TREATMENT OF ITP WITH CHINESE MEDICINE

by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon

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.

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.

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.

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.

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