Transcript Heme/onc Board Review - UNC School of Medicine

Heme/onc Board Review
Taylor Wofford
June 8, 2010
Board review topics
• “Benign” heme
– Anemia
– Transfusion medicine
– Hemostasis
– Platelet disorders
– Thrombotic disorders
– Heme issues in pregnancy
Board review topics
• Malignant
– ALL, AML, CLL, CML, MDS, MPD, marrow
failure
– Multiple myeloma, MGUS, amyloid,
Waldenstrom’s, POEMS
– Solid tumors: risk, dx, staging, rx, monitoring
– Onc emergencies
– Toxicities of cancer therapies
Anemia - MKSAP 23
• 27 yo F in ED with 2 day hx of diffuse h/a,
fatigue, and gingival bleeding while
brushing her teeth. She is otherwise
healthy. Only med: OCP. FHx:
unremarkable.
• PE: a&o with h/a. fundoscopy normal.
There are a few scleral hemorrhages and
mild icterus noted. Petichiae that had gone
unnoticed by the pt are visible on LE’s.
Cardiac and pulm exams are normal.
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Hg 8 g/dL
Plt 34,000/uL
Reticulocyte count 12% of erythrocytes
INR 1.1, aPTT 32 s, Thrombin time 16s
LD 2000 U/L, D dimer negative
Serum creatinine 0.8 mg/dL
Peripheral smear: schistocytes
Which of the following is the most
appropriate next step in management:
• 1) aPTT mixing study
• 2) direct antiglobulin (Coombs) test
• 3) IVIG
• 4) Plasma exchange
• 5) Platelet antibody test
Thrombotic thrombocytopenic
purpura
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Microangiopathic hemolytic anemia
Thrombocytopenia with normal coags
CNS sx
Rx: plasma exchange. Reverses plt
consumption that is responsible for
thrombus formation causing characteristic
sx
Transfusion medicine
• Acute hemolytic transfusion rxn:
– Fever, chills, flank pain, abd pain, ATN, tachy
– 2/2 ABO mismatch
– + Coombs (detects IgG or complement on erythrocyte
surface)
– Stop tx and maintain UOP
• Delayed hemolytic transfusion rxn
– Unexplained drop in hg, ↑ bili, LDH, retic,
↓ haptoglobin
– A new alloantibody
Transfusion medicine
• Post transfusion purpura: IVIG
• Febrile non-hemolytic transfusion rxn: from
donor leukocyte cytokines or recipient antibodies
against donor leukocyte antigens.
• TRALI: donor antileukocyte antibodies reacting
with recipient leukocytes, causing leukocyte
agglutination in the pulmonary capillary bed
• Allergic reactions/anaphylaxis
• Volume overload
Hemostasis – MKSAP 5
• 18 yo M evaluated 5 hrs after a routine tooth
extraction in which he experienced excessive
bleeding that the dentist was able to control.
The patient is healthy and takes no medications,
including aspirin or NSAIDs. Medical hx
includes easy bruisability and occasional nose
bleeds that are easily controllable. The patient
was circumcised at birth and recalls his mother
saying that he had more bleeding than expected
from the circumcision site. His father also has
easy bruisability.
• PE: unremarkable, no petichiae, ecchymoses, or
abnormal vasculature.
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Lab studies:
Hg 14.2 g/dL
Platelets 195,000/uL
INR 1.1
aPTT 41 s
aPTT mixing study:
corrects to normal
• Thrombin time 16 s
(control 15 s)
• Fibrinogen 266 mg/dL
• D-dimer assay
Negative
• Bleeding time 10 min
• Factor VIII activity
60% (normal 65120%)
• Which of the following is the most likely
diagnosis:
• A) Factor XI deficiency
• B) Hemophilia A (factor VIII deficiency)
• C) Presence of a lupus inhibitor
• D) Vitamin K deficiency
• E) von Willebrand disease
von Willebrand’s Disease
• Hx
• Labs with qualitative platelet defect AND
mild coagulopathy
Hemostasis clues
• Petechiae, mucosal: TCP, vWF, vascular
dz
• Palpable purpura: vasculitis
• Joint destruction: hemophilia
• Soft tissue hematoma: hemophilia or
coagulopathy
• Periorbital purpura: amyloidosis
• Perifollicular and soft tissue hemorrhage:
scurvy
Platelet disorders – MKSAP 42
• 67 yo F admitted to hospital from ED for new dx
of LLE DVT, confirmed by duplex u/s. PMHx
significant for a 2 day hospitalization 4 wks ago
for a NSTEMI for which she underwent cardiac
cath and was given LMW heparin. Her current
meds include ASA, clopidogrel, pravastatin, and
lisinopril.
• PE: L thigh swollen and tender. Labs: cbc, lytes,
and liver chemistry tests are unremarkable
except for a platelet count of 102,000/uL.
• Unfractionated heparin is administered. Twelve
hours later the pt’s plt count is 27,000/uL.
• Which of the following is the most
appropriate next step in treatment?
– A) Continue heparin and administer a platelet
transfusion
– B) Continue heparin and initiate high-dose
corticosteroid therapy
– C) Stop heparin and initiate argatroban
– D) Stop heparin and initiate warfarin
HIT
• Thrombocytopenia and thrombosis
• Antibodies directed against a complex of
heparin and platelet factor 4 (PF4)
• Leads to platelet activation and release of
prothrombotic platelet microparticles.
Thrombosis pearls
• Venous and arterial clots: APLA (long
aPTT and DRVVT and +anticardiolipin Ab)
or homocysteine (MTHFR gene)
• Old pt: think malignancy
• Most common inherited thrombophilia:
Factor V Leiden mutation (amino acid
substitution, factor V made more resistant
to cleavage by activated protein C)
Thrombosis – MKSAP 35
• A 33 yo F who has been trying to become
pregnant for 8 years is evaluated after receiving
positive pregnancy test results. Medical history
is significant for 3 miscarriages (6 years ago, 3
years ago, and 1 year ago), each of which
occurred early in her pregnancies. Following
her last miscarriage, laboratory studies indicated
the presence of a lupus inhibitor and
antiphospholipid antibodies. She has no history
of venous thromboembolism. Her LMP was 5
weeks ago.
• PE including vital signs and abdominal
examination is normal.
• Which of the following is the most
appropriate anticoagulation regimen for
the duration of this patient’s pregnancy?
a) Full-dose unfractionated heparin
b) Low-dose aspirin
c) Prophylactic-dose low-molecular-weight
heparin plus aspirin
d) Prophylactic-dose LMWH
e) Warfarin
Pregnancy and Platelets
• Gestational: 2-3rd trimester, incidental
• ITP: prior or early in pregnancy.
Prednisone if plt <50k.
• TTP: increased risk during pregnancy,
plasmapherese.
• HELLP: plt <100k, AST>70 U/L, maha, tbili
>1.2mg/dL, LD > 600 U/L. Deliver.
• Preeclampsia: tcp, HTN, proteinuria,
deliver.
Topics in malignant heme
• Malignant
– ALL, AML, CLL, CML, MDS, MPD, marrow
failure
– Multiple myeloma, MGUS, amyloid,
waldenstrom’s, POEMS
– Solid tumor risk, dx, staging, rx, monitoring
– Onc emergencies
– AE’s of cancer/cancer therapies
Heme malignancies -MKSAP 91
• 75 yo F c CLL who was previously asymptomatic
on no therapy undergoes f/u eval for CAP for
which she was hospitalized for 5 days and d/c’ed
14 days ago. The pt completed a course of abx
therapy and currently feels well. She reports no
fevers, chills, night sweats, weigh loss,
abdominal pain, or new LAD, and her pulm sx
have resolved.
• PMHx: prior PNA for which she was hospitalized
within the last year.
• PE: temp 36.7 C, bp 130/78, p 72, rr 14,
bmi 22. No palpable LAD. Cardiopulm
exam is normal. Abd exam shows
splenomegaly.
• Labs: Hg 11 g/dL, Leukocyte count
24,000/uL with 80% mature lymphocytes,
plt 120,000/uL, ALC 20,000/uL, IgG
500mg/dL
• AP/lat CXR during hospitalization:
resolving RLL infiltrate.
• Which of the following is the most
appropriate next step in management?
• A) IVIG
• B) Prophylactic tmp-smx
• C) Splenectomy
• D) Repeat blood counts in 1 month
Chronic Lymphocytic Leukemia
• Accumulation of mature lymphocytes
• Immunophenotype: CD5+, CD20+, CD23+
B cells
• Pancytopenia
• ITP, autoimmune hemolytic anemia
• Hypogammaglobulinemia and recurrent
infections: manage with IVIG
MKSAP 60
• 64 yo M c 3-year hx of stage II, grade 1 follicular
lymphoma is evaluated because of cervical and
axillary lymph nodes that have been gradually
enlarging since diagnosis. He is unable to wear
a tie, cannot fasten the top button of his shirt,
has trouble shaving, and is concerned about the
appearance of the cervical lymph nodes. The
enlarged axiallary LN are also uncomfortable.
The pt feels otherwise well and has not had
night sweats, weight loss, or fevers.
• PE: t 37.1, bp 124/64, p 64, rr 12, BMI 24.
Bilateral cervical LAD (largest aggregate LN
measuring 6 cm) and bilateral axillary LAD
(largest aggregate LN measuring 5-6 cm) are
present. There is no palpable inguinal LAD or
organomegaly.
• Lab: hg 12.0 g/dL, leukocyte count 9000/uL, plt
165,000/uL
• Contrast-enhanced CT-neck, c/a/p: progressive
axillary, mediastinal, and cervical LAD. No
measurable nodes below the diaphragm.
• Which of the following is the most appropriate
next step in managing this patient?
– A) Cyclophosphamide, vincristine, and prednisone
with rituxumab
– B) High-dose chemotherapy followed by stem cell
transplantation
– C) Fine-needle aspiration biopsy of a cervical lymph
node
– D) Cyclophosphamide, vincristine, prednisone, and
radiation therapy
– E) Observation with follow-up in 3 months
Follicular lymphoma
• Indolent
• CD20+, CD10+
• Offer palliative therapy for symptoms,
threat to vital organs, concerns for
appearance, and pt preference
• Debulking with chemo + rituxumab
improves outcomes
MKSAP 21
• 42 yo F who is scheduled for hysterectomy for
endometrial carcinoma comes in for preop eval.
At the time of initial eval, she was discovered to
have thrombocytosis. In addition to
menorrhagia, the pt recently developed epistaxis
and easy bruising. Her only meds are OCP and
fe supplement.
• PE: temp normal, bp 110/70 mmHg, pulse 68,
and rr 16. Exam is wnl. No petichiae,
echhymoses, or splenomegaly is noted.
• Repeat labs:
– Hg 11.3 g/dL
– Leukocyte count 4600/uL
– Platelet count 1,500,000/uL
– Plt function studies: abnormal platelet
aggregation with decreased response to
adenosine diphosphate and collagen.
– Cytogenetics: + JAK 2 mutation
– BMBx: hypercellular marrow with increased
megakaryocytes in clusters.
• Which of the following is the most
appropriate treatment:
– A) Anagrelide beginning 2 days preop
– B) Hydroxyurea beginning the night after
surgery
– C) Low dose aspirin postoperatively
– D) Platelet apheresis preoperatively and
hydroxyurea postoperatively
Essential thrombocythemia
• Bleeding and clotting complications
• Prior to surgery, goal <1million
MKSAP 34
• An asymptomatic 35 yo M comes for a routine
annual examination. PMHx and FHx are
unremarkable. Only med: MVI.
• PE: temp nl, bp 120/70, p 64, rr 14. No abnormal
findings.
• Labs: hg 9.1 g/dL, leukocyte 2100/uL, plt
135,000/uL, LD 890 U/L, uric acid 11.6 mg/dL.
• Peripheral smear: circulating blasts and
promyelocytes. BM: hypercellular marrow with
80% myeloblasts and promyelocytes.
Cytogenetics: t(15:17).
• In addition to hydration and allopurinol,
which of the following is the most
appropriate management at this time?
– A) Broad spectrum antibiotics
– B) Chemotherapy
– C) Chemotherapy plus all-trans-retinoic acid
– D) HLA typing
Acute promyelocytic leukemia
• M3 subtype, 10% of AML
• t(15;17) = PML/RARα gene
• Present with pancytopenia, may be
asymptomatic
• ATRA differentiates (also arsenic trioxide)
• ATRA syndrome
Solid tumors
• Breast: BRCA 1&2 screening
– Prophylactic mastectomy
– Oophorectomy
– SERM therapy
• Tamoxifen - premenopausal and postmenopausal
• Raloxifene – postmenopausal
• Ovarian:
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No screening test, CA-125 nonspecific.
Staging at initial surgery.
Chemotherapy with platinum-based agent + paclitaxel
Advanced dz: survival advantage but greater toxicity if
intraperitoneal chemo added to systemic chemo.
Solid tumors, cont.
• Colorectal:
– AJCC TNM staging
– LN + disease (stage III)  adjuvant chemo
– Several monoclonal antibody therapies
• SCLC:
– Staging limited or extensive
– Prophylactic cranial irradiation
– Offer chemo even if extensive and poor performance
status
• NSCLC:
– Stages I, II, III, IV
– PET-FDG superior to CT scan for mediastinal LN
detection
Solid tumors, cont.
• Thyroid:
– RET proto-oncogene leads to medullary thyroid
cancer in MEN-2A, MEN-2B, and familial non-MEN
medullary thyroid cancer.
– If RET mutation is discovered offer prophylactic
thyroidectomy
– Check 24hr urine catecholamine levels to r/o
pheochromocytoma
• Testicular:
– Seminoma
– Nonseminoma (embryonal cell, choriocarcinomas,
yolk sac tumors, teratomas). Any elevated AFP 
treat as nonseminoma.
Onc emergencies
• SVC syndrome: rx with radiation, chemo,
consider anticoagulation and
angioplasty/stenting
• Brain mets/increased ICP: rx with steroids,
mannitol, NSG
• Spinal cord compression
• Tumor lysis syndrome: rx with IVF’s,
allopurinol, rasburicase, HD.
• Hypercalcemia
Chemotherapy Toxicities
References
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MKSAP 14 and 15
Virginia Health Systems online atlas
Chieh Lin Fu, MD
Soham Puvvada, MD