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A153
Post-tonsillectomy hemorrhage associated with nutraceutical use
#397
Brianna K. Crawley, MD; Aaron R. Morrison, M.D.; Garth T. Olson, MD; David Garcia, M.D.; Mark L. Beauchamp, M.D.
Departments of Internal Medicine (Division of Hematology-Oncology) & Surgery (Division of Otolaryngology)
University of New Mexico School of Medicine, Albuquerque, NM.
ABSTRACT
REPORT OF A CASE
Objective: to report a case of serious post-operative bleeding, the first in the
otolaryngologic literature, associated with the use of forskolin, and to
review its activity.
A 25-year-old man was referred to otolaryngology as he had experienced 6-9 episodes of non-streptococcal
pharyngitis each year for the preceding four years. There was no evidence of sleep-disordered breathing or
tonsillar asymmetry. His other medical problems included asthma and hypospadias for which he had undergone
multiple surgeries, the most recent of which preceded his presentation by six months. He denied any history of
unusual bleeding after his prior surgeries and no family history of bleeding was elicited by any of his care
providers. The patient underwent outpatient tonsillectomy without complication. On the evening of his third postoperative day, the patient was awakened from sleep coughing up small amounts of bright red blood. The patient
was brought to the emergency room where he was confirmed to have stable vital signs and the presence of bright
red blood in the left tonsillar fossa. He denied non-compliance with diet and activity instructions, and denied postoperative usage of NSAIDs. He was taken to the operating room where electrocautery was utilized to control his
hemorrhage. Upon induction of anesthesia and placement of the mouth gag, his bleeding appeared to increase in
the left tonsillar fossa. After several areas of bleeding had been controlled on the left, brisk new bleeding was
noted in the right tonsillar fossa, which was subsequently controlled.
Following the procedure, the patient was extubated and awakened without incident, but it was noted upon
transfer to his gurney that he was wearing a drug-delivery patch on his right thigh (Image 1). The patch was
determined to be a Nexagen USA product distributed over the counter, called Jen Fe Next. This is a transdermal
patch containing forskolin, chromium poly-nicotinate, epicathechin, black pepper, and guarana. The patch was
removed and the patient was admitted for 24-hour observation and subsequently discharged home. On his second
post-operative day four, the patient again began to bleed orally. He bled several times throughout the day before
returning to the ED and shortly thereafter, was taken to the operating room. Initially blood emanated from the right
superior and mid tonsillar fossa before diffuse bleeding was elicited from the left tonsillar fossa, as well.
Hemostasis was achieved with cautery and the patient was awakened, recovered, and discharged home .
Laboratory results obtained throughout the post-operative period demonstrated that liver function tests and blood
chemistries were entirely within normal limits. The prothrombin and activated partial thromboplastin times were
normal. The patient’s hematocrit remained stable at 40% and his platelet count rose from 289 to 333 x 103/μl. The
patient returned for follow-up two days after his surgery and he had experienced no further bleeding.
Study design: This is the report of a case and associated literature
concerning the hematologic activity of forskolin.
Methods: A 25-year-old otherwise healthy, non-coagulopathic male
underwent tonsillectomy for chronic tonsillitis, suffering two atypical posttonsillectomy hemorrhages requiring operative control. Subsequent
examination revealed that the patient had been wearing the transdermal Jen
Fe Next patch on his right lower extremity. Investigation into the
constituents of this energy-enhancing patch revealed the presence of black
and white pepper, chromium, guarana, and forskolin.
Results: Forskolin, a diterpine derived from the Indian plant, Coleus
forskohlii, activates cell membrane adenylate cyclase which, in turn
converts cAMP to ATP. Its role in the cAMP signaling cascade effects many
changes in the body, from increasing cardiac contractility to influencing
differentiation of mesenchymal cells. It also inhibits platelet activation, an
action that may be potentiated by other platelet inhibitors and
anticoagulation agents.
Conclusions: Forskolin is marketed without regulation as a weight-loss agent
and energy-enhancer. It should be discontinued prior to undergoing
surgery, for at least two weeks. This report serves as reminder that all
forms of “nutraceuticals”, herbal supplements, and over-the-counter
“alternative” medications should be completely reviewed with a patient
during preoperative evaluation.
Courtesy PubChem
Common name
forskolin
Molecular formula
C22H34O7
Molecular weight
410.50 g/mol
IUPAC name
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10btrihydroxy-3,4a,7,7,10a-pentamethyl- 1-oxo-5,6,6a,8,9,10hexahydro-2H-benzo[f]chromen-5-yl] acetate
Synonyms
Colforsin, Coleonol, colforsina, colforsine, colforsinum,
Boforsin, Colforsine [French], Colforsinum [Latin],
Colforsina [Spanish]
CONCLUSIONS
INTRODUCTION
Post-tonsillectomy hemorrhage is the most significant, potentially lifethreatening, complication of tonsillectomy. Investigators have sought
predictors in order to anticipate which of the 500,000 patients who undergo
tonsillectomy each year in the United States possess a risk for this serious
complication. Post-operative hemorrhages are classified as primary, generally
defined as occurring within 24 hours of the initial surgery, or secondary,
usually occurring between postoperative days 5-10(2). Primary hemorrhages
are principally attributed to surgical technique and tissue trauma during the
procedure, whereas secondary hemorrhages are ascribed to other factors,
including age and gender of the patient, season, intraoperative injection and
topical application of vasoconstrictors. Medications with known
antithrombotic properties (e.g., warfarin, heparin, low molecular weight
heparin) are routinely discontinued prior to surgery in an effort to minimize
bleeding risk. Here we describe a case of atypical secondary posttonsillectomy hemorrhages attributed to the use of transdermal forskolin, a
nutraceutical product marketed for weight loss. This case highlights the
necessity for surgeons, anesthesiologists and hematologists to inquire about
the use of herbal or “alternative” substances that might affect the coagulant
potential of the blood prior to invasive procedures.
• This is the first report in the literature of a healthy patient requiring operative control on two occasions for
uncomplicated tonsillectomy while using forskolin. The reported incidence of post-tonsillectomy hemorrhage
varies from below 2 to 20%; 4.5% in Blakeley's meta-analysis(1).
• Screening laboratory tests can be normal both in patients with bleeding disorders as well as in patients taking
antithrombotic agents(4) and are poor predictors of post-tonsillectomy hemorrhage(5).
• Forskolin causes vasodilatation and a transient decrease in systolic blood pressure while increasing heart rate and
contractility. It's antithrombogenic effect is due to direct stimulation of adenylate cyclase which converts ATP to
cAMP, inhibiting platelet activation in whole blood(7). Its activity is potentiated by other platelet inhibitors(8), and
cyclooxygenase inhibitors which are often used for post-operative pain control.
• Forskolin is marketed as a “safe” alternative to most other weight loss drugs because a 2005 randomized, doubleblind, placebo-controlled study funded by the manufacturer indicated that Jen Fe Next has a negligible effect on
heart rate, blood pressure, and respiratory rate(6). A month’s supply is sold for $69.95. The product packaging
does not incorporate any warning concerning increased risks of bleeding or the necessity of disclosing the usage
of this patch to a physician prior to surgery .
• Many herbal supplements and over-the-counter “alternative” medications have been associated with perioperative
bleeding(9).
• The American Society of Anesthesiologists recommends stopping all herbal medications two weeks prior to any
operation(10).
References
1 Blakley BW. Post-tonsillectomy bleeding: how much is too much? Otolaryngol Head Neck Surg. United States, 2009, 288-90.
2 Windfuhr JP, Chen YS. Post-tonsillectomy and -adenoidectomy hemorrhage in nonselected patients. Ann Otol Rhinol Laryngol. 2003;
112: 63-70.
3 Collison PJ, Mettler B. Factors associated with post-tonsillectomy hemorrhage. Ear Nose Throat J. 2000; 79: 640-2, 4, 6 passim.
4 Windfuhr JP, Chen YS, Remmert S. Unidentified coagulation disorders in post-tonsillectomy hemorrhage. Ear Nose Throat J. 2004; 83:
28, 30, 2 passim.
5 Zagolski O. [Post-tonsillectomy haemorrhage--do coagulation tests and coagulopathy history have predictive value?]. Acta
Otorrinolaringol Esp. Spain: 2009 Elsevier Espana, S.L, 2010, 287-92.
6 Clinical Study Summary, Jen Fe Next Patch. NexagenUSA , LLC, 2006.
7 Christenson JT, Thulesius O, Nazzal MM. The effect of forskolin on blood flow, platelet metabolism, aggregation and ATP release.
Vasa. 1995; 24: 56-61.
8 Srivastava KC. Evidence for the mechanism by which garlic inhibits platelet aggregation. Prostaglandins Leukot Med. 1986; 22: 313-21.
9 Javed F, Golagani A, Sharp H. Potential effects of herbal medicines and nutritional supplements on coagulation in ENT practice. J
Laryngol Otol. 2008 Feb;122(2): 116-9.
10 Hodges PJ, Kam PC. The peri-operative implications of herbal medicines. Anaesthesia. England, 2002, 889-99.