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Background: No guidelines for administering and monitoring anticoagulants intraprocedurally are currently available in dogs, despite the prevalence of procedures necessitating systemic anticoagulation with heparin. Objectives: To evaluate an activated clotting time (ACT)‐based heparin dose‐response (HDR) test to predict the individual required heparin dose in dogs during intravascular procedures, and to investigate both the in vitro heparin – ACT and in vitro heparin – factor anti‐Xa activity (anti‐Xa) relationships in dogs. Methods: Blood was collected from eight healthy beagles undergoing a cardiac procedure and utilised to establish baseline ACT and for in vitro evaluation. Subsequently, 100 IU/kg heparin was administered intravenously (IV) and ACT was remeasured (HDR test). The required heparin dose for an ACT target response ≥300 s was calculated for each individual and ACT was remeasured after administration of this dose. For in vitro testing, a serial heparin blood dilution (0‐0.5‐1‐2‐4 international unit (IU)/mL) was prepared and ACT and anti‐Xa were determined using whole blood and frozen plasma, respectively. Results: The HDR test overestimated the required heparin dose in 3/7 dogs. In vitro, ACT and anti‐Xa increased significantly with increasing blood heparin concentration. Heparin – ACT was nonlinear in 4/8 dogs at heparin concentrations >2 IU/mL, whereas heparin – anti‐Xa remained linear throughout the tested range. Conclusions: The HDR test poorly estimated the required heparin dose in dogs. This is most likely attributed to a nonlinear heparin – ACT relationship, as observed in vitro. Anti‐Xa is a promising alternative for ACT; however, unavailability as a point‐of‐care test and lack of in vivo target values restrict its current use. [ABSTRACT FROM AUTHOR]

Abstract Background No guidelines for administering and monitoring anticoagulants intraprocedurally are currently available in dogs, despite the prevalence of procedures necessitating systemic anticoagulation with heparin. Objectives To evaluate an activated clotting time (ACT)‐based heparin dose‐response (HDR) test to predict the individual required heparin dose in dogs during intravascular procedures, and to investigate both the in vitro heparin – ACT and in vitro heparin – factor anti‐Xa activity (anti‐Xa) relationships in dogs. Methods Blood was collected from eight healthy beagles undergoing a cardiac procedure and utilised to establish baseline ACT and for in vitro evaluation. Subsequently, 100 IU/kg heparin was administered intravenously (IV) and ACT was remeasured (HDR test). The required heparin dose for an ACT target response ≥300 s was calculated for each individual and ACT was remeasured after administration of this dose. For in vitro testing, a serial heparin blood dilution (0‐0.5‐1‐2‐4 international unit (IU)/mL) was prepared and ACT and anti‐Xa were determined using whole blood and frozen plasma, respectively. Results The HDR test overestimated the required heparin dose in 3/7 dogs. In vitro, ACT and anti‐Xa increased significantly with increasing blood heparin concentration. Heparin – ACT was nonlinear in 4/8 dogs at heparin concentrations >2 IU/mL, whereas heparin – anti‐Xa remained linear throughout the tested range. Conclusions The HDR test poorly estimated the required heparin dose in dogs. This is most likely attributed to a nonlinear heparin – ACT relationship, as observed in vitro. Anti‐Xa is a promising alternative for ACT; however, unavailability as a point‐of‐care test and lack of in vivo target values restrict its current use.

The activated partial thromboplastin time (APTT) assay is a very common coagulation test, used for several reasons. The test is conventionally used for assessing the contact factor (intrinsic) pathway of blood coagulation, and thus for screening deficiencies in this pathway, most typically factors VIII, IX, and XI. The APTT is also sensitive to contact factor deficiencies, including factor XII, prekallikrein, and high-molecular-weight kininogen. The APTT may also be elevated in a variety of conditions, including liver disease, vitamin K deficiency, and disseminated intravascular coagulation. The APTT can also be used for monitoring unfractionated heparin (UFH) therapy, as well as for screening lupus anticoagulant (LA) or for assessing thrombosis risk. Which of these separate uses is important to a given laboratory or clinician depends on the laboratory and the clinical context. For example, UFH sensitivity is important in hospital-based laboratories, where UFH therapy is used, but not in hospital-based laboratories where low-molecular-weight heparin (LMWH) is largely employed or where UFH may be assessed by anti-factor Xa testing, or in private/community laboratories not associated with a hospital system. High sensitivity to (low levels of) factors VIII, IX, and XI is generally preferred, as their deficiencies are clinically significant. Also preferred, but not usually achieved, is low sensitivity to factor XII and other contact factors, as these deficiencies are usually asymptomatic. Nevertheless, a good knowledge of factor sensitivity is usually needed, if only to help explain the reasons for a prolonged APTT in a given patient, or whether factor testing or other investigation is required. A good working knowledge of reagents sensitivity to LA is also advisable, especially when the reagent is used as part of a LA test panel, or else as a "general-purpose screening reagent." The current report is aimed at providing some guidance around these questions, and is intended as a kind of "how to" guide, that will enable laboratories to assess APTT reagents in regard to their sensitivity to heparin, LA, and clotting factors. The report also provides some advice on generation of normal reference ranges, as well as solutions for troubleshooting prolonged APTTs, when performing factor testing or searching for inhibitors. [ABSTRACT FROM AUTHOR]

The most commonly used test for monitoring heparin therapy is the activated partial thromboplastin time (aPTT). The response of available aPTT reagents to heparin varies significantly. The aim of this study was to highlight the differences between aPTT reagents stored in a dried format to select the most suitable formulations to be used for the development of point-of-care diagnostic devices used for monitoring of unfractionated heparin dose response. Ten reagents were analysed in terms of their performance in liquid and in dried form after storage for 24 h and 14 days. Performance was assessed by measurement of the clotting time (CT) as evidenced by the onset of thrombin formation using a chromogenic thrombin substrate in plasma samples activated with these formulations. Reagents in all of the three forms tested (liquid, 24 h and 14 days) resulted in significant shortening of CTs in comparison with the nonactivated plasma CT. Liquids returned more rapid CTs in comparison with dried reagents. Most of the reagents were more sensitive to heparin in dried, rather than in liquid form. Dried reagents based on kaolin as a surface activator were notably more effective in achieving short CT than others, while dried reagents composed of silica and synthetic phospholipids were the most sensitive to heparin. Two reagents, namely aPTT-SP and SynthASIL both of which are based on synthetic phospholipids and silica, were identified as promising candidates for incorporation into point-of-care diagnostic device platforms as dried reagents. [ABSTRACT FROM AUTHOR]

The phospholipid content of different activated partial thromboplastin time (APTT) reagents was determined and compared to heparin sensitivity. The seven reagents included were those most widely used amongst participants of the U.K. National External Quality Assessment Scheme (NEQAS) at the time of study. Heparin sensitivity was assessed using the APTT ratios obtained by more than 300 NEQAS participants on five plasmas prepared from patients receiving unfractionated heparin. The concentrations of three neutral lipids and six phospholipids present in the seven APTT reagents were determined by high-performance thin-layer chromatography (HPTLC) and densitometry. Both the concentrations and the relative percentages of individual phospholipid components varied markedly between reagents. The total phospholipid concentration included a 12-fold range from 16 to 205 μg/ml. Phosphatidylserine (PS) was completely lacking from one reagent prepared from vegetable material and ranged from 3 to 22 μg/ml in the other six reagents containing extracts from animal tissue. The concentration of phosphatidylcholine ranged from 3 to 109 μg/ml. There was no demonstrable relationship between the concentration of any individual lipid components and heparin sensitivity. However, the relative percentage phospholipid composition was important since a lower % of PS or phosphatidylinositol (PI) correlated with increasing heparin sensitivity. [ABSTRACT FROM AUTHOR]

Whenever unfractionated heparin (UFH) is administered i.v. in therapeutic doses, therapeutic drug monitoring of the anticoagulant response should be mandatory and the dose should be adjusted accordingly. UFH therapy is usually monitored by the activated partial thromboplastin time (APTT). A 1.5- to 2.5-fold prolongation of APTT has become generally accepted as an indicator of effective i.v. anticoagulation, but it has become common to recommend this ratio without testing the APTT reagents used for their heparin sensitivity and for their actual therapeutic APTT ratio (actual APTT: normal control APTT). Internal heparin sensitivity testing of APTT reagents is managed using heparin sensitivity curves obtained from heparin-spiked normal plasma pool. The most common APTT reagents in Austria and a newly developed double activated APTT reagent were tested for their heparin sensitivity and therapeutic ratios on different automated analyzers, depending on their optical and chemical conditions. Also, newly developed, commercially prepared heparin standards (0.19, 0.52, 0.86 IU heparin/ml plasma) were tested. APTT reagents differ in their heparin sensitivity and therapeutic ratio: variations in heparin sensitivity are also seen between different analyzers. Therefore, therapeutic ratio should regularly be checked and the literature should always state which APTT reagent was used on which instrument. [ABSTRACT FROM AUTHOR]