hematology and cardiovascular system Flashcards
sickle cell anemia
normocytic hemolytic
autosomal recessive disease that results in abnormal hemoglobin characterized by hemoglobin S (HbS), resulting in hemolytic anemia (RBC destroyed every 17 days) and vaso-occlusion
HbS results from point mutation of ß-globin gene that substitutes valine for glutamic acid
clinical presentation of sickle cell anemia
acute events-
anemia
vaso-occlusive events
acute painful episodes
triggers include cold temperature, stress, alcohol, and menses
dactylitis- acute pain in hands and feet particularly common in children
acute chest syndrome
cerebrovascular accidents
myocardial infarction
priapism
renal infarction
splenic infarction
by 2-4 years of age, patients have functional asplenia
venous thromboembolism
chronic events
Pain, hemolytic anemia, renal disease, asplenia retinopathy, pulmonary HTN, cardiomegaly
Physical exam
splenomegaly
jaundice
pallor
bone/joint tenderness
hydroxyurea
Thalassenia anemia
microcytic (MCV < 80 IL )
Autosomal recessive disease caused by decreased production of hemoglobin
may involve mutations in α (α-thalassemia) or β (β-thalassemia) globin gene
see in asian and african
EVALUATION
Peripheral smear
target, hypochromic, microcytic cells
Hemoglobin gel-electrophoresis
β-thalassemia minor
↑ HbA2, HbF
↓ HbA
β-thalassemia major
↑ HbA2, HbF
no HbA
frequent transfusion
G6PD Deficiency
normocytic hemolytic
x linked genetic disorder
common in areas where malaria is endemic
sub-Saharan Africa
Middle East
southeast Asia
Mediterranean regions
Pacific islands
thought G6dp deficiency dec risk of malaria
6PD affects the pentose phosphate (hexose monophosphate) pathway
this pathway generates nicotinamide dinucleotide phosphate (NADPH), which protects red blood cells against oxidative stress
acute hemolytic anemia following exposure to oxidative stressors -
primaquine
dapsone
sulfa drugs
infections
fava bean ingestion
oxidative stressors cause
rapid depletion of reduced glutathione resulting in
precipitation of hemoglobin (manifested as Heinz bodies)
erythrocyte membrane damage, both extravascular and intravascular hemolysis
peripheral smear
bite cells
Heinz bodies
acute hemolytic anemia following exposure to precipitants, typically within 24-72 hours after ingestion
fatigue
jaundice
dark urine
back pain
Physical exam
jaundice
B 12 deficiency
vitamin B12 (cobalamin) is a water-soluble vitamin that is involved in the formation of hematopoietic cells and maintainance of myelin integrity
vitamin B12 deficiency results in a
megaloblastic anemia
reversible dementia
subacute combined degeneration( weakness, sensory, gait issues)
Etiology
decreased oral intake
strict vegan diet
breastfeeding in a vitamin B12 deficiency mother
decreased animal product intake
decreased absorption
gastrointestinal surgeries
bariatric surgery
grastrectomy
illness
Crohn disease
celiac disease
pancreatic insufficiency
Diphyllobothrium latum (fish tapeworm)
gastric atrophy
medications
proton pump inhibitors
histamine receptor antagonist
metformin
autoimmune disease
pernicious anemia
autoantibodies against intrinsic factor or gastric parietal cells
Pernicious anemia
macrocytic
autoimmune disease
autoantibodies against intrinsic factor or gastric parietal cells, impair absorption of Vit B 12
Folic acid Deficiency anemia
Macrocytic
megaloblastic anemia
Folic acid (or vitamin B9) is found in leafy green vegetables
Pathogenesis
folic acid is absorbed in jejunum and ileum
used in tetrahydrofolate (THF) as coenzyme
important for DNA and RNA synthesis
small reserve pool in liver
causes megaloblastic anemia due to impaired DNA synthesis
Associated with
alcoholism
malabsorption
celiac disease
pregnancy
risk of neural tube defects in infant
certain drugs (anti-folates)
phenytoin
methotrexate
Aplastic anemia
Normocytic non-hemolytic
caused by diminished, absent, or destructed hematopoietic stem cells of bone marrow. bone marrow aplasia
result of pancytopenia
idiopathic- immune-mediated destruction of stem cell
secondary-, exposure to drugs, infectious agents, or other environmental factors.
radiation, chemical agent
benzene
chloramphenicol
anti-epileptics (phenytoin and carbamazepine)
alcohol
alkylating agents
insecticides
viruses-EBV, HIV, CMV, HCV
parvovirus
can cause transient aplastic crisis
rarely can progress to aplastic anemia
complication- infection, bleeding
Labs-
anemia
leukopenia
thrombocytopenia
↓ reticulocyte count
Bone marrow biopsy
hypocellular bone marrow with fatty infiltration
TREATMENT
Withdrawal causative agent
RBC transfusion
platelet transfusion
Bone marrow transplant
Antithymocyte globulin plus cyclosporine
Hematopoietic growth factors (G-CSF and GM-CSF)
anemia of chronic disease
normochromic, normocytic anemia
results from a combination of (1) decreased erythrocyte life span, (2) suppressed production of erythropoietin, (3) ineffective bone marrow response to erythropoietin, and (4) altered iron metabolism and iron dynamics in macrophages.
Pathogenesis
iron is stored in macrophages or bound with ferritin
during inflammation, cytokine is released by lymphocytes, macrophages, and the affected tissue. increases hepcidin ( an acute inflammation reactant)
release by the liver
↑ hepcidin during inflammation
binds ferroportin on intestinal mucosa,
inhibits iron absorption from diet
prevents release of iron bound by ferritin from macrophages
causes anemia
characterized by low levels of circulating iron and reduced levels of transferrin.
Labs
↑ ferritin
↓ serum iron
↓ TIBC(total iron-binding capacity), transferrin saturation, and MCV
autoimmune hemolytic anemia
Extrinsic hemolytic anemia
type II hypersensitivity
autoantibodies, complement, directed against antigens on the surface of erythrocytes.
Warm autoimmune hemolytic anemia - The IgG-coated erythrocytes bind to the Fc receptors on monocytes and splenic macrophages and are removed by phagocytosis
Cold agglutinin autoimmune hemolytic anemia- IgM autoantibodies bind to circulating erythrocytes where they activate complement leading to phagocytosis by mononuclear phagocytes in the liver and spleen
Drug-induced hemolytic anemia
TREATMENT
Warm agglutinin
glucocorticoids
IVIG
splenectomy
immunosuppressant
Cold agglutinin
keep extremities warm
supportive therapy with folate ( to prevent aplastic anemia )
rituximab
plasmapheresis for those refractory to rituximab
leukemia
Acute Lymphoblastic Leukemia (ALL)
most common cancer in children
uncontrolled proliferation of immature WBC (blast cell )Crowding of bone marrow leads to bone marrow failure
chromosome translocation 12,21; 9, 22 (aka. Philadelphia chromosome )
down syndrome
B cell ALL 80 %
T cell ALL (mediastinal mass from infiltration of the thymus- overflow t cell deposited in lymphatic tissue)
Symptoms
most common symptom is fever
acute onset
recurrent infections
bleeding
fatigue
bone pain
Physical exam
mediastinal mass from infiltration of the thymus
hepatosplenomegaly
lymphadenopathy
CBC reflects bone marrow failure
anemia
thrombocytopenia
↓ mature WBCs
Bone marrow aspiration with cytogenetics
↑ lymphoblasts
TdT+, a marker of pre-T and pre-B cells
T-cell ALL
CD2+, CD3+ (surface marker)
B-cell AML
CD10+ CD19+
negative MPO (myeloperoxidase)
t(12:21)
Acute Myelogenous Leukemia (AML)
Subtypes
M3 aka acute promyelocytic leukemia (APL)
t(15;17)
disruption of retinoic acid receptor (RAR) required for cell division and myeloblast maturation
associated with DIC
presence of Auer rods
peroxidase positive eosinophilic cytoplasmic inclusions
acute megakaryoblastic leukemia
associated with Down syndrome
< 5 years of age (recall leukemia in Down syndrome occurring in > 5 years of age = ALL)
acute monocytic leukemia
infiltration of gums
Symptoms of pancytopenia (high WBC count but WBCs are dysfunctional)
fatigue
dyspnea
infection due to dysfunctional blasts
bleeding
Physical exam
lymphadenopathy
fever
hepatosplenomegaly
Peripheral blood smear, bone marrow biopsy
myeloblast cell ( larger than lymphoblast)
> 20% blasts in blood smear
myeloblasts with Auer rods in APL
Most accurate test = flow cytometry
Chronic Lymphocytic Leukemia (CLL)
Chromosomal abnormality cause clonal proliferation of incompetent B-cells (partially developed, don’t die as they should)
> 60 years of age
most common form of leukemia in adults in Western countries
more common in Caucasian males
Insidious onset of symptoms (chronic, not acute) often diagnosed incidentally
Associated conditions
warm autoimmune hemolytic anemia (IgG)
Symptoms
many are asymptomatic at presentation
most common symptom is fatigue, bleeding
recurring infections (secondary to leukopenia
anemia
thrombocytopenia )
Physical exam
painful lymphadenopathy
called small lymphocytic lymphoma when there is high degree of lymph node involvement ( can progress to cell cell lymphoma)
hepatosplenomegaly
EVALUATION
Most accurate test
flow cytometry – CD5, CD19, CD20, and CD23+ B-cells
Peripheral blood smear
smudge cells = hallmark
complications
Richter syndrome/transformation
transformation of CLL into aggressive large B-cell lymphoma
Chronic myeloid leukemia
Clonal hematopoietic stem cell disorder
Pathogenesis
Philadelphia chromosome
translocation t(9;22)
BCR-ABL fusion gene
hyperactive tyrosine kinase
Symptoms
fever, weight loss, fatigue
splenomegaly
LUQ discomfort
early satiety
Physical exam
splenomegaly common
EVALUATION
Complete blood count with differential
↑ WBC
↑ neutrophils
↑ basophils
↑ metamyelocytes
↓ leukocyte alkaline phosphatase
low activity in mature granulocytes
edical management
tyrosine kinase inhibitors are first-line
imatinib (Gleevec)
nilotinib
dasatinib
Complications
transformation to acute leukemia (blast crisis)
