A Randomized, Double Blind, Placebo-Controlled, Cross-over Study to Evaluate the Haemostatic Effects of Three Commonly Used Traditional Herbal Medicines, (Curcuma Longa, Angelicae Sinensis and Panax Ginseng)and Their Interactions with Aspirin

Background:

The use of herbal medicine is prevalent worldwide. Curcuma longa(CL), Angelicae sinensis (AS) and Panax Ginseng(PG), commonly known as Tumeric, Dong Quai and Ginseng respectively, are frequently used herbal medicines but were cautioned to have "blood thinning" effects and generally advised not to be taken with anti-platelets and anticoagulants. However, their effects on haemostasis and interaction with aspirin are unknown and occurrence of bleeding symptoms rarely documented.

Aim:

To investigate the in-vivo effects of CL (Tumeric), AS (Dong Quai) and PG (Ginseng) with and without aspirin on platelet function and thrombin generation.

Methods:

A randomized, double-blind, placebo-controlled crossover study was carried out for each herb. 75 healthy volunteers were recruited with 25 assigned to each of the 3 herb-groups (Tumeric, Dong Quai and Ginseng). The study subjects were first assigned to {herbal only} for 3 weeks, followed by a 2-week wash out period, after which they were randomly assigned to {aspirin + herbal} or {aspirin + placebo} for 3 weeks. Following another 2 week washout, the subjects crossed over to receive {aspirin + placebo} and {aspirin + herbal capsule} respectively for next 3 weeks. Dosages of herbs are Tumeric 500mg, Dong Quai 1000mg or Ginseng 1000 mg and aspirin 100mg once daily.

Blood samples were analysed at baseline and after each intervention phase for full blood counts (FBC), PT/aPTT, platelet function tests (PFT) and thrombin generation assays. PFT measured platelet aggregation using light transmission in platelet-rich plasma, induced with Adenosine diphosphate (ADP), Arachidonic acid (AA), Collagen, Epinephrine and Ristocetin. Thrombin generation (TG) assays on platelet poor plasma measured Endogenous Thrombin Potential(ETP), Time to peak (ttPeak), Peak height and Lag time (LT).

All clinical events experienced by the subjects were recorded during each phase.

Non-parametric statistical analysis was carried out through Wilcoxon-signed rank tests (SPSS Version 21, USA) and deemed significant if p<0.05.

Results:

FBC, PT and aPTT were normal at baseline and for all 3 phases in all 3 herbs, with and without aspirin.

For PFTs, Tumeric resulted in impaired AA-induced aggregation in 5, Dong Quai in 2 and Ginseng in 1 subjects. 2 other subjecys in Dong Quai group and 1 in Ginseng group also had reduction in Epinephrine-induced aggregation. Aspirin, as expected suppressed platelet aggregation to AA, Epinephrine, collegen and ADP but this was not further suppressed by concomitant administration of any of the 3 herbs.

All TG assays were normal in all 3 herbs with one exception where Tumeric showed a significant proplongation in LT over baseline.

Aspirin reduced ETP and peak height which was not further aggravated by concomitant administration of any of the 3 herbs.

There was no significant clinical events reported, in particular no bleeding complications.

Conclusion:

Overall, there was no meaningful nor severe suppression of PFTs. Only a few subjects demonstrated decreased % platelet aggregation while on one of these herbs. In each of these subjects, this was restricted to platelet aggregation by 1 inducer and normal for the rest. Hence, the overall platelet hemostatic function should not be significantly compromised as to cause clinical events. Importantly, addition of herb did not further impair PFTs due to aspirin alone

TG assays are more sensitive to subtle changes in global plasma hemostatic functions compared to conventional clotting times. Apart from a prolongation of LT seen in the Tumeric group, TG assays were largely unaffected by these herbs, indicating that these 3 herbs did not significantly affect the global plasma hemostatic function. Importantly, suppressed TG assays by aspirin was not further impaired by concomitant administration of any of the 3 herbs with aspirin, inferring that the herb addition to aspirin did not further impair hemostatic functions.

The widely held notion of "blood thinning" properties of Tumeric, Dong Quai and Ginseng were not demonstrated through PFT and TG assays. The concurrent usage of aspirin with these herbs individually did not result in compromise of hemostatic functions and was safe with no clinical bleeding. These findings will help mitigate the anxiety over bleeding complications of these 3 herbs, especially for patients who are on aspirin. Larger studies with more numbers will be required for further verifications.