Week 1 RR Flashcards
hypoxic injury and infarction w/ severe pain in the affected organ
Pain crises (vaso-occlusive)–> sickle cell disease
Transfusion rxn: Fever, Chills, back pain and headache; hemoglobinuria, hemoglobinemia
Acute hemolytic transfusion reaction
G6PD recovery phase
reticulocytosis.
Sickle Cell Anemia inheritance
Autosomal recessive
PIG-A is x-linked; significance?
when PIG-A is INACTIVATED–> PNH PIG-A may be inactivated through lyonization causing PNH
hydrops fetalis pathogenesis
high output cardiac failure–> Liver dysfunction–> Dec albumin–> EDEMA
pre-renal azotemia: oliguria or anuria
Acute blood loss
s/s of HTLV‐1 and HTLV‐2
T‐Cell lymphoma Demyelinating neuropathy
“bite cells
G6PD
OLDER RBCs have more damage
G6PD
what are Heinz bodies and where found
seen in G6PD def. Sulfhydryl groups in Hb is oxidized and precipitates forming Heinz bodies
Seen in Middle Eastern ppl
Mediterranean variant G6PD
secondary hemosiderosis (iron overload)
Thalassemia (from the transfusion) Sickle Cell anemia Hereditary spher.
Megaloblastic Anemia retic count; MCV
macrocytic MCV>100 ↓ retic count
PNH mutation
INACTIVATING somatic mutation of PIG-A
acute vs. delayed Hemolytic transfus. rxn: intra/extravascular hemolysis
acute–> intra delayed–> extravascular
Pernicious anemia diagnosis
anti-IF antibody
NO levels in Sickle cell disease; significance?
it is depleted b/c Hb from lysed sickle cells bind it; Result–> more vasconstriction leading to INC transit time and more problems
Erythroblastosis fetalis retic count
INC. because it is hemolytic
the direct Coombs detects (1) and the indirect detects (2)
- antibodies on red cells 2. antibodies in serum or plasma
Drug induced: Sudden, severe hemolysis w/ Hburia
Cephalosporins.
associated w/ chronic inflammation
Anemia of Chronic Disease (ACD)
intravascular hemolysis
G6PD PNH Microangiopathic Hemolytic Anemia
IgG vs IgM in erythro. fetalis
IgG can cross placenta; IgM too large;
(a) ineffective erythropoiesis (b) extravascular hemolysis
β-thalassemia
RBCs susceptible to destruction by complement. *i.e. decreased inhibition of complement activation*
PNH
Acute blood loss lab values
↑ platelets (thrombocytosis) ↑ WBC esp. granulocyte (leukocytosis)
Pseudo‐Pelger –Huet cells–>
dumb-bell shaped neutrophils seen in Myelodysplastic syndrome
↑serum homocysteine; ↑ methylmalonic acid
Vit. B12 def.
IgM antibodies bind to RBCs at less than 37 deg. C
Cold AIHA
how is metabolic complications in blood transfusion occur
Blood unit is anticoagulated w/ citrate; Rapid infusion chelates calcium
Manifestations of post transfusion purpura
severe bleeding thrombocytopenia 1-3 weeks post transfusion
HbC (Lys for Glu) cells lose 1) and become dehydrated, sickling
1) salt and water
hyper-segmented (>5 nuclei) neutrophils
Megaloblastic Anemia
extravascular hemolysis
Hereditary spherocytosis Immune Hemolytic Anemia Thalassemia
1) inhibits HbS polymerization
1) HbF
P. pneumoniae and H. influenzae
Encapsulated organisms; seen in Sickle patients
Hypoalbuminemia Generalized edema
Fetal compensation in erythro. fetalis
(Paroxysmal Nocturnal Hburia) inheritance
ACQUIRED; not inherited
Febrile non hemolytic transfusion reactions are caused by (1) antibodies in the recipients plasma which react with (2) leading to the release of endogenous pyrogens (3)
- anti‐leukocyte or antiplatelet 2. donor WBC’s 3. IL‐1 ,IL‐6 , TNF‐alpha
non-transmembrane proteins that attach to the cell membrane through GPI
PIGA
peripheral nucleated RBC’s, polychromatophylia (indicates ↑turnover), thrombocytopenia and ↑bilirubin
Erythroblastosis fetalis
Sickle cell pathogenesis: Deoxygenated HbS polymerizes–> aggregate into long needle-like structures–> ↓pH–> 1)
1) RBC sickles
Hereditary Spherocytosis–> intravascular or extravascular
Extravascular
(CD55
Decay-accelerating factor–>inhibitor of complement
coats the Rh positive cells of fetus and prevents sensitization of mother
Rho-gam; only effective against Rh(D)
Direct Coomb’s test: (-) Anti-IgG (+) anti-C3d
Cold AIHA
decreased reticulocyte count
Iron def. anemia Thalassemia Megaloblastic anemia ACD Aplastic anemia
Sickle cell hallmark in children
Hand-foot syndrome–> swollen hands and feet
Myelodysplastic syndrome: (1) gene is located on chromosome 8 and trisomy 8 is commonly seen in a variety of (2)
- MYC 2. myeloid malignancies
Acute hemolytic transfusion reactions are most often from transfusion of (1
- ABO incompatible red blood cells
β0-thalassemia vs. β+-thalassemia
β0-thalassemia: Absent functional β-globin protein β+-thalassemia: ↓ β-globin protein.
Sickle cell MCHC
Increased due to intracellular dehydration
Transfusion complication: HTN; SOB, pul. edema, etec.
Circulatory overload
Antigen antibody reactions from infusion of plasma proteins
Allergic Rxns to blood transfusion
IgM vs. IgG
Erythroblastosis fetalis: IgM can’t cross placenta IgG can. Autoimmune Hemolytic anemia: warm–> IgG Cold–> IgM Drug Induced Hemolytic anemia:
Disposal of the oxidant H2O2 is dependent on reduced glutathione (GSH), which is generated by the action of 1); without G6PD, 1) cannot be generated
NADPH
SEVERE anaphylaxis due to transfusion
IgA deficient pts
This cytokine released during (1) binds to hemoglobin leading to renal vasoconstriction
- acute hemolytic transfusion reactions; cytokine is NO (EDFR)
Myelodysplastic syndrome: 5q vs. 7q
5q–> often good prognosis in older women 7q–>worse prognosis
Point mutation in beta globiin gene;
β-thalassemia
Sicke cell diagnosis
Positive sickling w/ metabisulfate; Hb electrophoresis shows High HbS
More severe. Markedly reduced ½ life (reduction in protein stability
Mediterranean variant G6PD
anti-leukocyte or anti-platelet Abs in host plasma which react with donor WBCs
Febrile non hemolytic transfusion reaction
Cold agglutinins are associated with
mycoplasm pneumonia, infectious mono (EBV, CMV)
Transfusion complication: pt on ACE inhibitor (unable to break down bradykinin)
Hypotensive rxn;
Erythroid hyperplasia in the bone marrow (“crewcut” on scalp), extramedullary hematopoiesis (in liver, spleen, and lymph nodes).
Sickle cell
Drug induced: Direct or indirect Coombs’ test: Complement only
immune-complex type
PNH–> intravascular or extravascular
intravascular hemolysis
acute phase reactants such as ferritin and hepcidin ↑
Anemia of chronic disease (ACD)
INHERITED defect in RBC membrane
Hereditary Spherocytosis
Myelodysplastic syndrome has a high risk of transformation to (1)
Acute Myeloid Leukemia (AML).
Aplastic crises: RBC progenitors w/ parvovirus B19
Sickle cell disease
Antibodies against transfused leukocytes or platelets release endogenous pyrogens(IL‐1 ,IL‐6 , TNF‐alpha )
Febrile non hemolytic transfusion reaction:
hypocellular marrow with lots of fat; few erythroid progenitors
Aplastic Anemia
1 mutated β gene vs. 2 mutated
Thalssemia minor–> Mild anemia 2: Thalassemia major–> severe anemia; needs transfusion
PNH RBCs go through intravascular hemolysis caused by 1)
1) C5b-C9 MAC
small molecule that generates an immune response when attached to a larger molecule.
Hapten
↓haptoglobin.
Intravascular hemolysis
G6PD deficiency–> intravascular or extravascu
intravascular hemolysis
Splenomegaly
Extravascular
colon polyps/carcinoma in elderly
Iron-Deficiency Anemia
Sickle cell anemia s/s due to extravascular hemolysis
Bilirubin stones;
seen in conditions such as Diabetes, RA, SLE, neoplastic disorders
Anemia of Chronic Disease (ACD)
Poikilocytosis vs. aniscocytosis
aniScocytosis–> varying Sizes poikilocytosis–> varying SHAPES
Iron-Deficiency Anemia lab
↓serum iron ↓Ferritin; ↑TIBC;
Erythroblastosis fetalis LABS
Inc. UCB; Dec. platelets (thrombocytopenia)
G6PD s/s
Intravascular hemolysis therefore: Hbemia; Hburia ANEMIA
Myelodysplastic syndrome: Epigenetic factors
hyper methylation with silencing of tumor suppressor genes
Sickle cell lab test
Mix blood with metabisulfate–>
Mildly reduced ½ life of G6PD (protein misfolding)
African variant G6PD
most common cause of death in adults with sickle cell disease
Acute Chest Syndrome
Erythroblastosis fetalis: jaundice soon after birth. why not in utero
placenta handles the bilirubin in utero
extravascular hemolysis s/s
Splenomegaly, jaundice ↑risk of pigmented gallstones.
Hereditary Spherocytosis inheritance
AD; more severe when compound heterozygote
associated w/ PNH
Aplastic Anemia
Erythroblastosis fetalis direct coomb’s test
(+) direct Coombs test (IgG)
Acquired antibody mediated RBC destruction
autoimm. hemolytic anemia
MCV, Hb, Hct and MCH are all ↓.
Iron-Deficiency Anemia
Drug induced: penicillin
Hapten Mechanism
Cause of death in PNH
venous Thrombosis–> platelet pieces destroyed by compliment clump together;
What are the s/s of chelation of calcium?
Circumoral paresthesia and tingling of fingers
dumb-bell shaped neutrophils with two nuclei
Pseudo‐Pelger –Huet celll–>Myelodysplastic syndrome
Intravascular and extravascular hemolysis
Sickle Cell disease
associate w/ ankyrin, band 4.2 and band 3.1; alpha and beta spectrin dimers
Hereditary Spherocytosis
Which transfusion reactions are complement mediated?
Acute hemolytic transfusion reactions Delayed are not complement mediated
an excess of α-globin chains causes problems
β-thalassemia (↓β-globin mRNA)
Secondary to mycoplasma pneumoniae infection
Cold AIHA
target cells, microcytic hypochromic cells
Sickle cell
↑serum homocysteine; normal methylmalonic acid
Folate def.
blood from multiparous woman can cause:
TRALI (Transfusion acute LUNG injurY)
loss of central pallor
Hereditary Spherocytosis
Inc. susceptibility to oxidative damage
G6PD
myeloblasts in myelodysplastic syndrome vs. acute myeloid leukemia
Myelodys–> inc. but less than 20% AML–> myeloblasts less than 20%
Transfusion complication: Hypotensive rxn; s/s
HYPOTENSION facial flushing and abdominal pain
Acute Chest Syndrome s/s
chest pain, and pulmonary infiltrates; SOB; seen in Sickle cell pts
fava beans
G6PD–> generates oxidants when metabolized
hemoglobinemia, hemoglobinuria, hemosiderinuria
intravascular hemolysis
Transfusion complication: HBV vs. HCV
HBV–> jaundice 2 mos after; very few become chronic carrier HCV–> non-icteric; HIGH percent becomes chronic carriers
Transfusion complication in an IgA def. pt
anaphylaxis hypotension
Thalassemia–> intravascular or extravascular
Extravascular
Dec. pH on Sickle cell
INCREASES sickling
β-Thalassemia major vs. minor genetics
Major–>Homozygous (some compound heterozygous) minor–> heterozygous
vitamin B12 or Folic acid deficiencies
Megaloblastic Anemia
Sickle cell on xray; why?
crewcut appearance due to compensatory erythroid hyperplasia in the bone marrow of SKULL
Why should neonates get blood 7 day old or less for exchange transfusions?
To reduce the risk of a storage lesion in which potassium leaks out of RBC during storage
Drug induced: Drug stimulates IgM production against RBCs
Immune Complex Mechanism
If store blood for too long, what may occur?
Metabolic Complications: Storage lesion –> K+ leaks out of RBC during storage
“Underhemoglobinized” hypochromic microcytic cells
β-thalassemia
Transfusion related acute lung injury is due to antibodies in the donor plasma directed against the recipient’s (1); these are usually (2) antigens
- WBC’s 2. class I MHC
Hburia in the morning that disappears in the afternoon
Paroxysmal Nocturnal Hburia
Sulfhydryl groups in Hb is oxidized and precipitates forming 1)
1) Heinz bodies
G6PD inheritance
X-linked recessive
metabisulfate test
causes sickling in both sickle cell disease and trait
Due to slow transit times, Sickled cells show increased adhesion 1)
1) to vascular endothelium
Increased risk of sickling occurs w/
hypoxemia, dehydration and acidosis
Drug induced: Direct or indirect Coombs’ test: IgG only
hapten type or autoantibody type
What problem can occur as a result of a rapid infusion?
Rapid infusion results in chelation of calcium by citrate (which is used as an anticoagulant for blood)
↑ LDH
seen in hemolysis
Direct Coomb’s Test: (+) anti-IgG, (+) anti-C3d or both.
Warm AIHA
Sickle cell: polymers aggregate and RBCs lose 1) and have 2)pH;
1) intracellular K+ and h2O 2) ↓
Erythroblastosis fetalis s/s
ANEMIA hepato-splenomegaly; jaundice soon after birth; Generalized edema;
common infection in Sickle cell
Osteomyelitis w/ salmonella or other encapsulated organisms
CD59
inhibits C3 convertase and activation of the alternative complement pathway.
HPA-1a; what is it?
if pt lacks this, after transfusion, develops post transfusion purpura;
Fever; urticaria, pruritus, erythema after transfuion
allergic reaction
↑RDW
Iron def. anemia Hereditary spherocytosis
cell is expanding in size but nucleus is not dividing—hence macrocytic
Megaloblastic Anemia
Transfusion complication: pt LACK platelet antigen HPA-1a
post transfusion purpura
affect of pH on sickling
dec. pH reduces the oxygen affinity of hemoglobin, thereby increasing the fraction of deoxygenated HbS at any oxygen level increasing sickling
Pernicious anemia lab
↓ Intrisic factor ↓ Vitamin B12 therefore ↑serum homocysteine; ↑ methylmalonic acid
↑ risk of parvovirus–> aplastic crisis
Thalassemia Hereditary Spher. Sickle Cell
IgG abs opsonize RBCs at body temperature
warm AIHA
Pt with CHF or heart failure–> what transfusion complication?
Circulatory overload
Splicing mutations –> create an “ectopic” cryptic splice site within the intron
β+-thalassemia
Sickle Cell Anemia: amino acid change
Glutamic acid replaced by Valine
Destruction of splice donor or splice acceptor sites.
β0-thalassemia
hyper cellular bone marrow with ringed sideroblasts,
Myelodysplastic syndrome:
Structurally abnormal hemoglobin; quantity fine
Sickle Cell Anemia
Increased LDH and UCB, decreased Hct and haptoglobin; Hemoglobin normal!
Delayed hemolytic transfusion rxn
Promotor mutations–> ↓ transcription (i.e. affects pre-mRNA)
β+-thalassemia
conditions that decrease the MCHC (alpha thalassemia) reduce the disease severity
Sickle cell
Hand-foot syndrome: Dactylitis of bones—happens in children
Sickle cell
Hereditary Spherocytosis s/s
extravascular hemolysis therefore: ↑ UCB–> jaundice Bilirubin gallstone ANEMIA ↑LDH
att birth w/ marked jaundice and require transfusions.
compound heterozygote Hereditary Spherocytosis
Hereditary Spherocytosis treatment:
Splenectomy
compound heterozygote Hereditary Spherocytosis
birth w/ marked jaundice and require transfusions.
protected against P. falciparum malaria
Sickle Cell anemia Thalassemia G6PD
Febrile non hemolytic transfusion reaction labs
normal; no inc. LDH, UCB, Retic, count, no decrease in haptoglobin or Hct
monnuclear megakaryocytes with no platelets in periphery
Myelodysplastic syndrome:–> dysmegakaryopoiesis
How does transfusion related acute lung injury appear on chest x-ray?
diffuse bilateral pulmonary infiltrates which are unresponsive to diuretics
Oxidant drugs –> antimalarials, sulfonamids, and nitrofurantoins.
G6PD
Target cells
Thalassemia Sickle cell
decreased synthesis of the globin chains of Hb
Thalassemia
Thalassemia retic count
↑ Reticulocyte count (extravascular hemo)
Nonsense or frameshift mutations–> early stop codon
β0-thalassemia
Homozygous for HbS but also has coexistent 1), which reduces Hb synthesis and has milder disease
1) α-thalassemia
Drug induced: Drug stimulates IgG production against RBCs
Autoantibody Mechanism
Hereditary Spherocytosis diagnosis:
Osmotic fragility test: red cells lyse in hypotonic sln
microcytic, hypochromic RBCs, target cells, and basophilic stippling
β-thalassemia
Complement mediated RBC lysis, platelet aggregation, and hypercoagulability
PNH
Iron-Deficiency Anemia RBC indices
MCV, Hb, Hct and MCH are all ↓.
Vascular obstruction, particularly stroke (CVA)
Sickle cell disease
INACTIVATING somatic mutation of PIG-A
PNH
increased reticulocyte count
Immune Hemolytic Anemia Hereditary Spherocytosis G6PD deficiency PNH
Sickle cells s/s due to vasoocclusion
vascular necrosis of the femur renal infarcts Not comprehensive
PNH diagnosis
Deficient: Decay-accelerating factor (CD55 Membrane inhibitor of lysis (CD59) C8 binding protein
acquired clonal stem cell disorder; DYSMORPHIC blood cells and precursors
Myelodysplastic syndrome:
Sickling of RBCs either cause:
(a) Hemolysis: extravascular (spleen) (b) Microvascular occlusion (due to sickle shape)
Transfusion complication: Acute hemolytic transfusion rxn: what cytokines?
Pro inflammatory cytokines (IL‐1 ,IL‐6 ,IL‐8 ) TNF alpha NO (EDFR )
Sickle Cell Trait vs. disease inheritance
Sickle Cell Trait –> heterozygous Sickle Cell Disease –> homozygous
asymptomatic—only sickle on profound hypoxia
Sickle Cell Trait
Autoimmune Hemolytic Anemia intra/extravascular
EXTRAvascular; both warm and cold
Intravascular hemolysis s/s
Hbemia, Hburia, Hemosiderinuria, and ↓haptoglobin
Delayed hemolytic transfusion rxn lab
lack of expected rise in Hb;
ACD RBC indices
Normocytic normochromic
Drug induced: Mild to moderate hemolysis, w/ slow onset developing over days to weeks
• Penicillin • Methyldopa
Erythroblastosis fetalis complication
kernicterus due to Inc. UCB (fat soluble)
β-thalassemia Hb electrophoresis
↑in HbA2 (α2δ2)
Sickle cell: 1) in the sixth codon of β-globin that leads to the replacement of a glutamate with a valine residue.
1) point mutation
β-Thalassemia: ___ is temporarily protective
HbF
