Hematology Flashcards
What symptoms should you expect with the following Hematocrit:
25-30%
20-25%
<20%
25-30% = Dyspnea and fatigue
20-25% = Lightheadedness, angina
<20% = Syncope and chest pain
Causes of low MCV
Iron deficiency
Thalassemia
Sideroblastic anemia
Anemia of chronic disease
What is the only microcytic anemia to have an elevated reticulocyte count?
alpha thalassemia with 3 genes deleted
all other microcytic anemias have a low reticulocyte count
Cause of high MCV
B12 and folate deficiency
Sideroblastic anemia
Alcoholism
Liver disease or hypothyroidism
Macrocytic anemias all give what type of reticulocyte count?
Low
At what hematocrit do you transfuse a patient?
If the patient is symptomatic (SOB, lightheaded/confused, hypotensive/tachycardic, chest pain) = transfuse
If the hematocrit is very low (25-30) in an elderly patient or one with heart disease = transfuse
Each unit of PRBCs should raise the hematocrit by?
3 points per unit
Will raise the Hgb by 1 per unit
When is FFP NOT the answer?
NOT a choice for hemophilia A or B or von Willebrand disease
Used to replace clotting factors (elevated PT, aPTT, or INR)
Cryoprecipitate is used to replace
fibrinogen
Has some utility in DIC (high levels of factor VII and VWF)
When do you give platelets?
To a bleeding patient when platelet count is <50,000
CONTRAINDICATED for TTP and HUS
Where is iron absorbed in the body?
Duodenum (4 mg/day)
- Body needs roughly 1-2 mg/day*
- Menstruating women need 2-3 mg/day*
- Pregnant women need 5-6 mg/day*
What is hepcidin?
Regulates iron absorption
Hepcidin levels are low in anemia of chronic disease
What is the most likely diagnosis for anemia with:
- Blood loss
- Menstruation
- Cancer
- RA
- Alcoholic
- Asymptomatic
- Iron deficiency
- Iron deficiency
- Chronic disease
- Chronic disease
- Sideroblastic
- Thalassemia
Target cells are seen most commonly with
Thalassemia
However, they can be seen with all causes of microcytic anemia
Anemia with iron studies showing:
- Low ferritin
- High iron
- Normal iron
- Iron deficiency
- Sideroblastic anemia
- Thalassemia
TIBC in Iron deficiency vs Chronic disease
Low TIBC = chronic disease
High TIBC = iron deficiency
Most accurate test for:
Iron deficiency
Sideroblastic anemia
Thalassemia
Iron deficiency = bone marrow biopsy for stainable iron which is decreased (rarely done)
Sideroblastic anemia = prussian blue staining for ringed sideroblasts
Thalassemia = hemoglobin electrophoresis (exception = alpha thalassemia, which is diagnosed by DNA analysis)
Most appropriate next step when MCV is elevated
Peripheral blood smear
Only B12 and folate deficiency (and antimetabolite medications) cause hypersegmentation
Pancreatic insufficiency causes what type of anemia
Macrocytic (need pancreatic enzymes to remove B12 from the R-protein so it can bind with IF)
When the vignette suggests B12 deficiency, but the B12 level is equivocal, what is the next step?
MMA level (only elevated with B12 deficiency)
What is a complication of rapid B12 or folate replacement?
Hypokalemia
There is no other condition in which cells are generated so rapidly that they use all the potassium
Bilirubin gallstones
Osteomyelitis
Retinopathy
Stroke
Skin ulcers
Avascular necrosis
Common manifestation of SCD
Children present with dactylitis (inflammation of fingers)
The best initial test for SCD?
Peripheral smear
Sickel cell trait (AS disease) does NOT give sickled cells
The most accurate test is hemoglobin electrophoresis
What lowers mortality in SCD?
Hydroxyurea (prevents recurrences by increasing Hgb F)
Antibiotics (ceftriaxone, levofloxacin, or moxifloxacin) with fever
Exchange transfusion for SCD is used if there is severe vasoocclusive crisis presenting with:
Acute chest syndrome
Priapism
Stroke
Visual disturbance from retinal infarction
Best initial test for a patient with SCD with a decreasing hematocrit?
Reticulocyte count (first clue to parvovirus)
Patients with SCD have very high reticulocyte counts because of chronic compensated hemolysis. Parvovirus B19 causes an aplastic anemia crisis which freezes the growth of the marrow.
Most accurate test for parvo is a PCR for DNA. IVIG = best initial therapy
What is the only manifestation of sickle cell trait?
Defect in the ability to concentrate the urine (isosthenuria)
Most accurate test for Hereditary Spherocytosis
Osmotic fragility
Defect in cytoskeleton leading to abnormal round shape and loss of flexibility
Treatment for Hereditary Spherocytosis
Chronic folic acid replacement
Splenectomy to stop hemolysis
Treatment of Warm Hemolysis vs Cold Agglutinin Disease
Warm = glucocorticoids, then splenectomy, then IVIG, then rituximab
Cold = stay warm, rituximab (steroids and splenectomy DO NOT WORK)
Cyclophosphamide
Cyclosporine
Azathioprine
Mycophenolate mofetil
Alternative treatments to diminish the need for steroids
Heinz bodies and bite cells
Seen in G6PD deficiency
Both TTP and HUS are characterized by:
Intravascular hemolysis with fragmented red cells (schistocytes)
Thrombocytopenia
Renal insufficiency
TTP is also associated with neurological disorders and fever
What is paroxysmal nocturnal hemoglobinuria?
A clonal stem cell defect with increased sensitivity of red cells to complement in acidosis leading to aplastic anemia, myelodysplasia, or acute leukemia
Deficiency of CD 55 and 59 (decay accelerating factor)
Most common cause of death from PNH
Thrombosis
Mesenteric and hepatic veins are the most common sites
Define aplastic anemia
Pancytopenia of unclear etiology
Acts as an autoimmune disorder in which the T cells attack the patient’s own marrow
Treatment for aplastic anemia
allogenic bone marrow transplantation (BMT)
if the patient is over 50 or there is no matched donor, the treatment is antithymocyte globulin (ATG) and cyclosporine
Define polycythemia vera
Unregulated overproduction of all 3 cell lines, but red cell overproduction is the most prominent
Mutation in the JAK2 protein (red cells grow wildly despite a low EPO level)
Hypertension
Heptosplenomegaly
Bleeding and Thrombosis
Pruritis following warm showers
Polycythemia vera
Up to 40% of patients with PV have gout
Most accurate test for PV
JAK2 mutation
Also look for elevated hematocrit (>60), low EPO, and elevated B12
Treatment for PV
Phlebotomy and ASA to prevent thrombosis
Hydroxyurea helps lower the cell count
Allopurinol or rasburicase protects against uric acid rise
Antihistamines
Target Hct is < 45%
Apart from PV, what is a JAK2 mutation also associated with?
Essential thrombocytosis
What is myelofibrosis?
Disease of older persons with a pancytopenia associated with a bone marrow showing marked fibrosis; *blood production shifts to the spleen and liver (enlarged)
Teardrop-shaped cells and nucleated RBCs
*Extramedullary hematopoiesis
Lab values indicative of hemolysis for normocytic anemia
Increased LDH
Decreased haptoglobin
Increased Tbili
Not seen in hemorrhage (exception = production problem + hemolysis)
Why is iron increased in sideroblastic anemia?
Iron gets stuck in the mitochondria; cells cannot use the iron, so the body keeps sending more that also gets stuck
Reversible and Irreversible causes of sideroblastic anemia
Reversible = drugs, EtOH, and lead
Irreversible = B6 deficiency (cannot just replace) and MDS
What will the hemoglobin electrophoresis show for alpha thalassemia?
Nothing (i.e., it will be normal)
What must you consider when treating thalassemia?
Chronic transfusion = iron overload
Managed with deferasirox or deferiprone (PO iron chelators)
Deferoxamine is a parenteral version
phlebotomy is NEVER the answer
IgA attacks parietal cells
Pernicious anemia (leads to B12 deficiency d/t lack of IF)
How long is B12 and folate stored in the body?
B12 = 3-10 years (from animal products)
Folate = 3-6 weeks (from leafy greens)
Is the peripheral neuropathy from B12 deficiency reversible with replenishment?
No
What must you consider when replacing B12?
Whether to give IM or PO
Absorption problem (pernicious anemia, crohn’s, or gastric bypass) = IM
B12 deficient patients = PO
Schilling’s test helps distinguish between the two
Why is cow’s milk problematic in infants <1 or when consumed excessively before the age of 2?
Low in iron
Also causes occult intestinal blood loss
Result = Iron deficiency anemia
The most frequently tested type of acute leukemia
M3 or acute promyelocytic leukemia
this is because it is associated with DIC
Best initial test when suspecting leukemia
Blood smear (showing blasts)
Most accurate test = flow cytometry
Myeloperoxidase positive
AML
What translocation is associated with M3?
15 and 17
What are Auer rods and what are they associated with?
Eosinophilic inclusions associated with AML
M3 is the most common associaton
Tdt positive
ALL
Also cALLa positive
Unique treatment for ALL and M3
ALL = add intrathecal methotrexate to prevent relapse in the CNS
M3 = add all-trans-retinoic acid (ATRA)
Both AML and ALL are treated with chemo to remove blasts and induce remission
BCR-ABL
9:22 translocation
Philadelphia chromosome
All synonymous for CML
Which myeloproliferative disorder has the greatest likelihood of transforming into acute leukemia (blast crisis)?
CML
If untreated, 20% of patients per year
Treatment for CML
Translocation of 9:22 results in overlyactive tyrosine kinase
Tryosine kinase inhibitors = imatinib, dasatinib, or nilotinib
Only a BMT can cure CML, but this is never the initial therapy
What is the most important first step in acute leukostasis reaction?
Leukapheresis (removing the excessive white cells)
Define myelodysplastic syndrome
MDS is a preleukemic disorder presenting in older patients with a pancytopenia despite hypercellular bone marrow
5q deletion
characteristic abnormality of MDS
5q deletion has an excellent response to lenalidomide
Also look for increased MCV, nucleated red cells, and ringed sideroblasts
Pelger-Huet cell
most distinct lab abnormality in MDS (hyposegmented nucleus in WBC)
Treatment for CLL
Most people die with it, not from it
Stage III (anemia) and Stage IV (thrombocytopenia) are treated with fludarabine, cyclophosphamide, and rituximab
Massive splenomegaly
“Dry” tap
Hairy Cell Leukemia
A smear will show hairy cells; flow cytometry will show CD11c
Treat with cladribine or pentostatin
Best next step when patient presents with:
Painless lymphadenopathy
“B” symptoms
B symptoms = fever, wt loss, drenching night sweats
Next step = excisional biopsy
This is characteristic of NHL and HD
Most common wrong answer is needle aspiration
How to stage NHL?
CXR, if negative then CT chest/abd/pelvis, if negative then BM Bx
Stage 1 = 1 lymph node group
Stage 2 = 2 or more on the same side of the diaphragm
Stage 3 = both sides of the diaphragm
Stage 4 = widespread disease
How to treat advanced NHL (stage III or IV)?
R-CHOP
Rituximab (antibody against CD20)
Cyclophosphamide
Hydroxydaunorubicin (aka adriamycin or doxorubicin)
Oncovin (aka vincristine)
Prednisone
Note: Unlike HD, NHL presents in advanced stages in 80-90% of cases
Reed-Sternberg cells
aka lacunar histiocytes
Synonymous for Hodgkin Disease
Pel-Epstein (cyclical) fevers
Alcohol = painful lymphadenopathy
HD
Burkitt’s lymphoma
Extranodal disease
NHL
Treatment of HD
Stage I and II (80-90%) = local radiation with chemo
Stage III and IV = ABVD
Adriamycin (doxorubicin)
Bleomycin
Vinblastine
Dacarbazine
When is adriamycin (doxorubicin) contraindicated?
Adriamycin is cardiotoxic
Cannot use it when EF is < 50% (best determined with MUGA or nuclear ventriculogram which is more accurate than an echo)
Adverse Effects of:
Doxorubicin
Vincristine
Cyclophosphamide
Cisplatin
Chemo-man
Doxo = cardiomyopathy
Vin = peripheral neuropathy
Cyclo = hemorrhagic cystitis
Cisplatin = renal and ototoxicity
Most common presentation for multiple myeloma?
Bone pain from pathologic fracture (bone breaks under what would be considered normal use)
Most common cause of death in myeloma?
Renal failure and infection
RF d/t accumulation of immunoglobulins and Bence-Jones protein in the kidney (also 2/2 hypercalcemia and hyperuricemia)
Anion gap in myeloma?
Decreased anion gap
IgG is cationic (will increase chloride and bicarbonate levels)
SPEP for myeloma
IgG (60%)
IgA (25%)
Although these are all “M” spikes, remember IgM is a separate disease called Waldenstrom macroglobulinemia
What is the single most accurate test for myeloma?
Bone marrow biopsy showing > 10% plasma cells
The most common wrong answer is SPEP (99% of people with an “M-spike” do NOT have myeloma)
MGUS
IgG or IgA spikes on an SPEP without myeloma
1% a year transform into myeloma
Best initial therapy for Waldenstrom Macroglobulinemia
Plasmapheresis
IgM spike results in hyperviscosity
What is ITP
Diagnosis of exclusion
Look for isolated thrombocytopenia, normal-sized spleen, increased megakaryocytes, or antiplatelet antibodies
Treat with prednisone
Before splenectomy, what vaccinations must you give?
N meningitidis
H influenza
Pneumococcus
Best therapy for VWD?
DDAVP (desmopressin), which releases subendothelial stores of VWF
Look for bleeding related to platelets that is markedly worse after taking aspirin
Increased PT and aPTT
Low platelet count
Elevated d-dimer and fibrin split products
Decreased fibrinogen
Characteristic findings for DIC
How to confirm HIT
ELISA for platelet factor 4 (PF4) antibodies or the serotonin release assay
Treatment for HIT
Stop all heparin-containing products
Administer direct thrombin inhibitors: argatroban, lepirudin, bivalirudin, and fondaparinux
2 main antiphospholipid syndromes
Both cause thrombosis
- Lupus anticoagulant (associated with elevated aPTT)
- Anticardiolipin (associated with multiple spontaneous abortions)
Only cause of thrombophilia with an abnormality in the aPTT
APL syndrome
Requires lifelong anticoagulation
Best initial test = mixing study (aPTT will remain elevated even after the mix)
The anticoagulation effect only exists in vitro; in vivo (i.e., patients) it results in increased clot formation NOT bleeding disorders
Fever
Anemia
Thrombocytopenia
Renal Fx
Neuro Sxs
Think TTP
Symptoms = “FAT-RN”
Causes of thrombocytopenia
“Alphabet Soup”
HIT
TTP
DIC
ITP
Pt > 70
Hypercalcemia
Renal Fx
Anemia
Bone Pain
MM
Get skeletal survey to look for lytic lesion (caused by osteoclast activating factor - OAF), not a bone scan
SPEP (+)
UPEP (-)
Skeletal (-)
BM Bx < 10%
MGUS
SPEP (+)
UPEP (-)
Skeletal (-)
BM Bx > 10% lymphoma (not plasma)
Waldenstrom Macroglobulinemia
Treatment for ITP
Steroids
then IVIG
then Rituximab
Bernard Soulier
GlyIb deficiency
Glanzman thromobocytopenia
GlyIIbIIIa deficiency
