〈208〉 Anti-Factor Xa and Anti-Factor IIa Assays for Unfractionated and Low Molecular Weight Heparins

2021 ◽  
Keyword(s):  
Molecular Weight ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins

EXPERIMENTAL THROMBUS FORMATION AND HAEMOSTASIS OF DIFFERENT LOW MOLECULAR WEIGHT HEPARINS AND DOSAGES

1987 ◽  
Author(s):  
R A Zimmerman ◽  
C T Rieger ◽  
K Hübner ◽  
C W Harenber ◽  
W Kübler
Keyword(s):  
Molecular Weight ◽  
Thrombus Formation ◽  
Factor Xa ◽  
Bleeding Complications ◽  
Maximum Effect ◽  
Low Molecular Weight ◽  
Antithrombotic Effect ◽  
Low Molecular Weight Heparins ◽  
Antithrombotic Activity ◽  
Thrombosis Model

Low molecular weight heparin induces a higher anti factor Xa (a-Xa) and a lower antithrombin activity in plasma in comparison to conventional heparin. From this constellation a more pronounced antithrombotic effect and a minor incidence of bleeding Complications has been suggested.Therefore the antithrombotic activity of heparins was studied in a standardized experimental thrombosis model in rabbits. Three low molecular weight heparins with a mean molecular weight of 4.200 (heparin I),4.000 (heparin II),4.600 Dalton (heparin III) and standard heparin were tested at different dosages in 120 experiments. In the first series the dose of 60 anti Xa units (a-Xa U) given initially and 60 a-Xa U/kg/h induced a reduction of the thrombus size by 40 % (heparin I),37 % (heparin II) and 53 % (heparin III) and a prolongation of the aPTT to 45 (heparin I),66 (heparin II) and 79 sec (heparin III). The a-Xa activity was minor than 0.1 U/ml. In the second series heparins were given to aim at an a-Xa activity of 0.2-0.3 U/ml. Thereby the thrombus formation could be reduced by 84 % (heparin I), 62 % (heparin II) and 39 % (heparin III). aPTT and a-Xa activity were measured at 65.5 sec and 0.22 a-Xa U/ml (heparin I),67.3 sec and 0.3 a-Xa U/ml (heparin II) and 67.5 and 0.31 a-Xa U/ml (heparin III),respectively. In the third series the increase of the a-Xa activity to more than 0.3 U/ml showed no further reduction of the thrombus formation by heparin I, while heparins II and III already at this level reachedthe antithrombotic activity of heparin I.Our data on three different low molecular weight heparins demonstrate that already a heparin level ranging at a minimal a-Xa activity induces a clear and statistically significant antithrombotic effect. A higher heparin dosage with higher a-Xa activity increases the antithrombitic effect. At a level of 0.2-0.3 a-Xa U/ml an obvious and maximum effect could be reached, but the further elevation of the a-Xa activity produced no further antithrombotic action.

scholarly journals The anti-factor Xa range for low molecular weight heparin thromboprophylaxis

2015 ◽  
Vol 7 (4) ◽  
Author(s):  
Matthew Y. Wei ◽  
Salena M. Ward
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Dose Adjustment ◽  
Factor Xa ◽  
Research Data ◽  
Target Range ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Therapeutic Doses ◽  
Venous Thromboses

Low molecular weight heparins (LMWHs) are now the mainstay option in the prevention and treatment of venous thromboembolism. In some patients receiving therapeutic doses of LMWH, activity can be measured by quantifying the presence of Anti-factor Xa (AFXa) for dose adjustment. However, currently there are no guidelines for LMWH monitoring in patients on thromboprophylactic, doses, despite certain patient populations may be at risk of suboptimal dosing. This review found that while the AFXa ranges for therapeutic levels of LMWHs are relatively well defined in the literature, prophylactic ranges are much less clear, thus making it difficult to interpret current research data. From the studies published to date, we concluded that a reasonable AFXa target range for LMWH deep venous thromboses prophylaxis might be 0.2-0.5 IU/mL.

PHARMACOLOGIC INEQUIVALENCE OF LOW MOLECULAR WEIGHT HEPARINS

1987 ◽  
Author(s):  
J Fareed ◽  
J M Walenga ◽  
D Hoppensteadt ◽  
R N Emanuele ◽  
A Racanell
Keyword(s):  
Molecular Weight ◽  
Animal Models ◽  
Comparative Study ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
In Vivo Test ◽  
In Vitro Effects

Compared to unfractionated heparin, low molecular weight heparins (LMWHs) have been found to exhibit marked variations in in vitro effects due to variations in molecular weight and structure. Moreover, when the in vitro potency of these agents is equally adjusted bypharmacopeial assay (current and proposed) wide variations in the in vivo responses have been noted. These variations were strongly dependent on the route of administration. Utilizing defined animal models, a systematic comparative study of the in vivo responses of seven commercial LMWHs was undertaken. Choay Fraxiparine (CY 216} Choay CY 222, NovoLHN, Kabi Fragmin, Opocrin 2123 (OP), Hepar RD 11885 (RD), Pharmuka Enoxaparin (PK) and Choay porcine mucosal heparin (PMH) were tested in identical settings at equigravimetric dosages. The graded results are given in the following.Wide variations in the in vivo pharmacologic and toxicity responseswere noted suggesting that different LMWHs are not bioequivalent at equigravimetric levels. When these responses were expressed in anti-factor Xa or pharmacopeial potency, these differences were further magnified. The clinically reported dosimetric and safety problems may be minimized by profiling LMWHs in defined in vivo test systems to optimize their safety/efficacy ratio.

A NEW ONE STAGE CLOTTING ASSAY FOR HEPARIN AND LOW MOLECULAR WEIGHT HEPARINS

1987 ◽  
Author(s):  
Ch Giese ◽  
A Knodler ◽  
R Zimmermann ◽  
J Harenberg
Keyword(s):  
Molecular Weight ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Chromogenic Substrate ◽  
Clotting Time ◽  
Low Molecular Weight Heparins ◽  
One Stage ◽  
High Preference ◽  
Coagulation Tests ◽  
Plasma Assay

Heparin and its low molecular weight (LMW) derivatives are usually measured by chromogenic or fluorogenic synthetic substrate assays and by coagulation tests. Since the activated partial thromboplastin time (aPTT) and thrombin clotting time (TCT) are insensitive to LMW heparins, we report here of data obtained with heptest, a new one stage modification of the original heparin in plasma assay of Yin. The assay was compared with the antifactor Xa chromogenic substrate S2222 method, the TCT and aPTT tests in 100 patients receiving unfractionated pig intestinal mucosa heparin and 100 patients treated with low molecular weight heparin Kabi 2165. The results indicate a high correlation between the heptest and the anti Xa chromogenic substrate method, whereas the correlations were lower for the aPTT and TCT. correlations with LMW heparinThe lowest detection limit of the heptest is 0,005 heparin units per ml plasma. The test is very sensitive, simple, highly reproducable and reliable clotting assay for unfractionated and low molecular weight heparins in human plasma. The test detects with high preference the inhibition on factor Xa but also the other anticoagulant effects on die coagulation tractors.

COMPARATIVE CLINICAL PHARMACOLOGY OF LOW MOLECULAR WEIGHT HEPARINS IN MAN

1987 ◽  
Author(s):  
Y Ordu ◽  
J Augustin ◽  
E V Hodenberg ◽  
V Bode ◽  
J Harenberg
Keyword(s):  
Molecular Weight ◽  
Clinical Pharmacology ◽  
Ex Vivo ◽  
Average Molecular Weight ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Pharmacological Properties ◽  
Clotting Time ◽  
Activity Time ◽  
Low Molecular Weight Heparins

Low molecular weight (LMW) heparins are obtained by diffent chemical procedures from conventional pig intestinal mucosa heparin. The LMW heparins differ in their molecular weight distribution and physicochemical properties. Therefore, we report of comparative studies on the anticoagulant and lipolytic effects of low molecular weight heparins in man.The following LMW heparins were used: BM 21-23 (Braun, Melsungen, FRG), CY 216 (Choay Laboratories, Paris, France), Heparin NM (Sandoz, Niimberg, FRG), Kabi 2165 (Kabi Vitrum AB, Stockholm, Sweden), RD Heparin (Hepar Industries, Franklin, US A), normal heparin (Braun). All heparins were administered intravenously and subcutaneously to six volunteers each.The data show considerable differences in the anticoagulant and lipolytic effects between the different low molecular weight heparins. From the area under the activity time curves (AUC) of the clotting assays for factor Xa (heptest), aPTT and thrombin clotting time the aXa/aPTT ratio ex vivo and aXa/alla ratio ex vivo were determined (table, average values)It can be seen that there are clear differences in the ex vivo ratios of the LMW heparins. There is a good correlation between the average molecular weight of the LMW heparins and the aXa/aPTT ratio after s.c. administration and of the aXa/alla ratio ex vivo after s.c. administration. Therefore, LMW heparins differ significantly in their clinical pharmacological properties.

scholarly journals Standard and Method Independent Units for Heparin Anticoagulant Activities

1993 ◽  
Vol 70 (05) ◽  
pp. 724-728 ◽  
Author(s):  
H C Hemker ◽  
S Béguin
Keyword(s):  
Molecular Weight ◽  
Catalytic Effect ◽  
Anticoagulant Activity ◽  
Quantitative Description ◽  
Factor Xa ◽  
Assay Method ◽  
Low Molecular Weight ◽  
Laboratory Practice ◽  
Low Molecular Weight Heparins ◽  
At Iii

SummaryIt is discussed why the current USP unit of heparin anticoagulant activity necessarily will render inaccurately the anticoagulant activities of low molecular weight heparins. It is shown that the outcome is bound to vary with the method used for comparison of the sample and the standard and with the nature of the standard used. As an alternative we define a unit of heparin in terms of anti-factor Xa- and antithrombin-activity that is independent of the heparin standard and of the assay method, but that is based upon a quantitative description of the catalytic effect of heparin on AT III mediated thrombin- and factor Xa breakdown. Expression of the results of existing anti-factor Xa- and antithrombin tests in terms of these units will allow to express heparin levels in plasma in terms of concentrations of active anticoagulant material. This approach makes it possible to separate heparin pharmacodynamics from heparin pharmacokinetics. Introduction of this unit does not require adaptation of current laboratory practice but changes the way in which the results obtained are expressed.

Heptest-STAT, a new assay for monitoring of low-molecular-weight heparins, is not influenced by pregnancy-related changes of blood plasma

2009 ◽  
Vol 102 (11) ◽  
pp. 1001-1006 ◽  
Author(s):  
Ulyana Zharkowa ◽  
Elif Elmas ◽  
Parviz Ahmad-Nejad ◽  
Michael Neumaier ◽  
Martin Borggrefe ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Pregnant Women ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Plasma Samples ◽  
Third Trimester ◽  
Low Molecular Weight Heparins ◽  
Individual Calibration ◽  
Standard Calibration ◽  
In Pregnancy

SummaryMonitoring of anti-factor Xa activity is often performed during treatment with low-molecular-weight heparins (LMWHs) in pregnancy because the anticoagulant effect may decrease as pregnancy progresses, but assays for anti-factor Xa activity are unavailable in many clinical institutions caring for pregnant women. Heptest-STAT is a new clotting assay for monitoring of LMWHs, which has been optimised for use in near-patient laboratory instrumentation. It has been suggested that monitoring of LMWHs requires the use of individual calibration curves for each LMWH.We compared the dose response of four conventional LMWHs and fondaparinux in normal plasma, and plasma from women in first, second and third trimester of pregnancy. Three concentrations of LMWHs, fondaparinux, or unfractionated heparin were added to pooled plasma samples from nonpregnant women (n=10), and pregnant women in first (n=10), second (n=10) and third (n=10) trimester of pregnancy. Heptest results are not influenced by the stage of pregnancy. In contrast, dose-related aPTT prolongation declines during pregnancy. All LMWHs tested, as well as fondaparinux, display a similar doseresponse in Heptest compared to the chromogenic anti-factor Xa assay. Heptest-STAT can be used with the same standard calibration for non-pregnant and pregnant patients and for all LMWHs under investigation, including fondparinux. No individual calibrations are necessary.

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