Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting with immune thrombocytopenic purpura: a prospective cohort study

Abstract The pathogenetic role and the clinical importance of the presence of antiphospholipid antibodies (APAs) in patients with immune thrombocytopenic purpura (ITP) are not clear. In this study, the prevalence and clinical significance of APAs were investigated in patients with ITP. Eighty-two newly diagnosed ITP patients were prospectively studied. They were evaluated for the presence of lupus anticoagulant (LA) and immunoglobulin G/M anticardiolipin antibodies (ACAs). Thirty-one patients (37.8%) were APA positive at diagnosis. No statistically significant differences were found between the APA-positive and APA-negative groups regarding gender, initial platelet counts, or response to methylprednisolone therapy. After 5 years of follow-up, cumulative thrombosis-free survival of APA-positive (n = 31) and APA-negative (n = 51) ITP patients was 39% and 97.7%, respectively. A significant difference was found between these groups by log-rank test (P = .0004). In addition, LA was an important risk marker for the development of thrombosis in ITP patients. After a median follow-up of 38 months, 14 ITP patients (45%) who had APA positivity developed clinical features (thrombosis or fetal losses) of antiphospholipid syndrome (APS). There were no differences between the APA-positive patients with and without APS regarding the initial platelet counts, response to the therapy, or ACA positivity. The positivity rate for LA was significantly higher in those patients with ITP who developed APS (χ2: P = .0036; relative risk 7.15; 95% confidence interval, 1.7-47). In conclusion, this study indicates that a significant proportion of patients initially presenting with ITP and APA positivity developed APS. In patients with ITP, the persistent presence of APAs is an important risk factor for the development of APS.

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Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study

Blood ◽

10.1182/blood-2008-01-131029 ◽

2008 ◽

Vol 112 (4) ◽

pp. 999-1004 ◽

Cited By ~ 164

Author(s):

Bertrand Godeau ◽

Raphael Porcher ◽

Olivier Fain ◽

François Lefrère ◽

Pierre Fenaux ◽

...

Keyword(s):

Immune Thrombocytopenic Purpura ◽

Phase 2 ◽

Open Label ◽

Thrombocytopenic Purpura ◽

Platelet Counts ◽

Chronic Immune Thrombocytopenic Purpura ◽

Chronic Itp ◽

Phase 2 Trial ◽

Phase 2 Study

Abstract Whether rituximab could effectively and safely avoid splenectomy for adults with chronic immune thrombocytopenic purpura (ITP) remains unresolved. A multicenter, prospective, open-label, single-arm, phase 2 trial was conducted to assess rituximab safety and efficacy in adult splenectomy candidates with chronic ITP. Sixty patients with chronic (≥ 6 months) ITP and platelet counts less than 30 × 109/L received a weekly intravenous infusion of rituximab (375 mg/m2) for 4 weeks. All other ITP treatments were stopped. A good response was defined as a platelet count 50 × 109/L or more, with at least a doubling of the initial value at 1 and 2 years after the first rituximab infusion. Patients who required another treatment during follow up were considered nonresponders. Sixteen patients experienced transient side effects that necessitated treatment discontinuation for only 1. Good 1-year responses were obtained in 40% of the patients (24/60 [95% confidence interval: 28%-52%]). At 2 years, 33.3% (20/60 patients) had good responses and 6.7% (4/60) had sustained platelet counts of 30 × 109/L or more without treatment. Thirty-six (60%) patients failed to respond; 25 underwent splenectomy. Based on these results, rituximab was an apparently safe and effective splenectomy-avoiding option in some adults with chronic ITP. This trial is registered at http://clinicaltrials.gov as NCT00225875.

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Study on the Efficacy and Safety of IGIV3I Grifols (Human Intravenous Immunoglobulin) in Patients Diagnosed with Chronic Immune Thrombocytopenic Purpura.

Blood ◽

10.1182/blood.v108.11.3956.3956 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3956-3956

Author(s):

Antonio Julia ◽

Lidia Kovaleva ◽

Ignacio Alberca ◽

Fernando Hernandez ◽

Svetlana Loria ◽

...

Keyword(s):

Blood Pressure ◽

Platelet Count ◽

Intravenous Immunoglobulin ◽

Immune Thrombocytopenic Purpura ◽

Study Drug ◽

Efficacy And Safety ◽

Thrombocytopenic Purpura ◽

Platelet Counts ◽

Chronic Itp

Abstract Intravenous immunoglobulin (IVIG) products are considered a useful treatment in patients with chronic idiopathic/immune thrombocytopenic purpura (ITP) to prevent bleeding or prior to surgery, when platelet counts have to be rapidly increased. IGIV3I Grifols is a highly purified, unmodified human IgG product whose manufacturing process follows the same basic principles of Flebogamma® (another IVIG manufactured by Grifols in clinical use since 1992). The main differences between both processes are how purification steps are sequentially arranged, and the introduction of two specific steps to inactivate/remove any potential contaminating pathogen (solvent-detergent treatment and sequential nanofiltration through 35 and 20 nm pore size filters), as additional viral elimination steps to pasteurization, already present in Flebogamma®. An open prospective study was planned to investigate the efficacy and safety of IGIV3I Grifols in 20 adult patients with chronic ITP (at least 6 months after diagnosis). Twenty adult subjects were enrolled and 19 patients with chronic ITP in acute phase (platelet counts <20x109/l) were treated. Patients received 0.4 g/kg body weight for 5 consecutive days. Efficacy endpoints were the proportion of patients who reached a platelet count ≥50x109/l, the time taken for the platelet count to reach the target level and the duration of response. Regression of haemorrhages was documented during the first 14 days of follow-up. Safety parameters including adverse events (AEs), laboratory determinations and vital signs were regularly monitored. The follow-up of patients ended 3 months after first dose of IGIV3I Grifols to determine any change in viral markers for HIV, HCV, HBV and HAV. Results from intention to treat (ITT) population (n=20) and per protocol (PP) population (n=19) are presented. A patient was withdrawn from the study because she did not present an immune idiopathic thrombocytopenic purpura. A total of 14 patients (ITT = 70%; PP = 74%) responded to the study drug. The median time to platelet response was ≥2.5 days and the median number of days in which the platelet count remained ≥50x109/l was ≥7.0 days. For 17 patients (ITT = 85%; PP = 89%) a regression of the bleeding episodes was reported on day 14. Eight out of 20 patients presented 21 AEs potentially related to the study drug (16 mild and 5 moderate). Headache and fever (6 cases each), hypertension (2), decreased blood pressure (2) or hypotension (1), blood pressure fluctuation (1), thrombocythaemia (1), bradycardia (1) and asthenia (1) were AEs potentially related to study drug. No patients experienced clinically significant abnormalities in the laboratory values (haematology and renal and hepatic functions) and no patients changed their virological markers during the follow-up of the study. The results show that IGIV3I Grifols is safe and adequate to achieve a safe platelet count in patients with refractory chronic ITP.

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Antiphospholipid antibodies (APLA) in immune thrombocytopenic purpura (ITP) and antiphospholipid syndrome (APS)

American Journal of Hematology ◽

10.1002/ajh.20571 ◽

2006 ◽

Vol 81 (6) ◽

pp. 391-396 ◽

Cited By ~ 23

Author(s):

Carlos J. Bidot ◽

Wenche Jy ◽

Lawrence L. Horstman ◽

Eugene R. Ahn ◽

Miriam Yaniz ◽

...

Keyword(s):

Antiphospholipid Syndrome ◽

Immune Thrombocytopenic Purpura ◽

Antiphospholipid Antibodies ◽

Thrombocytopenic Purpura

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Does treatment with intermittent infusions of intravenous anti-D allow a proportion of adults with recently diagnosed immune thrombocytopenic purpura to avoid splenectomy?

Blood ◽

10.1182/blood.v99.6.1922 ◽

2002 ◽

Vol 99 (6) ◽

pp. 1922-1927 ◽

Cited By ~ 60

Author(s):

Nichola Cooper ◽

B. Michael R. Woloski ◽

Erin M. Fodero ◽

Maria Novoa ◽

Melissa Leber ◽

...

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenic Purpura ◽

Maintenance Treatment ◽

Thrombocytopenic Purpura ◽

Platelet Counts ◽

L 14 ◽

Lost To Follow Up ◽

Primary Predictor ◽

All Treatment

Abstract This study explored whether repeated infusions of intravenous anti-D could allow adults with recently diagnosed immune thrombocytopenic purpura (ITP) who had failed an initial steroid course to postpone and ultimately avoid splenectomy. Twenty-eight Rh+, nonsplenectomized adults with ITP diagnosed within 1 to 11 months and platelet counts 30 × 109/L (30 000/μL) or below were enrolled. Anti-D was infused whenever the platelet count decreased to 30 × 109/L (30 000/μL) or below. “Response” was defined as a platelet increase of more than 20 × 109/L (20 000/μL) to more than 30 × 109/L (30 000/μL) within 7 days of treatment. Patients were a median 3.5 months from ITP diagnosis at enrollment and had received a median of 2 previous therapies, including prednisone in 26 of 28 cases. They were followed for a median 26 months. A total of 93% responded to their initial infusion of anti-D, and 68% repeatedly responded with counts maintained above 30 × 109/L (30 000/μL) using anti-D alone. Currently, 12 (43%) of 28 patients have been off all treatment for more than 6 months without undergoing splenectomy, 6 maintaining counts above 100 × 109/L (100 000/μL). Seven continue on treatment, 8 underwent splenectomy, and 1 was lost to follow-up at 10 months. One patient discontinued anti-D because of toxicity. Patients with platelet counts at least 14 × 109/L (14 000/μL) at enrollment were more likely to discontinue treatment (P < .05). Anti-D was an effective maintenance treatment for two thirds of Rh+, nonsplenectomized adults with ITP who had failed an initial steroid course. Intermittent infusions of intravenous anti-D allowed more than 40% of these adults to avoid splenectomy and to achieve stable platelet counts off all therapy, even after many months of treatment. Platelet count at study entry was the primary predictor of outcome.

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Experience with protein A-immunoadsorption in treatment-resistant adult immune thrombocytopenic purpura

Blood ◽

10.1182/blood.v79.9.2237.2237 ◽

1992 ◽

Vol 79 (9) ◽

pp. 2237-2245 ◽

Cited By ~ 106

Author(s):

HW Snyder ◽

SK Cochran ◽

JP Balint ◽

JH Bertram ◽

A Mittelman ◽

...

Keyword(s):

Side Effects ◽

Immune Thrombocytopenic Purpura ◽

Protein A ◽

Staphylococcal Protein A ◽

Treatment Resistant ◽

Thrombocytopenic Purpura ◽

Specific Serum ◽

Clinical Responses ◽

Acute Increase

Abstract Extracorporeal immunoadsorption of plasma to remove IgG and circulating immune complexes (CIC) was evaluated as a therapy for adults with treatment-resistant immune thrombocytopenic purpura (ITP). Seventy-two patients with initial platelet counts less than 50,000/microL who had failed at least two other therapies were studied. They received an average of six treatments of 0.25 to 2.0 L plasma per procedure over a 2- to 3-week period using columns of staphylococcal protein A-silica (PROSORBA immunoadsorption treatment columns; IMRE Corp, Seattle, WA). The treatments caused an acute increase in the platelet count to greater than 100,000/microL in 18 patients and to 50,000 to 100,000/microL in 15 patients. The median time to response was 2 weeks. Responses were transient (less than 1 month duration) in seven of those patients (10%), but no additional relapses were reported over a follow- up period of up to 26 months (mean of 8 months). Clinical responses were associated with significant decreases in specific serum platelet autoantibodies (including anti-glycoprotein IIb/IIIa), platelet- associated Ig, and CIC. Thirty percent of treatments were associated with transient mild to moderate side effects usually presenting as a hypersensitivity-type reaction. Continued administration of failed therapies for ITP, which always included low-dose corticosteroids (less than or equal to 30 mg/d), had no demonstrable influence on the effectiveness of immunoadsorption treatment but did depress the incidence and severity of side effects. The degree of effectiveness of protein A immunoadsorption therapy in patients with treatment-resistant ITP is promising and further controlled studies in this patient population are warranted.

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The Relationship between Serum Ferritin Levels and 5-Year All-Cause Mortality in Hemodialysis Patients

Blood Purification ◽

10.1159/000515639 ◽

2021 ◽

pp. 1-7

Author(s):

Emre Erdem ◽

Ahmet Karatas ◽

Tevfik Ecder

Keyword(s):

Serum Ferritin ◽

Hemodialysis Patients ◽

Rank Test ◽

Significant Difference ◽

All Cause Mortality ◽

Group 3 ◽

Group 2 ◽

The Relationship ◽

Group 1

Introduction: The effect of high serum ferritin levels on long-term mortality in hemodialysis patients is unknown. The relationship between serum ferritin levels and 5-year all-cause mortality in hemodialysis patients was investigated in this study. Methods: A total of 173 prevalent hemodialysis patients were included in this study. The patients were followed for up to 5 years and divided into 3 groups according to time-averaged serum ferritin levels (group 1: serum ferritin <800 ng/mL, group 2: serum ferritin 800–1,500 ng/mL, and group 3: serum ferritin >1,500 ng/mL). Along with the serum ferritin levels, other clinical and laboratory variables that may affect mortality were also included in the Cox proportional-hazards regression analysis. Results: Eighty-one (47%) patients died during the 5-year follow-up period. The median follow-up time was 38 (17.5–60) months. The 5-year survival rates of groups 1, 2, and 3 were 44, 64, and 27%, respectively. In group 3, the survival was lower than in groups 1 and 2 (log-rank test, p = 0.002). In group 1, the mortality was significantly lower than in group 3 (HR [95% CI]: 0.16 [0.05–0.49]; p = 0.001). In group 2, the mortality was also lower than in group 3 (HR [95% CI]: 0.32 [0.12–0.88]; p = 0.026). No significant difference in mortality between groups 1 and 2 was found (HR [95% CI]: 0.49 [0.23–1.04]; p = 0.063). Conclusion: Time-averaged serum ferritin levels >1,500 ng/mL in hemodialysis patients are associated with an increased 5-year all-cause mortality risk.

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The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

Acta Haematologica ◽

10.1159/000514920 ◽

2021 ◽

pp. 1-9

Author(s):

Leonard Naymagon ◽

Douglas Tremblay ◽

John Mascarenhas

Keyword(s):

Hemophagocytic Lymphohistiocytosis ◽

Proportional Hazards ◽

Multivariable Analysis ◽

Cox Proportional Hazards ◽

Rank Test ◽

Kaplan Meier ◽

Hazard Ratios ◽

Significant Difference ◽

The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank p = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, p = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

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Comparing Zirconia to Anterior Strip Crowns in Primary Anterior Teeth in children, A Randomized Clinical Trial

10.21203/rs.3.rs-38319/v4 ◽

2020 ◽

Author(s):

Sumer M Alaki ◽

Bashaer S Abdulhadi ◽

Medhat A AbdelBaki ◽

Najla M Al-Alamoudi

Keyword(s):

Resin Composite ◽

Rank Test ◽

Random Allocation ◽

Tooth Structure ◽

Anterior Teeth ◽

Gingival Health ◽

Significant Difference ◽

Zirconia Crowns ◽

Restoration Failure

Abstract Background: Providing restorations to anterior teeth in children is a challenging task due to the need for high esthetics, strength, and durability. This study was done to compare prefabricated primary zirconia with resin composite strip crowns on primary maxillary central and lateral incisors with regards to gingival health, plaque accumulation, recurrent caries, restoration failure, and opposing teeth wear over a period of 3, 6 and 12 months. Methods: Children attending the King Abdulaziz University, Faculty of Dentistry (KAUFD) clinics who needed restorations were screened for inclusion criteria. A total of 120 teeth were treated; 60 with zirconia and 60 with strip crowns. Randomization was done by simple random allocation using SPSS software version 20.0 (Armonk, NY; IBM Corp.). A simple descriptive statistic was used for analysis by Wilcoxon Signed-Rank test and Chi-square test. Level of significance was set at (α = 0.05) and level of confidence at (95%). The presented research was registered retrospectively at ClinicalTrials.gov in 6th of August 2017, under registration number NCT03184012.Results: Zirconia crowns showed significantly less gingival bleeding at the 3- and 6-months follow up periods (p<0.006, p<0.001; respectively), less plaque accumulation at all follow up visits (p<0.001), no restoration failure (p<0.001), but more wear to opposing teeth (p<0.02). No significant difference was found between the two crowns with regards to recurrent caries (p<0.135).Conclusion: Based on our data we conclude that overtime teeth covered with zirconia crowns show better gingival health and less bleeding, plaque accumulation as well as less loss of material. On the other hand, zirconia can cause more loss of opposing tooth structure.

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Recovery rate of children with moderate acute malnutrition treated with ready-to-use supplementary food (RUSF) or improved corn–soya blend (CSB+): a randomized controlled trial

Public Health Nutrition ◽

10.1017/s1368980015001238 ◽

2015 ◽

Vol 19 (2) ◽

pp. 363-370 ◽

Cited By ~ 14

Author(s):

Gabriel Nama Medoua ◽

Patricia M Ntsama ◽

Anne Christine A Ndzana ◽

Véronique J Essa’a ◽

Julie Judith T Tsafack ◽

...

Keyword(s):

Nutrition Education ◽

Recovery Rate ◽

Energy Requirement ◽

Controlled Trial ◽

Acute Malnutrition ◽

Rank Test ◽

Supplementary Food ◽

Significant Difference ◽

Moderate Acute Malnutrition

AbstractObjectiveTo compare an improved corn–soya blend (CSB+) with a ready-to-use supplementary food (RUSF) to test the hypothesis that satisfactory recovery rate will be achieved with CSB+ or RUSF when these foods provide 50 % of the child’s energy requirement, the 50 % remaining coming from usual diet.DesignA comparative efficacy trial study was conducted with moderately wasted children, using a controlled randomized design, with parallel assignment for RUSF or CSB+. Every child received a daily ration of 167 kJ (40 kcal)/kg body weight during 56 d with a follow-up performed every 14 d. Every caregiver received nutrition counselling at enrolment and at each follow-up visit.SettingHealth districts of Mvog-Beti and Evodoula in the Centre region of Cameroon.SubjectsEight hundred and thirty-three children aged 6–59 months were screened and eighty-one malnourished children (weight-for-height Z-score between −3 and −2) aged 25–59 months were selected.ResultsOf children treated with CSB+ and RUSF, 73 % (95 % CI 59 %, 87 %) and 85 % (95 % CI 73 %, 97 %), respectively, recovered from moderate acute malnutrition, with no significant difference between groups. The mean duration of treatment required to achieve recovery was 44 d in the RUSF group and 51 d in the CSB+ group (log-rank test, P=0·0048).ConclusionsThere was no significant difference in recovery rate between the groups. Both CSB+ and RUSF were relatively successful for the treatment of moderate acute malnutrition in children. Despite the relatively low ration size provided, the recovery rates observed for both groups were comparable to or higher than those reported in previous studies, a probable effect of nutrition education.

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Abstract 14598: Multiple Arterial Coronary Bypass Grafting is Associated With Improved Survival in Females

Circulation ◽

10.1161/circ.142.suppl_3.14598 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Derrick Tam ◽

Rodolfo Rocha ◽

Jiming Fang ◽

Maral Ouzounian ◽

Joanna Chikwe ◽

...

Keyword(s):

Coronary Artery ◽

Propensity Score ◽

Propensity Score Matching ◽

Administrative Databases ◽

Rank Test ◽

Bypass Grafting ◽

Female Patients ◽

Significant Difference ◽

Arterial Grafting

Introduction: Multiple arterial grafting (MAG) in coronary artery bypass grafting (CABG) is associated with improved survival and freedom from major adverse cardiac and cerebrovascular events (MACCE) in observational studies of mostly males. It is not known whether the MAG is beneficial in females. Herein, we compared the late clinical outcomes of MAG versus single arterial grafting (SAG) in females undergoing CABG for multivessel coronary artery disease (CAD) Methods: Clinical and administrative databases for Ontario, Canada, were linked to obtain all female patients with angiographic evidence of left main, triple, or double vessel disease undergoing isolated non-emergent primary CABG from 2008-2019. Baseline characteristics were compared and 1:1 propensity score matching was performed to account for differences. 30-day mortality was compared in the matched groups. Late mortality and MACCE ( composite of stroke, myocardial infarction, repeat revascularization, and death) was compared between the matched groups with a stratified log rank test and Cox-proportional hazard model. Results: In total 2,961 and 7,954 females underwent CABG with MAG and SAG respectively for multivessel CAD. Prior to propensity-score matching, compared to SAG, those that underwent MAG were younger (66.0 vs. 68.9 years) and had less comorbidities. After propensity-score matching, 2,446 well-matched pairs were formed. In matched patients, there was no significant difference in 30-day mortality (1.6% vs 1.8%, P=0.43) between MAG and SAG. The median and maximum follow-up was 5.0 and 11.0 years respectively. Over the entire follow-up, MAG was associated with improved survival (Figure, hazard ratio (HR): 0.85, 95% confidence interval (CI): 0.75-0.98) and freedom from MACCE (HR: 0.85, 95%CI: 0.76-0.95). Conclusions: MAG was associated with improved survival and freedom from MACCE and should be considered for female patients with good life expectancy requiring CABG.

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