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case records of the massachusetts general hospital

Founded by Richard C. Cabot


Nancy Lee Harris, m.d., Editor Eric S. Rosenberg, m.d., Associate Editor
Jo-Anne O. Shepard, m.d., Associate Editor Alice M. Cort, m.d., Associate Editor
Sally H. Ebeling, Assistant Editor Christine C. Peters, Assistant Editor

Case 1-2007: A 40-Year-Old Woman


with Epistaxis, Hematemesis,
and Altered Mental Status
Michael Laposata, M.D., Ph.D., Elizabeth M. Van Cott, M.D.,
and Michael H. Lev, M.D.

Pr e sen tat ion of C a se

From the Departments of Pathology (M.L., Dr. Amy Jo Chien (Medicine): A 40-year-old woman was admitted to the emergency
E.M.V.) and Radiology (M.H.L.), Massachu- department of this hospital because of the sudden onset of headache, loss of con-
setts General Hospital; and the Depart-
ments of Pathology (M.L., E.M.V.) and Ra- sciousness, and coagulopathy.
diology (M.H.L.), Harvard Medical School. The patient had been in her usual state of good health until approximately
6 months earlier, when menorrhagia developed, with menstrual periods lasting for
N Engl J Med 2007;356:174-82.
Copyright © 2007 Massachusetts Medical Society.
2 weeks. Approximately 2 weeks before admission to the emergency department of
this hospital, she vomited blood clots after a meal. During the next several days,
intermittent epistaxis, gingival bleeding, and easy bruising occurred. Eight days
before admission to the emergency department of this hospital, she went to the
emergency department of a local hospital, where a physical examination was normal.
Results of liver- and renal-function tests were normal, as were the white-cell count,
differential count, and levels of serum protein, electrolytes, glucose, calcium, and
phosphorus; results of additional laboratory tests are shown in Table 1. She left
against medical advice to care for her children but returned 3 days later, after she
was called by a member of the emergency department staff; she was admitted to
that hospital (6 days before admission to the emergency department of this hospi-
tal). Overnight, she experienced hoarseness, tightness in her throat, and difficulty
swallowing; physical examination on the second hospital day showed enlargement
of the left tonsil and swelling in the left side of the neck. Results of liver- and
renal-function tests were normal, as were levels of serum protein, electrolytes,
glucose, calcium, phosphorus, and ferritin and iron-binding capacity; the serum
iron level was 22 μg per deciliter (3.9 μmol per liter), the erythrocyte sedimentation
rate was 114 mm per hour, and the lactate dehydrogenase level was 235 U per liter
(normal range, 100 to 190); results of additional laboratory tests are shown in
Table 1. Two units of fresh-frozen plasma were transfused, and the patient was
transferred to the intensive care unit of this hospital later that day (5 days before
the second admission to this hospital).
Computed tomographic (CT) scanning of the neck showed a left parapharyngeal
mass that was thought to be a hematoma. Vitamin K was administered orally,
subcutaneously, and intravenously, and multiple units of fresh-frozen plasma and

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5000 units of a concentrate of factors II, IX, and three pregnancies: two full-term deliveries and one
X and small amounts of factor VII (35%) (Profil- miscarriage. She was married and had two sons
nine SD, Grifols) were given. Results of laboratory who were well. She did not smoke, drink alcohol,
tests on the next 2 days are shown in Table 1. or use illicit drugs. She worked as a dog groomer.
There was no evidence of new bleeding. The pa- There was no family history of bleeding disorders.
tient was discharged on the fourth hospital day A complete metabolic panel, results of liver-
with no medications and with instructions to re- function tests, and a lipid profile were normal.
turn to the other hospital the next day for follow- Serum and urine toxicologic screening tests were
up laboratory tests. negative. Serum levels of creatine kinase and MB
The patient returned to the outpatient hema- isoenzyme were normal; the level of folic acid
tology clinic at this hospital 2 days later at the was 11 ng per milliliter (25 nmol per liter; normal
request of her hematologist because of abnormal range, 150 to 450 ng [340 to 1020 nmol]), vitamin
results of laboratory tests (Table 1). She was feel- B12 473 pg per milliliter (350 pmol per liter; nor-
ing well. An intravenous infusion of 5000 units mal value, >250 nmol [>180 pmol]), lactate dehy-
of a prothrombin complex concentrate was given drogenase 362 U per liter, and troponin T 0.72 ng
without immediate complications. During the car per milliliter. The results of other laboratory tests
trip home from the clinic (1 day before admission are shown in Table 1.
to the emergency department of this hospital), An electrocardiogram showed a normal sinus
she told her husband that she had abdominal rhythm with no acute ischemic changes. A chest
cramps and a headache and then rapidly became radiograph obtained at the bedside showed clear
confused and lost consciousness. Her husband lungs and a correctly placed endotracheal tube.
reported transient twitching of her left leg but no CT scanning of the head without the administra-
clear seizure activity. She was taken to a commu- tion of contrast material showed no evidence of
nity hospital emergency department, where she an acute territorial infarction or intracranial hem-
was reported to be agitated, combative, and unable orrhage. A CT angiogram and venogram of the
to follow commands. Her trachea was intubated head showed no stenosis or aneurysm of the in-
for airway protection with the use of vercuronium tracranial arteries. A laminar filling defect was
and succinylcholine during intubation. She was seen in the right superior ophthalmic vein. There
transferred to the emergency department of this was no evidence of venous sinus thrombosis.
hospital. In the emergency department, the patient was
On arrival, the patient was intubated, sedated, given 4 units of fresh-frozen plasma, 10 units
and paralyzed. The temperature was 36.2°C, blood of cryoprecipitate, recombinant factor VIIa, and
pressure 148/81 mm Hg, pulse 75 beats per min- 20 mg of intravenous vitamin K. The serum level
ute, and oxygen saturation 100% while the patient of haptoglobin was normal; results of other labo-
was breathing 100% oxygen. On physical exami- ratory tests are shown in Table 1. CT scanning of
nation, there was no sign of head trauma, but the abdomen and pelvis showed no evidence of
there was blood on the oral mucosa and there intraabdominal bleeding. Vancomycin, cefepime,
were ecchymoses on both arms and under the and metronidazole were given intravenously for
blood-pressure cuff. Petechiae were present dif- possible pneumonia. On the same day, the patient
fusely on the chest, arms, legs, and back. There was admitted to the intensive care unit of this
was bleeding at the sites of peripheral intravenous hospital. Results of laboratory tests are shown
administration. The neurologic examination was in Tables 1 and 2.
limited by sedation. The pupils were 2 mm in Vitamin K (10 mg) was administered intrave-
diameter, equal, round, and reactive. The patient nously three times daily. A test for the presence
was able to move all four extremities; there was of warfarin in a specimen of blood that had been
equivocal movement of the toes in response to obtained on the third day of the first hospitaliza-
noxious stimuli. Muscle bulk and tone were nor- tion was reported to be negative. An electroen-
mal. All reflexes were decreased. Examination of cephalogram showed no epileptiform activity.
the chest, heart, and abdomen showed no abnor- Magnetic resonance imaging (MRI) of the head
malities. Peripheral pulses were normal. before and after the administration of contrast
The patient had no other medical problems, material showed multiple foci of restricted diffu-
took no medications or nutritional supplements, sion involving the pons, and bilateral cerebellum.
and had no known drug allergies. She had had On the second hospital day, a repeated CT

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Table 1. Results of Hematologic and Coagulation Laboratory Tests.

Normal Range First Admission


Variable at This Hospital to Other Hospital First Admission to This Hospital
8 Days
before Second 5 Days 4 Days 3 Days
Admission to before Second before Second before Second
This Hospital Admission Admission Admission
Hematocrit (%) 36.0–46.0 42.1 32.2 29.0 31.0
Platelet count (per mm3) 150,000–350,000 232,000 188,000 179,000 210,000
Prothrombin time (sec) 11.3–13.3 >60.0 24.4 23.4 28.1
Prothrombin-time mixing study* Corrected Corrected
Partial-thromboplastin time (sec) 22.1–35.1 110.5 48.5 48.8 48.9
Partial-thromboplastin–time mixing Corrected Corrected
study*
Fibrinogen (mg/dl) 150–400 773
Fibrin split products (μg/ml) <5
D-Dimer (ng/ml) <500 700
Antithrombin III (%) 80–130
Factor II (%) 60–140 2
Factor V (%) 60–140 60
Factor VII (%) 60–140 <1
Factor VIII (%) 50–200 177
Factor IX (%) 60–140 <0.9
Factor X (%) 60–140 1
Protein S (%) 70–140
Protein C (%) 70–140
Activated protein C resistance >2.0

* Mixing study denotes 1:1 mix of patient’s plasma with normal plasma and multiple measurements during a 1-hour period.

angiogram of the head and neck showed stable and was able to follow commands. The trachea
left pontine and cerebellar infarcts and no evi- was extubated. Neurologic examination revealed
dence of new infarction or acute intracranial mild weakness of the right arm and left side of
hemorrhage. A transcranial Doppler study showed the face, with no other abnormalities. On ques-
normal flow velocities, spectral configurations, tioning, she specifically reported that she had
and directions of flow in the left and right, mid- not been exposed to warfarin or rat poison; she
dle, anterior, and posterior cerebral arteries, with had had occupational exposure to canine flea and
no spontaneous emboli detected during a 30-min- tick solutions containing fipronil, imidacloprid,
ute recording. No emboli were detected after the and permethrin. She drank four to five glasses
injection of agitated saline or with the the pro- of bottled iced tea with ginseng daily. Tests for
vocative maneuvers of abdominal compression, lupus anticoagulant, heparin–PF4 antibodies, and
inspiratory pause, and suctioning with coughing. the prothrombin gene mutation G20210A were
Treatment with unfractionated heparin was negative. Results of other laboratory tests are
initiated, with a target partial-thromboplastin time shown in Tables 1 and 2. No blood products were
of 40 to 50 seconds. Treatment with vitamin K required after the second hospital day.
was continued intravenously, and fresh-frozen On the fifth hospital day, swelling of the left
plasma was transfused as needed on the basis arm developed; ultrasonography showed a super-
of the prothrombin and partial-thromboplastin ficial cephalic-vein thrombus with no evidence of
times. The patient was alert, behaved normally, deep venous thrombosis. A transthoracic echocar-

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case records of the massachuset ts gener al hospital

On Visit to Hematology
2 Days before Second Clinic at This Hospital
Admission to This (1 Day before Second
Hospital Admission to This Hospital) Second Admission to This Hospital

In On
Emergency Admission
Department to the ICU Day 2 Day 3 Day 5 Day 8
31.5 32.0 23.4 26.6 28.2 29.2
201,000 125,000 119,000 70,000 98,000 137,000
18.6 23.0 28.5 >50.0 11.0 14.4 18.8 13.5

37.5 39.9 47.6 >150.0 33.3 28.3 36.4 43.8

<50 240 386 557


>20
>10,000 >10,000 8,696 3,227
32
31 43
85 104
<1 59
150
7.0 54.0
25 41
20
14
3.0

diogram obtained after injection of agitated saline which had resolved by the time of discharge. On
on the sixth hospital day showed no evidence of the second admission, a CT angiogram obtained
a patent foramen ovale. On the seventh hospital for the evaluation of neurovascular symptoms
day, the serum warfarin level in a specimen of showed poor filling of the right superior oph-
blood that had been obtained on admission to the thalmic vein, a finding suggestive of thrombosis.
emergency department the second time was re- This finding did not resolve on follow-up exami-
ported to be negative. Evaluation by the psychiat- nation (Fig. 1B). Both T2-weighted (Fig. 1C) and
ric service on the eighth hospital day showed that diffusion-weighted (Fig. 1D) MRI scans showed
the patient had no evidence of acute psychiatric punctate acute infarction of the pons and left
illness and no indication of suicidal intent or a cerebellum, although no hemorrhage was seen
desire to harm herself. on a magnetic resonance susceptibility sequence
The results of a diagnostic test were reported (not shown). CT scanning of the pelvis, performed
on the 10th hospital day. because of excessive bleeding after an attempted
femoral-line placement, showed an extensive su-
Differ en t i a l Di agnosis perficial soft-tissue hematoma. A transcranial Dop-
pler ultrasound study, which was performed the
Dr. Michael H. Lev: CT scanning of the neck on the next day to confirm the patency of the cerebral vas-
first admission to this hospital showed a high- culature, was normal. On the fifth hospital day,
density supraglottic soft-tissue hematoma (Fig. 1A), a deep-vein thrombosis ultrasonographic exami-

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Table 2. Serum Levels of Brodifacoum and Results of Coagulation Tests during Therapy with Vitamin K after Second Admission
to This Hospital.

Normal 2 Months after 4.5 Months after


Variable Range Day 2 Day 11 Day 14 Admission Admission*

Brodifacoum (ng/ml) Not detected 93 78 74 Not performed <5


Prothrombin time (sec) 11.1–13.1 14.1 16.8 25.8 13.0 13.0

Partial-thromboplastin time (sec) 22.1–35.1 29.0 48.4 37.7 35.7 30.1

* This was 10.5 months after the initial onset of the bleeding.

nation of the arms revealed a superficial cephalic mon pathway of the coagulation cascade (fibrin-
vein thrombosis. On the fifth hospital day, ultra- ogen, factor II, factor V, or factor X), which could
sonographic examination of the arms revealed a prolong both the prothrombin and partial-throm-
superficial cephalic vein thrombosis. In summary, boplastin times. Impaired platelet function would
this patient had radiologic evidence of both bleed- not prolong the prothrombin and partial-throm-
ing and thrombosis, including hemorrhage in boplastin times, and neither a deficiency or an
the regions of the neck and groin and thrombo- inhibitor of factors VIII, IX, XI, or XII nor von
sis of the superior ophthalmic vein, posterior ce- Willebrand’s disease would prolong the prothrom-
rebral microvasculature, and left cephalic vein. bin time. A selective deficiency or inhibitor of
Dr. Michael Laposata: This 40-year-old woman factor VII would not prolong the partial-thrombo-
presented with a hemorrhagic coagulopathy in plastin time. In this patient, the coagulation-factor
the absence of a personal or family history of deficiency is probably acquired rather than con-
bleeding and taking no identifiable medications genital, given the absence of a personal and fam-
or nutritional supplements that would predispose ily history of bleeding.
her to a bleeding disorder. The bleeding began at
least 6 months before her initial presentation, Acquired Deficiency of Vitamin K–Dependent
with menstrual periods lasting 2 weeks. Excessive Coagulation Factors
menstrual bleeding can be associated with non- The seriousness of the bleeding disorder became
hematologic disorders, but such disorders are un- apparent 5 to 6 days before the second admission
likely in this patient, since she later vomited to this hospital, when a parapharyngeal hemato-
blood clots after a meal and began to have inter- ma developed. Factor assays at that time showed
mittent epistaxis, gingival bleeding, and easy bruis- low or undetectable levels of the vitamin K–depen-
ing. These additional clinical findings strongly dent factors, with normal values for non-vitamin
suggested the presence of a hemorrhagic coagu- K–dependent coagulation factors. Treatment with
lopathy, which could be due to a low platelet 2 units of fresh-frozen plasma shortened the pro-
count, defective platelet function, or a coagulation- thrombin and partial-thromboplastin times, but
factor deficiency. did not normalize the values for these two tests.
Relatively small amounts of plasma can shorten
Causes of Hemorrhagic Coagulopathy the prothrombin and partial-thromboplastin times,
Laboratory test results 8 days before admission but much larger amounts are required for normal-
showed markedly prolonged prothrombin and ization or even near normalization. The hemato-
partial-thromboplastin times, both of which were crit had fallen, suggesting that the patient had
corrected in mixing studies. The patient had a blood loss. At that time, it was clear that she had
normal platelet count, and the results of liver- a hemorrhagic coagulopathy caused by multiple
function tests were normal. These findings rule acquired deficiencies of the vitamin K–dependent
out a decreased platelet count as a likely explana- factors.
tion for the hemorrhagic coagulopathy and pro- The differential diagnosis includes surrepti-
vide evidence of multiple coagulation-factor defi- tious or inadvertent ingestion of warfarin or a
ciencies. A less likely possibility is an acquired, warfarin-related compound or a very severe vita-
single coagulation-factor deficiency in the com- min K deficiency. Vitamin K (Fig. 2) is a cofactor

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case records of the massachuset ts gener al hospital

A B

Figure 1. CT and MRI Studies of the Head and Neck.


An axial CT scan of the neck, obtained after the administration of contrast material (Panel A), shows a left supraglottic
high-density soft-tissue hematoma (arrow) measuring 68 Hounsfield units. The appearance was the same on the
images obtained before and after the administration of contrast material. An axial CT scan of the head, obtained
after the administration of contrast material (Panel B), shows an unopacified right superior ophthalmic vein (arrow),
a finding consistent with the presence of a thrombus. An axial T2 -weighted MRI scan (Panel C) shows hyperintensity
of the left pons (long arrow) and superior cerebellum (short arrow). An axial diffusion-weighted MRI scan (Panel D)
confirms the presence of an acute stroke in these locations (long arrow and short arrow).

in the reaction in which the enzyme gamma car- animal poisons. The warfarin-related poisons can
boxylase catalyzes the production of factors II, have a much greater potency than warfarin and
VII, IX, and X, as well as the natural anticoagu- are thus called “superwarfarins.”
lants, protein C and protein S. Vitamin K is con-
verted to an inactive vitamin K epoxide in this Superwarfarin Pesticide Poisoning
reaction, and the enzyme vitamin K epoxide re- Five days before the second admission, the patient
ductase regenerates the active form. This enzyme was treated with large amounts of vitamin K. She
is the target of warfarin and warfarin-related also received multiple units of fresh-frozen plas-

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surreptitious or inadvertent ingestion of a super-


Vitamin K1
(phytonadione) warfarin pesticide.3,4
Epoxide reductase Reductase Because the patient’s prothrombin and partial-
inhibited by or NAD(P)H- thromboplastin times continued to rise, she re-
warfarin, dependent
brodifacoum dehydrogenase ceived a second treatment with a prothrombin-
complex concentrate. Shortly thereafter, abdominal
Vitamin K2,3- Vitamin K cramps, headache, and loss of consciousness oc-
epoxide hydroquinone
curred; she had evidence of both bleeding and
Carboxylase+oxygen+ thrombosis, with a thromboembolic stroke and
carbon dioxide
thrombosis in the right superior ophthalmic vein.
The results of coagulation studies, including the
prothrombin and partial-thromboplastin times,
Carbon dioxide is added to glutamate
on factors II, VII, IX, and X were elevated. There were also signs of dissemi-
(carboxylation) nated intravascular coagulation, with a low fi-
brinogen level, an elevated D-dimer level, a low
Figure 2. The Vitamin K Cycle.
platelet count, and a low antithrombin level (32%).
Vitamin K1 (also called phylloquinone or phytonadione),
Disseminated intravascular coagulation is one of
acquired from the diet or from medical administration,
is reduced to its active form (hydroquinone) by one of the major side effects of prothrombin-complex
two reductases. One of the reductases is not sensitive concentrates.1,2
to warfarin and requires NAD(P)H; the other reduc- At this point, the management issues became
tase is partially sensitive to warfarin. Active vitamin K especially challenging, since the thrombotic stroke
is required for carboxylation of coagulation factors II,
and coagulopathy had to be treated simultane-
VII, IX, and X (as well as protein C, protein S, protein
Z, and certain bone proteins). A carboxylase enzyme ously. The most appropriate management strat-
performs the carboxylation step using oxygen and carbon egy, which was applied in this case, was to nor-
dioxide, and in the process, active vitamin K becomes malize or nearly normalize the coagulation factors
oxidized to an inactive form called vitamin K2,3- epox- and then to administer anticoagulation therapy
ide. Epoxide reductase reduces vitamin K 2,3- epoxide
in a standard fashion as treatment for stroke.
back to vitamin K1, which permits the regeneration of
active vitamin K. Epoxide reductase is inhibited by warfa- After treatment with fresh-frozen plasma, cryo-
rin or warfarin-like agents, including superwarfarins precipitate, and large quantities of intravenous
such as brodifacoum. vitamin K, the patient’s prothrombin and partial-
thromboplastin times became normal for the
first time, and the fibrinogen level rose to the
ma and a prothrombin-complex concentrate, which normal range. Several risk factors for hyperco-
contains some activated coagulation factors and agulable states were ruled out, and both the bleed-
carries with it the potential complications of ing and disseminated intravascular coagulation
thrombosis and disseminated intravascular coagu- resolved. A serum test for warfarin was negative.
lation.1,2 After all of this therapy (3 days before This result was consistent with the presence of a
the second admission), the patient had a markedly superwarfarin pesticide, which was not likely to
reduced but still prolonged prothrombin time be detected in an assay to identify and quantitate
(18.6 seconds) and a nearly normal partial- warfarin.
thromboplastin time (37.5 seconds). Furthermore,
follow-up studies indicated that these times were Conclusions
gradually increasing, findings that are consistent I suspect that the diagnostic test result that was
with the persistent activity of a residual substance reported on the 10th hospital day was the detec-
that inhibits the action of vitamin K–dependent tion of a superwarfarin compound, possibly brodi-
clotting factor. The failure of very large amounts facoum, in the plasma. Ingestion of brodifacoum
of vitamin K to correct the problem makes the does not cause gastrointestinal symptoms, and
diagnosis of vitamin K deficiency or surreptitious it can be ingested in large quantities; neverthe-
or inadvertent warfarin ingestion unlikely, since less, once poisoning occurs, abdominal pain is
these disorders would have been effectively treat- common. Both brodifacoum and warfarin are
ed with much smaller amounts of vitamin K. The 4-hydroxycoumarins; chemical differences outside
fact that large amounts of vitamin K did not cor- the 4-hydroxycoumarin structure differentiate war-
rect the problem provides strong support for the farin from the superwarfarins. The 4-hydroxycou-

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marin superwarfarins include brodifacoum,5 bro- bleeding) or poisonings (defined as exposure with
madiolone,6 coumafuryl,7 and difenacoum.8 coagulation abnormalities and bleeding) is in-
I think that the events occurred in the follow- creasing, with 5133 exposures or poisonings re-
ing sequence. The patient was exposed to a super- ported in 1988, 13,423 in 1995, and 16,109 in
warfarin, either accidentally or intentionally. There 1998.9,10 The vast majority of these cases have
was a marked reduction in vitamin K–dependent been exposures, and only 24 cases were classified
coagulation factors. With replacement of vita- as poisonings in adults.10 Ninety percent of expo-
min K and vitamin K–dependent factors, the ad- sures are in children, usually those under 6 years
ditional use of a prothrombin-complex concen- of age and usually with no consequent coagula-
trate resulted in the desired hemostasis as well tion abnormalities.10,11 Minor exposures in chil-
as the undesired side effects of thrombosis and dren may not require treatment.11,12
disseminated intravascular coagulation. It would Cases of exposure to brodifacoum have includ-
be informative to learn from the patient how her ed accidental exposure, suicide attempts with the
exposure to large amounts of a superwarfarin substance, Munchausen’s syndrome, exposure of
might have occurred. factory workers, and exposure from smoking
Dr. Nancy Lee Harris (Pathology): Dr. Ellman, you marijuana or “crack” cocaine.10,13,14 In addition to
were this patient’s hematologist; will you tell us ingestion or inhalation, absorption through the
your thinking at the time of her admission? skin can occur.
Dr. Leonard Ellman (Hematology and Oncology): Brodifacoum is lipophilic. It is 100 times as
My thinking very closely paralleled Dr. Laposata’s, potent as warfarin and has a very long half-
and although the patient vehemently denied any life15,16; in this patient, the half-life was estimat-
exposure, I thought she must have ingested a ed to be 30 days. In contrast, the half-life of
superwarfarin. Specimens of blood were sent to warfarin is approximately 40 hours. The duration
a reference laboratory for testing. Before her ad- of coagulation abnormalities and the dosage of
mission, I was very concerned about the risk of vitamin K1 required to correct them vary among
serious bleeding, and the decision to give her the reported cases, probably at least in part because
concentrate of factors II, VII, IX, and X was of variations in the amount of brodifacoum con-
made in consultation with the director of the sumed, deliberate or unintentional noncompliance
blood bank. with vitamin K1 therapy in some cases, continued
exposure to brodifacoum in some cases, and the
Cl inic a l Di agnosis variable metabolism of brodifacoum, like that of
warfarin. With brodifacoum poisoning, every car-
Multiple vitamin K–dependent coagulation-factor boxylation reaction requires a new vitamin K1
deficiencies due to ingestion of brodifacoum. molecule, because vitamin K1 cannot regenerate
(Fig. 2).9 For these reasons, the treatment of brodi-
facoum poisoning requires large doses of vitamin
DR . MICH A EL L A P O S ATA’S
DI AGNOSIS K1, ranging from 50 to 800 mg per day, admin-
istered for an extended period.10,13,16-21 In this
Multiple vitamin K–dependent coagulation-factor patient, coagulation abnormalities resolved within
deficiencies due to ingestion of brodifacoum. 4.5 months after her second admission (Table 2),
and the highest vitamin K dose she received was
Pathol o gic a l Dis cus sion 60 mg per day.
Dr. Harris: Dr. Ellman, will you give us the fol-
Dr. Elizabeth M. Van Cott: The results of an assay for low-up information?
brodifacoum from a specimen of blood obtained Dr. Ellman: The patient continued to deny that
on the first hospital day were reported to the she had accidentally or intentionally ingested
hematologist on call on the 10th hospital day. brodifacoum or that anyone could have been try-
The level was 93 ng per milliliter (threshold for ing to poison her. The only explanation she could
detection, 5 ng per milliliter). offer was the ingestion of strange-tasting lun-
Brodifacoum is the most commonly used su- cheon meat about 1 week before her initial visit
perwarfarin in the United States. The number of to the local emergency department. The case was
superwarfarin exposures (defined as ingestion or reported to her city’s health department and to
inhalation without coagulation abnormalities or law enforcement officials. To the best of my

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knowledge, no additional information has been Dr. Laposata reports receiving consulting fees from BD Preana-
lytical Systems, Cubist Pharmaceuticals, T2 Biosystems, Roche
obtained. Point-of-Care Coagulation, Instrumentation Laboratory, Procter
Treatment with vitamin K and anticoagulation & Gamble, and Catalyst Oncology; having equity and ownership in
therapy initially with heparin and later with American Medical Diagnostics, MedPacks, and Pocket Medicine;
having anticipated stock options in T2 Biosystems; receiving lecture
fondaparinux were continued, and the patient fees from GlaxoSmithKline, Diagnostica Stago, InVein Treatment
was discharged home on the 15th hospital day. & Techniques, Gerson Lehrman, Novo Seven, Ortho, and Lab Info-
At the time of discharge, she had no focal neuro- Tech; serving as an expert witness in areas related to laboratory
testing and coagulation; receiving royalties from ASCP Press and
logic deficits. She was well, with no further Pocket Medicine, Lexi-Comp, ASCP, American Medical Diagnostics,
bleeding or clotting problems, at the last follow- and Thomas Weisel Venture Partners; and being a nonpaid advi-
up visit, 8 months later. sory board member for DiagnosisONE. Dr. Van Cott reports receiv-
ing lecture fees from Novo Nordisk, bioMerieux, and Diagnostica
Stago; grant support from Diagnostica Stago; and royalties from
PATHOL O GIC A L DI AGNOSIS American Medical Diagnostics. Dr. Lev reports serving on medical
advisory boards for GE Healthcare, Bracco Diagnostics, and CoAxia
and receiving lecture fees from GE Healthcare and Bracco Diagnos-
Multiple vitamin K–dependent coagulation-factor tics, and educational support from GE Healthcare. No other poten-
deficiencies due to ingestion of brodifacoum. tial conflict of interest relevant to this article was reported.

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