Questions for myself - oski Flashcards
1
Q
What are 3 causes of microcytic, hypo chromic anemia
A
- Iron deficiency
- Thalassemia
- Lead poisoning
2
Q
What are 2 causes of macrocytic anemia with hyper segmentation of polymorphonuclear leukocytes
A
- vitamin B 12 deficiency
2. folte deficiency
3
Q
What are the lab findings in iron deficiency anemia?
A
microcytic, hypochromic anemia with elevated RDW and low retic
Iron studies: low iron, high TIBC, low ferritin, low transferrin
4
Q
When do you expect to see improvement with treatment of iron deficiency anemia
A
improvement in retic in 2-3 days, increase in Hg in 1-4 weeks, increase in ferreting (i.e. iron stores) in 3 months
5
Q
True or false - iron deficiency even without anemia has adverse effect on attention span, behaviour and school performance
A
true - it does, even when not anemic
6
Q
Name 3 causes of folate deficiency
A
overall it is rare
1. malabsorptive states, medications, defects in folate metabolism
macrocytic anemia
low folate level, normal B 12, low retics, fruits and vegetables are main dietary sources
7
Q
Name 4 causes of vitamin B 12 deficiency anemia
A
again rare
1. strict vegan diets
2. pernicious anemia (aka people who lack intrinsic factor which is needed to absorb B12)
3. parasitic infections
4. diseases affecting the terminal ileum (i.e. crohnn’s disease) - since the receptors for IF are located here, so with disease here, cannot absorb B12.
labs with show macrocytic anemia, low B12, normal folate, low retic
8
Q
What are two risks of receiving chronic blood transfusions
A
- iron overload
- hemosiderosis - aka hemosiderin deposits itself into the bodies organs causing sickness
therefor should monitor serum ferreting and do chelation therapy if evidence of iron overload
9
Q
What is the normal life span of an RBC
A
100-120 days
10
Q
What type of anemia is found in chronic disease
A
anemia of chronic disease usually nomocytic but can occasionally be microcytic
other lab abnormalities include low serum iron, normal o high ferritin and normal TIBC
mechanism: increased cytokines ->increased hepcidin->regulates the release of iron stores
diseases with common anemia include: HIV, rheumatoid arthritis, SLE< chronic renal disease, malignancies and IBD
11
Q
When does Diamond-Blackfan anemia present?
A
presents in infancy
baby nelson says macrocytic
12
Q
What are associated abnormalities in Diamond-Blackfan anemia?
A
25% of patients have associated abnormalities
short stature, facial dysmorphism (include webbed neck, cleft lip), cardiac abnormalities and/or renal abnormalities
congenital baby nelson says autosomal recessive trait
triphalangeal thumb, late onset leukemia
13
Q
What are the lab findings in Diamond-Blackfan anemia?
A
Labs: macrocytic or normocytic anemia with low-retic , increased HgF, increased EPO, iron and erythrocyte adenine deaminase
bone marrow with absent or reduced erythroid precursors in the bone marrow
Hg may be as low as 25
Treament: continuous transfusions, 2/3 respond to steroids, BMT is curative
long term increased risk of leukaemia
14
Q
When does transient erythroblastic anemia of childhood present?
A
between ages 6 months - 5 years of age (most are >1 year old)
these kids are otherwise normal but have pure RBC defect (can be hard to tell apart from Diamond Blackfan, except Diamond Blackfan should be younger)
both have low erythroid precursors
thought to be autoimmune, possibly post infectious
15
Q
What are the lab findings in transient erythroblastic anemia of childhood?
A
Hg as low as 25, normocytic anemia with low retic, normal iron, HgF and erythrocyte adenine deaminase
low RBC precursors in the bone marrow
Treatment: self limited, occasionally need transfusions while they improve
16
Q
True or false - parvovirus aplastic crisis is clinically significant in normal healthy hosts
A
false - clinically insignificant in normal hosts but results in profound anemia in patients with hemolytic anemias (i.e. sickle cell disease
mechanism: parvovirus directly infects erythroid progenitor cells and inhibits RBC production for 1-2 weeks, can lead to cardiovascular decompensation, if patients get a severe anemia they may need transfusion)
17
Q
What will the reticulocyte count be in parvovirus-associated aplastic crisis? (high/low/normal)
A
low - will also have severe drop in Hg, and absence of RBC precursors in the bone marrow
positive antibody titers to parvovirus
treatment: supportive care
18
Q
True or false - the same patient can have multiple episodes of parvovirus associated aplastic crisis
A
false - does not recur in the same patient due to protective antibodies which develop
19
Q
What are the three classes of hemolytic anemias
A
- cell membrane defects - RBC instability, increased destruction in the spleen
- RBC enzyme abnormalities compromising ATP generation, inability to meet metabolic demands of the cell and shortened RBC survival
- Immune-mediated destruction of RBCs via antibodies
20
Q
What are clinical signs of hemolysis
A
pallor/fatigue/SOB
jaundice
splenomegaly
those with hemolytic anemia - increased risk of gallstones (because of increased bilirubin) and parvovirus-related aplastic crisis
21
Q
how many patients with hereditary elliptocytosis have a hemolytic anemia
A
only 10% have a hemolytic anemia,most are asymptomatic
AD inheritance
smear will show elongated RBCs, structural abnormality of spectrin will show abnormally shaped fragile RBCs
**see chart in OSCE for details
22
Q
When is the their hemoglobinuria in paroxysmal nocturnal hemoglobinuria
A
more hemolysis in sleep
more hemoglobinuria in the AM
often hemolysis is precipitated by infection
treat with steroids (limit duration), may need BMT
hemolytic anemia and hemoglobinuria, may have thrombycytopenia/leukopenia also
flow-cytometry shows absence CD59
23
Q
What are 4 substances that should be avoided by patients with G6PD
A
avoid oxidant substances:
1. sulfonamids
2. naphthalene
3. antimalarials
4. lava beans
X linked, common in meditarranean, africa, america, arab
hemolysis happens from oxidative stress
can have increased G6PD enzyme in acute crisis due to reticulocytosis
G6PD leads to decreased protection rom oxidative stress
24
Q
True or false - splenectomy is curative in pyruvate kinase deficiency
A
false - not curative but may help anemia in severe disease
PK deficiency RBC can’t make ATP->therefore increased 2,3 DPG and rightward shift of the oxygen dissociation curve (i.e. decreased oxygen affinity)
AR inheritance
smear: polychromatophilic RBCs
25
What are potential causes/triggers of autoimmune hemolytic anemia
autoantibodies can be
1. idiopathic
2. secondary to:
- underlying disease (SLE, lymphoma, immunodeficiency)
- viral/mycoplasma infection
- drug exposure
can have fulminant acute disease or chronic prolonged course
treatment: steroids for acute disease, immunosuppression/splenectomy for refractory disease
26
What does the direct Coombs test detect?
a) antibodies or complement on a patients RBCs
b) autoantibodies in the patient's serum
a)
direct - detects antibodies or compleemnt on patient's RBC
indirect: detects antibodies in patient's serum
27
What two cell lines are affected in Evans syndrome?
concomitant autoimmune hemolytic anemia and ITP
28
What are Heinz bodies
denatured and precipitated Hg within RBC secondary to oxidative stress
damage the RBC membrane and cause hemolysis
29
True or false - a patient was transfused and hemoglobin electrophoresis was done 1 moth later, are the results valid
false - not valid with recent transfusion, should repeat 3-4 months later
30
When does HgF (fetal) transition to Hg A
3-6 months
HgF has a higher O2 affinity than HgA, primary form of hemoglobin until 3-6 months when HgA pre dominants
Hg is a tetramer - 2 alpha chains, 2 non-alpha chains, iron containing heme group that binds O2
tons of hemoglobin variants, only a few cause disease
31
What is the amino acid substitution in sickle cell disease?
people with sickle cell have Hb S
single amino acid substitution (glutamic acid->valine in HbA)
HbS deoxygenated polymerzies to form a sickled erythrocyte - >these survive less than regular RBCs, can obstruct small blood vessels, cause tissue schema and necrosis
32
How much of the hemoglobin in a individual with HgSs (heterozygous) is hgS
only 30-40% are HgS, so not enough to cause sickling and have a benign course
meanwhile SS leads to severe chronic hemolytic anemia
clinical features present at 6 months since that's when the HgF transitions to HbS
Other:
HgSC: similar to HbSS but less severe
HbS-b0 thall: similar to HbSS in quality and severity
HbS-b+thall: similar to but less severe than SS
sickle trait - confers partial resistance to falciparum malaria
33
Name 8 acute complications of sickle cell disease
1. pain crisis
2. acute chest crisis (fever, new infiltrate on CXR, hypoxia)
3. dactilytis (infancy)
4. priapism
5. infection
6. stroke (even those without big strokes can have mini strokes with affect cognition). can detect with routine annual transcranial doppler , those with history of abnormalities/stroke may need chronic transfusion therapy
7. aplastic crisis
8. sequestration crisis
* *see list in Oski for deets
34
Name 5 chronic complications of sickle cell disease and recommended screening intervals
1. Gallstones (can be asymptomatic, biliar colic, cholecysticis, cholangitis)
2. pulmonary hypertension (asymptomatic, right heart failure)
- check with annual echo after 1 year old, aggressively manage pulmonary disease (i.e. asthma)
3. renal disease (intramedullary sickling, papillary necrosis, renal tubular defect)
4. ocular complications - proliferative or nonproliferative retinopathy. can be asymptomatic or decreased visual acuity
- annual eye exam starting at age 10
- retinopathy more likely in HgSC than SS
5. avascular necrosis
also because of lots of transfusion, risk of iron overload
35
What disease shows Howell-Jolly bodies in the peripheral smear?
sickle cell disease
peripheral smear will show:
- sickled RBCs, nucleated erythrocytes, and Howell-jolly bodies (nuclear remnants)
other lab anemia: 50-90 , increased reticulocytosis (5-15%)
36
What is the most common cause of death in sickle cell patients younger than 5 years?
a) acute chest crisis
b) stroke
c) infection
d) sequestration crisis
c) infection ist he most common cause of death in SC patients < 5 years old
should always get culture and antibiotics in patients with fever >38.5 without a source, hospitalize all <3 months, with inability to f/u, sick
37
What least common of the following organisms in acute chest crisis in children > 3 years old with sickle cell disease?
a) chlamydia pneumonia
b) . mycoplasma
c) strep pneumo
c) strep pneumo
most comon in >3 yo are chlamydia and mycoplasma
strep and other typical organisms are less common, but implicated in some cases
should treat with ceftriaxone and a macrolide
(for asplenic, CPS says ceftriazone and vanco)
38
Which organism should you think of in osteomyelitis in sickle cell patients
salmonella
39
What percentage of sickle cell patients age 15-18 have gallstones
42%
40
You are in a rural community and are asked to manage the routine and preventative care of one of your 3 year old patients with sickle cell disease. What are the important things to do
1. infection prevention:
- penicillin prophylaxis from 2 months -5 years of age
- childhood immunizations PLUS
- 23 valent pneumococcal vaccine age 2 (and 5?, check Canada)
-meningococcal vaccine after 2 years
- influenza vaccine
2. Hydroxyurea to increase HgF production and decrease crisis
3. in severe disease - may need chronic transfusion to maintain HgS<30%
routine surveillance with TC doppler yearly after age 2, yearly echo at 15-16 for PTHTN, eye exam yearly after age 10 to look for retinopathy
41
What are the clinical manifestations of severe thalassemia?
1. signs and symptoms of anemia - pallor, fatigue, weakness, FTT, CHF
2. abnormal facies due to extramedullaryhematopoeisis, expansion of medullary spaces (maxillary hyperplasia, flat nasal bridge, frontal bossing)
3. pathologic fractures
4. HSM with hypersplenism
42
When is Hemoglobin electrophoresis useful to diagnose alpha thalasemia?
only in the newborn period
shows 3-6% Bart's Hg instead of normal HgF
Bart's hemoglobin: (gamma 4)
HgH is beta 4 (also increased in alpha thall)
newborn screening includes hg electrophoresis to detect sickle cell
43
How is thalassemia diagnosed ?
1. abnormal Hg electrophoresis results (see charts as well as my own handwritten algorithm)
2. hypochromic microcytic anemia with nucleated RBCs, poikilocytes (abnormally shaped cell)and target cells
44
What is the gold standard for diagnosis of hemosiderosis?
quantitative iron measurement by liver biopsy
hemosiderosis - iron overload - from multiple transfusions, inevitable and fatal consequence of multiple transfusions
early marker is elevate ferritin, non-invasivee methods to diagnose: MRI ferrous scan, superconducting quantum interference device
Treatment: chelation thearpy - ie deferoxamine
45
What is the most common cause of acquired neutropenia in children?
a) medications
b) cancer
c) autoimmune
d) infectius
d) infectious diseases are the most common cause of acquired neutropenia in children
include viral infection: hepatitis A/B, varicella, influenza, HSV, RSV, CMV, EBV, HIV, parvo; bacteiral (sepsis/TB), misc (incl ricketsia, malaria, toxo) **likely viral most common
46
What is the most common cause of chronic neutropenia in children?
a) medications
b) cancer
c) autoimmune
d) infectius
c) autoimmune neutropenia
usually between 6-26 months of age
usually don't need any intervention, recover without specific therapy
steroids, IVIG or G-CSF may be helpful in some cases
47
What are the two main components of the reticuloendothelial system
1. spleen
2. lymph nodes
fixed phagocytic cells interact with circulating lymphocytes to filter and remove damaged cells and debris from the blood stream and also to deliver antigens to the immune system
ONLY the spleen can filter encapsulated bacteria - hence why in hyposplenism, we worry about infections
48
Which organisms are functionally asplenic patients at risk for ?
encapsulated organisms: S. pneumo, Haemophilus influenza and Neisseria
can have anatomic or function, congenital and acquired
ie CHD with polysplenia- congenital functional
49
What cell line is most commonly deficient in hypersplenism
overactive spleen can lead to deficiencies in one or more peripheral cell lines, most commonly thrombocytopenia, depending on the severity and underlying aetiology, splenectomy may be indicated and is curative
50
Please name 4 big categories of causes of splenomegaly
1. viral infection - CMV, EBV
2. malignancy - lymphoma, HLH
3. portal venous congestion
4. storage disorders
why does splenomegaly happen: excessive antigenic stimulation, excessive cell destruction or passive congestion
51
How many patients with ITP have a preceding viral illness?
>50% have a preceding viral illness 1-4 weeks before
most common in 1-4 year olds
likely immune mediated phenomenon (although etriology not completely known)
most common cause of acquired thrombocytopenia in childhood
CNS bleed most scary complication but happens in
52
How common is CNS bleed in ITP?
a) <1%
b) 20%
c) 60%
d) 80%
a) t change the natural course of disease, but sometimes considered for severe cases to reduce risk of complications, can do wait and see for more mild cases (this is evolving)
treamtent options include IVIG, anti-D immunoglobulin and steroids
53
What will a bone marrow done on a patient with ITP show?
a) decreased megakaryocytic
b) normal to increased megakaryocytic
b) normal to increased - think of the body making more since they are getting destroyed; DON't need bone marrow for diagnosis, but sometimes done if unclear diagnosis
CBC should shown ONLY decreased platelets, other cell lines normal
blood smear - smaller number of platelets but normal morphology
54
Which cause of thrombocytopenia will have small platelets?
a) thrombocytopenia absent radius
b) amegakarocytic thrombocytopenia
c) Wiscott-Aldrich syndrome
d) none of the above
c) Wiscott Aldrich syndrome
cause of congenital thrombocytopenia
inheritance is x linked recessive
presents with thrombocytopenia, eczema and/or immunodeficiency (i.e. hypogammaglobinemia)
peripheral thrombocytopenia, tiny platelets
treatment: IVIG, steroids, bone marrow transplant
55
How many children recover from ITP within 4 weeks without treatment?
a) 20%
b) 40%
c) 50%
d) 80%
c) more than 50% recover within 4 weeks without treatment
>80% recover within 6 months
chronic ITP is symptoms lasting more than 6 months
relapses are common in chronic ITP, rare in acute ITP
56
Name 4 drugs that are commonly causes of thrombocytopenia
1. penicillin
2. benzodiazapine
3. heparin
4. valproic acid
bactrim, digoxin, quinine
usually acute onset, within hours of drug administration
usually severe thrombocytopenia
usually resolve with withdrawal of agent
57
A child develops thrombocytopenia 1 day after heparin administration. What do you tell her mother about the course and prognosis?
two forms - this is the non immune mediated form which occurs within 1-2 days and is mild and benign
the other form si the immune form - occurs 4-10 days after, is severe, and is associated with an increased risk of arterial and venous thrombosis (which is a super opposite effect)
58
Name some side effects of IVIG
1/3 of patients - transient complications - h/a nausea aseptic meningitis, can also get allergic reactions
how IVIG works in ITP: blocks RES, decreases splenic clearance of platelets, promotes clearance of anti-platelet antibodies and inhibits phagocytosis of platelets
59
Which patients can get anti-D immunoglobulin for ITP
only RH + patients can get it
more sustained treatment than IVIG
can get some decrease in Hg
60
What is the difference between neonatal autoimmune thrombocytopenia and alloimmune thrombocytopenia
neonatal autoimmune thrombocytopenia: antibodies from a mother with ITP transferred via placenta - direct platelet antibody test positive with mother's platelets, postnatal IVIG may be helpful
neonatal alloimmune thrombocytopenia- mom is making antibodies to antigens on the baby's platelet's which were inherited from dad
therefore direct platelet antibody test on the mom is negative, but when tested with mother's serum and baby's platelets is positive; severe cases- intrauterine transfusion or IVIG to mom
(big risk is risk of intracranial bleeding during delivery or in utero)
61
What is the most commonly implicated pathogen in hemolytic ureic syndrome ?
E. coli O157: H7
blood diarrhea, followed by renal failure, anemia and thrombocytopenia
shortened platelet survival secondary to microangiopathic process involving fibrin deposition
Treatment: supportive, dialysis in severe cases
62
A child has fever, neurological symptoms, microangiopathic hemolytic anemia and thrombocytopenia, what is the diagnosis
Thrombotic thrombocytopenic purpura
less common in children than adults, thrombocytopenia from platelet aggregation and clumping in vessels
ADAMTS13 activity decreased
63
A med student wants to treat the patient above with platelet transfusions. What do you tell them?
a) go for it
b) don't do it
b) don't do it - platelet transfusions are contraindicated as they may worsen CNS and cardiac symptoms
64
A patient has thrombocytopenia and large hemangiomas, what is one potential diagnosis
kasabach -merrit syndrome - platelets can get sequestered and destroyed in large hemangiomas
65
A child presents to you with >1 million platelets. they are previously healthy but mom repots a long fever and rash which resolved 10 days ago. What is the most important test
a) echo
b) bone marrow
c) blood culture
d) iron studies
1. echo - Kawasaki disease can cause extreme thrombocytosis more than 1 million 7-14 days after
66
Which drug is most frequently associated with aplastic anemia?
a) ionizing radiation
b) chloramphenicol
c) antineoplastic drugs
d) none of the above
b) chloramphenicol (an antibiotic) is the drug most frequently associated with aplastic anemia, although only 1/20000 to 50000 people taking chloramphenicol develop aplastic anemia
other causes of aplastic anemia (baby nelson) : febamate, radiation
viral causes of aplastic anemia include: EBV CMV, hepatitis B and C ( particularly severe form, no causative factor for the hepatitis in half), HIV, parvovirus (in people with abnormalities of Hg see previous). aplastic anemia secondary to virus is often transient and self-limited
clinical manifestation - of anemia, leukopenia or thrombocytopenia
treament: depends on severity and aetiology: severe, transfusions, immunosuppressive therapy (steroids, etc ) or BMT
67
Which of the following is the most common congenital aplastic anemia ?
a) Diamond-Blackfan syndrome
b) Scwachman-Diamond syndrome
c) Dyskeratosis congenital
d) Fanconi anemia
d) Fanconi anemia - most common congenital aplastic anemia; overall , congenital aplastic anemias are very rare, the other options are the other congenital aplastic anemias
Autosomal recessive, caused by defect in DNA
cells are susceptible to damage by environmental toxins - >predisposes the patient to marrow failure
68
Which cell line is the first one affected in Fanconi syndrome?
usually thrombocytopenia before anemia and leukopenia->present with petechiae and bruising between the ages of 2-22 years (average is 7 years) progressive pancytopenia and hypoplasia of the bone marrow
hematologic abnormalities are progressive, not present during infancy and early childhood
69
Please list some associated physical anomalies with Fanconi syndrome:
1. short stature
2. hyperpigementation
3. thumb or radii abnormalities - absent thumbs
4. renal abnormalities
5. microcephaly
6. cafe au lait spots
7. can get leukaemia in 10% (because of DNA repair problems)
macrocytosis and increased Hg F precedes marrow failure
severe pancytopenia and eventual bone marrow failure
Treatment: platelet and erythrocyte transfusions, 2/3 of patients respond to androgenic hormone therapy, most eventually become refractory to androgens, BMT
70
What is the diepoxybutane test:
peripheral lymphocytes exposed to diepoxybutane show chromosomal abnormalities in Fanconi syndrome
71
How is hemophilia A inherited?
X linked - one of the most common inherited bleeding disorders ; female carriers are asymptomatic. spontaneous mutations are common (many won't have a family history)
defect in factor VIIII procoagulant activity
factor VIII - part of the intrinsic pathway->therefore leads to increased PTT alone
hemophilia B is also X linked, factor IX ->also part of the intrinsic pathway
clinically indistinguishable
coagulation cascade - activation of several enzymes, ultimately activation of thrombin and the subsequent deposition of an insoluble fibrin clot
72
True or false - a patient with mild haemophilia is unlikely to have life-threatening bleeding
false - although eh severity of hemophilia is related to hw much factor activity is present, life-threatening bleeding can occur even in patients with mild disease (although unlikely to be spontaneous as per baby nelson)
73
What is the most common site of life threatening bleeding in hemophilia?
hemarthrosis
| treatment for acute bleeds : factor replacement as soon as possible
74
Please describe 5 ways that hemophilia can present
1. excessive bleeding after circumcision (half of patients)
2. mucosal bleeding and bruising
3. intracranial hemorrhage
4. hemarthrosis
5. excessive bleeding with dental procedures, sutures, surgeries, etc
75
How much factor activity is present in moderate hemophilia?
a) 5-25%
b) 1-5%
c) <1%
d) none of the above
b) moderate hemophilia: 1-5% of normal activity in moderate hemophilia - will bleed significantly only after some sort of trauma
mild is 5-25% - usually bleed only after surgery or major trauma
severe: <1% of normal activity: subject to spontaneous bleeding
76
What will the labs show in haemophilia?
a) increased PT normal aPTT
b) increased aPTT, normal PT
c) increased PT and aPTT
d) none of the above
b) increased aPTT (intrinsic pathway which includes factor 8 and 9), normal PT
(screening test)
confirmatory testing after abnormal aPTT to determine which factor is having problems - specific factor assays:
hemophilia A: low factor VIII activity with a normal vWF assay
hemophilia B: low factor IX activity
in factor 8 or factor 9 deficiency, the aPTT is quite prolonged but should correct to normal when mixed 1:1 with normal plasma
other option for diagnosis is prenatal molecular diagnosis
77
When should factor replacement be given in hemophilia
1. maintenance therapy to keep activity greater than 1%
2. prophylactic prior to procedures
3. acutely in response to acute bleeding episodes
other supportive treatment: epsilon aminocaproic acid, tranexamic acid, FFP, DDAVP
prevent bleeding - avoid contact spots and similar activities
78
Which of the following is not part of factor VII deficiency?
a) symptomatic mucosal bleeding and/or intracranial hemorrhage
b) isolated aPTT prolongation
c) autosomal recessive
d) treatment with recombinant factor VII or FFP
b) false - in fact, isolated PT prolongation with normal aPTT
79
Which factor deficiency classically presents with delayed bleeding from the umbilical stump?
factor 13 deficiency
| normal coags - blood forms an unstable clot
80
Which of the following is the most common inherited coagulopathy?
a) hemophilia A
b) hemophilia B
c) von willebrand disease
c) von willebrand disease is the most common inherited coagulopathy, affects 0.8-1.6% of the general population
multiple disorders
81
What are some consequences of insuffieicny vWF activity
vwf mediates platelet adhesion at sites of tissue injury and acts as a carrier for factor VIII
results in
1. decreased platelet adhesiveness, impaired platelet agglutination, increased bleeding time
3 forms of vWD
82
Which form of von Willebrand disease is mild-moderate bleeding?
a) type I
b) type II
c) type III
a) type I diseaes: mild-to-moderate bleeding
- presents with epistaxis, menorrhagia, easy bruising, excessive bleeding after dental extraction
type II and III more severe bleeding tendenies
labs: prolonged aPTT and prolonged bleeding time with a normal platelet count
confirmatory testing: decreased vWF measured by ristocetin activity and vWF antigen levels
83
How is type III vWD inherited
autosomal recessive, type 1 and 2 are AD
84
How do you treat type I vWD?
a) DDAVP
b) vWF
c) none of the above
a) DDAVP: useful for type I disease, given intranasally 20-30 minutes prior to minor procedures for prophylaxis and/or for minor bleeding
aminocaproic acid - for prophylaxis of mucosal bleeding
vWF concentrates - useful for severe bleeding in all types, not just 1 and 2
85
Which clotting factors are vitamin K dependant?
1972 Canada soviet - aka 10, 9, 7, 2 protein C and S
| dietary vitamin K found primarily in green, leafy vegetables
86
Please name 3 causes of vitamin K deficiency
1. inadequate dietary intake
2. malabsorption secondary to pancreatic insufficiency, biliary atresia, prolonged diarrhea
3. drugs
- rifampin, phenytoin, isoniazid
vit K deficiency - presents with bleeding tendency, easy bruising, oozing, visceral bleed
87
What will labs be in vitamin K deficiency?
increased PT vs aPTT, normal fibrinogen
| treatment is vitamin K (PO/SQ but can be given IV if life-threatening bleed)
88
Which clotting factor is not primarily made in the liver?
factor VIII - has significant extra hepatic synthesis
therefore any process that impaired liver synthetic function will results in a coagulopathy with prolongation of both PT and aPTT
however factor VII deficiency will cause a elevation of PT but the rather coats will be normal
89
What are the lab findings in DIC:
1. thrombocytopenia
2. increased aPTT and PT
3. low fibrinogen
4. increased d-dimer
```
peripheral smear with microangiopathic changes
baby nelson (pg 531)
Ddx with liver failure (same labs but jaundice in liver failure), vitamin K deficiency and sepsis 0will have increased PT and aPTT but nomal fibrinogen, platelets and D-dimer
```
90
What is the differential diagnosis of isolated prolongation of PT?
1. vitamin K deficiency(including hemorrhagic disease of the newborn, malabsorption, rat poison, oral anticoagulants)
2. factor VII deficiency (check, baby nelson doesn't have this)
3. liver disease
91
How do you calculate the ANC?
WBC x (percentage bands + percentage neutrophils)
92
When does the ANC nadir occur after myelosuppressive chemotherapy
a) immediately
b) 10-14 days after
c) 14-21 days
d) 1 month after
b) 10-14 days after
93
Which special organism must be covered in the treatment of a febrile neutropenia patient?
pseudomonas
| antibiotics which can cover it include ceftaz, cefepime, and carbapenems (imipenem and meropenem)
94
Which two tumours are the most common causes of timor lysis syndrome?
1. Burkitt's Lymphoma
| 2. ALL ->especially T cell ALL
95
Thalassemia - what are the different types?
1. beta thalassemia
2. alpha thalassemia
both cause microcytosi, weither with or without mmild hypo chromic microcytic anemia
ethnic groups: meditarranaean, southeast asian, african americans
asians - can have deletion of 3 or 4 alpha genes - results in hemoglobin H disease (gamma 4) or hydrous fettles (with 4 alpha chains)
96
Thalassemia
1. alpha chain - needed for fetal erythropoiesis and production of hemoglobin F - present in utero
4 alpha chains are on the number 16 chromosome
a) single gene deletions - silent carrier state, no disorder
b) two gene deletion - alpha thalassemia minor - mild or no anemia and microcytosis
c) deletion of 3 genes - moderate hemolytic anemia with gamma 4 tetramers (which are called Bart hemoglobin in the fetus) and beta 4 tetramers (called hemoglobin H) in older kids and adults ; clinically microcytic anemia and mild hemolysis; not transfusion dependent
d) deletion of 4 genes - hydrops fetalis and death in fetus possible without intrauterine transfusions
2. beta chain - more prevalent in US- alter the beta chain production ; usually manifest between 4-12 months (i.e. when fetal hemoglobin is transitioning)
**most are not clinically severe unless both chains are abnormal
a) both beta chains abnormal - thalassemia major - clinical severe hemolysis, ineffective erythropoiesis, transfusion dependency, HSM (from extra medullary erythrompoiesis) , iron overload (because of increase in rate of iron absorption) , severe anemia can lead to growth failure and high output heart failure
b) one beta chain abnormal - moderate hemolysis, splenomegaly, moderately severe anemia but not transfusion dependent, main life-thretening complication is iron overload
c) thalassemia minor- microcytosis and mild anemia -
Treatment of beta thal major: is hyper transfusion programs) ; splenectomty may reduce the transfusion volume, but adds to risk of infection
if have iron overload should start deforaxime, and before clinical signs of iron overload (non immune diabetes mellitus, cirrhosis, heart failure, skin bronzing and multiple endocrine abnormalities
stem cell transplant - before organ dysfunction - treatment of choice in beta thal major
97
abnormalities in beta chain
function: Hg SCED
production: beta thalassemia
98
hereditary spherocytosis what is the test for it
osmotic fragility test
99
Hemolytic anemia caused by disorders extrinsic to the RBC -
1. isoimmune hemolysis - maternal antibodies
2. autoimmune hemolytic anemia -
a) post infectious - i.e. mycoplasma, EBV, other viruses
b) autoimmune disease - SLE, lymphoproliferative disorders, immunodeficiency
c) drug induced - i.e. tom penicillin or quinidine ; alpha methyldopa and a few others (they modify the membrane)
3. mechanical damage to RBCmembrane:
a) thrombotic microangiopathy - trapped by burin in the circulation - broken by shear stress
ie) HUS< DIC< TTP, malignant hypertension, toxemia, hyperacute renal graft rejection
usually have large platelets
DIC - will have major consumption of clotting factors (especially in DIC)
Smear: RBC fragment s - schistocytes, teadrops, polychromasia
from artificial heart valves
from high flow and shear - i.e. Kasabach Merritt syndrome
4. alterations in plasma lipids, especially cholesterol - can damage the RBC membrane
ie) abetalipoproteinemia - leads to spur cells
5. toxins - ie snake venoms and heavy metals
6. renal failure - burr cells
7. vitamin E deficiency - ie in prems, CF, or with iron overload from transfusion
100
what will your blood smear show in autoimmune hemolytic anemia
spherocytes
occasionally nucleated RBCs
reticulocytes can vary
101
management of hemolytic anemia (autoimmuen)
tricky with transfusion, can get cross reactivity
steroids
IVIG are the other options
more than 80% of kids with autoimmune hemolytic anemia will recover on their own
102
How to calculate the amount of factor replacement in hemophilia
life threatening bleedings - levels of 80-100% of normal factor 8 or 9
mild to moderate bleeding - ie hemarthrosis:
- 40% of factor 8 or 30-40% of factor 9
dose of factor replacement - for mild-moderate bleeding:
factor 8: desired level (%) x weight (kg) x 0.5
factor 9 - desired level (%) x weight (kg) x 1.5
103
which type of hemophilia might DDAVP help with?
might help with hemophilia A (mild or moderate, can tripe or quadruple the initial factor 8 level of a patient) but no effect on factor 9 levels
104
true or false - new recombinant factor 8 or 9 - risk of infections
false - safe from infections
| (the older plasma derived factors had high risk of hep BCD and HIV
105
Most common cause of hereditary thrombosis predisposition
factor 5 leiden
