Hematology Flashcards
What test should be ordered on all pts with anemia?
peripheral smear
What abnormal labs will be found in von willebrand dz?
VWF or antigen level
VWF activity
prolonged aPTT (affects levels of factor 8) in 50% of cases
*bleeding problem is a platelet adhesion issue
could do a mixing study (tells you if you are missing a factor)
What is the pentad of TTP?
intravascular hemolysis
low platelets
renal insufficiency
fever
neuro deficits
*not all 5 have to be present
How would you check for an inhibitor or deficiency?
Mixing study - all studies should correct when normal blood is mixed with the pt’s bloods
*if it doesn’t, there must an inhibitor eating up the old and new factors
How can you monitor response to iron oral repletion in iron deficiency anemia and what is long term management?
- check for increased reticulocytes 10-14 days after starting therapy
*if it hasn’t incr, may be a malabsorption issue and need IM or IV iron (but not great bc can cause necrosis)
- Check CBC in 1 month
- continue to tx for 2 months after Hgb recovers to replete stores
4*. can add vit C to incr iron absorption (elderly)
What are CBC and pertinent lab findings in TTP?
CBC: anemia and thrombocytopenia
Thrombi are tearing up the red blood cells in the little vessels
schistocytes on peripheral smear
LDH elevated
retic elevated (compensatory)
BUN and Cr elevated
What are causes of macrocytic anemia?
Vit B12 deficiency
folate deficiency
alcoholism
liver disease
How to treat Heparin induced thrombocytopenia?
stop all heparin! (including line flushes)
start argatroban (for renal fx), bivalirudin, or fondaparinux (for liver fx)
stop warfarin (could go back to warfarin after 5 days or stay on other anticoagulant) - or cont warfarin if INR is therapeutic (2-3)
repeat CBC, PT, PTT, INR
NEVER USE HEPARIN AGAIN
What are the iron study findings in anemia of chronic dz?
low serum iron
high ferritin
TIBC low bc can sense that there is ferritin and it doesn’t increase to try to compensate
How do you work up new bleeding with concern for hemopathy or liver pathology?
PT, PTT
Fibrinogen (helps look at DIC)
AST/ALT
LDH
Alk phos
Bilirubin
How to treat HUS?
Supportive care
(no plasmapharesis - different mechanism that TTP)
What is the differential for an older pt with ataxia, decr sensation in extremities, mild confusion/change in personality, and hyperreflexia?
vit B12 deficiency
tertiary syphilis
chronic alcoholism
thyroid dz (dementia - but doesn’t cause sensory deficits)
depression
How to work up a PLT drop with pt on heparin?
re-check CBC and peripheral smear
check serotonin release assay and platelet factor 4 assays to dx HIT (will be abnormal)
What to think of if sickle cell pt has sudden drop in Hgb of more than 3-4 pts?
Parvovirus B19 or folic acid deficiency
What is the most common cause of Vit B12 deficiecny?
(in USA) pernicious anemia
*antibiodies made to intrinsic factor and parietal cells
(in other countries) nutritional anemia
What is the natural hx of ITP in adults?
chronic and relapsing
only tx if PLTs <20K and symptoms
*if refractory to steroids - splenectomy
*if still refractory - rituximab
When can you confirm G6PD?
Test may be normal in acute period (bc old cells are gone and new cells don’t have low level of G6PD yet)
Must measure G6PD level later (2 months)
How do you treat acute hemolysis from G6PD?
transfusion if Hgb low and symptomatic
IV hydration
What clinical signs/symptoms are associated with TTP?
fatigue, dark urine, evidence of thrombosis (arterial: stroke), jaundice, fever
*microangiopathic syndrome causing thrombosis in kidneys, brain…etc
How do you treat von willebrand disease?
DDAVP (vasopressin) intranasally daily
*causes the release of subendothelial stores of VWF and factor 8
Avoid aspirin
If DDAVP doesn’t help in an acute bleed (rare), can replace factor 8 (contains both VWF adn Factor 8)
What physiologic conditions must be considered in sickle cell patients?
functional asplenia - cover encapsulated organisms
susceptible to dehydration due to renal damage and difficulty concentrating urine
can have severe anemia due to destruction of RBCs that can cause dyspnea (esp with parvovirus)
What factors are being tested in PT and PTT?
PT - factor 7
PTT - other factors
What electrolyte abnormality can go along with vit B12 deficiency treatment?
decreased K as cells are rapidly being made - if getting muscle cramps/proximal weakness need to check and replace K
How to dx heparin induced thrombocytopenia and what to think about for complications?
>50% drop in PLTs within several days of starting heparin
check serotonin release assay (abnormal) and platelet factor 4 antibodies (positive)
*get thombosis more often than bleeding - can lead to venous thrombosis (DVT, PE)
What is happening in thormbotic thrombocytopenic purpura and what is HUS?
large conglomerates are forming with vWF/platelets that get stuck in small vessel and cause shredding of RBCs as they pass through
*microangiomapthic hemolytic anemia
hemolytic uremia syndrome - renal failure with microangiopathic hemolytic anemia (happens from shigella toxin with E Coli 0157
How to work up reversible causes of dementia and concern for B12 deficiency?
CBC, peripheral smear
T4, TSH
BUN, Cr
CT head
VDRL, RPR
Homocystein level, methylmalonic acid level
What tests help you confirm pernicious anemia and vit B12 deficiency?
B12 level (may be low)
Anti-intrinsic factor and anti-parietal cell antibody (tells you if pernicious anemia vs nutritional)
methylmalonic acid (* BEST test)
How to treat iron deficiency anemia?
oral ferrous sulfate (3 times per day)
servere anemia - transfusion then oral
What must be considered in iron deficiency anemia in someone outside of pregnancy aged women?
occult GI bleed if it is a man or women outside of child-bearing age range
*less common - malabsorption - celiac, whipple’s disease
What is an important side effect of sulfa drugs?
bone marrow suppression (usually pancytopenia)
How to work up pts with acute jaundice and pallor?
CBC, LFTs, PT, PTT, Peripheral Smear, UA, U/S abdomen
What are the differences between extravascular and intravascular hemolysis?
Extravascular - subacute from RBC destruction in spleen and liver
*liver dz, infection ,heme malignancy, autoantibodies, membrane abnormalities
Intravascular - acute onset with hemoglobinemia and decrease in haptoglobin (gets consumed rapidly)
*TTP, HUS, DIC, malignant HTN
Why does Vit B12 deficiency causes neuro issues?
bc you need vit B12 to form myelin!
How to manage sickle cell patients inpatient after once admitted?
repeated morphine/hydromorphone
contineu IV NS and oxygen
continue abx until ruled out
follow reticulocyte count
if not sure baout sickle cell dx, do hemoglobin electrophoresis
How to treat and f/u PE or proximal DVT?
Start LMW heparin, then bridge to Warfarin
recheck CBC in a couple days to check for HIT
check INR
need anticogaulation for 6 months
How do you calculate the A-a gradient?
150 - 1.2(PCO2) - PO2
if elevated - makes sense with lung process/decreased oxygen/co2 exchange?
DDx for spontaneous superficial bleeding?
Immune thrombocytopenic purpura (ITP) (antibody mediated)
acute leukemia
DIC (need to be very sick)
drug related thrombocytopenia (heparin, chemo, NSAIDs, ranitidine, linezolid, sulfa drugs)
aplastic anemia (pancytopenia)
vWD (wouldn’t have low PLTs)
malignancy (marrow infiltration)
SLE
What drugs can cause drug-related thrombocytopenia?
heparin, chemo, NSAIDs, ranitidine, linezolid, sulfa drugs
How to think about causes of thrombocytopenia?
production issue vs premature destruction issue
*bone marrow can help you decide (GOLD STANDARD) bc if increased megakaryocytes (incr production) tells you that the cause is peripheral destruction
What is the inheritance pattern of G6PD?
x-linked disorder - more common in men
*most common enzyme abnormality of RBCs
What chronic conditions must you think about when you see ITP?
Lupus, CLL (chronic lymphocytic leukemia), HIV
What is long term therapy for sickle cell disease?
hydroxyurea to increase HgF and decr crisis events
pneumococcal vaccine (+ booster after 5 yrs)
folate supplementation
How to workup a bleeding disorder?
CBC, PT, aPTT, LFT
type and cross if worried about significant bleeding
get CBC in 5-10 hours to make sure no big bleed
What is paroxysmal nocturnal hemoglobinuria?
Where red bloods cells are not very stable and when pt gets a little acidic overnight, the stress causes blood cells to break down and they have blood in their urien in the mornings
For what 3 conditions do we use DDAVP?
central DI
von Willebrand disease
Mild factor 8 deficiency
How to treat and further w/u thrombocytopenia (ITP)?
start predisone orally, continue 4-6 wks, then taper when PLTs >50k (if can’t taper - can do splenectomy)
*may need IV Ig if not improving, sign bleeding
check HIV, repeat CBC, heme consult
check ANA, bone marrow biopsy
check spleen with abd US
*only consider PLT transfusion in life-threatening bleeding
How to tx TTP?
IV fluids
Plasmapharesis (plasma exchange) to remove the antibodies to ADAMST13
*DO NOT GIVE PLATELETS!!! Will make TTP/HUS worse.
Heme consult
What CBC findings are diagnostic for B12 or folate deficiency?
macrocytic anemia
hypersegmented neutrophils
+
B12 has neuro deficits
How do you treat sickle cell pts in acute crisis whose oxygen saturation is not improving with supplemental oxygen?
exchange transfusion for acute chest syndrome
What is aplastic anemia?
fibrosis of the bone marrow/failure of the bone marrow (pancytopenia)
How do you tell the difference between folate and vit B12 deifciency?
Both will have increased homocysteine levels, but only vit B12 has elevated methylmalonic acid
Also, only B12 has neuro deficits
What are causes of microcytic anemia?
iron deficiency
thalasseemia (trait is asympptomatic, nml RDW, very low MVC compared to anemia which is minor)
anemia of chronic dz (can’t access iron stores)
sideroblastic anemia (B6 deficiency in alcoholics, can’t use iron and iron builds up around RBCs)
What encapsulated organisms must we consider in sickle cell patients?
pneumococcus
haemophilus influenzae
klebsiella pneumoniae
neisseria meningitidis
What is the natural hx of ITP in children?
often comes after a viral illness
dz is transient and will resolve in 2-8 wks, need temporary tx with steroids to get through
Why does B12 cause anemia?
Need B12 to make all cell lines in the bone marrow, what hapens is that cells are being made (but not correctly) but then rapidly destroyed as they leave the bone marrow
How do you treat vitamin K deficiency?
give vitamin K!
What are lab findings of thalassemia?
very mild anemia (10-11)
nml RDW
very low MVC (60-70) compared to anemia
Peripheral smear - target cells
How to read hemoglobin electrophoresis in sickle cell?
if HgS and 2-4% HgA2 and 2-20% HgF and NO HgA- has sickle cell
if HbS and HgA - sickle trait (no symptoms except microscopic hematuria)
How do you treat and detect parvovirus infection in a sickle cell pt?
IgM level or PCR for parvovirus DNA
tx with IV IgG infusion
What are the iron study findings in iron deficiency anemia?
low serum iron
low ferritin (pathopneumonic for iron def anemia)
total iron binding capacity is high (lots of available proteins to hold ironin response to low esrum iron)
*of note ferritin is an acute phase reactant - so could look normal due to inflammatory state
What is the differential diagnosis for a sickle cell pt with increase in pain?
vaso-occlusive crisis
acute chest syndrome (pulmonary infarction)
pulmonary infection (if SOB)
What are common triggers for G6PD?
oxidative stress (infection ,sulfa drugs, DKA, antimalarials, ingestion of mothballs/fave beans)
meds (dapsone, primaquine, nitrofurantoin)
How is B12 absorbed?
has to bind to intrinsic factor in proximal ileum and then get absorbed in distal ileum
What test do you follow when you start treating vit B12 defiiciency?
follow the methylmalonic acid to see it go down over time
What specific tests should you get when thinking abotu G6PD?
retic count, LDH, unconjugate bilirubin (all elevated)
haptoglobin (decreased)
coombs test (neg) *tells you if autoimmune
What are physical findings of iron deifiency anemia?
brittle fingernails
spooning of nails
esophageal webs
pagophagia (eating ice)
What 2 types of anemia cause elevated PLT counts?
iron deficiency anemia and anemia due to blood loss
What complication can happen after mycoplasma pneumonia 10-14 days later?
cold agglutinin IgM anemia
*IgM destroys RBCs in Kupffer cells of liver
What 2 conditions shoudl come to mind when you see schistocytes on a peripheral smear?
TTP and HUS
*if neuro - TTP
*if renal and hx of eating uncooked meat - HUS
What is the differential for new spontaneous bleeding with elevated PT/PTT?
vit K deficiency (can be affected by broad spectrum abx for long periods - 5-7+ days)
factor deficiency (8 or 9 -genetic hemophilia)
factor inhibitor (autoimmune dz - acquired hemophilia)
DIC
liver disease
When do you see indirect (unconjugated) bilirubin elevation vs direct (conjugated) bilirubin elevation?
indirect (unconjugated) - from red blood cells and bound to albumin in the serum - from breaking open of blood cells like hemolytic anemia (ex. TTP)
direct (conjugated) - biliary obstruction, backed up in the liver (biliary atresia, hepatitis)
Where do indirect and direct bilirubin come from?
indirect comes from the RBCs breaking down
direct comes from the liver
Where is iron absorbed?
duodenum and proximal jejunum
*will see iron deficiency in Celiac!
Ddx for long bleeding times for lifetime?
Hemophilia A (factor 8) and B (factor 9) *only men (sex linked recessive)
Von Willebrand disease
ITP
Factor XI deficiency (autosomal dz)
How to treat aplastic anemia?
Remove toxin if it is caused by exposure.
If autoimmune: bone marrow transplant after high-dose chemo to get rid of autoimmune cells first
What are lab findings of iron deficiency anemia?
CBC with low RBC (anemia), PLTS elevated
MCV <80
incr RDW (diff sizes of RBCs)
peripheral smear hypochromic and microcytic
retic count (1-2%) (it is “normal” so it is not correctly compensating bc there is not enough iron)
How to treat B12 defieincy?
injection of B12 daily (if neuro deficits)
monthly injection or daily high oral dose B12 if no neuro deficits
*replace K
(high oral dose gets around the intrinsic factor mechanism and will be absorbed)
What helps iron absorption?
acidic environment (asorbic acid or citric acid)
What causes aplastic anemia and how to dz?
autoimmune, toxins, meds (indomethicin, sulfonamides, radiation, chemo), infections (hep C, mono)
bone marrow biopsy with fat filled marrow
First steps in treating sickle cell crisis?
- oxygen, IV normal saline
- morphine or hydromorphone
- Antibiotics if concerned about infection - fever or incr WBCs (cover encapsulated and community acquired organisms) - Ceftriaxone/cefepime/ cefotaxime IV or moxifloxacin/levofloxacin
- labs - blood cultures, CBC, bilirubin, UA, CXR (if SOB or worried about acute chest syndrome), ABG, peripheral smear (confirm sickle cells)
What tests should be ordered for spontaneous superficial bleeding?
CBC w/ diff and peripheral smear
PT/PTT (testing factors not platelets)
fibrinogen
