Transcript Hematology Board Review

Hematology Board Review
Alice Ma, MD
UNC
Hematology-Oncology
June 9, 2006
Case 1 (Item 22 from MKSAP)
• 68 y.o. woman from Minnesota seen
in ER for fatigue, DOE, and episodic
dark urine. Dark urine noted
following extended periods of time in
the cold. No medications
• PEX. T nl, HR 90, BP 110/75
• Hgb 7.1, retic count 18%. Normal
indices, normal remainder of CBC
• Lab notes sample appears
agglutinated, and clumping of RBCs
on smear.
Case 1
• 68 y.o. woman from Minnesota seen
in ER for fatigue, DOE, and episodic
dark urine. Dark urine noted
following extended periods of time in
the cold. No medications
• PEX. T nl, HR 90, BP 110/75
• Hgb 7.1, retic count 18%. Normal
indices, normal remainder of CBC
• Lab notes sample appears
agglutinated, and clumping of RBCs
on smear.
Case 1
• Which of the following is the most
important study for establishing the
diagnosis in this patient?
– A. Osmotic fragility
– B. Cold Agglutinin screen
– C. Serum complement determination
– D. Sucrose hemolysis test
– E. G6PD determination
Case 1
• A - No, since this is for hereditary
spherocytosis.
• Buzzwords for HS
– Recurrent jaundice
– Early pigment gallstones, cholecystectomy
– Autosomal dominant, so + FHx
– Splenomegaly
– Increased osmotic fragility
Case 1
• B - Cold agglutinin Screen. Yes
• Buzzwords for cold agglutinin disease:
– Recurrent hemolysis in the cold
– RBC clumping on smear
– DAT (+) for C3/complement, (-) for IgG
– May follow infection with mycoplasma
or mono
– IgM mediated
– No benefit from steroids or splenectomy
– Keep warm
Case 1
• C. Sucrose Hemolysis test. No. This
is for PNH
• Buzzwords for PNH
– Dark/red urine in early AM
– May have clots and/or pancytopenia
– May follow chemo/aplastic anemia
– Tests:
•
•
•
•
sucrose hemolysis test
Acidified serum hemolysis test (Ham’s test)
Flow cytometry for CD55/CD59
Urine hemosiderin positive
Case 1
• E. G6PD determination
• Buzzwords for G6PD deficiency
– African-American or Mediterranean
– X-linked
– Hemolysis follows infection or drugs
– Susceptible to aplastic crisis after parvo
– Drugs - sulfa/dapsone/antimalarials
– Heinz bodies (need special stain)
– Bite cells
Blister cells
More Hemolytic Anemia Buzzwords
• Warm AIHA
– Spherocytes
– Positive DAT, IgG positive, C3 positive
– Associated with CLL, NHL, SLE
– Treat with steroids first, splenectomy
second.
• Drug-related AIHA
– Spherocytes.
– Positive DAT, usually for C3 only.
Case 2 (Item 55 from MKSAP)
• 22 y.o. man brought from work to ER
for abdominal pain and fever.
• Two recent episodes of red urine
• Previously treated for syphilis
• Works as a butcher’s assistant,
unloading refrigerated meat trucks
• PEx - chronically ill. Nl Temp and BP
Case 2
• 22 y.o. man brought from work to ER
for abdominal pain and fever.
• Two recent episodes of red urine
• Previously treated for syphilis
• Works as a butcher’s assistant,
unloading refrigerated meat trucks
• PEx - chronically ill. Nl Temp and BP
Case 2
• Laboratory studies
– Hgb 4.0
– WBC nl. Nl diff except for NRBCs
– Plts nl
– Rapid Plasma reagin test - positive
– U/A. Strongly positive for hemoglobin.
No intact erythrocytes
Case 2
• Which of the following is the most
appropriate diagnostic study for this
patient’s hemolytic anemia?
– A. Donath-Landsteiner test
– B. Sickle Cell Preparation
– C. Urine Hemosiderin preparation
– D. Heinz body preparation
Case 2
• B. Sickle Cell preparation - no
• U/A shouldn’t be red, may have
microscopic hematuria, not
hemoglobinuria
• No association with syphilis
• Peripheral smear should show
sickled cells, especially if pt is quite
ill now
Case 2
• C - urine hemosiderin determination.
No, since we know that there is
hemoglobin in the urine. Urine
hemosiderin is useful if there is the
suspicion for chronic intravascular
hemolysis, as in PNH, valve
hemolysis, AAA/aortic dissection
hemolysis.
Case 2
• D. Heinz body preparation - no
• This is useful if there is suspicion for
oxidative stress, usually from drugs.
• bite cell hemolytic anemia
• Usually G6PD deficiency, but if
oxidative stress is bad enough,
anyone can get Heinz body hemolytic
anemia.
• African americans with G6PD
deficiency can have falsely nl G6PD
levels immediately after hemolysis
Case 2
• A - Donath Landsteiner test - correct
• Paroxymal Cold Hemoglobinuria
(PCH)
– Episodic cold-induced intravascular
hemolysis
– DAT positive only for Complement
– Seen in pediatrics, also classically with
syphilis, now most are idiopathic
– IgG antibody binds only in the cold, but
fixes complement. No spherocytes
– Special test for DL antibody detection.
Case 3 (Item 65 from MKSAP)
• 22 y.o. man seen in the ER for red
urine and fatigue. 3 days ago,
started on TMP-SMZ for UTI.
• Hbg 6.5 retic 18%
• Blood smear - polychromatophilia,
blister cells
• G6PD - low normal
Case 3
• In order to confirm the diagnosis,
which of the following should be
done?
– A. repeat G6PD determination in 1
month
– B. perform osmotic fragility test
– C. perform sucrose hemolysis test
– D. perform bone marrow aspirate
Case 3
• Two normal forms of enzyme. Most
prevalent type is B. 20% of healthy
Africans have type A.
• Deficiency is X-linked.
• In Africans, mutant protein is A-, which is
unstable and loses activity as the red cell
ages.
• Mediterranean variant has baseline low
activity
• Low G6PD activity results in low levels of
NADPH and reduced glutathione, which
are required to protect hemoglobin from
oxidative damage.
Case 3
• Typically, hemolysis can be triggered by
drugs or infections.
• Anemia is maximal 7-10 d after exposure.
In individuals with A-, reticulocytosis
begins to compensate for the anemia,
despite continuation of the drug.
• Immediately after a hemolytic episode,
G6PD levels in the with A- may be normal,
since the mature cells have been lysed,
and only younger cells with normal G6PD
levels, are present. Need to repeat in 1
month
Case 3 - blister cells
Case 4
• A 27-year-old woman is referred to you for
evaluation of thrombocytopenia, which was
discovered incidentally during an evaluation for life
insurance.
• She is healthy, active, and taking no medications.
• Findings on the history and physical examination
are normal.
• The complete blood count results are normal,
except for a platelet count of 72,000/ L.
• The blood chemistry profile is normal, urinalysis is
normal, and the test for HIV is negative.
• Examination of the peripheral blood smear is
normal except for the mild thrombocytopenia.
Case 4
• What is the most appropriate management for this
patient?
(A)
(B)
(C)
(D)
(E)
Suspect ITP. do no further diagnostic
studies other than a repeat complete
blood count in 1 month.
Suspect ITP; begin prednisone, 1 mg/kg/d
Suspect ITP or possibly myelodysplasia;
do a bone marrow aspiration and biopsy.
Suspect the possibility of lymphoma; do a
CT of the chest and abdomen for
lymphadenopathy.
Doubt the history and suspect alcoholism;
do a liver and spleen ultrasonography.
Case 4
• In the absence of any gold standard
tests to diagnose ITP, the diagnosis
can only be based on the
observation of thrombocytopenia
without other hematologic
abnormalities.
• Also, recognize that the goal for
treatment of ITP is only to prevent
bleeding, which is not an issue in
this woman with mild
thrombocytopenia.
Case 4
• Prednisone therapy
– the initial choice for adults with ITP
– does not induce a cure
– may only provide a temporary remission or
provide symptomatic relief until a spontaneous
remission occurs.
• Therefore, prednisone is not indicated in
the absence of thrombocytopenia that
poses no hemostatic risk.
• Prednisone may be appropriate if the
platelet count is less than 20,000 to
30,000/ L.
Case 4
• When there are no other hematologic
abnormalities on routine CBC and on
peripheral blood smear, examination of the
bone marrow does not provide additional
important information.
• It is unnecessary to routinely do a bone
marrow examination in the evaluation of a
patient with suspected ITP.
• If pt were older or had abnormal counts
other than plts, marrow exam may have
been appropriate.
Case 4
• Other etiologies for thrombocytopenia
such as occult liver disease with
hypersplenism or occult lymphoma may
be considered, but in the absence of a
suggestive history or physical
examination, these possibilities warrant
no further diagnostic evaluation.
• Alcohol excess itself may cause
thrombocytopenia due to marrow
suppression.
Case 4
• ITP therapy in adults
• First - if plts < 30-40, or if pt bleeding,
use steroids +/- IVIg to raise platelet
count, await spntaneous remission.
• If pt relapses after steroid taper,
move to splenectomy - effective in
two thirds of pts.
Case 4
• If pt fails splenectomy, lower your
target plt count to 30. Use
immunosuppression at this point.
This can include azathioprine,
cyclophosphamide, cyclosporine,
• Also can try danazol, protein A
column,
• If pt initially responds after
splenectomy, then relapses after,
consider accessory spleen.
Case 5
• A 76-year-old man presents to the emergency
department with numerous ecchymoses and
bleeding from the gums.
• He has been previously well, and he takes no
medications.
• There is a history of uncomplicated
appendectomy and cholecystectomy.
• On physical examination, he has extensive
bruising, and there is oozing from intravenous
puncture sites. In addition, he has a swollen,
painful left knee.
Case 5
• Laboratory studies:
• Platelet count
264,000/L
• Activated partial 112 sec
thromboplastin time
• Prothrombin time
11 sec
• Plasma fibrinogen
2.4 g/L
• A 1:1 mix of patient and normal plasma does
not correct the prolonged activated partial
thromboplastin time.
• The patient had an activated partial
thromboplastin time of 28 seconds at the time
of his appendectomy 12 years ago.
Case 5
The most likely cause of this patient’s
coagulopathy is:
(A)
(B)
(C)
(D)
(E)
Disseminated intravascular coagulation
A lupus anticoagulant
Factor XII deficiency
Acquired prothrombin inhibitor
Acquired factor VIII inhibitor
Case 5
• The patient has an acquired coagulation
disorder that is associated with bleeding.
• Although disseminated intravascular
coagulation (DIC) is associated with
prolongation of the activated partial
thromboplastin time, this diagnosis is
unlikely given the normal platelet count,
prothrombin time and fibrinogen level.
Also there is no associated systemic
illness that could provoke DIC.
• Factor XII deficiency is ruled out by the
presence of bleeding, because factor XII
deficiency does not cause bleeding.
Case 5
• Lupus anticoagulants are not
associated with hemorrhage unless
there is associated deficiency of
prothrombin. This possibility is
excluded by the normal PT; the
normal PT rules out an acquired
prothrombin inhibitor.
• Therefore, the most likely diagnosis
is an acquired inhibitor against factor
VIII.
Case 5
• Acquired inhibitors against factor VIII are
uncommon. They can occur post partum or in
association with lymphoproliferative diseases or
autoimmune disorders. They also can occur
without any associated condition.
• Patients frequently present with massive
bleeding.
• Treatment is aimed at 1) bypassing the inhibitor
by using factor VIIa, porcine factor VIII (provided
that the inhibitor does not cross-react), or
activated prothrombin complex concentrates;
and 2) lowering the antibody levels using
plasmapheresis or immunosuppression.
• Postpartum factor VIII inhibitors will often resolve
spontaneously.
Case 6
• A previously healthy 50-year-old man is admitted to
the hospital with a 2-week history of fatigue and
dyspnea.
• He is currently taking propranolol, clonidine, and
ranitidine for hyper-tension and peptic ulcer.
• Physical examination, including blood pressure, is
normal. He is mentally alert.
Case 6
• Laboratory evaluation:
• Hgb 4.6 g/dL, Hct 14%, WBC 10,800/ L, normal
differential, Plts 21K.
• Cre 0.8 mg/dL, T bili 2.8 mg/dL, Dbili 0.4 mg/dl,
LDH 2463 U/L.
• Examination of the blood smear shows
fragmented erythrocytes and
polychromatophilia.
• The direct antiglobulin test is negative.
• Coagulation studies (prothrombin time,
activated partial thromboplastin time, and
fibrinogen) are normal.
Case 6
What is the most appropriate management for
this patient?
(A)
Suspect TTP and initiate plasma exchange
therapy.
(B)
Suspect autoimmune thrombocytopenia and
hemolytic anemia (Evans syndrome), and initiate
prednisone treatment, 1 mg/kg per day.
(C)
Suspect disseminated carcinoma, and initiate a
workup that includes chest radiographs, bone
marrow examination, and abdominal CT scan.
(D)
Suspect drug-induced thrombocytopenia and
hemolytic anemia, and discontinue the three
medications he is taking.
(E)
Suspect pernicious anemia, and do a bone
marrow evaluation to confirm megaloblastic
hematopoiesis.
Case 6
• The answer is A - even though the
patient does not have renal
manifestations, neurologic
symptoms, or fever, he does have
microangiopathic hemolytic anemia
and thrombocytopenia. Moreover, he
is not in DIC, since his PT/PTT are
normal. Recognize that not every
patient with TTP will have “the
pentad” at the time of presentation,
though many will have all symptoms-shortly before dying!!
Case 7
• A 65-year-old man underwent bilateral
knee replacement surgery 5 days ago.
• His mobilization has been slow because of
persistent pain, and he is only now getting
up in a chair.
• Because of a previous history of acute
proximal venous thrombosis complicating
a cholecystectomy 8 years ago, he has
been given subcutaneous heparin three
times daily in doses sufficient to achieve
an activated partial thromboplastin time of
35 sec.
Case 7
• There are no clinical signs of fresh
hemorrhage although ecchymoses and
hematomas from the first ICU day are still
evident.
• There are no signs of hemorrhage from
mucous membranes, needle stick sites, or
tubes.
• The hemoglobin is 12.5 Gm/dl, the white
blood count is 4,500/ micro liter, no
fragmented cells are seen, no platelet
clumping is noted on the peripheral blood
smear, the BUN is 35, the creatinine 1.6,
the LDH is 180 (normal 84 - 197).
Case 7
– The most likely cause of the
thrombocytopenia is:
•
•
•
•
•
(A)
(B)
(C)
(D)
(E)
Ranitidine
Sepsis
Heparin
Crystalloid given during surgery
None of the above
Case 7
The best management approach for the patient is:
(A)
(B)
(C)
(D)
(E)
Stop the ranitidine because it is the
cause of the thrombocytopenia.
Obtain blood cultures, and culture any
drainage from the left knee incision
before starting antibiotic therapy.
Stop the heparin.
Send serum and plasma for studies to
exclude heparin-induced
thrombocytopenia; continue the
heparin until the results are available.
Continue heparin, but follow the
platelet count daily and give platelet
transfusions if the count falls below
20,000/ L.
Case 7
• The answers are c) and c). This
patient has HIT, unless proven
otherwise. Need to stop the heparin-may need to start alternate
anticoagulation. Remember that 3050% of pts with HIT will go on to
develop thrombosis, so stop the
heparin, then send off tests!!
• Ranitidine is blamed too much for
thrombocytopenia, but it’s easy
enough to stop.
Case 8
• You are asked to provide a consultation
for a 22 year old man with
thrombocytopenia.
• He was admitted to the ICU following a
motorcycle accident in which he sustained
head trauma, a ruptured spleen, two
fractured ribs, and a fractured pelvis.
• On the fourth ICU day the platelet count is
reported to be 2,000
Case 8
• Which of the following is the most likely
diagnosis?
A.
B.
C.
D.
Disseminated intravascular coagulation
Post-splenectomy thrombocytopenia.
Thrombotic thrombocytopenic purpura
Pseudothrombocytopenia.
Case 8
• Remember that multiple trauma
predisposes to DIC. The answer is A