Dear Ghada,

The following paper covers the answer to your question.

Br J Haematol. 2001 Mar;112(4):1076-8.

A dose of 75 microg/kg/d of i.v. anti-D increases the platelet count more rapidly and for a longer period of time than 50 microg/kg/d in adults with immune thrombocytopenic purpura.

Newman GC1, Novoa MV, Fodero EM, Lesser ML, Woloski BM, Bussel JB.

Author information

http://www.ncbi.nlm.nih.gov/pubmed/11298610

Abstract

Treatment with 75 microg/kg/d intravenous (i.v.) anti-D was compared with 50 microg/kg/d in a prospective randomized study of 27 RhD-positive, human immunodeficiency virus-negative, adult, acute, non-splenectomized patients with immune thrombocytopenic purpura (ITP) and platelet counts < or = 30 x 109/l. The higher dose resulted in greater median d 1 (43 x 109/l vs. 7.5 x 109/l; P = 0.012) and d 7 (153 x 109/l vs. 64.5 x 109/l; P = 0.001) platelet increases despite no greater haemoglobin decrease. Children with acute ITP receiving 75 microg/kg/d had overnight platelet increases in seven out of nine cases. The duration of effect at the 75 microg/kg/d dose was 46 d vs. 21 d (P = 0.03). Adverse events were mild to moderate and ameliorated with prednisone and acetaminophen premedication.

Hoping this will be helpful,

Rafik

but this paper about anti-D not hydroxychloroquine

Dear Ghada,

Yes. But this paper was reference by a paper in J Med Case Rep. 2013; 7: 91.

Published online 2013 Apr 4. doi: 10.1186/1752-1947-7-91 entitled "Refractory immune thrombocytopenia successfully treated with high-dose vitamin D supplementation and hydroxychloroquine: two case reports". Please read the introduction of the latter paper and check reference 3.

Introduction

Immune thrombocytopenic purpura (ITP) is thought to be an autoimmune disorder mediated by autoantibodies with no known etiology, and the incidence is approximately 2.5 per 100,000 persons per year [1]. The goal of treatment is to keep the platelet count above 3×104/mm3 to prevent major internal organ bleeding.

Current treatment involves intravenous corticosteroids, immunosuppressants such as mycophenolate mofetil and azathioprine, Cytoxan® (cyclophosphamide), and intravenous immunoglobulin (IVIg) [2]. Anti-D immunoglobulin can only be given to RhD-positive individuals, thus limiting treatment options for RhD-negative persons [3]. Rituximab, a chimeric monoclonal antibody, has also been tried as an experimental treatment [4], and combinations of therapies have been used with some success [5]. Each of these therapies may be associated with significant side effects and efficacy is often temporary, requiring either additional and/or alternative treatment.

To read the full text of this paper please use the following link:

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623781/

Hoping this will be helpful,

Rafik

The problem is that the so-called "primary ITP with a positive ANA" may not be ITP at all, bur rather systemic lupus from the very beginning. I have seen many patients presenting initially with what looked like ITP, turning into full-blown lupus 4-5 years later. You can finish an entire rheumatology or hematology fellowship (usually 2 years of training) and leave the program not realizing that this can happen because you need time to understand and witness this natural progression, which can take many years, as above-mentioned, 

ok even if this true . why hdroxychloroquine can treat this subgroup and can't treat primary ITP with negative ANA

 Dear Ghada Abdallah,

There are 2 components to your question. Let me tackle the easy part first. 

1. Evidence for efficacy for Hydroxychloroquin in ANA positive ITP: It was always known that almost 5% of SLE might start with isolated thrombocytopenia alone. Mechanisms of immune thrombocytopenia in SLE differs from those observed in primary ITP and is probably multifactorial, including antiplatelet glycoprotein antibodies such as in ITP but also immune complexes, antiphospholipid antibodies, autoantibodies to the c-MpL receptor and megakaryocytes.

Since Hydroxychloroquin works so well in treatment of multiple domains in SLE, it was but natural to study it in SLE associated throbocytopenia too where it was found useful. Next, about 20% of all ITP patients are ANA positive without meeting the criteria of SLE and this was the natural target to be studied for the effect of hydroxychloroquin. Interestingly, ANA positivity in ITP has been shown to a risk factor of chronic ITP and resistance to classical second-line treatment for ITP.

In the 2014 study by Khellaf et al, they looked at both SLE with thrombocytopenia and ANA positive ITP who had failed multiple drugs and tried hydroxychloroquin on them. As expected the SLE group indeed did very well with 83% response but even the other group showed a robust 50% response. Considering the excellent safety profile of hydroxychloroquin, these numbers are very encouraging. If these findings are replicated, hydroxychloroquin will very likely make its way into ITP treatment guidelines soon.

2. Why does it not work in ANA negative ITP? 

Where is the evidence that hydroxychlororquin "does not" act in ANA negative ITP as stated by you. Evidence is just emerging that it might be useful to some extent in the ANA positive variety. It requires another study to prove its inefficacy" in ANA negative ITP.

It was a natural step to use a time tested drug like hydroxychloroquin with proven efficacy in SLE to the subgroup of ANA positive ITP (who do not fulfil criteria for SLE). The next logical step seems to be to compare role of hydroxychloroquin in ANA positive Vs ANA negative ITP. I am not aware of any study that has specifically looked at this aspect. Maybe you can plan one such study.

If we are able to show in future that hydroxychloroquin "DOES NOT" act in ANA negative ITP, then we need new studies to study molecular mechanisms to understand the "why". 

hope this helps

I agree with Dr. Subramanian. Hydroxychloroquine  (HCQ) helps prevent lupus flares and progression of disease. This was clearly shown in the LUMINA cohort studies (where only about 60% of lupus patients were on the drug). In this day and age, every patient with lupus should be on HCQ, an effective immunomodulator. However, we need to point out that once a lupus complication develops, on a patient who has not been on the drug, then HCQ is not as effective. HCQ should be used in a "prophylactic" manner, i.e., it needs to be started when lupus is first diagnosed to prevent later progression of disease,