Milan, Italy, June 12 – 15, 2014

identified a subset who achieved a normal kinetics and that is no longer disorders relapsed 4 years after discontinuation of the drug. Aims: To validate the study of platelet kinetics as a predictor of response to therapy with romiplostim and if the its early normalization can identify a subset PB2015 of patients who may discontinue the drug . Methods: A total of 18 adult patients, female (63%),median (range) age 55 (31 A COLLECTIVE DESCRIPTIVE STUDY OF MANAGEMENT OF IMMUNE – 78) years, median (range) baseline platelet count 19 (3 – 32) x 109/L.,median THROMBOCYTOPENIC (ITP) IN THREE HOSPITALS of 4 (1 – 7) prior ITP therapies, received romiplostim administered once weekly D Gunawardena 1,* N Senadheera 1,2, IS Wijesiriwardena 1, SS Lorensu Hewage 1 1 2 sc, with dose adjustments to maintain platelet counts in the target range of Heamatology, University of Sri Jayawardenapura, Colombo, Heamatology, 50–150x109/L. The median time since ITP diagnosis was 6,8 years (range, General hospital,Ratnapura, Ratnapura, Sri Lanka 0.6–12.8 years) and 10% had undergone a . Patients received romiplostim for a median of 98 weeks (range, 18–104); taking the average weekly Background: Adult idiopathic (ITP) is an dose of all patients, the median was 4 mcg/kg. Home administration was started autoimmune disorder caused by antiplatelet autoantibodies that cause platelet by 16% of patients (3/18) but 2/3 patients discontinued home administration and destruction by the reticuloendothelial system. The disease has been well- resumed weekly outpatient injection. All patients achieved a platelet count documented in Sri Lanka and the rest of the south East Asia. Since the disease 50x10 9/L. itself gives rise to minimum morbidity and mortality, we often find that the patient Results: Results: 3 out of 18 experienced thrombocytosis and rebound suffers from complications of overtreatment rather than the disease itself. . A PKS with (111)In oxine-labeled autologous platelets was Therefore it is vital to have an understanding of “when to treat the patient” which performed in all patients failing steroid treatment, before romiplostim was is mostly decided on an individualized patient basis. Countries where expensive started. A gamma function was used for the calculation of platelet mean life span treatments such as and thrombopoietine receptor agonists are not a (MLS) that was greatly reduced in 100% of patients.3 patients, who had freely available option, management has to be optimized at an “individual basis”. achieved early a stable platelet count 150x109/L. despite the discontinuation We studied 72 patients with chronic ITP followed up over a minimum period of of romiplostim maintain normal platelet count after 48 months of follow-up. 2yr to 8yr in three tertiary care hospitals in Sri Lanka. We looked at the age Stricking a second PKS six months after starting the treatment showed in these groups and gender, modes of presentation and time taken for response to subset, a normal platelet half-life with normal uptake on the spleen and liver. initial therapy and the current options of therapy with their side effects. Our Summary and Conclusions: In our opinion early PKS normalization is a study evaluates the relationship between the severity of the thrombocytopenia strong predictor of sustained responses after discontinuing romiplostim without and the incidence of and thereby to come to a consensus on the best additional therapy and may easily detect patients cured by the drug. approach to management options. Aims: To study the characteristics of immune thrombocytopenic purpura(ITP), response and side effects of standard therapy, other possible options of PB2017 management in three centers in Sri Lanka. Methods: Retrospective data was collected from 72 patients with diagnosed THROMBOEMBOLISM RISK IN PATIENTS WITH IMMUNE ITP and followed up for a minimum of 2 years from January 2007, at three THROMBOCYTOPENIA (ITP) tertiary care hospitals in Sri Lanka. Department of Haematology, University of MH Hu 1,2, *YC Liu 2,3 Sri Jayawardenapura. General Hospital, Ratnapura. General Hospital, 1Division of Haematology and Oncology, Department of Medicine, Cardinal Gampaha. Tien Hospital, New Taipei City, 2Division of Haematology and Oncology, Results: The platelet coun t was below 10x10 9/l in 40(55%) at presentation.Skin Department of Medicine, Taiepi Veteran General Hospital, Taipei City, bleeding was the commonest presentation and seen in 37(51%). In 17(23.6%)it 3Department of Medicine, Taipei City Hospital, Taipei, Taiwan, Republic of China was an incidental finding. Out of the total 72 patients, 69 were considered for treatment either due to the degree of thrombocytopaenia (< 30x10 9/l) or the Background: Patients with immune thrombocytopenia (ITP) may be at presence of significant bleeding manifestations. All of them were treated with increased risk of thromboembolism because of the abnormal platelet function. steroids initially and 67(97%) achieved a platelet count of more than 50 x 10 9/l Aims: This study aimed to characterize risk of thromboembolic events in ITP patients. during the first course.But only 12(17%) patients managed to retain this Methods: We retrospectively evaluated 239 patients (107 men, 132 women; response and achieve a remission. Out of the patients who relapsed, 6 median age: 61 years) diagnosed between January 1997 and August 2011. underwent splenectomy which led to a remission in 3(50%). In the 54(78%) who Every patient received steroid treatment according to the platelet count and the did not achieve remission, medical second line therapies were not effective. Out extent of bleeding. Logistic regression analysis was used to identify risk factors of the 69 patients who were treated only 15 (22%) went in to complete associated with the development of thromboembolic event after ITP diagnosis. remission. Out of the patients who were considered for treatment, 11(16%) had Results: Sixty-four (26.7%) patients had operation after ITP diagnosis. Among platelets counts less than 30x10 9/l but were asymptomatic and were managed those who had operation, most of them were treatment-responsive (complete by a ‘watch and wait’ policy. Only 1 (9%) of them had bleeding episodes. response 63.7%, response 18.9%) and had manageable postoperative blood Summary and Conclusions: Our study revealed that majority of patients was loss (<250ml) (89.1%). Ten patients (4.2%) developed a thromboembolic event middle aged females with muco cutaneous bleeding. Most of the study subjects after diagnosis. Multivariate analysis revealed that operation (HR 9.998, 95% continued to have low counts througout the disease and remained CI 1.999~50.004, p=0.005) and higher platelet count (>30.0 ×10 9/l) at diagnosis dependent which caused significant long term side effects due to treatment. ITP (HR 4.636, 95%CI 1.157~18.574, p=0.03) were independent risk factor for has a very tumultuous clinical course and assessing each patient and tailoring thromboembolism (Table 1). the management on an individual basis is important. In this study16% of patients with a platelet count below 30 x 10 9/l were safely managed without treatment. Table 1. Demographic and clinical characteristics of patients with immune thrombocytopenia. PB2016 PLATELET KINETIC EARLY NORMALIZATION IS A STRONG PREDICTOR OF SUBSTAINED RESPONSE AFTER DISCONTINUATION OF TREATMENT WITH ROMIPLOSTIM IN IMMUNE THROMBOCYTOPENIC PATIENTS.4 YEARS FOLLOW-UP F Iuliano 1,* A Perricelli 1, E Iuliano 2, A Pomillo 1, G Cervo 1, F Corea 3, S Fortino 1, D Leone 1, F Barbano 4 1Internal Medicine, U.O di Onco-Ematologia S.O. “N.Giannettasio” ASP1 Cosenza, Rossano (CS), 2Internal Medicine, Magna Grecia University S.Venuta Campus, Catanzaro, 3Tor Vergata University , Rome, 4Nuclear Medicine, Casa Sollievo della Sofferenza, S.Giovanni Rotondo, Italy

Background: Background: (TPO)-receptor agonists (romiplostim and eltrombopag) are new therapeutic modalities in the treatment of ITP. Romiplostim treatment was associated with a number of benefits compared with the standard of care in non splenectomized ITP patients: higher platelet response rate, lower rates of treatment failure and splenectomy, fewer bleeding events, and fewer blood transfusions. As reported in different case series only 15% of patients achieve a durable response after treatment discontinuation Summary and Conclusions: ITP patients who had operation have increased Furthermore, there are no criteria to identify patients potentially cured and that risk of thromboembolism, although clinical bleeding was minimal and could stop therapy. For all these reasons we have carried out a study of platelet manageable. Patient who had higher platelet count (>30.0 ×10 9/l) at diagnosis kinetics in all patients treated with TPO- receptor agonists and we have also have increased risk of having thromboembolic event.

haematologica | 2014; 99(s1) | 769 19 th Congress of the European Association

PB2018 P Pecos 1, MJ Rodríguez-Salazar 1, MT Hernández 1 1Hematology, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain THROMBOPOIETIN RECEPTOR AGONISTS (TPO-RA) IN REFRACTORY IMMUNE THROMBOCYTOPENIC PURPURA (ITP): ABSENCE OF CROSS- Background: ITP is an characterized by increased RESISTANCE BETWEEN ELTROMBOPAG AND ROMIPLOSTIM IN TWO platelet destruction and suboptimal platelet production. Thrombopoietin PATIENTS. receptor agonists (TRA) romiplostim and eltrombopag have changed in the L Scaramucci 1,* A Tendas 1, P Niscola 1, D Piccioni 1, A Perrotti 2, M Giovannini 1, last years the treatment of ITP. Both can increase platelet production without P de Fabritiis 1 acting on the , and they are approved for treatment of chronic 1Hematology, Sant’Eugenio Hospital, 2Hematology, San’Eugenio Hospital, ITP in adults. Rome, Italy Aims: To describe the efficacy and safety of romiplostim use for ITP in our center. Background: The recent availability in clinical practice of thrombopoietin (TPO) Methods: We retrospectively analyzed a total of 20 adult patients at our receptor agonists (TPO-RA), such as eltrombopag and romiplostim, which are institution, who were treated with romiplostim for ITP. Clinical and biological effective in increasing the platelet count by stimulating TPO receptor on parameters were recorded as well as treatment response and tolerability. progenitors of megakaryocytic and inducing their proliferation and maturation Results: Our series comprises 9 men and 11 women with a mean age of 59 with relatively low toxicity, has lead to important advances in the therapeutic years (range 19-85). All the patients received steroids as the first line treatment. management of ITP. After that, 65% received rituximab, 65% received anti-D immunoglobulin and The potential absence of cross-resistance between the two drugs, likely Aims: in only 25% splenectomy was performed before starting romiplostim. None of due to their different mechanisms of action, is illustrated by the following them had been previously treated with eltrombopag. The mean number of description of two cases, recently observed by us, with therapeutic response previous lines before romiplostim was 2.7 (range 1-4), and only 3 patients symmetrically opposite to these thrombomimetic drugs, having these two (15%) received romiplostim as second line. Romiplostim was effective, patients failed previous treatment with one or the other agents. increasing platelet count over 50.000/mm 3, in 75% (15/20 cases) of our adult The first case regarded a 54-year old female (Patient A, Figure 1) with Results: ITP patients. However, only six of these patients (30%) are still on treatment. an ITP which was refractory to steroids and intravenous immunoglobulins For the remaining 9 patients in whom romiplostim was successful, the evolution (IVIG); the patient was also unresponsive to romiplostim, which dosage was was as follows: four patients achieved a resolution of ITP and they are currently appropriately escalated and maintained at the maximum weekly dose of 10 without treatment; two patients stopped the treatment after 4 and 43 months, mcg/kg for about 4 weeks. So that, eltrombopag (50 mg/day) was started because of poor adherence; finally, three patients died while they were on (Figure 1). A prompt platelet response (platelet count: 41 × 10 9/L) was observed treatment with normal platelet count. The average dose among patients in 1 week after the start of treatment (Figure 1). A complete response was which romiplostim was effective was 2.9 μg/kg/week. In five patients (25%) achieved after other 4 weeks of treatment, being the patient on 50 mg/day of romiplostim was not effective, and the maximum dose they received ranged eltrombopag without any adverse events. However, at that time, after four from 5 to 10 μg/kg/week before stopping the treatment. Two of these patients additional weeks of eltombopag, the platelet count exceeded 350 × 10 9/L. died while they were on treatment without response. Change of TRA from Therefore, eltrombopag was withdrawn. Since then, 19 months after treatment romiplostim to eltrombopag took place in 5 patients due to three circumstances: discontinuation (Figure 1), her platelet count was maintained between 189 and lack of efficacy (2 cases), platelet count fluctuations (1 case), and poor 367 × 10 9/L; the last platelet count performed in February 2014 was of 312 × adherence (2 cases). In this setting, eltrombopag was effective in 4 of these 5 10 9/L. The second case (Patient B, Figure 1) was a 73 years old woman with cases (80%). We have analyzed if age, duration of the disease, number of a 5-years history of steroid-refractory ITP and occasional IVIG requirement. She previous lines of therapy, the previous use of rituximab or anti-D refused splenectomy so that eltombopag was started at the dose of 25 mg/day immunoglobulin, or previous splenectomy, may be associated with efficacy of and then escalated to 50 mg/day and finally 75 mg/day; the last dose was romiplostim. We found statistically significant association only with the number maintained for 4 weeks without any benefit (Figure 1). Therefore, she was of prior lines, with a higher probability of efficacy in patients with fewer prior lines started on gradually increasing subcutaneously doses (from 1, 3, 7 to 10 (p=0.033). In terms of drug tolerability, our results were: no adverse effect in mcg/kg/week) of romiplostim for a total of eight weeks, achieving platelet counts 12 patients (60%); a mild adverse event (grade <2) which did not require higher than 20 and 80 x 10 9/L after 4 and 8 weeks respectively. To date, about decrease or suspension of any dose, mostly headache, joint and muscle pain, 29 months after the first dose (Figure 1), a normal platelet count is maintained in 5 cases (25%); an adverse event grade 3 (headache) requiring dose by romiplostim without any side effects. reduction was observed in two patients (10%); finally, only one patient (5%) presented a severe adverse event, grade 4 (deep venous and ) which required temporary suspension of the treatment. Five deaths occurred on treatment, but none of them seems to be related to romiplostim; three of them (60%) had an infectious etiology, in which previous immunosuppressive treatments may have played some role. Summary and Conclusions: In our series, romiplostim was effective in 75% of ITP adult patients, including ITP resolution in 20% of cases. The number of prior lines of therapy seems to be related to the efficacy of treatment, achieving a better response those patients with fewer prior lines. In our experience, tolerability to romiplostin is quite good and only a dose reduction or a temporary suspension of the drug is occasionally required.

PB2020 RITUXIMAB IN HAEMATOLOGICAL AUTOIMMUNE DISEASES: A SINGLE CENTRE EXPERIENCE MP Simula 1,* E Usala 1, A Emanuele 1 1Ematologia e CTMO Ospedale Oncologico Cagliari, Cagliari, Italy

Background: Rituximab is a anti-CD20 monoclonal antibody broadly used in the treatment of lymphomas CD20+ that have shown efficacy also in the treatment of autoimmune disorders. Aims: We report the outcome results of 21 consecutive adult patients (14 Figure 1. females and 7 males) with autoimmune diseases treated with Rituximab in our Hematology Department. Sixteen of them had primary immune Summary and Conclusions: In conclusion, we suggest that further thrombocytemia (pITP), 1 ITP secondary to HCV infection, 1 cyclic ITP, 2 confirmation of a distinct pattern of response and the absence of cross- suffered from autoimmune hemolytic anemia (AHA), 1 from Evans syndrome resistance between these two thrombomimetic drugs should be explored by (ES). All the patients received Rituximab after failure of at least one previous prospective studies by directly comparing the two TPO-RAs. line of therapy (always including also steroids) or after relapse. Tirthteen had a standard dose (SD) of Rituximab (375 mg/m 2 weekly for four administrations) PB2019 and 8 low dose (LD) (100 mg flat dose weekly for four administrations); all EFFICACY AND SAFETY OF ROMIPLOSTIM FOR TREATMENT OF patients but 2 completed the planned 4 doses of drug: 1 of these, a pITP INMUNE THROMBOCITOPENIA (ITP): EXPERIENCE OF A SINGLE patient, had 3 administrations and the other (the ES patient) had only 2 doses CENTER because of sudden hearing loss considered probably related to the drug. C Stoica 1, S Lakhwani 1,* JM Raya 1, M Fernández-González 1, B Soria 1, During the therapy with monoclonal antibody all of our patients continued low

770 | haematologica | 2014; 99(s1) Milan, Italy, June 12 – 15, 2014 doses steroids that stopped when the response occurred.The median age at from). IVIG and steroid responses were too historical to be analyzable and too infusion of Rituximab was 55 years (range 26-80 y).The median time between few patients had had a splenectomy. Based on the initial analysis, an updated, diagnosis and Rituximab therapy was 43 months (range 1-345). simplified version of the questionnaire will be used in a larger study to identify Results: The overall response was 61.9% (13/21: 11 females (78%) and 2 sub-groups of patients in whom onset of ITP and other characteristics can be males (28%)), particularly 9 out of 16 pITP patients had a complete response related to outcomes including but not limited to treatment response. (CR) (56%), the HCV associated ITP had a partial response (PR) (100%), the 2 AHA had a CR as the Evans syndrome patient (100%). Only 2 of the responders relapsed (15%), they had both pITP (relapse rate: 22%) and their PB2022 recurrence of disease occurred after 6 months in one case and 71 months in the other. Tirthteen patients were less than 60 years old (62%) and 8 more PREDICTORS OF PLATELETS COUNT IN PEDIATRIC PATIENTS WITH than 60 y (38%) at the time of anti-CD20 immunotherapy; in the first age group CONGENITAL CYANOTIC HEART DISEASE R Matter 1, I Ragab 1,* A M Roshdi 2, A G Ahmed 1 6 responded (46%), in the older one 7 (87%) (p 0.058). Considering only pITP: 1Pediatrics, 2cardiology, Ain Shams University, Cairo, Egypt 4 (25%) received Rituximab in the first year of disease, 12 (75%) after 1 y and between those 9 (56%) after 5 y; the responses were 75%, 37%, 44% Congenital heart defects are the commonest non-infectious respectively (p 0.38). The median time to response was 1.4 months (range: 5 Background: causes of mortality in newborns in the western world. Erythrocytosis, days-8 months) and its median duration 17.6 months (1-70). Nine of 11 patients thrombocytopenia, platelet function defects, factors deficiencies still in response had a follow up (FU) shorter than 2 y (81%), 2 (19%) had a are the main hematologic disorders described in cyanotic congenital heart longer FU time. Considering the dose, 7 of the recipients of SD responded disease. (54%) , so did 6 of those had LD (75%). P(0.058). Considering sex of to assess the immature platelets fraction in pediatric patients with responders 11 were females and 2 males (p 0.026). The side effects were 4, Aims: congenital heart disease and thrombocytopenia compared to non reported in 3 patients: we observed a grade 1 , a grade 1 abnormal thrombocytopenic , detecting the risk factors that may predispose patients with liver function test , 1 reversible hearing loss and 1 relapse of a sarcoma. congenital heart disease to low platelet count Summary and Conclusions: Our experience confirms that Rituximab is an Methods: The study included 60 pediatric patients with congenital cyanotic effective and safe therapy option in the management of autoimmune diseases heart diseases attending at pre-catheter visit at Ain-Shams University- and, although the small number of people analyzed could represent a limitation, cardiology department between October 2012 and July 2013.Patients were does show better response in females but there was not significant differences subjected to history taking including data for age , gender , type of congenital according the age, the dose of the drug and the duration of the disease. cyanotic heart disease, age of onset of cyanosis , cyanotic episodes and their frequencies , drugs and family history. Physical examination included anthropometric measures, oxygen saturation by pulse-oximetry and vital PB2021 signs. Laboratory investigation included complete blood count (CBC) using A SURVEY OF THE ETIOLOGY OF IMMUNE THROMBOCYTOPENIA (ITP) Coulter Counter GEN-S (Coulter Corporation, USA), C-reactive protein (CRP) N Haq 1, S Darwish 1, V Arias 1, J Stein 2, E Shabbir 1, J Bussel 1,* by latex agglutination test using spectrum kits latex (Fortress, England), 1Department of Pediatrics, Division of Hematology, Weill Cornell Medical reticulated platelet count as a marker of platelet production using Sysmex XE- College-New York Presbyterian Hospital, New York, 2Biostatistics Unit, The 2100 (Sysmex, Japan), Prothrombin Time (PT , Pro Time) test, Partial Feinstein Institute for Medical Research North Shore- LIJ Health System, thromboplastin time (PTT ) and D-dimer for patients with thrombocytopenia. Manhasset, United States Results: Our patients had a median age of 18.5 months and interquartile range of 51 months 30, (65.2%) males and 16 (34.8%) females. Nine patients had Background: Immune Thrombocytopenia Purpura (ITP) is an autoimmune transposition of great arteries, 30 patients had tetralogy of Fallot, 6 patients had disorder characterized by accelerated platelet destruction and suboptimal double outlet right ventricle and one of them had single ventricle. There was no platelet production. Patients with ITP have variable disease progression and significant difference between patients with thrombocytopenia and patients with response to treatment indicating that ITP has a heterogeneous etiology. Factors normal platelet count as regard demographic data or clinical presentation, type contributing to this heterogeneity are not well understood. of congenital cyanotic heart disease or C-reactive protein status. Immature platelets fraction (IPF) was higher in patients with thrombocytopenia 14.15±5.2 Aims: To determine patterns relating socioeconomic, environmental and lifestyle factors associated with treatment response in ITP patients. compared to non-thrombocytopenic 6.68± 3.39(P=0.003), and PT was longer (17.08±3.37, 13.99±1.41 sec, P= 0.01 respectively) with no difference in PTT Methods: A self-reported prospective questionnaire-based study was created based on literature searches and 45 ITP patient interviews. The survey was between both groups (P=0.272). A significant positive correlation was found reviewed by Platelet Disorder Support Association (PDSA) members and between platelets count with D-Dimer and a significant negative correlation hematologists, revised and then administered to ITP patients at Weill Cornell with PT and IPF. A significant positive correlation was also found between IPF Medical College-New York Presbyterian Hospital. The survey comprising of 83 and hemoglobin, RBC count , Hematocrit, PT and reticulocytic count, and a multi-step questions relating to socioeconomic, environmental and other patient significant negative correlation between IPF and MCHC, D Dimer, platelets characterization factors was given to 110 patients or the patients’ parents if the count, reticulocyte hemoglobin content and platelets large fraction. Patients patient was <18 years old. 95 subjects were analyzed for the treatment with different types of CCHD had no significant difference as regard platelets responses (15 did not receive treatment) and all 110 subjects for overall patient count. There was significant higher RDW and D Dimer in patients with TOF. There was significant higher mean platelet volume and PT in patients with characteristics. Associations between responses to rituximab and CRP positive compared to those with CRP negative. thrombopoietic (TPO) agents (Eltrombopag and/or Romiplostim), and potential thrombocytopenia was detected in 13% of the factors influencing ITP were assessed using chi-square and fisher’s exact test. Summary and Conclusions: screened pediatric patients with congenital cyanotic heart disease. Immature All analyses were performed using SAS version 9.3 (Cary, NC). platelets fraction as a marker for platelets production; together with D-dimer Results: Patients were between 1 - 89 years old (median age: 37 years). Of were elevated in patients with thrombocytopenia suggesting peripheral platelets 110 patients, 19 had ITP for<6 months, 80 had ITP for > 6 months and 11 did destruction as an underlying mechanism for thrombocytopenia. RBC count not specify duration. Rituximab treatment outcomes: 63 subjects received ,hemoglobin level, hematocrit and reticulocyte hemoglobin content as a marker Rituximab, of which 21 had complete response (CR), 10 partial response (PR), for iron deficiency were not significant determinants for platelet count. and 32 no response (NR). Factors significantly associated with poor response to Rituximab included: more stress prior to diagnosis, specifically having a relative pass away (p=0.001 for CR/PR vs. NR and p=0.007 for CR vs. NR); PB2023 easy bruising/increased petechiae (p=0.027 for CR vs. NR) and exercise infrequency prior to diagnosis (p=0.025 for CR vs. NR). TPO agent treatment THROMBOTIC THROMBOCYTOPENIC PURPURA AND SJOGREN outcomes: 56 subjects received TPO agents, of which 45 had CR, 8 PR, and SYNDROME, A RARE ASSOCIATION 3 NR. Factors significantly associated with poor response to TPO agents R Mendes Silva 1,* M Santos 1, R Guilherme 1, E Cortesao 1, L Rito 1, ML Ribeiro 1 included subjects experiencing fatigue prior to diagnosis (P=0.02 for CR vs. PR 1Hematology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal vs. NR); frequent drinking of cranberry juice prior to diagnosis (p=0.005 for CR vs. PR vs. NR) and having diabetes (P=0.007 for CR vs. PR vs. NR). Background: Thrombotic thrombocytopenic purpura (TTP) is a rare and serious Summary and Conclusions: Preliminary analysis in this pilot study indicates disease that is potencially lethal without prompt recognition and treatment. The potential associations between unexpected epidemiologic factors and treatment classic pentad of symptoms consists of microangiopathic hemolytic anemia, response. Subjects who did not experience stress from a relative passing away, thrombocytopenia, renal impairment, central nervous system involvement and exercised more prior to the diagnosis of ITP, and who did not have easy fever. However, virtually any system may be affected. Sjögren’s syndrome (SS) bruising/increased petechiae responded better to rituximab treatment. Subjects is a common autoimmune disease with exocrine gland damage, with special who did not experience fatigue, did not frequently drink cranberry juice prior to salivary and lacrimal envolvement. TTP is frequently associated with connective the diagnosis of ITP, and those who did not have diabetes appeared to respond tissue diseases (1-6% in general population), but association with Sjogren better to TPO agents. Surprisingly, these results did not identify environmental, syndrome (SS) is rare. The etiology remains unclear in about 37% of the cases chemical or toxic exposures to be related to response to treatment (outcome of TTP and can be associated with autoimmune diseases in 13% of the cases.

haematologica | 2014; 99(s1) | 771 19 th Congress of the European Hematology Association

The association of SS and PTT is a rare condition, with high death rate, only 14 1Pediatric hematology department, 2Necmettin Erbakan University Meram cases reported to date, at our knowledge. Measuring of ADAMTS13 activity is Medical Faculty, Konya, 3Ankara University medical faculty, Ankarak, Turkey helpful for a correct diagnosis of PTT which has a specific treatment, differentiating it from another thrombotic microangiopathies. Background: Glanzmann thrombasthenia (GT) is an inherited disorder of Aims: Report of two cases of TTP in context of a SS, with different clinical platelet aggregation, characterized by qualitative and quantitative defect on outcomes. platelet αIIb- β3 integrin (GpIIb/IIIa), resulting in lifelong bleeding tendency due Methods: Review of clinical data about two patient admitted in 2013 in our unit to defective platelet plug formation. with diagnosis of TTP associated with SS. Abnormal levels of ADAMTS13 Aims: In this study, we examined 20 patients with Glanzmann thrombasthenia activity were considered under 40% and abnormal titer of ADAMTS13 antibody for clinical findings and molecular genetic analysis to determine whether there above 15 U/I, according to our lab. was any mutation in the GPIIb gene, and a correlation between clinical Results: Case 1: A 40 year old healthy woman presented to the emergency phenotype and genotype. This is the first genetic study conducted in Turkey service (ES) with subit aphasia, hemiparesia and confusion. Images studies about GT. were normal. Laboratory data showed Hb 10,1 g/dL, platelets 6 G/L, Methods: There were twelve females and eight males with a median age of schystocyte on blood smear, LDH 709 U/I and indirect bilirrubin 1,4 mg/dL. 15.25 years. The most common bleeding type was epistaxis (85%). Life Creatinine and hemodinamic status were normal. Patient started immediately threatening were seen in five patients. plasma ex-change (PEX), after collecting blood samples for study of an Results: Seven (35%) patients showed various mutations (five novel and two eventual TTP. Extreme low activity (0%) of ADAMTS13 and high level of anti- previously described mutations) in the GPIIb gene. Novel mutations including ADAMTS13 confirmed the diagnosis of acquired TTP. Patient was furtherly 9079 T>A (p. S416G), 9092 G>T (p. V420L) and 9179 T>A (p. P448T) were studied and autoimmune panel showed strong positivity for anti-SSA60 and located in exon 13. The others including 4466 G>T (p.G159V) and 11453A>G anti-SSB what was suggestive of SS, besides lacking classic symptoms of this (p.T646A) were located in exon 4 and exon 19, respectively. Previously autoimmune disease. After 6 sessions of daily PEX and corticotherapy, patient described mutations including 4420 T>G (p.V147G) and 9607 T>G were was in complete response (>48h of platelets > 150 G/L and no symptoms) and located in exon 4 and exon 13, respectively. No correlation was found between remains stable. Case 2: A 59 year old woman, with know history of SS and clinical phenotype and genotype. already under corticotherapy (5mg prednisolone daily) presented to the ES Summary and Conclusions: In conclusion, our findings showed that exon 13 with epistaxis, gingivorrhagia and mild abdominal pain. Blood analytics showed was an important region for platelet aggregation; therefore, we suggest that 13 Hb 12,1 g/dL, platelets 6 G/L, creatinine 1,49 mg/dL (acute renal insufficiency), patients without diagnosis of mutation may have mutations in β3 integrin gene. LDH 1683 U/L, and indirect bilirrubin of 3,2 mg/dL. No schizocytes reported at Furthermore, molecular genetic analysis should be performed in these presentation. Corticotherapy was intensified, but clinical situation deteriorated patients. with appearance of paresthesia and general muscle weakness. Blood smear showed schizocytes and the possible diagnosis of TTP was assumed, with beggining of PEX. Patient became hemodynamic unstable, with neurologic PB2026 aggravation and elevation of cardiac enzymes. The situation had a quick and inexorable evolution to death. Low levels of ADAMTS13 activity (0%) and very THROMBOPOIETIN LEVEL IN HCV EGYPTIAN PATIENTS high antibody titer (>99 U/L) confirmed the diagnosis of acquired PTT. N El- Husseiny 1,* HM fahmy 1 Summary and Conclusions: Either TTP or SS are rare entities. Association 1Clinical Haematology Unit, Kaser Al Aini, Giza, Egypt of both is far rarer. The combination of SS and TTP has particular high death rate, so high suspicion is essential to quick start of therapy. Background: Thrombocytopenia is a common finding in patients with chronic hepatitis. A variety of pathogenic mechanisms are reported to be implicated in thrombocytopenia related to chronic HCV infection. PB2024 Aims: The aim of the present study is to evaluate the role of thrombopoitin (TPO) in pathogenesis of thrombocytopenia in HCV infected patients and to THE ROLE OF THROMBOPOIETIN RECEPTOR AGONISTS (TPO-R) IN THE demonstrate if there is a correlation between TPO level and viral load, degree TREATMENT OF CHRONIC IMMUNE THROMBOCYTOPENIA OF ADULT- of inflammation and degree of fibrosis. THE EXPERIENCE OF FUNDENI CLINIC OF HEMATOLOGY This study was carried out on a group of 30 HCV infected patients I Ursuleac 1,* AC Colita 1, M Vasilica 1, RA Stoia 1, D Coriu 1 Methods: 1Hematology, Fundeni Clinical Institute, Bucharest, Romania recruited from Kasr El-Eini hospital. Liver function tests, polymerase chain reaction (PCR) for HCV, complete blood counts, serum TPO levels and abdominal ultrasonography were done to all case. Patients were classified according to their Background: TPO-R agonists represent an available therapeutical option for those patients with chronic immune thrombocytopenia ( ITP) refractory or with viral load into 3 groups Group I (6 cases) with low viral load Group II (14 cases) contraindication for splenectomy. The two agents are : Eltrombopag( Revolade) with moderate viral load and Group III ( 10 cases) with high viral load. with oral ,daily administration and Romiplostim( N’Plate), with subcutaneously, Results: showed that platelets count and serum TPO are significantly higher weekly administration. Clinical trials showed their efficacy in order to maintain in patients with mild viremia compared with groups with moderate or high a safe number of platelets ~50000/mmc ,prevent fatal bleeding and offer to the viremia . No statistically signific ant differences were found between group II and patients a good quality of life with few adverse reactions. III. Liver biopsies were done for 17 patients. It was found that the platelets Aims: To evaluate indications for TPO-R treatment of patients diagnosed with count is significantly higher in patients with mild inflammation ( Group A) when ITP and clinical evolution after the treatment. compared with patients with moderate inflammation ( Group B) . Again TPO Methods: a clinical epidemiological retrospective study of 33 patients with ITP, was found to be significantly higher in Group A when compared with Group B. treated with TPO-R agonists in Fundeni Clinic of Hematology between 2011- When those patients were classified according to degree of fibrosis, the platelet 2013. count showed significant relationship with degr ee of fibrosis being higher in Results: therapeutical indications were – third line therapy ( failure after patients with less fibrosis. A positive correlation between platelets counts and splenectomy and ):6 patients; bridging through splenectomy -11 serum TPO was found. patients; second line therapy- 13 patients( 4 patients with hepatitis C and B Summary and Conclusions: several contributing factors may lead to HCV active infection, who undergone concomitant antiviral therapy, maintaining related thrombocytopenia , of which TPO level which is affected by viral load , normal level of platelets).The age was variable, between 21-68 years old. 27 grade of inflammation , stage of fibrosis ,being the higher viral load and the patients received Eltrombopag and 9 patients Romiplostim. 2 patients received more inflammation and fibrosis ,the lower level of TPO and accordingly the both Eltrombopag and Romiplostim. 29 patients responded with platelets above lower platelets counts. 50000/mmc,9 of them had a sustained response,maintained after stopped medication :4 after Romiplostim therapy and 5 after Revolade treatment . 2 patients were lost from evidence. During treatment were reported as adverse PB2027 reactions headache, artralgias and one female patient had a transient episode of hepatocytolysis and cholestasis, but without clinical evidence. BONE MARROW EXAMINATION IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA: IS THERE ANYTHING DIFFERENT IN OLDER Summary and Conclusions: the TPO-R agonists are a good option for the treatment of ITP refractory patients , for splenectomy bridging or for those with PATIENTS? E Gunduz 1,* B Kara Kivanc 2, M Karagulle 1, D Arik 3, S İsiksoy 3, C Bal 4, OM antiHCV/HVB therapy. The terapy is safe, with minimum adverse events. 1 Because of the financial reasons the period of the treatment is limited. Akay 1Hematology, 2Internal Medicine, 3Pathology, 4Biostatistics, Eskisehir Osmangazi University School of Medicine, Eskisehir, Turkey Immune thrombocytopenia (ITP) is a disorder characterized by PB2025 Background: immune-mediated accelerated platelet destruction and supressed platelet NOVEL MUTATIONS IN THE GPIIB GENE IN TURKİSH CHILDREN WITH production. In the bone marrow examinations of patients with ITP, some GLANZMANN THROMBASTHENIA investigators found megakaryocyte numbers to be increased while others have H Tokgoz 1,* U Caliskan 2, N Akar 3 found them to be normal. Similarly,abnormal megakaryocyte morphology

772 | haematologica | 2014; 99(s1) Milan, Italy, June 12 – 15, 2014 including diminished granularity and decreased nuclear ploidy among other PB2029 findings were observed by some investigators but not by others. Although recent guidelines recommend against bone marrow examinations in typical ITP CHANGES IN PLATELET AGGREGATION DURING PREGNANCY AND patients the recent introduction of thrombopoietin receptor agonists as an IMMEDIATE POSTNATAL PERIOD B Hussein 1,* J Davies 1, K Gomez 1, R Kadir 1 effective treatment for ITP has refocused attention on abnormalities of bone 1 marrow megakaryocytes. Centre and Thrombosis Unit, Royal Free Campus, University College London, London, United Kingdom Aims: In this sudy, we retrospectively analysed the bone marrow aspiration, flow cytometry-CD45 sidescatter (SSC) and biopsy results of our patients with Platelet dysfunction is implicated in uteroplacental disorders. ITP by dividing them into two groups according to age (<60 years and ≥60 Background: During the early stages of gestation platelets have important roles in the process years) and tried to determine the differences between two groups. of placentation. Platelet function contributes to enhanced haemostasis at Methods: Ninety eight newly diagnosed ITP patients who were admitted delivery. However, there is limited data on the changes of platelet function between 2010-2013 and who had available bone marrow aspiration, CD45 during normal pregnancy. Understanding physiological changes of platelet SSC and biopsy results are included in the study. ITP was diagnosed according aggregation during different stages of pregnancy is helpful for better to American Society of Hematology criteria with a platelet count below understanding of pathophysiology of abnormal placentation. 100x10 9/L and no cytopenias except iron deficiency anemia. Since all patients To assess platelet aggregation during three trimesters of pregnancy and with thrombocytopenia (<100x10 9/L) undergo bone marrow biopsy regardless Aims: immediate postnatal period in normal healthy women compared to control non- of age in our clinical practice, patients are divided into two groups: <60 years pregnant group. old (group 1) and ≥60 years old (group 2). All bone marrow aspirates and Cross-sectional cohort study including a total of 46 women: 10 biopsies were performed using the same techniqueand the same method of Methods: participants for each trimester, 10 postnatal cases and 6 control non-pregnant slide preparation. CD45 SSC results were recorded as percentages of women. Case selection was based on specific inclusion criteria. 30mL of venous normoblasts, granulocytes, lymphoctes, monocytes and myeloid/erythroid ratio. blood was obtained from each participant following consent. Light transmission Bone marrow biopsies were evaluated by experienced pathologist. Length of aggregometry was performed with Dual channel Payton 600B aggregometer the specimen, cellularity, presence of dysplasia or fibrosis with number, using six platelet aggregating agonist (epinephrine, adenosine triphosphate, morphology and distributionof megakaryocytes were recorded. Informed collagen, ristocetin, arachidonic acid and U46619). consent was obtained from patients. Results: Platelet aggregation in response to ADP and epinephrine was In group 1 there were 49 patients. Mean age was 41.31±12.77 years, 31 Results: decreased in 4/10 and 3/10 women in the first trimester, respectively. A (63.3%) female and 18 (36.7%) male. In group 2 there were 49 patients. Mean age significant difference ( p=0.0075) was detected in percentage aggregation at 3 was 70.78±7.88 years, 26 (53.1%) female and 23 (46.9%) male. All blood and bone minutes induced by epinephrine 2 µM in the first trimester group compared to marrow samples were obtained before starting therapy for ITP. Unfortunately, non-pregnant controls (47% vs 82%). In addition, mean aggregation at 3 megakaryocyte numbers on bone marrow aspirates were not recorded in most minutes induced by epinephrine 3µM was reduced in the first trimester (48% patients so we could not comment on this point. However, flow cytometry results vs 82%) ( p=0.0042). 6/10 and 4/10 women in the third trimester had abnormal and bone marrow findings were not different between two groups. aggregatory response to ADP 2 μM and ADP 3 μM respectively. A significant Summary and Conclusions: In conclusion, we could find no difference difference ( p=0.0005) was detected in percentage aggregation at 3 minutes with between bone marrow examinations of young (<60 years) and older (≥60 years) ADP 2 μM in the third trimester compared to non-pregnant controls (45% vs patients with ITP and our study supports that biopsy should not be 81%). One woman had abnormal aggregation response in the third trimester recommended in typical ITP patients as already mentioned in guidelines. including prolonged lag time and reduced maximal aggregation with collagen, and reduced maximum aggregation with ristocetin 1.5 mg/ml, arachidonic acid and U46619. PB2028 Summary and Conclusions: Pregnancy is associated with reduced platelet IMMUNE THROMBOCYTOPENIA IN THE ELDERLY: CLINICAL COURSE reactivity in response to epinephrine during early pregnancy and an abnormal AND TREATMENT aggregation response to ADP in the third trimester. These changes may have C Ionita 1,* I Ionita 1, L Cheveresan 1, M Ionita 1, D Calamar 1, D Oros 1, I Hortensia 1 important role in the process of placentation in early pregnancy as well as 1Hematology, University of Medicine and Pharmacy “Victor Babes” Timisoara, haemostasis at delivery. Timisoara, Romania

Background: Immune thrombocytopenia (ITP), which is often diagnosed in PB2030 the elderly, is a hematologic disorder characterized by thrombocytopenia THE ANTIOXIDANT TREATMENT IN PATIENTS WITH IMMUNE induced by autoimmune mechanism. THROMBOCYTOPENIA Aims: In this study, we evaluated the clinical features, the risk of bleeding and AM Gaman 1,2 , * MA Gaman 3 the response to various treatment options in elderly ITP patients (age≥60 yr) at 1Hematology, Filantropia City Hospital, 2Pathophysiology, University of our center from 1980 to 2012. Medicine and Pharmacy of Craiova, Craiova, 3”Carol Davila” University of Methods: A retrospective study for 210 ITP patients was performed in Medicine and Pharmacy, Bucharest, Romania Department of Hematology, County Hospital, Timisoara, Romania. Patients demographics, medical history, current treatments and side effects, were Background: Oxidative stress (OS) plays a role in the pathophysiology of abstracted from the patient’s medical charts for the 12 months prior to their most immune thrombocytopenia (ITP). Several studies revealed increased reactive recent visit. oxygen species (ROS) levels and a decreased antioxidant capacity in ITP, Results: The median age was 65 years with 61% women and 39% men. The suggesting a possible antioxidant mechanism of therapy in chronic ITP. 9 median platelet count was 22×109/L (range 1-75×10 /L) at diagnosis. Median Aims: To evaluate the response of treatment in patients with ITP, with and time from the diagnosis of ITP to the start of the observational period was 23 without antioxidants. months. Prior to the observational period, 28% of patients had been Methods: We studied 24 patients with chronic immune thrombocytopenia splenectomized and the most reported treatment was corticosteroids. During hospitalised in the Clinic of Hematology from Craiova (Romania) between 2011 the observational period, 65% of all patients were treated. The most frequent and 2013, with high levels of reactive oxygen species (FORT test) and low reasons given for treatment were platelet count (58%), followed by bleeding antioxidant capacity (FORD test). The patients were distributed in two groups: symptoms (49%). Corticosteroids represented 63% of treatments, followed by 12 patients (group A) received only corticosteroids as first line therapy and 12 IVIg (20%), azathioprine (8%) and rituximab (3%). Splenectomies (4% of patients (group B) received corticosteroids and antioxidant supplementation patients) and platelet transfusions (38% of patients) were performed during the (informed consent obtained). observational period. For monitoring the platelet levels, 70% of patients visited Results: In group A, seven patients responded to corticosteroids and the non- their hematologist 1 to 6 times during the observation. Main reasons for a visit responders were treated, as second line therapy, with Vinca alkaloid regimens were a low platelet count (42% of visits) and bleeding (34% of visits). (one), laparoscopic splenectomy (two) or thrombopoietin receptor agonists In the evaluable 15 patients who died during follow up, eight deaths were (two). In group B, eleven patients responded to corticosteroids plus antioxidant considered. To be directly attributable to hemorrhage induced by supplementation; at one there was necessary a second line therapy thrombocytopenia. (thrombopoietin receptor agonist). Follow-up at one year revealed that all eleven Summary and Conclusions: There are more females in the ITP patients over patients who received antioxidant supplementation and had a healthy diet were 60 years of age. The risk of bleeding is quite high in elderly ITP patients, but in clinical complete remission, whereas only seven patients from group A were life-threatening bleeding events rarely occur. This study provides the results in clinical remission. of treatment practices in our country. Summary and Conclusions: In our small groups of patients, the antioxidant supplementation had a beneficial role in the response to therapy and the evolution of patients with ITP.

haematologica | 2014; 99(s1) | 773 19 th Congress of the European Hematology Association

PB2031 prophylactic measure during delivery), 2 required blood and platelet transfusion, 2 received blood alone and one only platelet transfusion. Pregnancy outcome DEMOGRAPHICAL AND CLINICAL CHARACTERISTICS OF ELDERLY was 10 alive babies without any complications. PATIENTS WITH IDIOPATHIC THROMBOCYTOPENIC PURPURA: A Summary and Conclusions: This review revealed a high risk of PPH in RETROSPECTIVE MULTICENTER STUDY 1 * 2 2 3 1 1 2 women with HPS. Close collaboration between obstetric and haemophilia team I Nizam , H Terzi , S Korkmaz , M Keklik , I Kuku , E Kaya , M Sencan , is essential to reduce this risk. M Cetin 3, L Kaynar 3, O Ilhan 4 1Hematology, Inonu University, Malatya, 2Hematology, Sivas University, Sivas, 3Hematology, Erciyes University, Kayseri, 4Hematology, Ankara University, Ibni Sina Hospital, Ankara, Turkey

Background: Idiopathic thrombocytopenic purpura (ITP) is a chronic, immune- mediated disease characterized by a temporary or sustained decrease in platelet counts. ITP is associated with various clinical consequences which may be serious, especially for the elderly, when it’s not properly treated. Aims: We aimed to present our experience about 50 elderly patients with ITP from 4 different centers. Methods: Data from 4 centers in Anatolia were collected and analyzed in order to put forward the demographical and clinical characteristics of elderly patients with ITP over the age of 65. Results: Total of 50 patients who were above the age of 65 at the time of ITP diagnosis were evaluated retrospectively. Sixty-two percent of the patients were female. The mean age was 71,5±6 (SD) years. Among the comorbidities, hypertension was the most common disease with a percentage of 24%, followed by coronary artery disease and diabetes mellitus, both with a rate of 8% and chronic obstructive pulmonary disease with a rate of 3%. Ninety-two percent of the patients had no organomegaly, while 4% had mild hepatomegaly and 2% had mild splenomegaly and 2% had mild hepatosplenomegaly. Mean followup duration was 31,6 ±25 (SD) months. At the time of evaluation, 94% of the patients were alive, 6% were deceased, and reasons of death were not related to ITP. Mean hemoglobin value was 13,13±1,9(SD) gr/dl. Female patients had statistically significant lower hemoglobin levels, compared to male patients. Mean platelet count was 12.760±10.000(SD)/µl . There was no significant difference between two genders in terms of platelet count. As first line therapy, 86% of the patients were given methylprednisolone, 8% were given dexamethasone and 6% were followed up without therapy. Mean remission duration after first line therapy was 27,9±22,8(SD) months. As second line therapy, 45% of the patients were given methylprednisolone, 35% were given dexamethasone, 10% were performed splenectomy and 10% were treated with other modalities. Ninety percent of the patients responded well to the second line therapy. Mean remission duration after second line therapy was 12,9±8,5(SD) months. Twelve percent of the patients needed third line therapy, where 50% of these were given eltrombopag, 33% had splenectomy and 17% were given rituximab. All patients responded well to the third line therapy. Mean remission duration after third line therapy was 17,9±18,9(SD) months. Summary and Conclusions: Female and male patients had similar platelet counts, where female patients tend to have lower hemoglobin levels. Female patients had longer remission durations at first line therapy, compared to the male patients and the difference was statistically significant. Studies with larger patient groups should be performed in order to see if there’s a difference between genders in terms of response to therapy.

PB2032 HERMANSKY-PUDLACK SYNDROME DURING PREGNANCY: A SYSTEMATIC REVIEW B Hussein 1,* A Chaqmaqchi 2, K Gomez 1, R Kadir 1 1Haemophilia Centre and Thrombosis Unit, Royal Free Hospital , London, United Kingdom, 2Haematology Department, Nanakali Hospital For Blood Disorders and Cancer, Erbil, Iraq

Background: Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive disorder, it is characterised by oculocutaneous albinism, and decreased visual acuity. HPS can also cause pulmonary fibrosis, inflammatory bowel disease and renal diseases. The prevalence of HPS is 1 in 500000 – 1000000 and in Puerto Rico is 1 in 1800 with carrier rated 1 in 21. Aims: To see how does Hermansky-Pudlack syndrome affect the pregnancy, labour/delivery and postpartum period. Methods: Review of literature of HPS during pregnancy wa performed for the period of 1970 to 2010 which is revealed 7 articles including 11 pregnancies in 8 women (4 were from Puerto Rico). Results: The commonest bleeding symptoms in these women were menorrhagia, easy bruising and nose bleeding. There was no reported ante partum haemorrhage. Haemostatic coverage for labour and delivery was given in 7 pregnancies, platelet transfusion in 2 and DDAVP in 5 pregnancies. Mode of delivery was emergency caesarean section in 3 pregnancies (all for obstetric indications) and remaining had vaginal delivery. Regional analgesia used in one woman without haemostatic cover and no complications. Postpartum haemorrhage reported in 6 pregnancies (including one who had DDAVP as

774 | haematologica | 2014; 99(s1)