COVID-19 vaccination associated severe immune thrombocytopenia

Abstract Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has emerged as a deadliest global pandemic after its identification in December 2019 in Wuhan, China resulting in more than three million deaths worldwide. Recently FDA issued emergency authorization for three vaccines for prevention of COVID-19. Here in, we report three cases of severe immune thrombocytopenia (ITP) following COVID-19 vaccination and their clinical course. Case presentations Case #1: 53 year old male with past medical history of Crohn’s disease was admitted for myalgias and diffuse petechial rash 8 days after receiving second dose of Pfizer-BioNTech COVID-19 vaccine. A complete blood test showed a platelet count of 2 × 109/L. Patient did not have a prior history of thrombocytopenia and other causes of thrombocytopenia were ruled out by history and pertinent lab data. He received two doses of intravenous immunoglobulin and oral dexamethasone for 4 days resulting in normalization of platelet counts. Case #2: 67 year male with past medical history of chronic ITP in remission was admitted for melena 2 days after receiving his first dose of Pfizer-BioNTech COVID-19 vaccine. A complete blood test showed a platelet count of 2 × 109/L. Physical exam showed generalized petechiae. There was no history of recent flares of ITP and patient had normal platelet counts following his splenectomy 4 years ago. He received two doses of IVIG and oral dexamethasone for 4 days with gradual improvement in platelet counts. Case #3: 59 year old female with past medical history of chronic ITP secondary to SLE was admitted for bloody diarrhea 2 days after receiving her first dose of Johnson and Johnson COVID-19 vaccine. Physical exam was unremarkable. A complete blood test showed platelet count of 64 × 109/L which dropped to 27 × 109/L during hospital course. She received oral dexamethasone for 4 days with improvement in platelet counts. Conclusion COVID-19 vaccination induced ITP has been recently acknowledged. However, given very few cases and limited data, currently there are no guidelines for management of ITP caused by COVID-19 vaccine as well as vaccination of people with predisposing conditions.

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What Goes Down, Might Come Up!

Pediatric Medical Emergencies ◽

10.1093/med/9780190946678.003.0009 ◽

2020 ◽

pp. 83-94

Author(s):

Sharon E. Mace

Keyword(s):

Weight Gain ◽

Family History ◽

Medical History ◽

Diagnostic Testing ◽

Physical Exam ◽

Past Medical History ◽

Bilious Vomiting ◽

Underlying Illness ◽

History Of ◽

Comprehensive History

In infants, vomiting is usually benign, but it can also portend significant underlying illness or injury. It is important to remember that although vomiting is commonly from the gastrointestinal (GI) tract itself, it may also be due to more generalized, systemic disorders or injuries (non-GI causes). As with most pediatric complaints a comprehensive history and physical exam is critical to direct both diagnostic testing and management. Remember the past medical history in infants includes neonatal history, growth and developmental history (include weight gain), social and family history. A history of bilious vomiting in an infant should always raise concerns occurs with obstruction, therefore, bilious vomiting always warrants evaluation.

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Effects Of Thrombopoietin Receptor Agonists On APRIL Plasma Levels In Patients With Immune Thrombocytopenia

Blood ◽

10.1182/blood.v122.21.1083.1083 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1083-1083

Author(s):

Nora V. Butta ◽

Mayte Álvarez Román ◽

Ihosvany Fernández Bello ◽

Elena G. Arias Salgado ◽

Isabel Rivas Pollmar ◽

...

Keyword(s):

Platelet Count ◽

T Cell ◽

Regulatory T Cell ◽

Plasma Levels ◽

Immune Thrombocytopenia ◽

Cell Activity ◽

Healthy Controls ◽

Platelet Counts ◽

Chronic Itp ◽

Thrombopoietin Receptor

Abstract Introduction Immune thrombocytopenia (ITP) is an example of an autoimmune disease in which B-lymphocytes produce autoantibodies against platelets. Antibody-mediated platelet destruction and suboptimal platelet production leads to a decrease in platelet count. ITP patients with thrombocytopaenia have increased plasma levels of a proliferation-inducing ligand (APRIL), a factor that can promote B-cell maturation and survival. Two new compounds that bind to the thrombopoietin receptor (TPO-R) and activate the megakaryopoiesis have been recently approved for the treatment of chronic ITP as second-line treatment. Objective It has been recently reported an improved regulatory T-cell activity in patients with chronic ITP treated with TPO-R agonists (TPO-RA) (Bao et al, 2010). So we aimed to evaluate the effect of TPO-RA treatment on APRIL plasma levels in ITP patients before (ITP-1) and after responding (ITP-2) to the treatment. Methods This was an observational and prospective study. Thirteen patients with chronic ITP in whom treatment with a TPO-RA was indicated, and thirty-three healthy controls were included. ITP patients were studied at two times: at inclusion (ITP-1), when platelet count was less than 30x109/L for patients without concomitant medication or less than 65x109/L for patients receiving corticosteroids or intravenous immunoglobulin; and after a response to TPO-RA therapy was elicited (ITP-2). The response to TPO-RA was defined as a platelet count >30x109/L in patients without additional treatment or >65x109/L for those with concomitant treatments. EDTA-anticoagulated whole blood was centrifuged at 1,500 g for 15 min at 23°C to obtain platelet poor plasma which was then centrifuged at 10,000 g for 15 min at room temperature. Supernatant plasma was stored at –70°C until analysis. Plasma TPO and APRIL concentrations were determined using a commercially available enzyme-linked immunosorbent assay (ELISA, Duoset-R&D, Minneapolis, Mn, USA). Platelet counts were determined with a Coulter Ac. T Diff cell counter (Beckman Coulter, Madrid, Spain). Comparisons of quantitative variables were made with ANOVA and Dunn test. Results were expressed as mean±SD. Correlations were calculated with Spearman test. Values of p≤0.05 were considered statistically significant. Results Platelet count in the ITP-1 group ((23±17)x109/L) increased after responding to TPO-RA to values similar to controls (controls: (233±77)x109/L and ITP-2: (140±36)x109/L). TPO plasma level was higher in ITP-1 patients (30.05±26.81 pg/ml, p<0.005) than in healthy controls (7.36±11.74 pg/ml) but not significantly different when compared with the values of the ITP-2 group (26.81±17.62 pg/ml). ITP-1 patients showed significantly higher APRIL plasma levels (37.60+28.73 ng/ml, p<0.0001) than controls (2.20±3.11 ng/ml) and ITP-2 patients (4.92+4.68 ng/ml), indicating that TPO-RA treatment caused a diminution in APRIL plasma levels. When looking into the relationship between APRIL plasma levels and platelet count, a significant correlation was only found in the ITP-1 group (r=-0.5919, p<0.05). This supports the potential role of APRIL in the reduction of platelet counts in ITP patients. Conclusion ITP patients with thrombocytopaenia that responded to TPO-RA treatment increased their platelet count reducing plasma APRIL levels and without changing the moderately high levels of plasma TPO. Reductions in APRIL levels caused by TPO-RA treatment could be an additional mechanism that contributes to an increased platelet count in ITP patients treated with these agents. Bao W, Bussel JB, Heck S, et al. Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents. Blood. 2010 Nov 25;116(22):4639-4645 Disclosures: No relevant conflicts of interest to declare.

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A Comparative Prospective Observational Study of Children and Adults with Immune Thrombocytopenia: 2-Year Follow-up

Blood ◽

10.1182/blood.v128.22.3741.3741 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3741-3741 ◽

Cited By ~ 1

Author(s):

Thomas Kuehne ◽

Alexandra Schifferli

Keyword(s):

Platelet Count ◽

Research Funding ◽

Immune Thrombocytopenia ◽

Initial Diagnosis ◽

Diagnostic Methods ◽

Newly Diagnosed ◽

Time Points ◽

Platelet Counts ◽

Chronic Itp

Abstract Introduction It is widely accepted that immune thrombocytopenia (ITP) of children differs from that of adults in the clinical course, such as the rate of spontaneous remission, the bleeding risk and the need of treatment. However, this assumption is limited by incongruity of study populations and divergences of collected information, definitions, study objectives and end-points. Surprisingly, data of the Pediatric and Adult Registry on Chronic ITP (PARC-ITP) at initial diagnosis demonstrated far less differences in clinical and laboratory findings between children and adults than expected (Kühne et al. Haematologica 2011). This suggests that newly diagnosed ITP may be driven by similar pathophysiological mechanisms. Differences may occur in the ability of restoring tolerance. We analyzed 6-, 12-, and 24-month follow-up data of children and adults recorded in the PARC-ITP Registry. Design and Methods PARC-ITP is an international multi-center registry designed to collect data prospectively of children and adults with newly diagnosed ITP, and was opened in May 2004. Demographic information, diagnostic methods, clinical data, and efficacy and safety of management are continuously registered at the time of diagnosis, 6 and 12months and then yearly. Patients younger than 3 months (n=167) and those with a platelet count of >100x109/l were excluded from the analysis. Patients with missing follow-up data at certain time-points were not excluded. Remission of ITP was defined as a platelet count of >100x109/l at any time point and regardless of therapy. Platelet counts of chronic ITP were defined as being <100x109/l at 12 or 24 months. The data were analyzed with descriptive statistics. Results A total of 3'780 evaluable patients with the initial diagnosis of primary ITP were recorded in the PARC-ITP database between 2004 and 2015. There were 3360 children (3 months - 16 years) and 420 adults (≥16 years). The pediatric female: male ratio was 1:1.09, and that of adults was 1:0.54. Follow-up information was available for 67% of children at the 6-month, 49% at the 12-month and 31 % at the 24-month evaluation and in adults in 77%, 64%, and 47%, respectively. In children remission was seen at 6, 12 and 24 months in 70%, 70%, and 71%, and in adults in 45%, 49%, and 56%, respectively. Of the patients with a platelet count of <100x109/l at 6 months, 212/590 children (36%) and 42/152 adults (28%) achieved again a remission at 12-months. The platelet counts of children and adults with chronic ITP at 12 months were 46±30x109/l and 51 ±26x109/l. Adults with a diagnosis of chronic ITP at 12 and 24 months reported having no bleeding in 69% and 65% for the last follow-up period, children in 37% at both time-points. Children with thrombocytopenia at 6, 12 and 24-months received platelet-enhancing drugs in 58%, 46% and 47% and adults in 58%, 52% and 40%, respectively. The diagnosis of secondary ITP and other causes of thrombocytopenia was reported for 123 children, i.e. 3.5%, 1.9% and 1.3% at 6, 12 and 24 months, respectively and 21 adults, i.e. 3.7%, 2.3% and 1.7% at 6, 12 and 24 months, respectively. The reported cause was an infectious disease in both children (49%) and adults (52%). Discussion The PARC-ITP Registry is the first cohort of ITP patients including a mixed pediatric and adult population. Limitations include the variety of participating centers (n=74), data registration on a voluntary basis, a high percentage of loss of follow-up and an unbalanced number of children and adults. Preliminary analyses of follow-up data demonstrate similarities between children and adults in much more areas, than previously assumed. Differences in remission rates where confirmed but in a smaller extent than expected. Treatment requirement in patients with active disease was very similar in both age groups. Surprisingly, adults with a diagnosis of chronic disease exhibited a greater number of a non-bleeding phenotype than children. Conclusion Understanding differences or similarities among children and adults with ITP may guide in finding immune modulatory strategies with the goal of achieving early sustained responses. Disclosures Kuehne: Amgen: Research Funding; UCB Biosciences GmbH: Consultancy. Schifferli:Amgen: Research Funding.

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Rituximab As Second-Line Treatment For Chronic Immune Thrombocytopenia: Investigator-Initiated Clinical Trial In Japan

Blood ◽

10.1182/blood.v122.21.3554.3554 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3554-3554

Author(s):

Yoshitaka Miyakawa ◽

Shinya Katsutani ◽

Takahiro Yano ◽

Shosaku Nomura ◽

Kaichi Nishiwaki ◽

...

Keyword(s):

Clinical Trial ◽

Platelet Count ◽

Research Funding ◽

Immune Thrombocytopenia ◽

Pharmaceutical Research ◽

Japanese Patients ◽

Efficacy And Safety ◽

Platelet Counts ◽

Chronic Itp ◽

Chronic Immune Thrombocytopenia

Abstract The American Society of Hematology guidelines recommend rituximab as second-line treatment, as well as splenectomy and thrombopoietin receptor agonists (TPO-RAs), for chronic immune thrombocytopenia (ITP). However, rituximab has not been approved for the treatment of chronic ITP in Japan. To establish chronic ITP as a new indication for rituximab, we conducted an investigator-initiated clinical trial to clarify the efficacy and safety of rituximab for Japanese patients with ITP. This study was designed as a single-arm, multicenter phase III study. Patients diagnosed with chronic ITP who were previously treated with at least one therapy for ITP and whose platelet count was ≤ 30,000/μL were included. Patients with a past history or current hepatitis B virus, hepatitis C virus or HIV infection, who were treated with splenectomy within 12 weeks or with TPO-RA within 4 weeks were excluded. Rituximab at a dose of 375 mg/m2was intravenously infused once weekly for 4 weeks. Patients were premedicated with acetaminophen, restamin and hydrocortisone to prevent infusion reactions. Platelet counts, bleeding symptoms, and B lymphocyte counts were observed once monthly following the protocol. The primary endpoint was the proportion of patients whose platelet count was ≥ 50,000/μL 24 weeks after treatment with rituximab. Between October 2011 and January 2013, 26 patients were enrolled in this study from 10 hospitals in Japan. Median age of the patients was 40 years and 89% were female. Baseline platelet counts were 23,000/μL. Median interval from diagnosis of ITP to commencing rituximab therapy was 5.9 years. Previous treatment of ITP was corticosteroids (69%), splenectomy (15%), TPO-RA (27%) and intravenous immunoglobulins (39%). At baseline, 58% of patients had some bleeding symptoms. Median number of previous ITP treatments was two. All patients completed the study. At 24 weeks after treatment, 30.8% (95% CI: 14.3–51.8%) of patients achieved platelet counts > 50,000/μL. Seven of eight responders demonstrated improvement until 8 weeks. Platelet count was significantly increased compared with baseline (P<0.001). No unknown severe adverse events were observed. Subgroup analyses showed that ITP duration was numerically associated with the efficacy rate (46% vs 15% for duration< median vs ≥ median, respectively). Bleeding symptoms measured with the WHO bleeding scale were improved compared with baseline. We demonstrated the efficacy and safety of rituximab in Japanese patients with chronic ITP. The response rate was similar to that in previous reports in the US and Europe. We plan to propose that the Japanese government approve chronic ITP as a new indication for rituximab. Disclosures: Miyakawa: Fuji film: Consultancy; Alexion pharmaceuticals: Honoraria; GlaxoSmithKline: Consultancy, Honoraria; KyowaHakkoKirin: Consultancy, Honoraria; Shire: Honoraria. Off Label Use: rituximab, clinical trial. Nishiwaki:Chugai pharmaceutical: Research Funding; Zenyaku Kogyo: Research Funding. Higashihara:Alexion: Honoraria; Asahi Kasei Pharma: Honoraria; Janssen pharma: Honoraria, Research Funding; Takeda: Honoraria; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Shionogi: Honoraria, Research Funding; Nippon Shinyaku: Honoraria, Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; KyowaHakkoKirin: Honoraria, Research Funding; Boehringer-Ingeheim: Honoraria; Daiichi Sankyo: Honoraria; Yakurt: Honoraria; Astellas: Research Funding; Pfizer: Research Funding; Teijin: Research Funding; Meiji Seika pharma: Research Funding; Venesis: Research Funding; Baxter: Research Funding; Torii pharmaceutical: Research Funding; Bristol-Myers Squibb: Research Funding; Dainippon Sumitomo: Research Funding; Taiho: Research Funding; Taisho Tomiyama: Research Funding; MSD: Research Funding. Nishikawa:Daiichi-Sankyo: Research Funding. Ozaki:Chugai pharmaceutical: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Kyowa Hakko Kirin: Honoraria. Kanakura:Alexion Pharmaceuticals: Research Funding, Speakers Bureau. Okamoto:Novartis : Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; GlaxoSmithKlein: Honoraria, Research Funding; KyowaHakkoKirin: Honoraria, Research Funding; Chugai: Honoraria, Research Funding.

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Efficacy Of Helicobacter Pylori Eradication For The First Line Treatment Of Immune Thrombocytopenia Patients With Moderate Thrombocytopenia

Blood ◽

10.1182/blood.v122.21.2324.2324 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2324-2324

Author(s):

Hyo Jung Kim ◽

Won Sik Lee ◽

Hawk Kim ◽

Jung-Hee Lee ◽

Sang Min Lee ◽

...

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenia ◽

Base Line ◽

Line Treatment ◽

First Line ◽

Platelet Counts ◽

Chronic Itp ◽

Significant Difference ◽

H Pylori ◽

First Line Treatment

Abstract Background Since the first case report of Gimaz et al., several investigators have reported that the secondary immune thrombocytopenia (ITP) can occur in patients with Helicobactor pylori (H. pylori) infection. Eradication of H. pylori has been shown to result in improvement in thrombocytopenia. In one systematic review of 696 patients with H. pylori infection it showed 50.3% overall response (platelet count >= 30 X 109/L and at least a doubling of the base line count) after H. pylori eradication. Under these results, ASH 2011 guidelines for ITP recommended that eradication therapy be administered in adult patients who are found to have H. pylori infection (grade 1b). But also they recommended that treatment be administered for newly diagnosed patients with a platelet count < 30 X 109/L. To the best of our knowledge, there was no prospective study to evaluate the efficacy of H. pylori eradication for ITP patient with moderate thrombocytopenia and positive H. pylori. In Korea, the prevalence of H. pylori was reported as high as 60 – 65% in general adult population. The response rate and price of 1st line triple regimen for H. pylori eradication were known to be 70 - 80% and around 100 US dollars in Korea. With these circumstances, tolerable treatment like H. pylori eradication for ITP patients with platelet count >=30 X 109/L is challengeable. Thus, we performed the prospective multicenter phase II study to evaluate the efficacy of H. pylori eradication for the 1st line treatment of persistent or chronic ITP patients with moderate thrombocytopenia. Methods We enrolled patients with persistent (3 to 12 months from diagnosis) or chronic (lasting for more than 12 months) ITP defined by international working group. The platelet counts of patients were between 30 X 109/L and 70 X 109/L. And all patients had positive result of C13-urea breath test (UBT) and had never been treated for ITP or H. pylori. Patients with other secondary ITP could not be enrolled. Patients received lansoprazole 30mg twice daily, amoxicillin 1000mg twice daily and clarithromycin 500mg, twice daily for one week. Eradication of H. pylori was evaluated at eighth week after treatment by UBT. Platelet counts were monitored at 2 weeks and after then at every month for a year. Complete response (CR) was defined as a platelet count >= 100 X 109/L. Partial response (PR) was defined as a platelet increase of >= 30 X 109/L and at least a doubling of the base line count. The primary endpoint was CR rate at 3 months after treatment. All patients provided written informed consents and this trial was registered at www.ClinicalTrials.gov (NCT01255332). Results Twenty-six patients were enrolled between November 2010 and May 2013 from 6 medical centers in Korea. Two patients with HCV infection and one patient with more than 70 X 109/L of platelet counts were excluded from analysis. The mean initial platelet counts of 23 patients (7 males, 16 females, median age 43 years and range 19 - 58 years) was 52.7 ± 9.5 X 109/L (range 39 – 68 X 109/L). All patients except one checked UBT after treatment and H. pylori eradication was achieved in 86.3% (19/22) of patients. CR was obtained in 13 of 23 patients (56.5%) within 3 months after treatment. And no PR was found until this time point. The median time to CR after initiating treatment was 4 weeks (range 2 – 8 weeks). CR rate of the patients who achieved H. pylori eradication was 63.2% (12/19). Unlike other reports, there was no significant difference on initial platelet counts among CR group and non-responder group and no significant correlation on the platelet levels between baseline and initial 3 months (Fig 1). Only 2 of 26 patients could not continue medication due to nausea and diarrhea, respectively. There was no other significant adverse event. Conclusion The eradication of H. pylori is an effective first line treatment for persistent or chronic ITP with moderate thrombocytopenia with high CR rate and rapid onset. And it has acceptable toxicity and relatively low cost. This study supports routine detection and eradication of H. pylori infection in ITP patients especially in populations with a high prevalence of this infection. Disclosures: No relevant conflicts of interest to declare.

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Efficacy and Safety Of Eltrombopag In Korean Adult Patients With Refractory Chronic Immune Thrombocytopenia

Blood ◽

10.1182/blood.v122.21.4758.4758 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4758-4758

Author(s):

Yeo-Kyeoung Kim ◽

Sung-Hoon Chung ◽

Jae-Sook Ahn ◽

Deok-Hwan Yang ◽

Il-Kwon Lee ◽

...

Keyword(s):

Platelet Count ◽

Treatment Outcome ◽

Maintenance Dose ◽

Immune Thrombocytopenia ◽

Conflicts Of Interest ◽

Platelet Counts ◽

Chronic Itp ◽

Insufficient Response ◽

Korean Adult

Introduction Eltrombopag is a synthetic non-peptide thrombopoietin receptor agonist (TPO-RA), which shows an excellent treatment outcome in immune thrombocytopenia (ITP) patients. For East Asians, starting dose of eltrombopag is generally recommended as a 25 mg/day and maximal dose is restricted as a 50 mg/day because of higher plasma eltrombopag AUC values. Furthermore, sensitivity to TPO-RA may increase or decrease over time. Here, we attempted to analyze the effective eltrombopag doses to achieve and maintain safe platelet counts in Korean ITP patients. Methods A total of twelve adult chronic ITP patients were enrolled, which showed insufficient response to previous ITP treatments (platelet counts less than or equal to 30,000/uL). All patients were allowed to take concomitant low dose prednisolone or danazol. Ten patients started eltromobopag at a dose of 25 mg/day and two patients started 25 mg every other day (EOD) because of previously detected hepatic problem. The doses increased every two weeks to achieve a target platelet count (equal to or more than 50,000/uL). For patients achieving platelet count within the range of 50,000 to 200,000/uL, firstly, we reduced concomitant ITP medications and then reduced eltrombopag doses to find the lowest effective dose of eltrombopag to maintain platelet counts more than 50,000/uL (maintenance dose). Results Before starting eltrombopag treatment, patients received median 4 (ranges; 3-9) ITP treatments including 1 case of splenectomy (Table 1). Bone marrow (BM) examinations including reticulin / Masson-trichrome staining were performed and all patients confirmed not to have BM fibrosis before eltrombopag treatment. Follow-up BM examinations were performed at 1 and 2 year of eltrombopag medication. Of total 12 patients, 10 (83.3%) achieved platelet counts more than 100,000/uL, 1 (8.3%) achieved platelet between 50,000-100,000/uL and 1 (8.3%) failed to increase platelet counts. One failed patient was diagnosed as ITP 114 months ago and received eight ITP treatments before starting eltrombopag. Eleven (91.7%) patients who achieved the target platelet counts (equal to or more than 50,000/uL) could quit or reduce the dose of concomitant ITP medications and median time to achieve the target platelet counts was 21 days (6-151 days). Most common initially required dose to achieve the target platelet counts was 25 mg/day (63.6%). Others were 25 mg EOD (9.1%), 50 mg/day (18.2%) and 75 mg/day (9.1%). After achieving the target platelet counts, most common adjusted maintenance dose was 25 mg/day (63.6%). Others were 25 mg twice a week (27.3%) and 50 mg/day (9.1%). There was no more than gr. 2 bleeding episode during eltrombopag treatment. One patient who required 75 mg/day to achieve the target platelet was diagnosed as ITP 91 months ago and received nine ITP treatments before starting eltrombopag. In 11 responded patients, 9 discontinued eltrombopag medication. Among them, 6 (66.7%) were relapsed and median relapse-free survival (RFS) was 11 days (6-574 days). In an aspect of adverse events, seven (58.3%) showed hepatobiliary laboratory abnormalities (HBLA, two gr. 3), however, all HBLA resolved after reduction or short-term discontinuation of eltrombopag. Eight patients underwent follow-up BM assessment. In 2 year BM, one patient revealed gr. 1 BM fibrosis during eltrombopag medication, however, there was no significant hematologic abnormality or lactate dehydrogenase (LDH) elevation in peripheral blood and no definitive abnormal immature cell clusters in his BM specimen. Conclusions Eltrombopag was generally well tolerated and showed an excellent treatment outcome in refractory chronic ITP patients in Korea. Low doses eltrombopag (25 mg/day or 25 mg twice a week) were effective to maintain safe platelet counts in most Korean patients. However, some of the patients needed longer time and higher doses (50 or 75 mg/day) to initially achieve and to maintain the target platelet counts, especially in heavily pre-treated patients with longer time from diagnosis to starting eltrombopag treatment. Disclosures: No relevant conflicts of interest to declare.

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Past medical history of tumors other than meningioma is a negative prognostic factor for tumor recurrence in meningiomas WHO grade I

Acta Neurochirurgica ◽

10.1007/s00701-021-04780-9 ◽

2021 ◽

Author(s):

Annamaria Biczok ◽

Philipp Karschnia ◽

Raffaela Vitalini ◽

Markus Lenski ◽

Tobias Greve ◽

...

Keyword(s):

Medical History ◽

Tumor Recurrence ◽

Clinical History ◽

Study Endpoint ◽

Past Medical History ◽

Who Grade ◽

Increased Risk ◽

History Of ◽

Meningioma Recurrence ◽

The Impact

Abstract Background Prognostic markers for meningioma recurrence are needed to guide patient management. Apart from rare hereditary syndromes, the impact of a previous unrelated tumor disease on meningioma recurrence has not been described before. Methods We retrospectively searched our database for patients with meningioma WHO grade I and complete resection provided between 2002 and 2016. Demographical, clinical, pathological, and outcome data were recorded. The following covariates were included in the statistical model: age, sex, clinical history of unrelated tumor disease, and localization (skull base vs. convexity). Particular interest was paid to the patients’ past medical history. The study endpoint was date of tumor recurrence on imaging. Prognostic factors were obtained from multivariate proportional hazards models. Results Out of 976 meningioma patients diagnosed with a meningioma WHO grade I, 416 patients fulfilled our inclusion criteria. We encountered 305 women and 111 men with a median age of 57 years (range: 21–89 years). Forty-six patients suffered from a tumor other than meningioma, and no TERT mutation was detected in these patients. There were no differences between patients with and without a positive oncological history in terms of age, tumor localization, or mitotic cell count. Clinical history of prior tumors other than meningioma showed the strongest association with meningioma recurrence (p = 0.004, HR = 3.113, CI = 1.431–6.771) both on uni- and multivariate analysis. Conclusion Past medical history of tumors other than meningioma might be associated with an increased risk of meningioma recurrence. A detailed pre-surgical history might help to identify patients at risk for early recurrence.

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Abstract 1122‐000214: Clinical Factors Associated rTPA Administration in Acute Ischemic Stroke Patients with History of Atrial Fibrillation

Stroke: Vascular and Interventional Neurology ◽

10.1161/svin.01.suppl_1.000214 ◽

2021 ◽

Vol 1 (S1) ◽

Author(s):

Chase A Rathfoot ◽

Camron Edressi ◽

Carolyn B Sanders ◽

Krista Knisely ◽

Nicolas Poupore ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Medical History ◽

Clinical Decision Making ◽

Past Medical History ◽

Clinical Factors ◽

Stroke Patients ◽

Factors Associated ◽

History Of

Introduction : Previous research into the administration of rTPA therapy in acute ischemic stroke patients has largely focused on the general population, however the comorbid clinical factors held by stroke patients are important factors in clinical decision making. One such comorbid condition is Atrial Fibrillation. The purpose of this study is to determine the clinical factors associated with the administration of rtPA in Acute Ischemic Stroke (AIS) patients specifically with a past medical history of Atrial Fibrillation (AFib). Methods : The data for this analysis was collected at a regional stroke center from January 2010 to June 2016 in Greenville, SC. It was then analyzed retrospectively using a multivariate logistic regression to identify factors significantly associated with the inclusion or exclusion receiving rtPA therapy in the AIS/AFib patient population. This inclusion or exclusion is presented as an Odds Ratio and all data was analyzed using IBM SPSS. Results : A total of 158 patients with Atrial Fibrillation who had Acute Ischemic Strokes were identified. For the 158 patients, the clinical factors associated with receiving rtPA therapy were a Previous TIA event (OR = 12.155, 95% CI, 1.125‐131.294, P < 0.040), the administration of Antihypertensive medication before admission (OR = 7.157, 95% CI, 1.071‐47.837, P < 0.042), the administration of Diabetic medication before admission (OR = 13.058, 95% CI, 2.004‐85.105, P < 0.007), and serum LDL level (OR = 1.023, 95% CI, 1.004‐1.042, P < 0.16). Factors associated with not receiving rtPA therapy included a past medical history of Depression (OR = 0.012, 95% CI, 0.000‐0.401, P < 0.013) or Obesity (OR = 0.131, 95% CI, 0.034‐0.507, P < 0.003), Direct Admission to the Neurology Floor (OR = 0.179, 95% CI, 0.050‐0.639, P < 0.008), serum Lipid level (OR = 0.544, 95% CI, 0.381‐0.984, P < 0.044), and Diastolic Blood Pressure (OR = 0.896, 95% CI, 0.848‐0.946, P < 0.001). Conclusions : The results of this study demonstrate that there are significant associations between several clinical risk factors, patient lab values, and hospital admission factors in the administration of rTPA therapy to AIS patients with a past medical history of Atrial Fibrillation. Further research is recommended to determine the extent and reasoning behind of these associations as well as their impact on the clinical course for AIS/AFib patients.

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Osteopetrosis - A Case Series Exploring Complications and Multidisciplinary Management

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.425 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A209-A209

Author(s):

Catherine Stewart ◽

Paul Benjamin Loughrey ◽

John R Lindsay

Keyword(s):

Back Pain ◽

Lumbar Spine ◽

Medical History ◽

Scaphoid Fracture ◽

Past Medical History ◽

Dxa Scan ◽

X Ray ◽

Management Of Complications ◽

History Of ◽

Spine Mri

Abstract Background: Osteopetrosis is a group of rare inherited skeletal dysplasias, with each variant sharing the hallmark of increased bone mineral density (BMD). Abnormal osteoclast activity produces overly dense bone predisposing to fracture and skeletal deformities. Whilst no cure for these disorders exists, endocrinologists play an important role in surveillance and management of complications. Clinical Cases: A 43-year-old female had findings suggestive of increased BMD on radiographic imaging performed to investigate shoulder and back pain. X-ray of lumbar spine demonstrated a ‘rugger jersey’ spine appearance, while shoulder X-ray revealed mixed lucency and sclerosis of the humeral head. DXA scan showed T-scores of +11 at the hip and +12.5 at the lumbar spine. MRI of head displayed bilateral narrowing and elongation of the internal acoustic meatus and narrowing of the orbital foramina. Genetic assessment confirmed autosomal dominant osteopetrosis with a CLCN7 variant. Oral colecalciferol supplementation was commenced and multi-disciplinary management instigated with referral to ophthalmology and ENT teams. A 25-year-old male presented with a seven-year history of low back pain and prominent bony swelling around the tibial tuberosities and nape of neck. Past medical history included repeated left scaphoid fracture in 2008 and 2018. Recovery from his scaphoid fracture was complicated by non-union requiring bone grafting with open reduction and fixation. Plain X-rays of the spine again demonstrated ‘rugger jersey’ spine. DXA scan was notable for elevated T scores; +2.9 at hip and +5.8 lumbar spine. MRI spine showed vertebral endplate cortical thickening and sclerosis at multiple levels. The patient declined genetic testing and is under clinical review. A 62-year-old male was referred to the bone metabolism service following a DXA scan showing T scores of +11. 7 at the hip and +13 at the lumbar spine. His primary complaint was of neck pain and on MRI there was multi-level nerve root impingement secondary to facet joint hypertrophy. Past medical history was significant for a long history of widespread joint pains; previous X-ray reports described generalized bony sclerosis up to 11 years previously. Clinical and radiological monitoring continues. Conclusion: Individuals with osteopetrosis require a multidisciplinary approach to management. There is no curative treatment and mainstay of therapy is supportive with active surveillance for complications.

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Long Term Discontinuation of Eltrombopag after Remission in Primary Immune Thrombocytopenia: 8-Year Follow-up Data from 15 Spanish Centers

Blood ◽

10.1182/blood-2019-129274 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2352-2352

Author(s):

Tomas Jose Gonzalez-Lopez ◽

Fernando Fernandez-Fuertes ◽

Maria Cristina Pascual Izquierdo ◽

Isabel Caparros ◽

Silvia Bernat ◽

...

Keyword(s):

Platelet Count ◽

Median Time ◽

Research Funding ◽

Immune Thrombocytopenia ◽

Previous Treatment ◽

Complete Response ◽

Platelet Response ◽

Platelet Counts

Background: Successful discontinuation of eltrombopag in certain immune thrombocytopenia (ITP) patients after complete response has already been demonstrated. However, the frequency of this phenomenon and type of candidate patients are still matter of discussion. Moreover, possibility of long term discontinuation responses is not clearly established. Methods: Here we retrospectively evaluated our whole cohort of 508 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry with a focus on the patients who achieved a durable (at least six months) platelet response after stopping eltrombopag. Successful discontinuation of eltrombopag (SDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 6 months in absence of eltrombopag or any rescue therapies administered. Long term discontinuation of eltrombopag (LTDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 36 months in the absence of eltrombopag or any rescue therapies administered. The study was approved by the Hospital Universitario de Burgos Ethics Committee and fulfilled Helsinki declaration standards. Results: While 37.4% of our patients relapsed of ITP with subsequent platelet count drop sometime during first six months of discontinuation of eltrombopag, a total of 74 patients (14.6%) were able to achieve SDOE. The median age of SDOE patients was 62 [range, 47-79] years. There were 47 women and 27 men. According to the standard definition, patients were allocated to newly diagnosed (n=17), persistent (n=15) and chronic (n=42) ITP groups. The median time from diagnosis to eltrombopag initiation was 31 [range, 4-104] months. The median number of previous therapies was 2 [range, 1-2], including splenectomy (14%), rituximab (18%) and romiplostim (12%). As expected, all patients but 1 achieved a complete response (platelet count ≥100 x 109/L) prior to eltrombopag discontinuation The median duration of eltrombopag treatment was 7 [range, 2-19] months. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=43), platelet count >400x109/L (n=16), aspartate aminotransferase elevation (n=5), diarrhea (n=4), thrombosis (n=3), patient's request (n=2) and other reasons (n=1). Analysis of these SDOE discontinued patients show that with a median follow-up of 55 [range, 29-79] months, 38 patients (51.3%) maintained treatment-free response 36 months after stopping eltrombopag with no need of additional ITP therapies (median time of eltrombopag discontinuation was 70 [range, 50-77] months).This condition is what we define now as LTDOE. Nevertheless, 36 patients relapsed beyond 6 months but before 36 months of eltrombopag discontinuation (median time of eltrombopag discontinuation was 10 [range,7 -22] months). Characteristics of LTDOE population were a median time since ITP diagnosis of 32 [range, 5-88] months with 15/38 patients having ITP <1 year. 9 patients (24%) were male and their median age was 50 [range, 37-64] years. They had received a median of only two previous treatment lines [range: 1-2 lines]. The median platelet count before starting eltrombopag was 19 x 109/L [range, 8-40]. Meanwhile, platelet count before eltrombopag stop was 218 x 109/L [range, 123-356]. The main characteristics (age, gender, duration of ITP, prior ITP lines, platelet count before starting eltrombopag, duration of eltrombopag treatment, and platelet count before eltrombopag withdrawal) of the 38 patients with LTDOE were compared with those of the SDOE cohort who did not achieve a LTDOE. Unfortunately, no predictive factors of LTDOE could be identified. Conclusion: Durable platelet response following eltrombopag cessation may be observed in only 15% of primary ITP patients treated with this drug. On the contrary, half of patients who achieve a sustained response after eltrombopag withdrawal will get a long term discontinuation. However, we are lacking predictor factors for successful and long-term discontinuation of eltrombopag in primary ITP. Disclosures Gonzalez-Lopez: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Pascual Izquierdo:Novartis: Consultancy; Sanofi: Consultancy. Sánchez-González:Amgen: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Navartis: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Jarque:Takeda: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; Shionogi: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Grifols: Consultancy; Gilead: Consultancy, Speakers Bureau; CellTrion: Consultancy; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Abbie: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau.

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