Module 5 (Case Study)

SUPERWARFARIN:
A WIFES MEANS TO AN EVIL END
 A 50 year old man came to the emergency room presenting with red urine and
epistaxis within the last seven days. He is a lifelong non smoker, non alcoholic,
exercises regularly, is relatively fit and had no history with any bleeding or
thrombotic disorder himself nor within his relatives. He denied intake of any
other drugs except for his cholesterol which is Lipitor. Initial lab tests include:

HEMOGLOBI PROTHROMBI
N:12.5g/dL INR:
N TIME:
(RI: 13.5- greater than 10
137s
28.0g/dL) (RI: 9.2-12.8s)
(RI: 0.7-1.2)

ACTIVATED
PARTIAL
HEMATOCRIT THROMBOPLASTI
: 37% N TIME:
(RI: 40-47%) 180s
(RI: 24-34s),
 A +3 result was obtained in the dipstick urine test and in microscopy
about 80-90RBCs were found per HPF. Results of the mixing study show
correction of the PT and aPTT by addition of normal plasma.
An assay was made to determine the activities of the coagulation factors
and prothrombin group or vitamin k dependent factor activities were
seen to be significantly decreased. Factor V, factor XI, factor XIII and
vWF activities were normal. Finally, liver tests were within the normal
ranges.
 Based on the given lab results, a diagnosis of vitamin K deficiency was
presumed. However, the patient denied any ingestion of anticoagulants.
Vitamin K deficiency due to malabsorption or diet insufficiency was also
highly unlikely.
Although, the patient recollected that he had been seeing empty
containers of some sort in their garbage disposal and that his meals had
been tasting off and disregarded this as fatigue from work. The patient
said that he had always been busy at work and so his wife had been
preparing their meals. When asked if his wife joins him in eating, he
answered that recently they had been having marital quarrels and has
been distant ever since.
 Suddenly, a suspicion had occurred that his wife might have been
tampering with his food. High-performance liquid chromatography
(HPLC)/tandem mass spectrometry (LC-MS/MS) assay was performed
and showed positive levels for brodifacoum - rat poison. It was later
discovered that the wife had an affair and needed him to die to claim
insurance money and live off it with her boyfriend.
FFP was administered and the initial vitamin K1(Phytomenadione)
dosage was upped to 100mg/day for five days which will eventually be
decreased to 50mg/day until the lab tests show improvement and
normalization.
Questions
 1) Discuss the significance of identifying factor V
activity in diagnosing the patients condition.

Identifying factor V activity is vital for the reason that this factor is not
vitamin K dependent and is unaffected by dietary vitamin K
deficiency. As a result, declining coagulation factor V activity is a more
specific marker of liver disease than deficient factor II, VII, IX, or X
(prothrombin group). Moreover, when combined with the factor VII
assay, the factor V activity assay can be used to differentiate liver
disease from vitamin K deficiency.
 2) Explain why the treatment for
superwarfarin poisoning requires
a longer time than the usual
warfarin poisoning?

According to Sparh, J. E. & Rodgers, G. M.

(2007), Superwarfarins are anticoagulant rodenticides
similar to warfarin, but which have various
substituted phenyl groups replacing the terminal
methyl group, resulting in a fat-soluble, long-acting
anticoagulant that is nearly 100 times more potent
than the parent compound. Since their development,
many accidental and intentional cases of consumption
have been reported.
 2) Explain why the treatment for superwarfarin
poisoning requires a longer time than the usual
warfarin poisoning?

In addition, Brodifacoum is more potent than

warfarin as a vitamin K antagonist . The elimination
half-life in rats is 156 hr compared to the 17-hr half-life
of warfarin. In humans, the half-life is between 243-1656
hr for brodifacoum, compared to 17–37 hr for warfarin.
Since appropriate treatment consists of massive doses of
vitamin K for prolonged duration, obtaining an initial
brodifacoum level on admission, followed by a repeat
value in 24–48 hr, can provide an estimate of the duration
of treatment needed.
 2) Explain why the treatment for
superwarfarin poisoning requires a
longer time than the usual warfarin
poisoning?

Administration of FFP and vitamin K should rapidly correct the coagulopathy of

warfarin ingestion, given warfarin’s relatively short half-life. The half-life of
superwarfarin, on the other hand, will result in the repeat prolongation of the
PT and PTT 12–16 hr after administration of FFP and vitamin K, even if
correction to normal was initially achieved. In overdose, their elimination half-
life is longer-acting, ranging from weeks to months, 22 up to 60 times longer than
warfarin's half-life of 35 hours. Which is why they have a considerably longer
duration of action than the usual warfarin poisoning.
3) Is it still possible to thrombose in superwarfarin
posoining and why?

Superwarfarin drugs are highly potent, long-acting anticoagulant, vitamin K

antagonists. Exposure to these commonly available rodenticides can result in
potentially fatal hemorrhage particularly due to coagulopathy therefore the
occurrence of thrombosis is less likely to happen. Accordingly, all of the super
warfarin drugs work by blocking the formation of activated vitamin K (vitamin
K1) via inhibition of vitamin K 2,3-epoxide reductase enzyme complex. When
vitamin K1 is not regenerated, the clotting factors II, VII, IX and X cannot be
activated and a coagulopathy will develop.
 3) Is it still possible to thrombose in superwarfarin
poisoning and why?

However, some vitamin K antagonist drugs can elicit a procoagulant effect

which can induce imbalances to pro and anti-coagulant factors which can result to
bleeding and, in some cases, thrombosis occurs.
 References
• Keohane, E. M., Smith, L. J., & Walenga, J. M. (2016). Rodak’s Hematology: Clinical Principles and Applications
(5th ed.). Elsevier (Singapore) Pte.Ltd
• De Paula EV, Montalvao SA, Madureira PR, et al. (2009). Simultaneous bleeding and thrombosis in superwarfarin
poisoning. Thromb Res;123:637–9 
• Card, D. J., Francis, S., Deuchande, K., & Harrington, D. J. (2014). Superwarfarin poisoning and its
management. BMJ case reports, 2014, bcr2014206360. https://doi.org/10.1136/bcr-2014-206360
• “Case Definition: Long-Acting Anticoagulant (Super Warfarin)” (n.d.). CDC.
https://emergency.cdc.gov/agent/superwarfarin/casedefinition.asp
• Yan et al. (2012). Determination of bromadiolone and brodifacoum in human blood using LC-ESI/MS/MS and its
application in four superwarfarin poisoning cases.
https://www.researchgate.net/publication/230713584_Determination_of_bromadiolone_and_brodifacoum_in_hum
an_blood_using_LC-ESIMSMS_and_its_application_in_four_superwarfarin_poisoning_cases
• Sparh, J. E. & Rodgers, G. M. (2007). Superwarfarin Poisoning: A Report of Two Cases and Review of the
Literature. https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajh.20784
Thank you 