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192 Cards in this Set

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define anemia
- decrease in whole body red cell mass
- precludes relative decreases in RBC count, hemoglobin, or hematocrit <- occur when plasma volume decreases
is anemia of pregancy true anemia?
- no. just a reflection of increased plasma volume
what is a practical working definition of anemia?
- decrease in RBC, Hb, or hematocrit
what causes anemia?
1. decreased RBC production from:
- hematopoeitic cell damage
- deficiency of factors for heme or DNA synthesis
2. increased RBC loss:
- external blood loss
- RBC destruction
what can cause hematopoietic cell damage?
- infection
- drugs
- radiation
what is necessary for heme synthesis?
- iron
what is necessary for DNA synthesis?
- vit B12/ folate
what is hemolytic anemia?
RBC destruction
acute posthemorrhagic anemia
- first few hours, prior to hemodilution, there may be no decrease in Hb, hematocrit, and RBC count b/c of parallel loss of both RBCs and plasma
- marked reactive increase in platelets
what are the clincical findings in posthemorrhagic anemia?
- similar to hypovolemia
what is hemodilution?
- a compensatory increase in plasma volume
what causes iron deficiency anemia?
- chronic blood loss
- dietary deficiency
- increased iron requirement
what can cause chronic blood loss?
- GI bleeds or menorrhagia
- major cause of iron deficiency in adults
define menorrhagia
Excessive bleeding during menstruation.
what can cause GI bleeds?
- carcinoma of the colon
- hookworm disease in less developed countries
iron deficiency anemia
- impaired heme synthesis
- you see hypochomia and microcytosis; decreased serum Fe and increased total Fe-binding capacity; decreased serum ferritin
what are the major etiologic factors of iron deficiency anemia?
- dietary deficiency in infants and preadolescents
- excess menstrual bleeding
- chronic GI blood loss
pernicious anemia
- autoimmune gastritis -> lack of intrinsic factor and failure of B12 absorption -> delayed DNA replication
what are the diagnostic features of pernicious anemia?
- pancytopenia, oval macrocytes, and hypersegmented neutrophils; megalobalstic hyperplasia; acholorhydria; anti-intrinsic factor antiboides; hyperreflexia, absent position and vibration sense; impaired vit B12 absorption
define acholorhydria
no stomach acid; condition may be physiological or pharmacological (eg, omeprazole (Prilosec (R) ) or other antisecretory proton-pump blocking drugs prescribed commonly for gastric ulcers)
what is the Schilling test?
The Schilling test is a medical investigation used in patients with vitamin B12 deficiency. The purpose of the test is to determine if the patient has pernicious anemia.
what are the major etiologic factors of pernicious anemia?
- autoimmunity
folate deficiency anemia
delayed DNA replication
- pancytopenia, oval macrocytes, and hypersegmented neutrophils; megaloblastic hyperplasia
what are the major etiologic factors of folate deficiency anemia?
- dietary deficiency
- malabsorption syndromes
aplastic anemia
- generally diminished hematopoiesis
- pancytopenia, reticulocytopenia, marked hypocellualrity of bone marrow
what are the major etiologic factos of aplastic anemia?
- toxic drugs and chemicals
- often idiopathic
anemia of chronic disease
- most often normochormic and normocytic or macrocytic; maybe hypochormic and microcytic with decreased serum iron and decreased serum-iron binding capacity
what are the major etiologic factors of anemia of chronic disease?
- various chronic diseases (RA, renal disease, chronic infection
myelophthisic anemia
- bone marrow replacement, usually by malignant tumor
- severe anemia; small numbers of nucleated RBCs and immature granulocytes in the peripheral blood; tumors in the bone marrow
define: pancytopenia
an abnormal deficiency in all blood cells (red blood cells and white blood cells and platelets); usually associated with bone marrow tumor or with aplastic anemia
define macrocyte
Macrocytes (larger than normal RBCs) are present.
how does dietary deficiency cause anemia?
- rare, except in infants
- human milk is low in iron -> infant iron storage is delepted by 6 months unless there is dietary supplementation
- a risk in premies
- a risk in elderly
increased iron requirement during pregnancy
- fetus can deplete maternal iron stores
- can also occur in infants and preadolescents that outgrow borderline iron stores
what are the clincial manifestations of anemia?
- pallor, fatique, dyspnea on exertion
- sometimes may have angina pectoris in people with coronary artery narorrowing from atherosclerotic disease
what happens during extreme anemia?
- glossitis
- gastritis
- koilonychia
- Plummer-Vinson syndrome
define koilnychia
Koilonychia means literally "spoon nails." It refers to nails (usually of the hand) which have lost their convexity, becoming flat or even concave in shape. In a sense, koilonychia refers to the opposite nail shape abnormality described as nail clubbing.
define glossitis
Glossitis is inflammation or infection of the tongue. It causes the tongue to swell and change color. Papillae may be lost, causing the tongue to appear smooth.
Plummer-Vinson sydrome
aka Paterson-Kelly syndrome or sideropenic dysphagia
- linked to severe, long-term iron deficiency anemia, which causes dysphagia due to esophageal webs. The cause of Plummer-Vinson syndrome is unknown; however, genetic factors and nutritional deficiencies may play a role. Women are at higher risk than men, particularly in middle age.
- squamous cell carcinoma risk is increased.
what are the lab findings in anemia?
- decreased Hb, hemocrit, and RBC count
- hypochromic microcytic erhthrocytes on peripheral smear
- decreased [Fe] and increased total iron binding capacity (TIBC)
- decreased in body stores
how do you measure body stores of Fe?
- look at bone marrow for stainable hemosiderin or for serum ferritin
what is the DDX for anemia like syndromes?
- iron deficiency anemia: hypochoromic microcytic anemia (e.g. anemia of chronic disease or b-thalassemia minor)
- anemia of chornic disease: serum Fe is low, but TIBC is also low
- b-thal: A2 Hb is increased
define megaloblastic anemias
large, abnormal looking erythroid precursor cells (megaloblasts) in the bone marrow
what causes megaloblastic anemias?
- vit B12 or folate deficiency -> decreased DNA synthesis -> delay in nuclear division
- unimpeded cytoplasmic maturation
how do megaloblastic anemias appear morphologically?
- nuclear-cytoplasmic asynchrony of large erythroid precursor cells with open, loose-appearing chromatin
what happens when you have megaloblastic anemia?
- impaired RBC production
- RBC destriction also in the bone marrow prior to release of mature RBCs into the peripheral blood
what is 'ineffective erythropoiesis'?
- RBC destriction in the bone marrow prior to release of mature RBCs into the peripheral blood
what lab abnormalities do you see with megaloblastic anemia?
1. peripheral blood:
- pancytopenia
- oval macrocytosis
- hypersegmented neutrophils
2. bone marrow:
- megaloblastic hyperplasia
describe the oval macrocytosis you see in megaloblastic anemia
- mean corpuscular volume (MCV) > 110 fl (normally, about 87 fl)
what do lab folate levels have to do with megaloblastic anemia?
- further define the specific type of megaloblastic anemia
list the different types of megaloblastic anemia
1. vit B12 deficiency
2. Folate deficiency
what are the different types of vit B12 deficiency megaloblastic anemia?
1. pernicious anemia
2. other forms:
- total gastric resection
- disorders of distal ileum
- vegetarian diet
- blind loop syndrome
- broad spectrum antibiotic therapy
- diphyllobothrium latum
pernicious anemia
- most common form of vit B12 deficiency meg. an.
- autoimmune disorder -> autoimmune gastritis -> no intrinsic factor production -> no vit B12 absorption
what is often seen associated with pernicious anemia?
- other autoimmune diseases (e.g. thyroid disease)
what was autoimmune gastritis previously referred to as?
- fundal or type A gastritis
what is chronic autoimmune gastritis associated with?
- achlorhydria
- anti-intrinsic factor and antiparietal cell antibodies
- increased incidence of gastric carcinoma
what are clinical findings associated with pernicious anemia?
- insidious onset with extreme RBC reduction
- lemon-yellow skin color
- stomatitis and glossitis
- subacute combined degeneration of the spinal cord
describe the insidious onset of pernicious anemia in elderly persons
- preceded by lengthy subclincial period, where clinical manifestations are minimal
describe the morphologic changes in subacute combined degeneration of the spinal cord in pernicious anemia
- combined systems disease and posterolateral degeneration
- demyelination of posterior and lateral columns
describe the clinical symptoms in subacute combined degeneration of the spinal cord in pernicious anemia
- ataxic gait
- hyperreflexia with extensor plantar reflexes
- impaired position and vibratory sense
what is different neurologically between patients with folate vs. vit B12 deficiency?
- vit B12: associated neuro abnormalities
- folate def: no neruo abnormalities
what are the lab findings associated with pernicious anemia?
- pancytopenia, hypersegmented neutrophils, and megaloblastic hyperplasia of bone marrow
- anti-intrinsic factor antibodies
- abnormal schilling test
how do you differentiate pernicious anemia from other types of megaloblastic anemias?
- anti-intrinsic factor is seen in pernicious anemia, but not in other conditions.
- you may, however, see antiparietal cell antibodies in other conditions, but most frequently in pernicious anemia
what is the Schilling test?
- abnormal results: impaired absorption fo vit B12 correctable by intrinsic factor
what happens when you can't correct impaired absorption of vit B12 by using intrinsic factor?
- intestinal malabsorption caused by crohn's disease, blind-loop syndrome, and giant tapeworm infestation
what may absolute vegetarians have?
- normal absorption by decreased vit B12 due to dietary deprivation
total gastric resection and vit B12 deficiency
- intrinsic factor is produced in the gastric fundus
- clinical picture is same as that for pernicious anemia
disorders of the distal ileum and vit B12 deficiency
intrinsic factor- vit B12 complex is absorbed int he distal ileum
strict vegetarian diet and vit B12 deficiency
vit B12 is only found in foods of animal origin
blind-loop syndrome and vit B12 deficiency`
- bacterial overgrowth in a surgically induced intestinal blind loop results in depletion of vit B12
broad spectrum antibiotic therapy and vit B12 deficiency
- can result in bacterial overgrowth and vit B12 depletion
diphyllobothrium latum infestation and vit B12 deficiency
- the giant tapeworm of man, acuqired by ingestion of freshwarter fish, inhabits the intestines
-> vit B12 depletion
folate deficiency
- no neurologic abnormalities (contrasted with vit B12 deficiency)
how can you get folate deficiency megaloblastic anemia?
- severe dietary deprivation
- pregnancy
- Dilantin (phenytoin)
- folic acid antagonist chemo
- relative folate deficiency
- intestinal malaborption
how does severe dietary deprivation cause folate deficiency?
- most often seen in alcoholics and fad dieters
how does pregnancy cause folate deficiency?
- additonal demands of the fetus
how does dilantin (phenytoin) therapy cause folate deficiency?
- interferes with absorption of folate, or OCPs
relative folate deficiency
increased demand of folate bc of compensatory accelerated erythropoiesis in hemolytic anemia
what is intestinal malabsorption caused by?
- sprue
- Giardia lamblia
what is the prevalence of anemia of chronic disease?
- second most common form, after iron deficiency anemia
for which diseases does anemia of chronic disease secondarily occur?
- RA
- renal disease
- chronic infection
define: normochromic anemia
anemia in which the hemoglobin content of the red cells as measured by the MCHC is in the normal range.
define: normocytic anemia
- marked by a proportionate decrease in the hemoglobin content, the packed red cell volume, and the number of erythrocytes per cubic millimeter of blood.
how would you characterize anemia of chronic disease? it's normo___ and normo ____.
- normochronic and normocytic
- may be moderately macrocytic when associated with renal disease
what serum markers may accompany anemia of chronic disease when associated with chronic inflammatory states (e.g. RA)
- accompanied by decreased serum iron
- hypochromia
- microcytosis
- symptoms look like iron deficiency anemia
how do you differentiate anemia of chronic diesease from iron deficiency anemia?
- TIBC ( Total iron binding capacity) is decreased in anemia of chronic disease
what are the general characteristics of aplastic anemia?
- markedly hypocellular bone marrow with almost total loss of hematopoietic cells:
- eryhroid and myeloid precursor cells
- megakaryocytes
- peripheral pancytnemia
- reticulocytopenia
what is peripheral pancytopenia?
- anemia
- leukopenia
- thrombocytopenia
aplastic anemia is most often secondary to what?
- toxic exposure
what autoimmune condition can cause aplastic anemia?-
- autoimmune dysfunction of cytotoxic T cells
what are some other etiologic agents that can cause aplastic anemia?
- radiation exposure
- chemicals (e.g. benzene and other organic compounds)
- therapeutic drugs
- viral infection
which drugs can cause aplastic anemia?
- chloramphenicol
- sulfonamides
- gold salts
- chlorpromazine
- anti-inflammatory and antimalarial drugs
- alkylating agents used in cancer treatmetn
what is chlorampenicol?
a bacteriostatic antibiotic originally derived from the bacterium Streptomyces venezuelae, isolated by David Gottlieb.
- In the West, the main use of chloramphenicol is in eye drops or ointment for bacterial conjunctivitis.
which viruses can cause aplastic anemia?
- human parvovirus
- hep C virus
what is myelophthisic anemia? what is it most commonly caused by?
- form of bone marrow failure that is caused by replacement of the bone, most often by malignant neoplasm
what is a less common cause of myelophthisic anemia?
- bone marrow destruction from marrow fibrosis
what may make you suspicious of myelophthisic anemia?
- leukoerythroblastosis- a small number of nucleated RBCs and immature granulocytic precursors are seen in the peripheral blood smear
broadly define hemolytic anemias
- anemias resulting from increased RBC destruction
list the hemolytic anemias
1. warm antibody autoimmune hemolytic anemia
2. hemolytic isease of the newborn
3. hereditary spherocytosis
4. G6PD deficiency
5. Sickle cell anemia
6. b-thalassemia major
7. a-thalassemias
what do you seen when you have increased RBC destruction- the liberation of Hb and its degredation products?
- increased unconjugated bilirubin
- increased urine urobilinogen
- Hemoglobinemia and hemoglobinuria
- disappearance of serum haptoglobins
what can increased unconjugated (indirect reacting) bilirubin result in?
- acholuric jaundice: jaundice not accompanied by bilirubinuria (not liver disease)
- can eventually lead to pigment containing gallstones
define bilirubinuria
the presence of bilirubin in the urine; often a symptom of liver disease
what is a late complication of hyperbilirubinemia?
- pigment containing gallstones, as a late complication
define hyperbilirubinemia
abnormally high amounts of bile pigment (bilirubin) in the blood
what happens when you get very rapid RBC destruction within the circulation (intravascular hemolysis)?
- hemoglobinemia
- hemoglobinuria
- methemalbuminemia
- hemosiderinuria
what is methemoglobin?
a form of the oxygen-carrying protein hemoglobin, in which the iron in the heme group is in the Fe3+ state, not the Fe2+ of normal hemoglobin. Methemoglobin is unable to carry oxygen. It is blue in color. The NADH-dependent enzyme methemoglobin reductase (AKA diaphorase I) is responsible for converting methemoglobin back to hemoglobin.
what are haptoglobins?
- protein in the blood plasma that binds free Hb released from RBCs, and thereby inhibits its oxidative activity.
- the haptoglobin-hb complex will then be removed by the reticuloendothelial system (mostly the spleen)
- In clinical settings, the Haptoglobin assay is used to screen for hemolytic anemia
when will you finally be able to see elevation of serum Hb after intravascualr hemolysis (e.g hemolytic transfusion reactions)
- only after the serum haptoglobins are used up and not detectable
what else, besides increased red cell destruction, do you see in hemolytic anemias?
- increased erythropoiesis: compensates for shortened RBC survival
1. normoblastic erythroid hyperplasia in bone
2. reticulocytosis
3. polychromatophilia
how do you realize that your patient has reticulocytosis?
- increased number of circulating reticulocytes can be identified by residual stainable RNA
why do you get a moderate increase in MCV in hemolytic anemia?
- reticulocytes are slighlyt larger than other RBCs
- MCV can be increasd to ~105fl
how do you detect polychromatophilia?
- increased number of slightly larger BRCs that stain with a bluish cast, roughly equivalent to increased reticulocyte count
define: polychromatophilia
- aka polychromasia
1. the property of being stainable with various stains;
2. a condition in which the erythrocytes, on staining, show various shades of blue combined with tinges of pink
what is intracorpuscular hemolytic anemia?
- defects are often genetically determined
- in the RBC itself
what is extracorpuscular hemolytic anemia?
- defects are aquired from irculating antibodies or an enlarged spleen
how do immune hemolytia anemias present? list the four types
- recent onset
1. warm antibody autoimmune hemolytica anemia
2. cold agglutinin disease
3. chronic cold agglutinin disease
4. hemolytic disease of the newborn
what is the prevalence of warm antibody autoimmune hemolytic anemia?
- most common form of immune hemolytic anemia
- usually secondary to SLE, Hodgkin disease, or non-Hodgkin lymphomas
what causes warm antibody autoimmune hemolytic anemia?
- iGG autoantibodies react with cell surface antigens
- these antibodies are active at 37 degrees
what are the general clincial characteristics of immune hemolytic anemias?
- general features of hemolytica anemia
- spherocytosis
- postiive direct COombs test
why do you get spherocytosis in immune hemolytic anemias?
- you get loss of membrane protein by serial passage of antibody coated RBCs through the spleen
what is a Direct Coombs test?
The direct Coombs tes is used to detect if antibodies or complement system factors have bound to RBC surface antigens in vivo.
- used clinically when immune-mediated haemolytic anaemia is suspected.
- A positive Coombs test indicates that an immune mechanism is attacking the patient's own RBC's. This mechanism could be autoimmunity, alloimmunity or a drug-induced immune-mediated mechanism.
what is an indirect Coombs test?
The indirect Coombs test is used to detect in-vitro antibody-antigen reactions.
- In antenatal care, the IAT is used to screen pregnant women for antibodies that may cause hemolytic disease of the newborn.
what causes cold agglutinin disease?
- IgM antibodies optimally active at temperatures below 30
- usually, the antibodies target the I blood group antigen
Notes: All individuals have circulating antibodies directed against red blood cells, but their concentrations are often too low to trigger disease (titers under 1:64 at 4°C). In individuals with cold agglutinin disease, these antibodies are in much higher concentrations (titers over 1:1000 at 4°C).
what is clod agglutinin disease often complicated by?
- mononucleosis infection
- mycoplama pneumoniae infection (can help facilitate the diagnosis by demonstrating cold agglutinins)
what is chronic cold agglutinin disease often associated with?
- lymphoid neoplasms
- mediated by anti-i antibodies
- Raynaud phenomenon
who is chronic cold agglutinin disease clincially characterized?
- agglutination and hemolysis in tissue sites exposed to the cold
- associated with Reynaud phenomenon
- worse in cold weather
- some episodes of jaundice
- sometimes hemoglobinemia and hemoglobinuria
what causes hemolytic disease of the newborn (aka erythroblastosis fetalis)?
- maternal antibodies cross the placenta and react with fetal
RBCs -> fetal hemolytic anemia
1. maternal alloimmunization ot fetal RBC antigens (D antigen of the Rb blood groups system)
2. ABO incompatibility
what is the mom's blood type for the most frequently occurring form of Rh-mediated hemolytic disease of the newborn?
- mom: d
- fetus: D
what permutations of blood groups can you have for ABO incompatibility?
1. mother is O and child is A, or B
2. mother is A, child B or AB
3. mother is B, child A or AB
what does hemolytic disease of the newborn cause?
1. kernicterus: stainign of the basal ganglia and other CNS structures by unconjugated bilirubin -> neurologic damange
2. stillbirth
3. hydrops fetalis
define hydrops fetalis
- gross edema of the entire body wih severe anemia occurring in the hemolytic diseaseas in the newborn.
- can cause heart failure with massive generalized edema
how can you prevent hemolytic disease of the newborn?
- by administration of anti-D IgG antiserum to D-negative mothers at the time of delivery (or at time of terminatioN) prevents maternal alloimmunization
what is paroxysmal nocturnal hemoglobinuria?
- uncommon acquired intracorpuscular defect
- increases sensitivity to complement-induced RBC lysis -> intravascular hemolytic anemia, pancytopenia, and increase incidnece of venous thrombosis
what do you see when you get up in the mornings if you have paroxysmal nocturnal hemoglobinuria?
- hemoglobin containing urine in the first pee of the morning
define: paroxysmal
recurring "sudden attacks" of symptoms.
tell me about the molecular cause of paroxysmal nocturnal hemoglobinuria
- somatic mutation of PIG-A
- causes impaired synthesis of the GPI anchor needed to tie proteins to cellular surfaces (CD 55, CD59, C8)
- these proteins protect RBCs, granulocytes, and platelets from complement mediated lysis
which proteins protect RBCs, granulocytes, and platelets from complement mediated lysis?
- CD55
- CD59
- C8
- attached to the cellular surface by GPI
how do you diagnose paroxysmal nocturnal hemoglobinuria?
- use flow cytometry to show a poluation of CD59- negative erythrocytes
- used to be diagnosed by the Ham test for in vitro completment induced hemolysis of acidified serum
mwahahaha.. in which disease do you find the key words 'PIG' and 'HAM'?
- paroxysmal nocturnal hemoglobinuria
list the hemolytic anemias caused by membrane slektal protein abnormalities
1. hereditary spherocytosis
2. hereditayr elliptocytosis (ovalocytosis)
epidemiology of hereditary spherocytosis
- autosomal dominant hemolytic anemia
- most common intracorpuscular inherited hemolytic anemia observed in whites
what characterizes hereditary spherocytosis?
- spherocytes selectively trapped in the spleen -> splenomegaly
- increase in erythrocyte osmotic fragility to hypotonic saline
- increase in mean corpuscular hemoglobin concentration (MCHC)
what do you see in spherocytosis that you don't usually see in other forms of anemia?
- increase in the MCHC
what genes cause hereditary spherocytosis?
- variety of molecaulr defects in the genes encoding:
- spectrin
- ankyrin
- protien 4.1
- other erythrocyte membrane skeletal proteins
-> deficinecy in SPECTRIN
what is spectrin?
- Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane of many cell types in pentagonal or hexagonal arrangements
- cleavage causes the membrane to form blebs and ultimately to be degraded
- Association with the intracellular face of the plasma membrane is by indirect interaction, through direct interactions with protein 4.1 and ankyrin, with transmembrane proteins.
what is hereditary elliptocytosis (ovalocytosis)?
- autosomal dominant disorder characterized by elongated, oval red cells
- may be marked by hemolytic anemia and splenomegaly
- often does not cause anemia
which is the most common form of enzyme deficiency hemolytic anemia?
- G6PD deficiency
describe the genetics behind G6PD deficiency
- X-linked
- occurs in 10% of African americans and in mediterranians
- G6PD is an enzyme in the PPP pathway; it serves to maintain levels of NADPH
- NADPH is needed to maintain levels of glutathione and protect cells from oxidative stress
what do you see in G6PD deficiency? what causes these symptoms?
- hemoglobinemia
- hemoglobinuria
- caused by oxidative stress brought on by infection and drugs
which drugs can cause increase levels of oxidative stress and cause hemolytic anemia in G6PD deficiency?
- primaquine (antimalarial)
- sulfonamides
- fava beans
what do you see in the peripheral blood smear in a patient with G6PD deficiency?
- bites cells (RBCs that look like they have a bite taken out of them)
list the two types of enzyem deficinecy hemolytic anemias
1. G6PD deficiency
2. pyruvate kinase deficiency
pyruvate kinase deficiency
- second most common enzyme deficinecy hemolytic anemia
- autosomal recessive disorder characterized by hereditary nonspherocytic hemolytic anemia
what is one way to differentiate G6PD deficiency from pyruvate kinase deficiency?
- G6PD is self-limited
- PK deficiency is chronic and sustained
list the hemoglobinopathies
1. hemoglobin S disorder
2. hemoglobin C disorder
3. hemoglobin E disorder
what is the general characteristic of hemoglobinopathies?
- genetically determined abnormalities of hemoglobin strucutre
- S is most common
- C less common
- E is found in some urban centers
describe the epidemiology of hemoglobin S disorders
- 7% of african americans carry the Hb S gene
- in africa, some parts have more than 1/3 affected
- may be connected to falciparum malarial resistance
what is seen in persons of african origin that may protect against malaria?
- erythrocyte G6PD deficiency
- absence of Duffy blood group antigens (Duff Fy a- b-)
where is the mutation for hemoglobin S?
- point mutation in codon 6 of the b-globin gene; valine -> glutamic acid -> abolishes recognition site for restriction endonuclease Mst II
how do you perform prenatal diagnosis for hemoglobin S disorders?
- either a chorionic villus sample or amniotic sampling for the point mutation in codon 6 of the b-globin gene
what is abnormal about hemoglobin S?
- polymerizes at low oxygen tension -> form tactoids that distort RBC shape:
- sickle, elongated shapes
- repeated sickling episodes stiffen the RBC membrnates -> more likely to hemolyse
- also more likely to obstruct the microvasculature
how do you test for hemoglobin S disorders?
- characterized by a positive sickle cell preparation (in vitro sickling of RBCs on exposure to reducing agents like sodium metabisulfite)
in which disorders is hemoglobin S present?
- sickle cell anemia
- sickle cell trait
- sickle C disease
- sickle cell thalassemia
what causes sickle cell anemia?
- homozygous form of hemoglobin S
what do you see in sickle cell anemia?
1. severe hemolytic anemia
2. chronic leg ulcers
3 vaso-occlusive painful crises
4. infarctions in lungs and spleen
5. aplastic crises
6. infectious complications (Salmonella osteomyelitis)
what are vaso-occlusive 'painful crises' seen in sickle cell disease?
- severe pain in the limbs, back, chest and abdomen
- often precipitated by infection or dehydration
what happens with repeated lung and spleen infarcts in sickle cell disease?
- spleen becomes congested and enlarged in childhood
- with repeated infarcts, it gets smaller and fibroses (autosplenectomy)
what are aplastic crises seen in sickle cell disease?
- not the same as painful crises
- precipitous fall in Hb concentration
- usually provoked by viral infection like human parvovirus
what causes sickle cell trait?
- hemoglobin S in heterozygous form
- usually has no clincial consequences
in what population are hemoglobin C disorders mainly seen?
- africans
- homozygous: mild hemolytic anemia with slenomegaly, target cells, and intraerythrocytic crystals
- heterozygous: result in disease only when coinherited with other abnormal hemoglobins (e.g. Hb S)
in what population are hemoglobin E disorders mainly seen?
- southeast asia
- have increased significantly in urban areas in recent years
- clinical and lab findings are similar to Heme C disorders
what are thalassemias?
- genetic disorder characterized by deficient production of a or b-globin chains of Hb.
- heme synthesis is NOT affected
what is the epidemiology of b-thalassemia?
- most common form of thalassemia in the mediterranean and in the US
what is the genetic defect in b-thalassemia?
- defects in the promoter, intron, or coding sequence of b-globin gene
what is b-thalassemia major?
- aka Mediterranean anemia
- aka Cooley anemia
- compound heterozygosity or homozygosit of the thalassemic variants of the B-globin gene
what is the clinical presentation of b-thalassemia major?
1. marked anemia
2. splenomegaly
3. distortion of skull, facial bones, and long bones
4. thalassemic RBC morphology
5. increased Hb F
6. generalized hemosiderosis
what causes the marked anemia seen in b-thalassemia major?
- decrease in Hb synthesis
- shortened RBC lifespan due to aggregation of insolube excess of a-chains
- ineffective erythropoisis
- relative folate deficiency
why do you get skull, facial bone and long bone distortion in b-thal major?
- expansion of erythroid bone marrow
what is thalassemic RBC morphology?
- microcytosis
- hypochromia
- target cells
- changes in size and shape
what is Hb F?
- fetal Hb (a2g2)
- increased throughout life in b-thal major patients
why do you get generalized hemosiderosis in b-thal major patients?
- chronic hemolysis
- ineffective erythropoiesis
- repeated transfusions
what causes b-thalassemia minor?
- heterozygous inheritance of thalassemic variants of the b-globin gene
what are the clincial manifestations of b-thal minor?
- minimal hypochromic microcytic anemia
- INCREASE in Hb A2 (a2g2)
what is the normal fraction of Hb A2 in the blood?
- very minor fraction
what are the types of b-thalassemias?
1. B-thal major
2. B-thal minor
3. sickle cell thal
what is sickle cell thal?
- a type of b-thal
- results from coinheritance of Hb S gene and a tahlassemic ariant of the b-globin gene (compound heterozygosity)
what is the clinical presentation of sickle cell thal?
- similar to, but often less severe than, sickle cell anemia
what is the epidemiology of a-thalassemia?
- most common form in SE Asia
what is the genetic basis for a-thalassemia?
- deletions of one or more of the four a-globin genes
- in normal people, there is a duplication of the a- globin gene, with a pair of identical a-globin genes on each member of chr. 16
what are some variants of a-thal characterized by?
- increased concentration of Hb Barts (g4) or Hb H (b4)
hemolytic anemias due to mechanical disruption of circulating erythrocytes- what are they associated with?
- aortic valve prostheses
- thrombotic thrombocytopenic purpura
- microangiopathic hemolytic anemia
what is microangiopathic hemolytic anemia?
- partial occlusion of small vessels that causes the mecahnical disruption of RBCs
what do you see in the blood when you have hemolytic anemia due to mechanical disruption of circulating erythrocytes?
- RBC fragements:
- schistocytes
- helmet cells