TREATMENT OF ITP WITH CHINESE MEDICINE
Idiopathic Thrombocytopenic Purpura (ITP) is a somewhat archaic term for a condition of low platelets (thrombocytes). Idiopathic means that the cause is unknown; with advances in modern technology, a substantial amount has been learned about the causes. While one may not be able to definitively point to all the causative factors and agents involved in any one patient, as is the case with many diseases, now it is often possible to describe much of the etiology and pathology of ITP quite accurately. Purpura refers to the splotches seen on the skin where capillaries have leaked blood to yield a bruise or many red or purple petechia (flat, pin-head sized spots). However, with careful monitoring of the platelet counts and appropriate treatment when the platelets approach a low level, people with this disease may rarely show any such symptom. Nonetheless the moniker ITP has stuck in the medical literature and will, as a result, continue to be used here.
The deficiency of platelets has two basic origins: autoimmune attack against platelets (primary ITP) and bone marrow disorder (usually: secondary ITP). In primary ITP, the bone marrow produces platelets as fast as usual (at least in the early stages of the disease), but even before they have a chance to mature, they are taken out of circulation. An antibody of the G series (the type involved in several autoimmune diseases), IgG, attaches to the platelets and marks them to be removed from circulation. It is likely that individuals who suffer this disease have a genetic propensity to get it, and that a viral disease triggers it. Many autoimmune disorders have this characteristic. In such cases, treatment is often aimed at inhibiting the immune system with corticosteroids (e.g., prednisone). If necessary, the spleen is removed (splenectomy) in order to both reduce the production of anti-platelet antibodies and to slow the clearance of the platelets from the system (the spleen filters out the platelet-immune complex). A suitable name for this disease is autoimmune thrombocytopenia.
Autoimmune thrombocytopenia occurs mostly in children and young adults (typically before age 30), though it can rarely occur later in life. Many times, it manifests as an acute disease, lasting a few weeks and then clearing up completely. It might recur again later after another viral infection or with reactivation of a chronic virus, but eventually it ceases to be a problem in the majority of children who experience it. The acute manifestation can usually be controlled by a course of therapy using steroids to inhibit the immune response for a period of several weeks. Chronic autoimmune thrombocytopenia develops in a small percentage of patients. In that case, steroid therapy eventually fails (due to the side effects from prolonged administration). Until recently, the main therapy for chronic autoimmune thrombocytopenia has been splenectomy, which is sometimes curative, but at least reduces the disease severity. More recently, intravenous (IV) infusion of normal IgG (hence the treatment initials: IVIG) to replace the body’s anti-platelet IgG has been tried with some success and may replace splenectomy for some patients. IVIG has also been proposed as an alternative to the initial therapy with prednisone. Other therapies are also being developed. Medical opinion appears to be leaning towards finding an alternative to splenectomy.
A defect in the production of platelets by the bone marrow, resulting in ITP, can occur as part of a general bone marrow dysfunction, in which both red and white blood cells are also produced insufficiently. Or, it can occur secondary to leukemia, in which the stem cells that yield white blood cells proliferate and crowd out the stem cells that produce platelets and red blood cells (yielding high white cell count and low RBC and platelet counts). Low platelets can also occur as the result of certain medical treatments, such as chemotherapy for cancer. Some chronic diseases that affect the immune system, such as HIV, hepatitis C, and systemic lupus, may yield a combination of inhibited platelet production and shortened time that platelets persist in the blood, with resulting ITP. For these situations, the platelet deficiency is called secondary ITP, because there is something else going on first or at the same time that yields the clinical result. The platelet disorder that may be resolved if the other disease process or medical treatment is removed.
CHINESE HERB THERAPY
In China, both primary and secondary ITP are noted in the medical literature, though primary ITP is the main subject of the reports and is the object of the current article. Treatment, other than Western medical therapies, is based on using Chinese herbs: reports of acupuncture therapy are rare or non-existent. The Chinese herbal therapies vary markedly from one physician to the next and sometimes among different patients, depending on the differential diagnosis.
The general theory of treating primary ITP, at least as it occurs in children and young adults, is that there is a heat syndrome causing the blood to escape the vessels. Therefore, clearing heat is the primary concern. Also, since bleeding is the symptom, treatment with hemostatic herbs, especially those which are also cooling, is standard procedure. There are two major causes of the blood heat, one being an excess heat syndrome that might be associated with a viral infection and the other is a yin deficiency syndrome, which may arise from nutritional deficits, prior diseases, or inherent factors. In the case of the yin deficiency syndrome, nourishing yin (tonification) is deemed the most important aspect of therapy.
Except in the cases of dominant excess syndrome, there are usually some herbs included in the ITP treatment to tonify the spleen, owing to the concept that the spleen restrains the blood within the vessels and the spleen helps produce new blood and replenishes the yin. In patients who show an evident spleen qi deficiency syndrome, the qi tonics may become a major part of the therapy, with less emphasis on clearing heat or nourishing yin. In cases where there is prolonged disease, the deficiency of qi often extends to a deficiency of the kidney and additional tonic therapies may be added. For most cases of secondary ITP, the theory is that the bone marrow is inadequate to produce the cells and this is addressed by tonifying the kidney (to invigorate marrow), nourish the liver (to increase the blood storage), and tonify the qi to help produce blood and essence.
Within the theoretical framework, a number of different herbs are selected. Among the most commonly used herbs for primary ITP are the ones listed in Table 1.
Table 1: Herbs Commonly Used in the
Treatment of Primary ITP in Four Categories.
Note that some of the herbs are classified differently than the standard Materia Medica categories.
|
Heat Clearing |
Hemostatic |
Qi Tonifying |
Liver Nourishing |
|
rehmannia, raw |
agrimony |
astragalus |
tang-kuei |
|
gardenia |
imperata |
licorice |
gelatin |
|
moutan |
eclipta |
codonopsis |
tortoise shell |
|
red peony |
rubia |
hoelen |
ho-shou-wu |
|
salvia |
san-chi |
atractylodes |
lycium |
|
lithospermum |
biota tops |
jujube |
millettia |
|
isatis leaf |
sanguisorba |
dioscorea |
cuscuta |
Within
these four groups are herbs that vitalize blood circulation (red peony, moutan,
salvia, san-chi, tang-kuei, millettia), which is another method of therapy that
has been proposed, to be described later in this article.
According to the Chinese medical reports, administration of decoctions made with the above-mentioned herbs in appropriate combinations will raise the platelet levels in patients with persistent ITP, often to an acceptable level, though only rarely will they return to the normal range. Normal platelet levels are usually defined as 150 or above (billions of platelets per liter of blood). According to the clinical reports, the use of herbs will often raise the platelets from the unacceptable level (below 50, at which bleeding that is difficult to stop may occur) to an average of about 75–85. Some patients described in the literature had their platelet levels reach over 100 and very few attained a completely normal level.
Primary ITP spontaneously resolves at a rate that is better with younger age; overall only about 20% of cases are persistent and refractory to standard treatments. If the Chinese herb therapy can raise the platelets to an acceptable level, the condition may stabilize for most individuals within a few days or weeks; if there is a relapse, then the same kind of treatment might be applied again.
For persisting ITP, which is a greater concern because of the difficulty of finding suitable modern medical therapy, Chinese herbal treatment will usually be administered for several weeks or months. In the Chinese clinical evaluations, the success of the therapy for the chronic disease is often monitored in terms of the relapse rate after the herbs have been stopped. Herbal therapy is reported to be of some benefit to nearly all patients, though the degree of improvement varies markedly and the relapse rate (within a year, if monitored that long) is often high.
Virtually all studies of ITP treatment include a control group that receives steroids, usually at high doses (about 45 mg/day). The Chinese herbal therapies are claimed to be superior in their results and lacking in the characteristic side effects of the drugs. Because the randomization and matching of patients in the herb treatment and control groups is usually not clear in the Chinese reports, the value of the comparisons can be questioned. Further, it is unclear in the reports to what extent the corticosteroid dosage is manipulated according to methods commonly recommended in modern clinical practice. Therefore, in the summaries of the medical journal articles presented here, the results for the control group are usually not indicated. The main purpose of conveying the information presented in the Chinese journal articles is to illustrate the selection of herbs, the dosage (described in a separate section of this article), duration of therapy, time to obtain changes in platelets, and the claimed results of therapy.
Much of the work done on ITP in China has been carried out at the Shanghai College of Traditional Chinese Medicine. This very large college has a number of affiliated hospitals where studies can be carried out. There are also other medical universities in Shanghai that cooperate with the TCM College in conducting some of the studies.
CLINICAL REPORTS INVOLVING DIFFERENTIAL DIAGNOSIS
The majority of the recent Chinese clinical reports describe trials involving a single herb formula that may be modified slightly according to presenting conditions. However, outside of the trial setting, differential diagnosis is the rule, so this aspect is presented first.
A study of patients with ITP according to their traditional Chinese diagnostic category was carried out by the Shanghai College of Traditional Chinese Medicine and published in 1991 (1). It involved 103 patients (75 female) with an age range of 12–58 years. The differentiation went this way:
Table 2: Division of 103 Patients with ITP
into Four Diagnostic Categories
with Group Characteristics: Age, Disease Duration (years), IgG Levels,
and Platelet Counts.
|
Differentiation Group |
Number of Patients |
Mean Age |
IgG |
Platelets |
|
Qi Deficiency |
20 |
24 (3) |
115 |
29 |
|
Blood heat |
22 |
26 (4) |
63 |
44 |
|
Yin deficiency |
43 |
36 (7) |
80 |
39 |
|
Yang deficiency |
18 |
40 (12) |
112 |
34 |
The qi-deficiency group was described as a spleen-deficiency type; the blood-heat type was described as an excess syndrome, the yin-deficiency type was described as a syndrome secondary to chronic spleen deficiency; and the yang-deficiency type was said to be a deficiency of spleen and kidney. The control group of non-ITP patients involved 20 individuals with a similar ratio of the two sexes, mean age of 30, and similar range of ages as the differentiation group. The control group was included for obtaining relative blood values.
Looking at the mean values for patient age and disease duration only, it can be seen that the disease generally started before age 30 and falls in the category of chronic ITP. According to the analysis, the most common type of the disease is a yin-deficiency syndrome. Both the blood-heat and yin-deficiency syndromes can be described as being of the general heat-type of ITP, accounting for 2/3 of the cases. The deficiency of qi and of yang correlated with the most dramatic elevation of IgG. In the report, there were also slight elevations noted in IgA and IgM for all the ITP patients, but not sufficient to explain the disease manifestation. The platelet numbers did not vary much from one group to the next (the control group level is quite low to begin with, suggesting that these numbers are not directly comparable to those from other laboratories). The report also presented information on T-cell subsets, but there were no significant differences in their numbers or ratios among the different groups, including the controls.
In 1991, a research team at the Shanghai College of TCM presented a formula for ITP (2) with the following ingredients: astragalus, codonopsis, tang-kuei, moutan, agrimony, isatis leaf, perilla stem, licorice, raw rehmannia, cooked rehmannia, and eclipta. The trial group of 36 patients receiving this formula ranged in age from 13–60 years. Treatment time was at least three months (average 110 days) and it was reported that all but 3 of the patients had improvement of symptoms. The average increase of platelets was from 38 to 79, and the average decrease in IgG was from 74 to 32. The formula included herbs for tonifying qi (astragalus, codonopsis, licorice), nourishing yin (rehmannia and eclipta), clearing heat (moutan, isatis leaf, raw rehmannia), and inhibiting bleeding (agrimony and eclipta). The use of perilla stem (zisugeng) is unique; it is not found in other formulations for ITP (see key herbs section, below).
This basic formula was later adopted by another group at the same college using differential diagnosis and treatment (3). According to their report, there were four categories of disorder and treatments, but the data for all the patients were then pooled for analysis rather than divided by group. The above-mentioned formula was adopted for the yin-deficiency group and modifications of it were used for the other groups as shown in Table 3.
Table 3: Differential Therapy for ITP at the Shanghai College of
Traditional Chinese Medicine.
|
Differentiation Group |
Herb Formula |
|
Qi Deficiency |
astragalus, codonopsis, tang-kuei, moutan, agrimony, isatis leaf, perilla stem, licorice, etc. |
|
Blood heat |
buffalo horn, raw rehmannia, red peony, moutan, eclipta, trachycarpus, rubia, isatis leaf, perilla stem, licorice, etc. |
|
Yin deficiency |
astragalus, codonopsis, tang-kuei, moutan, agrimony, perilla stem, licorice, raw rehmannia, cooked rehmannia, eclipta, etc. |
|
Yang deficiency |
astragalus, codonopsis, tang-kuei, moutan, agrimony, perilla stem, licorice, raw rehmannia, cooked rehmannia, eclipta, epimedium, cuscuta seed, etc. |
As in the previous report on differentiation of the syndrome, the most common form was the yin deficiency type and the combined heat syndromes (yin deficiency and excess heat as blood heat) comprised 2/3 of the cases. All of the formulas included moutan, perilla stem, and licorice, and all but the qi-deficiency formula included raw rehmannia, while all but the blood-heat formula included astragalus, codonopsis, tang-kuei, and agrimony. For the kidney-deficiency cases, the formulas included cooked rehmannia and eclipta. The herb formulas were prepared as a liquid syrup and consumed three times per day. A control group was given prednisone; treatment time was at least three months. Side effects of the herb therapy were limited to a few cases of loss of appetite and thin stools. The prednisone group presented side effects in half the patients including the typical increase of body weight and upset stomach. Mean values for platelets in the herb group rose from 38 before treatment to 68 after treatment. The control group had nearly identical mean values. Some patients were treated for six months to a year, and the platelet values continued to rise slowly in the herb treatment group, reaching 75 at six months and 88 at one year. The IgG values in the herb treatment group declined from 99 at the beginning of treament to 41 at the end of treatment (three months); the values for the control group were similar. The authors claimed that the best therapeutic responses were among the patients suffering from qi deficiency and yin-deficiency syndromes.
In a more recent study (4) conducted Shenyang (rather than Shanghai), patients were simply divided into two groups, one being the common yin-deficiency type with heat symptoms (30 patients), and a spleen-kidney deficiency group, involving spleen qi deficiency and kidney/liver yin deficiency (31 patients) with pallor signs The treatments were:
· Yin deficiency type: codonopsis, cuttlebone, rehmannia, moutan, artemisia, gelatin
· Kidney/Spleen deficiency type: ho-shou-wu, lycium, ginseng, astragalus, tang-kuei, san-chi.
The herbs for the yin deficiency type were made as a decoction with 10–15 grams of each herb (except cuttlebone at 25 grams). The herbs for the kidney/spleen type were made into tablets, given 4–6 each time, three times daily, with 380 mg/tablet. A control group was treated with prednisone. At the end of four weeks, 35 of the herb treated patients had some level of improvement; after one year, 56 of the 61 herb treated patients had some degree of improvement.
According to the report, the time from starting herb therapy until the platelet counts started to rise was, on average, 24 days (compared to 8 days for the prednisone group), and it took three months for the herb treated group to reach its maximum level of platelets, compared to 22 days for the prednisone group. After one year of therapy, the herbs were stopped. The relapse rate for the patients who did best in the herb treatment group (in terms of platelet improvements and corresponding improvements in symptoms), of which there were 24, was examined. There were 11 patients that remained stable (no relapse), while 13 patients had a relapse (between 3.5 and 11 months after stopping the herbs).
A similar pair of differential groups was described in an earlier study
(1987) with the following formulas (5):
· Yin-deficiency type: tortoise shell, oyster shell, phellodendron, imperata, biota tops, sanguisorba, lycium, eucommia, scute, lycium bark, gardenia, san-chi.
· Kidney/Spleen-deficiency type: astragalus, imperata, schizandra, codonopsis, hoelen, tang-kuei, atractylodes, lycium gelatin, san-chi.
These formulas were ground into powder, made into pills and taken in the amount of 5 grams of herb powder twice per day. The patients had been treated with Western medicine without success. The results from the two groups were pooled, and it was claimed that all patients showed some improvement.
These
studies that involve differential diagnosis do not clearly demonstrate that
such differentiation is essential to the outcomes. All of the formulas include herbs that clear heat, inhibit
bleeding, and nourish yin. While kidney
deficiency is mentioned in the reports, there is very little reliance on
kidney-yang tonic herbs in the prescriptions.
Even when kidney-tonic herbs are included (such as the yin-nourishing
rehmannia and eclipta or the yang tonics eucommia, cuscuta, and epimedium), the
ones selected are also traditionally classified as nourishing the liver, so
that a liver-nourishing principle would describe the basis of treatment equally
well.
CHINESE CLINICAL REPORTS WITH BASE FORMULAS THAT MAY BE MODIFIED
There are a substantial number of reports in the Chinese medical literature published during the 1980’s and early 1990’s describing treatments for ITP. They usually present a basic formula that can be modified slightly for individual presentation of symptoms; the modifications may not be directly relevant to the experience of ITP. Due to concerns about the quality of clinical testing and reporting, and due to the fact that most of these reports are available only in summary or abstract form, only the most basic information is presented here in table format to illustrate the nature of the prescriptions used.
Table 4: Clinical Reports
on Herbal Therapy for ITP.
The majority of these reports were summarized in The Treatment of Difficult and Recalcitrant
Diseases with Chinese Herbs (5), translated from Compendium of Secret Chinese TCM Formulas, a three-volume book of
medical report summaries first published in 1989. In a few cases, the study reported here was available only as an
abstract in Abstracts of Chinese Medicine (a quarterly journal) or other source. A total of 600 patients were involved in the
herbal treatments; most studies also had a control group of about 20 patients
using steroids.
|
Author (Citation) |
Formula Ingredients;
Modifications |
Comments |
|
Sha
Bingyi (5) |
agrimony, jujube, oyster shell, licorice, forsythia, salvia |
Symptom improvement reported after 5 days, substantial platelet increase after 10 days. |
|
Yang Jin
(5) |
agrimony, sanguisorba, codonopsis, atractylodes, cornus, salvia, astragalus, shou-wu, rehmannia, scrophularia, licorice, phytolacca (this herb is boiled a long time to reduce toxicity); for yin deficiency, remove codonopsis and atractylodes, add phellodendron, anemarrhena, moutan, tortoise shell; for qi deficiency, add hoelen, jujube |
All but 2 patients improved; after treament was concluded there was no relapse during a six month follow-up. |
|
Su Eryun
(5) |
millettia, agrimony, licorice, tang-kuei, ixeris, biota tops, astragalus, raw rehmannia; for yin deficiency, increase rehmannia, decrease astragalus; for blood stasis, double the millettia dose |
Improvements claimed for 25 of the 33 patients. |
|
Zhang
Yisheng (5) |
gardenia, raw rehmannia, red peony, moutan, tang-kuei, astragalus; for heavy bleeding, add lithospermum, rubia, agrimony; for anemia, add gelatin, millettia, ho-shou-wu; for yin deficiency add yu-chu, glehnia, ophiopogon, imperata; for qi deficiency, add codonopsis, atractylodes, hoelen, dioscorea |
Bleeding brought under control in all cases. |
|
Deng Youan, et al. (5) [31] |
cnidium, salvia, tang-kuei, carthamus, millettia, red peony, leonurus; for qi deficiency add codonopsis, astragalus, dioscorea; for weak digestion, add atractylodes, hoelen, crataegus, malt, citrus, magnolia bark; for kidney yang deficiency, add morinda, cuscuta; for kidney yin deficiency add ligustrum, lycium |
For treatment of chronic platelet deficiency but not for use when the platelets are very low, causing purpura. Average treatment time was one month. IgG was greatly decreased after treatment. A few patients had no relapse for at least 6 months. |
|
Liu
Shaoxiang (5) |
agrimony, rumex, millettia; for qi deficiency add astragalus and codonopsis; for blood deficiency add tang-kuei and gelatin; for weak digestion, add atractylodes |
Secondary ITP was mainly treated, with chemotherapy and radiation the cause. Reported platelet restoring effect took place in 5 days on average. |
|
Han
Weigang and Qi Rongfang (6) |
buffalo horn, raw rehmannia, moutan, red peony, isatis leaf, paris, agrimony, lithospermum; for blood heat, add fresh lotus node; for qi deficiency, add astragalus; for yin deficiency, add ho-shou-wu |
24 of 27 patients reported to respond well with 12 days treatment. |
|
Gao
Xiang, et al. (7) |
astragalus, codonopsis, hoelen, atractylodes, rehmannia, tang-kuei, psoralea, drynaria, cuscuta; for nose bleed add agrimony; for purple petechia, add salvia; for poor appetite, add red atractylodes and citrus |
30 day treatment course (could be extended), 31 of 35 patients showed some improvement. Platelet counts increased from average of 52 to 79. |
|
Cui Shuzhen, et al. (8) [100] |
cnidium, salvia, red peony, millettia, leonurus; digestive disturbance, add crataegus, malt, citrus, atractylodes, malt; serious bleeding, add raw rehmannia, moutan, and cirsium |
See Dong Youan study above, with nearly identical in treatment. This study involved children 6 months to 13 years with persistent ITP. One month treatment course; platelet increased from 26 to 109. All patients “improved.” |
|
Peng Xiang, et al. (9) |
astragalus, codonopsis, atractylodes, licorice,
rumex, scute, coptis, frankincense, myrrh, tribulus |
Improvements noted in 20 of 24 patients. |
|
He
Guoxing and Wang Xiuhua (10) |
rehmannia, deer antler gelatin, tortoise shell gelatin, ho-shou-wu, codonopsis, tang-kuei, astragalus, epimedium, salvia, rubia, ligustrum, licorice |
Improvements noted in 50 of 52 patients. |
|
Zhang
Gaochen and Mao Yuwen (11) |
tang-kuei, agrimony, moutan, gardenia, san-chi, biota tops |
Treatment time was 9–36 days, and mean platelet count rose from 58 to 78; 2/3 of patients improved. |
|
Li
Zhiyuan (12) |
astragalus, codonopsis, tang-kuei, nutmeg, rehmannia, cinnamon bark, aconite, dioscorea, agrimony, gelatin |
20 of 23 patients improved. No relapse during 3–6 month follow-up. |
|
Duan Yu,
et al. (13) |
bupleurum, codonopsis, scute, licorice, jujube, equisetum, pyrrosia, verbena, rehmannia |
Average treatment time was 4 weeks; an IV drip of hemostatic drugs and vitamins was given for an average of 3 day. Mean platelets increased from 19 to 121. |
|
Xiang
Renpu (14) |
raw rehmannia, agrimony, ho-shou-wu, lycium, psoralea, cistanche, salvia, red peony, rubia, tang-kuei, moutan, cornus |
All but 1 patient has some improvement, but relapse was common. Platelet count increased by an average of 32. |
BLOOD STASIS HYPOTHESIS FOR CHRONIC AUTOIMMUNE THROMBOCYTOPENIA
It has been proposed by some authors that the symptomatic manifestation of purpura signifies a blood stasis syndrome and that the chronic disease, in particular, should be treated mainly by vitalizing blood circulation. One of the first descriptions of this approach was from the Heilongjiang College of Traditional Chinese Medicine, published in 1981 and then republished in English in 1983 (15). The authors reported that in a group of 200 ITP patients, there were 46 who had chronic cases and, of these, 30 had “varying degrees of blood stasis.” The remaining 16 chronic cases had varying degrees of spleen qi deficiency with inability to restrain the blood and yin deficiency with glowing fire.
The symptoms of blood stasis were: bruising and petechia; dry, lusterless hair; dark facial color; purplish congestion in the eye vessels; lower eyelid shows purplish dark case; pulse was thready and/or astringent. Two or more of these signs were needed to place an ITP patient in the diagnostic category of blood stasis. Since the purpura signs are to be expected in chronic cases of ITP in those seeking treatment, only one other sign would be necessary to yield the diagnosis. The proposed formula was: millettia, red peony, san-chi flowers, rubia, tang-kuei, salvia, codonopsis, jujube, eclipta, rehmannia. If there was a high level of bleeding, the formula could be modified by temporarily removing red peony and salvia and adding agrimony, lotus node, charred hair, and trachycarpus. Additional anti-hemorrhage herbs might be added according to their reputation for treating a specific site of bleeding. The authors claimed that improvements occurred in all but 3 of the 30 cases of blood stasis that were so treated. The average duration of therapy was 85 days (about three months) and the platelet levels increased from 41 before treatment to 85 after treatment.
The authors of this report quoted earlier physicians as stating that one should not just attempt to stop bleeding, but should move or circulate the blood. This should be done whether the blood is fresh or black, and whether the condition is associated with cold or heat. The authors then relayed their own experience:
In the beginning stage [of treatment] if we use the principle of following the etiology (e.g., kidney yin deficiency with uprising and flaming of deficiency fire; spleen deficiency with loss of control and blood not returning to the vessels), we will have some patients respond poorly to this treatment. These patients will present the signs of blood stasis....Chinese researchers using animal experiments found that the treament method of vitalizing blood and dissolving blood stasis inhibit the formation of IgG and regulates the T-cell balance....The treatment of vitalizing blood and dissolving blood stasis lowers capillary fragility and decreases the permeability of vessels and, in this way, resistance to bleeding is increased.
In two of the studies cited in Table 4, the base formula that is applied is: cnidium, salvia, tang-kuei, carthamus, millettia, red peony, leonurus. The ingredients in common here are salvia, red peony, millettia, and tang-kuei.
The principle of using a blood-vitalizing therapy for ITP, incorporating many of the same herbs, was mentioned recently in a reported clinical trial 16). The herb therapy was comprised of astragalus, atractylodes, polygonatum, tang-kuei, millettia, red peony, moutan, carthamus. According to the authors, 2/3 of the patients showed improvements, and the average platelet count for the whole group increased from 34 to 57, while the IgG level decreased from 195 to 122. In addition, the researchers measured hepatoglobin, a substance produced by the liver that is elevated in patients with ITP; this substance declined by 1/3 following the herb treatment. The authors expressed the view that ITP had the characteristic of a dysfunctional immune system which could be corrected by tonifying the qi (with astragalus, polygonatum, and atractylodes; this method of therapy promotes the correct qi and reduces the pathological qi) and invigorating blood circulation (which inhibits autoimmune attacks).
A disorder similar in symptoms to primary ITP, idiopathic multifocal bleeding and platelet aggregation defect (IMBPAC), was addressed with a blood-vitalizing therapy by physicians working at the Tongji Medical University in Wuhan (17). They used Xiaoyu Zhixue Pian (Reduce Stagnation, Regulate Blood Tablets) made with astragalus, codonopsis, licorice, peony, tang-kuei, and persica. The herbal material, corresponding to 1.2 grams crude herb per tablet, was administered 5–8 tablets each time, 2–3 times daily. They reported a hemostatic effect in most patients in 5–7 days (total treatment time was four months). Instead of relying on hemostatic herbs, the formula boosts the qi and vitalizes blood circulation
NORMALIZING PLATELET FUNCTIONS
There is considerable concern raised in modern medical practice about altering platelet functions. During the 20th century, the primary cause of premature death in the Western world was a blood clot that either caused a heart attack or stroke. As a result, the stickiness of platelets, which contributes to forming the blood clot, has been deemed one of the most serious pathological problems. Patients who experienced a non-fatal blood clot event would often be placed on life-long therapy to inhibit platelet sticking, so as to avoid a second event.
The ease with which a clot could form in the population (especially those past 45 years of age) appears to be due to several factors, including excess blood sugars and lipids, high oxidation status (lipid peroxidation products in the membranes), and the influence of smoking, excessive alcohol consumption, use of exogenous estrogens (menopause treatment), and the effects of sedentary lifestyle. These factors help explain why there was such a dramatic increase in fatality due to blood clots during the 20th century compared to the 19th century, and also why there were declines in incidence of these problems in the latter part of the 20th century after recommendations were made for adjusting life style and using drugs to inhibit clotting.
However, one effect of the high incidence of clotting and the corresponding medical attention to the clotting problem is to generate an image of platelets as being inherently harmful and to view substances that alter bleeding and clotting to be something that must be strictly controlled medically. In relation to herbal medicine, this has meant serious concerns about using herbs that influence clotting (many of them do if the dosage is high enough), and especially using these herbs along with medical therapies that influence clotting.
Chinese physicians have emphasized the use of blood-vitalizing herbs ever since Wang Qingren, in the first half of the 19th century, proposed that blood stasis was a major factor in several serious diseases. His blood-vitalizing formulas had dramatic effects in many cases, and were widely adopted for use during the 20th century when the cardiovascular diseases became prominent.
One of the issues that was raised was whether or not blood-vitalizing herbs might worsen, or even induce, bleeding; the other was whether or not hemostatic herbs might worsen or induce undesired blood clotting. A traditional theory, that some bleeding disorders are due to blood stasis, meant that Chinese doctors would sometimes treat bleeding with herbs that had a reputation for getting rid of clotted blood (e.g., bruising as occurs with injuries). Those herbs were shown in some pharmacology experiments to reduce platelet aggregation, which, one would think, would worsen rather than aid bleeding. An explanation for the apparent contradiction between clinical observations and the laboratory experiments is that at low dosage the herbs can regulate platelet function and stop bleeding when the function is deficient, while at very high doses (as used in laboratory experiments and some decoctions), the herbs specifically reduce platelet sticking.
One of the apparent paradoxes of modern Chinese herbal medicine is the use of san-chi (Panax notoginseng) to treat bleeding and also to help resolve blood clots and vitalize blood circulation. Other herbs that might have this effect are agrimony, rubia, and leonurus. While this diversity of actions may appear contradictory, it is not inherently so. For example, if the dietary and other lifestyle factors yield platelets which function abnormally, then lifestyle changes and herbs that help normalize their functions can have several beneficial effects. Normal-acting platelets will not be likely to spontaneously clot in the blood vessels, but they will clot promptly when there is a damaged vessel causing leakage of blood. Herbs that regulate blood circulation might normalize platelet functions and, at the same time, influence blood vessel dilation, vessel wall integrity, and other factors. The idea that the Chinese herbs will have a normalizing function, rather than causing an adverse effect, is one which is difficult to prove, leaving some question in the minds of concerned practitioners and patients. Chinese physicians, for the most part, have adopted the view that the use of the herbs to regulate blood conditions is safe.
KEY HERBS FOR REGULATING BLOOD
Table 5 presents hemostatic herbs that are included in several of the formulas for treating ITP. There are a wide range of botanical sources represented here (each herb being from a different plant family) and wide range of active constituents that might ultimately contribute to hemostatic action, including essential oils, flavonoids, saponins, and alkaloids. Other herbs that are used to treat bleeding, such as fried schizonepeta, typha, and the thistles (breea and cirsium), are not commonly used for ITP, suggesting that the physicians have focused on a small group of herbs that may be more suited to treating this particular disorder.
The possible mechanisms of action of the hemostatic herbs include:
· increasing the production of platelets
· promoting the ability of platelets to aggregate when there is blood leakage
· decreasing capillary permeability
· contracting peripheral blood vessels
· inhibiting autoimmune attack against platelets
These effects should be expected to be observed within a few days of administering the herbs. In most of the Chinese medical reports, improvement in symptoms (such as spontaneous bleeding and petechia) were observed within about 10 days. Changes in bone-marrow functions and autoimmune processes may require somewhat longer therapy, at least several weeks (typically one to three months treatment time), with increasing effect in responsive patients. The reported changes include higher platelet counts and lower IgG levels. Three groups of active constituents are known to have some hemostatic effects and may influence autoimmune processes:
· anthraquinones, found in rubia and rumex and also an ingredient of rhubarb root (which has hemostatic effects, but is not included in the ITP formulas)
· flavonoids, found in eclipta and agrimony, and also in scute (used to inhibit bleeding but rarely in the ITP formulas)
· alkaloids, found in lotus (all plant parts), eclipta, and san-chi
The role of essential oils (which usually dilate vessels; some might increase bleeding), triterpenes, and saponins found in several of the herbs remains unknown. One of the most frequently-used herbs in the formulas, raw rehmannia, contains iridoid glycosides that have hemostatic effects (see: Rehmannia). The same active constituents are found in gardenia, which is mentioned in a few of the ITP treatments, as well as in scrophularia and cornus (only rarely mentioned in the ITP formulas).
Table 5: Hemostatic Herbs Used for ITP.
All of the herbs listed here are reported to shorten bleeding time in laboratory testing.
|
Common Name |
Botanical Name |
Comments |
|
Agrimony xianhecao |
Agrimonia pilosa; agrimonin (essential oil); agriminolide (flavonoid) |
Agrimonin has been developed into a hemostatic drug in China, but pharmacology studies give conflicting results. The clinical effectiveness is not confirmed. |
|
Biota tops |
Biota orientalis essential oils: juniperic acid, thujone |
Biota leaves are frequently used (applied topically and taken internally) to treat alopecia, which is thought to involve an autoimmune disorder. |
|
Eclipta hanliancao |
Eclipta prostrata (ecliptine, wedelolactone) |
Though classified as a yin tonic, it is often used to control bleeding. The flavonoids may reduce capillary permeability. |
|
Imperata |
Imperata cylindrica triterpenes: simiarenol, fernenol |
The triterpenes reduce inflammation; there may be flavonoids in the flower that reduce capillary permeability. |
|
Lotus node |
Nelumbo nucifera alkaloids: nuciferine, liriodenine |
The alkaloids shorten bleeding time. |
|
Rubia |
Rubia cordifolia alizarin, purpurin anthraquinones |
The herb extract dilates vessels and shortens bleeding time. |
|
Rumex |
Rumex spp. anthraquinones: emodin |
Although not frequently mentioned in the Chinese literature, the rumex plants are recommended for bleeding in association with blood stasis. |
|
San-chi |
Panax notoginseng dencichine |
This is the key ingredient in the popular hemostatic remedy Yunnan Baiyao. |
|
Sanguisorba |
Sanguisorba officinalis saponins: sanguisorbin |
Sanguisorba is especially used in cases of rectal bleeding. |
In development of herbal formulas for ITP, there may be some influence of what has been called the “doctrine of signatures” in selecting some of the herbs. The hallmark of the disease, as seen from the traditional viewpoint without laboratory tests, is the petechia with a red to purple color. Several of the herbs recommended for the treatments also have a red to purple color. Examples are the purple-colored (zi) lithospermum (zicao) and perilla stem (zisugeng), the cinnabar-colored (dan) salvia (danshen) and moutan (mudanpi), and the red-colored (chi or hong) herbs red peony (chishao) and carthamus (honghua). The herb jujube used in the treatments may have been the red one (hongzao), rather than the more common black one (dazao), though the variety was not clearly specified in the literature. Similarly, there is the blood-colored millettia (jixueteng; xue = blood), and the reddish herbs which are noted for their color in their botanical names (Sanguisorba; sangui = blood; Rubia; rubi = red). Isatis leaf, used in some formulas, is the source of the purple dye indigo. The yin-tonic lycium fruit, which is used in some formulas, is a bright-red colored fruit, while the astringent cornus fruit has a purplish color. It is not clear to what extent the red to purple color of the herbs has influenced their selection for treatment of ITP by modern practitioners, but the color of herbs is known to have been a factor in the early development of the Chinese herbal medical system.
DOSAGE
Information about herb dosage was not available for all the studies, but in many cases doses of herbs used in decoction were given. The description for most of the treatments is use of “heavy dosage” of the individual herbs, with amounts of 9–15 grams per day of each ingredient, sometimes more. Typically, the herbal formulas (or at least, the portion described) would contain 8–10 ingredients, with possible additions (for particular symptoms or disease manifestation) of 1–3 other ingredients. As a result, the decoctions would be made from a minimum of about 100 grams to a maximum of about 150 grams, with 125 grams being typical. In the West, it is common to use dried extracts in place of decoctions; these dosages correspond to about 18–27 grams per day. In most of the reports, the decoctions were divided into two doses per day. It is understood that children receive lower doses, based on their age. In the Pharmacopoeia of China, a dosage schedule relating children’s dosage to adult dosage is presented as follows:
|
Age |
Dosage Range |
|
1–2 years |
1/5–/14 of the dose for
adult |
|
2–4 years |
1/4–1/3 of the dose for
adult |
|
4–6 years |
1/3–2/5 of the dose for
adult |
|
6–9 years |
2/5–1/2 of the dose for
adult |
|
9–14 years |
1/2–2/3 of the dose for
adult |
|
14–18 years |
2/3 to full dose for adult |
A good example of dosing for adults and for children is offered by examining two studies published in 1991, one (7) aimed at treating adults (ages 18–53) and the other (8) aimed at treating children (ages 6 months to 13 years). Both studies involved decoctions that had a basic formula which could be modified for the individual cases. The adult formula was based on tonifying the spleen and kidney yang and was comprised of 12 grams each of psoralea, drynaria, cuscuta, atractylodes, and hoelen; 15 grams of tang-kuei; and 20 grams each of astragalus, codonopsis, and rehmannia. The total dosage of the base formula was 135 grams. Modifications to the formula involved adding from 10–30 grams of one or two herbs, such as agrimony or salvia. For the children’s study, the formula was based on vitalizing blood circulation and the formula was: 15 grams of leonurus; 10 grams each of salvia, red peony, and millettia; and 5 grams of cnidium. The base formula dosage was 50 grams. Modifications involved adding from 1 to 6 herbs, with dosages of 5–15 grams each. In this case, the dosage was about one-third the adult dosage, which corresponds to the Pharmacopoeia dosing for ages 2–6 years of age. These two formulas also illustrate a difference in therapeutic approach; the young children generally suffer from the early stage of an acute ITP which is treated here by the principle of invigorating blood circulation while the older patients, many of whom suffered the disease chronically and therefore suffer the effects of the persistent disease and the medical treatments (including steroids used before) were treated with herbs that tonify the liver, kidney, and spleen.
In one study (5) of acute ITP (treatment time 10 days), a very large dose of agrimony root (whole herb is more commonly used) is given. The dosing of this ingredient in decoction form is described as follows: 100 grams for adults, 50 grams for 7–12 years, 30 grams for 5–6 years, 20 grams for 2–4 years, 10 grams for infants.
In two of the ITP reports (and
the one report on IMBPAD), pills and tablets were used rather than
decoctions. The pills for ITP were made
from powdered herbs, consumed in the amount of 5 grams each time, twice daily;
the tablets for ITP were poorly described; they contained 380 mg per tablet,
with a dosage of 12–18 tablets per day, for a daily intake of about 5–7 grams
per day. It is common practice to use
about 5–10 times as much herb to make a decoction as to make a pill when
treating the same disorder, so these dosages fit the usual pattern. For IMBPAD, the dosages reported for the
tablets corresponded to 12–29 grams per day of crude herbs, but the processing
to yield the tableted material was not specified. The limited reporting of using non-decoction forms such as these
makes it difficult to know if they are as effective as the high dosage
decoctions.
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May 2000