Reports
of thrombocytopenia associated with complementary and alternative medicines,
herbal remedies, nutritional supplements, foods and beverages
Reproduced from the Eur J Haematol. 2010; 84: 421-429 [Full Text]
For the criteria
for article assessment and the definition of levels of evidence click here
Substance |
Case
report summary |
Substances
with definite evidence for a causal association with thrombocytopenia |
|
Milk22 |
33 M
with ulcerative colitis developed thrombocytopenia (5 x 103/µl)
and rectal bleeding requiring transfusions.
Platelet count recovered after food intake discontinued and remained
normal until cow’s milk was added to diet; then thrombocytopenia recurred
(150 →11 x 103/µl). Platelet counts remained normal and
ulcerative colitis resolved with a milk-free diet. |
Cranberry
juice23 |
68 M
developed thrombocytopenia (1 x 103/µl) with mucocutaneous
bleeding and hematuria. Platelet counts recovered
to normal (200 x 103/µl) with steroid treatment. Dietary history suggested cranberry juice,
taken for 10 days for urinary retention, was associated with the
thrombocytopenia. Using indirect immunoflorescence,
cranberry juice-dependent platelet-reactive IgG and
IgM antibodies were detected using dialyzed juice
of the same brand and batch. Challenge with cranberry juice not reported. |
Jui
herbal tea24 |
51 F
developed thrombocytopenia (16 x 103/µl) with mucocutaneous
bleeding associated with Jui herbal tea taken several days before her annual health
examination. Challenge with Jui caused thrombocytopenia (305 →2 x 103/µl)
within one day. |
Jui herbal tea25 |
54 M
with liver cirrhosis had 3 episodes of thrombocytopenia with platelet counts
of zero and mucocutaneous bleeding. Association
with Jui was noted. Platelet counts following
recovery from each episode are not reported but are described as “his usual
range”. Challenge with Jui
caused the platelet count to rapidly decrease to zero in 6 hours and
recovered to “pre-challenge levels” on day 6. Thrombocytopenia did not recur
after stopping Jui.
|
Lupinus
termis
bean26 |
13 M
developed thrombocytopenia on 5 occasions after Lupinus termis bean ingestion, 3 times as a
supervised challenge with a single bean. At the last challenge, the platelet
count decreased from 160 →10 x 103/µl in 2 hours. Recovery
platelet counts not reported. |
Tahini 27 |
28 F
with multiple episodes of thrombocytopenia (lowest platelet count, 6 x 103/µl)
with mucocutaneous bleeding. The patient associated
thrombocytopenia with ingestion of tahini. Following
challenge, the platelet count fell from 161 to 34 x 103/µl in one
day and recovered (189 x 103/µl) in 9 days. |
Substances
with probable evidence for a causal association with thrombocytopenia |
|
Bajiaolian28 |
38 F
(Case 2) developed thrombocytopenia (70 x 103/ µl) and leukopenia (2270/µl) in addition to ataxia and paresthesias 2 hours after drinking Bajiaolian
infusion. Platelet count recovered to normal (227 x 103/µl) in 12
days, leukopenia in 25 days, but paresthesias persisted. Criteria 1, 2, and 3 were met. |
Cupressus
funebris (Mourning
cypress)29 |
62 F
developed acute systemic illness (acute renal failure, liver toxicity,
hemolytic anemia and thrombocytopenia [nadir, 2 x 103/ µl on day
4]) 2 hours after ingesting hot water extract from sliced wood (C. funebris).
Her first ingestion 1 week previously had caused no symptoms. “Recovery from
thrombocytopenia within days” is stated but no recovery platelet counts are
reported. Increased serum creatinine persisted for
>1 month. Criteria 1, 2, and 3 were met. |
Milk,
Potato30 |
26 F
(Case 2) with repeated episodes of nausea, vomiting, and bloody diarrhea
associated with thrombocytopenia; milk and potato were suspected
etiologies. Challenge with potato:
platelet count decreased from 104 to 91 x 103/µl at 30 minutes.
Challenge with milk: platelet count decreased from 56 to 46 x 103/µl
at 30 minutes. Following elimination of milk and potatoes from her diet,
platelet counts were 140 to 190 x 103/µl for the following 9
months. Criteria 1, 2, and 3 were met;
challenge criterion not met. |
Vitamin
A palmitate31 |
3
month-old M developed thrombocytopenia (30 x 103/µl) and anemia.
Marrow aspirate demonstrated decreased megakaryocytes
and erythroid dysplasia. He had received 62,000 U
of vitamin A each day (41-times the recommended requirement) since 10 days of
age because of misunderstood instructions.
Platelet count recovered to 220 x 103/µl 30 days after
vitamin A stopped. Criteria 1, 2, and 3 were met. |
Substances
with possible evidence for a causal association with thrombocytopenia |
|
Chromium
picolinate33 |
33 F
developed acute renal failure, liver toxicity, hemolytic anemia and
thrombocytopenia (15 x 103/µl) after taking chromium picolinate tablets for 4-5 months for weight loss. Plasma
chromium concentration was more than twice normal. Platelet count and other
abnormalities returned to normal by day 26 after stopping chromium tablets.
Criteria 1 met; insufficient data to assess criteria 2 and 3. |
Echinacea pallida34 |
32 M
used Echinacea pallida for treatment of a respiratory
infection for one week. Paracetamol was also used. Two weeks after stopping Echinacea he developed thrombocytopenia (20 x 103/µl),
microangiopathic hemolytic anemia, and
seizures. He recovered following one
month of plasma exchange treatment. Criterion 1 met; insufficient data to
assess criteria 2 and 3 |
Hypericum
perforatum
(St. John’s Wort)35 |
22 M
was admitted to hospital with fever, pharyngitis,
anemia (6 g/dl), agranulocytosis (absolute neutrophil count, 12/µl). He had been taking St. John’s Wort for 3 weeks and fluoxetine
for 3 months for depression. Thrombocytopenia developed on day 3 (464 →83
x 103/µl). Marrow biopsy demonstrated necrosis. The patient died
on day 8. Although platelet count did not recover, criterion 1 may have been
met if the patient had survived.
Criteria 2 and 3 not met; a viral infection etiology as well as St.
John’s Wort toxicity was considered. |
Nicotinamide36 |
Patient
(age, gender not reported) developed thrombocytopenia (platelet count decreased
from 168 to 83 x 103/µl) after 12 weeks of treatment with nicotinamide for hyperphosphatemia
while on chronic hemodialysis. Platelet count
recovered to 180 x 103/µl 2 weeks after nicotinamide
discontinued. Criteria 1 met;
insufficient data to assess criteria 2 and 3.
|
Complete
Thymic Formula37 |
Patient
(age, gender not reported) with hepatitis C developed thrombocytopenia (4 x
103/µl) following 5 months use of the dietary supplement, Complete
Thymic Formula. The patient was also taking
naproxen; both were discontinued and “the platelet count returned to
baseline”. Criteria 1 met; insufficient data to assess criteria 2 and 3. |
Substances
with an unlikely association with thrombocytopenia |
|
Bajiaolian28 |
3
patients (Cases 3-5) developed thrombocytopenia (20-56 x 103/µl)
after drinking Bajiaolian infusions, but data on
recovery from thrombocytopenia are not reported, therefore criterion 1 not
met. All 3 patients also had
neurologic abnormalities. |
Kelp38 |
54 F
developed thrombocytopenia (16 x 103/µl) with mucocutaneous
bleeding after 6 weeks of kelp tablets (that contained 1.3µg/g arsenic) and a
multivitamin. Marrow aspirate
demonstrated normal megakaryocytes and dyserythropoiesis. Platelet count recovered to 60 x 103/µl
with treatment with steroids and azathioprine.
Complete recovery not reported; criterion 1 not met. |
Milk39 |
F,
age 10-60 days, born with thrombocytopenia-absent radius syndrome had recurrent
diarrhea, eosinophilia, and thrombocytopenia associated
with 2 periods of cow’s milk feeding. Diarrhea and eosinophilia,
but not thrombocytopenia, recurred with a third introduction of cow’s milk.
Criteria 1 and 4 not met. |
Milk40 |
Infant
M born to mother with ITP had platelet count of 11 x 103/µl at
birth that persisted, in spite of steroid treatment for 11 weeks, when milk
stopped because of diarrhea. Platelet
count increased from 11→150 x 103/µl after 6 days (3 days,
no milk; 3 days half-strength milk). After 10 days on normal milk, platelet
count 30 x 103/µl; 3 weeks after stopping milk, platelet count 200
x 103/µl. Milk resumed at
age 1 year when platelet count platelet count 300 x 103/µl; mother
reported bruising after 2 attempts to resume milk; no platelet counts
reported. The challenges with milk appeared to fulfill criterion 4 but the
diagnosis was uncertain because of the mother’s ITP and the unspecified
nature of the milk products. |
Niacin
(nicotinic acid, vitamin B3)41 |
51 M
(Case 2) developed thrombocytopenia (92 x 103/µl) and leukopenia (2.1 x 103/µl) while
taking 2.5 g/day nicotinic acid for about 3 years. Platelet counts increased
after stopping nicotinic acid, but remained low (118 x 103/µl) 2
months later. Criterion 1 not met. |
Herbal
“Ultimate Colon Cleanse Program TM” 42 |
51 F
developed thrombocytopenia (24 x 103/µl), neutropenia
(24 x 103/µl) and anemia (8.5 g/l) following 30 days of this
product which contained 39 different herbal ingredients. Marrow aspirate
demonstrated aplasia (<5% cellularity).
No follow-up reported. Criterion 1 not met. |
Substances
in reports that were excluded from analysis |
|
Aspartame43 |
Case
1: 10 F developed
thrombocytopenia (1 x 103/µl) and hepatosplenomegaly
that resolved when aspartame stopped. Two recurrences after ingesting
aspartame “with remissions when abstaining from aspartame”, but no data
reported. Case 2: 11 F developed thrombocytopenia after chewing
aspartame gum; resolved when aspartame was stopped; recurred with aspartame
candy. No data reported. Case 3: 61 M developed thrombocytopenia (54 x
103/µl) after drinking diet colas for two years; resolved when
aspartame stopped; “retest trial resulted in an immediate exacerbation”. No
data reported. Case 4: F (age not reported) developed thrombocytopenia
(30 x 103/µl) with hypertension following pregnancy while drinking
diet colas; resolved when aspartame stopped.
There is insufficient data in these small patient descriptions to
assess criteria. |
Chinese
herbal medicine44 |
Patient
(age, gender not reported) developed thrombocytopenia (3 x 103
platelets/µl) with mucocutaneous bleeding. “The
patient had taken an unidentified Chinese herbal medicine.” No additional
data reported. |
Foods
(cocoa, egg, potato, wheat)30 |
5
case reports excluded because of insufficient evidence to assess criteria (Case
3) or platelet counts not less than 100 x 103/µl (Cases 1,
4, 5, 6) |
Garbhapal
ras45 |
F
(age no reported) presented with thrombocytopenia after repeated use of this Ayurvedic medicine that contained multiple metals and
herbal preparations. No platelet count data reported. |
Niacin
(nicotinic acid, vitamin B3)46 |
32 M
developed thrombocytopenia (118 x 103/µl) and liver toxicity after
taking niacin and other vitamins for 10 years. Niacin stopped; other vitamins continued;
platelet count recovered to 193 x 103/µl in 11 days; serum transaminase levels also returned to normal. Excluded because platelet count not <100
x 103/µl. |
Nicotinamide47 |
6
patients on hemodialysis with hyperphosphatemia
treated with nicotinamide, 1000 mg/day; 5 developed
thrombocytopenia (mean values: 188 ± 17 x 103/µl before therapy;
122 ± 41 x 103/µl within 3 months of beginning nicotinamide;
150 ± 9 x 103/µl 10 days after discontinuing nicotinamide.
Excluded because data are insufficient
to meet criterion for platelet count <100 ± 9 x 103/µl. |
Sho-saiko-to48 |
67 M
with hepatitis C developed thrombocytopenia (5 x 103/µl) with mucocutaneous bleeding. Thrombocytopenia improved with
intravenous immunoglobulin and steroid treatment, but platelet counts are not
reported. Exposure one year previously was also associated with
thrombocytopenia (98 x 103/µl). Reported data are insufficient to
assess Criterion 1. |
Traditional
African herbal remedies49
|
5
patients reported who had “complete absence of platelets” on the peripheral
blood film. Excluded because of insufficient evidence to
assess criteria. |
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