereditary, while most extrinsic hemolytic anemias are acquired
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what are the intracorpuscular anemias due to a membrane defect?
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spherocytosis
elliptocytosis paroxysmal nocturnal hemoglobinuria |
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what are the intracorpuscular anemias due to enzyme deficiency?
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G6PD-deficiency (glucose-6-phosphate deficiency)
pyruvate kinase deficiency |
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what are the intracorpuscular anemias due to hemoglobinopathies?
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unstable hemoglobins, eg HbC
HbS or HbAS, sickle cell anemia - qualitative change in synthesis of hemoglobin chains HbH, thalassemia - quantitative change in synthesis of hemoglobin chains |
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what are the principal types of extracorpuscular anemias?
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autoimmune hemolytic anemia (AIHA)
isoimmune = alloimmune hemolytic anemia microangiopathic hemolytic anemia |
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which intrinsic HA are acquired?
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PNH
and acquired alpha thalassemia (most commonly secondary to MDS) |
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what is the laboratory test to distinguish intravascular from extravascular hemolysis?
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haptoglobin
normal in extravascular hemolysis decreased in intravascular hemolysis or hemolytic crisis in extravascular hemolysis |
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what are laboratory findings in intravascular hemolysis?
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SERUM
decreased haptoglobin increased free plasma hemoglobin URINE free urine hemoglobin hemosiderin in urine sediment >7 days after the incident |
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what are laboratory findings common to both intra- and extravascular hemolysis in the serum?
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increased LDH, particularly isoenzyme 1
increased unconjugated bilirubin decreased Hb, RBC count and hematocrit |
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what are the effects of free hemoglobin in the blood?
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free hemoglobin binds NO and thus leads to dysregulation of smooth muscle cells
effects are vasoconstriction with PAHT, dysphagia, abdominal discomfort and diathesis |
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what are laboratory findings common to both intra- and extravascular hemolysis in the urine?
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urobilinogenuria, if resorption from intestine is large enough
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what are symptoms of an acute hemolytic crisis?
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fever, chills
abdominal pain and back pain |
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which is the most common hereditary hemolytic anemia in Europe?
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spherocytosis
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what is the prevalence of spherocytosis in Europe?
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1:5000
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what is the most common pattern of inheritance in spherocytosis?
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autosomal dominant in 75%
autosomal recessive in most other cases |
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what are the most common defects in spherocytosis?
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autosomal dominant ankyrin deficiency with secondary spectrin deficiency
autosomal dominant beta-spectrin deficiency autosomal recessive alpha-spectrin deficiency |
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what is a common complication in chronic hemolytic anemias?
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bilirubin gallstones, especially in those with concomitant Gilbert syndrome (reduced activity of glucuronyltransferase)
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what is important in the diagnosis of hereditary spherocytosis?
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detection of spherocytes is not sufficient to establish a diagnosis of hereditary spherocytosis
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what are causes of acquired spherocytes?
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intrinsic HA due to G6PD deficiency or hemoglobin H disease
extrinsic immune in auto- or alloimmune HA extrinsic non-immune in mechanical hemolysis |
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what are the specific diagnostic tests for hereditary spherocytosis?
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osmotic fragility test, but not very sensitive
flow cytometry with eosin-5-maleimid (EMA) with high sensitivity and specificity |
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what is the most helpful red cell index in hereditary spherocytosis?
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elevated MCHC, together with elevated RDW
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of what diagnostic value is the use of the MCV in hereditary spherocytosis?
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of little diagnostic value, as it is often normal or only slightly low
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what is a synonym for G6PD deficiency?
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favism
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what is the inheritance pattern in G6PD deficiency?
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X chromosomal recessive, as in haemophilia
mnemonic: g-siX-dehydrogenase |
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what is the pathophysiology in G6PD deficiency?
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decreased production of reduced gluthatione, which normally protects erythrocytes from oxidative damage
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what is the characteristic presentation of G6PD deficiency?
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hemolytic crises due to increased oxidative stress
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what are principal triggers of hemolytic crisis in G6PD deficiency?
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infections
fava beans medications |
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what medications can trigger hemolytic crisis in G6PD deficiency?
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antimalaria medication, such as quinine, primaquin, chloroquin
sulfonamides, eg antibiotics aspirin |
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what classification is used for the G6PD variants?
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5 classes according to WHO, classes I to III indicate deficiency states
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what are important G6PD variants?
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G6PD-A variant (normal is G6PD-B) with around 15% of normal activity
Mediterranean variants with rest activity <1% |
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what are the essential of diagnosis in pyruvate kinase deficiency?
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autosomal-recessive disorder leading to impaired glycolysis with acanthocytes in the peripheral blood smear and detection of decreased pyruvate kinase activity
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what are characteristics of enzymopenic hemolytic anemias?
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normal morphology of red cells (to a large extent)
normal hemoglobin normal osmotic resistance (cf spherocytosis) negative Coombs test |
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what are the two most common forms of hemoglobinopathies?
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sickle cell anemia and thalassemia
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what are the essentials of diagnosis in sickle cell anemia?
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irreversibly sickled cells on peripheral blood smear
positive family history and lifelong history of hemolytic anemia recurrent painful episodes due to vasoocclusion hemoglobin S is the major hemoglobin seen on electrophoresis |
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what is the inheritance pattern of sickle cell anemia?
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autosomal recessive
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what is the most common hemoglobin type?
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hemoglobin A, tetramer of 2 alpha and 2 beta subunits
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what percentage of American blacks carry the hemoglobin S gene?
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8%
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what is the tetrad of chronic hemolytic anemias?
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jaundice
pigment (calcium bilirubinate) gallstones splenomegaly poorly healing ulcers over the lower tibia |
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what are common sites of the painful episodes seen in sickle cell anemia?
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bones, especially the back and long bones
chest pain, rib pain |
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what are osseous complications of sickle cell anemia?
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ischemic necrosis of bone with increased risk for osteomyelitis due to staphyloccocci or less commonly by salmonellae
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what are specific renal complications of sickle cell anemia?
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infarction of the papillae causes
renal tubular concentrating defects and gross hematuria more often encountered in sickle cell trait than in in sickle cell anemia |
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what is a splenic complication of sickle cell anemia?
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recurrent often subclinic episodes of splenic infarctions leads to autosplenectomy and hyposplenism
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what are factors increasing sickling in sickle cell anemia?
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not enough water, dehydratation
not enough oxygen, hypoxemia too much hydrogen, acidosis |
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what is a factor retarding sickling in sickle cell anemia?
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presence of hemoglobin F, as it cannot participate in polymer formation
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in which year of life does sickle cell anemia have its onset?
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first year of life, when hemoglobin F levels fall and production of gamma-globin is switched to beta-globin
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what sort of crises can occur in sickle cell anemia?
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hemolytic and aplastic crises
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when do aplastic crises in sickle cell anemia occur?
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viral or other infection or folate deficiency
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what are hemolytic crises in sickle cell anemia related to?
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splenic sequestration (primarily in childhood before occurence of autosplenectomy)
coexistent disorders such as G6PD deficiency |
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what are laboratory findings in sickle cell anemia?
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hematocrit between 20-30%
peripheral blood smear with sickled cell comprising up to 50% of red cells reticulocytosis (10-25%) hallmarks of hyposplenism such as Howell-Jolly bodies and target cells leukozytosis 12-15 G/l |
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what are symptomatic therapy principles in sickle cell anemia?
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avoidance of hypoxemic states (>2000 m, flights) and dehydration
active immunization against pneumococci and H. influenzae |
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what are the genotypes in sickle cell anemia?
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genotype AA is normal
genotype AS is called the sickle trait, with Hb S accounting for 40% of total hemoglobin genotype SS is sickle cell anemia, with Hb S accounting for >80%, with variable increase in Hb F |
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what are the diagnostic tests in sickle cell anemia?
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sickle cell test (peripheral blood smear -> sickling after 24 h)
Hb-electrophoresis |
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what differentiates sickle cell anemia from thalassemia?
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both are disorder of Hb synthesis
sickle cell anemia is caused by a qualitative, while thalassemia is caused by a quantitative disorder in Hb synthesis |
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what are disorders of the red cells conferring a partial resistance against malaria?
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sickle cell anemia and thalassemia, as well as G6PD deficiency
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what are the components in HbA2?
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two alpha-globins, two delta-globins
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what are the components in HbF?
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two alpha-globins, two gamma-globins
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what are the major forms in thalassemia?
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alpha thalassemia
beta thalassemia |
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what is the pathophysiology in thalassemia?
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reduction of synthesis in normal globins
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where is alpha thalassemia present?
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Southeast Asia, South China, Middle East, Mediterranean Area
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where is beta thalassemia present?
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Meditarrenan Area
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what is the pathogenesis in alpha thalassemia?
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reduction of alpha chain production due to destruction of alpha-globin genes
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what is the normal gene count for alpha globin chains?
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2 genes, thus 4 alleles
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what are the types of alpha thalassemia?
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minima, minor, hemoglobin H and hydrops fetalis
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what are the details for the subtypes of alpha thalassemia?
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alpha thalassemia minima with one allele affected
alpha thalassemia minor with two alleles affected hemoglobin H disease with 3 alleles affected hydrops fetalis with 4 alleles affected --> ad exitum |
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what is the pathogenesis in beta thalassemia?
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mutation of beta-globin chain gene with reduced production of beta chains and compensatory production of gamma or delta chains
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what are the types in beta thalassemia?
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beta thalassemia minor when heterozygous
beta thalassemia major (Cooley anemia) when homozygous beta thalassemia intermedia when homozygous or heterozygous |
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what does hemoglobin H consist of?
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4 beta chains (ßß/ßß)
mnemonic: Homotetramer |
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what is another therapy option in sickle cell anemia with frequent symptoms?
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cytotoxic agents to increase hemoglobin F levels by stimulation of erythropoiesis in more primitve erythroid precursors
hydroxyurea |
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what are the laboratory findings in hemoglobin H disease?
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microcytic hypochromic anemia with target cells and Heinz bodies
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what are characteristics of unstable hemoglobins?
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prone to oxidative denaturation even in the presence of a normal G6PD system
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what is the inheritance pattern in unstable hemoglobins?
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autosomal dominant
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what are the diagnostic steps in unstable hemoglobins?
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finding of Heinz bodies and normal G6PD levels
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what are Heinz bodies?
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erythrocytes with inclusions composed of denaturated hemoglobin
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in what disorders can Heinz bodies be found?
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alpha thalassemia, with beta-subunits precipitating out of solution
G6PD deficiency chronic liver disease |
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what are the essentials of diagnosis in paroxysmal nocturnal hemoglobinuria (PNH)?
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episodic hemoglobinuria
thrombosis is common suspect in confusing cases of hemolytic anemias or pancytopenia flow cytometry is the best screening test |
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what is PNH?
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acquired clonal stem cell disorder that results in abnormal sensitivity of the RBC membrane to lysis by complement
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what is the underlying cause of PNH?
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defect in the gene for phosphatidyl-inositol class A (PIG-A) wich results in a deficency of the GPI anchor for membrane proteins
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which proteins are deficient in PNH?
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in particular the complement-regulating proteins CD55 and CD59
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what is the clinical presentation of PNH?
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episodic hemoglobinuria resulting in reddish brown urine, most often in the first morning urine
prone to thrombosis, especially mesenteric and hepatic vein thromboses, other sites include the brain and the skin (painful nodules) |
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of what type is the hemolysis in PNH?
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intravascular
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what is the diagnostic test in PNH?
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flow cytometry to demostrate deficiency of CD59 on RBC
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what are the treatment principles in PNH?
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iron replacement
prednisone eculizumab (Soliris) --> anti-complement C5 antibody |
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what are characteristic laboratory findings in PNH?
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iron deficiency due to chronic iron loss through hemoglobinuria
urine hemosiderin |
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what are the hematologic disorders in PNH?
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intravascular hemolysis with hemoglobinuria and hypercoagulopathy
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what globin chains is hemoglobin F composed of?
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two alpha and two gamma chains (αα/γγ)
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what globin chains does hemoglobin H consist of?
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only 1
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which viral infection causes the most severe aplastic crisis in sickle cell anemia?
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parvovirus B19
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what is aplastic crisis in sickle cell anemia characterized by?
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decrease in the hemoglobin level and reticulocytopenia <50 G/l
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what are the sites of extravascular hemolysis
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spleen and liver
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