Haemostatic alterations induced by treatment with asparaginases and clinical consequences

2015 ◽  
Vol 113 (02) ◽  
pp. 247-261 ◽  
Author(s):  
Tommaso Za ◽  
Angela Ciminello ◽  
Silvia Betti ◽  
Elena Rossi ◽  
Valerio De Stefano
Keyword(s):  
Risk Factors ◽  
Factor Xa ◽  
Central Venous Line ◽  
Fresh Frozen Plasma ◽  
Lymphoid Leukaemia ◽  
Inherited Thrombophilia ◽  
Clinical Consequences ◽  
Fresh Frozen ◽  
Fibrinolytic Proteins ◽  
Near Future

SummaryThe benefit of asparaginase for treating acute lymphoid leukaemia (ALL) has been well established. Native asparaginase derives from Escherichia coli (colaspase) or Erwinia chrysanthemi (crisantaspase); in a third preparation, colaspase is pegylated. Depletion of asparagine leads to decreased synthesis of procoagulant, anticoagulant, and fibrinolytic proteins, with resultant hypercoagulability and greater risk of venous thromboembolism (VTE). Colaspase and crisantaspase are not dose-equivalent, with crisantaspase displaying haemostatic toxicity only at dosages much higher and administered more frequently than those of colaspase. Cerebral venous thrombosis and pulmonary embolism are two life-endangering manifestations that occur during treatment with asparaginase particularly in children and in adults with ALL, respectively. Approximately one-third of VTEs are located in the upper extremities and are central venous line-related. Other risk factors are longer duration of asparaginase treatment and concomitant use of prednisone, anthracyclines, and oral contraceptives. The risk associated with inherited thrombophilia is uncertain but is clearly enhanced by other risk factors or by the use of prednisone. VTE prevention with fresh frozen plasma is not recommended; the efficacy of antithrombin (AT) concentrates has occasionally been reported, but these reports should be confirmed by proper studies, and AT should not be routinely employed. Therapeutic or prophylactic heparin doses are only partially effective, and direct thrombin or factor Xa inhibitors could play significant roles in the near future.

Case Report

2016 ◽  
Vol 29 (4) ◽  
pp. 427-430 ◽  
Author(s):  
Tina Harrach Denetclaw ◽  
Jacqueline Tam ◽  
Victor Arias ◽  
Rachel Kim ◽  
Christopher Martin
Keyword(s):  
Risk Factors ◽  
Prothrombin Complex Concentrate ◽  
Factor Xa ◽  
Fresh Frozen Plasma ◽  
Successful Management ◽  
Reversal Agents ◽  
Fresh Frozen ◽  
Frozen Plasma ◽  
Underlying Risk ◽  
Three Factor

Apixaban, an oral factor Xa inhibitor, has no commercially available assay to measure its activity and no specific antidote. To date, recommendations for managing bleeding associated with apixaban are based on studies with animal models and healthy volunteers (who do not have identified thrombogenic risk factors) and expert opinion. No clinical experience has been published in the literature. Ideally, apixaban would be reversed sufficiently to stop a perilous bleed without producing more thrombogenic risk than the patients’ underlying risk factors. Three-factor prothrombin complex concentrate (PCC3) is the least thrombogenic among the suggested reversal agents. Fresh frozen plasma (FFP) is sometimes recommended to add to PCC3, but it adds considerable volume. We describe successful management of an active left gluteal arterial extravasation due to trauma and associated apixaban, in a patient with aortic stenosis and atrial fibrillation, by administration of PCC3 alone, without the added volume of FFP.

Preparation of Highly Purified Human Thrombin and Factor Xa in a Simultainous Procedure

1975 ◽  
Author(s):  
M. Miller-Andersson
Keyword(s):  
Specific Activity ◽  
Factor Xa ◽  
Fresh Frozen Plasma ◽  
Factor X ◽  
Serum Factors ◽  
Human Thrombin ◽  
Fresh Frozen ◽  
Brain Material ◽  
The Brain ◽  
Chromatography Step

A preparation procedure that purifies Thrombin and activated factor X in a simultainous process has been worked out. Prothrombin complex was first prepared from fresh frozen plasma by chromatography on DEAE-Sephadex. Prothrombin activator was prepared from human brain thromboplastin and bovine serum factors. The activation was performed at 20° C and followed by assaying thrombin activity. After activation the brain material was removed by centrifugation. The protein mixture was immediately adsorbed on to Amberlite IRC-50 and both enzymes were fully adsorbed to the resin. They were eluted in a CaCl2 gradient and the two enzymes eluted in two slightly owerlapping peaks.The thrombin obtained in this procedure was highly purified with a specific activity of 2100 U per mg protein. The activated factor X contained traces of thrombin. It was fully suitable for anti Xa assays of heparin. When higher degree of purity was needed the activated factor X was further purified in an iron-exchange or affinity chromatography step.

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 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.

Real-world management of oral factor Xa inhibitor-related bleeds with reversal or replacement agents including andexanet alfa and four-factor prothrombin complex concentrate: a multicenter study

2021 ◽  
Vol 17 (1) ◽  
pp. 127-135
Author(s):  
Craig I Coleman ◽  
Paul P Dobesh ◽  
Sherry Danese ◽  
Julie Ulloa ◽  
Belinda Lovelace
Keyword(s):  
Length Of Stay ◽  
Hospital Mortality ◽  
Real World ◽  
Prothrombin Complex Concentrate ◽  
Factor Xa ◽  
Fresh Frozen Plasma ◽  
Factor Xa Inhibitor ◽  
Fresh Frozen ◽  
Andexanet Alfa ◽  
Frozen Plasma

Aim: We describe the real-world utilization and outcomes associated with managing oral factor Xa inhibitor (FXai)-related major bleeds. Materials & methods: Electronic records from 45 US hospitals were queried (ICD-10-CM billing codes D68.32, T45.515x or T45.525x) to identify major bleed hospitalizations related to FXai use. Patient demographics, bleed type (intracranial hemorrhage, gastrointestinal, critical compartment, traumatic, other), FXai taken, reversal or replacement agents administered (including andexanet alfa, four-factor prothrombin complex concentrate, fresh frozen plasma, others), in-hospital mortality and length of stay were recorded. Results: Of 3030 FXai-related hospitalizations for major bleeds, patients averaged 68 years old and 47% were women. In-hospital mortality was highest for intracranial hemorrhage (23%, n = 507) and lowest for gastrointestinal bleeds (4%, n = 1453). In-hospital mortality was lowest (4%) for bleeds managed with andexanet alfa (n = 342), compared with 10% for four-factor prothrombin complex concentrate (n = 733), 11% for fresh frozen plasma (n = 925) and 8% for both other agents (n = 794) and no agents (n = 438). Median length of stay was 5 days across all agents, while ICU length of stay was shorter andexanet alfa (2 days) compared with other agents (3 days). Conclusion: In-hospital mortality differed by bleed type and agents administered. Andexanet alfa was associated with the lowest rate of in-hospital mortality across all bleed types.

scholarly journals Intervention and Therapies Associated Mortality in Intensive Care Unit of BSMMU, Dhaka

2009 ◽  
Vol 20 (1) ◽  
pp. 9-12
Author(s):  
Labib Imran Faruque ◽  
Qumrul Huda ◽  
Debasish Banik ◽  
AKM Shafiqur Rahman
Keyword(s):  
Mechanical Ventilation ◽  
Platelet Rich Plasma ◽  
Central Venous Line ◽  
Fresh Frozen Plasma ◽  
Tube Insertion ◽  
Central Venous ◽  
Fresh Frozen ◽  
Frozen Plasma ◽  
Nasogastric Tube Insertion ◽  
Significant Mortality

In the general ICU of BSMMU, Dhaka. 157 critically ill patients were studied for association between mortality and interventions/therapies. Among the patients 123 received mechanical ventilation (major interventions) and 100 of them expired which is very highly significant (P< 0.001). Among the patients who got minor interventions (urinary catheterization, nasogastric tube insertion, central venous line, tracheostomy)-none was significant. The patients who received therapies (fresh frozen plasma, whole blood, ionotropes/vassopressor drugs, platelet rich plasma)-no parameter was significant except the patients who got ionotropes /vassopressor therapy ( P<0.05). From our study it is apparent that mortality is more associated with major interventions like mechanical ventilation and mortality associated with minor interventions are non-significant. Mortality associated with ionotropes /vassopressor therapy was significant.   Journal of BSA, Vol. 20, No. 1, January 2007 p.9-12

scholarly journals ANALYSIS OF EARLY RELAPAROTOMY IN OBSTETRIC & GYNAECOLOGICAL SURGERIES

2016 ◽  
Vol 21 (4) ◽  
pp. 247
Author(s):  
Shumaila Zia ◽  
Muhammad Rafique ◽  
Muhammad Atif Qureshi ◽  
Baha Ahmad
Keyword(s):  
Risk Factors ◽  
Placenta Previa ◽  
Tertiary Care ◽  
Fresh Frozen Plasma ◽  
Maternal Deaths ◽  
Packed Red Blood Cells ◽  
Abdominal Bleeding ◽  
Primary Surgery ◽  
Fresh Frozen ◽  
Early Relaparotomy

AbstractObjectives:Evaluation of risk factors, frequency, causes and measures took to save patients life in relaparotomies.Methods:This retrospective, descriptive study was conducted from January 2012 December 2014 in a tertiary care hospital.Results:This study includes 38 cases, 29 (76.3%) obstetrical and nine (23.7%) gynaecological Relaparotomy incidence was 0.43%. It was 0.55% for obstetrical and 0.24% for gynaecological indications. The leading causes were suspected intra-abdominal bleeding in 24 (63.2%), uncontrolled postpartum haemorrhage (PPH) in nine (23.7%) and suspected abdominal caesarean sections (CS) 28/29(96.5%). Of 28 previous CS cases, multiple CS were in13 (46.4%), placenta previa in five (17.85%) and antepartum hemorrhage in four (14.28%) cases. Majority (92.1%) of patients underwent relaparotomy within 24 hours after primary surgery. Patients received (mean SD) 7.2 5.4 packed red blood cells, 4.3 5.5 fresh frozen plasma and 1.2 2.3 platelets units. Third operation was needed in seven (18.4%) cases. Twelve (31.6%) women develo-ped complications. There were three (7.9%) maternal deaths following relaparotomy.Conclusion:Intra-abdominal bleeding is main cause for reoperation and multiple CS is major risk factor. Recognition of risk factors, careful primary operation, involvement of seniors in complicated surgeries and early intervention can prevent majority of the relaparotomies.Key words:Relaparotomy, reoperation, complicated caesarean section, maternal mortality, obstetrics and gynaecology, intra-peritoneal haemorrhage.

scholarly journals The epidemiology of overtransfusion of red cells in trauma resuscitation patients in the context of a mature massive transfusion protocol

2021 ◽  
Author(s):  
Timothy Cowan ◽  
Natasha Weaver ◽  
Alexander Whitfield ◽  
Liam Bell ◽  
Amanda Sebastian ◽  
...  
Keyword(s):  
Injury Severity ◽  
Haemoglobin Concentration ◽  
Fresh Frozen Plasma ◽  
Trauma Patients ◽  
Trauma Resuscitation ◽  
Packed Red Blood Cells ◽  
Clinical Consequences ◽  
Fresh Frozen ◽  
Transfusion Protocol ◽  
Frozen Plasma

Abstract Purpose Packed red blood cell (PRBC) transfusion remains an integral part of trauma resuscitation and an independent predictor of unfavourable outcomes. It is often administered urgently based on clinical judgement. These facts put trauma patients at high risk of potentially dangerous overtransfusion. We hypothesised that trauma patients are frequently overtransfused and overtransfusion is associated with worse outcomes. Methods Trauma patients who received PRBCs within 24 h of admission were identified from the trauma registry during the period January 1 2011–December 31 2018. Overtransfusion was defined as haemoglobin concentration of greater than or equal to 110 g/L at 24 h post ED arrival (± 12 h). Demographics, injury severity, injury pattern, shock severity, blood gas values and outcomes were compared between overtransfused and non-overtransfused patients. Results From the 211 patients (mean age 45 years, 71% male, ISS 27, mortality 12%) who met inclusion criteria 27% (56/211) were overtransfused. Patients with a higher pre-hospital systolic blood pressure (112 vs 99 mmHg p < 0.01) and a higher initial haemoglobin concentration (132 vs 124 p = 0.02) were more likely to be overtransfused. Overtransfused patients received smaller volumes of packed red blood cells (5 vs 7 units p = 0.049), fresh frozen plasma (4 vs 6 units p < 0.01) and cryoprecipitate (6 vs 9 units p = 0.01) than non-overtransfused patients. Conclusion More than a quarter of patients in our cohort were potentially given more blood products than required without obvious clinical consequences. There were no clinically relevant associations with overtransfusion.

Das Smith-Lemli-Opitz-Syndrom

2005 ◽  
Vol 5 (04) ◽  
pp. 178-182
Author(s):  
Wieland Kiess ◽  
Manuela Schulz ◽  
Sabine Liebermann ◽  
Roland Pfäffle ◽  
Peter Bührdel ◽  
...  
Keyword(s):  
Fresh Frozen Plasma ◽  
Therapeutische Möglichkeiten ◽  
Fresh Frozen ◽  
Frozen Plasma

ZusammenfassungDas Smith-Lemli-Opitz-Syndrom wird durch einen Defekt des letzten Schrittes der Cholesterolbiosynthese, den Mangel an 7-Dehydrocholesterolreduktase, verursacht. Die Akkumulation der Metaboliten 7-Dehydrocholesterol und 8-Dehydrocholesterol, die die wichtigsten biochemischen Marker für die Diagnose der Erkrankung darstellen, sowie der Mangel an Cholesterol können zu multiplen kongenitalen Anomalien führen. Die Ursache des Enzymmangels sind Mutationen innerhalb des DHCR7-Gens, welches auf Chromosom 11q13 lokalisiert ist. Therapeutische Möglichkeiten bestehen in der Gabe von Cholesterol und im Notfall Fresh Frozen Plasma (FFP); der therapeutische Nutzen von Statinen befindet sich zurzeit in der klinischen Erprobung.

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