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PHARMACOTHERAPY Volume 22, Number 8, 2002
Table 1. Ingredients in Intravenous Chelation Therapy
Administered over 3 Hours
denied missing any warfarin doses; he was taking
25 mg/week. He reported no drug or dietary
changes and had no new illness that could have
affected his INR. He was instructed to take
warfarin 10 mg that day and then restart the
previous regimen of 5 mg on Monday,
Wednesday, and Friday and 2.5 mg on Tuesday,
Thursday, Saturday, and Sunday, for a total of 25
mg/week. With this dosing regimen the patient’s
INR remained stable within the therapeutic target
range (2.1–2.7). He did not receive further
chelation therapy.
Volume
(dl)
Osmolality
(mOsm)
Ingredient
Sterile water
500
20
10
10
0.5
14
1
1
1
10
1
—
Sodium EDTA 3 g
Magnesium chloride 2 g
Procaine HCl
Heparin 2500 U
Vitamin C 7 g
Potassium chloride 2 mEq
Pyridoxine (vitamin B )
Thiamine (vitamin B )
Sodium bicarbonate 840 mg
Trace elements
26.80
29.50
1.40
0.46
81.20
4.00
1.11
0.62
17.90
—
6
1
In vitro, EDTA inhibits coagulation by binding
to calcium ions that are required for the
progression of blood coagulation. One would
expect EDTA to have an anticoagulant effect and
increase INR. Prolonged prothrombin times have
been reported, although infrequently, in patients
receiving chelation therapy.4 The mechanism of
this potential interaction is not clear. One
possible explanation is that the high dose (7 g) of
vitamin C in the chelation therapy might have
contributed to the decreased anticoagulation
effect of warfarin.5 Whether vitamin C actually
interacts with warfarin is a controversial issue
and has not been verified. Furthermore, in
theory, oral administration of vitamin C decreases
warfarin absorption. Our patient was given
vitamin C intravenously, so the interaction would
not be expected to occur. Other possible
explanations for the drop in his INR, such as
missed doses, laboratory errors, or other factors,
cannot be ruled out.
EDTA = ethylenediaminetetraacetic acid.
Table 2. Warfarin Dosing and INR Values in a Warfarin-
Treated Patient Who Received Chelation Therapy
Date
(2000)
INRa
Warfarin Dosage
2/7
2/8
2/9
2/10
2/11
2/14b
1.0
1.0
1.3
1.8
2.5
3.4
10 mg/day (first dose in hospital)
7.5 mg/day
No change
No change
5 mg/day (discharged from hospital)
15 mg/wk (skip 2/16, then 5 mg
Th, Sa; 2.5 mg F, Su)
17.5 mg/wk (skip 2/21, then 5 mg F,
2.5 mg all other days)
25 mg/wk (5 mg MWF, 2.5 mg all
other days)
2/21
2/28
3.5
2.1
3/6
2.6
1.6
No change
3/8c
10 mg x 1 dose, then 25 mg/wk
(5 mg MWF, 2.5 mg all other days)
25 mg/wk (5 mg MWF, 2.5 mg all
other days)
3/14
2.8
3/21
4/17
5/8
6/5
7/3
2.3
2.7
2.3
2.6
1.5d
2.7
2.7
No change
No change
No change
No change
No change
No change
No change
Conclusion
Based on our experience with this patient, we
cannot determine with certainty whether
chelation therapy decreases the effectiveness of
warfarin anticoagulation. In fact, this case seems
to contradict previous findings. However, since
chelation therapy can consist of numerous
ingredients, different formulations may have
various effects on warfarin. Clinicians may see
increases, decreases, or no change in the INR of
warfarin-treated patients who receive chelation
therapy. Until more is known about how
chelation therapy might affect warfarin, clinicians
should consider increased INR monitoring in
patients undergoing chelation treatment.
7/10
8/11
INR = international normalized ratio.
aAll INRs were obtained at a Munson Healthcare facility laboratory
that uses the same blood draw technique (venipuncture),
equipment (CA 1000), and thromboplastin value (international
sensitivity index = 2.0) for all INR calculations.
bPatient visited anticoagulation clinic.
cDay after patient received chelation therapy.
dPatient reported missing 2 doses.
Approximately 3 weeks after starting warfarin,
the patient received chelation therapy at his
primary care provider’s office (Table 1); his
international normalized ratio (INR) on the
previous day was 2.6. The patient returned to
the clinic the next day for a scheduled visit, and
his INR had fallen to 1.6 (Table 2). The patient
References
1. Ghen MJ, Rozema TC. Chelation therapy. In: Novey DW,
ed. Clinician’s complete reference to complementary
and alternative medicine. St. Louis, MO: Mosby, 2000:
508–16.