Hematology Flashcards
megaloblastic anemias
Macrocytic-Normochromic Anemias
Pernicious anemia
folate deficiency anemia
Methylmalonic acid and homocysteine levels are elevated early in the disease
pernicious anemia evaluation
Folate (folic acid) deficiency anemia s/s
Severe cheilosis: Scales and fissures of the lips and corners of the mouth
Stomatitis: Mouth inflammation
Painful ulcerations of the buccal mucosa and tongue: Characteristic of burning mouth syndrome
Dysphagia (difficulty swallowing), flatulence, and watery diarrhea
Folate (folic acid) deficiency anemia and CNS s/s
usually not seen
Pernicious anemia s/s
Weakness, fatigue
Paresthesias of the feet and fingers, difficulty walking
Loss of appetite, abdominal pains, weight loss
Sore tongue that is smooth and beefy red, secondary to atrophic glossitis
“Lemon yellow” (sallow) skin as a result of a combination of pallor and icterus
Neurologic symptoms from nerve demyelination - Not reversible
- Most common type of anemia worldwide
Iron-deficiency anemia
Sideroblastic anemia cause
defect in mitochondrial heme synthesis. Altered mitochondrial metabolism causes ineffective iron uptake and results in dysfunctional hemoglobin synthesis
o Sideroblasts
Erythroblasts contain iron granules that have not been synthesized into hemoglobin.
- Reversible sideroblastic anemia a/w
Associated with alcoholism
Sideroblastic anemia s/s
o Iron overload (hemochromatosis)
o Enlarged spleen (splenomegaly) and liver (hepatomegaly)
Sideroblastic anemia diagnostic
o Dimorphism
o Dimorphism
Normocytic and normochromic cells concomitantly observed with microcytic-hypochromic cells
Sideroblastic anemia tx (hereditary)
Pyridoxine (B6) therapy; life-long maintenance therapy at a lowered dose
Sideroblastic anemia tx (congenital)
Stem cell transplantation
Sideroblastic anemia tx (myelodysplastic synd (decreased RBC production))
Recombinant human erythropoietin
- Pancytopenia
Reduction or absence of all three types of blood cells
- Most aplastic anemias are
autoimmune disorders
Aplastic anemia patho
Hypocellular bone marrow that has been replaced with fat
- Paroxysmal nocturnal hemoglobinuria: deficiency in
CD55 and CD59: Cause complement-mediated intravascular lysis and release of hemoglobin
hapten model
Drug-induced hemolytic anemia
Drug-induced hemolytic anemia most common cause
cephalosporins. others also PCN and hydrocortisone
hemolytic anemia s/s
o May be asymptomatic
o Jaundice (icterus)
o Splenomegaly
hemolytic anemia tx first line
Corticosteroids
hemolytic anemia tx 2nd line
Splenectomy and Rituximab (Rituxan) (monoclonal antibody)
o Paroxysmal nocturnal hemoglobinuria tx
Eculizumab (Solaris)
- Polycythemia vera: acquired mutation in
Janus kinase 2 (JAK2) - * Negates the self-regulatory activity of JAK2 that allows the erythropoietin receptor to be constitutively active, regardless of the level of erythropoietin.
Polycythemia vera can convert to
acute myeloid leukemia (AML)
Polycythemia vera s/s
splenomegaly. painful itching by heat or water
Polycythemia vera tx
phlebotomy )300-500cc). spirin, interferon-a, hydroxyurea, radioactive phosphorus
- Hereditary hemochromatosis: autosomal…
recessive
Hereditary hemochromatosis
increased gastrointestinal iron absorption with subsequent tissue iron deposition
Hereditary hemochromatosis s/s
Hepatomegaly, abnormal liver enzymes, bronzed skin, diabetes, and cardiomegaly
Hereditary hemochromatosis tx
Phlebotomy; refrain from taking iron and vitamin C supplements and consuming raw shellfish; alcohol use in moderation
AML mutation
tyrosine kinase FLT3
ALL genetic anomoly
Philadelphia chromosome on chromosome 9and 22
CML genetics
Philly chromosome present and BCR-ABL1 causes intiaiton
CLL most common s/s
lymphadenopathy
CML cure
no cure
non hodgkins lymphoma cells
B cells, T cells, and NK cells
more localized: hodgkins or non?
hodgkins
Burkitt lymphoma
highly aggressive B-cell non-hodgkin lymphoma of jaw. EBV 90%. abd swelling. Rituximab tx
lymphoblastic lymphoma
rare non-hodgkin type.
lymphoblastic lymphoma population
1/3 in male children and adolescents
lymphoblastic lymphoma origin
T-cell in thymus 85%
lymphoblastic lymphoma first s/s
painless lymphadenopathy in neck
multiple myeloma translocation
imglobulin heavy chain on chromo 14
multiple myeloma patho
production of too much M protein (abnorm antibody). Light chains (Bence Jones proteins) pass through glomerulus and cause kidney damage
multiple myeloma s/s
hypercalc, renal failure, anemia, lytic lesions, infections
Occurs before multiple myeloma
Monoclonal Gammopathy of Undetermined Significance
Monoclonal Gammopathy of Undetermined Significance diagnosis
presence of an M protein in the blood or urine without additional evidence of multiple myeloma
Waldenström Macroglobulinemia
lymphoplasmacytic lymphoma. rare type of slow-growing plasma cell tumor that secretes a monoclonal immunoglobulin M (IgM) molecule. Arises from plasma cells that have genetic rearrangement of region genes (V, D, J)
Thrombocytosis
Plt >400k
Immune thrombocytopenic purpura: Ig_ antibody targets platelet _.
IgG, glycoprotein
procoagulant factors
7,9,10
vitamin K makes
prothrombin, procoag factors 79,10), and protein c and s (anticoags)
DIC patho
release of tissue factor leading to increased fibrin and thrombin activity. and increased fibrinolysis. overconsumption of platelets and clotting factors
primary thrombophilia
hereditary. defect in proteins for hemostasis
secondary thrombophilia
acquired. decreased anticoag proteins
hereditary thrombophilia (primary) are mostly autosomal…
dominant
antiphospholipid syndrome
autoimmune antibodies against plasma membrane phospholipids. tx: heparin with aspirin
normal rbc lifespan for full term infants
60-80 days
rbc lifespan for preemies
20-30 days
when are normal adult hgb % established
6-12 M
when do erythrocyte production begin in bone marrow
5 M gestation
hemolytic disease of newborn
erythroblastosis fetalis. alloimmune disease. Maternal blood and fetal blood incompatibility.
hemolytic disease of newborn test and prevention
Coombs test. Rhogam
glucose 6 phosphate dehydrogenase deficiency: genetics
x-linked, recessive
glucose 6 phosphate dehydrogenase deficiency
G6PD maintains RBC metabolic processes. Deficiency shortens lifespan. Only happens when stressors are present
Heinz bodies
denatures hgb in RBCs. seen in glucose 6 phosphate dehydrogenase deficiency.
Hereditary spherocytosis
congenital hemolytic anemia causing abn proteins and increased intracellular Na+. no hemoglobin abnormality exists
Hereditary spherocytosis is autosomal…
dominant
Hereditary spherocytosis s/s and tx
anemia, jaundice, splenomegaly. Folic acid and partial splenectomy.
Sickle cell genetics
valine is replaced with glutamic acid. Autosomal recessive
aplastic crisis
occurs d/t a viral infxn in sickle cell disease
Thalassemias are autosomal…
recessive
beta-thalassemia minor
mild-mod microcytic-hypochromic anemia.
alpha-thalassemia minor
2 genes
alpha-thalassemia major
4 genes, fatal
hgb H disease
3 genes
Hemophilia A
Factor 8 deficiency. X-linked
Hemophilia B
Xmas disease. Factor 9 deficiency
Hemophilia C
Factor 11 deficiency
von wilibrand disease
autosomal dominant. factor 8 defiency
Primary use for cryo
Hemophilia A. Blood factor 8
What increases factor 8 activity
Desmopressin (ADH)
Heparin requires what for action
antithrombin 3
Heparin inhibits what factors
9a, 10a, 11a, 12a, and thrombin (2)
t1/2 of heparin increases with
liver or renal disease
heparin is found in
mast cell and nerve terminal vesicles
heparin structure
glycosaminoglycan
dextran -_ is fromed from dextran -_
40,70
dextran-40 is removed in
the glomerulus
dextran-70 is converted to
glucose
which blood sub is actual O2 carrying
perfluorocarbons. not in market d/t surfactant destruction
the platelet plug is strengthened by the addition of
fibrin via coag cascade
PG-I2 produced by and action
COX-2. inhibits plt aggreg and vasodilates
TX-A2 produced by and action
COX1. plt aggreg and vasoconstricts
apsirin is covalently bonded to
COX-1> COX-2
high CAMP levels _ aggregation
inhibits
CAMP is controlled by
TX-A2 and others
Diprydamole
PDE-5 inhibitor. weaky anitplt. given with warfarin. can induce angina
ADP inhibitor MOA and examples
blocks decrease in CAMP by P2Y12 proteins
- clopidogrel: prodrug
- ticlopidine: prodrug
-Cangrelor
-Ticagrelor
-Prasugrel
ADP inhibitor who cant tolerate aspirin
ticlopidine
irreversible oral ADP Inhibitor
prasugrel
reversible oral ADP Inhibitor
ticagrelor
glycoprotein 2b/3a receptors. Inhibitors ex:
where fibrinogen binds on plts
-abciximab
-eptifibatide: peptide
-tirofiban: non peptide tyrosine
Hirudin
thrombin inhibitor. peptide. doesnt need AT3 like heparin and can replace heparin
bivalirudin
similar to hirudin
Argotraban. What does it trigger?
thrombin inhibitor. arginine derivative. Triggers nitric oxide release
does heparin cross placenta?
no
LMWH
Lovenox. requires PENTAsacchiride like heparin
fondaparinux inhibits?
LMWH. acts with AT3 to inhibit 10a, not thrombin
warfarin reversal
vit K or FFP to provide prothrombin
warfarin clearance rated decreased by
amio, cimetadine, omeprazole
does warfarin cross the placenta?
yes
Dabigatran
esterase prodrug activated by by plasma and liver esterases
-XABANs MOA
inhibitors of factor 10a
apixaban also inhibits
prothrombinase which converts prothrombin (factor 2) to thrombin (2a)
Adexanet alfa
reverses factor 10a inhibitors
Thrombolytic agents
streptokinase, alteplase
streptokinase isoalted from
beta-hemolytic streptococci. possible allergic reaction
alteplase
Tissue plasminogen activator (TPA)
