A 50-year-old businessman presents to your office for an insurance
examination. He smokes a pack of cigarettes a day, is moderately (20 lb)
overweight, and has a history of hypertension treated with hydrochlorothiazide.
Except for some job-related stresses, he feels well. Systems review is normal.
Findings on physical exam are as follows: BP, 155/90; P, 92; T, 37.0 C; wt,
195 lb. Plethoric facies are noted, but examination of the heart, lungs, and
abdomen is normal. Laboratory results are as follows: Hb, 18.5; HCT, 55; WBC,
6,800 with normal differential; platelets, 325,000; peripheral blood smear,
normal; Na+, 140; K+, 3.2; Cr, 1.5; COHb, 4.2; RBC
volume, 31 (upper limits of normal); plasma volume, 36 (low normal); Pao2,
94; Paco2, 42; pH, 7.41; HCO3, 24; Hb P50,
normal; erythropoietin, 25.
Which of the following is the most likely diagnosis?
Polycythemia vera
Relative polycythemia
Renal cell carcinoma
Obstructive sleep apnea
High-affinity hemoglobinopathy
Answer 1 is
not correct. Answer 2 is correct.
Key Concept: Recognize the syndrome of relative polycythemia (Gaisbock's
syndrome)
This patient has all of the classic features of relative polycythemia, also
called stress erythrocytosis or Gaisbock's syndrome. Patients with this
syndrome characteristically are 45 to 55 years of age (a bit younger than PRV
patients), smokers, obese, and hypertensive. Modest increase in
carboxyhemoglobin levels and diuretic therapy may contribute to the
high-normal RBC masses and reduced plasma volumes, respectively, that are
commonly seen in these patients. The absence of splenomegaly, leukocytosis,
and thrombocytosis, as well as the high-normal erythropoietin, exclude
polycythemia vera. Renal cell carcinoma (or other renal and hepatic lesions)
should be considered in the differential but is not the most likely diagnosis,
in light of the characteristic presentation for relative polycythemia. Sleep
apnea should also be considered in the differential diagnosis, but the patient
has no symptoms of excessive daytime somnolence. The normal P50
(the Po2 at which 50% of the hemoglobin is deoxygenated) excludes a
hemoglobinopathy with increased oxygen affinity.
Question #10
A 78-year-old man presents for evaluation of progressive headache, dizziness,
and weakness of 6 months' duration. Hot showers cause generalized pruritus.
The past medical history and systems review are otherwise normal. He had a
normal health maintenance examination 5 years ago, including routine
laboratory studies. Physical examination shows the following: BP, 130/70; P,
70; T, 37.0 C; wt, 165 lb. The skin of the face is plethoric and dusky red.
Heart and lungs are normal. A spleen tip is palpable 2 cm below the costal
margin. There is no lymphadenopathy. The rest of the examination is normal.
Laboratory results are as follows: Hb, 19.5; HCT, 65; WBC, 12,800, with normal
differential; platelets, 525,000; peripheral blood smear, increased basophils,
myelocytes, and metamyelocytes; Na+, 140; K+, 4.0; Cr,
1.0; uric acid, 10.5; Pao2, 94; Paco2,
42; pH, 7.41; ; HCO3, 24; erythropoietin, 5
Which of the following is the most likely diagnosis?
Polycythemia vera
Relative polycythemia
Renal cell carcinoma
Hypoxic polycythemia
High-affinity hemoglobinopathy
Answer 1 is
correct.
Key Concept: Diagnose polycythemia vera
The elevated hematocrit (> 60% in men, > 57% in women), splenomegaly,
elevation and immaturity of other myeloid cell lines, and the reduced
erythropoietin level are virtually diagnostic of polycythemia vera. These
findings and the normal Pao2 level virtually exclude the
other diagnostic options, especially since the question asks for the most
likely diagnosis. Determination of the RBC mass is probably unnecessary in
light of a markedly elevated hematocrit and reduced erythropoietin level.
Other laboratory evidence of polycythemia vera would include elevations of
leukocyte alkaline phosphatase (reduced in chronic myeloid leukemia), vitamin
B12-binding capacity, vitamin B12 levels, and uric acid
levels. Endogenous erythroid colonies are found in 97% of polycythemia vera
patients. Note that a normal erythropoietin level does not exclude hypoxic
polycythemia, though an elevated level is commonly seen in patients with
disorders such as COPD and cyanotic congenital heart disease.
Question #11
For the patient described in Question 10, therapeutic weekly phlebotomy is
initiated with a goal of reducing the hematocrit to a level of 40 to 45.
In addition to phlebotomy, which of the following therapeutic options also
would be indicated at this time?
Aspirin
Anagrelide
Radioactive phosphorus (32P)
Busulfan
Hydroxyurea
Answer 1 is
not correct. Answer 5 is correct.
Key Concept: Know the appropriate therapy for patients with
polycythemia vera
Myelosuppressive agents are indicated in patients with thrombotic risks (high
platelets, age greater than 70 years, prior thrombosis) or in patients
requiring frequent phlebotomy to maintain a hematocrit of 40 to 45. Compared
with patients treated with phlebotomy and myelosuppressive drugs, patients
managed with phlebotomy alone have an increased risk of thrombosis in the
first 3 years after diagnosis. Hydroxyurea (usually in a dosage of 500 to
1,000 mg/day) is the preferred agent because of ease of administration, low
cost, and low risk of secondary leukemia (compared with busulfan and 32P).
Anagrelide will reduce the platelet count but is expensive and has not been
shown to decrease the thrombotic risk. Aspirin, in conjunction with
dipyridamole, failed to demonstrate a reduced risk of thrombosis in one study.
Aspirin may also exacerbate the tendency toward peptic ulcer disease and iron
deficiency anemia commonly seen in such patients; however, low-dose aspirin
(81 mg/day) is commonly used in patients who have high platelet counts,
thrombotic risk, and no bleeding history.
Question #12
A 50-year-old man is evaluated for impotence. His wife states that he has had
progressive loss of interest in sex, personality change, and fatigue for 6
months. He has always been obese but has gained 25 lb in the past year since
he discontinued smoking, after 30 pack-years. The patient has moved to a
basement bedroom so that his wife and children can sleep without being
awakened by his snoring. He claims to sleep soundly yet awakens feeling tired;
he frequently falls asleep while watching TV or reading the paper and has
occasionally even fallen asleep at the dinner table. He denies feelings of
depression and complains only of feeling tired. Physical examination shows the
following: BP, 140/80; P, 92; T, 37.0 C; wt, 265 lb. Office oximetry shows Sao2
to be 92% at rest and following a walk in the hallway. Except for obesity, the
physical examination is normal. Laboratory findings are as follows: Hb, 18.5;
HCT, 55; WBC, 4,600, with normal differential; platelets, 275,000; peripheral
blood smear, normal; Na+, 142; K+, 4.2; Cr, 1.0; Hb P50,
normal; erythropoietin, 55.
Which of the following is the most likely cause of the erythrocytosis in this
patient?
Polycythemia vera
Relative polycythemia
Familial erythrocytosis
Hypoxic polycythemia (due to obstructive sleep apnea)
High-affinity hemoglobinopathy
Answer 1 is
not correct. Answer 4 is correct.
Key Concept: Diagnose hypoxic polycythemia in the face of a normal Sao2
or Pao2 level
The clinical stem is sketchy; the reader craves more historical and laboratory
information. The patient could conceivably have one of the two rare causes of
erythrocytosis offered (familial erythrocytosis, high-affinity
hemoglobinopathy) or relative polycythemia. However, in the context of a
multiple-choice question, little information is provided to support these
diagnoses. The history provided is highly suggestive of obstructive sleep
apnea, and this diagnosis is therefore the most likely cause of the
erythrocytosis in this patient with an elevated erythropoietin level, no
splenomegaly, and normal WBC and platelet counts. Further history (observed
apneic episodes during sleep) and laboratory studies (arterial blood gases,
pulmonary function studies, overnight oximetry, and polysomnography) would be
appropriate at this time to confirm the suspected diagnosis. If these studies
are negative, studies to investigate alternative diagnoses would be
appropriate. Because the patient's hypoxia is intermittent (i.e., during
sleep-disordered breathing) and because the patient apparently does not have
severe COPD or cor pulmonale, the oxygen saturation and Pao2
levels can be normal during the day. The elevated erythropoietin level points
to tissue hypoxia as a cause of the erythrocytosis.
Question #13
A 75-year-old woman has been treated for polycythemia vera for 10 years with
phlebotomy and hydroxyurea. She has not required phlebotomy for 4 years, and
the dose of hydroxyurea has been gradually reduced because of cytopenia. The
hydroxyurea was discontinued 3 weeks ago. Physical examination reveals pallor
and an enlarged spleen, palpable 12 cm below the left costal margin.
Laboratory findings are as follows: Hb, 9.5; HCT, 25; WBC, 2,200; platelets,
55,000; blood smear, normal; Na+, 140; K+, 4.1; Cr, 1.2;
peripheral blood smear, teardrop-shaped red cells, nucleated red cells,
myelocytes, promyelocytes, and 1% myeloblasts.
What is the most likely cause of the anemia, thrombocytopenia, and leukopenia
in this patient?
Aplastic anemia
Delayed myelosuppression from hydroxyurea
Post-polycythemic myeloid metaplasia
Transformation to acute myeloid leukemia
Hypersplenism
Answer 1 is
not correct. Answer 3 is correct.
Key Concept: Recognize the syndrome of myeloid metaplasia following
polycythemia vera
Approximately 20% of patients with polycythemia vera (and the other
myeloproliferative disorders) eventually develop myelofibrosis or myeloid
metaplasia (MM), a process indistinguishable from agnogenic myeloid metaplasia
(AMM). Myeloid metaplasia is caused by progressive fibrosis of the bone marrow
and a shift of hematopoiesis from the marrow to the liver and spleen. Some of
the largest spleens encountered in clinical medicine are seen in AMM and MM.
These patients present with progressive cytopenia, and the smear shows
characteristic teardrop-shaped red cells and a leukoerythroblastic picture.
Although these patients can progress to acute myeloid leukemia, the presence
of a small percentage of myeloblasts should not suggest the diagnosis of acute
leukemia in this patient at this time.
Question #1
A 72-year-old man develops epistaxis that is difficult to control. He has no
prior history of bleeding problems. Evaluation shows a platelet count of
158,000/µl and normal bleeding time, PT, and TT. An elevated PTT is found
that does not correct with a mixing study.
Which of the following would be appropriate treatment for uncontrollable
bleeding in this patient?
Discontinuance of aspirin
Platelet infusion
Porcine factor VIII infusion
Cryoprecipitate infusion
Prednisone, 60 to 100 mg/day
Answer 1 is
not correct. Answer 3 is correct.
Key Concept: Recognize the presence of acquired clotting factor
inhibitors
This patient has a bleeding problem that began in adulthood and suggests an
acquired platelet or coagulation factor disorder. The prolongation of the PTT
in the absence of other laboratory abnormalities suggests a problem in the
intrinsic pathway of the clotting cascade. Presence of an inhibitor is
confirmed by failure of the PTT to correct with a 1:1 mixing study. A factor
VIII inhibitor would be the most common problem in this setting and is treated
acutely with porcine factor VIII.
Question #2
A 28-year-old woman develops a rash on her legs. She has been tired for
several weeks but has no other symptoms. On examination, she has a palpable
spleen and lower extremity petechiae. Her platelet count is 55,000/µl.
Which of the following tests is most likely to yield a diagnosis in this case?
ß-HCG
Monospot
ETOH level
ANA
TSH
Answer 2 is
correct.
Key Concept: Know the differential diagnosis of thrombocytopenia in a
young woman, and recognize the importance of physical examination
Causes of thrombocytopenia in this young woman could include ITP, pregnancy,
systemic lupus erythematosis, drug or alcohol use, infectious mononucleosis,
HIV, varicella, Graves disease, and Hashimoto thyroiditis. Of these
etiologies, only chronic ITP, chronic liver disease from alcohol abuse, and
infectious mononucleosis would be accompanied by splenomegaly. In the absence
of other signs of chronic liver disease, and given the patient's history,
infectious mononucleosis would be the most likely diagnosis.
Question #3
A 68-year-old woman with coronary artery disease calls your nurse on Friday
and reports bleeding of the gums, which is new for her. She takes baby aspirin
and a beta blocker, as well as quinine for nocturnal leg cramps.
Which of the following would you advise this patient to do?
Stop the quinine and make an appointment if the bleeding continues
Make an urgent appointment for today for further evaluation
See her dentist
Stop the aspirin and make an appointment if the bleeding continues
Make an appointment on Monday for further evaluation
Answer 1 is
not correct. Answer 2 is correct.
Key Concept: Recognize the spectrum of drug-induced thrombocytopenia
Although most drug-induced thrombocytopenia is mild and rarely causes
clinically significant bleeding, this patient warrants further evaluation. In
addition to being associated with mild thrombocytopenia that resolves after
discontinuance of the medication, quinine is associated with more severe
thrombocytopenia, as well as hemolytic-uremic syndrome. This patient needs a
further history and physical exam for evidence of bleeding; a peripheral smear
to evaluate platelet count and look for microangiopathic changes; and a
creatinine test.
Question #4
On routine blood studies, a 58-year-old man is found to have a platelet count
of 690,000/µl. He is asymptomatic and has normal red blood cell and white
blood cell counts.
Which of the following would be an appropriate next step for this patient?
Bone marrow biopsy to look for cause of thrombocytosis
Starting aspirin, 325 mg/day
Starting hydroxyurea therapy
Watchful waiting for signs of bleeding or thrombosis, with serial
platelet counts
Starting prednisone, 30 to 60 mg/day
Answer 1 is
not correct. Answer 4 is correct.
Key Concept: Recognize essential thrombocytosis and indications for
therapy
The diagnosis of essential rather than reactive thrombocytosis is suggested in
this patient by the absence of symptoms and the normal red and white blood
cell counts. Bone marrow biopsy is not necessary. Aspirin should be initiated
for symptoms such as digital discomfort but is not used routinely to prevent
thrombosis and can promote bleeding in patients without symptoms. Hydroxyurea
is used in symptomatic patients as well, and there is no threshold platelet
count at which it is started in the absence of symptoms. Prednisone is not
used in this disease.
Question #5
A 67-year-old woman has known chronic idiopathic thrombocytopenic purpura (ITP).
In association with an upper respiratory tract infection, she develops
gingival bleeding and has a platelet count of 25,000/µl. She is treat-ed as
an outpatient with prednisone, and her symptoms resolve. Five weeks after
completing the prednisone, she remains asymptomatic and has a platelet count
of 40,000/µl.
Which of the following treatments would you choose for this patient at this
time?
Retreatment with prednisone to maintain a platelet count > 50,000/µl
Splenectomy
Azathioprine
IGIV
Watchful waiting for bleeding episodes and intermittent platelet
counts to ensure a level > 20,000/µl
Answer 1 is
not correct. Answer 5 is correct.
Key Concept: Understand treatment for chronic ITP
While children usually have acute ITP, the course is more likely to be chronic
in adults. Exacerbations can occur at times of emotional stress, during viral
illness, or with the development or worsening of other medical problems.
Prednisone is useful in acute exacerbations, and IGIV can be added in this
setting if the patient has significant bleeding or sufficiently low platelet
counts (< 20,000/µl) to be at risk of intracranial hemorrhage. Splenectomy
is very successful for producing remissions in patients who require prednisone
between episodes, and azathioprine is reserved for splenectomized patients who
remain steroid dependent or who cannot take steroids. In the absence of
bleeding, there is no reason to increase this patient's platelet count to
greater than 50,000/µl.
Question #6
A 57-year-old man presents for evaluation of impotence. He is diabetic and
complains of symptoms consistent with peripheral neuropathy. You decide that
his symptoms are consistent with hemochromatosis.
Which of the following diagnostic tests should you order for this patient?
Plasma ferritin
Liver biopsy
Transferrin saturation
Bone marrow biopsy
None of the above, because the patient's symptoms are not suggestive of
hemochromatosis
Answer 1 is
not correct. Answer 3 is correct.
Key Concept: Understand the best screening test for hemochromatosis
Hemochromatosis is a common, underdiagnosed, hereditary disease. In the United
States, approximately 0.5% of the population is homozygous for this disorder.
Hypogonadism, type II diabetes, and peripheral neuropathy are common
presenting symptoms. Although a liver biopsy is the most definitive method for
assessing the parenchymal iron overload characteristic of hemochromatosis, it
is invasive and carries risk to the patient. Transferrin saturation is the
best screening test for hemochromatosis. Values greater than 50% to 60% should
prompt further investigation. Plasma ferritin provides a good indication of
total body iron stores but may be elevated in a number of inflammatory,
infectious, and malignant conditions. Bone marrow iron stores do not reflect
parenchymal iron overload and therefore are not useful in the diagnosis of
hemochromatosis.
Question #7
The man in Question 6 is diagnosed with hemochromatosis and begins phlebotomy.
What are your treatment goals for this patient?
Continue phlebotomy until the cirrhosis seen on original liver biopsy
has resolved
Continue phlebotomy to maintain normal transferrin saturation and a
ferritin level < 50 µg/L
Continue phlebotomy at an interval such that the hematocrit remains
below 35
Because the patient has too many complications of hemochromatosis,
treatment will not change the course of his disease
Because there is no effective treatment for hemochromatosis, educate the
patient about the genetic aspects of the disease and screen his family for
early detection
Answer 1 is
not correct. Answer 2 is correct.
Key Concept: Understand the goals of therapy for hemochromatosis
Phlebotomy, removal of excess iron, is indicated in almost all patients with
hemochromatosis. Appropriate phlebotomy can help slow the progression of the
disease, preventing further complications. If the patient has cirrhosis at the
time of diagnosis, the risk of hepatocellular carcinoma is not changed by
phlebotomy, nor will the cirrhosis resolve. The goal of treatment is to reduce
iron overload and maintain normal iron stores. The patient should not be made
anemic; in fact, phlebotomy should be postponed if the patient is anemic.
Normal transferrin saturation and a ferritin level less than 50 µg/L are
reasonable goals of therapy. Education about the genetic aspects of this
condition is important for all patients.
Question #8
Which of the following signs and symptoms is most specific for iron deficiency
anemia?
Pagophagia
Angular cheilitis
Pale palmar creases
Terry nails
Atrophic glossitis
Answer 1 is
correct.
Key Concept: Recognize history and physical exam findings that are
relatively specific for iron deficiency anemia
Pale palmar creases can be seen in any form of anemia. Angular cheilitis and
atrophic glossitis, although clues to iron deficiency anemia, can be seen in
other non-anemia-related conditions. Koilonychia (spoon nails), not Terry
nails, is the nail finding that is relatively specific for iron deficiency.
Pagophagia, or the desire to eat ice, is also fairly specific for iron
deficiency. Other forms of pica are seen in various types of anemia.
Question #9
A 35-year-old paraplegic woman has chronic osteomyelitis of the left hip
secondary to decubitus ulcers. Her hematocrit has slowly fallen over the past
year to 31.
What is the best indirect test to determine the cause of this patient's
anemia?
Serum iron
Bone marrow biopsy
Ferritin
Transferrin saturation
Transferrin receptor assay
Answer 1 is
not correct. Answer 5 is correct.
Key Concept: Understand how to differentiate anemia of chronic disease
from iron deficiency anemia
This woman has a chronic inflammatory condition and may have anemia of chronic
disease or iron deficiency anemia secondary to menstrual blood loss or other
site of bleeding. The best test to differentiate iron deficiency from anemia
of chronic disease is a bone marrow biopsy, which would show an absence of
stainable iron in the marrow. However, this direct measure is not without
discomfort and risk and should be used only if indirect measures fail to
identify the cause of the anemia. Serum iron and transferrin saturation will
be low in both anemia of chronic disease and iron deficiency, and this
patient's ferritin, an acute-phase reactant, is likely to be normal or high,
given her underlying condition. The transferrin receptor concentration
increases in iron deficiency but not in anemia of chronic disease and would be
the best initial test to differentiate the two.
Question #10
In the absence of acute inflammation, infection, or malignancy, which is the
most useful indirect test for iron deficiency?
Serum iron
Total iron-binding capacity
Ferritin
Bone marrow biopsy
Transferrin saturation
Answer 1 is
not correct. Answer 3 is correct.
Key Concept: Understand the best screening test for iron deficiency
anemia in the absence of other complicating conditions
The pattern of low serum iron, transferrin saturation, and ferritin, combined
with an elevated total iron-binding capacity, is very suggestive of iron
deficiency. Of these indirect tests, a ferritin level below 12 µg/L is the
most specific for iron deficiency. A normal or high ferritin level does not
eliminate the possibility of iron deficiency, but a value below this level is
virtually diagnostic. Serum iron and transferrin saturation can be low in
anemia of chronic disease, and total iron-binding capacity can be elevated in
other conditions. Bone marrow biopsy, a direct measure of marrow iron stores,
is the best diagnostic test but should be reserved for difficult diagnostic
cases.
Question #1
A 26-year-old man presents with new-onset left lower extremity swelling and
pain of 6 hours' duration. He takes no medications and has no history of
trauma, immobilization, or prior thrombosis. His family history is remarkable
for two "blood clots" in his mother. Compression ultrasonography
confirms occlusive thrombus in the left superficial femoral vein.
Which of the following is the most appropriate sequence of interventions for
this patient?
Start heparin and warfarin immediately, send tests for the
hypercoagulable state before warfarin reaches therapeutic levels, and
discontinue heparin after the international normalized ratio (INR) reaches
therapeutic levels
Send tests for the hypercoagulable state, then start heparin and
warfarin concurrently, and discontinue heparin after 5 days' overlap
Send tests for the hypercoagulable state, then start heparin and
warfarin concurrently, and discontinue heparin when the INR reaches
therapeutic levels
Start heparin and warfarin immediately, discontinue heparin after 5
days' overlap, and evaluate for the hypercoagulable state after warfarin
therapy is completed
Evaluate for the hypercoagulable state, but no anticoagulation is
indicated for superficial thrombophlebitis
Answer 1 is
not correct. Answer 4 is correct.
Key Concept: Understand the timing of workup and duration of therapy
for patients presenting with a new DVT
A 26-year-old male presenting with new-onset thrombosis and a positive family
history is highly suspicious for a hereditary hypercoagulable state and should
be worked up for this. Because the levels of protein C and antithrombin III
can be diminished in the setting of acute thrombosis and because heparin and
warfarin also alter these levels, the optimal time for the workup is after the
patient has completed therapy. Exceptions to this rule include the
antiphospholipid antibody syndrome, in which early diagnosis can affect
therapy and disorders for which specific genotypic tests are available (e.g.,
factor V Leiden), which will be accurate at any time. Because the INR (prothrombin
time) is heavily dependent on factor VII, which has a short half-life, it
rises fairly quickly after warfarin is begun. However, therapeutic
anticoagulation may take several days longer because of the persistence of
factor X and prothrombin. Overlapping heparin and warfarin by 5 days is
thought to limit the risk of propagation of thrombus caused by delayed
therapeutic anticoagulation. The confusingly named superficial femoral vein is
in fact in the deep system and warrants therapy.
Question #2
A 34-year-old woman presents with transient aphasia and mild right hemiparesis.
Symptoms have lasted about an hour and are resolving at the time of the exam.
Her past history is remarkable for a prior deep vein thrombosis (DVT) of the
leg while she was taking oral contraceptives and for two spontaneous abortions
in the second trimester. Which of the following is the most likely diagnosis
for this patient?
Factor V Leiden
Protein C deficiency
Antiphospholipid antibody syndrome
Antithrombin III deficiency
Prothrombin mutation 20210A
Answer 1 is
not correct. Answer 3 is correct.
Key Concept: Recognize clinical features suggestive of
antiphospholipid antibody syndrome
This patient presents with symptoms of transient ischemic attack, an arterial
thrombotic event. Of the disorders listed, only antiphospholipid antibody
syndrome frequently manifests with arterial thrombosis. A history of recurrent
late fetal loss is also quite suggestive of this diagnosis.
Question #3
A 47-year-old man weighing 60 kg presents with new-onset DVT without prior
risk factors. I.V. heparin is started with a 5,000-unit bolus and infusion of
1,000 units an hour. Six hours later, his partial thromboplastin time (PTT) is
only 38 seconds (normal is 24 to 32). He is rebolused with 1,500 units, and
his infusion is increased to 1,200 units an hour. Six hours after the change,
his PTT is 42 seconds.
What is the most likely underlying disorder in this patient?
Factor V Leiden
Protein C deficiency
Antiphospholipid antibody syndrome
Antithrombin III deficiency
Prothrombin mutation 20210A
Answer 1 is
not correct. Answer 4 is correct.
Key Concept: Recognize the manifestation of heparin resistance as a
clinical feature of antithrombin III deficiency
This patient is manifesting heparin resistance: a minimal prolongation of the
PTT despite therapeutic doses of heparin. Because heparin requires
antithrombin III as a cofactor, patients with significant deficiency of
antithrombin III occasionally do not respond to heparin alone. These patients
require addition of antithrombin III concentrate or fresh frozen plasma to
achieve therapeutic short-term anticoagulation with heparin. Warfarin remains
effective in the long term, as its mechanism of action is independent of
antithrombin III.
Question #4
A 58-year-old woman is 2 days' status post-total hip replacement. She has been
receiving subcutaneous heparin as prophylaxis for DVT. You are asked to see
the patient to evaluate new-onset dyspnea. On exam, the patient is tachypneic,
tachycardic, and diaphoretic. She is agitated and complains of substernal
chest pain. Chest exam reveals few bibasilar crackles. Cardiac, abdominal, and
extremity exams are normal except for her surgical wounds, which seem to be
healing well. Labs were sent before your arrival, and the results were pH,
7.47; Paco2, 31; Po2, 65; WBC, 11,500; Hb,
11.2; HCT, 33; platelets, 54,000; prothrombin time, 14 sec; INR, 1.1; PTT, 44
sec (normal 24-32; therapeutic range for heparin, 60-80); and chemistry panel,
within normal limits. ECG reveals 2 mm ST depression in leads II, III, and aVf;
and chest x-ray is normal.
Which of the following is the best course of action for this patient at this
point?
Bolus with I.V. heparin; begin heparin infusion; and arrange for
urgent coronary angiography
Bolus with I.V. heparin; begin heparin infusion; and arrange for urgent
ventilation-perfusion scan
Switch to low-molecular-weight heparin (LMWH) subcutaneously while
arranging further diagnostic testing
Stop all heparin, and bolus with I.V. methylprednisolone and
diphenhydramine for allergic reaction to heparin
Stop all heparin, and anticoagulate with hirudin while arranging
further diagnostic testing
Answer 1 is
not correct. Answer 5 is correct.
Key Concept: Recognize heparin-induced thrombocytopenia, and
understand appropriate therapy
This patient is status post-hip surgery and has been receiving heparin for 2
days. She now presents with a clinical scenario that suggests pulmonary
embolism or myocardial ischemia, or both, as well as a platelet count of
54,000. In this setting, one should be highly suspicious of heparin-induced
thrombocytopenia, which can present with venous or arterial thrombosis. While
the next diagnostic test is a matter of clinical judgment, the crucial first
step is discontinuing all heparin, including I.V. flushes, and initiating
anticoagulation with hirudin (a potent thrombin inhibitor derived from
medicinal leeches). Other alternatives would be lepirudin or danaparoid. LMWH,
unfortunately, is not considered safe in the setting of heparin-induced
thrombocytopenia and would not be a good alternative in this setting.
Question #5
A 68-year-old man presents with new onset of right-sided DVT without apparent
risk factors. Therapy is initiated, and the possibility of underlying cancer
is raised. You are consulted regarding appropriate evaluation for occult
malignancy. What would you recommend for this patient?
Careful history, physical exam, routine blood counts and chemistries,
chest x-ray (CXR), fecal occult blood testing (FOBT), and
prostate-specific antigen (PSA); if these are not revealing, no further
evaluation is necessary
Careful history, physical exam, routine blood counts and chemistries,
CXR, FOBT, and PSA; if these are not revealing, proceed with colonoscopy
Careful history, physical exam, routine blood counts and chemistries,
CXR, FOBT, and PSA; if these are not revealing, proceed with CT scan of
the chest, abdomen, and pelvis
Careful history, physical exam, routine blood counts and chemistries,
CXR, FOBT, and PSA; if these are not revealing, proceed with bone scan
Answer 1 is
correct.
Key Concept: Understand the appropriate extent of a malignancy workup
that should be undertaken in a patient presenting with new-onset DVT
There is a documented association between malignancy and thrombosis; in a
recent prospective trial, patients with idiopathic DVT had an 8% incidence of
diagnosis of cancer in the following 2 years, with an odds ratio of 2.3.
However, it has never been shown that an exhaustive workup for malignancy is
cost-effective or beneficial. On the basis of a recent large cohort study, it
has been recommended that the evaluation of idiopathic DVT be limited to a
careful history, physical exam, CXR, routine blood counts and chemistries,
FOBT, and possibly PSA in men and pelvic ultrasound in women. Further studies
should be directed by this initial evaluation; if it is unrevealing, then
additional tests will not likely help and may produce substantial
psychological stress in the patient.