scholarly journals Venous Thrombosis in Children with Acute Lymphoblastic Leukemia Treated on DCOG ALL-9 and ALL-10 Protocols: The Effect of Fresh Frozen Plasma

TH Open ◽  
2019 ◽  
Vol 03 (02) ◽  
pp. e109-e116
Author(s):  
Irene Klaassen ◽  
Charlotte Zuurbier ◽  
Barbara Hutten ◽  
Cor van den Bos ◽  
A. Schouten ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Plasma Levels ◽  
Medical Center ◽  
Lymphoblastic Leukemia ◽  
Academic Medical Center ◽  
Fresh Frozen Plasma ◽  
Thrombotic Risk ◽  
Fresh Frozen ◽  
Frozen Plasma

Background Venous thromboembolism (VTE) is an important complication for treatment of acute lymphoblastic leukemia (ALL) in children. Especially, ALL treatment, with therapeutics such as asparaginase and steroids, increases the thrombotic risk by reduction in procoagulant and anticoagulant proteins. Replacement of deficient natural anticoagulants by administration of fresh frozen plasma (FFP) may have a preventive effect on the occurrence of VTE. Methods We retrospectively analyzed all consecutive children (≤18 years) with ALL, treated on the Dutch Childhood Oncology Group (DCOG) ALL-9 and ALL-10 protocols at the Emma Children's Hospital Academic Medical Center between February 1997 and January 2012, to study the effect of FFP on VTE incidence, antithrombin and fibrinogen plasma levels, and VTE risk factors. Results In total, 18/205 patients developed VTE (8.8%; 95% confidence interval [CI]: 4.9–12.7%). In all patients, VTE occurred after asparaginase administration. In total, 82/205 patients (40%) received FFP. FFP supplementation did not prevent VTE or alter plasma levels of antithrombin or fibrinogen. In the multivariate analysis, VTE occurred significantly more frequently in children ≥12 years (odds ratio [OR]: 3.89; 95% CI: 1.29–11.73) and treated according to the ALL-10 protocol (OR: 3.71; 95% CI: 1.13–12.17). Conclusion FFP supplementation does not seem to be beneficial in the prevention of VTE in pediatric ALL patients. In addition, age ≥12 years and treatment according to the DCOG ALL-10 protocol with intensive and prolonged administration of asparaginase in combination with prednisone are risk factors. There is a need for effective preventive strategies in ALL patients at high risk for VTE.

Impact of Prophylactic Fresh Frozen Plasma On Venous Thromboembolism in Adults Treated for Acute Lymphoblastic Leukemia Receiving Asparaginase,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3345-3345
Author(s):  
Mandy N Lauw ◽  
Bronno Van der Holt ◽  
Saskia Middeldorp ◽  
Joost CM Meijers ◽  
Bart J Biemond
Keyword(s):  
Venous Thromboembolism ◽  
Acute Lymphoblastic Leukemia ◽  
Treatment Period ◽  
Plasma Levels ◽  
Lymphoblastic Leukemia ◽  
Fresh Frozen Plasma ◽  
Prophylactic Measures ◽  
Total Treatment ◽  
Fresh Frozen ◽  
Frozen Plasma

Abstract Abstract 3345 Background: Acute lymphoblastic leukemia (ALL) is frequently complicated by venous thromboembolism (VTE). The reported incidence varies from 2% to 37%, with the highest risk arising in the first weeks after treatment initiation. VTE leads to morbidity, mortality and premature termination of therapy. Prevention of VTE in ALL is complicated, as thrombotic and bleeding factors need to be balanced. The efficacy of prophylactic antithrombotic measures is not clear yet, and standardized guidelines are lacking. We assessed the effect of various prevention protocols on the VTE risk in adults treated for ALL. Methods: Between April 1999 and November 2005, 240 consecutive patients aged 16–59 years with newly diagnosed ALL were treated with the same anti-leukemic protocol in a Dutch-Belgian multicenter study, which included L-asparaginase in cycle 1 (5000 U/m2/day, day 15–28). All VTE events during treatment were prospectively recorded. VTE prophylaxis was applied only in cycle 1 during asparaginase administration, and varied between different centers: no prophylaxis, fresh frozen plasma (FFP), or antithrombin (AT) concentrate. A centers' prevention protocol was used as a proxy for all patients treated in that center. AT plasma levels were assessed of patients with VTE and 22 controls without VTE. We determined VTE incidence in cycle 1, the impact of the various prophylactic measures, and VTE incidence during the total treatment period for ALL. Secondly, we assessed the clinical relevance of VTE on ALL outcome. Results: 25 of 240 patients (10.4%; 95% CI 6.6–14.3) experienced objectively diagnosed, symptomatic VTE in cycle 1 (10 cerebral thromboses of which 8 in the sagittal sinus, 11 upper limb vein thromboses (10 central venous catheter (CVC)-related), 3 deep vein thromboses of the leg, 1 pulmonary embolism). VTE incidence in patients receiving FFP prophylaxis was reduced by 70% as compared to patients without prophylactic measures (7.2% vs. 23.9%; RR 0.3; 95% CI 0.1–0.6; Table 1). Age, sex, ALL-type and CVC-placement did not differ significantly between patients with and without FFP prophylaxis. The effect of prophylactic AT concentrate could not be properly assessed as it was only rarely given in two centers. Mean AT plasma levels did not differ significantly between VTE patients with or without FFP, neither between patients with VTE and controls without VTE (Figure 1). During the total treatment period, VTE occurred in 36 of 240 patients (15.0%; 95% CI 10.5–19.5). Patients with VTE in cycle 1 were less likely to obtain complete remission after cycle 1 (HR 0.5; 95% CI 0.3–0.9), but did not have a significantly decreased overall survival (HR 1.5; 95% CI 0.9–2.6). Conclusions: FFP significantly reduced VTE incidence by 70% during ALL treatment, without reversing the AT deficiency induced by asparaginase. Our observation is in contrast with two previous studies on the effect of FFP on VTE in ALL. The mechanisms by which FFP accomplishes this antithrombotic effect are not clear yet and require further investigation. Since this was a retrospective, observational study, the effect of prophylactic FFP on VTE risk in adults treated for ALL should be confirmed by a randomized controlled trial. Disclosures: No relevant conflicts of interest to declare.

The impact of prophylactic fresh-frozen plasma and cryoprecipitate on the incidence of central nervous system thrombosis and hemorrhage in children with acute lymphoblastic leukemia receiving asparaginase

Blood ◽  
2009 ◽  
Vol 114 (25) ◽  
pp. 5146-5151 ◽  
Author(s):  
Lesleigh S. Abbott ◽  
Mariana Deevska ◽  
Conrad V. Fernandez ◽  
David Dix ◽  
Victoria E. Price ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Health Centre ◽  
Expectant Management ◽  
Fresh Frozen Plasma ◽  
Fresh Frozen ◽  
The Impact ◽  
Frozen Plasma

Abstract Asparaginase (ASP) therapy is associated with depletion of antithrombin (AT) and fibrinogen (FG). Potential toxicities include central nervous system thrombosis (CNST) and hemorrhage. Historical practice at the Izaak Walton Killam Health Centre (IWK) involves measuring AT and FG levels after ASP administration and transfusing fresh-frozen plasma (FFP) or cryoprecipitate (CRY) to prevent thrombotic and hemorrhagic complications. To determine whether this reduced these complications in children with acute lymphoblastic leukemia (ALL), incidence, outcome, and clinical characteristics of ASP-related CNST in ALL patients at IWK were compared with a similar cohort from BC Children's Hospital (BCCH), where prophylaxis was not performed. Costs associated with preventative versus expectant management were estimated. From 1990 to 2005, 240 patients were treated at IWK and 479 at BCCH. Seven BCCH patients developed venous CNST (1.5%), compared with none at IWK. CNST occurred exclusively during induction. Six patients received anticoagulation and continued ASP. All 7 patients remain in remission. National Cancer Institute high-risk ALL predicted CNST risk (P = .02), whereas sex, age, race, and body mass index did not. Neither FFP nor CRY protected against CNST, suggesting prophylaxis is unwarranted for unselected ALL patients. However, prophylactic replacement for HR patients in induction may be cost-effective.

scholarly journals Cerebral infarction in a patient with acute lymphoblastic leukemia after fresh-frozen plasma replacement during l-asparaginase therapy

1992 ◽  
Vol 41 (4) ◽  
pp. 295-296 ◽  
Author(s):  
Hideshi Ishii ◽  
Hakumei Oh ◽  
Nobuko Ishizuka ◽  
Yasuhiro Matsuura ◽  
Hirotoshi Nakamura ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cerebral Infarction ◽  
Lymphoblastic Leukemia ◽  
Fresh Frozen Plasma ◽  
Fresh Frozen ◽  
Frozen Plasma

Fresh Frozen Plasma Partial Exchange Transfusion and Necrotizing Enterocolitis

PEDIATRICS ◽  
1986 ◽  
Vol 77 (5) ◽  
pp. 786-787
Author(s):  
THOMAS E. WISWELL ◽  
J. DEVN CORNISH
Keyword(s):  
Prospective Study ◽  
Necrotizing Enterocolitis ◽  
Exchange Transfusion ◽  
Medical Center ◽  
Fresh Frozen Plasma ◽  
Live Births ◽  
Army Medical ◽  
Exchange Group ◽  
Fresh Frozen ◽  
Frozen Plasma

To the Editor.— In their article, Black et al1 cite a surprising incidence of complications of polycythemia in their partial exchange transfusion-treated v their nonexchange populations. Of particular note is the remarkable incidence of necrotizing enterocolitis (eight of 43 patients or 18.6%) in the exchange group. In the nonexchanged group, no infants were so affected. In a previously reported prospective study of 7,133 consecutive live births at Tripler Army Medical Center, Hawaii, a total of 82 infants were identified as having neonatal polycythemia (venous hematocrit 65% or greater).2

scholarly journals Thromboembolism Prophylaxis in Adult Patients with Acute Lymphoblastic Leukemia Treated in the GRAALL-2005 Study

Blood ◽  
2020 ◽  
Author(s):  
Corentin Orvain ◽  
Marie Balsat ◽  
Emmanuelle Tavernier ◽  
Jean-Pierre Marolleau ◽  
Thomas Pabst ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Fresh Frozen Plasma ◽  
Adult Patients ◽  
Bleeding Complications ◽  
Thromboembolism Prophylaxis ◽  
Prophylactic Measures ◽  
Increased Risk ◽  
Fresh Frozen ◽  
Grade 3

Patients undergoing treatment for acute lymphoblastic leukemia (ALL) are at risk for thrombosis, in part due to the use of L-asparaginase (L-ASP). Antithrombin (AT) replacement has been suggested to prevent VTE and thus might increase exposure to ASP. We report herein the results of the prophylactic replacement strategy in the pediatric-inspired prospective GRAALL-2005 study. Between 2006 and 2014, 784 adult patients with newly diagnosed Philadelphia-negative ALL were included. The incidence rate of VTE was 16% with 69% of them occurring during induction therapy. Most patients received AT supplementation (87%). After excluding patients who did not receive L-ASP or developed thrombosis before L-ASP, AT supplementation did not have a significant impact on VTE (8% versus 14%, OR: 0.6, p=0.1). Fibrinogen concentrates administration was associated with an increased risk of VTE (17% versus 9%, OR 2.2, p=0.02) whereas transfusion of fresh-frozen plasma had no effect. Heparin prophylaxis was associated with an increased risk of VTE (13% versus 7%, OR 1.9, p=0.04). Prophylactic measures were not associated with an increased risk of grade 3-4 bleeding complications. The rate of VTE recurrence after L-ASP reintroduction was 3% (1/34). In ALL patients receiving L-ASP therapy, the use of fibrinogen concentrates may increase the risk of thrombosis and should be restricted to rare patients with hypofibrinogenemia-induced hemorrhage. Patients developed VTE despite extensive AT supplementation which advocates for additional prophylactic measures. While this large descriptive study was not powered to demonstrate the efficacy of these prophylactic measures, it provides important insight to guide future trial design. NCT00327678.

A Retrospective Multicenter Study from the Nordic Society of Pediatric Hematology and Oncology (NOPHO) on Cerebral Sinus Venous Thromboses in Children with Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 584-584
Author(s):  
Susanna Ranta ◽  
Nadine Gretenkort Andersson ◽  
Ulf R. Tedgard ◽  
Tony Frisk ◽  
Maria Winther Gunnes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Clinical Risk Factors ◽  
Bleeding Complications ◽  
Cerebral Veins ◽  
Thrombotic Risk ◽  
Clinical Risk ◽  
Cerebral Sinus ◽  
D Dimer

Abstract Introduction Cerebral sinus venous thrombosis (CSVT) is potentially life-threatening thrombosis with mortality around 10%. Venous thromboembolism (VTE) is a common complication in children with cancer. These children have several thrombotic risk factors such as the malignancy itself, severe infections, prothrombotic medication and immobilization. The treatment of acute lymphoblastic leukemia (ALL) includes steroids and asparaginase (ASP), raising the VTE risk. In children with ALL the central nervous system (CNS) is a common localization for VTE. However, retrospective studies on small numbers of patients, larger studies and population-based data in children are scarce. The five Nordic countries, Estonia and Lithuania have a common treatment protocol for children with ALL between 1 and 18 years of age with prospective registration of toxicities, including CSVT offering a unique opportunity to study CSVT in this patient group. This is to our knowledge the largest report of children with ALL and CSVT describing the incidence, symptoms, treatment and the effect of CSVT on ALL treatment. Methods We assessed the symptoms, treatment, clinical risk factors and outcome of all children between ages 1 and 17 years at diagnosis of B-cell precursor or T-cell ALL between June 2008 and July 2013 and with CSVT. Data were collected from the patients’ medical records and the NOPHO leukemia registry. Results In total, 20 (1.9%) of the 1038 children with ALL treated according to the NOPHO ALL 2008 protocol developed CSVT. The cumulative incidence of CSVT was 2.0%. All the thromboses occurred within the first 5 months of treatment. The most common symptoms at the diagnosis of CSVT were headache, convulsions, weakness/fatigue and cerebral nerve palsy/hemiparesis/hemiplegia. The most frequent localizations for CSVT were sinus sagittalis (n=16) and sinus transversus (n=10). However, in most cases multiple cerebral veins were involved ( 70%). Median D-dimer at time of the CSVT diagnosis was 0.85 mg/L (range 0.19-4.7 mg/L) with 5 patients having normal D-dimer. We could not identify any clinical risk factors for CSVTs. CSVT was associated with steroids (treatment within 2 weeks before the diagnosis of CSVT) in 16/20 and with Pegylated asparaginase in 16/20. Fifteen patients were later screened for the inherited thrombophilic factors; one child had heterozygous prothrombin G20110A mutation and another heterozygous factor V (R506Q) Leiden mutation. Most patients (19/20) were treated with anticoagulants: mostly low molecular weight heparin (LMWH). The median treatment with LMWH was 26 weeks (range 14-119 weeks). No bleeding complications were observed in connection with LMWH. Two deaths were directly related to CSVT. Asparaginase was omitted from the treatment in 7 and delayed or reduced in 5 of the cases raising the risk for subsequent suboptimal leukaemia treatment. Of the surviving 18 patients, follow-up imaging revealed complete recanalization in 7 and partial recanalization in 7 cases. No imaging was available for the remaining 4 patients. Conclusions The incidence of CSVT in children with ALL was approximately 2%. No statistically significant clinical predictors for CSVT were identified. The mortality related to CSVT was 10%. Anticoagulation with LMWH was the treatment of choice in most cased and was well tolerated. Disclosures No relevant conflicts of interest to declare.

scholarly journals Fresh frozen plasma transfusion – a risk factor for pulmonary hemorrhage in extremely low birth weight infants?

2017 ◽  
Vol 45 (5) ◽  
Author(s):  
Jakob Usemann ◽  
Lars Garten ◽  
Christoph Bührer ◽  
Christof Dame ◽  
Malte Cremer
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Birth Weight ◽  
Pulmonary Hemorrhage ◽  
Fresh Frozen Plasma ◽  
Extremely Low Birth Weight ◽  
Low Birth Weight Infants ◽  
Platelet Counts ◽  
Fresh Frozen ◽  
Frozen Plasma

AbstractAim:To evaluate risk factors for pulmonary hemorrhage (PH) in extremely low birth weight infants (ELBW) taking into consideration coagulation screens, platelet counts, transfusion of fresh frozen plasma (FFP), and platelet concentrates prior to PH.Patients and methods:A retrospective case-control study consisting of 20 ELBW infants with PH and 40 matched controls. Coagulation screens, platelet counts at birth and at onset of PH, and transfusion frequencies prior to PH were compared to case-controls at birth and 24–96 h after birth.Results:While the initial platelet counts, fibrinogen concentrations, and international normalized ratios were similar in PH infants and controls, the activated partial prothrombin time was prolonged (P=0.05). Compared to 28% of case controls (P<0.05), 55% of infants with later PH received FFP prior to PH. Platelet counts were significantly lower at onset of PH (median 81/nL; range: 37–236/nL) compared to controls (166/nL; 27–460/nL; P<0.005). Multivariate analysis indicated a lack of antenatal steroids, supplemental oxygen, and transfusion of FFP as independent risk factors for PH.Conclusion:Prolonged activated partial thromboplastin time (aPTT) might be associated with PH. PH does not primarily depend upon severe thrombocytopenia. A developmental mismatch in hemostasis by transfusion of adult donor plasma should be considered a risk factor for PH.

scholarly journals Peri- and Postpartum Management of Patients With Factor XI Deficiency

2019 ◽  
Vol 25 ◽  
pp. 107602961988026 ◽  
Author(s):  
Gloria F. Gerber ◽  
Kelsey A. Klute ◽  
John Chapin ◽  
James Bussel ◽  
Maria T. DeSancho
Keyword(s):  
Pregnant Women ◽  
Medical Center ◽  
Academic Medical Center ◽  
Fresh Frozen Plasma ◽  
Neuraxial Anesthesia ◽  
Factor Xi ◽  
Antifibrinolytic Agents ◽  
Factor Xi Deficiency ◽  
Severe Deficiency ◽  
Fresh Frozen

Factor XI (FXI) deficiency is an uncommon autosomal disorder with variable bleeding phenotype, making peripartum management challenging. We describe our experience in pregnant women with FXI deficiency and identify strategies to minimize the use of hemostatic agents and increase utilization of neuraxial anesthesia. Electronic records of 28 pregnant women with FXI deficiency seen by a hematology service in an academic medical center from January 2006 to August 2018 were reviewed. Data on bleeding, obstetric history, peripartum management, and FXI activity were collected. Partial FXI deficiency was defined as >20 IU/dL and severe <20 IU/dL. Median FXI activity was 42 IU/dL (range <1-73 IU/dL), and median activated partial thromboplastin time was 32.2 seconds (range: 27.8-75 seconds). There were 64 pregnancies: 53 (83%) live births and 11 (17%) pregnancy losses. Postpartum hemorrhage occurred in 9 (17%) pregnancies. Antifibrinolytic agents and fresh frozen plasma were used only in women with severe deficiency (42% with bleeding and 17% with no bleeding phenotype, respectively). Neuraxial anesthesia was successfully administered in 32 (59%) deliveries. Most women with FXI deficiency have uncomplicated pregnancies and deliveries with minimal hemostatic support. Neuraxial anesthesia can be safely administered in most women.

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