Because I have seen four cases who were provisionally diagnosed as case of ITP and all of them received steroid for treatment of ITP but all of these cases all came to us as relapse of acute lymphoblastic leukemia.
The American Society of Hematology Guidelines for ITP do not require a marrow prior to the use of steroids. In patients over 60 years or age and in patients for whom a splenectomy is a consideration marrow studies are suggested. This assumes the peripheral smear is normal except for thrombocytopenia. Any hint of myelodysplasia or other abnormalities should motivate one to do a marrow
It may not be necessary, if you have other means of proofing that the platelet depletion is immune-mediated. As you know in some cases of ITP, the marrow also lacks megakaryoctes, which are also destroyed by the same immune process. However, a marrow packed with megakaryocytes in a thrombocytopaenic patient may help you rile out other causes of thrombocytopaenia.
True ITP in adults is typically relapsing, especially if steroids are tapered too quickly. Furthermore, ITP is often refractory. This course is not anticipated by a marrow examination. As Jeffrey has already stated, a bone marrow smear and biopsy is needed when the diagnosis is uncertain on clinical grounds. In my opinion ITP is mainly a diagnosis of exclusion; to rule out other diagnosis is mandatory at presentation. The CBC should be otherwise normal except in the case of Evans syndrome and splenomegaly should question the diagnosis of ITP.
As you know, the diagnosis of ITP is confirmed by excluding other possible causes of acute onset thrombocytopenia. In pediatric age group, you can be hardly ever certain to exclude other important and serious etiologies such as aplastic anemia, acute leukemia or mylodysplasia, even though other elements of CBC are not affected. Therefor, I recommend to do marrow aspiration to assure that you are on the right way.
you are absolutely right Dr. Ravi i have also seen 4-5 cases of relapse ALL who were misdiagnosed as ITP and received steroids during treatment. If you are not going to do bone marrow examination and have not excluded other causes such as leukemia than i will highly recommend use of IVIg and Anti D for treatment of acute ITP.
No!! If the rest of the CBC is normal the chances are that one is dealing with ITP. It is a good idea to exclude drug mediation which is usually not present. If one is going to treat, the modern therapy is NOT steroids ad infinitum with cushinoid production and all the attendant side effects, but high dose daily dexamthasone (40 mg) x 4 days, possibly with rituximab weekly x 4. If the patient does not respond to the dexamethasone, they will not respond to prednisone at much lower doses.
For chronic ITP where the platelets are low and cause potential problems, a thrombopoetomimetic drug should be added.
Splenectomy is a whole other subject and generally should be avoided if possible. Be sure to immunize patients against pneumococcus (and probably H. influenza and meningococcus) prior to surgery.
To misdiagnose multiple cases of ITP for ALL is quite surprising. As Dr Cabot and I stated, CBC in ITP should be normal (except in the case of associated AIHA - i.e., the Evans syndrome). Instead, my usual work-up include a search for antiphospholipid antibodies and lupus anticoagulant, and at least a fecal test for H. pylori antigen.
Rituximab plus DEX is undoubtedly "modern", however to my knowledge there is only a preliminary trial (http://bloodjournal.hematologylibrary.org/content/121/11/1976.full) that included only 62 patients in the rituximab arm, with a median follow-up of 922 days. Rituximab is highly efficacious but not completely safe and, in my opinion, it should be reserved to refractory cases. Romiplostim seems to be safe after 5 years of treatment (http://onlinelibrary.wiley.com/doi/10.1111/bjh.12260/abstract) and I suspect that it may replace splenectomy in the near future.
Unfortunately, I have seen also two cases, starting out as if they had ITP : one ended up as Aplastic Anemia and an other one later became Myelodysplasia.
Marion Sternbach
As Dr. Cei points out with Evan's syndrome, I have seen a few cases of apparent chronic ITP with severe anaemia which turned out to be iron deficiency. All were pre-menopausal women who had severe meno/metrorrhagia due to the low platelet count and became iron deficient on that basis. The age/sex group (although also typical of Evan's syndrome) and characteristics of the anaemia (hypochromic/microcytic) should be a clue.
acute otherwise unexplained isolated thrombocytopenia can be only an ITP. Evan's syndrome or Mosckowitz syndrome should be considered , bu hemolitc anemia should be present. any way bone marrow biopsy is not required for diagnosis, and prompt streoid therapy is warranted. only when thromocytoprnia is slow progreessingand peripheral distructinon on different clotting disorders as antiphospholipid, DIC, an so on have been excluded I consider bome marrow histology and bloood smear and sometimes electron microscopy for platelet disorders.
I agree with all above statements, no need for BM examination in isolated thrombocytopenia in young people. It has to be proposed for the ederly, patients unresponsive to standard steroid treatment and especially before a second line treatment like rituximab (to avoid "missing" an underlying low grade lymphoma for instance)
obviously, but a history of previous hematologic malignancy was present. sometimes also lymphomas or CLL may begin with acute thrombocytopenia!
No ! If the differntial blood smear is without abnormalities and no medication responsible for thrombocytopenia and antinuclear antibodies are negative.
No!, I agree with Dr. Lang. However, in older patients with refractory thrombocytopenia BM examination should be done to avoid missing underlying MDS or low grade lymphomas
Bone marrow in ITP is not rcommended unless patient is going for splenectomy,
lymphoma suspected ,or patient above 60 year old
Iidiopathic thrombocytopenic purpura: it is an exclution diagnosis!
The diagnosis of ITP is made by exclusion of secondary causes of thrombocytopenia as there are no diagnostic tests to confirm ITP. We must rule out all autoinmune and infection (acute and chronic ones) causes of thrombocitopenia (please, do not forget Helicobacter pylori). The initial history and physical examination should be aimed at identifying evidence of bleeding and excluding other causes of thrombocytopenia or secondary ITP.
In case of isolated thrombocitopenia, without coagulation or biochemical alterations, and normal smear (please, do not forget the optical mycroscope), bone marrow examination is not required in chidren, youngs and mature (under 60 or 65 yo).
In patients presenting with suspected ITP, abnormalities in the complete blood count and peripheral blood smear other than thrombocytopenia (and perhaps microcytic anemia attributed to chronic blood loss) should be further investigated, for example, with a bone marrow examination or other appropriate investigations, before the diagnosis of ITP is made.
ASH Guidelines recommendations:
They find no evidence for the routine use of bone marrow examination in several situations, therefore:
1.1.A. They recommend:
Bone marrow examination is not necessary in children and adolescents with the typical features of ITP (grade 1B).
Bone marrow examination is not necessary in children who fail IVIg therapy (grade 1B).
1.1.B. They suggest:
Bone marrow examination is also not necessary in similar patients before initiation of treatment with corticosteroids or before splenectomy (grade 2C).
I also agree that bone marrow examaniation is not necessary, if the diagnosis of ITP is established (by exlusion). Only if there is uncertainty (e.g. abnormal RBC/WBC in addition to thrombocytopenia), I would consider bone marrow examination.
The ASH guidelines (Neunert et al, Blood) posted by Jose are very useful.
I always suggest to do BM examination in suspected cases of ITP particularly in developing countries where all investigations may not be available. When some body says isolated thrombocytopenia without any other changes in the formed elements of blood, then they are speaking about a small number of cases in a developing country.
As ITP itself can produce blood loss and anaemia, associated viral infections can cause atypical lymphocytosis and sometimes eosinophilia. Vitamin B12 and folate deficiency is also not uncommon in our set up and with concomitant iron deficiency many of the features of B12 and folate deficiency may be masked.
Viral infection may also cause neutropenia. Classically spleen should not be palpable. The major problem is making a mistake in the diagnosis of ALL for ITP. This does not make much difference in developed countries where primarily Iv Ig or Rh immunoglobulin is the preferred mode of initial treatment in a case of symptomatic ITP and easy availability of flowcytometry can easily pick up a small clonal leukaemic population from peripheral blood if there is one.
However in my country a large number of ITP patients are treated with cortico steroids and flowcytometry is not widely available. Missing an ALL as ITP and treating it with corticosteroids may not only permanently impair the chances of long term survival in the patient this mistake in the days of litigant medicine may have dire implication. I will always do bone marrow examination in an ITP patient if I have a plan to treat the patient with corticosteroids and I dont agree with ASH guidelines.
I also have seen quite a few patients of ALL initially diagnosed as ITP.
Once again, medicine is equal only in our books!
Nice debate!
Great differences between countries, regions, etnical origin, economies and measure availibity. Probably, we must adapt ourselfs to our place and our patients!
I totally agree with dr Kanjaksha Ghosh as in this part of world still corticosteroids have been used for the management of ITP. I have also seen 4-5 cases of ALL who were initially presents as ITP and treated with steroids elsewhere but after sometime they admittted in our hemato oncology unit as cases of ALL relapse. Because all of them were treated with steroids and they had gone in remission. In Indian scenario i always prefer BM examination before going to steroids otherwise i prefer anti - D or IVIg
Also, I consider the BM examination necessary before a diagnosis of ITP is established in 60-65 old patients, and even younger, because the myelodysplastic syndrome (MDS) is frequent in this category and the morphologic features of MDS could be missed on a a routine periferal blood smear and the flow cytometry for MDS is not yet available, especially in some countries. In MDS, the morphology of megakariocytes could be relevant and the cytogenetics too.
It has to be mentioned that in Eastern countries the median age of MDS patients is 10-20 years lower than in the Western countries.
Complete blood counts, peripheral blood smear findings and correlation with the clinical details of the patient is crucial; whether we are talking about viral infections, vitamin B12/Folate deficiency, mixed nutritional deficiency, acute leukaemia or MDS. A good clinical history and examination supplemented by an experienced eye for the appropriate morphological findings on peripheral blood, can resolve the query in most instances.
I'm sure everyone will agree, that most of us will think a zillion times, before getting a bone marrow biopsy done ourselves, if God forbid, we suffer from isolated thrombocytopenia, whether we belong to a developing or a developed country.
Hi. All your answers are justified. It's always necessary to do BM examination because it still's a diagnosis of exclusion. In my exeprience I've even had some lymphomas in BM examination without circulating malignant cells, beside other Viral infections (CMV, Parvo virusB19..)
No. Bone marrow examination is only required if the diagnosis of ITP has not been established. Most cases of ITP do not require treatment as there are no symptoms. In children and adolescents and adult less than 60 or 65 years as Jose has rightly said ASH prescribed that treatment is not necessary except the patient is symptomatic. If you are unsure of ITP diagnosis for instance, where CBC suggest thrombocytopenia in your patient you may adopt wholistic approach based on medical history. Other causes of thrombocytopenia must be ruled out by ordering relevant tests- ANA (in case of suspected systemic involvement), PT, APTT and FDP (to rule out suspected DIC in case of peripheral pancytopenia from CBC analysis), H. pylori test etc. In developing countries, I want to add that caution should be exercised before administering corticosteroids in suspected cases. Diagnosis must be established first. Bone marrow examination is only required if the clinical and routine diagnostic findings are insufficient
The European Journal of Haematology has recently published a retrospective paper that has shown that there is no difference between bone marrow examinations of young and older patients with ITP (http://onlinelibrary.wiley.com/doi/10.1111/ejh.12320/abstract), thus reducing the importance of BM examination in ITP even in older patients.
Bone marrow aspiration may not be done to diagnose ITP, however in patients above 60 years suspected to have ITP, there is a need to rule out the possibility of of MDS as a cause of thrombocytopenia. Thus BMA would be necessary.
In children with a preliminary diagnosis of ITP, and symptomatic (necessisating treatment), if corticosteroids are to be used we suggest BMA prior to corticosteroid examination, since there has been cases that are dşişagnosed with ALL although they had only thrombocytopenia at diagnosis. . If IVIG may be used we do not recommend BMA upfont.
Prof Dr Rejin Kebudi
Bone marrow is recommeneded if patient is going for splenectomy or above 60 year of age otherwise there is consensus not todo it please review
ASH guideline and IWG guidelines
I guess my point is still not clearly understood.....if we are to suspect acute lymphoblastic leukaemia (with no spill over into blood) shouldn't we be looking for lymph nodes, visceromegaly etc. first???.....If for that matter, there are none of these even on a good physical examination, then my question would again be...how many times do we come across such patients...and secondly, should we start thinking about an occult ALL in every patient presenting with thrombocytopenia and perform a marrow biopsy, just because we have come across a rare atypical case??? What is the justification for this? What is the Evidence-base? Have we gathered enough data regarding this to justify this end? Have we published our local guidelines grading this with high level of evidence? Have we really truly done enough to nullify the ASH Guidelines which have been published by human beings just like us; but who believe in a rationale and evidence-base behind each act of commission or omission and put in great efforts to pursue this end...are we going to continue relying on anecdotal experiences to guide us in such crucial decision-making? Aren't we treating human beings over here, and isn't it our ethical & moral obligation towards human beings of the third world to provide them what we would want for our own selves???
I agree with Kashif. We have all seen atypical cases and that is why close follow up is required. Even though we all practice evidence-based medicine we always quote the couple of odd cases we have seen in our lives. However, sometimes, even in odd cases, if one looks back through the history there may be some warning signs.
iIs there someone who can speak in terms of NNT (number needed to test, in this case) to diagnose just 1 case of ALL in a population of patients with isolated thrombocytopenia (obviously excluding those with multiple abnormalities on CBC that make BM biopsy otherwise mandatory)?
its depend on the experience of doctors who treat ITP.I think an expert in hematology never misdiagnose ALL .it is better to say the ITP cases should be consulted by a pediatric hematologist before starting corticosteroid.if there is any suspicious of malignancy the bone marrow aspiration must be done
Actually, reading the stem question and the short summary re the four patients with suspected ITP who turned out to have relapsed ALL, it is pretty obvious that the warning point in all 4 patients' history was a past history of ALL, which would have made it mandatory to marrow all 4 patients.
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