scholarly journals Initial Experience with Thrombopoetin Receptor Agonists (TRA) in 5 Patients with Refractory HIV-Associated Immune Thrombocytopenic Purpura (ITP)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5014-5014
Author(s):  
Mark Kowalczyk ◽  
Paul G. Rubinstein ◽  
David M Aboulafia
Keyword(s):  
Myocardial Infarction ◽  
Platelet Count ◽  
Viral Load ◽  
Cd4 Count ◽  
Sustained Response ◽  
Bleeding Complications ◽  
Lumbar Spine Surgery ◽  
Hiv Viral Load ◽  
Platelet Counts ◽  
Post Surgery

Abstract Introduction: In the pre-highly active anti-retroviral therapy (HAART) era, ITP was a relatively common hematologic abnormality, which was seen in as many as 30% of patients infected with HIV. With the advent of HAART, the incidence of HIV-associated ITP has been reduced substantially, with some epidemiological studies showing contemporary rates as low as 1 to 3% (Vannappagari, Platelets 2011). In cases where HAART does not lead to adequate improvement in platelet counts, next lines of therapy have traditionally consisted of corticosteroids, including dexamethasone and prednisone, intravenous immunoglobulin (IVIG), anti-Rho(D) immune globulin, rituximab and, in the current era, more sparingly, splenectomy. When platelet counts remain persistently <20 x 109/L despite medical and surgical interventions, patients with ITP retain a heightened risk of bleeding complications (Frederiksen, Br J Haematol 2014). The TRAs eltrombopag (Promacta®) and romiplostim (Nplate®) are effective in 59% to 88% of ITP cases in patient without HIV, and loss of response while on continued therapy is uncommon. The agents’ use in treatment of refractory HIV-associated ITP has not, however, been sufficiently studied or reported. Methods: Herein we perform a retrospective chart review of 5 patients with HIV-related ITP treated from 2009-2014. All 5 patients with HIV-associated ITP had failed at least two lines of ITP therapy before they received a TRA (table). Mean age was 34 years (18-47), 3 males and 2 females. 4 patients had CD4+ counts >200 cells/ µL, viral loads < 40 copies/mL, and platelet counts ≤20 x 109/L before starting TRA therapy. Results: Each patient responded to TRA use with a mean pre-treatment platelet count of 15 x 109/L, and this increased to a mean of 110 x 109/L 6 weeks following treatment initiation. 2 of the patients have maintained a sustained response with adequate platelet counts 3 years after discontinuing TRA therapy. 1 patient succumbed to a myocardial infarction while on eltrombopag and 1 patient, while on romiplostim, expired from complications of a presumed pulmonary embolus after undergoing lumbar spine surgery. Abstract 5014. Table: Characteristics of HIV-related ITP patients given TRA Case Nadir CD4+ count (cells/µL) /HIV viral load (copies/mL) HAART Regimen CD4+ count (cells/µL) /HIV viral load (copies/mL) at time of use of TPA Platelet count pre-TRA treatment Lines of ITP treatment before TRA TRA (dose where response was observed and sustained) 6 month f/u platelet count Sustained Response after stopping TRA (duration) Case 1 261/ 5,000 Atripla® 340 / <40 20 x 109/L 1. Pred + IVIG 2.Rituximab + Dex Romiplostim (4µg/kg) 158 x 109 /L Yes (3 years) Case 2 a 284/ 74,743 Atripla® 300/ <40 2 x 109/L 1. Pred 2. Pulse Dex 3.Rituximab + Dex 4. IVIG Romiplostim, then Eltrombopag (50mg) N/A N/A Case 3 261/ 5,000 Atripla® >300 / <40 13 x 109/L 1. Pred + IVIG 2.Rituximab + Dex Romiplostim (2µg/kg) 128 x 109 /L Yes (3 years) Case 4 100/ 100,000 Zidovudine + Epivir + Nevirapine 180 / <40 39 x 109/L 1. IVIG 2. Pred 3. Rituximab Romiplostim (3µg/kg) 52 x 109 /Lb N/A Case 5 100/ 2,400 Truvada + darunavir + detravirine + raltegravir + ritonavir >200 / 54,000 13 x 109/L 1. Anti-Rho(D) 2. IVIG 3. Rituximab 4. Pulse Dex 5. Pred 6.Rituximab + Dex Eltrombopag (50mg) 48 x 109 /Lc No aPatient expired prior to 6 month f/u due to myocardial infarction bPatient sustained response for 2 weeks after discontinuation of TRA cPatient to be reinitiated on maintenance therapy due to lack of compliance Abbreviations: efavirenz, tenofovir, and disoproxil fumarate (Atripla®); prednisone (Pred) dexamethasone (Dex); follow-up clinic visit (f/u) Discussion: Due to insufficient evidence, a definitive association between TRA use and the two patients who suffered thrombotic events remains speculative. Nonetheless, these events emphasize the importance of using these TRAs cautiously during periods of heightened risk of thrombosis such as post-surgery and during periods of immobility, or in patients with risk factors for thrombotic complications. While HIV-associated ITP remains an important clinical problem in the era of widespread HAART use, the availability of both romiplostim and eltrombopag give medical providers additional options in treating this disease. Further experience is needed, however, to better determine the effectiveness and, most importantly, the safety of these drugs in the context of HIV-associated ITP. Disclosures No relevant conflicts of interest to declare.

Treatment of Immune-Mediated Thrombocytopenia Purpura with Concurrent IVIg and Platelet Transfusion: A Retrospective Review of 40 Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3972-3972
Author(s):  
Joseph E. Spahr ◽  
Neeraj Agarwal ◽  
George M. Rodgers
Keyword(s):  
Platelet Count ◽  
Side Effects ◽  
Retrospective Review ◽  
Combined Treatment ◽  
Age Groups ◽  
Optimal Dose ◽  
Active Bleeding ◽  
Bleeding Complications ◽  
Platelet Counts ◽  
Immune Mediated

Abstract Introduction: In January 2000, two patients with severe Immune-Mediated Thrombocytopenia (ITP) at our institution were successfully treated with prolonged infusions of IVIg and platelets. The dose of IVIg was 1 g/kg given by continuous infusion over 24 hours with concurrent platelets (1 pheresis unit every 8 hours). Based on these preliminary results, we evaluated this protocol in a larger series of 40 ITP patients. Methods: We performed an IRB-approved retrospective review of adult hospitalized patients with ITP treated with this regimen from January 2000 - December 2005. Patients with clinically significant thrombocytopenia and either active bleeding, need for anticoagulation, or requirement for a surgical procedure received the combined treatment. The subjects received IVIg and platelets as described above. Additional treatments, such as steroids, immunosupressives, or rituximab, as well as splenectomy were utilized at the discretion of the hematologist overseeing their care. Results: The average age of patients treated was 52 years. The majority of patients ranged from 20–80 years old, but 12.5% were older than 80 years. The average pretreatment platelet count was 10,000/μl, with an increase to 55,000/μl after 24 hours, and 69,000/μl after 48 hours. By 72 hours, the average platelet count had begun to decline, although the platelet count remained at an acceptable level (58,200/μl). After 24 hours, 62.7% of patients had a platelet count &gt; 50,000/μl. Bleeding was controlled initially in all patients, and those requiring a procedure experienced no bleeding complications. Over half of the patients (52.5%) required additional treatments for recurrent or refractory ITP, and 32.5% of the patients underwent splenectomy. Six of the 21 patients requiring later retreatment (29%) received IVIg and platelets again in a similar fashion. The average retreatment platelet counts after 24 and 48 hours were 53,000/μl and 49,000/μl respectively, with clinical improvement in bleeding in all patients. No side effects of the combined treatment were noted. The response rates for the 3 IVIg products used were similar. Discussion: For ITP, IVIg and platelets are considered to be first line treatment for patients with very low platelet counts, active bleeding, or those requiring urgent procedures. There is limited literature on the optimal dose and schedule for administration of IVIg and platelets. Our approach for administration of IVIg and platelets concurrently was associated with minimal side effects, resolution of bleeding, ability to safely undergo procedures, and rapid restoration of adequate platelet counts. Additionally, elderly patients had equivalent benefit with no increased side effects, indicating that this regimen is appropriate and safe for patients of all age groups.

ARL-IPI - A New Prognostic Score for AIDS-Related Lymphomas in the Rituximab Era

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1564-1564
Author(s):  
Stefan K Barta ◽  
Xiaonan Xue ◽  
Dan Wang ◽  
Jeannette Y Lee ◽  
Lawrence D. Kaplan ◽  
...  
Keyword(s):  
Viral Load ◽  
B Cell ◽  
Risk Groups ◽  
Cd4 Count ◽  
Test Model ◽  
Training Set ◽  
Hiv Viral Load ◽  
Specific Factors ◽  
The Difference ◽  
Validation Set

Abstract Abstract 1564 INTRODUCTION: The International Prognostic Index (IPI) and the age-adjusted IPI (aaIPI) are commonly used to predict outcomes in immunocompetent patients with aggressive B-cell Non-Hodgkin Lymphomas (NHL). Although the IPI has also been validated for AIDS-related lymphomas (ARL), HIV-infection is an important competing risk that has not been adequately evaluated as a factor contributing to prognosis in the context of contemporary rituximab-containing chemoimmunotherapy. Here, we assessed whether HIV-specific factors in addition to the IPI provided more accurate prediction of clinical outcomes than IPI alone. METHODS: We obtained patient-level data for 487 patients from 8 prospective phase 2 or 3 clinical trials including patients with HIV-associated aggressive B-cell NHL receiving initial therapy with rituximab containing chemoimmunotherapy identified by systematic literature review, and randomly divided the population in a training (N=244) and validation set (N=243). We defined an HIV-score by combining individual HIV risk-factors: (1) baseline CD4 count (cells/ul): <50 =3, 50–199=2, 200–499=1, 500 or more =0; (2) HIV viral load (copies/ml): <400=0; 400-9, 999=1,10,000 or more =2; (3) prior history of AIDS=1, thereby yielding an HIV-score that could range from 0–6. We examined the association of HIV-score in addition to patient-, and lymphoma-specific factors with overall survival (OS) using a Cox-PH-model in the training and validation set independently by comparing 4 different multivariate models by a LR-chi2 test: model 1 (included age, sex, & histology), model 2 (model 1 + aaIPI), model 3 (model 2 + number of involved extranodal disease sites [ENS]) and model 4 (model 3 + HIV-score). Next, we defined a new score (ARL-IPI) by assigning appropriate weights to each significant predictor depending on the strength of association in the multivariate model in the training set: 2 for aaIPI score (0,1,2 or 3); 1 for ENS: no ENS=0, 1 ENS=1, 2 ENS=2, 3 or more ENS=3; and 1 for HIV-score. We examined the difference in OS for 3 risk groups: low (LR), intermediate (IR) and high risk (HR) based on the ARL-IPI in the validation set. We compared the discrimination power of the ARL-IPI with the aaIPI by comparing the difference in OS across the 3 groups defined by each score. RESULTS: 487 patients were included in the analysis with a median follow-up of 2.3 years (0.1–12.1). There were no significant differences in patient characteristics between training and validation set. Considering the entire population, 77% were male, median age was 42 years (20–74), median CD4 count 174 cells/ul (0–2,457), and median HIV viral load 23,802 copies/ml (0–6×106). The histologies included DLBCL (69%), BL or BLL (29%), and other histologies (3%). All patients received rituximab plus either CHOP (49%), EPOCH (19%), CDE (15%), or other multi-agent intensive regimens (16%). In the training set, only aaIPI, ENS and HIV-score were significantly associated with OS, but not age, sex, extranodal sites as defined in the IPI (<2 or 2 or more), or histology. When tested in the validation set, the addition of the HIV-score (model 4; ARL-IPI) showed a significant improvement in predictive power for OS over all other models (p-value=0.009). When we compared the risk groups defined by the aaIPI (LR: <1, IR: 1–2, HR: 3) versus the ARL-IPI (aaIPI + ENS + HIV-score: LR: <7, IR: 7–10, HR: >10) in the validation set, the ARL-IPI was able to more clearly define prognosis based on the 3 risk groups in regards to OS (p=0.013; Table 1), which was confirmed by KM survival analysis (Figure 1). The ARL-IPI also compared favorably to a score defined by aaIPI and ENS (LR: <4, IR: 4–6, HR: >6), demonstrating the significant impact of the HIV-score on prediction power. In our dataset, the ARL-IPI could not significantly improve prediction power for CR rate or PFS compared with the two other scores. CONCLUSION: By combining HIV-associated factors with known prognostic patient- and lymphoma factors into a composite prognostic risk score (ARL-IPI) we were able to more accurately define prognosis for patients with ARL treated with chemoimmunotherapy. Disclosures: No relevant conflicts of interest to declare.

Romiplostim For Thrombocytopenia in Patients with Hepatitis C (HCV)-Associated Liver Disease: Preliminary Report Of An Ongoing Clinical Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3555-3555
Author(s):  
Howard Liebman ◽  
Laurie Hornor ◽  
Tse-Ling Fong ◽  
Casey O'Connell ◽  
Ilene C Weitz
Keyword(s):  
Clinical Trial ◽  
Platelet Count ◽  
Viral Load ◽  
Liver Disease ◽  
Phase I ◽  
Phase Ii ◽  
Hcv Treatment ◽  
Platelet Counts ◽  
Hcv Therapy ◽  
Cirrhotic Patients

Abstract Background Thrombocytopenia (Tp) is frequently observed in individuals with advanced cirrhotic liver disease. Patients with HCV may develop Tp even in the absence of significant liver disease. Decreased thrombopoietin production may also contribute to the Tp. The current management of HCV infection includes the use of the Peg-interferon α (IFN) and ribavirin (RIB), which can induce a sustained viral remission in 40 to 50% of treated patients. However, Peg-INF is a known inhibitor of megakaryocyte growth and maturation and can result in treatment related Tp. Therefore, patients presenting with platelet counts <70,000/mcl are frequently excluded from treatment or often fail treatment due to the development of critically low platelet counts. With this understanding, we initiated a clinical trial of the thrombopoietin receptor agonist, romiplostim, in HCV cirrhotic patients with Tp to determine if platelet count can be increased to >100,000/mcl to allow for HCV treatment with Peg-INF/RIB. Methods This is a two phase clinical trial of HCV infected patients with Child-Pugh class A liver disease. All patients were required to have platelet counts <70,000/µl and have liver biopsy confirmed early cirrhosis. Phase I is a double-blind placebo controlled trial of romiplostim given up to 8 weeks to raise platelets to >100,000/mcl before initiating Peg-INF treatment. There are separate 1 to 1 randomizations for patients with platelets 70 to 50,000/µl and patients with platelets<50,000/mcl. Initial treatment dose is 1 µg/kg with weekly progressive increases in dose. For patients who failed to obtain platelet counts >100,000/µl by week 8, blind is terminated and placebo patients can enter the romiplostim arm. Phase II is a dose escalation study of romiplostim during Peg-INF/Rib treatment up to week 24 of HCV treatment. If patients are viral load negative by week 24, romiplostim treatment is held to see if the patients can sustain a safe platelet count with continued HCV therapy. If not, romiplostim is continued until completion of HCV treatment. A protocol amendment allowed the addition of HCV protease inhibitors for genotype 1a patients. Results At the time of this report 21 patients (7F/14M; mean age 54.9 yrs, range 28-72yrs) have been enrolled in this trial; 13 with platelets 70 to 50,000/µl (Mean 62,000/µl; range 55 to 70,000µl) and 8 with platelet counts<50,000/µl (Mean 35,000/µl; range 25-46,000/µl). 17 patients have completed Phase I; 2 patients are ongoing, 1 patient withdrew at wk 5 with no platelet response (Blind remains) and one patient was withdrawn at wk 2 when review of the pre-randomization ultrasound found evidence of an old partial portal thrombosis. Five patients failed to obtain a platelet count of >100,000/ul by wk 8; all on placebo and were rolled over to romiplostim. The mean romiplostim dose for patients completing Phase I with platelets 70 to 50,000/µl was 2.2 mcg/kg and 3.1 mcg/kg for patients with platelets of<50,000/µl. During the 8 wk course of romiplostim there were no SAEs and no change in HCV viral load. Eleven patients have successfully completed Phase II with 24 wks of HCV treatment; with 4 patients on HCV treatment at wks 21, 20, 13 and 9. One patient was withdrawn at wk 14 due to intractable pancytopenia. 7/11 (64%) were HCV viral load negative at wk 24 and continued to completion of their HCV treatment. The mean romiplostim dose for the 11 patients completing Phase II with HCV treatment was 7µg/kg (3 to 10µg/kg). Three major SAEs occurred during Phase II. A 61 y.o. female developed pancytopenia at wk 14 unresponsive to growth factor support with a hypocellular bone marrow. She had a slow recovery of counts over several months. A 63 y.o. female developed portal vein thrombosis at wk 22 of HCV therapy. Her platelet count was 92,000/µl. She was treated with LMW heparin, continued HCV treatment with romiplostim off study and was viral load negative at wk 44 of treatment. A 50 y.o. female had a sudden death at home at wk 20 of HCV therapy. She has a platelet count of 32,000/µl on a clinic visit the day before her death and her romiplostim dose was 10µg/kg. No autopsy was performed. Conclusion In this interim analysis of ongoing clinical trial, romiplostim appears well tolerated and effective in increasing platelet counts in HCV cirrhotic patients and can maintain a safe platelet count in the majority of patients during HCV antiviral therapy with Peg-INF/RIB. This study was funded by a grant from AMGEN. Disclosures: Liebman: Amgen: Research Funding. Off Label Use: A clinical trial of romiplostim to treat hepatitis C-related thrombocytopenia performed under an FDA IND.

HIV-positive Kaposi sarcoma and immune checkpoint blockade.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 63-63 ◽  
Author(s):  
Natalie Galanina ◽  
Aaron Goodman ◽  
Philip R Cohen ◽  
Razelle Kurzrock
Keyword(s):  
Viral Load ◽  
Immune Checkpoint ◽  
Kaposi Sarcoma ◽  
Immune Checkpoint Blockade ◽  
Cd4 Count ◽  
Checkpoint Blockade ◽  
Hiv Positive ◽  
Hiv Viral Load ◽  
Gastrointestinal Discomfort ◽  
Count Table

63 Title: HIV-Positive Kaposi Sarcoma and Immune Checkpoint Blockade Background: Kaposi sarcoma (KS) is an incurable, virally mediated malignancy arising in HIV-positive patients. We report the first observations on the safety and efficacy of checkpoint blockade in these patients. Methods: We identified eight evaluable patients with HIV-related Kaposi sarcoma who received ≥1 dose of checkpoint blockade. Data on demographics, treatment efficacy, and the effects on immune function (HIV and HHV8 viral load, CD4 count) and toxicity were curated. Results: Median age was 45.5 years (range, 38-63); all men; median, one prior regimen; all were treated with nivolumab 3mg/kg IV days 1 and 14 of each 28-day cycle. PD-L1 expression was assessed retrospectively and was low in 3 out of 4 patients with available data. All patients were receiving anti-retroviral therapy. The majority (75%) had preserved CD4 count and undetectable HIV viral load (Table). The response rate (RR) was 62.5% (5 of 8 patients) with 1 complete remission and 4 partial remissions; the remaining 3 patients have stable disease. Median follow up to date is 3.5 months and no patients has discontinued therapy. No grade >2 toxicities were noted. Most common side effects included fatigue, gastrointestinal discomfort, pruritis, and onycholysis. There was an overall increase in CD4 counts. Conclusions: Preliminary observations suggest that checkpoint blockade with nivolumab has low toxicity and high anti-tumor activity in KS. Additionally, patients experienced improvement in CD4 count. [Table: see text]

scholarly journals Treatment of Immune Thrombocytopenia (ITP) with Eltrombopag - Results of the 4 th Interim Analysis of the German Non-Interventional Trial RISA

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3150-3150
Author(s):  
Oliver Meyer ◽  
Rudolf Schlag ◽  
Thomas Stauch ◽  
Bastian Fleischmann ◽  
Marcel Reiser ◽  
...  
Keyword(s):  
Platelet Count ◽  
Interim Analysis ◽  
Receptor Agonist ◽  
Immune Thrombocytopenia ◽  
Bleeding Complications ◽  
Bleeding Events ◽  
Interventional Trial ◽  
Platelet Counts ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist

Abstract Background: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder with increased platelet destruction and impaired platelet production. Patients present with bleeding complications of various severity. Another common symptom of ITP is fatigue, which can severely affect patient's quality of life. Eltrombopag (EPAG) is an oral thrombopoietin receptor agonist, which is proved to be effective and safe in the treatment of ITP. In Europe, it is approved for the therapy of patients who were diagnosed with ITP at least 6 months ago and who have not responded to other treatments. Here we present data from the 4 th interim analysis of the RISA study. Methods: RISA is a prospective multicenter non-interventional trial in Germany. It was launched in December 2015, and it will be continued until December 2023. In accordance with the inclusion criteria, adults with persisting or chronic pITP (primary ITP) have been enrolled. Patients with pre-treatment could only be included if it was terminated 4 weeks prior to the patient's consent to participate in the study. Exclusion criteria comprised pregnancy, hepatitis C infection and severe aplastic anaemia. Dosage of EPAG and treatment of patients follows the SmPC and the routine of treating physicians. According to the study protocol, patient questionnaires must be completed at 0,1,3,6,9,12,18 and 24 months. Fatigue is assessed using the FACIT-F score, which includes a score range from 0 to 52, with score values &lt;30 indicating severe fatigue. Statistical elaboration is predominantly descriptive. Calculations of confidence intervals and significance values are performed only for explorative purposes. Results: Data cutoff for this 4 th interim analysis was 23.02.2021. 275 patients were enrolled. 261 of them received at least one dose of EPAG and completed one post baseline assessment. Mean duration of participation was 5.2 years. Mean±SD age was 62.7±17.6 years. 54.8% of the patients were female. Median (range) duration of ITP at baseline was 5.3 (0.0-44.9) years. Comorbidity was present in 80.5% of all patients. 79 (28.7%) patients completed all scheduled visits before data cutoff. Median treatment duration was 395.0 days. Treatment with EPAG was carried out at a median dosage of 50 mg daily. In 255 patients, baseline platelet counts were available. The proportion of patients with a platelet count ≥50x10 9/L was 30.6% at baseline. With EPAG treatment, it increased to 75.4% within the first month (N=224) and to 89.0% within 24 months (N=73) from baseline. 12.6% of the patients who completed at least one assessment visit after baseline were pre-treated with the thrombopoietin receptor agonist romiplostim. Within this subgroup as well, platelet counts responded well to EPAG treatment. In 35.6% of patients, at least one bleeding event had occurred in the 12 months prior to baseline. During EPAG therapy, the incidence of bleeding events per patient year was reduced from 1.40 before baseline to 0.60 and 0.13 within the first and second treatment year respectively. This corresponds to a relative reduction in bleeding events of 57% and 91% respectively. Over the entire two years treatment period, the average incidence of bleeding events per patient year accounted for 0.44, which is 69% below the incidence at baseline. Bleeding events were mostly of low severity. (Tab.) Median FACIT-F score was 37.0 at baseline (N=202; mean 36.0±11.0) and 42.5 after 24 months (N=48; mean 38.1±12.1). This difference was not statistically significant. According to exploratory calculations, severity of fatigue was not correlated to platelet count, hemoglobin concentration or incidence of bleeding events. Discussion: In line with previously published randomized controlled trials (Birocchi et al. Platelets 2021), this non-interventional study confirmed the effectiveness of EPAG in adults with persistent or chronic ITP in a routine care setting. During treatment with EPAG, the prevalence and severity of thrombocytopenia, as well as the incidence of bleeding events, decreased. We could also confirm that fatigue is a significant issue in patients with ITP. A FACIT-F score of 37.0 is comparable to average score values in cancer patients (Montan et al. Value Health 2018). Under treatment with EPAG, we observed a decrease in fatigue that was clinically relevant but not statistically significant. Further research is needed to explore possible additional effects of EPAG, for example on fatigue. Figure 1 Figure 1. Disclosures Meyer: Swedish Orphan Biovitrum: Consultancy, Honoraria; Grifols: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Stauch: Novartis: Honoraria, Research Funding; Amgen: Honoraria. Willy: Novartis Pharma: Current Employment.

scholarly journals Influence of HLA-B*5701 on 20 year survival rate among patients living with HIV

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255834
Author(s):  
Bogusz Jan Aksak-Wąs ◽  
Miłosz Parczewski ◽  
Anna Urbańska ◽  
Małgorzata Hackiewicz ◽  
Justyna D. Kowalska
Keyword(s):  
Viral Load ◽  
Cd4 Count ◽  
Baseline Viral Load ◽  
People Living With Hiv ◽  
Hiv Viral Load ◽  
Cross Sectional ◽  
End Point ◽  
Lower Baseline ◽  
Route Of Transmission ◽  
Living With Hiv

Background The life expectancy of people living with HIV (PLWH) remains shorter than that of the general population, despite significant improvement in the recent years. Mortality in HIV-infected individuals may be associated with a higher viral load at of diagnosis, a lower CD4 count, or clinical variables such as sex or route of transmission. This article investigated the role of the HLA-B*5701 varian on mortality among PLWH. Methods Material for the analysis consist of the data of 2,393 patients for whom the HLA-B*57 variant was known. Those patients were followed under the care of the Infectious Diseases Hospital in Warsaw (n = 1555) and the Clinic of Acquired Immunodeficiency of the Pomeranian Medical University in Szczecin (n = 838). Factors such as age, gender, date of HIV diagnosis, route of transmission, date of death, baseline HIV viral load and baseline CD4 counts, were collected, and end-point cross-sectional analyses were marked at 60, 120, 180 and 240 month of observation. Results HLA-B*5701 allele was found in 133 (5.5%) analyzed cases. Median age was notably higher for HLA-B*5701 positive patients [32.7 (28.3–41.3) vs. 31.6 (26.8–38.3)years p = 0.02]. HLA-B*5701 was associated with lower baseline viral load [4.21 (3.5–4.8) vs. 4.79 (4.2–5.3)log copies/ml p<0.001] and higher CD4count [448 (294.5–662) vs. 352 (176–514) cells/μl p<0.001]. There were no association between HLA-B*5701 and survival for any given end-point. Higher mortality was associated to male gender, intravenous drug users, lower CD4 count at baseline and higher baseline viral load. Conclusions In our study, the presence of HLA-B*5701 allel was not associated with mortality rate of HIV infected patients, irrespective of being associated with both higher baseline CD4 + cell count and lower baseline HIV viral load.

scholarly journals Severe Thrombocytopenia Does Not Increase Bleeding Complications in Patients Undergoing Bronchoscopy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4293-4293
Author(s):  
Lakshminarayanan Nandagopal ◽  
Muthu Veeraputhiran ◽  
Tania Jain ◽  
Ayman Soubani ◽  
Charles A. Schiffer
Keyword(s):  
Platelet Count ◽  
Renal Dysfunction ◽  
Platelet Transfusion ◽  
Conflicts Of Interest ◽  
Bleeding Complications ◽  
British Thoracic Society ◽  
Severe Thrombocytopenia ◽  
Platelet Counts ◽  
Number Of Patients ◽  
Platelet Transfusions

Abstract Introduction Prophylactic platelet transfusions are often performed prior to bronchoscopy or broncho-alveolar lavage (BAL) to prevent bleeding in thrombocytopenic patients. There is a paucity of data to validate this approach, with a platelet transfusion threshold of <50,000/mm3 largely based on expert opinion. We conducted a retrospective study on the incidence of bleeding complications in thrombocytopenic patients undergoing bronchoscopy. Methods We identified 150 consecutive patients with platelet counts <100,000/mm3 who underwent bronchoscopy and/or BAL from January 2009 to May 2014 at our institution. Bronchoscopies performed in patients with frank hemoptysis and trans-bronchial lung biopsy procedures were excluded. Patient characteristics, underlying diagnosis, platelet count prior to bronchoscopy, administration of platelet transfusions and bronchoscopy details were recorded. Factors affecting bleeding risk including presence of renal dysfunction (defined as BUN >30 and/or Cr>2.0) and coagulation studies (PT, PTT, INR) were identified. The British Thoracic Society guidelines1 were used to categorize bleeding as a result of bronchoscopy. Data were analyzed using descriptive statistics. Results The median age was 59 years (range 27-90), with two-thirds of patients (63%) being male. One hundred and seventeen (78%) patients had underlying malignancy and 55 (37%) had thrombocytopenia related to malignancy. Fellows and residents under the supervision of a bronchoscopy certified attending performed all but 4 of the bronchoscopies. Infection (40%) was the primary indication for bronchoscopy with BAL performed in 127 (85%) patients. Fifty-eight of 89 (65%) patients with baseline platelet counts <50,000/mm3 received prophylactic transfusions compared to 8% of those with platelet counts >50,000/mm3. The platelet count did not rise to >50,000//mm3 in many transfused patients. Seventy patients (47%) had counts <50,000/mm3 and eighty patients (53%) had counts >50,000/mm3 at the time of bronchoscopy. 49% were receiving immunosuppressive medications, 45% had renal dysfunction and 8% had INR >1.5. Bloody lavage that resolved spontaneously without continuous suctioning (Grade 0) was observed in 9 (6%) patients. Bleeding that required continuous suctioning but then resolved spontaneously (Grade 1) was noted in 1 patient with a platelet count of 61,000/mm3. Of 10 total bleeding events, 7 occurred in patients who were intubated. Two additional patients with platelet counts of 30,000/mm3 and 53,000/mm3 had diffuse alveolar hemorrhage, which was present before bronchoscopy. “Old” blood and blood clots were observed in 6 patients. Discussion The low incidence of bleeding complications from bronchoscopy +/- BAL even in patients with platelet counts <30,000/mm3 (3 episodes in 31 patients, all grade 0) demonstrates that bronchoscopy can be safely done in severely thrombocytopenic patients. Adopting a lower threshold for prophylactic transfusions could save a considerable number of platelet units and translate into significant cost savings and decreased risk of transfusion-related complications. Table 1 Platelet count, transfusion history and bleeding complications during bronchoscopy Platelet count at the time of bronchoscopy Number (n) and percentage (%) of patients who underwent bronchoscopy Number of patients who received prior platelet transfusion Bleeding during bronchoscopy n % 0-15,000/mm3 9 6% (9/150) 5 Grade 0=1 pt 16-29 22 15% 16 Grade 0=2 pts 30-39 17 11% 9 Grade 0=1 pt 40-49 22 15% 9 Grade 0=3 pts 50-75 44 29% 14 Grade 1=1 pt 76-100 36 24% 10 Grade 0=2 pts Total 150 63 Grade 0=9 pts, Grade 1=1 pt. 1.Du Rand IA, Blaikley J, Booton R, et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE. Thorax. 2013:68 Suppl 1:i1-i44 Disclosures No relevant conflicts of interest to declare.

scholarly journals Management of acute myocardial infarction in a patient with idiopathic thrombocytopenic purpura, the value of optical coherence tomography: a case report

2020 ◽  
Author(s):  
Kumayl Al-Lawati ◽  
Mohammed Osheiba ◽  
Will Lester ◽  
Sohail Q Khan
Keyword(s):  
Myocardial Infarction ◽  
Optical Coherence Tomography ◽  
Platelet Count ◽  
Management Plan ◽  
Bleeding Complications ◽  
Optical Coherence ◽  
Rare Presentation ◽  
Thrombocytopenic Purpura ◽  
Thrombotic Complications ◽  
St Elevation

Abstract Background  Treating myocardial infarction in the setting of immune thrombocytopenic purpura (ITP) is always a challenge especially if the platelet count is labile. Cardiologists dealing with such patients should keep a delicate balance between thrombotic and bleeding complications. Case summary  A 50-year-old gentleman with treatment-challenging ITP presented with acute inferior ST elevation myocardial infarction after receiving recent intravenous immunoglobulin. Using optical coherence tomography (OCT) guidance, it was decided to treat him with percutaneous old balloon angioplasty especially with the labile nature of his platelet count. Subsequently, dual antiplatelet therapy was a challenge and he remained on clopidogrel for a period of only 10 weeks. Conclusion  This case highlights the rare presentation of patients with ITP with thrombotic complications and the usefulness of OCT in formulating a management plan.

scholarly journals A rare presentation of an elderly patient with acute lymphocytic leukemia and platelet count of zero associated with ST-elevation myocardial infarction, pulmonary thromboembolism in the setting of SARS-CoV 2: a case report

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Arash Hashemi ◽  
Fady Gerges ◽  
Haseeb Raza Naqvi ◽  
Irina Kotlar ◽  
Sara Moscatelli ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Elderly Patient ◽  
Platelet Count ◽  
Acute Lymphocytic Leukemia ◽  
Platelet Transfusion ◽  
Pulmonary Thromboembolism ◽  
Antiplatelet Agent ◽  
Lymphocytic Leukemia ◽  
Bleeding Complications ◽  
St Elevation

Abstract Background Novel coronavirus disease 2019 (COVID-19) is known to lead not only to severe acute respiratory syndrome, but also can result in thromboembolic events in both the venous and the arterial circulation by inducing coagulation disorders. The potential causes of coagulopathy are inflammation, platelet activation, endothelial dysfunction, and stasis. The thrombotic events including pulmonary embolism, deep venous thrombosis as well as intracatheter thrombosis are more likely to develop in patients infected with severe form of SARS-CoV-2 who are admitted to ICU. Furthermore, these events contribute to multi-organ failure. Case presentation Herein, we report a case of an immunocompromised COVID-19 elderly patient with acute lymphocytic leukemia who developed myocardial infarction with ST elevation in the setting of acute pulmonary thromboembolism in the presence of zero platelet count. Despite successful urgent coronary revascularization and platelet transfusion, the patient eventually died after failed resuscitation efforts. Conclusion Patients with COVID-19 infection are at a greater risk of developing cardiovascular complications, but their appropriate management can decrease the risk of fatal events. Coronary thrombosis associated with pulmonary thromboembolism in the setting of thrombocytopenia is a rare and a complex to manage condition. Significance of single antiplatelet agent in STEMI with thrombocytopenia merits further studies. According to expert opinions and literature reviews, we must avoid dual antiplatelet therapy in these patients and keep platelet transfusion as a standard therapy to avoid drastic bleeding complications.

Sign in / Sign up

Export Citation Format

Share Document