Intra-Abdominal Venous Thrombosis: Characteristics of Pediatric and Adult Patients

Abstract Abstract 4219 Background: Clinical characteristics associated with abdominal vein thrombosis (including hepatic, portal, and mesenteric veins; renal veins; and inferior vena cava [IVC]) overlap with characteristics associated with deep vein thrombosis (DVT) in the legs and pulmonary embolism (PE) but also possess unique attributes. These characteristics may differ between adult and pediatric patient groups. Methods: Using a standardized data-collection form, demographic and baseline characteristics were prospectively collected from consecutive consenting patients enrolled within one of seven Thrombosis and Hemostasis Centers over a seven-year period, August 2003 to June 2010. Patients with intra-abdominal venous thrombosis (defined as abdominal and renal veins, and IVC) were divided into pediatric (age <18 years) and adult (age ≥18 years) groups and compared to patients in the same age ranges with lower extremity DVT and/or PE. RESULTS: As of June 2010, the Patient Registry contained a total of 3105 patients with venous thromboembolism (VTE). A total of 270 patients had intra-abdominal thrombosis (9%) compared to 2276 with lower extremity DVT and/or PE (73%). Of the intra-abdominal clots, pediatric patients were more likely to have IVC thrombus (22 of 42; 52%) than adults (38 of 228; 17%; p<0.0001); conversely, pediatric patients were less likely to have hepatic, portal, and mesenteric thrombosis (n=25; 60%) than adults (n=195; 86%, p<.0001). For adult patients, proportionately more women had abdominal thrombosis (157 of 228; 68.9%) than DVT/PE (1306 of 2140; 61%; p=0.02); in contrast, comparable numbers of female pediatric patients had abdominal thrombosis (20 of 42; 47.6%) and DVT/PE (68 of 136; 50%). The mean age for patients having abdominal thrombosis was lower than patients having DVT/PE for both adults (38.3 vs 43.0 yrs; p<0.0001) and pediatric patients (9.0 vs 11.9 yrs; p=0.014). Similarly, the mean body mass index was lower for patients having abdominal thrombosis than patients having DVT/PE for both adults (28.1 vs 30.8; p<0.0001) and pediatric patients (21.5 vs. 24.7; p=0.05). There were no relationships with race, ethnicity, or inherited thrombophilic disorders. In adults, autoimmune conditions (21.9 vs 13.6; p=0.0007) and recent surgery (14.0 vs 9.2; p=0.02) were more common in patients with abdominal thrombosis, whereas, hyperlipidemia was more frequent in patients with DVT/PE (8.3 vs 13.2; p=0.04). None of these relationships were seen in the pediatric patients, but trauma was more frequently seen in pediatric patients with DVT/PE than abdominal thrombosis. Sixty-one adult (26.8%) and 6 pediatric patients (14.3%) had another VTE elsewhere, with most occurring after the initial event (21 DVT and 7 PE). Similar proportions of adult and pediatric patients had arterial thromboembolic events for both abdominal thrombosis and DVT/PE. CONCLUSIONS: Adult patients with abdominal thrombosis are more likely female, have hepatic, portal and/or mesenteric vein thrombosis, and common co-morbid conditions include recent surgery and autoimmune disorders. Pediatric patients are evenly divided between male and female, more commonly have IVC thrombosis, and co-morbid conditions include recent trauma. Both adult and pediatric patients with abdominal thrombosis tend to be younger and have a lower BMI than patients with DVT and/or PE. We also found a high rate of concurrent thrombosis in both adult and pediatric patients with abdominal thrombosis. In summary, patients with abdominal thrombosis display different clinical characteristics when compared to those with DVT/PE, specifically in terms of gender, location of thrombosis, and associated co-morbidities. Some of these differences, such as higher rates of IVC thrombosis in pediatric patients with abdominal thrombosis, might be caused by variance between genetic and anatomic factors. Further studies are warranted to explain these differences. Disclosures: Kulkarni: Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Participate in clinical trials. Philipp:Baxter: Research Funding; Wyeth: Research Funding; Octapharma: Research Funding. Ortel:Sanofi-Aventis: Consultancy, Research Funding; Ortho-McNeil: Consultancy; GlaxoSmithKline: Research Funding; Eisai: Research Funding; Pfizer: Research Funding.

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Different Clinical Characteristics of Paroxysmal Nocturnal Hemoglobinuria in Pediatric and Adult Patients

Blood ◽

10.1182/blood.v126.23.3341.3341 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3341-3341

Author(s):

Alvaro Urbano-Ispizua ◽

Petra Muus ◽

Hubert Schrezenmeier ◽

Antonio Medina Almeida ◽

Amanda Wilson ◽

...

Keyword(s):

Research Funding ◽

Paroxysmal Nocturnal Hemoglobinuria ◽

Clinical Characteristics ◽

Pediatric Patients ◽

Adult Patients ◽

Vascular Event ◽

Clone Size ◽

History Of ◽

Pnh Clone ◽

Hypoplastic Anemia

Abstract Introduction: Studies of children with paroxysmal nocturnal hemoglobinuria (PNH) are scarce and include a very limited number of patients. The objective of this analysis was to describe characteristics of PNH at enrollment for the largest available registry of pediatric patients, and to compare demographic and clinical characteristics with those of adult patients. Methods: The International PNH Registry is a prospective, multi-center worldwide, observational study of patients with a PNH clone of 0.01-100%. Data are collected from patient medical records at the time of Registry enrollment and every six months thereafter. Adult patients were ³18 years of age at enrollment and disease start and pediatric patients were <18 years at enrollment. Demographics and clinical parameters in patients untreated with eculizumab at enrollment for the two age cohorts were compared using the Wilcoxon-Mann-Whitney test for medians and PearsonÕs chi-square for frequencies. The rate of thrombotic events (TE) between disease start (defined as the earliest reported PNH symptoms, granulocyte clone, or PNH diagnosis) and enrollment was calculated per 100 person-years. Results: As of March 2, 2015, a total of 2,184 patients were eligible for analysis: 94 (4.3%) pediatric patients and 2,090 (95.7%) adult patients. Median age (range) at enrollment was 14.0 years (3-17) in pediatrics and 45.5 years (18-100) in adults; median disease duration was 0.7 years and 2.1 years, respectively (p<0.001). More pediatric than adult patients had a PNH clone of <10% and severe cytopenia (Table). Pediatric patients had lower percent of reticulocytes compared with adults (2.1% vs. 2.6%, respectively; p=0.015). History of aplastic or hypoplastic anemia was more frequent in pediatric than adult patients (76.5% vs 54.4%, respectively; p<0.001). History of TE and any major adverse vascular event was less frequent in pediatrics (2.1% vs 8.7%; p=0.025, and 4.3% vs. 14.4%; p=0.005). The rate of TE between disease start and enrollment was lower in pediatric patients, but not statistically significant: 1.4 per 100 person-years (95%CI 0.2-5.2) compared to adult patients (2.3 per 100 person-years (95%CI 2.0-2.6). More pediatric patients than adults had abdominal pain at enrollment. Conclusions: The International PNH Registry provides the largest available pediatric cohort of patients with a PNH clone to characterize this understudied population and demonstrate an important disease burden. Pediatric patients were more likely to have smaller PNH clones and a higher component of aplastic/hypoplastic anemia. Pediatric patients had fewer vascular events. These findings may reflect the natural evolution of the disease and can be useful in the clinical management of PNH. Table 1. Clinical Characteristics at Enrollment of Pediatric and Adult Patients with PNH Pediatric(n=94) Adult(n=2,090) P-value Clone size (percent GPI-deficient granulocytes), n (%)<10% 10 to < 50% ³50% 47 (55.3) 16 (18.8) 22 (25.9) 550 (38.3) 322 (22.4) 565 (39.3) 0.006* Cytopenia status, n (%)None (neutrophils ³ 1.5 x 109/L and platelets ³100 x 109/L) Moderate (neutrophils <1.5 x 109/L or platelets <100 x 109/L) Severe (neutrophils <0.5 x 109/L or platelets <20x109/L) 22 (29.3) 28 (37.3) 25 (33.3) 735 (42.2) 784 (45.1) 221 (12.7) <0.001* Percent reticulocytesMedian (Q1, Q3) 2.1 (1.1, 3.5) 2.6 (1.6, 4.6) 0.015 Hemolytic status, n (%)Hemolytic (LDH ³1.5 x ULN and/or reticulocytes ³60 x 109/L) Not hemolytic (LDH <1.5 x ULN and reticulocytes <60 x 109/L) 33 (58.9) 23 (41.1) 1,038 (65.3) 551 (34.7) NS LDH Ratio, n (%)<1.5 x ULN³1.5 x ULN 30 (58.8) 21 (41.2) 684 (47.0) 770 (53.0) NS History of TE, n (%)Yes No 2 (2.1) 92 (97.9) 181 (8.7) 1,902 (91.3) 0.025 Rate of TENumber of TE, n Person-years (disease start to enrollment) Rate/100 person-years (95% CI) 2 139.9 1.4 (0.2-5.2) 255 11,119.8 2.3 (2.0-2.6) NS History of MAVE, n (%) 4 (4.3) 300 (14.4) 0.005 GPI, glycosylphosphatidylinositol; LDH, lactate dehydrogenase; MAVE, major adverse vascular event; TE, thrombotic event; ULN, upper limit of normal *P-values for clone size and cytopenia status represent overall comparison of categories. Disclosures Muus: Alexion Pharmaceuticals: Honoraria. Schrezenmeier:Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Almeida:Celgene: Consultancy; Novartis: Consultancy; Bristol Meyer Squibb: Speakers Bureau; Shire: Speakers Bureau. Wilson:Alexion Pharmaceuticals: Employment. Ware:Bayer Pharmaceuticals: Consultancy; Biomedomics: Research Funding; Eli Lilly: Other: DSMB membership; Bristol Myers Squibb: Research Funding.

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Few predictors of massive deep vein thrombosis

Thrombosis and Haemostasis ◽

10.1160/th05-05-0314 ◽

2005 ◽

Vol 94 (11) ◽

pp. 986-990 ◽

Cited By ~ 1

Author(s):

Hylton Joffe ◽

Nils Kucher ◽

Victor Tapson ◽

Samuel Goldhaber

Keyword(s):

Deep Vein Thrombosis ◽

Lower Extremity ◽

Odds Ratio ◽

Clinical Characteristics ◽

Adjusted Odds Ratio ◽

Independent Predictor ◽

Multivariable Logistic Regression Analysis ◽

Vein Thrombosis ◽

Younger Age ◽

Deep Vein

SummaryFactors that predispose to thrombus propagation from the femoropopliteal veins to the pelvic veins are poorly understood. Our goal was to determine whether there are characteristics that identify patients with massive deep vein thrombosis (DVT). We compared the 122 (2.5%) patients presenting with massive DVT (pelvic plus lower-extremity DVT) to the 4,674 (97.5%) patients with isolated lower-extremity DVT from a prospective United States multicenter DVT registry. Patients with massive DVT were younger (59.4±18.9 years vs. 64.3±16.8 years; p<0.01), less likely to have hypertension (40% vs. 51%; p=0.02), and more likely to smoke (21% vs. 13%; p=0.02) and have on- going radiation therapy (7% vs. 3%; p=0.02). The massive DVT group more commonly presented with extremity edema (80% vs. 69%; p<0.01) and erythema (21% vs. 12%; p<0.01) than the isolated lower-extremity DVT group. However, after multivariable logistic regression analysis, extremity erythema (adjusted odds ratio 1.86; 95% CI 1.13–3.04) was the only independent sequela of massive DVT and younger age (adjusted odds ratio 1.17 per decreasing decade of age; 95% confidence interval: 1.02-1.34) was the only independent predictor of massive DVT. Thrombus propagation from the femoropopliteal system cannot be reliably predicted using demographic or clinical characteristics.

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A case-controlled study on AngioJet rheolytic thrombectomy and catheter-directed thrombolysis in the treatment of acute lower extremity deep venous thrombosis

Vascular ◽

10.1177/1708538119877322 ◽

2019 ◽

Vol 28 (2) ◽

pp. 177-182 ◽

Cited By ~ 2

Author(s):

Jun Zhu ◽

Cai-Fang Ni ◽

Zhen-Yu Dai ◽

Li-Zheng Yao ◽

Wen-Hui Li

Keyword(s):

Deep Vein Thrombosis ◽

Lower Extremity ◽

Controlled Study ◽

Efficacy And Safety ◽

Vein Thrombosis ◽

Catheter Directed Thrombolysis ◽

Rheolytic Thrombectomy ◽

Thrombus Removal ◽

The Mean ◽

Deep Vein

Objective This study aims to compare the efficacy and safety of AngioJet rheolytic thrombectomy vs. catheter-directed thrombolysis in patients with acute lower extremity deep vein thrombosis. Methods Between the period of February 2015 and October 2016, 65 patients with documented acute lower extremity deep vein thrombosis were treated with catheter-directed intervention. These patients were divided into two groups: AngioJet group and catheter-directed thrombolysis group. Comparisons were made with regard to efficacy and safety between these two groups. Results In the AngioJet group, complete or partial thrombus removal was accomplished in 23 (72%) and 3 (9%) patients, respectively. In the catheter-directed thrombolysis group, complete or partial thrombus removal was accomplished in 27 (82%) patients and 1 (3%) patient, respectively. In the AngioJet group, the perimeter difference between the suffered limb and healthy one declined from 5.1 ± 2.3 cm to 1.4 ± 1.2 cm ( P < 0.05). In the catheter-directed thrombolysis group, the perimeter difference declined from 4.7 ± 1.6 cm to 1.5 ± 0.9 cm ( P < 0.05). The mean urokinase dose was 0.264 ± 0.135 million units in the AngioJet group and 1.869 ± 0.528 million units in the catheter-directed thrombolysis group ( P < 0.05). The duration of thrombolysis was 4.2 ± 1.7 h in the AngioJet group and 73.6 ± 18.3 h in the catheter-directed thrombolysis group ( P < 0.05). The occurrence of complications in these two groups was 19% and 18%, respectively (not significant). Conclusion AngioJet rheolytic thrombectomy is a new, safe and effective approach for treating acute lower extremity deep vein thrombosis. When compared to catheter-directed thrombolysis, this treatment provides similar success with lower urokinase dosage and shorter duration of thrombolysis.

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Target Joint Bleeding in Pediatric Patients with Hemophilia Α Receiving Twice Weekly Prophylaxis with a Pegylated Full-Length Recombinant Factor VIII with Extended Half-Life

Blood ◽

10.1182/blood.v128.22.3778.3778 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3778-3778

Author(s):

Amy L. Dunn ◽

Alexis A. Thompson ◽

Werner Engl ◽

Marlies Sharkhawy ◽

Brigitt E. Abbuehl

Keyword(s):

Factor Viii ◽

Board Of Directors ◽

Half Life ◽

Research Funding ◽

Pediatric Patients ◽

Hemophilia A ◽

Point Estimate ◽

Severe Hemophilia ◽

Advisory Committees ◽

The Mean

Abstract Introduction: Patients with hemophilia A are at risk for acute bleeding which may affect muscles and other soft tissues but characteristically involves joints. Prophylaxis with factor VIII (FVIII) is the optimal treatment to prevent bleeding into joints and, when begun at a young age, may prevent arthropathy. BAX 8551, a polyethylene glycol (peg)ylated, full-length, recombinant FVIII built on ADVATE2, demonstrated extended half-life, efficacy, and safety for prophylaxis and treatment of bleeding in patients with severe hemophilia A. Methods: A phase 3, prospective, uncontrolled, multicenter study was performed in pediatric patients with severe hemophilia A without history of inhibitors. To be eligible, patients aged <6 years had to have ≥50, those aged 6 to <12 years ≥150 previous exposure days (EDs) to FVIII. Patients received twice weekly infusions of 50 ±10 IU/kg of BAX 855 over a period of 6 months or ≥50 EDs. The prevalence of target joints, defined as a single joint with ≥3 spontaneous bleeding episodes in any consecutive 6-month period, was assessed at baseline. Annualized rates of target joint bleeds and the course of target joints were evaluated by age (<6 and 6 to <12 years). The study was performed in accordance with the principles of the Declaration of Helsinki of the World Medical Association. Results:Sixty-six patients were treated with a mean (SD) BAX 855 dose of 51.1 (5.5) IU/kg at a mean (SD) frequency of 1.8 (0.2) infusions/week. Fourteen of 66 patients (21.2%), 3/32 (9.4%) in the younger and 11/34 (32.4%) in the older cohort, had a total of 23 target joints at screening. The number of target joint bleeds decreased during a mean (SD) of 48.5 (7.7; median: 49.0) prophylactic EDs/patient. Five of 66 (7.6%) patients had at least 1 target joint bleed, 1/32 (3.1%) in the younger and 4/34 (11.8%) in the older cohort. The point estimate for the mean (95% CI) annualized rate of target joint bleeds was 0 (0 - infinity; median: 0) compared to an annualized rate of all joint bleeds of 1.1 (0.6 - 1.9; median: 0) and an annualized rate of all bleeds of 3.0 (2.2 - 4.2; median: 2.0) (Table 1). The point estimate for the mean (95% CI) annualized bleeding rate (ABR) in 52 patients without target joints was 2.9 (2.0 - 4.2; median: 2.0) and was similar in 14 patients with target joints at screening at 3.5 (1.9 - 6.6; median: 2.1). In the younger cohort, the ABR was lower in patients with than those without target joints. However, the number of patients <6 years with target joints (N = 3) was too small to draw any conclusions (Table 1). During BAX 855 prophylaxis, no new target joints developed in any patient. Ten of 14 patients had at least 1 target joint revert to a non-target joint. In 8 of these 10 patients, 4 with 1 and 4 with 2 target joints, all target joints resolved. Conclusions:These results suggest that twice weekly infusion of BAX 855 is effective in the prevention of bleeding into target joints and may revert target to non-target joints in pediatric patients with severe hemophilia A. 1BAX 855 (Baxalta US Inc., now part of Shire) is licensed in the US and Japan under the trade name ADYNOVATE. 2ADVATE is a trade mark of Baxalta US Inc., now part of Shire. Disclosures Dunn: NovoNordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kedrion: Research Funding; Pfizer: Research Funding; CSL Behring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxalta (now part of Shire): Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Research Funding. Thompson:Eli Lily: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; bluebird bio: Consultancy, Research Funding; ApoPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Mast: Research Funding; Amgen: Research Funding; Baxalta (now part of Shire): Research Funding. Engl:Shire: Employment, Equity Ownership. Sharkhawy:Baxalta (now part of Shire): Employment. Abbuehl:Baxalta (now part of Shire): Employment.

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Clot busting in kids: less PTS?

Blood ◽

10.1182/blood-2007-04-082867 ◽

2007 ◽

Vol 110 (1) ◽

pp. 4-5

Author(s):

Leslie Raffini

Keyword(s):

Deep Vein Thrombosis ◽

High Risk ◽

Lower Extremity ◽

Thrombolytic Therapy ◽

Retrospective Analysis ◽

Pediatric Patients ◽

Postthrombotic Syndrome ◽

Mechanical Thrombolysis ◽

Vein Thrombosis ◽

Deep Vein

Goldenberg and colleagues' retrospective analysis of pediatric patients with high-risk, occlusive lower extremity deep vein thrombosis (DVT) suggests that thrombolytic therapy with tPA (with or without mechanical thrombolysis) may decrease the risk of postthrombotic syndrome (PTS).

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Use of Pegylated Interferon in Six Pediatric Patients with Myeloproliferative Neoplasms

Blood ◽

10.1182/blood-2019-124023 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4194-4194 ◽

Cited By ~ 1

Author(s):

Nicole Kucine ◽

Shayla Bergmann ◽

Spencer Krichevsky ◽

Devin Jones ◽

Michael E. Rytting ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Pediatric Patients ◽

Myeloproliferative Neoplasms ◽

Adult Patients ◽

Specific Information ◽

Advisory Committees ◽

Oncology Research ◽

Increased Risk ◽

Future Fertility

Introduction: The classical BCR-ABL1 negative myeloproliferative neoplasms (MPNs) are clonal disorders of marrow overproliferation. Clinical phenotypes include polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). In adults, both risk stratifications and treatment guidelines are available to physicians. Various agents, including clinical trial agents, are utilized for treatment in adults. Conversely, there are no management guidelines for children with MPNs, and therapeutic options are limited. Hydroxyurea (HU) is the most commonly used agent in children, likely because of physician experience using this medication for sickle cell anemia. Children with MPN have been treated with HU with effective cytoreduction, although its use is controversial because of the concern for leukemogenicity. While it is still considered as first-line therapy in adults with MPNs, some guidelines recommend avoiding hydroxyurea in younger adult patients. Interferon (IFN) has been utilized in adults with MPNs for many years, and pegylated forms (PEG) have made the medication more tolerable. Enthusiasm in IFN is increasing, due to reports in adult patients of hematologic remissions and significant molecular responses, including molecular remissions in rare cases. Given its improved tolerability and potential benefits, IFN may be an appropriate choice for treatment in many children with MPNs. Given the limited experience in this population and available literature, we sought to review a small cohort of pediatric MPNs treated with PEG. Methods: We reviewed the charts of pediatric patients with MPNs who have been treated with PEG and pooled de-identified data. Demographic, mutational, laboratory, and treatment-specific information was documented. This study was approved by institutional IRBs. Results: Six children were identified at four institutions who had been treated with IFN (Table 1). Age at diagnosis of MPN ranged from 2-14 years, and age at onset of PEG therapy ranged from 3-16 years. Two children are female, and four are male. Three children were diagnosed with PV and three with ET. One child with PV is positive for a JAK2 Exon 12 mutation, three children have JAK2V617F mutations (two with PV and one with ET), one child with ET has a CALR mutation, and one child has triple-negative ET. Cytoreductive therapy was started in this cohort for a variety of reasons, including worsening counts, concerning marrow findings, and symptoms (headache being the most common.) Three of the children in this cohort had been treated with HU prior to starting PEG. Reasons for switching cytoreduction to PEG included family concern for increased risk of malignancy and concern for negative effects on future fertility, interest in a disease-modifying agent, and poor side-effect profile of HU. PEG doses ranged from 45 to 90 mcg per dose (Table 2), with dosing frequency ranging from one dose every 1-4 weeks. Blood counts remained generally stable or improved in this cohort; no children required stopping and switching to another cytoreductive agent. One subject developed a pulmonary embolism while on PEG, but was able to remain on therapy; no other MPN-related complications occurred while on PEG. Some children experienced improvement in clinical disease-related symptoms. Mild side-effects reported by subjects included headache, flu-like symptoms, injection site reaction, and abdominal pain. One child had PEG dosed less frequently because of issues with depression and anxiety, and ultimately had therapy discontinued due to normalization of platelet counts. No other dose-limiting drug-related toxicity was reported. All other subjects remain on therapy with PEG, and the duration of therapy ranges from 3-168 months. Conclusion: This cohort of young MPN patients has been treated with PEG with no major dose-limiting toxicity, and with sustained tolerability. While further study is needed, it is clear that PEG can have a role to play in the management of children with MPNs. Having multiple options for cytoreduction available for families to discuss with their pediatric practitioners allows for greater family autonomy. Our results to date highlight the need for prospective study of a larger group of young patients with MPNs treated with PEG. Disclosures Bergmann: Novartis: Research Funding, Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Shire/Takeda: Research Funding; NovoNordisk: Research Funding. Mascarenhas:Pharmaessentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merus: Research Funding; Promedior: Research Funding; Janssen: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Roche: Consultancy, Research Funding; Merck: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Verstovsek:Gilead: Research Funding; Promedior: Research Funding; CTI BioPharma Corp: Research Funding; Genetech: Research Funding; Blueprint Medicines Corp: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Research Funding; Pharma Essentia: Research Funding; Astrazeneca: Research Funding; Ital Pharma: Research Funding; Protaganist Therapeutics: Research Funding; Constellation: Consultancy; Pragmatist: Consultancy; Incyte: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding. Hoffman:Merus: Research Funding. OffLabel Disclosure: Use of interferon and hydroxyurea in children with MPNs is off-label

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Transition of Care for Pediatric and Adult Patients with Venous Thromboembolism in the American Thrombosis Hemostasis Network

Blood ◽

10.1182/blood-2018-99-117533 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4711-4711

Author(s):

Madhvi Rajpurkar ◽

Maura Malone ◽

Jim Munn ◽

Julie Jaffray ◽

Crystal Watson ◽

...

Keyword(s):

Quality Improvement ◽

Venous Thromboembolism ◽

Research Funding ◽

Pediatric Patients ◽

Anticoagulation Therapy ◽

Adult Patients ◽

First Episode ◽

Transition Of Care ◽

Significant Difference

Abstract Background Venous thromboembolism (VTE) is the third leading cause of cardiovascular morbidity and mortality worldwide in adults and is increasingly seen in children. Optimal transition of care (TOC) from the inpatient to the outpatient setting may lead to improved outcomes for patients with VTE. Although several examples of TOC for patients with VTE exist, this project (ATHN 4: Transition of Care for Patients with VTE) is the first to create a uniform TOC model in the U.S that includes both pediatric and adult patients. The aim of this study was to improve the transition of care of adult and pediatric patients discharged on an anticoagulant after a first episode of VTE and evaluate patient/parent understanding and adherence to anticoagulation therapy-related instructions at seven and 30 days after hospital discharge. Methods Pediatric and adult hospitalized patients with a first episode of VTE requiring anticoagulation therapy were eligible to participate in ATHN 4, a multi-center quality improvement (QI) project conducted by the American Thrombosis and Hemostasis Network (ATHN). The project has two phases: a pre-intervention (PI) phase with no change in standard TOC practice, and a QI intervention phase consisting of enhanced education with standardized Comprehensive Discharge Instruction Modules (CDIM) for each anticoagulant. Demographics, disease, treatment characteristics, and outcomes were collected. Knowledge and feedback questionnaires were administered at 30 days post-discharge. Adult and pediatric data from the PI phase are presented. Results Complete data were submitted for 188 (91%) patients who were enrolled in the PI phase between May 2016 and March 2017 (Table 3). Results show that 73 (39%) were under 18 years of age, 90 (48%) were female, and 156 (83%) were non-Hispanic. A significant difference (p<0.001) in the location of the first VTE was noted among the pediatric and adult patients (Table 4). Approximately 66% (n=48) of the pediatric patients had a DVT, compared to 30% (n=34) of the adult patients. There were more adults with PE as compared to pediatric patients(43% vs. 3%). Adult and pediatric patients differ substantially (p <0.001) with respect to anticoagulant prescriptions. Pediatric patients were more likely to be prescribed Enoxaparin at discharge compared to adults (86% vs. 21%). Additionally, a significantly larger proportion of adult compared to pediatric patients was prescribed Warfarin (17% vs. 3%). Direct oral anticoagulants (DOACs) were mainly prescribed in the adult patients: Apixaban (24% vs. 0%) and Rivaroxaban (18% vs. 3%) compared to the pediatric patients. Based on the responses provided by the patients or guardians (for pediatric patients) during the Day 30 follow-up, there was almost an equal distribution among pediatric and adult patients who by clinical assessment were determined to have correctly taken the prescribed anticoagulant between the time of discharge and follow-up (98.6% of pediatrics and 97.4% of adults). Conclusions Our quality improvement study shows that the majority of pediatric and adult patients correctly took the anticoagulation medication prescribed to them at discharge for at least a month. Majority of pediatric patients presented with a DVT while PE was the most common presentation in adult patients. Enoxaparin and Apixaban were the most commonly prescribed anticoagulants to pediatric and adult patients, respectively. Factors affecting anticoagulation adherence and outcomes in these patients are currently being analyzed. Disclosures Rajpurkar: Bristol Myers Squibb: Research Funding; Shire: Honoraria; HEMA biologics: Honoraria; Pfizer: Honoraria, Research Funding; Novonordisk: Honoraria. Jaffray:Octapharma: Consultancy; CSL Behring: Consultancy, Research Funding; Bayer: Consultancy.

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Determinants of Complicated Pneumonia in Hospitalized Pediatric Patients

ACTA MEDICA IRANICA ◽

10.18502/acta.v59i3.5786 ◽

2021 ◽

Author(s):

Mohammadreza Mirkarimi ◽

Mohsen Alisamir ◽

Parastoo Nasiri ◽

Shahriar Barouti ◽

Shooka Mohammadi

Keyword(s):

Clinical Characteristics ◽

Pediatric Patients ◽

Length Of Hospital Stay ◽

Failure To Thrive ◽

Underlying Disease ◽

Hospitalized Children ◽

History Of ◽

The Mean ◽

Iranian Children ◽

Complicated Pneumonia

Pediatric complicated pneumonia (PCOMP) is the leading cause of mortality in children under the age of five. The study was conducted to determine the epidemiological and clinical characteristics of children with PCOMP. A retrospective study was carried out among all pediatric patients who were hospitalized due to complicated pneumonia in Abuzar Hospital (Ahvaz, Iran) during two years. The patients were evaluated in terms of epidemiological and clinical characteristics. A total of 65 hospitalized children and infants were identified. More than half of the patients were females (n=36; 55.3%). Their mean age was 4.21±3.80 years (range six months-15 years), and 64.1% of them (n=42) were under the age of five. There were 12 (19.4%) patients with failure to thrive (FTT). In addition, 58.5% of patients (n=38) had no history of hospitalization, and 66.2% of them (n=43) did not have any underlying disease. The mean length of hospital stay (LOS) was 12.46±6.85 (range 4-45) days. Admission was more common in winter (40%) and autumn (33.8%). Moreover, there were no significant associations between the types of complications and patients’ gender, age, FTT, and LOS. Further studies are warranted to identify factors contributing to disease severity and develop appropriate strategies for the prevention and treatment of PCOMP among Iranian children.

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Baseline Characteristics of Patients in Peak: A Global, Longitudinal Registry of Patients with Pyruvate Kinase Deficiency

Blood ◽

10.1182/blood-2020-136634 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 39-40

Author(s):

Rachael F. Grace ◽

Audra Boscoe ◽

Chris Bowden ◽

Bertil Glader ◽

Hitoshi Kanno ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Pediatric Patients ◽

Chelation Therapy ◽

Treatment Patterns ◽

Missense Mutations ◽

Private Company ◽

Advisory Committees ◽

The Mean

Background: Pyruvate kinase (PK) deficiency is a rare, inherited hemolytic anemia caused by autosomal recessive mutations in the PKLR gene, whereby a glycolytic defect causes a reduction in adenosine triphosphate generation. Current treatment options are supportive and include splenectomy, blood transfusions, and iron chelation therapy. To better understand the natural history, treatment patterns, and burden of disease, the observational PK Deficiency Natural History Study (NHS) (NCT02053480) enrolled 254 adult and pediatric patients with PK deficiency at 30 sites in 6 countries between 2014 and 2017 and followed patients for 2 years. The Peak Registry (NCT03481738) was developed to continue and expand on this research. This retrospective and prospective observational registry aims to enroll 500 adult and pediatric patients at ~ 60 sites in up to 20 countries over 7 years, with 2-9 years of follow-up. Objective: This analysis aimed to characterize the baseline demographics and clinical characteristics of patients with PK deficiency enrolled in the Peak Registry as of 24March2020. Methods: Demographic, diagnostic, medical history, laboratory, treatment, and other relevant data were collected from participating clinicians via electronic case report forms. To be eligible for inclusion in this analysis, patients were required to have genetically confirmed PK deficiency and available demographic information. All analyses reported here are descriptive and based on data as of the date of enrollment in the registry. Continuous variables are summarized by the number of non-missing observations, mean, standard deviation (SD), median, and range. Categorical variables are summarized as counts and percentages. Results: A total of 141 patients met the inclusion criteria, across 11 countries in North America and Europe. A summary of baseline demographics and clinical characteristics is shown in the Table. Fifty patients (35.5%) had completed 2 years of follow-up in the NHS and then moved to the Peak Registry; the remainder were newly recruited to the Peak Registry. The mean age of study participants at enrollment was 25.5 years (SD 19.1); 78 patients (55.3%) were female. Mean reported age at first symptoms was 5.8 years (SD 13.2) and mean age at diagnosis was 11.7 years (SD 16.0). Fifty-seven percent of patients were classified as having missense/missense mutations, 34.4% as having missense/non-missense mutations, and 8.6% as having non-missense/non-missense mutations. The mean hemoglobin at enrollment was 8.8 g/dL (range: 5.8-12.9 g/dL). Mean reticulocyte count was 19.8% (range: 2.2-42.4%), mean lactate dehydrogenase was 382 IU/L (range: 135-849 IU/L), and mean indirect bilirubin was 4.3 mg/dL (range: 0.8-23.1 mg/dL). Among the 45.2% of patients who had been splenectomized, the mean age at splenectomy was 7.2 years. Chelation therapy had been previously prescribed to 40.3% of patients. Among the 27 patients for whom ferritin data were available, the mean was 867.9 ng/L (range: 78.1-2499.0 ng/L), and 18 patients (66.7%) had a level > 500 ng/L. Ninety-nine patients (70.2%) had received at least one transfusion in their lifetime. Among the 45 patients who were known to have received at ≥ 1 transfusion in the 12 months prior to enrollment, the mean number of transfusions during that period was 5 (SD 4.3), with 18 of those patients (40.0%) having received ≥ 6 transfusions. Conclusions: New data emerging from the Peak Registry will provide valuable insights into the patient characteristics, treatment patterns, and burden associated with PK deficiency. The population is demographically heterogenous and represents a broad geography. Patients have a wide range of hemoglobin levels, and iron overload is common. The substantial rates of splenectomy, cholecystectomy, transfusions, and chelation use are indicative of a high disease and treatment burden in patients with PK deficiency. This abstract is presented on behalf of the Peak Registry Steering Committee and Peak Registry Investigators. Disclosures Grace: Novartis: Research Funding; Pfizer: Research Funding; Agios: Research Funding; Dova: Membership on an entity's Board of Directors or advisory committees. Boscoe:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Bowden:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Glader:Agios Pharmaceuticals, Inc.: Consultancy. Layton:Cerus: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees. van Beers:Novartis: Research Funding; Pfizer: Research Funding; RR mechatronics: Research Funding; Agios: Membership on an entity's Board of Directors or advisory committees, Research Funding. Yan:Agios Pharmaceuticals: Consultancy. Bianchi:Agios Pharmaceuticals: Other: Scientific Advisor.

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Clinical Characteristics of Classic Paroxysmal Nocturnal Hemoglobinuria (PNH) in Pediatric Patients: A Comparison with Classic PNH in Adults. An International PNH Registry Study

Blood ◽

10.1182/blood.v118.21.2102.2102 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2102-2102 ◽

Cited By ~ 1

Author(s):

Alvaro Urbano-Ispizua ◽

Hubert Schrezenmeier ◽

Petra Muus ◽

Jaroslaw P Maciejewski ◽

Gérard Socié ◽

...

Keyword(s):

Kidney Disease ◽

Board Of Directors ◽

Research Funding ◽

Pediatric Patients ◽

Event Rate ◽

Adult Patients ◽

Employment Equity ◽

Advisory Committees ◽

Clone Size ◽

Equity Ownership

Abstract Abstract 2102 Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, life-threatening hematopoietic stem cell disorder characterized by deficiency of the GPI-anchored complement inhibitory proteins CD55 and CD59. Uncontrolled complement activation is responsible for chronic hemolysis that leads to the serious clinical morbidities including thromboembolism (TE) and chronic kidney disease, which increase risk of mortality. PNH is infrequent in children and as such, there is a paucity of data in the literature examining their burden of disease. This is the largest series of pediatric patients with PNH, and the first comparison with adult PNH patients. AIM: To assess the clinical differences between pediatric and adult PNH patients with classic/hemolytic PNH. Methods: Data from 1143 PNH patients from 204 clinical sites in 21 countries on 5 continents (as of 6/30/11) were analyzed to evaluate clinical characteristics of PNH. Patients registered as having classic/hemolytic PNH were initially included (n=559). Of these, 62 additional patients were excluded due to either a <30% granulocyte clone size, or missing data on enrollment date, date of birth, sex, date of disease start and history of TE. The final population for this study was 497 patients, classified into two groups, those first diagnosed at age <18 years (pediatric patients N=49) and at age ≥18 years (adult patients N=448). Baseline demographics, laboratory values, PNH-related medical history, and physician-reported PNH symptoms were compared for pediatric and adult patients. Patients/guardians gave informed consent prior to enrollment. Results: The median age at disease start for pediatric patients was 15 years (5–17), and for adults was 33 years (18–87). Hemoglobin, leucocytes, neutrophils, reticulocytes, LDH, and number of transfusions were similar between both pediatric and adult patients. There were no differences in GPI-deficient granulocyte or RBC clone sizes between pediatric and adult patients. Follow-up was longer for children (mean + SD, in years: 14.5 + 13.6 vs 9.6 + 9.1, P<0.001, respectively). The number of pediatric and adult patients receiving concomitant medications such as anticoagulants (peds 49% vs adults 54.9%; P=0.43) and eculizumab (peds 40.8% vs adults 45.5%; P=0.53) prior to enrollment were similar. No differences between pediatric and adult patients were observed in bone marrow disorders, renal impairment, hemoglobinuria, abdominal pain, dysphagia, headache and shortness of breath. In contrast, pediatric patients reported less fatigue (57.1% vs. 76.8%; P=0.001). TE incidence was 12.2% for pediatric and 23.9% for adults, which was statistically significant when the length of the time of exposure to this complication was taken into account; TE event rate was significantly lower in pediatric patients compared to adults (1.0/100 pt-yrs vs 4.4/100 pt-yrs; P<0.001 by Poisson regression). Patients with TE had a mean granulocyte clone size of 85.7% vs 81.0% for patients without TE (P=0.026). Both in children and adults the risk of TE was much higher than expected for the general population (general pediatric population: TE incidence is 0.07 per 10,000 or 0.0007%, vs 12.2% in this study). TE events at venous sites (hepatic/portal, mesenteric/visceral, renal, and cerebral veins) and arterial sites were less frequent in pediatric patients compared to adults. The most striking difference in TE type was thrombophlebitis/deep vein thrombosis, which occurred significantly less frequently in pediatric than adult patients (2.0% vs 11.8%; p=0.037). In multivariate analysis, age >18 years at disease onset and kidney disease were predictors of TE (odds ratio [OR] 3.01, 95% CI 1.15–7.72; P=0.02, and OR 1.87, 95% CI 1.03–3.4; P=0.04, respectively), while clone size was not a significant predictor of TE (OR 1.010, 95% CI 0.995–1.025; P=0.18). Conclusions: Pediatric PNH patients experience a significant burden of disease similar to adult PNH patients. There were no differences in LDH levels, GPI-deficient clone size, or in the incidence of bone marrow disorders, renal impairment, hemoglobinuria, abdominal pain, shortness of breath and dysphagia between pediatric and adult patients. TE event rate was lower in pediatric PNH patients when compared to adults, especially for those with concomitant kidney disease However, TE still remains an issue in this population and pediatric PNH patients are at significant risk for TE. Disclosures: Urbano-Ispizua: Alexion: Membership on an entity's Board of Directors or advisory committees. Schrezenmeier:Alexion Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Muus:Celgene: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novarts: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Celgene: Research Funding; Eisai: Research Funding; Alexion: Consultancy. Socié:Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees. Szer:Alexion Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Brodsky:Alexion Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Bessler:Alexion Pharmaceuticals, Inc.: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Taligen: Consultancy. Rosse:Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kanakura:Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees. Khursigara:Alexion: Employment, Equity Ownership. Bedrosian:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Hillmen:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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