ITP Treatment – 1 Powerful Way to Treat Idiopathic Thrombocytopenic Purpura

ITP Treatment is not a monolithic one-size-fits-all.

You are probably here because you are looking additional ITP treatment. Perhaps your PLT levels have stabilized, but are still low. Perhaps you are using steroids and seek to lower steroid dosage over time. Read on to find out more.

ITP Treatment: Primary and Secondary ITP

ITP can be broadly classified into primary ITP and secondary ITP.

Primary ITP is when bone marrow activity is normal, but PLTs are attacked by IgG before maturation. Antibodies bind to the platelets, leading to a Fcγ-R-mediated clearance of platelet by phagocytic pacmen in the Spleen.

Secondary ITP is when bone marrow activity is faulty. The low production of PLTs, RBCs, WBCs is caused by (or “secondary to”) a condition like leukemia.

Th1 and Th2 in Autoimmune Disorders

TCM often speaks of an imbalance in Yin and Yang. In ITP treatment and the treatment of other autoimmune disorders, biomedicine also speaks in a similar manner, creating binary or polarized classifications. One of these dichotomies is that of Th1 vs Th2 cells.

Th1 Cells: 

Th1 cells are involved in cell-mediated immune responses. There are delayed hypersensitivity (IgG) reactions resulting in the production of complement-fixing IgG antibodies.

Th1 produces the following better known cytokines:

1. IL-2
2. IFN-γ
3. TNF-α)
4. GM-CSF

Th2 Cells: 

Th2 cells are involved in suppressing cell-mediated immune responses and are associated with anaphylactic and allergic reactions like asthma, atopic dermatitis and allergic rhinitis.

The most well-known Th2 cytokines, produced during a type 2 immune response, are:

1. IL4
2. IL5
3. IL13

In general, Th1 cells promote organ-specific autoimmune disorders while Th2 cells tend to protect against them. This concept is important and should come in handy as you read on to deepen your understanding.

Impaired Breg and Treg cells in ITP Treatment

ITP is caused by immune dysregulation where there are impaired regulatory compartments (Breg and Treg cells).

Treg Cells in ITP:

Treg in normal conditions is able to express high levels of CD25 surface marker and transcription factor forkhead box protein 3 (foxp3) on CD4+ cells.

These will suppress proliferation of many immune cells like T and B cells either via direct cell contact or indirectly via cytokine activity.

In ITP, Treg levels are greatly decreased which leads to reduced suppression of immune cell proliferation (via reduced cell contact and anti-inflammatory cytokines like IL10, TGFβ, IL35).

In ITP, there is also increased resistance of Th cells towards suppression. Because the body is unable to inhibit proliferation of these Th cells, these Th cells subsequently kill PLTs, causing an increase in proinflammatory phenotype.

Breg Cells in ITP:

Breg on other hand inhibits T cell and monocyte activation by using anti-inflammatory cytokine IL10. It regulates Th polarization, proinflammatory differentiation of antigen processing cells (APCs) and autoimmune responses.

In ITP, reduction of CD19+CD24hiCD38hi cells make the body unable to respond to IL10. When IL10 cannot be used to inhibit T cell and monocyte activation, leading to faulty Bregs.

Some findings suggest that faulty Bregs may lead to faulty Tregs.

Monocyte Differentiation in ITP

Monocytes differentiates into macrophages and dendritic cells, which then

1. Triggers and polarizes Th responses
2. Stimulate and suppress T cell responses

during infection and autoimmune diseases.

In normal conditions, our body has mostly CD14 monocytes and almost no CD16 monocytes.

However, in ITP patients, there is increased CD16+ cells which reduces Treg and Th17 but increases Th1 via cytokine IL12.

Imbalances in Th1/Treg results in T and B cell effector responses against PLT.

Fcγ-R receptors presented on monocytes, differentiated into activating (FcγRI, FcγRII, FcγRIII) and inhibitory (FcγRIIb) receptors.

In an ITP patient, FcγRIIb is greatly reduced which decreases inhibition against phagocytosis, leading to increased clearance of PLT in the reticuloendothelial system.

T Cell Imbalances in ITP

In chronic primary ITP, adults have high Th1/Th2 & Tc1/Tc2 ratios.

The higher the Th1/Th2 ratio, the lower the PLT count.

Th17 cells secretes IL17 which is pro-inflammatory.

In ITP patients, Th1, Th17 and Th22 are increased.

It is also noteworthy that cytokine IL-21 produced by some CD4+ T cells and natural killer cells can upregulate Th17 and B cells.

Treatment: Known Interventions

Present ITP treatment using conventional medicine includes use of:

• Glucocorticoids
• Platelet transfusion
• Gamma globulin
• Immunosuppressants
• Splenectomy

Many of these treatments, including the use of glucocorticoids, are able to bring a stop to the acute phase of inflammation, which is life-saving and tremendously helpful. This has to be recognized.

However, about thirty percent of the patients receiving these forms of treatment observe no obvious treatment effect (Yuan YP, Yang X, Hu BN, et al.)

There is ongoing research on new drug therapies for adult primary immune thrombocytopenic purpura (J Exp Hematol 2020;28:677–81.)

ITP Treatment using TCM Herbs?

There are several parts to understanding and accepting how Chinese herbs can be employed in the treatment of ITP.

The first part is understanding that perhaps herbs have the ability to alter the immune status of an inflammatory condition. While glucocorticoids are able to limit the effectiveness of inflammatory mediators, they generally suppress cellular immunity more than humoral immunity.

How do Chinese herbs enhance immunity in ITP?

Enhance immunity in general

Instead of suppressing the immune system like steroids do, some Chinese herbs are able to enhance humoral and/or cellular immunity.

These herbs include adaptogens like astragalus or ginseng, and are generally seen as ‘tonics.’

Regulate immune system

There are other herbs that do well when used together with the above-mentioned ‘tonics.’ These herbs, which include Caulis Lonicera Japonica and Rhizoma Smilacis Glabra, are able to regulate/inhibit immune function. They may not do so with the precision of a biologic; at the same time, they also are likely not to carry the side-effects wrought by immunosuppressive agents like MTX or cyclosporine.

Inhibit humoral immunity but enhance cellular immunity

In addition, there are also herbs like Rehmannia that are able to inhibit humoral immunity while enhancing cellular immunity. This is important because humoral immunity is often over active in many autoimmune diseases like ITP.

ITP Treatment using Chinese Herbs

In ITP treatment, what matters most in Chinese herbal formulation is the clinical presentation of the patient, which then determines the herbs and herbal formulations to consider. We lay out below some herbs for which some research has been done to explore their effects on ITP.

Agrimony 仙鹤草 for ITP

Agrimony contains agrimonin and flavonoids which have hemostatic effects. Vitexin, quercetin O-galloyl-hexoside and kaempferol O-acetyl-hexosyl-rhamnoside were found to have anti-inflammatory properties.

Radix Lithospermi 紫草 for ITP

Lithopspermi is able to inhibit PMA plus A23187-induced increase in proinflammatory cytokines IL6, IL8 and TNF-α expression in HMC1 cells. It is also able to reducd histamine, hence reducing vasodilation and vascular permeability. It helps to reduce inflammation and support hemostatic activity in ITP.

Cortex Moutan 牡丹皮 for ITP

Gallic acid is the major active ingredient from Cortex Moutan that can dose-dependently inhibit release of IL12-p40 and the functional surface marker expressions of CD40, CD80, CD83 and CD86 from cytokine cocktail-activated moDC.

Gallic acid is also able to lower the concentration of hydrocortisone required to inhibit the maturation and activation of dendritic cells from monocytes.

Astragalus 黄芪 for ITP

Astragalus polysaccharides (APS) is the key active ingredient extracted from Astragalus. APS decreased the expression of pro-inflammatory cytokines, cytotoxicity, and apoptosis induced by ochratoxin A. How it does this is by activating AMPK (5′-AMP-activated protein kinase), also known as a metabolic master switch, through which cells in mammals sense and decode changes in energy.

Literature has documented that astragalus has promising immunomodulatory ability to regulate innate immunity. Specifically, it is able to change levels of macrophages, NK cells, dendritic cells (DCs) and microglia. It also has an effect on acquired immunity, meaning it can tweak immunity by changing the dynamics in T and B lymphocytes.

Astragaloside IV is able to decrease the activity of high mobility group box 1 protein (HMGB1) and down-regulated the shift of Th 2 to Th1 through increasing Foxp3 expression in CD4+CD25- Treg.

AST II is able to down-regulate the production of IL-2 and IFN-γ and the proliferation of splenic T cells in CTX-induced immunosuppressed mice.

Angelica Sinensis 当归 for ITP

Angelica or Dong Quai is able to reduce TNF-α levels, which is helpful in treating ITP, which is associated with high levels of Th1 cytokines. The active ingredient of Angelica Sinensis is called paeoniflorin, and is able to reduce IL1β, TNFα and ICAM1 levels.

Semen Cuscuta 菟丝子 for ITP

Kaempferol is a major flavonoid that is able to reduce cytokines and chemokines produced by LPS-stimulated dendritic cells without causing cytotoxicity on DCs.
DC maturation is also impaired by kaempferol (via reduced production of CD40, CD80 and CD86).
Furthermore, kaempferol abrogated the ability of LPS-stimulated DCs to promote Ag-specific T cell activation, both in vitro and in vivo.
In conclusion from one paper, we know that Semen Cuscata exhibits an immunosuppressive effect on DCs and that the active ingredient kaempferol attenuates DC function
This suggests that kaempferol has potential in the treatment of chronic inflammatory and autoimmune diseases through the reduction of TNFα, IL6, IL12 p70 as well as some other chemokines.

Fructus Lycii 枸杞子 for ITP

Lycium barbarum can activate T cells, B cells, macrophages, NK cells and other major immune cells that regulate the body’s cellular immune function and humoral immune function.

Conclusion

If you are already being treated for ITP and want additional support, do consider the use of  Chinese herbs to tweak your immune system.