www.symbiosisonline.org Symbiosis www.symbiosisonlinepublishing.com Case Report International Journal of Hematology and Blood Disorders Open Access Immunopathology of Immune thrombocytopenia: Essentials for oncologists and haematologists Piyush Vyas* *Department of Haematology, Oncology and Internal Medicine, Medical University of Warsaw Hospital, Warsaw, Poland Received: 8 October, 2017; Accepted: 26 October, 2017; Published: 16 November, 2017 *Corresponding author: Piyush Vyas, Department of Haematology, Oncology and Internal Medicine, Medical University of Warsaw Hospital, Warsaw, Poland; email: [email protected] Abstract primarycongenital, ITP or can systemic only be(autoimmune diagnosed bydiseases thoroughly like for examining example aSLE) patient and whicha platelet would count include of less detailed 100 G/l. history Thus taking, a diagnosis physical of An in depth knowledge is essential about the pathology of immune thrombocytopenias before we start managing these aetiologyautoimmune is known, disorders. we tryIt’s toimportant eliminate to the differentiate antigen which whether triggers the patient has primary or secondary immune thrombocytopenia. If the thrombocytopeniaexamination, full blood except count the andprimary a bone ITP.Secondary marrow biopsy. ITP Thecan secondary ITP broadly include all the other forms of immune aetiology is unknown then as per international working group criteria, wefurther diagnose formation such immuneof autoantibodies thrombocytopenia directed asagainst primary platelets. immune If thrombocytopenias. Primary immune thrombocytopenias are be H. Pylori related, drug related, HIV related, related with managed primarily by administering intravenous immunoglobulins autoimmune disorders like SLE etc..(1) thrombocytopenia with secondary immune thrombocytopenia drugs like azathioprine, cyclosporine, rituximab, vinca alkaloids like Of prime importance here is to differentiate primary immune vincristine,or steroids ascyclophosphamide first line treatment. or other In second drugs line like immunosuppressiveandrogens- danazol, are managed differently thus it should be assured that the patient relapsed ITP splenectomy remains as an important surgical option be screened for HIV or HCV. A bone marrow aspiration and a TPO mimetics etc. are administered. And of course for refractory or however now-a-days less popular. trephine biopsy are further advised for all patients ( especially Keywords: ITP- immune thrombocytopenia; ALPS – Autoimmune elderly patients >60 years) to rule of myelodysplastic syndromes as(MDS) their and initial haematological stages thus such malignancies diseases should .Of course also autoimmunebe excluded. VZV- Varicella zoster virus; APS – Antiphospholipid syndrome; CVID diseases like SLE also can present as isolated thrombocytopenias lymphoproliferative Syndrome; SLE –Systemic lupus erythematosis; If patient has autoimmune haemolytic anaemia (AIHA), always – IntravenousCommon variable immunoglobulins; immune deficiency; TPO- Thrombopoeitin MMR- Measles, mimetics; mumps, can be suspected (2). rubella.; MDS –Myelodysplastic syndrome; GP- Glycoprotein; i.v.Ig Evans syndrome along with thrombocytopenic Evans syndrome Definition of different phases of ITP NK-natural killer; MHC- Major histocompability Complex; APC- insulinantigen dependent presenting diabetes cells; TCR mellitus – T cell ;CTL- recerptor; cytotoxic Tregs T lymphocyte. –T relulatory The International working group recommended the use Lymphocytes ;IL-interleukin ; TGF-transforming growth factor; IDDM- Introduction of “newly diagnosed ITP” for all cases at diagnosis. The term “persistent ITP,” was introduced for patients with ITP to define Immune thrombocytopenia (ITP) are autoimmune disorders category includes patients not achieving spontaneous remission the period lasting between 3 and 12 months from diagnosis. This which characterize that autoantibody mediated platelet destruction, suboptimal platelet production and T cell mediated or not maintaining their response after stopping treatment platelet lysis occurs leading to decrease in platelet count. between 3 and 12 months from diagnosis. The term “chronic Clinical Definition of primary and secondary immune ITP” was suggested for patients with ITP lasting for more than 12 months. Term ”severe” ITP was reserved for ITP with “clinically thrombocytopenias relevant bleeding” which was defined by the presence of bleeding As per the International working group criteria, primary ITP symptoms at presentation sufficient to mandate treatment, or by agentthe occurrence or an increased of new dose. bleeding symptoms requiring additional therapeutic intervention with a different platelet-enhancing is clinically defined by the presence of thrombocytopenia in the absence of demonstrable causes be it be pathogenic, therapeutic, Symbiosis Group *Corresponding author email: [email protected] Immunopathology of Immune thrombocytopenia: Essentials for Copyright: oncologists and haematologists © 2017 Vyas P. Immune thrombocytopenias and solid tumours There have been isolated case studies or isolates case series Opinions are very conflicting, some authors advocate that these are paraneoplastic phenomena of cancers {Krauth et.al. tumours with immune thrombocytopenias. Our group was 2012(17)}, others are of the opinion that no correlation exists reported of incidences of co-existent cancers especially solid between these 2 diseases if they coexist. Whether there exists duodenal cancer with coexistent immune thrombocytopenia some significant correlation between immune thrombocytopenias the first to publish a case report of a patient with metastatic and cancers remains still is a topic of further research. patients with coexistent immune thrombocytopenias are that (P.Vyas et.al.) (7). In this case we first treated the immune Some of the proposals about treating these solid tumour thrombocytopenia and when the platelet count of more than 75 like cyclophosphamide, vincristine, vinblastine, cyclosporine, theG/l cancerwas achieved, responded we to treated treatment, this thepatient platelet with count chemotherapy increased. procarbazine,of using protocols etoposide with ,steroidscombined in chemotherapy their regimens. drugs In cases(21) without any episodes of bleeding. Our observation showed as where radical resection is possible (ovarian cancers, breast coexistent immune thrombocytopenia{P.Vyas et.al. (9)} where cancers, lung cancers etc.) it is advised to resect radically the initiallyAfterwards the againpatient we was reported treated awith case endocrine of breast therapies, cancer withand casestumour splenectomy after attaining is an an optionoptimal now-a-days platelet count less from popular ITP directed among when the disease got endocrine refractory, chemotherapy was physicianstherapies and(steroids/immunoglobulins patients too.Since endocrine etc.). therapiesIn referactory can be treatedadministered with steroidssuccessfully and immunoglobulins,achieving long periodswhen the of immune stable disease. As far as ITP is concerned our patient was initially steroids , treatment with rituximab, vincristine, danazol was administered safely in thrombocytopenias ,we recommend thrombocytopenia got refractory to immunoglobulins and to start treatment with endocrine therapies for example in breast cancer (ER/PR + patients), prostate cancer patients. Sinceadministered these 2 withdisease good entities(immune effects , attaining thrombocytopenia satisfactory levels and of patients.Our observations Protocols found like thatAC (Doxorubicine, protocols like FOLFOX/Cyclophosphamide) FOLFIRI / solidplatelet tumours) counts occurto further rarely treat or rarelythe patient are diagnosed with chemotherapy. as immune Capecitabine can be safely administered in gastrointestinal cancer to conduct prospective randomised clinical trials .Thus we treat cancer/Docetaxel patients monotherapy with coexistent /Cyclophosphamide immune thrombocytopenias. monotherapy / thrombocytopenias with coexistent solid tumours , it is difficult InVincristine a situation monotherapy when no guidelines can be exists,safely weadministered recommend in to breast treat .It seems that many patients with immune thrombocytopenias withthese coexistent patients on solid the tumours basis of availableare not diagnosed knowledge by in oncologists literature , as chronic thrombocytopenia in these cases is misunderstood patients as have been done the world over based on case studies/ caseImmune series asthrombocytopenias far as solid tumors with coexistentand Haematological ITP is concerned. malignancies as massive tumour infiltration to the bone marrow. Many a times trephine biopsy is not done to find out the reason of occur with haematological malignancies. In chronic lymphocytic thrombocytopenia / cytopenias. Isolated thrombocytopenia Certain protocols are advised if immune thrombocytopenias if it occurs in a patient should not be understood a priori as diseases is high, among others autoimmune haemolytic anaemia , withinfiltration coexistent by tumour chronic unless thrombocytopenia we find massive have tumour chronic infiltration immune leukaemia where the incidence of coexisting autoimmune in bone marrow biopsy. Many of these patients with solid tumours some authors have suggested administering protocols like autoimmune immune thrombocytopenia and of Evan’s syndrome thrombocytopenia which get resolved with effective treatment surgeryof immune or chemotherapythrombocytopenias or other with treatment steroids modalitiesor