scholarly journals Long-term, intermittent, low-level elephant endotheliotropic herpesvirus 1A viremia in a captive Asian elephant calf

2018 ◽  
Vol 30 (6) ◽  
pp. 917-919 ◽  
Author(s):  
Kendra L. Bauer ◽  
Erin Latimer ◽  
Mitch Finnegan
Keyword(s):  
Platelet Count ◽  
Clinical Signs ◽  
Asian Elephant ◽  
Elephas Maximus ◽  
Conventional Pcr ◽  
Low Level ◽  
Platelet Counts ◽  
Additional Information ◽  
Time Period

A 2-y-old male Asian elephant ( Elephas maximus), with an elevated platelet count (1,100 × 109/L [1,100 × 103/mm3]), tested positive for elephant endotheliotropic herpesvirus 1A (EEHV-1A) on conventional PCR (cPCR) of EDTA whole blood. No clinical signs were ever reported and no treatment was administered, but low-level viremia persisted for 2.5 y based on results of cPCR and/or real-time PCR (rtPCR). Sequencing confirmed that the EEHV-1A detected was identical at the beginning through the end of the time period. No other elephants in the herd tested positive for EEHV-1 during this time period. Platelet counts remained elevated throughout the viremia and throughout the animal’s life, and direct correlation between the elevated platelet counts and EEHV-1A viremia could not be confirmed. We document long-term, intermittent, low-level viremia of EEHV-1A and provide additional information to consider when determining if treatment is warranted in a case of EEHV infection.

Repeated Occupational Exposure to Low-level Blast in the Canadian Armed Forces: Effects on Hearing, Balance, and Ataxia

2021 ◽  
Author(s):  
Ann Nakashima ◽  
Oshin Vartanian ◽  
Shawn G Rhind ◽  
Kristen King ◽  
Catherine Tenn ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Occupational Exposure ◽  
Armed Forces ◽  
Cross Sectional ◽  
Low Level ◽  
Additional Information ◽  
Adverse Health Effects ◽  
Blast Overpressure ◽  
Blast Exposure

ABSTRACT Introduction Recently, there has been increasing concern about the adverse health effects of long-term occupational exposure to low-level blast in military personnel. Occupational blast exposure occurs routinely in garrison through use of armaments and controlled blast detonations. In the current study, we focused on a population of breaching instructors and range staff. Breaching is a tactical technique that is used to gain entry into closed spaces, often through the use of explosives. Materials and Methods Initial measurements of blast overpressure collected during breaching courses found that up to 10% of the blasts for range staff and up to 32% of the blasts for instructors exceeded the recommended 3 psi exposure limit. Using a cross-sectional design, we used tests of balance, ataxia, and hearing to compare a sample of breachers (n = 19) to age-and sex-matched military controls (n = 19). Results There were no significant differences between the two groups on the balance and ataxia tests, although the average scores of both groups were lower than would be expected in a normative population. The prevalence of hearing loss was low in the breacher group (4 of 19), and hearing thresholds were not significantly different from the controls. However, the prevalence of self-reported tinnitus was significantly higher in the breacher group (12 of 19) compared with the controls (4 of 19), and all breachers who were identified as having hearing loss also reported tinnitus. Conclusions Our results suggest that basic tests of balance, ataxia, and hearing on their own were not sensitive to the effects of long-term occupational exposure to low-level blast. Some of the blast exposure levels exceeded limits, and there was a significant association of exposure with tinnitus. Future studies should supplement with additional information including exposure history and functional hearing assessments. These findings should be considered in the design of future acute and longitudinal studies of low-level blast exposure.

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

Blood ◽  
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.

Long-Term Treatment with Romiplostim in Patients with Chronic Immune Thrombocytopenic Purpura (ITP): 3-Year Update from An Open-Label Extension Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 402-402 ◽  
Author(s):  
David J Kuter ◽  
James B Bussel ◽  
Adrian Newland ◽  
Joost TM de Wolf ◽  
Troy Guthrie ◽  
...  
Keyword(s):  
Platelet Count ◽  
Term Treatment ◽  
Duration Of Treatment ◽  
Open Label ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Long Term Treatment ◽  
Open Label Extension ◽  
Grade 3

Abstract Chronic ITP is characterized by increased platelet destruction and suboptimal platelet production. Romiplostim is an investigational Fc-peptide fusion protein (peptibody) being studied for its ability to increase platelet counts in patients with chronic ITP. We report data from an open-label extension study of romiplostim in adult patients with chronic ITP. Collection of safety and efficacy data from long-term treatment of these patients is ongoing. Eligible patients had completed a prior romiplostim study and had platelet counts □50×109/L. Romiplostim was administered subcutaneously once weekly with dose adjustments to maintain a platelet count of 50–250×109/L. As of July 13 2007, 142 patients had been treated with romiplostim. Their median time since diagnosis was 6.4 years (range 0.6–46.4 years). Most were female (67%) and had previously undergone a splenectomy (60%). The median baseline platelet count was 17×109/L (range 1–50×109/L). The median duration of treatment was 65 weeks (range 1–156 weeks). Twenty-nine (20%) patients discontinued the study, 10 (7%) due to adverse events (AEs) [2 each of bone marrow reticulin and thrombosis; 1 each of bleeding, pain, cardiac arrest, pneumonia, hepatic and renal failure, and monoclonal gammopathy of undetermined significance]. Different measures of platelet count response were analyzed; any platelet counts within 8 weeks of receiving rescue medications were excluded from these analyses. Platelet counts were increased from baseline by ≥20×109/L more than 80% of the time in 54% of patients and more than 50% of the time in 73% of patients. Platelet counts remained above 20×109/L more than 90% of the time in 67% of patients and more than 50% of the time in 94% of patients. A platelet count &gt;50×109/L and double baseline was achieved by 30% (42/138) of patients after the first dose, by 51% (71/138) of patients after the third dose, and by 87% (124/142) of patients overall. The durability of platelet count increases was analyzed: platelet counts &gt;50×109/L were sustained for ≥10, ≥25, and ≥52 consecutive weeks in 78% (102/131), 54% (66/122), and 35% (29/84) of patients, respectively. The patient incidence of bleeding events both of any severity and of clinical significance (≥Grade 3) declined over time (Table). AEs were reported in 95% of patients, with most mild to moderate in severity. The most common were headache (37%); nasopharyngitis (32%); and contusion, fatigue and epistaxis (each 30%). AE frequency did not increase with time on study (Table). Bone marrow reticulin was present or increased in 8 patients with no evidence of progression to collagen fibrosis or chronic idiopathic myelofibrosis. Thrombotic events were reported in 7 (5%) patients; 6 had pre-existing risk factors for thrombosis. In conclusion, romiplostim increased platelet counts in most patients for most of the time, and clinically relevant bleeding was reduced over time. Romiplostim was well-tolerated and AEs did not increase with longer duration of treatment. Table. Summary of patient incidence of AEs by study period &lt;24 wks (N=142) n (%) 24 to &lt;48 wks (N=126) n (%) 48 to &lt;72 wks (N=97) n (%) 72 to &lt;96 wks (N=65) n (%) 96 to &lt;120 wks (N=29) n (%) 120 to &lt;144 wks (N=25) n (%) AEs 129 (91) 110 (87) 64 (66) 36 (55) 23 (79) 21 (84) Serious AEs 25 (18) 13 (10) 7 (7) 4 (6) 4 (14) 1 (4) Treatment-related AEs 48 (34) 14 (11) 12 (12) 7 (11) 4 (14) 3 (12) Treatment-related serious AEs 6 (4) 3 (2) 1 (1) 2 (3) 1 (3) 1 (4) Study withdrawals due to AEs 4 (3) 5 (4) 0 (0) 0 (0) 0 (0) 1 (4) Bleeding any grade 60 (42) 37 (29) 22 (23) 13 (20) 11 (38) 8 (32) Bleeding ≥ Grade 2 (moderate) 25 (18) 12 (10) 8 (8) 4 (6) 3 (10) 2 (8) Bleeding ≥ Grade 3 difference in thisresponsebetween refractory (severe) 9 (6) 1 (1) 1 (1) 1 (2) 0 (0) 0 (0)

Post-Transplant Platelet Recovery Kinetics and Its Association with Overall Survival in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2049-2049
Author(s):  
Jie Li ◽  
Jillian Alyse Deppa ◽  
Zahir Ali ◽  
Michael Graiser ◽  
Amelia Langston ◽  
...  
Keyword(s):  
Overall Survival ◽  
Platelet Count ◽  
Early Death ◽  
Disease Status ◽  
P Value ◽  
Term Survival ◽  
Allogeneic Hsct ◽  
Post Transplant ◽  
Platelet Counts

Abstract Abstract 2049 Background: Post-transplant thrombocytopenia is universal among recipients of hematopoietic stem cell transplantation (HSCT). We have previously reported a secondary post-transplant thrombocytopenia following autologous HSCT which is associated with poor survival (Ninan MJ, et al., BBMT 2007), however the clinical significance of a fall post-engraftment in platelet counts among recipients of allogeneic HSCT has not been studied. Methods: A total of 929 consecutive pts who underwent allogeneic HSCT between 1993 and 2009 were studied in an IRB-approved retrospective analysis. 55% of pts were male and 45% were female with a median age of 43 ± 12.6 years. Diagnoses included: acute leukemia (423, 46%), chronic leukemia (197, 21%), non-Hodgkin's lymphoma (110, 12%),myelodysplastic syndrome (93, 10%), multiple myeloma (26, 3%), and other less common malignancies (80, 8%). Disease status was classified into five different categories: complete remission (287, 31%), partial remission (297, 34%), refractory (180, 19%), untreated (28, 3%) and incompletely classified (137, 15%). Grafts were obtained from related donors in 595 pts (64%), and unrelated donors in 334 pts (36%), with 55% peripheral blood stem cell (PBSC), 42% bone marrow (BM), and 3% cord blood units or multiple sources. Blood platelet counts and platelet transfusions were collected from 15 days pre-transplant until 100 days post-transplant. Platelet engraftment was defined as a platelet count ≥ 50 x10E3/mcL without a platelet transfusion in the previous 7 days. Pts (n=816) who achieved platelet engraftment and survived at least 30 days were selected for further analysis. Results: The 816 evaluable pts were divided into cohorts based upon their post-transplant survival: 146(18%) who died within 100 days post-transplant (early death); 267 (33%) that survived 100 days −2 years post-transplant (late death), 319 (39%) who survived > 2 years (long-term survival), and 84 (10%) were lost of follow-up within the first 2 years. Transfusion-independent platelet engraftment was achieved at median of 15 days post-transplant with no significant differences seen in the kinetics of initial engraftment among the different pt cohorts. Median platelet counts at different time points post-transplant were plotted for each pt cohort (Figure 1). Pts in the early-death cohort had a continuous decline in median platelet counts from engraftment values of > 50 x10E3/mcL to a median values of ∼20 x10E3/mcL. Univariate analyses indicated that higher platelet counts at day −15 (prior to conditioning) or at day 100 post-transplant were significantly associated with improved overall survival (HR of 0.63 and 0.39 respectively, P < 0.01). Cox-regression analysis was performed to evaluate significance of pre- and post-transplant platelet counts with clinical covariates that have been previously associated with survival including age, diagnosis, disease status and the source of the grafts. The multivariate model confirmed the significant association of the following factors with overall survival: higher platelet counts on day 15 pre-transplant (HR:0.81; 95%Cl:0.70∼0.93; P-value <0.01), the platelet count on day 100 post-transplant (HR: 0.62; 95%Cl:0.55∼0.70; P-value:<0.01 ), a diagnosis of acute leukemia (HR:1.64; 95%Cl:1.13∼2.39; P-value <0.01), a diagnosis of multiple myeloma (HR: 2.12; 95%Cl:1.05∼4.23; P-value= 0.04), a disease status of complete remission (CR) versus not in CR (HR: 0.66; 95%Cl:0.44∼0.97; P-value = 0.04), and age (HR: 1.01; 95%Cl:1.00∼1.02; P-value= 0.08). Kaplan-Meier estimates for survival were performed based upon stratification of pt groups on the platelet count at day-15 pre-transplant or the day +100 post-transplant platelet count (Figure 2). Pts with a platelet count > 80 × 10E3/mcL on day +100 had 5 year survival of more than 50% compared with 30% survival in the pt cohort with platelet counts < 50 x10E3/mcL on day +100. Conclusion: Pts with continuously low platelet count after initial platelet engraftment are at high risk for early death. Higher pre-transplant platelet may be a surrogate for disease status and extent of prior therapy and are associated with long-term survival among pts undergoing allogeneic HSCT. Post-transplant thrombopoiesis at day 100 is highly correlated with long-term survival after allogeneic HSCT, identifying a high-risk group of transplant pts for whom additional treatment strategies are needed. Disclosures: Gleason: Celgene, Merck, Millenium: Consultancy.

scholarly journals Linezolid induced thrombocytopenia

2020 ◽  
Vol 9 (7) ◽  
pp. 1130
Author(s):  
P. Muthamil
Keyword(s):  
Platelet Count ◽  
Renal Transplantation ◽  
Antibiotic Prophylaxis ◽  
Rare Case ◽  
Gram Positive ◽  
Platelet Counts ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant

Linezolid, an oxazolidinone antibiotic active against gram-positive bacteria is used in the treatment of vancomycin resistant Enterococci and MRSA. It is generally tolerated except for the 32% chance of thrombocytopenia on long term usage of linezolid. A 25-year-old male after renal transplantation was administered linezolid for antibiotic prophylaxis. His platelet count dropped from 1,68,000 cells to 74,000 on day 2. The platelet counts further dropped to 58,000 on day 3, followed which linezolid was withdrawn. His platelet improved to 88,000 on day 5 following withdrawal of linezolid. Though we are vigilant about thrombocytopenia on long term usage of linezolid, here we report a rare case of linezolid induced thrombocytopenia within 2 days of starting the antibiotic. This necessitates the increased vigilance on linezolid usage. Platelet count needs to be monitored as early as the start of treatment with linezolid.

scholarly journals Hepatobiliary and Thromboembolic Events during Long-Term E.X.T.E.N.Ded Treatment with Eltrombopag in Adult Patients with Chronic Immune Thrombocytopenia (ITP)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1368-1368
Author(s):  
Mansoor N. Saleh ◽  
James B Bussel ◽  
Raymond SM Wong ◽  
Balkis Meddeb ◽  
Abdulgabar Salama ◽  
...  
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Adult Patients ◽  
Phase Iii ◽  
First Year ◽  
Thromboembolic Events ◽  
Advisory Committees ◽  
Platelet Counts

Abstract Introduction: ITP, characterized by a reduction in platelets leading to thrombocytopenia, which persists for >12 months is considered chronic (cITP). Eltrombopag is an oral thrombopoietin receptor agonist approved for treatment of patients with cITP aged ≥1 year refractory to other treatments (eg corticosteroids, immunoglobulins). The recently completed Phase III EXTEND (Eltrombopag eXTENded Dosing) study was a global, open-label, extension study of patients with cITP, who received eltrombopag or placebo in prior eltrombopag clinical studies. The primary objective of EXTEND was to describe the long-term safety and tolerability of eltrombopag treatment in these patients. Here, we examine the occurrence of hepatobiliary and thromboembolic events (TEEs) as adverse events (AEs) of special interest in this study. Methods :Adult patients (≥18 years old) diagnosed with cITP according to ASH/BCSH guidelines were enrolled and received eltrombopag starting at 50 mg/day. Dose was titrated to 25-75 mg per day or less often as required, based on individual platelet count responses (targeted range ≥50-200x109/L). Patients who received 2 years of treatment and transitioned off eltrombopag due to commercial availability of eltrombopag were considered to have completed the study, whether or not they continued treatment with eltrombopag. The primary endpoint included detection and documentation of investigator-reported AEs, which included hepatobiliary AEs and TEEs. Analyses were conducted using the safety population, defined as all subjects who entered the study and had taken at least one dose of the study medication. Results:302 patients were enrolled and received at least one dose of eltrombopag: 67% were female; 38% splenectomized; 49% aged 18-49 years. Median duration of exposure was 2.4 years (range, 2 days to 8.8 years) and mean average daily dose was 50.2 (range, 1-75) mg/day. Overall, 259/302 (86%) achieved platelet counts of ≥50×109/L at least once during the study and 126/248 (51%) patients maintained continuous platelet counts ≥50×109/L for at least 31 weeks. Incidence of bleeding symptoms (WHO grades 1-4) generally decreased over time in patients with available data, from 57% (n=171/302) at baseline to 16% at 1 year (n=13/80), and 21% (12/58) at 2 years. 45 (15%) patients experienced at least one hepatobiliary AE, with the highest incidence within the first year of treatment (Figure A). AEs of increased ALT or AST led to the discontinuation of five and three patients, respectively and four patients discontinued due to an AE of increased blood bilirubin. Nine patients experienced ALT and/or AST >3 x upper limit of normal (ULN) and total bilirubin >1.5xULN. 19 (6.3%) patients experienced a total of 23 TEEs. Most events occurred in the first year (Figure B), and none after year 4. TEEs included deep vein thrombosis (n=6), cerebral infarction (stroke) [n=3], myocardial infarction (n=4), transient ischemic attack (n=2), others (n=8, 1 occurrence of each). A clear association with elevated platelet counts was not observed. Platelets >200x109/L at the time of the TEE were recorded in 8/19 patients; 6/19 experienced the TEE at or shortly after achieving their maximum platelet count. In total, 10 patients discontinued because of TEEs. Conclusions: Long-term treatment with eltrombopag in patients with cITP led to sustained platelet increases and reduced bleeding symptoms. The highest incidences of hepatobiliary AEs and TEEs occurred during the first year of treatment, though several events were recorded after 3 years of therapy. Long-term eltrombopag therapy was well-tolerated with a positive benefit-risk relationship in adults with cITP, with decreasing events after the first year of treatment. Disclosures Saleh: GSK: Consultancy, Research Funding, Speakers Bureau. Bussel:Amgen, Novartis & GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer Ingleheim, Prophylix Pharma, Protalex, Rigel Pharmaceuticals: Research Funding; Momenta Pharmaceuticals, Novartis, Prophylix Pharma, Protalex, Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; UptoDate: Patents & Royalties; Physicians Education Resource: Speakers Bureau. Wong:Bayer, Biogen-Idec and Novartis: Consultancy; Bayer, Biogen-Idec, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Pfizer, and Roche: Research Funding; Biogen-Idec and Novartis: Membership on an entity's Board of Directors or advisory committees. El-Ali:Novartis: Employment. Quebe-Fehling:Novartis: Employment.

scholarly journals Treatment of adult chronic autoimmune thrombocytopenic purpura with repeated high-dose intravenous immunoglobulin

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1415-1421 ◽  
Author(s):  
B Godeau ◽  
S Lesage ◽  
M Divine ◽  
V Wirquin ◽  
JP Farcet ◽  
...  
Keyword(s):  
Body Weight ◽  
Platelet Count ◽  
Treatment Protocol ◽  
Complete Response ◽  
Long Term Results ◽  
High Dose ◽  
Thrombocytopenic Purpura ◽  
Autoimmune Thrombocytopenic Purpura ◽  
Platelet Counts

Intravenous (i.v.) infusions of Ig concentrates are an effective but expensive treatment for patients with autoimmune thrombocytopenic purpura (AITP). The optimal treatment protocol and the long-term results are uncertain, and the precise mechanism by which the platelet count increases is poorly understood. Twenty adult patients with chronic AITP were enrolled in a prospective study to compare the respective efficacy of two high-dose IVIgG induction regimens (1 g v 2 g/kg body weight) and the long-term effect of six 1 g/kg body weight i.v. IgG reinfusions. An initial response was observed in all 18 evaluable patients: the platelet count increased to a mean value of 251 x 10(9)/L (range 72 to 836 x 10(9)/L) and the mean pretreatment platelet count was multiplied by 14.6. No difference in efficiency was observed between the two i.v. IgG dosages. The degree of the platelet count increment correlated in both groups with the increase in the clearance of antibody-coated red blood cells, measured by an isotopic method, but not with the serum IgG elevation. Treatment was considered to have failed in 11 patients, 90 days after the last i.v. IgG reinfusion (D90), because the platelet counts were comparable with pretreatment values. In contrast, a complete response was observed at D90 in five patients (mean platelet count: 184 x 10(9)/L; range: 150 to 250 x 10(9)/L) and a partial response at D90 was obtained in the remaining two patients (platelet counts: 70 and 104 x 10(9)/L). Five of the 7 responders at D90 kept a platelet count above 50 x 10(9)/L during the entire follow-up period (mean 33 months; range: 5 to 66) with no further treatment; unfortunately, no clinical or biologic criteria were found to be predictive of the long-term response. This study shows that an i.v. IgG infusion regimen of 1 g/kg body weight could safely replace the classical 2 g/kg body weight dosage, at least in patients who do not have life-threatening thrombocytopenia. Moreover, repeated i.v. IgG reinfusion could be an alternative for AITP patients in whom splenectomy is contraindicated.

scholarly journals Treatment of adult chronic autoimmune thrombocytopenic purpura with repeated high-dose intravenous immunoglobulin

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1415-1421 ◽  
Author(s):  
B Godeau ◽  
S Lesage ◽  
M Divine ◽  
V Wirquin ◽  
JP Farcet ◽  
...  
Keyword(s):  
Body Weight ◽  
Platelet Count ◽  
Treatment Protocol ◽  
Complete Response ◽  
Long Term Results ◽  
High Dose ◽  
Thrombocytopenic Purpura ◽  
Autoimmune Thrombocytopenic Purpura ◽  
Platelet Counts

Abstract Intravenous (i.v.) infusions of Ig concentrates are an effective but expensive treatment for patients with autoimmune thrombocytopenic purpura (AITP). The optimal treatment protocol and the long-term results are uncertain, and the precise mechanism by which the platelet count increases is poorly understood. Twenty adult patients with chronic AITP were enrolled in a prospective study to compare the respective efficacy of two high-dose IVIgG induction regimens (1 g v 2 g/kg body weight) and the long-term effect of six 1 g/kg body weight i.v. IgG reinfusions. An initial response was observed in all 18 evaluable patients: the platelet count increased to a mean value of 251 x 10(9)/L (range 72 to 836 x 10(9)/L) and the mean pretreatment platelet count was multiplied by 14.6. No difference in efficiency was observed between the two i.v. IgG dosages. The degree of the platelet count increment correlated in both groups with the increase in the clearance of antibody-coated red blood cells, measured by an isotopic method, but not with the serum IgG elevation. Treatment was considered to have failed in 11 patients, 90 days after the last i.v. IgG reinfusion (D90), because the platelet counts were comparable with pretreatment values. In contrast, a complete response was observed at D90 in five patients (mean platelet count: 184 x 10(9)/L; range: 150 to 250 x 10(9)/L) and a partial response at D90 was obtained in the remaining two patients (platelet counts: 70 and 104 x 10(9)/L). Five of the 7 responders at D90 kept a platelet count above 50 x 10(9)/L during the entire follow-up period (mean 33 months; range: 5 to 66) with no further treatment; unfortunately, no clinical or biologic criteria were found to be predictive of the long-term response. This study shows that an i.v. IgG infusion regimen of 1 g/kg body weight could safely replace the classical 2 g/kg body weight dosage, at least in patients who do not have life-threatening thrombocytopenia. Moreover, repeated i.v. IgG reinfusion could be an alternative for AITP patients in whom splenectomy is contraindicated.

Anticoagulation with Low Molecular Weight Heparin (LMWH) during Autologous Peripheral Blood Stem Cell Transplantation (PBSCT). Single Institution Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1885-1885
Author(s):  
Rajasree Roy ◽  
Baruch Wieder ◽  
Christina Johnson ◽  
Bhoomi Mehrotra
Keyword(s):  
Molecular Weight ◽  
Stem Cell ◽  
Platelet Count ◽  
Low Molecular Weight Heparin ◽  
Peripheral Blood Stem Cell ◽  
Median Number ◽  
Low Molecular Weight ◽  
Platelet Counts ◽  
Therapeutic Anticoagulation

Abstract BACKGROUND: Management of a chronic hypercoagulable state during the cytopenic phase of peripheral blood stem cell transplant (PBSCT) poses a significant clinical challenge. Anticoagulation in the presence of significant thrombocytopenia raises the risk of bleeding. However, withholding anticoagulation may increase the risk of thrombotic events. The purpose of this study was to evaluate the safety and efficacy of low dose thromboprophylaxis with low molecular weight heparin (LMWH) during the thrombocytopenic phase of PBSCT. METHODS: We undertook a retrospective analysis of all patients who underwent an autologous PBSCT at our institution from 1998 to 2005 and identified patients that were on therapeutic anticoagulation prior to their admission for transplantation. Institutional review board approval was obtained for this study. Information regarding indication of PBSCT, age, gender, indication for anticoagulation, bleeding or thrombotic event during hospitalization including bleeding or clotting at the site of indwelling central venous catheter, nature of anticoagulation, time to platelet engraftment, and number of platelet transfusions were recorded. Patients at known high risk for thrombosis were maintained on therapeutic dosage of warferin or LMWH until platelet counts decreased to < 50,000/μ liter, at which time LMWH 40 milligram/day subcutaneously was administered. Platelet counts were maintained at > 20,000/μ liter with transfusion support as needed. RESULTS: Eight of seventy evaluable patients were identified during the pre-transplant screening to be maintained on long term anticoagulation. Median age of these patients was 57 years (range: 38–67); Male: Female ratio 1:1; Indications for PBSCT were relapsed non-hodgkins lymphoma (n=2), multiple myeloma (n=5), acute myeloid leukemia (n=1). Indications for long term anticoagulation prior to PBSCT included: Upper extremity DVT (n=1), lower extremity DVT (n=5), pulmonary embolism (n=1), atrial fibrillation (n=1), superior sagital sinus thrombosis (n=1). Prior to transplant, therapeutic anticoagulation was maintained with warfarin (n=4) and LMWH (n=4). Median number of days with platelet counts < 20,000 = 3 (range 1–5); median number of platelet transfusions required = 3 (range 1–4); median number of days requiring LMWH = 8 (range 1–11); median number of days with platelet count < 50,000 = 6 (range 4–9). Median time to platelet transfusion independence was 11 days post stem cell infusion (range 8–15 days). One patient had an indwelling IVC filter at the time of transplantation. No clotting events were noted during and immediately post-transplantation. One patient developed microscopic hematuria and one patient developed macroscopic hematuria during the hospitalization which resolved spontaneously. No additional clinically significant bleeding complications were noted. CONCLUSION: Patients on chronic anticoagulation therapy can be safely transplanted with PBSCs and maintained on prophylactic doses of LMWH during the phase of moderate thrombocytopenia (platelet count < 50,000) without any increased incidence of clotting or bleeding events.

scholarly journals Thrombopoietin Receptor Agonists in the Treatment of Chronic Resistant Primary Immune Thrombocytopenia: Efficacy and Safety Data in Real Clinical Practice

2018 ◽  
Vol 90 (7) ◽  
pp. 70-76 ◽  
Author(s):  
V V PTUSHKIN ◽  
O Yu VINOGRADOVA ◽  
M M PANKRASHKINA ◽  
M V CHERNIKOV ◽  
E G ARSHANSKAYA ◽  
...  
Keyword(s):  
Platelet Count ◽  
Clinical Practice ◽  
Safety Data ◽  
Treatment Withdrawal ◽  
Long Term Results ◽  
Efficacy And Safety ◽  
Platelet Response ◽  
Platelet Counts ◽  
Real Clinical Practice

Objective: To analyze the long-term efficacy and safety of ATR in adult patients with primary resistant ITP in real-world clinical practice. Materials and methods.The article contains long-term results analysis of ATR application under real clinical practice conditions in 138 patients (40 men and 98 women) whose median age at the beginning of therapy was 59 (18-86) years. Two ATR medicines-romiplostim (100 patients) and eltrombopag (38 patients) were used. Results. During the first month of therapy, the median platelet count in the romiplostim group increased from 17·109 / L to 60·109 / L (9-600·109 / L), and the elethrombopag from 16.109 / L to 56.109 / L (9-400·109 / L). The minimal response (reaching platelet counts over 30·109 / L) was achieved in 92% of cases in both groups. Partial response (achievement of platelet count more than 50·109 / L) was achieved in 91 and 84% of patients in the rhombostim and eltrombopag groups, respectively. The frequency of complete response (an increase in platelet counts above 100·109 / L) was noted somewhat more often in the rhyploistim group-69% compared to 47% in the eltrombopag group (P = NS). Most patients demonstrated a long-term stable effect in the form of an increase in blood platelet count to a safe level during months and years of ATR treatment. The achievement of at least partial remission for 3 months or more was 70 and 71% in romiplostim and elthrombopag groups, respectively. Patients who started ATR- therapy are currently continuing treatment: 51% - in romiplostim group and in eltrombopag group-39%. The main reason of discontinuation the initially effective therapy were the loss of platelet response, toxicity, withdrawal from treatment (withdrawal with preservation of remission) and patients death. The tolerability of drugs with long-term admission was satisfactory. The most common AE were headache, bone pain, thrombosis, increased blood pressure and petechial hemorrhagic eruptions. The overall incidence of complications did not differ significantly between the romiplostim and eltrombopag groups -15.6 and 15.8%, respectively. Conclusion. Long-term ATR-therapy using in patients with resistant chronic ITP is an effective and largely safe treatment option.

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