IM Hematology Flashcards
1
Q
anemia
what is the mos tlikley dx
A
sx are generaaly bast not on the etiology but on the severity of dz so you cant answer this one
2
Q
anemia
best initial test
A
cbc
3
Q
Hct >30-35%
symptoms
A
none
4
Q
Hct 25-30% sx
A
dypsnea (worse on exertion), fatigue
5
Q
hct 20-25% sx
A
lightheadedness and angina
6
Q
hct under 20-25% sx
A
syncope and chest pain
7
Q
what kills you in anemia
A
cardiach ishcemia
8
Q
anemia
mean corpuscular volume
A
although cbc establishes the presence of anemai mcv si the first clue to the etiology
9
Q
anemia
low mcv causes
A
microcytosis:
iron deficinecy
thalassemia
sideroblastic anemia
anemia of chronic disease
10
Q
low mcv overvies
A
microcytic anemias generally have a low reticulocye count. mos t causes of microcytosis are production problems. production problems are nearly synonymous with low retic counts
only alpha thalaseemia with 3 genes deleted has an elevated reic count
11
Q
low mcv smear
A
doesnt tell you diference between the types of microcytosis bc they will all be hypchroic and can all have target cells
12
Q
anemia
macrocytic anemia causes
A
low mcv from:
b12 and folate dieficiency
siderblastic anemia
alcoholism
antimetabolite meds such as asathioprine 6 mercaptopurin or hydroxyurea
liver dz or hypothyroidism
zidovudine or phenytoin
myelodysplastic syndrome
cold agglutinins can elevefate mcv falesly by clumping the cells
13
Q
sideroblastic anemia can be
A
macro or microcytic
14
Q
macrocytic anemias all give
A
a low reticulocyte count
15
Q
blod loss and hemolysis will raise the
A
reticulocyte count
16
Q
anemia
normocytic overview
A
acute blood loos or hemolysis can give a drop in hct so rapid that there is no time for mcv to change. blood loss ultimatley leads to iron deficiency and microcytosis. eventually hemolysis will increase reitc count and this will raise the mcv since reiculocytes are slitghtly larger than normal cells
17
Q
methotrexate and ra
anemia
A
methotrexate causes macrocytic anemia
ra causes monocytic anemia
18
Q
anemia
treatment
A
if severe treate with packed red blood cells
is the pt symptomatic then transufes
is the hct very low in an elderly pt or in a pt with heart disease, then transfuse
19
Q
very low hct in the elderly or those with heart disease
A
25-30
20
Q
sypmtomatic from aneami
A
sob
lighheaded confused and sometiems syncope
hypotension and tachycardia
chest pain
21
Q
use ifa deificient donor ffp for
A
iga deficienty receipients
22
Q
packed red blood cells
A
a concentrated form of glooc. ths blood product is a unit of whole blood with about 150ml of plasma removed. the hct of prbs is about 70-80% bc of the removeal plasma
each unit of prbcshould reaise the hct by 3 ponts per unit or 1g/dl of hg
23
Q
Fresh frozen plasma
A
rplaces clotting factors in those with an elevated prothromibni time, actiaved parital thromboplastin time or inr and bleeding
ffp is sued as replacement with plasmapheresis
24
Q
when is ffp not used
A
hemophili a or b
vonwillebrand disease
25
cryoprecipitate
used to replace fibrinogen and has some utility in disseminated intravascular coagulation. it provied high amounts of clotting factors in a smaller palsma volume. high levels of factor 8 and vwf are found in it
26
platelets
pooled from donations of mulitple donors. give to bleeding pt if platelet count is <50000. platelet infusion is ci in TTP
27
when is whole blood correct
never it is divided into prbc or ffp
28
Microcytic Anemia
definition/ etiology
mcv that is lower than 80 fl
```
most common causes are:
iron deficiency
chronic disease
sideroblastic anemia
thalassemia
```
29
Microcytic Anemia
iron deficiency
caused by blood loss
only need 1 to 2 mg per day
menstruating women need 2-3 mg per day
pregnant women need 5-6 per day
duodenum can absorb about 4 mg per day, which is why even a little bit of blood loss every day will lead to iron deficiency over time
30
Microcytic Anemia
chronic disease
includes any form of cancer or chronic infection
iron is locked in storage or trapped in macros or in ferriting
hv synthesis will not occur bc the rion just does not moved forward
precise mechanism is clear only in renal faulure in which there is a dericiency or erythropoietin
initially mcv is normal and then dexreases
hepcidin regulated iron absorption and its levels are low in anemai of chornic disease
31
Microcytic Anemia
sideroblastic anemia
can be macrocytic also when it is associaed with myelodysplasia, a preleukemic syndrome
most common cause is alcohols suppressive effect on the bone marrow
less common causes are lead poisoning, inh and b6 deificncy
reuslts fromt eh inability of iron to be incorporated with heme
32
Microcytic Anemia
thalassemia
extremely common cause of microcytosis. mos tpts with thalassemia trait alone are asymptomatic
33
Microcytic Anemia
presentation/what is the most likely dx
cant tell from sx but hx might give you a clue
34
Microcytic Anemia
what is the most likely dx
blood loss (gi bleeding)
iron deficiency
35
Microcytic Anemia
what is the most likely dx
mensturation
iron deficiency
36
Microcytic Anemia
what is the most likely dx
cancer or chornic infection
chronic disease
37
Microcytic Anemia
what is the most likely dx
ra
chronic disease
38
Microcytic Anemia
what is the most likely dx
alcoholic
sideroblastic
39
Microcytic Anemia
what is the most likely dx
asymptomatic
thalassemia
40
Microcytic Anemia
smear
no useful bc all cuases are hypochromic and can have target cells
target cells are most common with thalassemia
41
Microcytic Anemia diagnostic tests
iron deficiency
a low ferritin is extremely specific
nearly 33% of all pts ahvce an increased ferritin bc it is an acute phase reactant
low serum iron level and an increase in total iron binding capacity (TIBC) (undbound sites on transferrin)
iron divided by tibc equals tranferring saturation
42
Microcytic Anemia diagnostic tests
chronic disease
the srum iron is low in circulation bc iron is trapped in storage
ferritin (stored iron) is elevated or normal
TIBC is LOW
43
Microcytic Anemia diagnostic tests
sideroblastic anemia
only form of microcytic aneami in which the circulating iron level is elevated
44
Microcytic Anemia diagnostic tests
thalassemia
genetic disease with normaml iron studies
45
chronic renal failure gives you
normocytic anemia
46
Microcytic Anemia unique lab features
Iron deficiency
the red cell distribution of width (RDW) is increased bc the newer cells are more iron deficienty and smaller. as the body runds out of iron, the newer cells have less hb and get progressively smaller
elevated platelet count
most accuarte test is a bone marrow biopsy for stainable iron which is decreased (rarely done but most accurate)
47
Microcytic Anemia unique lab features
sideroblastic anemia
prussion blue staining for ringed sideroblasts is the most accurate test
basophilic stipp;ing can occur in any cause of sideroblastic anemia
48
Microcytic Anemia unique lab features
thalassemia
hb electrophoresis is the most accurate test. for alpha thalassemia genetic studeis are the most accurate test
only 3 gene deletion alpha halassemia is assocaited wtih hb h and an increased retiulocyt count
all forms have a normal RDW
49
how is alpah thalassemia diagnosed
dna analysis
50
Alpha thalassemia
one gene dleleted: normal
two genes deleted: mild anemia, normal electrophoresis
3 genes deleted: moderate aneami with hb h, which are beta 4 tetrads, increased retics
4 genes deleted: gamma 4 tetrads or hb Bart. chf causes death in utero
51
Beta thalassemia
one gene deleted: incrased hb f and a2
2 genes delted: n/a
3 genes deleted: beta thalasseami intermedia
normal hb f
no transusion dependence
4 gene delted: n/a
52
only 3 gne deltion alpha talassemia has high
reticulocytes
53
Microcytic Anemia treatment
iron deficiency
replace iron with oral ferrous sulfate. if this is insufficient pts may be treated iwth im iron
54
Microcytic Anemia treatment
chronic disease
correct the underlying disease. only the anemia assocatied with end stage renal failure routinely responds to epo replacement
55
Microcytic Anemia treatment
siderblastic anemia
correct the cause. may give b6 or pyridoxine prelacement
inh can lead to this
56
Microcytic Anemia treatment
thalassemias
trait is not treated
beta major (cooley anemia) is managed with chronic transusion for life
iron overload is managed with deferasirox or deferiprone (oral iron chelators)
derexoamine is a parenteral version of an iron chelator
57
Macrocytic Anemia
initial test
get a smear first to detect hypersegmented neutros then get a b12 and folate levels
58
megaloblastic anemia is the presence of
hypersegmented neutrophils. many factors rease the mxv but only b12 and folate deficiency and antimetabolite meds cause hypersegmentation
59
Macrocytic Anemia
Vit b12 deficiency is cuased by:
pernicious anemia
pacreatic insufficieny
dietary deficiency (vegan/strict vegetarian)
chron dz, celiac, tropical spru, radiation, or any dz damaging the terminal ileum
blind loop syndrome (gastrectomy or gastric bypass for weigh tloss)
diphyllobothrium latum, hiv
60
Macrocytic Anemia
folate deficiency is caused by:
dietary deficicency (goats milk has not folate and provieds only limited iron and b12)
psoriasis and skin loss or turnover
phenytoin and sulfa
61
celiac dz causes
b12 folate and iron deficiency
62
what drug in ra cuases folate deficiency
methotrexate
63
Macrocytic Anemia
what is the most likely dx/presentation
alcohol can give macrocytic anemia and leuro problems it will not give hypersegmented neutros
64
b12 deficiency eruo abnormality
can give any neruo abnormality but peripheral neuropathy is the most common
dementia is the elast common
posterior column damage to position and vibratory sensation or subacute combined degeneraion of the cord is classic
look for ataxia
65
Macrocytic Anemia
diagnostic tests
megaloblastic anemia
increased ldh and incrased indiret bilirubin levels
decreased reticulocyte count
hypercellular bone marrow
macroovalocytes
increased homocysteine levels
66
b12 and folate deficiency on smear
are identical
67
only b12 deficiency is associated with
increased methylmalonic acid level
68
b12 deficiency mechanism
high ldh + high bilirubin + low retics = ineffective erythropoiesis
69
b12 and folate both increase
homocysteine levels
70
Tested facts about macrocytic anemia
schilling test is never the right answer
pernicious anemai is confirmed with antiintrinsic factor and antiparietal cell antibodies
red cells are destroyed as the leave the marrow so the reticulocyte count is low
b12 and folate deficiency can cause pancytopenia as well as macrocytic anemai
pancreatic enzymes are needed to absorbb12 they free it from carrier proteins
neurological abnormalities will improve as long as they are minor (peripheral) and of short duration
71
Macrocytic Anemia
treatment
replace what is deficient
folate replacement corrects the hematologic problems of b12 deficiency butno the neuro problems
72
b12 can give either
hematological or neurological abnormlaities alone it does not give both at the same time
73
what is a compication of b12 replacement
hypokalemia, bc of rapid cell production you use it up
74
what removes b12 from the r protein so it can bind with intrinic factor
pancreateic enzymes
75
Hemolytic anemia
can lead to
sudden diseacrea in hct
increaseed levels of LDH, indirect bilirubin, and reticulocytes
decreased haptoglobin level
slight increase in mcb bc reticulocytes are larger than normal cells
hyperkalemaifrom cell breakdown
folate deificiency from increased cell production using it up, folate stores are limited
76
chronic hemolysis is associated with
bilirubin gallstones
77
Sickle Cell Disease
definition
chronic, usually well-compensated hemolytic anemia with a reticulocyte coutn that is always high
78
Sickle Cell Disease
acute panful vasoconstrictor crisis is caused by
hypoxia
dehydration
infection/fever
cold temperatures
79
Sickle Cell Disease
what is the most likely diagnosis
look for an african american pt with sudden, severe pain in the chest backa nd thighs that may be acopmanied by fever
it is rare for an adult to present with an acute crisis without a clear hx of sickle cell dz
80
Sickle Cell Disease
common manifestations
bilirubin gallstones from chornically elevated bilirbuin levels
increased infection from autosplenectomy, particularly encapsulated organisms
osteomyelitis, most commonly from salmonella
retinopathy
stroke
enlarged heart with hyperdynamic features anda systolic murmur
lower extremity skin ulcers
avascular necrosis of the femoral head (xray is the first test, mri is most accurate)
81
Sickle Cell Disease
how do children present
with dactylitis (inflammation of fingers)
82
Sickle Cell Disease
kidney
papillary necrosis of the kidney happens from chronic kidney damage
83
Sickle Cell Disease
best initial test
peripheral smear
84
Sickle Cell Disease
most accurate test
hemoglobin electrophoresis
85
does sickle cell trait (AS) give sickled cells on smear
no
86
what lowers mortality in sickle cell disease
hydroxyurea in prevention
antibiotics with fever
87
why can you see howell-jolly bodies on peripheral smear in Sickle Cell Disease
bc they are seen in pts who dont have a spleen
88
morulae
seen inside neutrophils in ehrlichia infections
89
when do you see nucleated red blood cells
with premature release of precursor blood cells
90
Sickle Cell Disease
treatment (5)
1. begin with oxygen/hydration/nalagesia
2. if fever or a white cell count higher than usual is present, then abs are given. use ceftriaxone, levofloxacin, or moxifloxacin
3. folic acid replacement is necessary on a chornic basis
4. give pneumococcal vaccination bc of autosplenectomy
5. hydroxyurea prevents recurrecnces of sickle cell crises by increasing hemoglovin F
91
dont waite for reults of testing to start abs if there is a fever with Sickle Cell Disease
the absence of a functional spleen leads to overwhelming infection
92
Sickle Cell Disease
exchange tranfusion is used if there is severe vasoocclusive crisis presenting with
acute chest syndrome
priapism
stroke
visual disturbance from retinal infarction
93
Aplastic crisis
pts with sickle cell dz usually have very high reticulocyte counts bc of the chronic copmensated hemolysis. parvovirus b19 causes an aplastic crisis which freezes the rought of the marrow. nothing will be visible on blood smear.
the bone marrow will show fiant pronormoblasts this would not be done routinely and is never the initial test
the first clue to parvovirus is a sudden drop in reticulocyte level
94
Hereditary Spherocytosis
etiology
this is a defect in the cytoskeleton of the red cell leading to an abnormal round shape and loss of the normal flexibility characteristic of the biconcave disk that allows red cells to bend in the spleen
95
Hereditary Spherocytosis
what is the most likey dx
recurrent episodes of hemolysis
intermittent jaundice
splenomegaly
family hx of anemia or hemolysis
bilirubin gallstones
96
Hereditary Spherocytosis
diagnotstic tests
low mcv
increased mean corpuscular hemoglobin concentration (MCHC)
negative coombs test
97
Hereditary Spherocytosis
most accurate test
osmotic fragility. when cells are placed in a slightly hypotonic solution, the increased swelling of hte cells leads to hemolysis
98
Hereditary Spherocytosis
treatment
chronic folic acid replacement supports red cell production
splenectomy stops the hemolysis but does not eliminate the spherocytes
99
Autoimmune (warm or igg) hemolysis
etiology
fifty percent of cases have no identified etiology clear cases are causes by:
chronic lymphocytic leukemia (CLL)
lymphoma
systemic lupus erythematous (SLE)
drugs: penicillin, alpha-methyldopa, rifampin, phenytoin
100
Autoimmune (warm or igg) hemolysis
diagnostic tests
most accurate test is the coombs testh, which detects igg antibody on the surgace of the red cells. the direct an dindirect coombs coombs tests tell basically the same thing, but the indirect test is associated with a greater amount of antibody
autoantibodies remove small amounts of red cell membrane and lead to a smaller membrane, forcing the cell to become round. biconcave disks need a greter surface area than a sphere. autoimmune hemolysis is assocaited with microspherocytes
101
autoimmune hemolysis is associated with
spherocytes
102
why does a smear not show fragmented cells in autoimmune hemolysis
bc the red cell destruction occursin side the psleen or liver not in the blood vessel
103
Autoimmune (warm or igg) hemolysis
treatment (4)
1. glucocorticoids such as prednisone
2. recurrent erpisodes respond to splenectomy
3. severe, acute hemolysis not responding to prednisone is controlled with ivig
4. rituximab, azathiprine, cyclophosphamide, cyclosporine is used when splenectomy does not control hemolysis
104
Autoimmune (warm or igg) hemolysis
alternate treatments to diminish the need for steroids in general are:
cyclophosphamide
cyclosporine
azathioprine
mycophenolate mofetil
105
Cold agglutinin disease
definition/etiology
coldagglutinins are igm antibodies against the red cell developing in association with epstein-barr virus, waldenstrom macroglobulinemia or mycplasma pneumonia
106
Cold agglutinin disease
presentation
sx occcur in colder parts of the body such as nubmness or mottling of ht enose, ears, fingers, and toes. sx resolve on warming up the body part
107
Cold agglutinin disease
diagnostic tests
the direct coombs test is positive only for compleemnt. the smear is normal or may show only spherocytes. cold agglutinin titer is themost accurate test
108
Cold agglutinin disease
treatment
1. stay warm
2. administer rituximab and sometimes plasmapheresis
3. cyclophosphamide, cyclosporine, or other immunosuppressive agents stop the production of the antibody
109
most common wrong answer in Cold agglutinin disease
prednisone is the most common wrong answer, dont do steroids or spleenctomy
110
cryoglobulines are often mixed up with cold agglutinins. although both are igm and do not respond to steroids, cryoglobulins are associated with
hepatitis c
joint pain
glomerulonephritis
111
Glucose 6 phosphate dehydrogenase deficiency
etiology
x linked recessive disorder leading to an inability to generate gluathione reductase and protect the red cells from oxidatn stress. the most common oxidant stress is infection. other causes are dapsone, quinidine, sulfa drugs, primaquine, nitrofurantoin, and fava beans
112
Glucose 6 phosphate dehydrogenase deficiency
what is the most likely dx
look african american or mediterranean men with sudden anemia and jaundice who have a nomral sized spleen with an infection or are using one of the drugs previously listed
113
Glucose 6 phosphate dehydrogenase deficiency is almost exclusively in
men
114
Glucose 6 phosphate dehydrogenase deficiency
diagnostic tests
best initial test is form heinz boeids and bite cells, the g6pd level will be normal after a hemoytic event
the most accurate test is the g6pd level after waiting 1 to 2 months after an acute episode of hemolysis
115
what stain shows heinz bodies
methylene blue
116
Glucose 6 phosphate dehydrogenase deficiency
treatment
nothing reverses the hemolysis, aboid oxidant stress
117
Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura
they are different versions of hte same basic disease cuased by deficiency of metalloproteinase ADAMTS 13.
118
HUS is assocaited with
E Coli 0157h7 and more frequent in children
119
TTP is associated with
ticlopidine clopidogrel cyclosporine AIDS and SLE
neurological disorders and fever and is more common in adults
neurological sx include confusion and seizures
120
Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura
are characterized by
intravasuclar hemolysis with fragmented red cells (schistocytes)
thrombocytopenia
renal insufficinecy
121
Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura
diagnostic test
no specific test
normal pt/aptt and negative coombs tests
122
Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura
treatment
plamapheresis or plasma exhange
steroids if not related to drugs or diarrhea
123
Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura
if there is a delay to plasmapheres
infuse ffp
124
why dont you transfuse platelets into pts with hus or ttp
bc they make the disease worse
125
Paroxysmal Nocturnal Hemoglobinuria
etiology
a clonal stem cell defect with increased sensitivity of red cells to complement in acidosis. this is from deficiency of the complement regulatory proteins CD55 and 59 also known as decay accelerating factor. the gene for phosphatidylinositol class a (PIGA) is defective. this leads to overactibation of the complement system . this does nothing to an unaffected person but in pnh it leads tohemolysis and thrombosis
126
Paroxysmal Nocturnal Hemoglobinuria
presenation/ what is the most likely dx
episodic dark urine
pancytopenia and iron deficiency anemia
clots in unusual places (not just DVT or pulmonary embolism)
127
most common cause of death in Paroxysmal Nocturnal Hemoglobinuria
thrombosis
128
Paroxysmal Nocturnal Hemoglobinuria
diagnostic tests
cbc often shows pancytopenia in addtion to anemia. the momst accurate test is a decreased level of CD55 and CD59. the ham test and the sucrose hemolysis test are obolete. flow cytometry is another way of saying cd55/cd59 testing
129
Paroxysmal Nocturnal Hemoglobinuria
treatment (4)
1. prednisoneis hte best initial therapy for hemolysis. the mechanism is not clear
2. allogeneic bone marrow trasplant is the only method of cure
3. eculizumab inactivates c5 in the com;lement pathway and decreases red cell destruction. complement overactivation is the mechanism of pnh. eculizumab is for hemolysis and thrombosis
4. give folic acid and replacement with transfusions as needed
130
pnh is a stem cell defect that
may cause aplastic anemia, myelodysplasi or acute leukemia
131
most common site of thrombosis in Paroxysmal Nocturnal Hemoglobinuria
large vessel thrombosis of the mesentreic and hepatic veins
132
Aplastic Anemia
Definition
aplastic anemia is pancytopenia of unclear etiology
any infection or cancer can invade the bone marrow causing decreased production or hypoplasia
133
Aplastic Anemia
etiology
radiation and toxins such s toluene, insecticides (DDT), and benzen
drug effect: sulfa, phenytoin, carbamazepine, chloramphenicol, alcohol chemo
sle
pnh
infection: hiv, hepatitis, cmv, ebv
b12 nd folate deficiency
thyroid inhibiting medications such as ptu and methimazole
134
Aplastic Anemia
presentation
pts present with th fatigue of anemia, infections from low htie cell counts, and bleeding from thrombocytopenia
135
Aplastic Anemia
diagnostic tests
confimred by excluding all cuases of pancytopenia
most accurate test is a bone marrow biopsy
136
Aplastic Anemia
Treatment
transfusion for anemia, abs for infection, and platelets for bleeding
allogeneic bone marrow tranplantation
when the bt is older (above 50), or there is no donoruse anithymocyte globulin and cyclosporine
tacrolimus is alternative to cyclosporine
alemtuzumab is an anticd52 that suppresses t cells
137
aplastic anemia acts as an autoimmune disorder in which the T cells
attack the pts own marrow. treatment is based on meds like cyclosporine that inhibit t cells. this brinkg sthe marrow back to life
138
Polycythemia Vera
Definition
the unregulated overproduction of all 3 cell lines, but red cells overproduction is the mos tprominent. there is a mutation in the JAK2 protein which regulates marrow production. the red cells grow wildly despite a low erythropoeitin level
139
Polycythemia Vera
wha tis the most likely dx
headache, blurred vision, and itnnitus
htn
fatigue
splenomegaly
bleeding from enjorged blood vessels
thrombosis from hyperviscosity
140
Polycythemia Vera
pruritus
often follows warm showers bc of histamine release from increased numbers of basophils
141
Polycythemia Vera
diagnostic tests
hct is elevated above 60%, platelets and wbc are elevated also
must exclude hypoxia as a cause of erythrocytosis
total rec cell mass is elevated
oxygen levels are normal
epo levels are low
B12 is elevated
iron levels are low bc you have so many red cells
142
Polycythemia Vera
most accurate test
jak2 mutation
found in 95% of pts
143
Polycythemia Vera
| convert to
AML
a small number of them, basophils can be up
144
Polycythemia Vera
treatment
1. phlebotomy and aspirin prevent thrombosis
2. hydroxyurea helps lower the cell count
3. allopurinol or rasburicase protects against uric cid rise
4. antihistamines
145
Polycythemia Vera
target hct
45%
146
Polycythemia Vera
vs
Renal cell cancer
both have elveated hct but the epo level is elevated with kidney cancer
147
Polycythemia Vera
mcv
low
148
platelet counts eleveate temporalily after
splenectomy
149
Essential Thrombocytosis
markedly elevated platelet count above one million leading to both thormbosis and bleding. essential thrombocytosis can be very difficult to distingush from an elevated paltelet count as a reaction to another stress such as infection, cancer, or iron deficiency
150
ruxolitinib
inhibits jak2
also suppresses myelofibrosis
151
jak2 is found in
50% of ET cases
152
Essential thrombocytosis
treatement
if pt isunder age 60 and asymptomatic with a platelet count under 1.5 million no treatment is necessary
if pt is above 60 and there are thromboses or platelet count is 1.5 million begin treatment
153
Essential thrombocytosis
best initial therapy
hydroxyurea
anagrelide is used whe there is red cell suppression from hydroxyurea
aspirin is used for erythromelalgia
154
Myelofibrosis
definition
disease of older persons with a pancytopenia associated with a bone marrow showing marked fibrosis
blood production shifts tot eh spleen and live rwhich become amrkedly enlarged
155
Myelofibrosis
dx
look for teardrop shaped cells and nucleated red blood cells on blood smear
156
Myelofibrosis
treatment
thaldiomide and lenalidomide are tumor necrosis factor inhibitore sthat inrease bone marrow production
if under 5 do allogneneic bone marrow transplant
157
Acute Leukemia
presentation
signs of pancytopenia:
fatigue
infection
bleeding
wbc count is normal or increases
infection is common bc leukemic blasts do not function normally
158
Acute Leukemia
most frequently tested
M3 or acute promyelocytic leukemia
associated with dic
no clincial difference in all of the all leukemias (3 types)
159
Acute Leukemia
best initial test
blood smear showign blasts
160
Acute Leukemia
most accurate test
flow cytometry which will distingush the different ssubtypes of acute leukemia
so you can find the specific cd sybtypes
161
Acute Leukemia
myeloperoxidase
characteristic of acyte myelocytic leukemia (AML)
162
Acute Leukemia
look for a hx of
myelodsyplastic syndrome
163
m3 is associated with translocation between
15 and 17
164
Auer rods
esosinophilic inclusions associated with aml. m3 or acute promyelocytic leukemia os mos tcommonly associated with auer rods
165
Acute Leukemia
treatment
both aml and all are treated with chomto remove blasts form the peripheral blood smear, this is known as remission
166
Acute Leukemia
if prognosis is poor
the proceed directly to bmt
167
Acute Leukemia
if prognosis is good
give more chemo
168
Best indicater of prognosis in acute leukemia is cytogenetics
specific chromosomal characteristicds found in each pt
169
Acute Leukemia
treatement of m3
add all trans retinoic acid
170
wha tdo you add to all treatment
intrathecal chom like methrotrexate to prevent relapseof all in the cns
171
m3 gives
dic
172
add atra to
m3
173
auer rods=
aml
174
add intrathecal methotrexate to
all
175
rasburicase prevents
tymor lysis related rise in uric acid
176
Chronic Myelogenous Leukemia
what is the most likely dx
persistnely high wbc that is all neutros
pruritus is common after showrs from histamine release from basophils
splenomegaly presents with early saitety abdominal fullness and luq pain
can present with vague sx of fatigue night seats and fever from hpyermetabolic syndrome
high wbc on routine exam
177
Chronic Myelogenous Leukemia
diagnostic tests
after hgih neutrophil count is found, you must determine if it is a reaction to another infection or stress leukemoid rxn, or genuinely represents a leukemia
may find blasts but should be under 5% in CML
178
Chronic Myelogenous Leukemia
what is the most accurate test
BCR-ABL, done by pcr or fish
179
BCR-ABL
9:22 translocation=philly chormosome in 95% of cases
180
Chronic Myelogenous Leukemia
treatment
tyrosine kinase inhibitors such as imatinib dastinip or nilotinib are the best initial therapy
only a bmt can cure cml but this should never the first therapy (it is the most effective cure
181
CML ahs the greatest likelihood of all myeloproliferative disorders to transform into
acute leukemia (blast crisis) if cml is untreated 20% turn into this within 1 year
182
in an acute leukostasis rxn
do leukapharesis first
183
Myelodysplastic Syndrome
Definition
mds is a preleukemic disorder presenting in older pts with a pancytpenia despite a hypercellular bone marrow
most pts never develop aml bc complications of infection and lbeeding lead to death before leukemia occurs
184
Myelodysplastic Syndrome
presentation
asymptomatic pancytopenia on routine cbc
fatigue and weight loss
infection
bleeding
splenomegaly
no single pathognomonic finding in the hx or physcial examination
185
Myelodysplastic Syndrome
diagnostic tests
CBC: aneiam with ain increased mcv, nucleated red ells, and a small number of blasts
hypercellular marrow
prussion blue stain shows ringed sideroblasts
severity is based on the percentage of blasts
5q deletion has an excellent response to lenalidomide
186
Myelodysplastic Syndrome
treatment
1. transfusion: support with blood products as needed
2. epo gives about 20% response
3. azaxitidine or decitabine
4. lenalidomide for those with the 5q election can decrease transfusion dependence
5. bone marrow transplant under age 50
187
azacitidine decreases
transfusion dependence and increases survival in MDS
188
pelger -huet cells are the
most distinct lab abnormality in mds (bilobed nucleus)
189
5q deletion
the characteristic abnormality in mds, pts with 5q have a better prognosis than thosewithout it
190
Chronic Lymphocytic Leukemia
presentation
can be asynptomatic at presentation with only an elevated wbc count
most common sympto is fatigue
lymphadneopathy (80%)
spleen or liver enlargement (50%)
infection from poor lymphocyte function
hemolysis sometimes
191
Chronic Lymphocytic Leukemia
definition
a clonal proliferation of normal, mature-appearing B lymphocytes that function abnormally, occurs ove the age of 50 in 90% of those affected
192
physical findings in cll
nothing unique
193
richter phenomenon
conversion of cll into high-grade lymphoma, happens in 5% of pts
194
smudge cell
lab artifact in which the fragile nucleus is crushed by the cover slip
195
CLL
treatment
for stage 0 (elevated WBC), stage 1 (lymphadenopahty, and stage II (hepatosplenomegaly), there is no treatment
Stage III (anemia) and stage IV (thrombocytopenia) are treated with gludarabine, cyclophsophamide, and rituximab
if there is a choice that lists fludarabine, cyclophosphamide and rituximabe then this is the best initial therapy for advanced stage 3 and 4 or any pt who is symptomatic (severe fatigue, painful nodes)
alemtuzumab (anticd52) is used when fludarabine fails.
196
for refractory cases of cll
cyclophosphamide (more efiicacy but more toxic)
197
for mild cases of cll
chlorambucil (elderly)
198
for severe infection
iv immunoglobulin
199
autoimmune thrombocytopenia or hemolysis
prednisone
200
Hairy Cell Leukemia
presents with
middle-aged men with:
pancytopenia
massibe splenomegaly
monocytopneia
inspirable "dry" tap desptie hypercellularity of the marrow
201
Hairy Cell Leukemia
best initial test
smear showing hairy cells
202
Hairy Cell Leukemia
most accurate test
immunoptyping by flow cytometry (CD11)
203
Hairy Cell Leukemia
treat with
cladribine or pentostatin
204
in ahir clel leukemia b cells are seen on smear
with filamentous projections
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Non-Hodgkin Lymphoma
Definition
is a proliferation of lymphocytes in the lymph nodes and spleen. nhl is most often widespread at presentation and can affect any lymph node or organ that has ;ymphoid tissue. nhl and cll are extrmely similar, but nhl is a solid mass and cll is liquied or circulating
206
Non-Hodgkin Lymphoma
presentation
painlessl ymphadenopathy
may involve pelvic, retroperitonieal or mesenteric structures
nodes not warm red or tender
b symptoms: fever, weight loss, drenching night sweats
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Non-Hodgkin Lymphoma
best initial test
excisional biopsy
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Non-Hodgkin Lymphoma
diagnostic tests
cbc is normal in most cases
high ldh levels correlatee with worse severity
staging determiens the intnesity of therapy
statign ngl does not often change treatment bc in most causes disease is weidpsread
209
Non-Hodgkin Lymphoma
staging steps
ct scan of the chest, abdomen, and pelvis
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infection not Non-Hodgkin Lymphoma gives nodes that are
warm red and tender
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Non-Hodgkin Lymphoma
stages
stage 1: 1 lymph node group
stage 2: 2 or more lymph node groups on the same side of the diaphragm
stage 3: both sides of the diaphragm
stage 4: widesperad disease
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Non-Hodgkin Lymphoma
treatment of local disease
stage 1a and 2a
local radiation and small dose/course of chemo
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Non-Hodgkin Lymphoma
treatement of advanced disease
compination chemo with chop and riguximab (antibody against CD20)
c=cyclophosphamide
h=adriamycin (doxorubicin)
o=vincristine (oncovin)
p=prednisone
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Non-Hodgkin Lymphoma
presents in advanced stages in
80-90% of cases
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Mucosal associated lymphoid tissue
lymphoma of the stomach assocaited with h pyloi
treat with clarithromycin and amoxicillin
216
Hodgkin Disease
same as nhl but has reed-sternberg cells on pathology
217
difference between hodgins and nhl
stage
hodgkins - stage 1 and 2 in 80-90% of disease
nhl - stage 3 and 4 in 80-90%
218
difference between hodgins and nhl
locations
hodgkin - centers around cervical area
nhl - disseminated
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difference between hodgins and nhl
pathology
hodgkin - reed sternberg cells
nhl - no reed sternberg cells
220
difference between hodgins and nhl
pathological classification
hodgkin - lymphocyte predominate has the best prognosis
lymphocyte depleted has the worst prognosis
nhl - burkitt and immunoblastic have the worst prognosis
221
hodgkin disease
treatment stage 1a and 2a
local radiation and a small course of chemo
222
hodgkin disease
treatment of stage 3 and 4
abvd
a=adriamycin (doxorubicin)
b=bleomycin
v=vinblastine
d=dacarbazine
223
hodgkin disease
relapses ater radiation therapy
are treated with choemo. relapses after chom are treated with extra high dose chemo and bone marrow transplantation
224
hodgkin disease
complications of radiation and chemo
radiation increases the risk of solid utmors such as breast, thyroid, or lung cancer. screening for breast cancer is recommended 8 years or more after treatmeent. radiation increases the chance of premature coronyar artery disease, the risk of acute leukemia, mds, and nhl as a compication of chemo is about 1% per year
225
hodgkin disease
how to determine the dosing of chemo
uga or nuclear ventriculogram bc adriamycin or doxorubicin is cardiotoxic
226
hodgkin disease
just radiation
never
227
doxorubicin ae
cardiomyopathy
228
vincristine ae
neuropathy
229
bleamycin ae
lung fibrosis
230
cyclophosphamide ae
hemorrhagic cystitis
231
cisplatin ae
renal and ototoxicity
232
Multiple Myeloma
definition
abrnomal proliferation of plasma cells. these plasma cells are unregulated in their production of useless immunoglobulin tht is usually igg or iga. igm is aseparate disease called waldenstrom macroglobulinemia. these immunoglobulins do not fight infection but clof up the kidney
233
Multiple Myeloma
what is the most likely dx
most common presnetation is bone pain from pathologic fractures. a pathologic fracture means that the bone breaks under what would be considered normal use. this is from osteoclast activating factor (OAF), which attacks the bone, causing lytic lesions. oaf is also the reason for hypercalcemia. infection is common bc the abnormal plasma cells do not make immunoglobulins that are effective against infections
234
Multiple Myeloma
presentation
hyperuricemia: from increased turnover of the nuclear material of palsma cells
anemia: from infiltration of the marrow with massive numbers of plasma cells
renal failure: from accumulation of immunoglobulins and bene-joens protein in the kidney; hypercalcemia and hyperuricemia also damage the kidney
235
most common cuases of death in Multiple Myeloma
renal failure and infection
236
Multiple Myeloma
first test
xray of the affected bone that will show lytic punched out lesions
237
Multiple Myeloma
diagnostic tests
serum protein electrophoresis (SPEP) shows and IGG of 60% or an iga of 25% spike of a single type or clone (called an m or monoclonal spike) fifteen percent have light chains or bence jones protein only
also have:
hypercalcemia
bnec-jones protein on urin immunoelectrophoresis
beta2 microglobulin levels correspond to severity of disease
smear with rouleaux
elevated bun and creatinine
bone marrow biopsy: greater than 10% plasma cells
elevated total protein with normal albumin
238
myeloma has a decreased
anion gap, igg is cationic and increased ationic substances will increase chlride and bicarb levels, this decreases the anion gap
239
rouleaux
form when the igg paraprotein sticks to the red cells, causing them to adhere to each other in a stack or roll
240
is bence-jones protein detected on dipstick?
no
241
Multiple Myeloma
most accurate test
bone marrow biopsy with grater tha n10% plasma cells
242
Multiple Myeloma
treatment
best initial therapy is a combo of dexamethasone and lenalidomide bortezomib or both
melphalan is useful in older fragile prs who cannot toelrate adverse effects.
most effective terhapy in those under age 70 is an autologus bone marrow traonplasnt with stem cell support, this is used fater induction chemo therapy with enalidomide and steroids
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Monoclonal gammopathy of unknown significancy
igg or gia spikes on an spep are common in older pts
main issue is to evaluate with bone marrow biopsy to exclude myeloma, this iwll have a smaller number of plasma cells
no therapy
1% per year transorm into myeloma
amount of ig in the spike is the main correlate of risk for myeloma, more mgus more myeloma
244
Waldenstrom Macroglobulinemia
definition
overproduction of igm from malignant b cells leading to hyperviscosity
245
Waldenstrom Macroglobulinemia
presents with
lethargy
blurry vision and vertigo
engorged blood vessels in the eye
mucosal bleeding
raynaud phenomenon
246
Waldenstrom Macroglobulinemia
tests
anemia is common
igm spike on spep results in hyperviscosit
no bone lesions
247
Waldenstrom Macroglobulinemia
treatment
plasmapharesis is the best initial therapy to remove igm and decrease viscosity
long temr treatment is with rituximab or prednison cyclophosphamide
control teh cell cells that make the abnormal ig, decrease the means of production
use bortezomib or lenalidoide like in myeloma
248
bleeding disorders
platelet bleeding overvies
superficial
epistaxis, gingival, petechiae, purpura, mucosal surgaces like gums and vaginal bleeding
249
bleeding disorders
factor bleeding overvies
deep
joints and muscles
250
Immune thrombocytopenic purpura
what is the most likely diagnosis
isolated thrombocytopenia (normal hct, normal wbc)
normal sized spleen
251
Immune thrombocytopenic purpura
mild bleeding
so no intracranial or major gi bleeding
use prednisone
252
Immune thrombocytopenic purpura
diagnostic tests
disgnosis of exlusion usually, can show:
antiplatelet antibodies lack specificity
us or ct to exclude hypersplenism
megakaryocytes are elevated in number
bone marrow not routine, indicated only before pslenectomy
increase in mean platelet volume
253
Platelets are large in
ITP
254
ITP Treatment
no bleeding count >30000
no treatment
255
ITP Treatment
mild bleeding count <30000
glucocorticoids
256
ITP Treatment
severe bleeding coutn <10000
ivig, antirho (anti-d)
257
ITP Treatment
recurrent episodes and steroid dependant
splenectomy
258
ITP Treatment
splenectomy or steroids not effectiv
romiplostin or elzombopag, rituximab azathioprine cyclosporine or mycophenolate
259
romiplsotim and etlrombopag are synthetic
thrombopoietin for ITP
260
before splenectom y vaccinate for
neisseria meningitidis
haemophilus influenzae
pneumococcus
261
Von Willebrand Disease
definition
is the most common inherited bleeding disorder with a decrease in the level or functioning of Von Willebrand Disease. autosomal dominant
262
Von Willebrand Disease
what is the most likely dx
look for bleeding related to paltelets (epistaxis, gingiva, gums) with a normal platelet count. Von Willebrand Disease is markedly worsened after the use of apsirin. the aptt may be elevated in half of the pts
263
Von Willebrand Disease
diagnostic tests
vwf level may be decreased
ristocetin cofactor assay: detects vwf dysfunction also called vwf activity
factor 8 activity
bleeding time: increased duration (rarely done)
264
Von Willebrand Disease
treatment
bets initial therapy is ddavp (demsopressin) which releases subendothelial stores of vwf. if there is no response use factor 8 replacement or vwf concentrated
265
Hemophilia
presentation
look for delayed joint or muscle bleeding in a male child, since the condition is xlinked recessive. bleeding is delayed bc the primary hesotatic plug is with platelets
266
hemophilia
tests
pt is normal and the aptt is prolonged
mixing sutdies with normal palsma will correct the aptt to rnomal
most accurate is a specific assay for factors 8 and 9
267
hemophilia
treatment
treat mild cases with ddavp
severe blededing with replacement of specific factor
268
Factor XI deficiency
most of the time thiere is no increase in bleeding with trauma or surery ther eis increased bleeding
look for a normal pt with a prolonged aptt, mixing study will correct the aptt to normal as occurs whenever there is a deficiency of clotting factors
uise ffp to stop bleeding
269
Factor XII deficiency
these pts ahve an elevted aptt but there is no bleeding, there is no therapy needed
270
Disseminated Intravascular Coagulation
bleeding is related to
clotting factor deficiency and throbocytopenia
271
Disseminated Intravascular Coagulation
risk factors
sepsis
burns
placenta abruption
amniotic fluid embolus
snake bites
trauma resulting in tissue factor release
cancer
272
Disseminated Intravascular Coagulation
diagnostic tests
elevation in both the pt and aptt
low platelet count
elevated ddimer and fibrin split products
decreased fibrinogen level (it has been consumed)
273
Disseminated Intravascular Coagulation
treatment
if platelets are under 50000 and the pt has serious bleeding, replace platelets as well as clotting factors by using ffp
heparin has no definit benefit
cyroprecipitate may be effective to replace finbrinogen levels if ffp does not control bleeding
274
Hypercoagulable States/Thrombophilia
overview
most common cause is factor V leiden mutation. there is no difference in the intensity of anticoaculation. use warfarin to an INR of 2 to 3 for 6 months
275
the only thrombophilis improtant to test for with first clost is
antiphospholipid antibody syndrome
276
HIT
more common wiht the use of unfractionated heparin, but can still occur with low moelcular weight heparin.
277
HIT
presnetation
5 to 10 days after the start of heparin with a marked drop in platelet coutn (more than 30%). both venous and arterial thromboses can occur, benous clots are more common. rarely leads to bleeding. the platelet just precipitate out
278
HIT
diagnostic tests
confirmed with elisa for platelet factor 4 antibodies or the serotonin release assay
279
HIT treatment
1. immediately stop all heparin containing products. you cnnot just witch unfractinated heparin to low molcular wieght heparin
2. administer direct thrombin inhibitors: argatroban, lepirudin, bivalirudin, and fondaparinux
3. warfarin should not be used first, but after a direct throbin inhibitor is started, use warfain, fondaparinux is safe
280
platelet therapy in hit
dont do it it will only get worse
281
apl i sthe one most likely to need lifelong
warfarin wiht only only clot
282
Anti phospholipids syndromes
definition
2 main syndromes are lupus anticoagulatn and the anticardiolipin antibodies are associated with multiple spontaneous abortions.
283
anticardiolipin antibodies are associated with
abortions
284
Anti phospholipids syndromes
are the only cause of thrombophilis with
an abnormality in aptt
285
Anti phospholipids syndromes
best initial test
mixing study bc it is a circulating inhibitor, ath aptt will remain elveated even after the ix
286
Anti phospholipids syndromes
most accurate test for lupus anticoagulant
russell viper venom test
287
Anti phospholipids syndromes
treatment
heprain and warfarin as you would for any cuase of dvt or pulmonary embolus. aply syndrome may require lifelong anticoag
288
fondaparinux is safe in
hit
