Heme/ONC Flashcards
Hemoglobin levels in iron deficiency anemia and thalassemia
decreased in both cases
MCV in both IDA and thalassemia
decreased in both cases
serum iron in both IDA and thalassemia
IDA: decreased
thalassemia: normal
ferritin in both IDA and thalassemia
IDA: decreased
thalassemia: normal
Hemoglobin electrophoresis in both IDA and thalassemia
IDA: normal
alpha thalassemia: normal
beta thalassemia: increased HbA2 and HbF
what happens if we give iron in IDA and thalassemias?
IDA: improvement
Thalassemias: no improvement
RDW (red cell distribution width) in IDA and thalassemias
increased in IDA and decreased/normal in thalassemias
blood smear for IDA vs thalasemias
IDA: pale RBC (central pallor)
thalassemias: target cells
tx for IDA vs thalassemias
IDA: oral iron supplementation
thalassemias: transfusions if severe
what is a thalassemia
abnormal synthesis of either the a or b globin chain and can present 1 of 2 ways on USMLE
microcytic anemia with normal ferritin + iron
OR
microcytic anemia despite iron supplementation
IDA is mostly seen in
mensturating women despite if they are bleeding heavy or not
what 3 drugs cause constipation
iron, aluminum, verapamil
each RBC transfusion contains
iron (chelators can be used to treat- deferoxamine)
A thalassemias
1 mutation- asymptomatic
2 mutations- similar to IDA with no improvement with iron supplementation
3 mutations (HBH disease)- sick as a kid
4 mutations (barts disease)- fatal in utero)
B thalassemias
1 mutation- IDA symptoms
2 mutations- sick as a kid
b thalassemia has increased what
hemoglobin HbA2 (a2/g2) and HbF (a2/y2)
chipmunk facies/skull and hepatosplenomegaly are seen in thalassemias because of
Extramedullary hematopoiesis
Anemia of chronic disease is caused by
chronic conditions that no longer respond to iron, iron is trapped in macrophages and cytokines are released suppressing hematopoiesis
lab studies for anemia of chronic disease
low iron
normal-high ferritin
low TIBC
increased hepcidin
what is the most common cause of anemia of chronic disease and why
renal failure because there is cytokine mediated erythropoietin deficiency
what is multiple myeloma
cancer of the plasma cells that increase serum immunoglobulins since plasma cells already secrete immunoglobulins
symptoms of multiple myeloma
middle aged patient with back pain and hypercalcemia
immunoglobulins will deposit in the heart and kidney
why does hypercalcemia occur in multiple myeloma?
the proliferating cancerous plasma cells cause lytic lesions of the bone.
this may present with pathological rib fractures or pepper pot skull
diagnosis algorithm for multiple myeloma
- serum electrophoresis which will show increase IgG kappa or lambda light chains - M spike
- bone marrow biopsy to confirm showing greater than 10% plasma cells
urinalysis in multiple myeloma will show?
bence jones proteinuria which is IgG light chains in the urine
blood smear in multiple myeloma will show what 2 things
blue plasma cells with clockface chromatin
OR
rouleaux RBC which is from IgG light chain sticking to RBCs causing them to stack
why can MCV be high in multiple myeloma
more immunoglobulins are being carried by the RBC and since less there is more plasma cell and less RBC the RBC enlarge to compensate
what B vitamin deficiencies can be caused by MM
B9 and B12
treatment of MM
IV bisphosphonates
monocolonal gammopathy of undetermined significance
bone marrow biopsy showing less than 10% plasma cells with fatigue and or increased MCV but not hypercalcemia or renal dysfunction
what is waldenstrom macroglobulinemia ?
this is a plasma-like clonal expansion/ cancer that causes a IgM M-protein spike
symptoms of waldenstrom macroglobulinemia
hyper viscosity: headache, blurry vision, tinnitus, Raynaud phenomenon
what is polycythemia vera
a JAK 2 mutation that causes proliferation of hematopoietic stem cells
at least 2 cell lines will be increased with RBCs always high (Hb)
increased Hb can cause what
hyper-viscosity syndrome
basophilia can cause
puritis after a shower
increased Hb in polycythemia vera suppresses what
EPO
treatment of polycythemia vera
phlebotomy to treat acute hyper viscosity syndrome like headache or blurry vision
serial phlebotomy and hydroxyurea to decrease symptom recurrence
what is secondary polycythemia
an isolated increase in RBC due to increased erythropoietin
WBC and platelets ar normal
what causes increased EPO production
lung diseases with low O2 in the arteries which is sensed by the kidneys to make EPO
renal cell carcinoma can secrete EPO and PTHrp
exogenous administration of EPO
Prothrombin time reflects what pathway
extrinsic
activated partial thromboplastin time reflects what pathway
intrinsic
normal PT time is
10-15 seconds
normal PTT time is
25-40 seconds
normal bleeding time is
2-7 minutes
bleeding time is related to?
platelets!!!
PT and PTT are related to
clotting factors!!!
Immune/idiopathic thrombocytopenic purpura
antibodies against glycoproteins IIb/IIIa on platelets that causes a decreased number of platelets and increased bleeding time
no change to PT and PTT because clotting factors are not affected
platelets in ITP are usually less than?
100,000
ITP is typically preceeded by?
viral infection (type 2 hypersensitivity)
treatment of ITP
steroids then IVIG then splenecetomy in this order
if a splenectomy is preformed in a patient with ITP, platelets return to normal within 6 months then start to fall what is the cause?
acessory spleen
symptoms of ITP
brusing
inheritance pattern of vonwilliebrand disease
autosomal dominant
what is vonwillibrand disease
typically vWF causes platelet adhesion by binding glycoprotein Ib to vascular endothelium and collagen
a disruption causes decreased platelet adhesion and decreased stabilization of factor 8
symptoms of vonwilliebrand disease
increased bleeding time, increased PTT (intrinsic, heparin), normal platelet count
platelet problems
petechiae, brusing, epistaxis
clotting factor problems
excessive with tooth extraction, heavy menses,
what cofactor is abnormal in vWD
ristocetin cofactor
treatment of vWD
desmopressin which releases vWB from weieble pallide bodies
hemophilia A is a deficiency in ?
factor VIII (8)
hemophilia B is a deficiency in?
factor IX (9)
blood studies in hemophilias?
isolated increased in PTT (intrinsic pathway)
symptoms of hemophilias
hemarthrosis, neonate excessive bleeding with circumcision
hemophilia A treatment
desmopressin and factor VIII replacement
hemophilia B treatment
factor IX replacement
How does vitamin K deficiency effect blood studies
increased PT and PTT
no affect on bleeding time ! (no platelets are affected)
vitamin K is a cofactor for what?
gamma-glutamyl carboxylase
gamma-glutamyl carboxylase activates what factors
II, VII, IX, X, C and S
symptoms of vitamin K deficiency
bleeding from umbilical stump , retinal hemorrhages
warfarin inhbits what vitamin functions
vitamin K
Disseminated intravascular coagulation
consumption of both platelets and clotting factors leading to an increase in bleeding time, PT, PTT, d-dimer, and plasmin activity
decrease in clotting factors, fibrinogen, and platelets
why is fibrinogen decreased in DIC
fibrinogen is converted to fibrin with the increased plasmin activity
what is D-dimer high in DIC
more fibrin is broken down and d-dimer is a measure of fibrin breakdown products
causes of DIC
trauma, sepsis, amniotic fluid embolism, treatment of AML
blood smear of DIC shows
schistocytes
hemolytic uremic syndrome triad
thrombocytopenia, hemolytic anemia with schistocytes, and renal insufficiency
pathogenesis of HUS
ecoli and shigella secrete toxins that cause inflammation of the renal vasculature and inactivate ADAMTS13 protein which leads to big bulky von willebrand multimers. The aggregates of platelets attached to the big vWF shear rbcs as they pass by leading to schistocytes
thrombotic thrombocytopenic purpura is
HUS (hemolytic anemia, thrombocytopenia, renal dysfunction) along with fever and neurological symptoms
cause of TTP?
antibodies against ADAMTS13 (can no longer breakdown vWF multimers)
treatment of TTP
plasmapheresis
sickle cell disease inheritance and mutation
autosomal recessive
a glutamic acid to valine missense mutation on the beta chain
why does sickle cell exist?
heterozygous advantage (protective against malaria)
sickle cell crisis can present as?
abdominal or chest pain
dactylitis (inflammation of the fingers)
sickle cell diagnosis
blood smear followed by electrophoresis to detect HbS
sickling occurs when
with dehydration and increased acidity
(hydrophobic interactions)
treatment of sickle cell
hydroxyurea to increased hemoglobin F and decrease sickling recurrence
myelofibrosis is a mutation in
JAK2 (same as polycythemia vera)
symptoms of myelofibrosis
fibrosis of the bone marrow
tear-drop-shaped RBCS/poikilocytes , dry tap on bone marrow aspiration
pathogenesis of myelofibrosis
Abnormal proliferation of megakaryocytes and granulocytes releases growth factors and cytokines that stimulate collagen deposition in the bone marrow leading to fibrosis
essential thrombocythemia
JAK 2 mutation that causes increased proliferation of platelets
symptoms of essential thrombocythemia
hyperviscosity: headache, raynaud phenomenon
platelet count is really really high- higher than 1 million
tx of essential thrombocythemia
aspirin and plateletpheresis
reactive thrombocytosis
a triggering event stimulates the production of thrombopoietin and increased platelet production
common triggering event is endocarditis
usually an incidental finding- asymptomatic
treatment of reactive thrombocytosis
treat underlying infection and give aspirin
glanzmann thrombasthenia
deficiency in glycoproteins IIb/IIIA on platelets which leads to defective aggregation ( increased bleeding time)
bernard- souiler
deficiency in glycoprotein Ib on platelets and causes defective adhesion
abnormal ristocetin cofactor
systemic lupus erythematous most common presenting symptom is
arthritis
the malar rash in SLE is what type of hypersensitivity reaction
III
what blood cell count is down in SLE
Platelets (thrombocytopenia)
all can be down but this is HY
SLE has an increased risk for?
lymphomas
what kind of renal dysfunction does SLE cause
diffuse proliferative glomerulonephritis
SLE in pregnant women can cause
Congenital heart block in neonates
treatment of SLE flares
steroids
paroxysmal nocturnal hemoglobinuria is what
increased complement mediated hemolysis
the deficiency of CD55 and CD59 which are GPI anchors can no longer protect RBCs from complement mediated breakdown
complement activity is highest at night–> will present with red urine in the morning
hageman factor is factor number?
XII (12)
aka the first clotting factor in the intrinsic pathway
what is hageman factor deficiency
a def in factor 12 that does not cause symptoms, it has a high PTT
decreased kallikrein
what is factor V leiden mutation
there is activated protein C resistance (resisting the anticoagulant)
clots and DVTS
Va stays activated
what is protein C deficiency
the anticoagulant protein C is not working and there are DVTs and clots
there is skin necrosis if the patient recieves warfarin
what is the job of Antithrombin III
to inactivate IIa, Xa, and IXa
what is antithrombin III deficiency
the inability to inactivate IIa, IXa, and Xa
symptoms of antithrombin III deficiency
nephrotic syndrome (antithrombin protein is lost in the urine)
superifical thrombophlemitis, renal vein thrombosis
what is antiphospholipid syndrome
antibodies against phospholipids that causes an increase in in vitro PTT and paradoxical thromboses
cause of antiphospholipid syndrome
idiopathic or secondary to SLE
what antibodies are in anti-phospholipid syndrome
antibodies against B2 microglobulin or cardiolipin
antiphospholipid syndrome can present with a false positive for what test
VDRL syphillis test
usmle symptoms for neutropenia
mouth ulcers, fever, sore throat
what is neutropenic fever
neutropenia with a fever caused by chemo/radiation, viruses
this is a medical emergency: infection but no way to clear it
treatment for neutropenic fever?
IV broad spectrum antibodies then G-CSF/filgrastim
viral induced neutropenia is caused by
Parvovirus B19 that can infect myeloid precursors and cause neutropenia
other viruses can make antibodies against neutrophils
what is cyclic neutropenia?
this is a gene mutation that causes episodes of fever, mouth ulcers in a kid 1-3 years of age
usually occurs every 21 days
what is aplastic anemia and what are some causes of it?
all cell lines are down (decreased RBC, WBC, platelets)
caused by ParvoB19, Hepatitis A, HIV, chemotherapy, fanconi anemia
what is pure RBC aplasia and what is it caused by?
only RBCs are decreased
caused by Parvo B19, thymoma, MG, diamond-blackfan anemia (triphalangeal thumbs)
Spherocytosis inheritance pattern
autosomal dominant
hereditary spherocytosis is a mutation in ?
ankyrin, spectrin or band proteins causing a RBC cell membrane defect changing them from biconcave discs to spherical
blood smear of hereditary spherocytosis
spherical red blood cells that lack central pallor
hereditary spherocytosis causes what kind of anemia
normochromic, normocytic
hereditary spherocytosis can cause what kind of stones
pigment stones because the spleen identifies the abnormal RBCs and increases RBC turnover
hereditary spherocytosis has what lab increased
mean corpuscular hemoglobin concentration (MCHC)
*decreased hemoglobin (Hb)
diagnosis of hereditary spherocytosis is made with?
osmotic fragility testing and eosin-5-malimide
hereditary spherocytosis has a postive or negative coombs test
negative
*coombs tests if there are antibodies against RBCs
treatment of hereditary spherocytosis
Splenectomy to decrease cell turnover
spherocytosis caused by a drug or infection induced hemolytic anemia would have what?
antibodies against RBCs and a positive coombs test
what is a leukemoid reaction
an exaggerated response to infection where the WBCs skyrocket and can resemble leukemia.
infection (like UTI) + WBC greater than 30,000 + neutrophils on blood smear + ALP is elevated
neutrophilia on labs (reactive granulocytosis)
what is leukemia
a cancer of white blood cells in the blood
leukemias are almost always from what cell origin
B cell origin
acute lymphoblastic leukemia
increased leukocyte count >60,000 with predominately lymphocytes
increased lymphoblasts
what is an important DDX for acute lymphoblastic leukemia
pertusis; will have a reactive lymphocytosis (increased WBC with 90% lymphocytes)
BUT will also have cough , post tussive emesis and or hypoglycemia
tumor markers for ALL
CD10 and TdT
people with what syndrome have an increased risk for ALL
down syndrome (excess lymphoblasts)
what is chronic lymphocytic leukemia
proliferation of mature WBC with 90% lymphocytes will show smudge cells in an old patient
diagnosis of CLL
quantitative immunoglobulin assay: will show monoclonal immunoglobulin
tumor markers for CLL
CD5 and CD23
CLL can be associated with?
warm autoimmune hemolytic anemia (IgG against RBC)
what is AML?
Acute myeloblastic lukemia that has an increae in myeloblasts (30% blasts)
acute promyelocytic leukemia is a subtype of AML that has a t(15:17 translocation)
what is the translocation for acute promyelocytic leukemia
t(15;17)
what is the characteristic blood smear for AML
auer rods that are composed of myeloperoxidase which is a blue green heme pigment
what is the treatment for acute promyelocytic leukemia
all trans retinoid acid which is a vitamin A derivative (matures blasts)
treatment of AML can cause a leukemic cell crisis where the Auer rods are released into circulation and can precipitate?
DIC
what is CML
chronic myelogenous leukemia that is caused by a 9;22 translocation (phildelphia chromosome)
bcr-abl tyrosine kinase fusion protein
low ALP
treatment of CML
imatinib (targets bcr/abl tyrosine kinase)
leukemia that is characterized by cytoplasmic projections that stains positive for tartrate-resistant acid phosphatase (TRAP)
hairy cell leukemia
what is sezary syndrome
a cutaneous T cell lymphoma that extends to the blood as a T cell leukemia
caused by the T-cell lymphotropic virus
cerebriform shaped T cells in the blood stream
sezary syndrome classically presents as?
erythroderma (red skin)
what is a lymphoma ?
cancer of the lymphatic system that it can start in the lymph nodes but be present in other areas of the lymphatic system like the spleen and the bone marrow
lymphomas are almost always of what origin
B cell origin
lymphomas are characterized by ?
hodgkins or non hodgkins
what increases the risk for lymphomas
EBV, HIV, immunosuppression, autoimmune diseases (SLE)
hodgkins lymphoma is characterized by
reed-sternberg cells that are CD15/CD30 positive
owl eye appearance
symptoms of hodgkins lymphoma
painless lateral neck mass, lymphadenopathy, hepatomegaly, mediastinal lymphadenopathy, virchow node, B signs- fever, night sweats, weight loss
the nodular sclerosing type of hodgkins lymphoma typically affects who
women
does leukocyte rich or leukocyte deplete hodgkins lymphoma have a better prognosis? why?
rich has a parallel increase in leukocytes to reed sternberg cells giving it a better prognosis
burkitt lymphoma translocation
8:14 translocation of the c-myc gene
what is c-myc
a transcription factor
presentation of burkitt lymphoma
jaw lesion in an african boy, abdominal lesion
histology for burkitt lymphoma
starry sky which is basophilic cells with translucent macrophages (tingible body)
what is the tingible body in burkitt lymphoma
the macrophage that eats the lymphamtous B cels undergoing apoptosis
follicular lymphoma translocation
t (14;18) translocation of the BCL-2 gene
what does the BCL-2 gene code for
an anti-apoptotic molecule
presentation of follicular nonhodgkins lymphoma
waxing and waning painless neck mass over 2 years that is indolent in its course
what is diffuse large b cell lymphoma
the most aggressive NHL
mantle cell lymphoma translocation
t(11;14) translocation that overexpresses cyclin D (no stopping the cell cycle)
what is mucoides fugoides
cutaenous T-cell lymphoma that has cerebreform shaped cells
presents as a skin rash
when it goes to the blood it is known as sezary syndrome
what is a postitive coombs test
antibodies against RBC
what is warm autoimmune hemolytic anemia
IgG antibodies against RBC
agglutination of RBC occurs at warm temperatures
occurs with drugs, infections, SLE, CLL, RA
what is cold autoimmune hemolytic anemia
IgM antibodies against RBC
RBC agglutinate at cold temperatures
seen in mycoplasma pneumonia and CMV mononucleosis
infectious mononucleosis is caused by
usually EBV but can be CMV
EBV invades _ cells and stimulates the immune production of _ cells
B cells
CD8+ T cells (attack B cells)- atypical lymphocytes/reactive
symptoms of mono
fever lymphadenopathy, tonsillar exudate, lack of cough
if amoxicillin or penicillin is given to treat EBV it can cause?
rash
test for mono
monospot test
following the primary infection of mono there can be recurrent episodes of?
extreme fatigue that arise at intervals of months to years
what is langerhans cell histiocytosis
an overproduction of langerhans aka dendritic cells
these are antigen presenting cells that takes antigen to the lymph nodes and presents it to CD4+ cells
with an overproduction of the dendritic cells in bone it causes lytic lesions most commonly the skull
electron microscopy of langerhans histocytosis
birbeck granules (tennis raquet shaped) or rod shaped inclusions in the langerhan cell
acanthocytes are seen with what pathology
liver failure due to heat stroke or hepatitis
or abetalipoproteinemia
acanthocytes (spiky red blood cells)
what is heat stroke
end organ damage due to hyperthermia (over 104 degrees)
abnormal liver or fenal function tests
glucose 6 phosphate dehydrogenase deficiency inheritance
X-linked recessive
(most common cause of hemolysis due to an enzyme deficiency)
presentation of G6PD deficiency
a boy who has jaundice after recieving a drug or having a viral infection
what agents can precipiate oxidative damage and exacerbate G6PD deficiency
fava beans, primaquine, dapsone, sulfa drugs
labs in G6PD
increased unconjugated hyperbillirubinemia and LDH
RBCs are packed with
LDH
the enzyme G6PD is necessary to produce what
NADPH (protects the RBC from oxidative damage)
blood smear findings for G6PD deficiency
bite cells and heinz bodies
pyruvate kinase deficiency pathogenesis
decreased ATP production and RBC ATPase pumps, this causes less Na to be pumped out of the RBC, water enters the RBC and causes it to swell and burst
B9 and B12 deficiencies cause macrocytosis how
these deficiencies both lead to impaired DNA synthesis causing the RBC to stay in the bone marrow longer and allowing them to grow larger and larger
nuclear lobes are also created in neutrophils causing hypersegmented neutrophils
high MCV as a result of impaired DNA synthesis is called?
megaloblastic anemia
sideroblastic anemia is a deficiency in?
the first step in the heme pathway
succiny coa–> ala synthase
def in : ALA synthetase
sideroblastic anemia is the failure to incorporate _ into heme
iron
blood smear of sideroblastic anemia
ringed sideroblasts ( iron forms a ring inside the mitochondria of erythroblasts)
lead posioning inihbiits what ( 2 things)
ALA dehydratase and ferrochelatase
lead posioning leads to a build up of what?
ALA
signs of lead posioning
microcytic anemia, mental decline, wrist drop
blood smear of lead poisoning
basophilic stippiling which is rRNA precipitates
what is the treatment of lead poisoning
calcium EDTA, dimercaprol or succimer
what is acute intermittent porphyria
an autosomal dominant deficiency in prophorbilinogen deaminase and causes a buildup of both prohobilinogen and ALA
symptom of acute intermittent porhyria
abdominal pain, port wine colored urine
+/- neurological findings
what is the treatment of acute intermittent porhyria
hematin and glucose
what is porphyria cutanea tarda
this is a deficiency in uroporhyrinogen decarboxylase that leads to increased urinary uroporhyins
photosensitivity blistering
urine is tea colored/dark
intravascular hemolysis
lysis of RBC within the bloodstream
billirubin is released into the blood stream
labs in intravascualr hemolysis
hemoglobinuria
low serum haptoglobin is decreased
examples of intravascular hemolysis
G6PD def, PNH, HUS, TTP, HELLP, DIC
what is extravascular hemolysis
phagocytosis and lysis of RBC in the spleen and liver
no hemoglobinuria or low haptoglobin
examples of extravascular hemolysis
hereditary spherocytosis , thalassemias, warm and cold autoimmune hemolytic anemia
what type of transfusion reaction is this: donor WBC scome in contact with antibodies in the recipients plasma and cytokines are released from the donor WBCs causing fever and chills?- within 2 hours
coombs test is negative
febrile non-hemolytic transfusion reaction
how to prevent febrile non-hemolytic tranfusion reaction
leukoreduction(remove wbc from the blood before transfusion)
what is a hemolytic transfusion reaction
host antibodies attack ABO antigens on donor RBC
this causes an intravascular hemolysis with release of hemoglobin into the blood stream
increased LDH, low haptoglobin
symptoms of hemolytic tranfusion reaction
fever, chills, flank pain within minutes
impeding sense of doom
get antiglobin /coombs test
delayed transfusion reaction
host antibodies against minor antigens on donors RBC like Rh, kell, duffy
coombs is positive
symptoms of delayed transfusion reaction
symptoms occur over a course of a week and hemoglobin starts falling
coombs _ and unconjugated bilirubin
transfusion associated lung injry (TRALI)
bilateral crackles and low O2 sat less than 6 hours after transfusion
neutrophils react to cytokines in the transfused rpoduct
“noncardiogenic pulmonary edema”
transfusion associated circulatory overload
cardiogenic pulmonary edema
ARDS > 6 hrs
ARDS+ cardiac disease <6 hours
greater than 6 hours after transfusion
get CXR
acute graph vs host disease mechanism and symptoms
CD8+ T lymphocyte mediated injury
symptoms: within 100 days of hematopietic stem cell transplant
maculopapular rash
profuse watery diarrhea
liver inflammation
acute gvhd is diagnoised with and treated how?
diagnosed with colonoscopy + biopsy
tx: glucorticoids
