RBC Disorders Flashcards
Results of renal papillary necrosis
Results in gross hematuria and proteinuria
Main cause of death in paroxysmal nocturnal hemoglobinuria
Thrombosis of the hepatic, portal or cerebral veins
*Destroyed platelts release cytoplasmic contents into circulation, inducing thrombosis
_____ inhibits dihydrofolate reductase.
Methotrexate
Why do cells sickle in sickle cell anemia?
HbS polymerizes when deoxygenated; polymers aggregate into needle-like structures, resulting in sickle cells
Blood smear in Hemoglobin C
HbC crystals in RBCs
What type of mutation is seen in B-thalassemia?
Point mutations in promotor or splicing sites
*Seen in individuals of African and Mediterranean descent
- Microcytic, hypochromic RBCs with target cells and nucleated red blood cells
- HbA2
- HbF
B-thalassemia major
- Macrocytic RBCs with hypersegmented neutrophils
- Glossitis
- Subacute combined degeneration of the spinal cord
B12 deficiency
What strain of malaria causes daily fever?
P. falciparum
- Severe anemia
- B chains form tetramers (HbH)
- HbH seen on electrophoresis
Three gene delection in a-thalassemia
Most common type of anemia in hospitilized patients
Anemia of chronic disease
Enterocytes transport iron across the cell membrane into blood via _______. _____ transports iron in the blood. Stored intracellular iron is bound to _________.
Ferroportin; Transferrin; Ferretin
Under what conditions does IgG bind to RBCs?
- In relatively warm temps of the central body
*Membrane of antibody-coated RBC is consumed by splenic macrophages, resulting spherocytes
Cause of paroxysmal nocturnal hemoglobinuria
- Acquired defect in myeloid stem cells resulting in absent glycosylphosphatidylinositol
- Cells are rendered desctructible by complement
Stored iron bound to ferritin prevents iron from forming free radicals via the _______ reaction.
Fenton
Presentation of a two gene deletion in a-thalassemia
- Mild anemia with increase in RBC count
- Cis: Asians; worse
- Trans: Africans
- Microcytic, hypochromic RBCs and target cells seen on blood smear
- Slightly decreased HbA
- Increased HbA2
- HbF
B-thalassemia minor
*The mildest form of disease and is usually asymptomatic with an increased RBC count
Laboratory findings:
- Increased ferritin
- Decreased TIBC
- Increased serum iron
- Increased % saturation
Sideroblastic anemia
What is the most common congenital defect in sideroblastic anemia?
Defect in aminolevunilic acid synthetase (ALAS)
What is the relationship between ferritin and TIBC?
Inverse
What causes sickling in the medulla of people with sickle cell trait?
- Extreme hypoxia and hypertonicity of the medulla
- Results in microinfarctions leading to microscopic hematuria and, eventually decreased ability to concentrate urine
Complications of paroxysmal noctunal hemoglobinuria
- Iron deficiency anemia
- Aute myeloid leukemia (develops in 10% of patients)
- Hemoglobinemia
- Hemoglobinuria
- Hemosiderinuria
- Decreased serum haptoglobin
Intravascular hemolysis
________ screen causes cells with any amount of HbS to sickle.
Metabisulfite
*;positive in both disease and trait.
Most common cause of vitamin B12 deficienct
Pernicious anemia
*Autoimmune destruction of parietal cells leads to intrinsic factor deficiency
Which proteins are most commonly affected in hereditary spherocytosis?
Ankyin
Spectrin
Band 3
Aplastic anemia results from damage to ___________ .
Hematopoietic stem cells
*Results in pancytopenia (anemia, thrombocytopenia, and leukopenia)
Aside from pernicious anemia. What are some other causes of vitamin B12 deficiency?
- Pancreatic insufficiency
- Damage to terminal ileum
- Crohn’s disease
- Diphyllobothrium latum
- Dietary deficiency in vegans
Causes of aplastic anemia
Drugs or chemicals
Viral infections
Autoimmune damage
Absorption of iron occurs in the _______.
Duodenum
*Enterocytes have heme and non-heme (DMT1) transporters. The heme form is more readily absorbed
In people with sickle cell trait, RBCs with <50% HbS do not sickle in vivo except in the _________.
Renal medulla
Causes of anemia due to underproduction
- Causes of microcytic and macrocytic anemia
- Renal failure-decreased EPO production by peritubular interstitial cells
- Damage of bone marrow presursor cells
Where is iron bound to transferrin delivered?
Luver and bone marrow macrophages for storage
Mutation in sickle cell anemia
Autosomal recessive mutation in B chain of hemoglobin; a signle amino acid change replaces normal glutamic acid (hydrophilic) with valine (hydrophobic)
In hemoglobin C, glutamic acid is replaced by ________.
Lysine
Dactylitis
Swollen hands and feet due to vaso-occlussive infarcts in bone (infants)
55% HbA, 43% HbS, 2% HbA2
Sickle cell trait
treatment for hereditary spherocytosis
Splenectomy
*Anemia resolves but spherocytes persist and Howell Jolly bodies emerge on blood smear
- Macrocytic RBCs and hypersegmented neutrophils
- Glossitis
- Decreased serum folate
- Increased serum homocysteine
- Normal methylmalonic acid
Folate deficiency anemia
Why are spherocytes consumed by splenic machrophages?
Spherocytes are less able to maneuver through splenic sinusoids
In paroxysmal nocturnal hemoglobinuria, why does intravascular hemolysis occur episodically during the night?
Mild respiratory acidosis develops with shallow breathing during sleep and activates complement
*RBCs, WBCs, and platelets are lysed
________ confirms the presence and amount of HbS.
Hb electrophoresis
alpha2delta2
HbA2
What causes the round shape of RBCs in hereditary spherocytosis?
Loss of membrane, due to loss of cytoskeleton-membrane tethering proteins
*These cells are called sperocytes
Treatment for aplastic anemia
- Cessation of any causative drugs and supportive care with transfusions
- Marrow-stimulating factors (EPO, GM-CSF, and G-CSF)
- Immunosuppression may be helpful
- Bone marrow transplantation as a last resort
RC <3%
Overproduction, normocytic anemia
90% HbS, 8% HbF, 2% HbA2
Sickle cell disease
Treatment for hereditary spherocytosis
Splenectomy
Role of acid in iron absorption
Acid aids iron absorption by maintaining the Fe 2+ state. which more readily absorbed thatn the Fe 3+ state
__________ attaches protoporphyrin to iron to make heme. Where does this occur?
Ferrochelatase; mitochondria
Fanconi anemia can progress to what neoplasm?
AML (>10%)
target cells
Decreased Hb in cytoplasm
a2B2
HbA
- Anemia with splenomegaly
- Jaudice
- Increased risk for bilirubin gallstones
- RC count >3%
Extravascular hemolysis
Extravascular hemolysis and sickle cell anemia
- Reticuloendothelial system removes RBCs with damaged membranes, leading to anemia, jaundice with unconjugated hyperbilirubinemia, and increased risk for bilirubin gallstone
*Cells continuously sickle and de-sickle while passing through the microcirculation, resulting in complications related to RBC membrane damage
IgG mediated immune hemolytic anemia is associated with which conditions?
- SLE
- CLL
- Certain drugs
- Penicillin and cephalosporins
4 alpha genes are pressent on chromosome _______. Two beta genes are present on chromosome ______.
16;11
Normal Hb males/females
Males: 13.5-17.5g/dL
Females: 12.5-16 g/dL
Under what conditions does Igm bind to RBCs?
Relatively cold temps of the extremities
*Also fixes complement
Stepwise synthesis of protoporphyrin
- Aminolevulinic acid synthesae converts succinyl CoA to aminolevulinic acid using vitamin B6 as a cofactor
- Aminolevulinic acid dehydratase converts aminolevulinc acid to porphobilinogen
- Porphobilongen to protoporphyrin
Percentage of HbS in sickle cell anemia
>90%
Treatment for anemia of chronic disease
- Treat underlying condition
- Exogenous EPO is useful in patients with cancer
Plummer-Vinson syndrome
Iron deficiency anemia with esophageal web and atrophic glottis; presents with anemia, dysphagia, and beefy-red tongue
Igm mediated immune hemolytic anemia is associated with what conditions?
Mycoplasma pneumoniae
Infectious mononucleosis
a2y2
HbF
Normocytic anemias predominantly associated with intravascular hemolysis
- Paroxysmal nocturnal hemoglobinuria
- Glucose-6-phosphate dehydrogenase deficiency
- Immune hemolytic anemia
- Microangiopathic hemolytic anemia
- Malaria
Causes of normocytic anemia
- Increased peripheral destruction
- Underproduction
process by which B12 is absorbed
- Salivary gland enyzymes liberate vitaming B12
- B12 then bound to R-binder and carried to the stomach
- Pancreatic proteases in the duodenum detach vitamin B12 from R-binder
- Vitamin B12 binds intrinsic factor
- Vitamin B12-intrinsic factor complex is absorbed in the ileum
How is hereditary spherocytosis diagnosed?
by osmotic fragility test, which reveals increased spherocyte fragility in hypotonic solution
Treatment for IgG mediated immune hemolytic anemia
Cessation of offending drug
Steroids
IVIG
Splenectomy (if necessary)
Causes of macrocytic anemia without megaloblastic change?
Alcoholism
Liver disease
Drugs
- X-linked recessive disorder
- Renders cells susceptible to oxidative stress
Gucose-6-Phosphate dehydrogenase deficiency
Total iron binding capacity
Measure of transferrin molecules in the blood
RC >3%
Peripheral destruction, normocytic anemia
*Marrow response (to increase RC in response to anemia) is good
- Hydrops fetalis
- Hb Barts seen on electrophoresis
Four genes deleted causing a-thalassemia
- Increased serum homocysteine
- Increased methylmalonic acids
- Decreased serum vitamin B12
Anemia due to B-12 deficiency
Which strain of malaria results in fevers every other day?
P.vivax and Povale
Treatment for B-thalassemia major
- Chronic transfusions
- Leads to risk for secondary hemochromatosis
Percentage of HbS in sickle cell trait
<50%
Subacute combined degeneration
–Demyelination lateral and dorsal columns
–Paraesthesia, loss of vibration and position, gait, spasticity
*Seen in B12 deficiency
malaria is transmitted by _________
Female anopheles mosquito
MCV >100
Macrocytic
a-thalassemia is usually due to ______________. B-thalessemia is due to _________.
Gene deletion; gene mutation
Which conditions are predominantly associated with extravascular hemolysis?
- Hereditary spherocytosis
- Sickle cell anemia
- Hemoglobin C
Stages of iron deficiency
- Storage iron deficiency
- Serum iron is depleted
- Normocytic anemia
- Microcytic, hypochromic anemia
Complications of extensive sickling
Vaso-occlusion
- Dactylitis
- Autosplenectomy
- Acute chest syndrome
- Pain crisis
- Renal papillary necrosis
Vitamin B6 deficiency can caused acquired sideroblastic anemia. When is this most commonly seen?
As a side effect of isoniazid treatment for TB
Aquired caused of sideoblastic anemia
- Alcoholism-mitochondrial poison
- Lead poisoning- inhibits ALAD and ferrochelatase
- Vitamin B6 deficiency
_________ is needed to regenerate reduced glutathione
NADPH
*By-product of G6PD
Biochem of folate B12, and methionine
- Methylytetrahydrofolate donates a methyl group to B12 and becomes folate
- B12 donates methyl grouo to homocysteine and becomes methionine
Clinical findings of B-thalassemia major
- Crewcut appearance on X-ray
- erythroid hyperplasia
- Expansion of hematopoiesis into the skull
- Chipmuck facies
- Hematopoiesis in facial nones
- Hepatosplenomegaly
Causes of microangiopathic hemolytic anemia
- Microthombi
- TTP-HUS
- DIC
- HELLP
- prostetic heart valves
- Aortic stenosis
*When prsent, microthrombi produce shistocytes on blood smear
Laboratory findings:
- Increased ferritin
- Decreased TIBC
- Decreased serum iron
- Decreased %saturation
- Increased free erythrocyte protoporphyrin
Anemia of chronic disease
Causes of macrocytic anemia with megaloblastic change
Folate and B12 deficiency
Methylmalonic builds up in ______ in spinal cord.
Myelin
What conditions lead to an increased risk of sickling?
Hypoxemia
Dehydration
Acidosis
Biopsy of aplastic anemia
Emplty, fatty marrow
Cause of immune hemolytic anemia
Antibody-mediated destruction of RBCs
B-thalassemia presents with a risk of aplastic crisis with __________ infection of erythroid precursors.
Parvovirus B19
What are the consequences of autosplenectomy seen with extensive sickling?
- Increased risk of infection with encapsulated organisms such as S. pneumonia and H. influenza
- Increased risk of Salmonella paratyphi osteomyelitits
- Howell-Jolly bodies on blood smear
Which vitamin is deficient in sideoblastic anemia?
B6
- Increased RDW
- Increased mean corpuscular hemoglobin concentration (MCHC)
- Splenomegaly, jaudice with unconjugated bilirubin
- Spherocytes with loss of central pallor
Hereditary spherocytosis
What is the confirmatory test for paraoxysmal nocturnal hemoglobinuria?
Acidified serum test or glow cytometry to detect lack of CD55 (DAF) on blood cells
Organs of reticuloendothelial system
Macrophages of spleen
Liver
Lymph nodes
MCV <80
Microcytic
Hb Barts
Gamma chains form a tetramer
Causes of folate deficiency
- Poor diet
- Increased demand (pregnancy, cancer, and hemolytic anemia)
- Folate antagonists (methotrexate)
Oxidative stress precipitates Hb as ___________.
heinz bodies
*heinz bodies are removed from RBCs by splenic macrophages, resulting in bite cells
________ on the surface of blood cells protects against complement-mediated damge by inhibiting C3 convertase.
Decay accelerating factor (DAF)
*DAF is secured to the membrane by GPI
Common cause of iron deficiency in the elderly?
Colon polyps/ carcinoma in the western world
Hookworm (Anyclostoma duodenale and Nectar americanus) in the developing world
parvovirus B19 infects __________.
Progenitor red cells
*Temporary halts erythropoiesis
Folate is absorbed in the ___________.
Jejunum
______ is used to diagnose immune hemolytic anemia
- Coombs test (direct or indirect)
Causes of oxidative stress
infections
drugs (primaquine, sulfa drugs, and dapsone)
Fava beans
Laboratory findings:
- Microcytic, hypochromic RBCs with increase in RDW
- Decreased ferritin
- Increase TIBC
- Decreased serum iron
- Decreased % saturation
- Increased free erythrocyte protoporphyrin
iron-deficiency anemia
What are the results of consumption of RBCs by macrophages?
This is extravascular hemolysis
- Hemoglobin is broken down
- Globin broken down into amino acids
- Heme is broken down to iron and protoporphyrin,
- Iron is recycled
- Protoporphyrin is broken down in unconjugated bilirubin, which is bound to serum albumin and delivered to the liver for conjugation and excretion into bile
Larger cells with bluish cytoplasm
Reticulocytes
*Due to residual RNA
Clinical feautres of iron deficiency
Anemia, koilonychia, and pica
___ (IgG/IgM)- mediated disease usually involves extravascular hemolysis. ____ (IgG/IgM) can lead to intravascular hemolysis.
IgG, IgM
intravascular hemolysis and sickle cell anemia
- RBCs with damaged memnranes dehydrate, leading to hemolysis with decreased haptoglobin and target cells on blood smear
*Target cells are due to dehydration
__________ is a inherited defect of RBC cytoskleton-membrane tethering proteins.
Hereditary spherocytosis
Plasmodium affects ______ and the ______.
RBCs ; liver
*RBCs rupture as a part of the Plasmodium life cycle
_________ is used to screen for paroxysmal nocturnal hemoglobinuria.
Sucrose test
*Sucrose activates complement
Role of hepcidin
Acute phase reactant that sequesters iron in storage sites by:
- Limiting iron transfer from macrophages to eythroid precursors
- Suppressing erythropoietin production
*Aims to prevent bacteria from accessing iron, which is necessary ofr their survival
What attributes to the production of spherocytes in IgM mediated immune hemolytic anemia?
- IgM binds to RBCs and fixes complement
- RBCs inactivate complement but residual C3b serves as an opsonin for splenic macrophages resulting in spherocytes
*Extreme activation of complement can lead to intravascular hemolysis
Cause and symptoms of acute chest syndrome
Cause: vaso-occlusion in pulmonary microcirculation
Symptoms
- Chest pain, shortness of breath, and lung infiltrates
- Precipitated by pneumonia
- Most common cause of death in adult patients
HbH
B chains forming a tetramer
*Damage RBCs
Types of microcytic anemias
- iron deficiency anemia
- Anemia of chronic disease
- Sideorblastic anemia
- Thalassemia
Treatment with _________ increases levels of HbF.
Hydroxyurea
What happens to iron is protoporphyrin is deficient?
Iron is trapped in the mitochondria
*iron-laden mitochondria form a ring around the nucleus of erythroid precursors called ringed sideroblasts
Frequent pigment gall stones
Hereditary spherocytosis
Against protein based antigens
IgG
Against carbohydrate based antigens
IgM
Indications for packed red blood cells
- (Restoration of red cell oxygen carrying capacity)
- Improve Tissue Oxygen Delivery
- Alleviation of signs & symptoms of anemia
Guidelines for packed red cells
General Guidelines:
- Maintain Hgb > 7mg/dl
- Increased mortality when Hgb drops to < 5 mg/dl
- Need to keep higher HCT in CAD, pulmonary disease (Hgb > 8mg/dl)
- Important to maintain normovolemia even with acute blood loss
Contraindications for Platelet Transfusion
- Thrombotic thrombocytopenic purpura (TTP)
- Heparin induced thrombocytopenia (HIT)
- Immune mediated thrombocytopenic purpura (ITP)
Cryoprecipitated AHF components
contains fibrinogen, Factors VIII and XIII,
von Willebrand factor
Cryoprecipitated AHF indications
- Hypofibrinogenemia/Dysfibrinogenemia
- Uremic bleeding
- Second-line treatment of Hemophilia A, Factor XIII deficiency and von Willebrand disease
Treatment for allergic transfusion reactions
diphenylhydramine
RBC receptors for Malaria
Glycophorin A for P. falciparum and Duffy antigen for P. vivax
Mode of transmission for leishmania
Sandlfy
Treatment for leishmania
Sodium stibogluconate
