Transcript Hematology Board Review

Ye Seventeenth of July
Two Thousand and Fourteen
Vince Herrin
A 45 year old woman presents with fatigue and nausea.
She has occasional palpitations and SOB with minimal
exertion. Her cardiac and pulmonary exams are
normal but she has spooning of her nails.
Which of the following should be true?
Low iron, low IBC, low ferritin
B) Low iron, high IBC, high ferritin
C) Low iron, low IBC, high ferritin
D) Low iron, high IBC, low ferritin
A)
Your iron studies are nondiagnostic for a diagnosis of
Iron deficiency. Which of the following would you
order next?
a) Soluble transferrin receptor
b) Beta 2 microglobulin
c) RBC mass
d) ESR
 However, remember the gold standard for proving
Iron deficiency anemia is……
?????
Treatment for iron deficiency is best accomplished
with……
a) IV iron replacement weekly
b) IV iron replacement
c) IM iron replacement
d) PO iron replacement
by indices
microcytic/low MCV
 iron deficiency
 thalassemia
 lead poisoning
macrocytic/high MCV
 B12/folate deficiency
 hemolysis
 liver disease
normocytic/normal MCV
-anemia of chronic disease
 by RDW
 normal
 Increased
 by reticulocyte response
 normal
 increased
 hemolysis
A 38 yo male patient is referred to you for
recommendations regarding their microcytic anemia.
The patient has no systemic symptoms.
The CBC shows: WBC 5.7 (normal differential), RBC
5.8, Hgb 12, HCT 37.1, platelets 340. MCV is 71 and
RDW is 15.
Ferritin is 50, iron 50, TIBC 300. Hemoglobin
electrophoresis is normal.
 Your recommendation should be:
 A. Referal for EGD and colonoscopy
 B. Iron infusion with a goal of replacing 1000 mg
storage iron
 C. Reassurance and a discussion about DNA testing
testing
 D. Iron absorption assay followed by 6 months of PO
iron supplementation
Know other anemias…..
 Anemia of chronic disease
 Hemoglobinopathies
 Aplastic anemia
 Hemolytic anemias
 AIHA
 Cold antibodies
 microangiopathic
 Anemia of inflammation
 Unable to utilize available storage iron
 Mediated by inflammatory cytokines such as TNF, IL 1,
and IFN beta
 Usually associated with a decreased erythropoietin
state or reduced responsiveness to erythropoietin
Clues for diagnosis
 Usually normochromic normocytic RBCs
 Occasionally may be hypochromic microcytic
 Decreased reticulocyte count
Comparison:
Fe deficiency
ACD
Fe
Low
Low
TIBC
High
Low
Transferrin
Saturation
Low
Low/Normal
Ferritin
Low
Normal/High
 Differentiate with neurological symptoms
 Check vitamin levels
 Check antibodies
 Suspect diagnosis but vitamin levels normal……
 Check MMA and Homocystine
WARM
 IgG antibodies
 Associated with lymphoproliferative and collagen
vascular diseases
COLD
 IgM antibodies
 Hemolysis is via the complement pathway
 Associated with lymphoproliferative diseases or
infection
 CIGAR/PENCIL SHAPES
 MACROOVALOCYTES
 SPHEROCYTES
 SCHISTOCYTES
 BITE CELLS
 BURR CELLS
 SPUR CELLS
 TARGET CELLS
 TEARDROP CELLS
 Primary platelet vs. coagulopathy can be differentiated
by the type of bleeding
 Primary platelet bleeding is mucosal with petechia,
epistaxis, gum bleeding and GI tract bleeding
 Coagulation cascade bleeds are generally joint and soft
tissue bleeds
A 42 year old female with complaints of epistaxis and
easy bruising for 2 weeks is seen in the ER. She has the
following CBC:
HGB 10
WBC 6200
HCT 30
PLTS 38,000
MCV 72
normal differential
A differential diagnosis includes:
A) Systemic Lupus
B) Hepatitis
C) Drug effect
D) ITP
E) All of the above
Decreased platelets result from
Decreased
Production
Increased
Destruction
Sequestration
As a general rule, if platelets above 20,000 the risk of
spontaneous bleeding is small. When the count goes
below 10,000 then the risk increases substantially and
transfusions should be considered.
 Not always idiopathic
 30-30-30-10 rule
 Idiopathic
 Drugs
 Disease states such as lymphoma, CLL, collagen
vascular diseases
 Viral illnesses such as HCV, HIV
Treatment options:
 Platelets > 30,000---observation
 Platelets< 30,000---treatment
 Steroids
 IVIG
 Splenectomy
 Up to 80% improved with these maneuvers
 You are evaluating a 40 yo female patient who fell at
home. She has no known significant medical history.
She is awake but lethargic and has the following test
results of concern:
 HCT 27, platelets 45, schistocytes on peripheral smear
 BUN 40, creatinine 1.8, LDH 800
 Coags are within normal limits; tox screen negative
 Your next move after completing your assessment
should be:
 A. Send an ADAMTS13 and consult Hematology for
urgent plasmapheresis
 B. Order a d-dimer to rule out early DIC
 C. One unit random-donor apheresed irradiated
platelets
 D. CT Chest/Abdomen/Pelvis to look for occult injury
or PE
DIAGNOSTIC PENTAD
 Fever
 Neurological signs
 Microangiopathic hemolytic anemia
 Thrombocytopenia
 Renal dysfunction
 Newly determined genetic determinant for TTP
 ADAMTS13 gene defect found in many patients
 Encodes for a vW antigen protease responsible for
cleaving unusually large vW multimers
 This syndrome is considered a medical emergency and
treatment should be instituted immediately
 Affects about 3% of patients treated with heparin
 Less risk with porcine heparin
 Less risk with LMWHs
 Occurs 5-8 days after starting heparin therapy unless
there has been prior exposure
 Amnestic response after prior exposure and can
develop thrombocytopenia within 1-2 days
 If platelet count falls by 50% or falls below 100,000
should immediately stop heparin
 You are doing a pre-op physical on a healthy 55 yo man
who injured his knee. He has a history of nosebleeds
as a child and his mother was a “free-bleeder” but had
no major episodes and died of an MI at age 74. He tells
you he was once tested for von-Willebrands, but that it
was negative.
 His CBC is entirely normal, as are his chemistries.
 His coags reveal a PT of 12.5 and a PTT of 40.
 You ordered a repeat PTT with a 1:1 mix, which
corrected. Your next step will be:
 A. Reassurance and clearance for surgery.
 B. Repeat testing for von Willebrand’s disease
 C. Order a bleeding time and clear the patient for
surgery if the result is normal.
 D. Recommend FFP prior to surgery at a dose of 15
mg/kg to cover whatever coagulation abnormality he
has.
 Most common inherited bleeding disorder
 Autosomal dominant inheritance
 Affected individuals are heterozygous
 Bleeding ranges from mild to severe and spontaneous
 Prolonged PT/PTT, BT, abnl platelet aggregation with
ristocetin
 Von Willebrand factor is a multimeric protein with
two functions
 Platelet adhesion---links platelet receptors to exposed
subendothelium
 Carrier protein for factorVIII
 Type I – quantitative defect
 Type 2 – qualitative defects
 2b – thrombocytopenia associated
 Type 3 – no protein detectable
 Also called the giant platelet syndrome
 Glycoprotein Ib platelet defect
 Unable to bind vWF which is important for adhesion
to the endothelium
 Have abnormal ristocetin aggregation
 Have mild thrombocytopenia
 Autosomal recessive inheritance
 Mucosal bleeding
 Glycoprotein IIb-IIIa defect
 Unable to crosslink fibrinogen which is important for
aggregation
 Have abnormal ADP and EPI aggregation
 1:1 mix of patient and normal plasma
 Will detect a factor deficiency---should see correction with
mix
 Will allow detection of an inhibitor---doesn’t correct with
mixing
 May need to do a 2 hour incubation to reveal an inhibitor--may correct initially put prolong with incubation if a weak
(slow) inhibitor is present
 Hemophilia A and B most common
 Third most common
 Autosomal recessive inheritance
 Correlation between factor level and bleeding
tendency is poor
 Less spontaneous bleeding
 Treat with FFP
 Deficiency is very rare
 Acquired deficiency occurs with amyloidosis****
 Treat with FFP
 XII is also known as the Hageman factor
 Have very prolonged PTT
 No evidence of clinical bleeding and have normal
hemostasis
 A healthy 50 yo female has followed with your for
several years and comes in with right leg swelling that
has been present for about 3 weeks. She is on no
medications except amlodipine. She has not injured
herself, been ill lately, or been on any trips. Her BMI is
24.
 You are suspicious based on the exam and order a
Doppler which reveals subacute nearly occlusive clot in
the right superficial femoral vein.
 Her CBC, chemistries, and coags are all wnl. Your
recommendation to her is:
A. Take aspirin, use warm soaks and wear support hose
because this is superficial thrombophlebitis.
B. Admit to the hospital for tPA infusion to prevent varicose
vein formation.
C. Order a JAK-2 analysis to assess occult myeloproliferative
disease
D. Recommend at least 6 months of anticoagulation, initiating
LMW heparin and warfarin today.
E. 3 months of anticoagulation beginning with Lovenox for a
week and then warfarin loading at 10mg per day for 3 days
 Hypercoaguable states result in unprovoked
thrombosis
 Generally there is a family history of thrombosis
 Most are undefined but there are several deficiencies
of the natural occurring anticoagulants that are
described
 Protein may be decreased or dysfunctional
 Check level prior to initiation of Heparin
PROTEIN C DEFICIENCY
 Should measure prior to the initiation of Warfarin
therapy
PROTEIN S DEFICIENCY
 Functions as a cofactor with Protein C
 Should measure prior to the initiation of Warfarin
therapy
 Mutation in factor V resulting in resistance to




Activated Protein C
Most common cause is Factor V Leiden mutation
Most common inherited hypercoaguable defect
Found in up to 25% of patients with recurrent
thrombosis
Additive to other risk factors (OCPs, pregnancy, other
defects)
 Prolonged PTT
 Paradoxical clotting
 may be venous or arterial
 Recurrent spontaneous fetal loss
A 72 year old man presents with fatigue and bruising.
He has been noted to be mildly pancytopenic with a
CBC as follows:
Hgb 9.4
WBC 2300
segs 35
HCT 28
Plt ct 65,000
monos 45
MCV 102
Retic 0.4%
lymphs 20
His peripheral smear shows basophilic stippling and a
dimorphic population.
The best diagnosis for this case would be:
A) Lymphoma with a leukemic phase
B) Sickle Cell disease
C) Evans syndrome
D) Myelodysplasia
E) Chronic lymphocytic leukemia
 Peripheral smear and lab findings suggestive of a MDS
state include
 Dimorphic RBC population
 Macrocytic RBC’s
 Pseudo Pelger-Huet anomaly
 Large agranular platelets
 Decreased reticulocyte count
 Cytogenetics
 Primarily see abnormalities of chromosomes 5,7,or 8
 Trisomy 8 very common
 5q- syndrome has a more favorable prognosis and
is usually found in females with thrombocytosis
 Abnormalities of chr 11 with secondary MDS
A 45 year old woman presents with fatigue, early satiety
and bruising. She has noted some night sweats and a
10 pound weight loss over the last 6 weeks. Her PE is
remarkable for splenomegaly and large ecchymosis.
Her CBC is as follows:
HGB 10
WBC 250,500
HCT 31
Plts 675,000
MCV 78
What would you like to see next?
A) Platelet aggregations
B) Coagulation studies
C) Iron studies
D) WBC differential
What is the most likely diagnosis?
A) Chronic Myeloid Leukemia
B) Polycythemia vera
C) Acute Myeloid Leukemia
D) Chronic Lymphocytic Leukemia
 Polycythemia vera
 Essential Thrombocytosis
 Myelofibrosis
 Chronic Myeloid Leukemia
 Peripheral blood looks like marrow
 Basophilia/Eosinophilia
 Decreased LAP
 Philadelphia chromosome -- t(9,22)
 Moves the abl proto-oncogene on chr 9 to the bcr
region on chr 22
 Results in production of an abnormal tyrosine kinase
Natural disease progression
CHRONIC PHASE
ACCELERATED PHASE
BLAST CRISIS
Imatinib , et al
 Prototype in the class of drugs designed to take
advantage of the t(9,22) abnormality
 A tyrosine kinase inhibitor
 Many patients with cytogenetic remissions but
duration unknown
 Few side effects—N/V/D, cytopenias
 Diagnosis requires exclusion of secondary causes of
erythrocytosis
 Gaisbock’s syndrome
 Hypoxic states
 Renal disease
 Malignancy
 VERA




LOW ERYTHROPOIETIN levels
JAK-2 association
TREAT with PHLEBOTOMY
LEUKEMIA/MYELOFIBROSIS
 SECONDARY
 HYPOXIA
 PHLEBOTOMY
 NO LEUKEMIA risk
 By definition - thrombocytosis sustained over 6
months that is unexplained
 May be associated with splenomegaly but not usually
massive
 No clear diagnostic tests exist
Must rule out other causes for “reactive”
thrombocytosis
 Iron deficiency anemia
 Malignancy
 Collagen vascular disease
 Infection
 Postsplenectomy state
 Other MPDs
 Characterized by a myelophthisic picture on
peripheral smear
 Teardrop-shaped RBC’s
 NRBC’s
 Left shifted WBC series
 Anemic
 LAP nondiagnostic
 Clues on peripheral smear
 Blasts==Acute leukemia
 Auer rods == myeloid blasts
 Mature cells==Chronic leukemia
 Mature lymphocytes==CLL
 Mature segs==CML
 Work up includes
 A bone marrow aspirate and biopsy
 Special stains on marrow or peripheral blood
 Flow cytometry on marrow or peripheral blood
 Cytogenetic studies on marrow
M0
UNDIFFERENTIATED
M1
WITHOUT MATURATION
M2
WITH MATURATION
M3
PROMYELOCYTIC
M4
MYELOMONOCYTIC
M5
MONOCYTIC
M6
ERYTHROID
M7
MEGAKARYOCYTIC
M2
 With t(8,21) has a good prognosis
M4
 With inverted 16 and associated eosinophilia is a good
prognostic category
M3
 Associated with t(15,17)
 Translocation involving the retinoic acid receptor gene
 Good prognosis category
 Prominent Auer rods
 Commonly associated with DIC
M5
 Commonly associated with skin and soft tissue
disease
 Gingival hyperplasia
 CNS disease may occur
 Treatment scheme:
 Induction chemotherapy—designed to take a patient
to aplasia with recovery of “normal” hematopoiesis and
a remission state
 Consolidation chemotherapy– designed to reinforce
the remission obtained. Usually multiple cycles given
 Treatment for APL is different
 Based on the translocation of the retinoic acid receptor
 Uses All Trans Retinoic Acid (ATRA) as a maturational
agent
 Must also include chemotherapy with at least an
anthracycline
 Heparin usually not necessary
 Primarily occurs in children
 Lymphadenopathy and splenomegaly occur in 50%
 An anterior mediastinal mass is common with the T-
cell subtypes
 CNS disease is common
L1
CHILDHOOD
L2
ADULT
L3
BURKITT’S
Treatment scheme
 Induction chemotherapy with multi-drug regimens
 Consolidation chemotherapy with multi- drug
regimens for multiple cycles
 important drugs include Vincristine, prednisone and
anthracyclines
Treatment scheme cont
 Maintenance chemotherapy is an important part of
ALL treatment and lasts for several cycles
 CNS prophylaxis is also necessary with chemotherapy
+/- radiation therapy
An 80 year old woman is seen for her yearly check up.
She feels well. A screening CBC is done and has the
following values.
Hgb 7
WBC 55,000 lymphs 98%
HCT 20
Plts 40,000
Her physical exam is remarkable for 2 cm
lymphadenopathy in the cervical chain. Her peripheral
smear looks like this:
What is this disease?
A) CML
B) CLL
C) HCL
D) PLL
Which of the following statements is true?
A) She has stage IV disease
B) She should be observed rather than treated at this
stage
C) Her life expectancy from this leukemia is less than 6
months
D) This is a leukemoid reaction
 The most common leukemia in the western countries
 Typically a disease of older individuals
 Flow cytometry is usually diagnostic
 Typically a B cell disorder
 CD19,CD20,CD23 Positive
 CD5 Positive
RAI staging system
Survival
O Lymphocytosis
I Lymphadenopathy
II Splenomegaly
III Anemia
IV Thrombocytopenia
> 10 yrs
6-7 yrs
6-7 yrs
2-3 yrs
2-3 yrs
Treatment options include
 Observation –many patients have no indication for
therapy at the time of presentation
 Indications for treatment include




Symptomatic disease
Rapid doubling of the WBC count
Anemia
Thrombocytopenia
Complications include
 Hypogammaglobulinemia
 Treatment with IVIG may be of benefit
 Autoimmune disorders such as AIHA or ITP
 Treat with high dose steroids
 Treat disease as well
 Commonly associated with second malignancies
 Lung cancer
 Head and neck cancer
 B cell phenotype-- CD 19,CD20 Positive
 also CD 11C, CD 25, and CD 103 Positive
 Increased risk for infections
 Affects males 4:1 over females
Usual presentation is
 Pancytopenia
 Large splenomegaly
 Inaspirable bone marrow
A 24 year old girl presents with painless
lymphadenopathy in her cervical chain that measures
up to 3 cm. She is asymptomatic and has not had any
recent URI symptoms.
Physical exam is pertinent for the lymph nodes
mentioned as well as several small inguinal nodes
measuring 2-3 cm.
She has an FNA of an inguinal node that is
nondiagnostic.
The next step should be
A) CT scan of chest, abdomen and pelvis
B) Observation
C) Fine needle aspiration of the cervical nodes
D) Excisional biopsy of a cervical node
Her pathology returns diffuse large cell lymphoma.
After discussion of her diagnosis with her, the next
most appropriate step in her management would be:
A) Referral to general surgery for debulking of all
disease
B) Check a GHS and begin chemotherapy with ABVD
C) Check a b2MG, LDH, and ESR
D) CT scan of chest, abdomen, and pelvis
Her CT scan returns with a mediastinal mass that
measures 12 cm as well as many nodes in her abdomen,
the largest being 3 cms.
She has a bone marrow that is negative for disease.
What is the stage of her disease?
A) IIB
IIIBE
C) IIBX
D) IIIAX
E) IV
B)
Staging system
Ann Arbor
Stage I
1 node or group
Stage II
2 or more lymph node groups, same
side of the diaphragm
Stage III
Spans the diaphragm
Stage IV
Disseminated disease
 Subscripts with the staging system include
 A --B symptoms absent
 B --B symptoms present
 X --Bulky disease --defined as any mass >10
cms or a mass > 1/3 the diameter of the chest
 E –Extranodal disease
You have now determined that your patient has stage
IIIAX disease. She asks your advice concerning
treatment options. You should tell her:
A) She does not yet need treatment
She should not agree to treatment as there is none
with proven efficacy
C) She should receive radiation therapy to her
mediastinal mass followed by rituxan
D) Multiagent chemotherapy will offer her a chance for
cure
B)
 Bimodal age distribution
 Often see the “B” symptoms
 Fever
 Night sweats
 Weight loss
 Pruritus is common
 Unusual complaint of pain with alcohol ingestion
 Classification includes




Lymphocyte Predominant
Mixed Cellularity
Nodular Sclerosing
Lymphocyte Depleted
 Prognosis is most closely linked to stage of disease
 Stage IA with survival rate of >90%
 Stage IV with survival rate of >60%
Long term complications after treatment for Hodgkin
Disease are common and include
 Hypothyroidism
 Infertility
 Secondary malignancy including
 MDS/AML
 Solid tumors such as Breast and Lung
 Most are B cell in origin
 Incidence is increasing in Western countries
 Many associated with immunodeficiency states
Burkitt’s lymphoma==L3
Endemic
Epidemic
African variety
US
Jaw mass
Abdominal mass
EBV +++
EBV +/-




Lymphoblastic lymphoma ==ALL
Typically young adults and children
Frequently a mediastinal mass at presentation
Often Stage IV at presentation
CNS involvement is common
 H PYLORI ASSOCIATED
 MALT
 EBV ASSOCIATED
 POST TRANSPLANT NHL
 HTLV-1 ASSOCIATED
 ATLL
A 72 year old man is seen for routine check up. He has
no complaints and his physical exam is benign.
Screening lab is as follows:
Hgb 12.0
Tprot 10
HCT 37
Alb 2.0
WBC 3300
AST 67
Plts 460,000
ALT 80
Work up should include which of the following?
A) Liver biopsy
B) Bone marrow aspirate and biopsy
C) SPEP/UPEP
D) Beta-2-Microglobulin
 Clues include
 A low anion gap
 Rouleaux on peripheral
smear
 An elevated globulin
fraction (TP-Alb)
 95% will have an abnormal protein on SPEP or UPEP
 The M spike is most commonly IgG followed by IgA,
light chain disease,and IgD
 <5% will be non-secretory and have no evidence of
protein secretion
 MGUS
 MM
 <10% PLASMA
 >30% PLASMA
CELLS
 < 3 GRAMS
PROTEIN
 NO LYTIC
LESIONS
CELLS
 >3.5 GRAMS
PROTEIN
 +/- LYTIC
LESIONS
 Affects about 5% of patients over 70
 About 25% will progress to MM over about 10 years
 No treatment required
 Follow lab studies every 6 months
MULTIPLE MYELOMA
 Treat for progressive disease
 BMT accepted treatment for MM
 Solitary plasmacytoma becomes MM in most patients
over time
 Increased IgM levels
 More common in older men
 Presentation is usually with
 Lymphadenopathy/organomegaly
 Purpura
 Neuropathy
 Hyperviscosity syndrome
 Cells best described as “plasmacytoid lymphocytes”
 Pluripotent cells found in the bone marrow
 Rare (less than 1 in 100,000 cells)
 No identifiable morphological characteristics
 CD 34 + (stem cell antigen)
 Can be induced to circulate
in the peripheral blood
 Need 2.0–5.0 x 106 CD 34 + cells/kg
of recipient body weight
Cell sources:
HPSCT
BONE MARROW
PBSC
Types of transplants:
HPSCT
AUTOLOGOUS
ALLOGENEIC




Use patient’s own cells
Has less acute mortality
Higher relapse rate
Some accepted indications for autologous
transplant include:





Lymphoma including NHL and HD
Leukemia including AML and ALL in CR
Multiple Myeloma
Breast cancer is controversial
Testicular cancer for
relapsed disease
 Related donor or unrelated donor(NMDP)
 Has a higher acute mortality rate
 Less relapse risk
 Some accepted indications
for allogeneic transplant
 Chronic leukemia including CML and CLL
 Relapsed acute leukemia including
AML and ALL
 Myelodysplasia
 Multiple myeloma (VIC)
 GVHD—a unique toxicity to allogeneic
transplant—higher risk with unrelated donor
source; may be fatal; acute looks like fever, skin
rash, GI track involvement; chronic looks like
scleroderma
 GV“T”—a benefit of GVHD is graft vs. tumor
effect, which may decrease relapse rate—
mediated by T lymphocytes