Intracranial Hemorrhage in Egyptian Children with Primary Immune Thrombocytopenia (ITP): Report of 24 Cases in 20 Years

Background: 35 million children < 18 years; approximately 1800 new cases of ITP were diagnosed annually in Egypt. Intracranial hemorrhage (ICH) is a rare devastating complication of childhood immune thrombocytopenia (ITP). Incidence of ICH among children with ITP varies markedly in different studies from 0.2 up to 1.0 %. Intracranial hemorrhage after head trauma in children with ITP leads to significant morbidity and mortality. We published data during 1997 - 2007 (10 ICH) in children with primary ITP; risk factors and outcome. Aim & Methodology: A follow-up study to assess any change in outcome of ICH from last decade; whether new therapies might change the landscape of ICH. Centers treating > 25 child with prim ITP /year and offered a complete data of >150 children with ITP over 2 decades were enrolled. We compared 2008 - 2018 with the decade before it; variation of ICH reporting from center to center and outcome in relation to therapy. All children with ITP and ICH during study period had been treated, within < 24 hours and referred to neurosurgical hospital complex facility for consultation and intervention. Time elapsed till receiving platelet enhancing therapy and neurosurgical intervention was assessed, Outcome whether a complete recovery, permanent sequalae or death was reported. Results: Four thousand, three-hundred and forty primary ITP were evaluated, ( 380 were excluded due to incomplete data ) Twenty-four (0.6%) ICH were reported over 2 decades (14 in this decade with 20% increase incidence) and 48 matched ITP control subjects were evaluated. Platelet counts were less than 10 x 10(9)/L in 90% of children with ICH. Four (16.2%) children developed ICH within 14 days of diagnosis of ITP; one of these, was the presenting feature of ITP. four were from 3-12 months and sixteen (66.6%) of children had chronic ITP. Centers treating > 50 case/year had a higher frequency of reporting 0.8 % compared to 0.2 % in centers < 50 cases/year. Outcome is better on early intervention as well as aggressive platelet enhancing therapy with 70% complete recovery compared with 30% complete recovery on delayed intervention. Head trauma and hematuria and PC < 10 were the mostly associated with ICH, identified in 33%, 25% and 90% respectively of the patients with ICH and in 1, none and 50% of the controls (P < .001). Bleeding beyond petechiae and ecchymoses was also linked to ICH. Mortality was 25%; a further 25% had neurologic sequelae. Neurosurgical intervention was done in 25% of cases with good outcome. Reporting was more in this decade with better outcome in bigger centers. Conclusion: A rise in the incidence of ICH in Children with severe thrombocytopenia over last decade; high risk for ICH among those with PC< 10,000 plus head trauma and/or hematuria. Platelet enhancing agents whether HDMP or IVIG or TPO-RAs could not prevent ICH. However they had a good impact on survival and lessen sequalae if used in combination. Strategies by which high-risk children could be identified and well managed in small centers. Disclosures No relevant conflicts of interest to declare.

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Intracranial hemorrhage (ICH) in children with immune thrombocytopenia (ITP): study of 40 cases

Blood ◽

10.1182/blood-2009-04-215525 ◽

2009 ◽

Vol 114 (23) ◽

pp. 4777-4783 ◽

Cited By ~ 123

Author(s):

Bethan Psaila ◽

Aleksandra Petrovic ◽

Lemke K. Page ◽

Jill Menell ◽

Matthew Schonholz ◽

...

Keyword(s):

High Risk ◽

Head Trauma ◽

Intracranial Hemorrhage ◽

Immune Thrombocytopenia ◽

The United States ◽

Severe Thrombocytopenia ◽

Aggressive Treatment ◽

Neurologic Sequelae ◽

Immune Thrombocytopenia Purpura ◽

High Risk Children

Abstract Intracranial hemorrhage (ICH) is a rare but devastating complication of childhood immune thrombocytopenia purpura (ITP). A survey of ICH from 1987 to 2000 identified cases of ICH in childhood ITP in the United States. Forty patients with ICH and 80 matched ITP control subjects were accrued. The estimated incidence of ICH was 0.19% to 0.78%. Platelet counts were less than 20 × 109/L in 90% and less than 10 × 109/L in 75% of children with ICH. Eighteen (45%) children developed ICH within 7 days of diagnosis of ITP; for 10 of these, ICH was the presenting feature of ITP. Twelve (30%) children had chronic ITP. Head trauma and hematuria were the most prominent features associated with ICH, identified in 33% and 22.5% of the patients with ICH and 1 and none of the controls (both P < .001). Bleeding beyond petechiae and ecchymoses was also linked to ICH. Mortality was 25%; a further 25% had neurologic sequelae. Strategies by which high-risk children could be identified were considered, and the costs of preventive combination treatment were estimated. Children with severe thrombocytopenia plus head trauma and/or hematuria appeared to be at particularly high risk of ICH. Aggressive treatment of these children may be appropriate.

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Megakaryocyte Abnormalities Occur In The Absence Of Cell-Mediated Immunity In a Murine Model Of Passive Immune Thrombocytopenia (ITP)

Blood ◽

10.1182/blood.v122.21.3537.3537 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3537-3537

Author(s):

John W. Semple ◽

Kristin Hunt ◽

Yu Hou ◽

Rukhsana Aslam ◽

Edwin R. Speck ◽

...

Keyword(s):

Bone Marrow ◽

Immune Thrombocytopenia ◽

Conflicts Of Interest ◽

In Vivo Model ◽

Cell Mediated Immunity ◽

Severe Thrombocytopenia ◽

Platelet Destruction ◽

Platelet Counts ◽

Antiplatelet Antibodies ◽

Platelet Antibodies

Abstract Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by increased peripheral immune platelet destruction and megakaryocyte defects in the bone marrow. Although ITP was originally thought to be primarily due to humoral mediated autoimmunity it is now evident that T cells can also play a contributing role to the thrombocytopenia. In fact, the exact interplay between platelet destruction, megakaryocyte dysfunction, and the elements of both the humoral and cell mediated immune systems still remain incompletely defined. In murine passive models of ITP, the direct administration of anti-platelet antibodies can result in severe thrombocytopenia which is evident within 24 hours of injection. While most studies have focused on immune platelet destruction in the spleen, an additional possibility is that the anti-platelet antibody also has an effect on megakaryocytes. To unequivocally determine if antiplatelet antibodies have an effect on megakaryocytes in an in vivo model, BALB/c mice were intravenously administered 2 ug of an anti-GPIIbIIIa antibody (MReg30) or 50 uL of a high tittered anti-GPIIIa (anti-β3) serum from BALB/c GPIIIa (CD61) knockout mice immunized with wild type platelets. Platelet counts were assessed over time and the bone marrow and spleens were harvested for histological examination of megakaryocytes. Both preparations of antiplatelet antibodies significantly reduced platelet numbers within 1 day of antibody or serum administration. This thrombocytopenia could be rescued by administration of 2 g/kg of IVIg ip. Compared with naïve control mice, histological (H&E staining) examination of the bone marrow and spleens revealed that megakaryocytes were significantly increased in number and all exhibited abnormalities consistent with apoptosis e.g. pyknotic nuclei. IVIg administration completely prevented these megakaryocyte abnormalities. These results show that passively administered anti-platelet antibodies not only affect platelet counts but also significantly affect megakaryocyte physiology in the absence of cell mediated immunity. Disclosures: No relevant conflicts of interest to declare.

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The First Case Report of Tazobactam Induced Thrombocytopenia

Blood ◽

10.1182/blood-2019-126227 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4897-4897 ◽

Cited By ~ 1

Author(s):

Minh-Tri H. Nguyen ◽

Pavneet Kaur ◽

Richard H. Aster ◽

Vidya Krishnan

Keyword(s):

Platelet Count ◽

Lower Extremity ◽

Immune Thrombocytopenia ◽

Conflicts Of Interest ◽

Complex Case ◽

Chronic Obstructive ◽

Severe Thrombocytopenia ◽

Beta Lactam ◽

Diffuse Abdominal Pain ◽

First Case

Drug-induced immune thrombocytopenia (DITP) is a rare and often overlooked cause for thrombocytopenia. It is a particularly difficult diagnosis given its rarity and because at least 100 different medication have been implicated. Cases of piperacillin-tazobactam-induced DITP have sparked growing interest given how common this antibiotic is used. Few studies, however, have defined the specific moiety causing the suspected DITP by serologic testing. When this has been done, only piperacillin has been implicated. Here, we describe the first case of DITP in which tazobactam was implicated by serologic studies. Case A 62 year-old-male with a past medical history of Crohn's disease, alcohol use disorder and chronic obstructive pulmonary disease (COPD) presented to the hospital with bilateral lower extremity pain and redness, and diffuse abdominal pain for 1 week. His home medications included pravastatin, meloxicam, pantoprazole and adalimumab. Physical exam, lab testing and imaging studies provided evidence for lower extremity cellulitis, multifocal pneumonia and possible colitis. In the Intensive care unit the patient was started on broad-spectrum antibiotics (vancomycin and piperacillin-tazobactam). He developed new onset thrombocytopenia to <20 K/UL (>50% drop within 72 hours) by hospital day 3, and vancomycin was discontinued. A peripheral smear showed no evidence of schistocytes or platelet clumps. Subcutaneous heparin was discontinued and supportive care with vasopressors, antibiotics and RRT was continued. Patient's septic shock improved, and he was eventually weaned off the vasopressor support. However, his thrombocytopenia persisted which prompted further workup as shown in Table 2. After initial workup remained unrevealing, piperacillin-tazobactam was discontinued and he was started on cefepime on hospital day 11. On day 12, his thrombocytopenia started to improve and showed an upward trend over next 48 hours. At this point antibiotic associated thrombocytopenia was highly suspected so antibiotic specific antibodies to piperacillin-tazobactam were requested. Platelet count on the day of discharge (hospital day 18) was 72 K/UL (Figure 1). IgM antibodies that reacted with normal platelets only when tazobactam was present in the reaction mixture were identified in laboratory testing performed by the Platelet and Neutrophil Immunology Laboratory of Versiti-BloodCenter of Wisconsin. Discussion Serologic findings made in this very complex case indicate that severe thrombocytopenia was caused by an IgM antibody that recognized normal platelets only in the presence of tazobactam. Tazobactam is almost invariably given with piperacillin to inhibit bacteria-derived penicillinase and prolong the lifespan of piperacillin in vivo but, although numerous cases of piperacillin-induced thrombocytopenia have been described, this is the first report in which tazobactam has been documented as the trigger for immune thrombocytopenia. While tazobactam, like piperacillin, contains a beta-lactam structure, tazobactam-specific antibiotic testing may have implications on choosing future antibiotic therapies (particularly penicillins) for a patient. DITP occurring in the ICU can often be over-looked because patients tend to be critically ill and there may be many other reasons for a low platelet count. It is important to keep this diagnosis in mind whenever severe thrombocytopenia develops. Additionally, further work may seek to understand whether a patient's penicillin allergy may be specific to a moiety such as tazobactam, allowing continued use of other types penicillin-class drugs. Disclosures No relevant conflicts of interest to declare.

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Immune Thrombocytopenia in Antiphospholipid Syndrome: Is It Primary or Secondary?

Biomedicines ◽

10.3390/biomedicines9091170 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1170

Author(s):

Riccardo Tomasello ◽

Giulio Giordano ◽

Francesco Romano ◽

Federica Vaccarino ◽

Sergio Siragusa ◽

...

Keyword(s):

High Risk ◽

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Immune Thrombocytopenia ◽

Antiplatelet Agents ◽

Warning Sign ◽

Severe Thrombocytopenia ◽

Appropriate Treatment ◽

Hemorrhagic Risk ◽

Antigenic Targets

Antiphospholipid syndrome (APS) is frequently associated with thrombocytopenia, in most cases mild and in the absence of major bleedings. In some patients with a confirmed APS diagnosis, secondary immune thrombocytopenia (ITP) may lead to severe thrombocytopenia with consequent major bleeding. At the same time, the presence of antiphospholipid antibodies (aPL) in patients with a diagnosis of primary ITP has been reported in several studies, although with some specific characteristics especially related to the variety of antigenic targets. Even though it does not enter the APS defining criteria, thrombocytopenia should be regarded as a warning sign of a “high risk” APS and thus thoroughly evaluated. The presence of aPL in patients with ITP should be assessed as well to stratify the risk of paradoxical thrombosis. In detail, besides the high hemorrhagic risk in secondary thrombocytopenia, patients with a co-diagnosis of APS or only antibodies are also at risk of arterial and venous thrombosis. In this narrative review, we discuss the correlation between APS and ITP, the mechanisms behind the above-reported entities, in order to support clinicians to define the most appropriate treatment strategy in these patients, especially when anticoagulant or antiplatelet agents may be needed.

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Anatomical Distribution of First VTE Event and Risk of VTE Recurrence: Long Term Follow-up and Retrospective Analysis of 346 Patients. Experience From a Single Center

Blood ◽

10.1182/blood.v118.21.1224.1224 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1224-1224

Author(s):

Emmanouil Papadakis ◽

Dionysia Theocharidou ◽

Anastasia Mpanti ◽

Anastasia Spyrou ◽

Konstantinos Loukidis ◽

...

Keyword(s):

Risk Factors ◽

Statistical Analysis ◽

High Risk ◽

Conflicts Of Interest ◽

Statistical Significance ◽

Recurrence Risk ◽

Published Data ◽

Anatomical Distribution ◽

Independent Risk Factors

Abstract Abstract 1224 Venous thromboembolism (VTE) is a chronic disease with recurrence risk that persists over the years. Predicting the chance of recurrence on an individual basis is of paramount importance for the appropriate tailoring of anticoagulant therapy. Recurrence risk is affected by thrombophilia and is lower in patients with provoked VTE than in patients with unprovoked thrombosis. Up to date there are no studies focused on the recurrence risk according to the anatomical distribution of the 1st VTE event. In order to evaluate the risk factors of VTE recurrence, after a review of relevant literature we set specific laboratory and clinical variables, which could be associated with VTE recurrence. Moreover, we evaluated retrospectively 346 patients of the Haemostasis Unit, who had already had an episode of VTE concerning the risk of VTE recurrence. Data statistical analysis was done with SPSS package 15.0. At first a monovariable statistical model was used with significance levels set at p= 0.05. For the multivariable statistical analysis model we used all variables with p< 0.1 from the previous model and those mentioned at recent medical literature as significantly related with VTE recurrence. The 346 patients enrolled had already suffered a first episode of VTE and are being followed up regarding VTE recurrence. The study population, 169 (48.7%) male and 178 (51.3%) female, had a mean age at first VTE of 41.54 years. The exclusion criteria of our study were: high risk patients for VTE recurrence who received indefinite anticoagulation (n=72), patients who have suffered VTE and had a follow up period after discontinuation of anticoagulation shorter than 2 years (n=73) and patients who were lost at follow up (n=15). Among 194 patients who were enrolled 108 (55.7%) were women and 86 (44.3%) men, with a mean age at 1st VTE of 40.10 years. 114 patients had only one VTE episode, 59 suffered two, 16 patients had tree episodes and 5 patients had >= 4 episodes. Based on previously published data we tried to define whether the following variables are high risk factors for VTE recurrence in our population: gender, age of diagnosis, thrombophilic factors (FVLeiden, FII, HCY, VIII, AT, PrC, PrS, PAI1, Lp(a), XII), the presence of unprovoked VTE episode and VTE location (DVT, PE, CNS Thrombosis). Male gender p=0,038, FVLeiden homozygous p=0.036, the presence of unprovoked VTE p=0.029, and VTE location p= 0.05 reached statistical significance on a monovariable analysis. Based on the previous analysis and on previously published data we applied gender, age at the time of diagnosis, presence of unprovoked VTE episode and VTE location on a multiple regression analysis in order to define independent risk factors concerning VTE recurrence (Table 1).Table 1Independent Risk factors concerning VTE recurrenceRisk FactorORCI 95%FVLeiden9.7931.07–89.62Unprovoked VTE9.7571.404–5.414Pulmonary embolism11.5321.419–93.746Deep Venus Thrombosis (DVT)17.7932.232–141.841 Concerning VTE location, CNS thrombosis has the lowest risk for VTE recurrence and Pulmonary embolism and DVT are independent risk factors compared to the first one. Among VTE events CNS thrombosis and DVT/PE share similarities regarding the transient risk factors and the presence of predisposing thrombophilias. As far as the recurrence risk after a first VTE our study demonstrates ( in agreement with current literature) that CNS thrombosis carries recurrence risk statistically lesser than PE and the highest recurrence risk carry the patients after a first DVT event. Our study is the first observational study regarding recurrence risk after VTE coming from Greece. Disclosures: No relevant conflicts of interest to declare.

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Platelet-Associated Antibodies By Flow Cytometry in Adult Patients with Immune Thrombocytopenia before and after Splenectomy

Blood ◽

10.1182/blood-2020-140945 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 4-5

Author(s):

Kseniya A. Nikiforova ◽

Elena K. Egorova ◽

Yuliya O. Davydova ◽

Nikolay M. Kapranov ◽

Elena I. Pustovaya ◽

...

Keyword(s):

Flow Cytometry ◽

Peripheral Blood ◽

Immune Thrombocytopenia ◽

Conflicts Of Interest ◽

Polyclonal Antibodies ◽

Fluorescein Isothiocyanate ◽

Platelet Glycoprotein ◽

Rank Test ◽

Severe Thrombocytopenia ◽

Becton Dickinson

Introduction Immune thrombocytopenic purpura (ITP), or primary immune thrombocytopenia is an autoimmune disease characterized by isolated thrombocytopenia (number of platelets in peripheral blood is less than 100×109/L) and splenic production of antibodies against platelet glycoprotein complexes and megakaryocytes, resulting in hemorrhagic syndrome. Circulating platelets attached by autoantibodies that leads to accelerated removal of these cells by spleen macrophages. The therapy for patients with newly diagnosed ITP with hemorrhagic syndrome and/or severe thrombocytopenia (number of platelets in peripheral blood <10-20×109/L) includes corticosteroids and characterized by a low rate of remission (just around 20-30%). For cases of ITP resistant to corticosteroid therapy recommends one of the second-line method of treatment - splenectomy (SE). Approximately 60-80% of the patients achieve complete remission after splenectomy. There is a technique for assessment of platelet-associated antibodies (PAA) classes IgG, IgM and IgA on platelets by flow cytometry. This method is a commodious, easy, quick, and relatively cheap and applied to estimate autoimmunity status of patients with thrombocytopenia. However, this method characterized by low specificity. Aim The aim of the study was to determine the correlation between level of PAA of IgG, IgM, and IgA classes in the peripheral blood of adults with ITP before SE, 5-7 days and 3 months after SE. Patients and methods The study included 21 patients with ITP (4 cases of persistent ITP and 17 cases with chronic form). Median age was 36.9 years, M:F ratio was 1: 4.25 (men was older than women - 46.0 years old versus 34.7). All patients underwent from 1 to 3 lines of therapy and were recommended for SE due to resistance to treatment. The PAA level was measured at three time points (before SE, 5-7 days, and three months after SE) by flow cytometry (Becton Dickinson FACS Canto II). Goat polyclonal antibodies against human IgG, IgM, IgA labeled with fluorescein isothiocyanate (FITC) (Cedarlane) were used to determine antibodies of various classes. Anti-CD41a labeled with phycoerethrin (Becton Dickinson) was used to determined platelets. PAA level was assessed based on the mean of fluorescence intensity (MFI) of the FITC-channel. Statistic analysis was carried out using GraphPad Prism 6.01. Wilcoxon signed-rank test had been used for pair comparison. The value of 0.05 had been taken as reliable. Results MFI levels of PAA IgA (391 vs 198, p = 0.005) and IgM (275 vs 142, p<0.0001) significantly decreased in patients after SE compared with the initial level (level before SE). Level of MFI PAA IgM also remained reduced (275 vs 138, p=0.0084) three months after SE (Fig. 1). MFI levels of PAA IgG did not change. Conclusions Using of flow cytometry to determinate platelet-associated immunoglobulins for diagnostic of ITP remains controversial. Despite the fact, this test can be recommended for monitoring of PAA from patients with ITP after SE. In addition, the results confirm the fact that most cells producing antiplatelet antibodies seems to be residing in a spleen. Disclosures No relevant conflicts of interest to declare.

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The Day 1 Postoperative Platelet Count Predicts Splenectomy Response in Patients with Immune Thrombocytopenia (ITP)

Blood ◽

10.1182/blood.v124.21.1448.1448 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1448-1448

Author(s):

Shylaja Mani ◽

Hashim Abbas ◽

Akhil Parashar ◽

Keith R. McCrae

Keyword(s):

Logistic Regression ◽

Platelet Count ◽

Medical Therapy ◽

Immune Thrombocytopenia ◽

Conflicts Of Interest ◽

Cleveland Clinic ◽

Complete Response ◽

Stepwise Logistic Regression ◽

Severe Thrombocytopenia ◽

Platelet Counts

Abstract Background: Immune thrombocytopenia (ITP) in adults is generally a chronic disorder that may lead to severe thrombocytopenia and bleeding. Though several medical modalities such as thrombopoietin receptor agonists have become available for the management of ITP withinin the last decade, splenectomy remains a valuable option for management of refractory ITP, with approximately 2/3 of treated patients remaining in complete remission 10 years afterwards. However, there are no consistent and reliable predictors of splenectomy response for an individual patient with ITP. Since patients with ITP who fail to respond to splenectomy can develop significant bleeding in the postoperative period it is important to identify those individuals early after their surgical procedure so that aggressive medical intervention may be employed. Despite this concern, there is little information available on the value of postoperative platelet counts obtained soon after splenectomy in predicting the ultimate outcome of surgery. Objectives: The goal of this study was to define the value of platelet counts determined soon after splenectomy on the ultimate success of splenectomy in inducing remission of ITP. Methods: We reviewed the medical records of 66 patients who underwent splenectomy for ITP at the Cleveland Clinic from 2000-2013. A complete response was defined as a stable platelet count >100 x109/L two months after splenectomy without medical therapy. Stepwise logistic regression with backward selection was used to identify significant predictors of complete response. Results: The 66 patients had a median age of 41(IQR 21-56) with a male:female ratio of 1:2. The median platelet count at the time of diagnosis was 12 x 109/L and 43% of the patients had severe ITP (defined per IWG guidelines as bleeding that mandates treatment). Ninety percent of patients were steroid dependent, and 39%, 15% and 5% had been treated with rituximab, eltrombopag or romiplostim respectively. The median time to splenectomy from diagnosis of ITP was 22 months (IQR 6-44 months). At a median follow up of 35 months after splenectomy, 39 patients (59%) achieved a complete response. The median platelet count prior to and 24 hours after splenectomy in responders and non-responders is shown in Table 1. Logistic regression analyses identified a post-op day 1 platelet count greater than the median platelet count of 112 x 109/L (OR- 3.72, CI- 1.14-12.16, p<0.03) and post-operative day 3 platelet count greater than median platelet count of 175x 109/L (OR- 4.87, CI- 1.37-17.2, p<0.01) as a significant predictor of splenectomy response. The probability of response based on the post-operative day 1 platelet count is depicted in Figure 1. The difference between the pre-splenectomy and post-operative day 1 platelet count was also a significant predictor of response (OR 1.01 (1.0001-1.02), p=0.04), (figure 2). The log of the time from the diagnosis of ITP to splenectomy (OR- 0.61, CI 0.40-0.94, p<0.02) was also a weak, but significant predictor. Increased numbers of prior treatments for ITP prior to splenectomy correlated with a decreased response, although this relationship was not statistically significant. Conclusion: The platelet count on postoperative day 1 is a significant predictor of long term response to splenectomy, with almost 4-fold increased probability of achieving remission if this value is >112 x 109/L .This is among the first studies to examine the prognostic value of the platelet count obtained this early after splenectomy, and suggests that in patients with severe ITP and a persistently low postoperative platelet count on day 1, medical therapy should be considered to prevent bleeding. Our data also suggests that responses to splenectomy may be less frequent in patients with a longer interval between ITP diagnosis and splenectomy. Disclosures No relevant conflicts of interest to declare.

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Treatment of Acute Promyelocytic Leukemia (APL) At Tawam Hospital UAE

Blood ◽

10.1182/blood.v120.21.4347.4347 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4347-4347

Author(s):

Arif Alam ◽

Harimohan Narayanan ◽

Shanaaz Sonday ◽

Sabir Hussain ◽

Amar Lal ◽

...

Keyword(s):

Retinoic Acid ◽

High Risk ◽

Supportive Care ◽

Arsenic Trioxide ◽

Acute Promyelocytic Leukemia ◽

Conflicts Of Interest ◽

Early Death ◽

Promyelocytic Leukemia ◽

Published Data ◽

Female Ratio

Abstract Abstract 4347 Acute Promyelocytic Leukemia (APL) is a unique sub-type of Acute Myeloid leukemia associated with a balanced reciprocal translocation between chromosomes 15 and 17 and 80% of the cases present with bleeding diathesis caused by severe coagulopathy. The translocation generates a fusion transcript joining the PML(promyelocyte) and RAR-α (retinoic acid receptor-α) genes. The therapy of APL has been revolutionized by the introduction of differentiating agents All Trans Retinoic Acid (ATRA) and Arsenic Trioxide. All patients were treated as per Pethema protocol. Initially LPA99 (Sanz MA. Blood. 1999 Nov 1;94(9):3015-21) and since January 2012 a risk adapted therapy based on LPA2005 (Sanz MA et al. Blood June 24, 2010 vol. 115 no. 25 5137–5146). Treatment included induction followed by 3 cycles of consolidation and two years of maintenance. Nineteen patients were diagnosed with APL between January 2009 and June 2012. Three patients are excluded from the analysis as karyotyping and/or PCR did not confirm the diagnosis. The median age was 35 years (range 22–53 years). Male to female ratio was 4:1. Nine (56%) patients were stratified as high risk (WBC ≥ 10 ×109/l) while, seven (44%) as intermediate risk and low risk (WBC < 10 ×109/l). Three (19%) patients had early death despite treatment and supportive care. The cause of death was intracranial hemorrhage (1) pulmonary hemorrhage (1) and multi-organ failure (1). Thirteen patients achieved a complete morphological and molecular remission (80%). There has been only 1 case of treatment failure (high risk at presentation). This patient was successfully re-induced with arsenic trioxide and achieved second molecular complete remission. Unfortunately he relapsed a second time and is currently alive in third morphological remission but remains PCR positive for PML/RARα 33 months after diagnosis. Our limited experience shows favorable outcome (CR 80%) for the treatment of APL using the Pethema protocol compared to published data (Tallman MS. Blood 2002;99(3):759–767). Early death rate remains high despite intensive supportive care. The only variable is the availability and initiation of ATRA at the clinical suspicion of diagnosis both at the referring hospitals and treatment center. Disclosures: No relevant conflicts of interest to declare.

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Efficiency and Safety of Eltrombopag for Multi-Line Failed Chinese Patients with Immune Thrombocytopenia: Cases with Decreased Megakaryocyte Response Well from Single Center Experience

Blood ◽

10.1182/blood-2021-149374 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2082-2082

Author(s):

Qi Liu ◽

Yingying Shen ◽

Yuzhu Li ◽

Huijing Hu ◽

Wenbin Liu ◽

...

Keyword(s):

Nk Cells ◽

Peripheral Blood ◽

Immune Thrombocytopenia ◽

Conflicts Of Interest ◽

Chinese Patients ◽

Ivig Treatment ◽

Severe Thrombocytopenia ◽

Line Treatment ◽

Upper Respiratory Tract ◽

First Line

Abstract Immune thrombocytopenia (ITP) is an autoimmune disease characterized by decreased platelet (PLT) count in peripheral blood and marrow megakaryocyte dysfunction, which was induced by antiplatelet antibodies or cytotoxic T cells. Many ITP patient were previously full response to first-line treatment such as corticoids (CIS) or immunoglobulin (IVIG), but were intolerant or relapse during the maintenance treatment, and turn to receive recombinant human thrombopoietin (rhTPO), rituximab (RTX), splenectomy as well as immunosuppressive therapy (IST). Unfortunately, there still some patients failed to multiple treatments are faced with high bleeding risk. Eltrombopag, the first oral non-peptide thrombopoietin receptor agonist (TPO-RA) that approved by US FDA in 2008, is the second-line treatment option for chronic ITP based on guideline recommendation. As reported, the effective rate of eltrombopag in ITP ranges from 59% to 89.7%, and limited predictive factors were available to assess the efficiency for individual. The characteristic of marrow megakaryocyte (MK) in ITP was reported as normal or hyper megakaryocytosis on the initiation (before treatment), however there are also ITP patients with decreased marrow MK, and the response of eltrombopag to these patients have not been fully reported. Bone marrow aspiration is a routine examination in China for the diagnosis of ITP with severe thrombocytopenia. Therefore, we conducted a research tried to assess the efficiency of eltrombopag to patients with multi-line failed ITP, and analyzing the possible factors may contribute to the differences based on personal characteristic. Thirty-five multi-line failed ITP patients with PLT count bellow 30× 10 9/L who received eltrombopag treatment were enrolled, and divided into three groups, the hyper-MK (MK count>35, n=17), normal-MK (8-35, n=10) and hypo-MK (≤7, n=8) groups. The average PLT count was 10.63±6.30×10 9/L before eltrombopag treatment, and it increased significantly to 12 (2-65)×10 9/L, 39 (2-212)×10 9/L, 68 (2-453)×10 9/L, 60 (3-358)×10 9/L, and 75 (3-308)×10 9/L in the 1st, 2nd, 4th, 6th , and 8th weeks after treatment (all P=0.000, except 1st week). The median intervals time required for platelet to reach 30×10 9/L and 100×10 9/L for the first time were 11 (4-40) and 21 (10-65) days, respectively (Fig. A-C). We found the overall, complete (PLT count ≥100×10 9/L) and partial response (PLT count ≥30×10 9/L or at least twice the baseline value) rates were 54.3% (n=19), 48.6% (n=17), and 5.7% (n=2) respectively to eltrombopag in our center. The overall response rate of patient with decreased MK was 75%, which was unexpectedly higher than the patient with increased or normal MK count (52.9% and 40%, respectively) (Fig. D). To explain the underling mechanism, we detected the peripheral T lymphocyte, B lymphocytes and NK cells before eltrombopag. Results showed that the patient with decreased MK were characteristic with higher T helper (Th) cells (39.62±2.01%) and regulatory T (Tregs) cells (7.93±1.63%) when compared to the hyper-MK (30.44±10.95%, 4.23±1.67%) and normal-MK group (25.67±5.72%, 4.81±2.12%). For patient with poorer eltrombopag response group, more percentage and absolute number of NK cells (15.48±7.12%, 234.4±91.80×10 6/L) were found in peripheral blood (Fig. E-F). We also discovered that previous first-line (CIS or IVIG) treatment, rhTPO effectiveness, RTX splenectomy and IST had no influence on eltrombopag response (Fig. G). As for safety, nine eltrombopag related adverse events were reported, and most commonly were upper respiratory tract infection (8.6%), elevated ALT (5.7%), and venous thrombosis (5.7%). All the side effect was cured by symptomatic treatment, eltrombopag dose reduction or discontinue. In summary, ITP patients with decreased megakaryocyte respond well to eltrombopag, and the abnormality of NK cells may play a role in patients exert a poor response. In further clinical practice, we should considering the megakaryocytes count as well as peripheral NK population to better predicting eltrombopag response in ITP patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Neuroradiologic timing of intracranial hemorrhage in abusive head trauma

Pediatric Radiology ◽

10.1007/s00247-020-04824-9 ◽

2021 ◽

Vol 51 (6) ◽

pp. 911-917

Author(s):

Mark S. Dias ◽

Krishnamoorthy Thamburaj

Keyword(s):

Head Trauma ◽

Intracranial Hemorrhage ◽

Abusive Head Trauma

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