Differences in Global Hemostasis Following rFVIIa Dosing: A Focus On Responders Versus Poor Responders.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3485-3485
Author(s):  
Donald Brophy ◽  
Erika Martin ◽  
John Christian Barrett ◽  
Mindy Nolte ◽  
Janice Kuhn ◽  
...  
Keyword(s):  
Platelet Function ◽  
Whole Blood ◽  
Thrombin Generation ◽  
Formation Time ◽  
Clot Formation ◽  
Group Differences ◽  
Poor Responders ◽  
Sample Type ◽  
Clot Structure ◽  
Clot Formation Time

Abstract Abstract 3485 Poster Board III-422 Introduction The clinical response of hemophilia patients with inhibitors to bypassing agent therapy can be unexpectedly poor. Indeed, there are reports of “poor responders” who either require alternative treatment or dose escalation. The lack of correlation between routine coagulation assays or factor antigen/activity levels with clinical efficacy contributes to the problem in these patients. Analysis of the clotting characteristics of “poor responders” is limited. In a recent study of rFVIIa PK in 10 non-bleeding hemophilia A and B patients, we noted that four of the ten had a remarkable attenuated response as seen in whole blood assays. We report here a comparison of clotting parameters in the “poor responders” versus robust responders to rFVIIa infusion, and attempt to define what might be the source of the altered response. Patients and Methods Ten severe FVIII or FIX deficient patients in a non-bleeding state were infused with a single-dose of rFVIIa (90 μg/kg). Platelet contractile force (PCF), clot structure (CEM,MA,MCF), and clot formation time (FOT,R,CT) were analyzed in whole blood by Hemodyne HAS, Thromboelastography, and Rotation Thromboelastography before, and at 0.5,1,2,4 and 6 hours following rFVIIa dosing. Thrombin generation parameters (Tlag, Cmax) were measured in PRP by the Calibrated Automated Thrombogram. Plasma concentrations of FVII:C and FVII:Ag were measured at each time point. Patients with a clot formation time (FOT, R, CT) ≥ 15 minutes following rFVIIa dosing were termed “Poor Responders”. Results There were few inter-group differences in baseline clotting characteristics. The values for all parameters are provided in Table 1. FVII PK were not different between the Responders and Poor-Responders. This can be appreciated from the PK parameters listed in the table as well as from relative lack of variability for the composite rFVIIa levels seen for the entire group of 10 patients (Figure 1, panels 1 and 2). Both groups had similar FVIIa Cmax and total body clearance values. However, the responders made significantly stronger clots (PCF, CEM) as can be appreciated in table 1 and even more dramatically in panels 3 and 4 of figure 1. In these panels, the responders and poor responders are plotted as separate groups. Even though the groups are small (n=6 vs 4) the minimal response (both in magnitude and duration) to rFVIIa in terms of platelet function (PCF) and clot structure (CEM) is grossly apparent. All three whole blood assays revealed significantly shorter time to clot formation (R, FOT, CT) in the responders. However, the MA (TEG) and MCF (ROTEG), and thrombin generation parameters (Tlag, max) failed to show significant inter-group differences following rFVIIa dosing. Conclusions These data suggest that the differences observed between Responders and Poor Responders are not due to PK influences, but may be related to differences in the effects of thrombin on platelet function. It is possible that whole blood assays may serve as a tool to monitor the clinical effects of rFVIIa. Changes in clot stiffness were better characterized by CEM compared to MA and MCF. There was good correlation between FOT, R and CT parameters to detect onset of clot formation. The thrombin parameters were highly dependent on sample type and triggering agent and did not significantly vary between the two groups. Further studies are needed to clarify the clinical significance of these findings. Disclosures: Ezban: NovoNordisk A/S: Employment. Hedner:NovoNordisk A/S: Employment.

Evaluation of Clotting Parameters in a Patient with Hemophilia A and Inhibitors Who Has a Poor Clinical Response to Standard Dose rFVIIa.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4440-4440
Author(s):  
Marcus E. Carr ◽  
Erika J Martin ◽  
John Christian Barrett ◽  
Mindy Nolte ◽  
Janice Kuhn ◽  
...  
Keyword(s):  
Clinical Response ◽  
Whole Blood ◽  
Thrombin Generation ◽  
Hemophilia A ◽  
Standard Dose ◽  
High Titer ◽  
Poor Responders ◽  
Sample Type ◽  
D Dimer

Abstract Abstract 4440 It is known that some FVIII deficient patients who develop high titer FVIII inhibitors do not respond as expected to inhibitor bypassing agents. During an IRB approved study of laboratory monitoring of rFVIIa infusion in hemophilia patients, we had the opportunity to extensively study a patient who was known to respond poorly to standard dose (90 mg/kg) rFVIIa. We present here results from this patient included in this study and question whether it might be possible to predict poor response from in vitro measurements. Case history The patient is a 43 year old male with severe hemophilia A (FVIII<1%) and a high titer FVIII antibody (10.4 BU). In 2003, attempts were made to treat spontaneous joint bleeds with standard (90 mg/kg) dose rFVIIa. Responses were poor and the patient was switched to FEIBA (>6000 IU per infusion) to which he responded. He continues to bleed frequently with 7 documented bleeds requiring 21 infusions of FEIBA for treatment during the first six months of 2009. Methods This patient was one of 10 hemophiliacs participating in a clinical study of rFVIIa. Blood samples were drawn at baseline and at 0.5, 1, 2, 4 and 6 hours after a single dose of rFVIIa 90 mg/kg. Parameters measured included PT, PTT, fibrinogen level and whole blood assays (Hemodyne HAS, TEG®, and ROTEG®). Thrombin generation was measured in PPP and PRP by CAT. Plasma samples were analyzed for Prothrombin Fragment 1.2, FVII:C, FVII:Ag, FVIIa:ATIII and D-dimer. In addition, in this patient an in vitro spiking study of rFVIIa corresponding to doses of 90, 180 and 270 mg/kg was performed to determine the clotting parameters. Results At baseline, his PT was 9.6 seconds, PTT was 112 seconds, and fibrinogen was 238 mg/dl. Samples for TEG, HAS and ROTEG analysis all failed to clot when re-calcified and monitored for up to 60 minutes. Thirty minutes post infusion of rFVIIa, HAS parameters slightly improved (FOT=16 min, PCF 2.0 Kdyn) but quickly reverted to grossly abnormal at one hour. This is in marked contrast to the typical response of most patients in the study as demonstrated in (Fig.1). The R for TEG shortened to 14.4 min and CT for ROTEM decreased to 1094 sec after 30 minutes and remained measurable but grossly abnormal (30 min and 2000 sec) for the next six hours. MA (60 mm) and MCF (60 mm) normalized at 30 min and remained normal for the next six hours. Results of CAT were dependent on the sample type and clot triggering agent. Re-calcification in PRP resulted in shortening of T-lag to 21.5 minutes and a C-max of 15.8 nM both of which were grossly abnormal. T-lag for PRP clotted with 1pm TF was 9.9 min and shortened to 5 min post rFVIIa infusion. ETP when measurable was very low. For PPP clotted with 0.5 pM TF and 4mM phospholipid, the T-lag decreased from a baseline of 5 to <3 min post rFVIIa infusion and remained <3 for six hours. Baseline antigen and coagulant rFVIIa, D-Dimer and F1+2 levels were normal in the patient and the pattern of response did not differ from those seen with patients who had normal responses to rFVIIa. The pharmacokinetics of rFVIIa in this patient were determined, and were consistent with other study participants (Cltot: 66.3, mean= 50.8 ml/hr*kg). During the in vitro experiment, addition of rFVII produced HAS results equivalent to those seen 30 minutes after rFVIIa infusion (Table). Addition of concentrations equivalent to 180 and 270 mg/Kg doses produced additional correction. Conclusion We have analyzed the response to rFVIIa infusion using multiple clotting parameters in a patient with known poor clinical response to standard dose rFVIIa. The clotting lag times of whole blood assays including the HAS, TEG and ROTEG appear to be sensitive to varying degrees to the decreased response to rFVIIa. Thrombin generation was grossly abnormal in PRP but appeared relatively insensitive in PPP to the decreased rFVIIa effect. Spiking studies in the HAS correlated with results from infusion and also indicated that the patient might respond to higher dose rFVIIa. This possibility has not been clinically confirmed, but these results raise the possibility of identifying poor responders and perhaps helping to predict doses that might be effective. Disclosures: Ezban: NovoNordisk A/S: Employment. Hedner:NovoNordisk: Employment.

Effect of Non-Heparin Thrombin Antagonists on Thrombin Generation, Platelet Function, and Clot Structure in Whole Blood

2003 ◽  
Vol 39 (2) ◽  
pp. 89-100 ◽  
Author(s):  
Marcus E. Carr ◽  
Pantep Angchaisuksiri ◽  
Sheryl L. Carr ◽  
Erika J. Martin
Keyword(s):  
Platelet Function ◽  
Whole Blood ◽  
Thrombin Generation ◽  
Clot Structure

Analysis of Racial Disparity in Plasma of Healthy Volunteers Using Rotational Thromboelastometry Reveals Higher Prothrombotic Profile in African Americans

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5972-5972 ◽  
Author(s):  
Maissaa Janbain ◽  
Walter J Liszewski ◽  
Cindy A Leissinger
Keyword(s):  
African Americans ◽  
Healthy Volunteers ◽  
Racial Differences ◽  
Whole Blood ◽  
Thrombin Generation ◽  
Alpha Angle ◽  
Formation Time ◽  
Rotational Thromboelastometry ◽  
Clot Formation Time ◽  
Maximum Clot Firmness

Racial differences in the incidence of arterial and venous thrombotic events are well established in literature, with a higher incidence noted in African Americans compared to Caucasians. Several studies have tried to explain this difference, by looking separately at chemical biomarkers, socioeconomic and clinical risk factors. Yet the exact reason behind this disparity remains unclear. At least one study of thrombin generation suggested that African ethnicity was associated with increased peak thrombin generation when compared to Caucasians. Rotational thromboelastometry is a visco-elastic methodology that offers a global assessment of hemostasis using either whole blood or plasma. We explored the racial differences in rotational thromboelastometry findings using plasma samples from healthy volunteers. We studied a cohort of 9 otherwise healthy adult volunteers with no history of cardiovascular nor thromboembolic events, 5 African Americans and 4 Caucasians. After informed consent, we collected citrated whole blood samples and processed them within 3 hours of phlebotomy. Platelet free plasma, obtained after centrifugation of whole blood for 20 minutes, was kept frozen at -70°C, and then thawed at 37°C for 5 minutes prior to testing. Samples were re-calcified with star-tem® reagent, and then the in-tem® reagent was added. The latter contains an optimized concentration of ellagic acid and partial thromboplastin phospholipid from rabbit brain. Thromboelastometry parameters including Clot Formation Time, Alpha Angle, and Maximum Clot Firmness were determined. We then compared the data between the two study populations using parametric unpaired Student’s t-test. Our results showed that the Clot Formation Time was higher in the plasma of Caucasians when compared to African Americans with a difference between means of 40.1 ± 4.4 seconds (p <.0001); the Alpha Angle was lower in Caucasians with a difference between means of 3.45 ± 0.3 degrees (p <.0001); and the Maximum Clot Firmness was lower in Caucasians with a difference between means of 9.75 ± 2 mm (p <.01). These findings demonstrated that the plasma of Caucasians took longer to reach the maximum firmness, and this maximum firmness was less than that reached in the plasma of African Americans. This reveals a significantly increased prothrombotic profile in the plasma of African Americans compared to Caucasians. Despite the limited number of participants, the striking observed differences in the thromboelastometry parameters suggest that global assays may offer benefit in assessing thrombotic risks in disparate patient populations, as they incorporate multiple components of the hemostatic system. Higher numbers of subjects and assessment of both whole blood and plasma are indicated. We are currently in the process of expanding our cohort to confirm these preliminary results. Disclosures No relevant conflicts of interest to declare.

Abstract 520: Acoustic Tweezing Thromboelastometry

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Daishen Luo ◽  
Damir Khismatullin ◽  
R. Glynn Holt
Keyword(s):  
Reaction Time ◽  
Whole Blood ◽  
Factor Xiii ◽  
Formation Time ◽  
Plasma Samples ◽  
Clot Strength ◽  
Plasma Coagulation ◽  
Coagulation Status ◽  
Clot Formation Time ◽  
Control Plasma

Background: Critical care patients such as trauma and major surgery patients often develop coagulopathy due to depletion of both pro- and anti-coagulants. They are at high risk of both bleeding and thrombotic complications and require monitoring of their coagulation status. The contact of a blood sample with artificial surfaces and its exposure to clot activators, which happen in all commercially available coagulation analyzers, may lead to improper assessment of blood coagulation and thus errors in predicting bleeding/thrombosis risks. Objective: Real-time assessment of whole blood or blood plasma coagulation by novel non-contact acoustic tweezing technology. Method: 4-5 microliter drops of whole blood collected from healthy volunteers or commercial control plasma were levitated in air by acoustic radiation forces. Their coagulation kinetics including reaction time, fibrin network formation time (FNFT), clot formation time and maximum clot strength was assessed from mechanical (drop shape) and photo-optical (light intensity) data. FNFT was determined as a difference between mechanical and photo-optical reaction times. Results: Whole blood samples were exposed to pro- or anti-coagulants during levitation in the acoustic tweezing device. Changes in the coagulation status between different experimental groups were detected within 10 minutes. Similarly, less than 7 minutes was required to detect significant changes in reaction time, clot formation time and maximum clot strength between low, normal, and high fibrinogen level control plasma samples. FNFT was shown to be significantly reduced in plasma samples with a higher level of Factor XIII. Conclusions: The acoustic tweezing technology integrates photo-optical tests used in plasma coagulation assays with viscoelastic tests used in whole blood analysis. Its key disruptive features are the increased reliability and accuracy due to non-contact measurement, small sample volume requirement, relatively short procedure time (<10 minutes), and the ability to assess the level of Factor XIII function from FNFT measurements. Our technology addresses a current lack of reliable methods to measure blood coagulation in patients with coagulopathy.

Influence of Nanopolymers with Different End-Functionalities on Platelet Function and the Coagulation Cascade - An Ex-Vivo Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4038-4038
Author(s):  
Meera Chitlur ◽  
Erin Ware ◽  
Sujata Kannan ◽  
Wendy Hollon ◽  
Steve Buck ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Platelet Aggregation ◽  
Surface Charge ◽  
Platelet Function ◽  
Whole Blood ◽  
Clot Formation ◽  
Coagulation Cascade ◽  
Cancer Drug ◽  
Dendritic Polymers ◽  
Drug Concentrations

Abstract Dendritic polymers are branched nanopolymers with a central core and multiple peripheral functional groups that offer great potential as high payload delivery vehicles carrying multiple copies of drug molecules, targeting ligands and imaging agents to their site of action. Their nanoscopic dimensions offer exciting possibilities for achieving high intracellular drug concentrations in many therapeutic areas including anti-cancer drug delivery. Biocompatibility and biodistribution of dendritic polymers may be influenced by surface charge and concentration. One of the major challenges in their use is the effect on coagulation. The objective of this study was to determine the effect of change in surface charge and concentration of dendritic polymer on cellular and enzymatic components of coagulation. Materials and Methods: The effect of increasing concentrations (1, 10, 100, and 1000mcg/ml) of polyamidoamine (PAMAM) dendrimers with -COOH (anionic), -OH (neutral), and -NH2 (cationic) end functionalities, on platelet function and coagulation was evaluated using thromboelastography, whole blood aggregation, and flow cytometry. The thromboelastographic profile and platelet aggregation studies were obtained on samples of whole blood incubated for thirty minutes with dendrimer. Platelets were incubated with FITC labelled dendrimer for 30,60 and 120 mins, to determine uptake and platelet activation using flow cytometry. All tests were performed in triplicate. RESULTS: Thromboelastography: No significant effect on clot formation (time to clot formation and size) was seen with PAMAM-COOH (COOH) or PAMAM-OH (OH). Prolonged time to initiation of clot and decreased size were noted with 100 and 1000mcg/ml of PAMAM-NH2(NH2) as shown in figure1, indicating impairment of both the enzymatic and cellular components of the coagulation system. Whole Blood Aggregation: Neither platelet aggregation nor secretion were significantly affected by COOH or OH. Platelet aggregation was significantly decreased with NH2 at 100 and 1000mcg/ml. Flow Cytometry: Spontaneous CD62 activation was seen in platelets incubated with NH2. No spontaneous CD62 activation was noted with COOH or OH even at 1000mcg/ml. Platelet uptake of FITC labeled dendrimer was assessed at 30, 60 and 120mins of incubation. Increased uptake of FITC labeled dendrimer was noted at 2 hours with NH2. TEG clotting Profiles with PAMAM-NH2. TEG clotting Profiles with PAMAM-NH2. CONCLUSIONS: Surface charge of the dendritic nanopolymers plays a significant role on its effect on coagulation and platelet function. The anionic -COOH terminated and neutral -OH terminated dendrimers had no effect on hemostasis even at the highest concentrations while the cationic-NH2 was associated with inhibition of platelet aggregation and delayed clot initiation at higher concentrations. This would indicate that the anionic and neutral dendrimers would serve as better vehicles than cationic dendrimers for targeted delivery of therapeutic agents.

Hemophilia a Clots Generated with Recombinant Factor VIIa Differed in Structure and Composition from Those Formed with Factor VIII

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3798-3798
Author(s):  
Lilley Leong ◽  
Irina N. Chernysh ◽  
Yifan Xu ◽  
Cornell Mallari ◽  
Billy Wong ◽  
...  
Keyword(s):  
Factor Viii ◽  
Whole Blood ◽  
Neutralizing Antibodies ◽  
Research Funding ◽  
Thrombin Generation ◽  
Hemophilia A ◽  
Clot Formation ◽  
Factor Vii ◽  
Wild Type ◽  
Independent Mechanism

Abstract Patients with severe factor VIII (FVIII) deficiency (hemophilia A [HemA]) develop neutralizing antibodies (inhibitors) against FVIII in up to ~30% of cases. For HemA patients with inhibitors, activated recombinant factor VII (rFVIIa) is a treatment option. High levels of rFVIIa are required for treating HemA patients with inhibitors to induce direct activation of factor X on the surface of activated platelets via a tissue factor (TF)-independent mechanism (Hoffman M, Monroe DM. Thromb Res. 2010;125(suppl 1):S16-S18). To assess how rFVIIa-mediated clot formation in HemA patients with inhibitors may differ from unaffected individuals, we compared the effect of rFVIIa on HemA versus control (or HemA supplemented with 100% FVIII) clot formation in human and/or mouse systems. By TF-induced thrombin generation assay, increasing rFVIIa from 5 nM to 100 nM did not appreciably alter the kinetics or extent of thrombin generation compared with the same human HemA plasma containing 100% FVIII. Confocal microscopy of human HemA plasma clots generated with 75 nM rFVIIa and TF showed few branching fibrin fibers and an open fibrin meshwork. In contrast, TF-induced coagulation of the same HemA plasma containing 100% FVIII formed fibrin clots with numerous branches, interconnecting to form a dense meshwork. To confirm that these findings reflect rFVIIa-mediated clot formation in vivo, we assessed the intrinsic coagulation of mouse HemA whole blood collected without anticoagulant and spiked with rFVIIa. Intrinsic coagulation with rFVIIa was assessed by T2 magnetic resonance (T2MR), a technique capable of monitoring the separation of whole blood into serum, loose-clot, and tight-clot compartments during coagulation (Skewis et al. Clin Chem. 2014;60:1174-1182; Cines et al. Blood. 2014;123:1596-1603). By T2MR, rFVIIa induced the separation of HemA whole blood into the serum and clot compartments, indicating that the reduced fibrin generation with rFVIIa did not interfere with whole blood coagulation. Furthermore, saphenous vein puncture of HemA mice treated with rFVIIa showed a dose-dependent decrease in clot times. Scanning electron microscopy of the clots extracted from these HemA mice indicated markedly different composition than clots extracted from wild-type mice. In wild-type clots, fibrin and polyhedral erythrocytes formed a large proportion of the total structures. In contrast, clots from rFVIIa-treated HemA mice consisted primarily of platelets and erythrocytes with forms intermediate between discoid and polyhedral but, surprisingly, low fibrin content. Taken together, these data suggest that rFVIIa-mediated clot formation may require greater activated platelet involvement, which would be consistent with the TF-independent mechanism of action proposed for rFVIIa in HemA. Finally, the compositional difference between clots from wild-type versus HemA mice dosed with rFVIIa suggest that evaluating HemA therapies for their ability to form more physiologic clots could be an approach to improve treatment options for patients with HemA. Disclosures Leong: Bayer: Employment. Xu:Bayer: Employment. Mallari:Bayer: Employment. Wong:Bayer: Employment. Sim:Bayer: Employment. Cuker:Stago: Consultancy; Genzyme: Consultancy; Amgen: Consultancy; Biogen-Idec: Consultancy, Research Funding; T2 Biosystems: Research Funding. Marturano:T2 Biosystems: Employment. Lowery:T2 Biosystems: Employment. Kauser:Bayer: Employment. Weisel:Bayer: Research Funding.

scholarly journals Bovine Heparin Compared to Porcine Heparin to Demonstrate Bioequivalence

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1253-1253
Author(s):  
Marco Khiella ◽  
Walter Jeske ◽  
Jeanine Walenga ◽  
Omer Iqbal ◽  
Rajan Laddu ◽  
...  
Keyword(s):  
Whole Blood ◽  
Thrombin Generation ◽  
Anticoagulant Activity ◽  
Maximum Amplitude ◽  
Clot Formation ◽  
K Value ◽  
Significant Difference ◽  
Heparin Monitoring ◽  
The U.S

Abstract Introduction: Heparin prevents blood clots from forming in patients undergoing heart surgeries, dialysis, multiple other procedures, and for medical treatment of thrombosis such as associated with cancer. Currently, all heparin products in the U.S. are derived from the intestinal mucosa of pigs. Seventy-five percent of the crude porcine heparin used to make the active pharmaceutical ingredient (API) comes from outside the U.S., with a majority originating from China. Reintroduction of bovine heparin into the U.S. market would expand sources for this critical drug, thus addressing concerns about potential shortages and product adulteration. This study was undertaken to determine the bioequivalence of bovine and porcine heparins using assays relevant to the clinical setting. The assays used in this study were chosen because they overcome limitations of the conventional APTT for heparin monitoring. Selected TEG and ACT assays use whole blood which better simulates physiologic conditions and assesses the full in vitro anticoagulation potential of heparin; these assays are also routinely used clinically for heparin monitoring. The thrombin generation assay is state-of-the-art for hemostatic clinical lab testing, and it provides a more sensitive endpoint of the final generation of thrombin once coagulation is activated. Heparins were studied at concentrations used clinically and tested by assays sensitive to these concentrations. Methods: Bovine heparin API (BH; 7 lots) and US clinical grade porcine heparin (PH: 3 lots) were tested in parallel using recalcified whole blood thromboelastography (TEG; Haemonetics), celite activated clotting time (ACT; Hemochron), and thrombin generation (TGA; Diapharma). Fresh blood was obtained from healthy volunteers under an IRB approved protocol (n=6 per group). Previous work from our lab (Jeske W, Thrombosis & Hemostasis Societies of North America, P57, 2018) identified a weaker potency of BH than PH when compared on an equigravimetric basis in pharmacopeial assays; however, equivalent potency could be obtained when BH was standardized against PH on a unitage basis. In this study, heparins were studied on both a gravimetric and a unitage basis for a comprehensive evaluation. The potency of the BH was determined by pharmacopeial compliant anti-Xa and anti-IIa chromogenic assays cross-referenced to the porcine USP Heparin Reference Standard. Results: All results are depicted in Table 1. For the TEG, the R value, time of latency from start to initial fibrin formation, and the K value, time to achieve a defined clot strength due to thrombin generation and platelet activation, bovine heparin and porcine heparin did not demonstrate a significant difference in anticoagulant activity. The TEG angle, a measure of the speed of fibrin build-up and cross-linking (clot strengthening or rate of clot formation), and the maximum amplitude (MA) value, a function of the maximum of fibrin and platelet binding representing the strongest point of fibrin clot formation, also revealed no significant difference between bovine and porcine heparin anticoagulant activity. For the ACT, at concentrations of 10 µg/mL and 25 µg/mL, there were no statistically significant differences between BH and PH. For the TGA, measuring the time delay until the initiation of thrombin generation following tissue factor (TF) activation, the highest amount of thrombin generated after TF activation, and the total amount of thrombin generated after TF activation (AUC), showed a trend that PH was more potent than BH, but wide variation in the results did not allow for statistical differences to be identified. Conclusion: The results of this investigation demonstrate that bovine heparin produces an equivalent anticoagulant activity as porcine heparin in the TEG, ACT, and TGA assay systems. The equivalent ACT results, in particular, were unexpected since gravimetric amounts of heparins were evaluated. As for all heparins, standardization of bovine heparin in accordance with the process used for porcine heparin will assure equivalent anticoagulant activity among bovine and porcine heparins in whole blood, plasma-based, and pharmacopeial assays. This study further demonstrates that the current assays used to monitor porcine heparin can be similarly used to monitor bovine heparin. Disclosures Walenga: Eurofarma: Research Funding.

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