Impact of exogenous antithrombin on low molecular weight heparin anti‐Xa activity assays in a pediatric and young adult leukemia and lymphoma cohort with variable antithrombin levels

2020 ◽  
Vol 67 (11) ◽  
Author(s):  
Beverly Schaefer ◽  
Adriane Hausfeld ◽  
Matthew Martin ◽  
Paul Steele ◽  
Jan Martin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Young Adult ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Adult Leukemia

scholarly journals Comparison of Low Molecular Weight Heparin Activity Assays with and without Addition of Exogenous Antithrombin in a Pediatric and Young Adult Leukemia Cohort

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4915-4915
Author(s):  
Beverly Schaefer ◽  
Adriane Hausfeld ◽  
Paul Steele ◽  
Jan Martin ◽  
Sandra Brannon ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Research Funding ◽  
Low Molecular Weight Heparin ◽  
Lymphoblastic Leukemia ◽  
Clinical Care ◽  
Low Molecular Weight ◽  
Plasma Samples ◽  
History Of ◽  
Heparin Activity ◽  
Adult Leukemia

Introduction: Enoxaparin (low molecular weight heparin, LMWH) is the most commonly prescribed anticoagulant for pediatric patients with venous thromboembolism (VTE) (Goldenberg et al. 2015). The gold-standard LMWH activity (anti-Xa activity) assays differ in whether they add exogenous antithrombin (AT) or dextran sulfate (Ignjatovic et al. 2007). Adding AT would "standardize" results in patients with low antithrombin, such as infants and asparaginase-treated patients (Mitchell et al 2010); however, questions remain about which assay best reflects the patient's anticoagulation effect and the degree of discrepancy between assays. We assessed LMWH activity in residual plasma samples from a cohort of anticoagulated pediatric acute lymphoblastic leukemia and lymphoma (ALL) patients, with history of VTE and variable AT levels, on four platforms (two instruments and their kits +/- exogenous AT). Methods: We analyzed 60 de-identified residual plasma samples from 12 anticoagulated ALL patients (2-19 years. Mean 13.75 yr) who had AT levels obtained for clinical care. All consented to the IRB-approved Oncology Tissue Repository. LMWH activity was assessed on Siemens and Stago instruments using their recommended kits that did or did not contain exogenous AT (Table 1), according to manufacturer recommendations, by experienced laboratorians. Results: Results were interpretable on 236/240 with 4 rejected for lipemia. Mean AT activity was 80 (42-138 ng/ml, lab normal >81%). Correlation was acceptable for the published kit ranges of LMWH activity when comparing kits +AT (Berichrom® to Stachrom®, r=0.82, p<0.0001), -AT (Innovance® to STA®-Liquid Anti-Xa: r=0.93, p<0.0001), and within the same manufacturer (Berichrom® to Innovance®, r=0.92, p<0.0001, Stachrom® to STA®-Liquid Anti-Xa r=0.98, p<0.0001) (Table 2, Figure 1, Figure 2). Comparing +AT or not by manufacturer, there was a nonsignificant trend to higher LMWH activity result with +AT kits. When AT levels were <70 ng/ml (n=19, mean 56 ng/dl) there was a trend to underestimate LMWH activity when AT was not added; this reached significance when the Stago methods were compared (Table 2.) Conclusions: There is acceptable correlation of LMWH activity using kits with or without exogenous AT in anticoagulated pediatric plasma samples; however, in low AT samples, LMWH activity trends lower in platforms without exogenous AT. Use of residual samples precluded conclusions about the clinical impact of this difference; however, there were a few instances where subtherapeutic activity in the -AT assay was in the therapeutic range (0.5-1 activity units) in the +AT assay. Clinicians should know whether exogenous AT is used in their own laboratory's assay and understand that added AT could overestimate the LMWH effect in patients with low AT levels. Disclosures Schaefer: Stago: Research Funding; Siemens: Research Funding.

Low-molecular-weight heparin in the prevention and treatment of thromboembolic disorders

1998 ◽  
Vol 1 (5) ◽  
pp. 166-174 ◽  
Author(s):  
Evelyn R Hermes De Santis ◽  
Betsy S Laumeister ◽  
Vidhu Bansal ◽  
Vandana Kataria ◽  
Preeti Loomba ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Prevention And Treatment

Effects of Low Molecular Weight Heparin and Unfragmented Heparin on Induction of Osteoporosis in Rats

1990 ◽  
Vol 63 (03) ◽  
pp. 505-509 ◽  
Author(s):  
Thomas Mätzsch ◽  
David Bergqvist ◽  
Ulla Hedner ◽  
Bo Nilsson ◽  
Per Østergaar
Keyword(s):  
Molecular Weight ◽  
Bone Mineral ◽  
Low Molecular Weight Heparin ◽  
Zinc Content ◽  
Low Molecular Weight ◽  
Dependent Manner ◽  
Bone Mineral Mass ◽  
Bone Ash ◽  
Dose Dependent ◽  
Mineral Mass

SummaryA comparison between the effect of low molecular weight heparin (LMWH) and unfragmented heparin (UH) on induction of osteoporosis was made in 60 rats treated with either UH (2 IU/ g b w), LMWH in 2 doses (2 Xal U/g or 0.4 Xal U/g) or placebo (saline) for 34 days. Studied variables were: bone mineral mass in femora; fragility of humera; zinc and calcium levels in serum and bone ash and albumin in plasma. A significant reduction in bone mineral mass was found in all heparin-treated rats. There was no difference between UH and LMWH in this respect. The effect was dose-dependent in LMWH-treated animals. The zinc contents in bone ash were decreased in all heparin-treated rats as compared with controls. No recognizable pattern was seen in alterations of zinc or calcium in serum. The fragility of the humera, tested as breaking strength did not differ between treatment groups and controls. In conclusion, if dosed according to similar factor Xa inhibitory activities, LMWH induces osteoporosis to the same extent as UH and in a dose-dependent manner. The zinc content in bone ash was decreased after heparin treatment, irrespective of type of heparin given.

Markers of Hemostatic System Activation in Acute Deep Venous Thrombosis-Evolution during the First Days of Heparin Treatment

1993 ◽  
Vol 70 (06) ◽  
pp. 0909-0914 ◽  
Author(s):  
Keyword(s):  
Molecular Weight ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Dose Adaptation ◽  
Heparin Treatment ◽  
Lung Scan

SummaryFibrin D-Dimer (D-Di), prothrombin activation fragment (F 1+2) and thrombin-antithrombin III complexes (TAT) were measured using ELISA procedures in the plasma of patients with an acute deep venous thrombosis (DVT), at presentation and on days 2, 6 and 10 after initiation of heparin treatment. Patients were randomly allocated into two treatment groups: 44 patients received adapted doses of continuous intravenous unfractionated heparin (UH) whereas 47 received 1 mg/kg every twelve hours of a low molecular weight heparin (enoxaparin) subcutaneously. A phlebography and a perfusion lung scan were performed before inclusion and on day 10. Failure of therapy (n = 9) was defined by venogram worsening or confirmed pulmonary embolism. Improvement (n = 44) or stationary state (n = 38) were defined by venogram evolution in the absence of new leg scan defects.At presentation, D-Di, F 1 + 2 and TAT were above cut-off values in 97, 66 and 89% of patients respectively. D-Di levels correlated with the extent of venous thrombosis whereas TAT and F 1 + 2 did not. Mean levels of D-Di decreased sharply during the first days of treatment but were still abnormal on day 10. A secondary increase of D-Di on days 6 or 10 by more than 3 μg/ml occurred in 4 of the 9 patients who developed a thromboembolic recurrence but in none of the 72 patients who had a more favorable outcome. F 1 + 2 and TAT time-courses were not related to clinical evolution. In the Enoxaparin group, there was no relationship between antifactor Xa activities and any biological markers. TAT and F 1 + 2 levels fell on day 2 and remained stable until day 10. In contrast, in the UH group, TAT and F 1 + 2 did not significantly decrease on day 2, probably due to a delay in dose adaptation, but they declined slowly until day 10.In conclusion, D-Di displays a higher sensitivity than F 1 + 2 or TAT for the diagnosis of D\T. D-Di, but not TAT or F 1 + 2, follow-up seems to be of potential value for early detection of recurrency. Hemostatic activation is controlled earlier by fixed doses of a low molecular weight heparin, irrespective of the plasma anti-factor Xa activities, than by unfractionated heparin at adapted doses.

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

Comparison of the Non-Specific Binding of Unfractionated Heparin and Low Molecular Weight Heparin (Enoxaparin) to Plasma Proteins

1993 ◽  
Vol 70 (04) ◽  
pp. 625-630 ◽  
Author(s):  
Edward Young ◽  
Benilde Cosmi ◽  
Jeffrey Weitz ◽  
Jack Hirsh
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Plasma Proteins ◽  
Low Molecular Weight Heparin ◽  
Specific Binding ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Heparin Binding ◽  
Fixed Amount

SummaryThe non-specific binding of anticoagulantly-active heparin to plasma proteins may influence its anticoagulant effect. We used low affinity heparin (LAH) essentially devoid of anti-factor Xa activity to investigate the extent and possible mechanism of this non-specific binding. The addition of excess LAH to platelet-poor plasma containing a fixed amount of unfractionated heparin doubled the anti-factor Xa activity presumably because it displaces anticoagulantly-active heparin from plasma proteins. Although dextran sulfates of varying molecular weights also increased the anti-factor Xa activity, less sulfated heparin-like polysaccharides had no effect. These findings suggest that the ability to displace active heparin from plasma protein binding sites is related to charge and may be independent of molecular size. In contrast to its effect in plasma containing unfractionated heparin, there was little augmentation in anti-factor Xa activity when LAH was added to plasma containing low molecular weight heparin (LMWH), indicating that LMWH binds less to plasma proteins than unfractionated heparin. This concept is supported by studies comparing the anticoagulant activity of unfractionated heparin and LMWH in plasma with that in buffer containing antithrombin III. The anti-factor Xa activity of unfractionated heparin was 2-fold less in plasma than in the purified system. In contrast, LMWH had identical anti-factor Xa activity in both plasma and buffer, respectively. These findings may be clinically relevant because the recovered anti-factor Xa activity of unfractionated heparin was 33% lower in plasma from patients with suspected venous thrombosis than in plasma from healthy volunteers. The reduced heparin recovery in patient plasma reflects increased heparin binding to plasma proteins because the addition of LAH augmented the anti-factor Xa activity. In contrast to unfractionated heparin, there was complete recovery of LMWH added to patient plasma and little increase of anti-factor Xa activity after the addition of LAH. These findings may explain why LMWH gives a more predictable dose response than unfractionated heparin.

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