Ginkgoaceae

Ginkgo

Ginkgo (maidenhair tree, silver apricot) contains ginkgolides, which inhibit platelet-activating factor, reducing aggregability; this may contribute to bleeding disorders in patients taking Ginkgo . Ginkgo has small beneficial effects in patients with intermittent claudication [ ] and dementias [ , ].

Extracts from the leaves of Ginkgo are marketed in some countries for the treatment of cerebral dysfunction and of intermittent claudication. In a review it was concluded that seven out of eight controlled trials of good quality showed positive effects of Ginkgo compared with placebo on the following symptoms: memory difficulties, dizziness, tinnitus, headache, and emotional instability with anxiety [ ]. For intermittent claudication, the evidence for efficacy was judged unconvincing.

No serious adverse reactions have been noted in any trial. However, Ginkgo has been associated with gastrointestinal complaints, headache, antiplatelet effects, and allergic skin reactions [ ]. Bleeding has been associated with chronic Ginkgo ingestion because of its adverse effects on platelet aggregability, since the ginkgolide constituents of Ginkgo inhibit platelet-activating factor.

Nervous system

Ginkgo can precipitate seizures in patients with well-controlled epilepsy [ ].

• A 78-year-old man and an 84-year-old woman with previously well-controlled epilepsy presented with recurrent seizures. There were no obvious reasons for these events, and the investigator suspected self-medication with Ginkgo extracts. Both patients had started taking Ginkgo within 2 weeks of the start of the seizures. The herbal remedy was withdrawn and both patients remained seizure-free several months later. No other change of medication was made.

The author postulated that 4-0-methylpyridoxine, a constituent of Ginkgo and a known neurotoxin, had caused the seizures.

Hematologic

Bleeding complications have been reported in patients taking extracts of Ginkgo , attributed to the antiplatelet properties of the extracts. In a systematic review of bleeding with Ginkgo 15 reports were found in which there was a temporal association between administration and a bleeding event, including eight episodes of intracranial bleeding [ ]. In 13 cases additional risk factors for bleeding were identified. In only six cases did the bleeding did not recur after Ginkgo was withdrawn. Bleeding times were measured in three patients only and were prolonged.

In a placebo-controlled study in volunteers a special extract of Ginkgo , EGb 761, was compared with placebo; there was no evidence of any effect on tests of primary hemostasis, coagulation, or platelet function [ ]. This particular extract could lack an effect on bleeding tendency, or routine laboratory tests do not reflect in vivo effects under all circumstances, or the previous anecdotal reports have been in patients who are in some way specifically susceptible.

Some studies (but not all) have shown that Ginkgo inhibits platelet aggregation. It could therefore theoretically cause bleeding, particularly when used in combination with other antiplatelet drugs.

A rare case of retrobulbar hemorrhage was associated with chronic intake of Ginkgo [ ].

• A 65-year-old woman was admitted for routine lens implantation. Immediately after injection of 5 ml of local anesthetic, there was sudden proptosis, bruising of her lower lid, pain, and reduced vision. The problems turned out to be caused by retrobulbar bleeding. She had taken 3 × 40 mg of Ginkgo extract daily for 2 years. Her blood count, prothrombin time, and partial thromboplastin time were normal.

A few new cases of bleeding have been reported in patients undergoing a variety of surgical interventions after taking extracts of Ginkgo regularly [ ]. Contrary to previous belief, this augmented bleeding tendency may not be related to inhibition of platelet-activating factor by ginkgolides. The concentration required to inhibit PAF-mediated aggregation of human platelets exceeds by more than 100 times the peak values measured after the oral administration of Ginkgo leaf extracts in recommended doses [ ].

• A 59-year-old man developed bleeding complications after liver transplantation while taking Ginkgo supplements [ ]. Postoperatively, he developed large hematomas in the subphrenic space and near the porta hepatis. They were drained and his hematocrit fell to 21%. Three weeks later he complained of blurring in the right eye, and a vitreous hemorrhage was diagnosed. He then admitted to taking an unknown amount of Ginkgo , which was withdrawn. Subsequently, no further bleeding episodes occurred.

• A 78-year-old man developed progressive muscular weakness after a fall [ ]. A CT scan showed a subdural hematoma. He had taken 150 mg of Ginkgo extract.

• A 56-year-old man had a stroke without apparent risk factors [ ]. A CT scan confirmed a right parietal hematoma. He had not taken any medications, except for a Ginkgo extract (3 × 40 mg/day) which he had started 18 months before.

• A 34-year-old woman had a laparoscopic cholecystectomy and started bleeding into the surgical wound postoperatively [ ]. This led to a fall in hemoglobin from 16.5 to 12.4 g/dl. She was given blood transfusions and recovered uneventfully.

• A hyphema led to temporarily impaired vision in a man who had taken Ginkgo for 2 weeks; no other cause was found; the lesion regressed after withdrawal and did not recur [ ].

• A spontaneous cerebellar bleed occurred in a man who had taken Ginkgo [ ].

In each case the authors believed that self-medication with Ginkgo had caused the bleeding through its effect on platelets. In some cases another factor that implicated the extract was the absence of recurrence after withdrawal, although this is a weak argument.

Spontaneous bilateral subdural hematomas and increased bleeding time have been associated with chronic ingestion of Ginkgo (120 mg/day for 2 years) [ ].