Interspecies differences in coagulation profile

SummaryMany animals are used in research on blood coagulation and fibrinolysis, but the relevance of animal models to human health is often questioned because of differences between species. The objective was to find an appropriate animal species , which mimics the coagulation profile in humans most adequately. Species differences in the coagulation profile with and without thrombin stimulation in vitro were assessed in whole blood by Rotation Thromboelastometry (ROTEM). Endogenous thrombin generation was measured in platelet-poor plasma. Measurements were performed in blood from five different species: humans, rats, pigs, sheep and rabbits. In humans and sheep, the clotting time (ROTEM) was in the same range with or without thrombin stimulation and a 100-fold lower dose of thrombin (0.002 IU) was required to cause a shortening in the clotting time as compared to rats, pigs and rabbits (0.2 IU) (p<0.05).Similarly, the endogenous thrombin potential (ETP) was in the same range in humans and sheep. The maximum clot firmness with or without thrombin stimulation was similar in rabbits and humans. The maximum lysis with or without thrombin stimulation was similar in humans and pigs. Significant species differences exist in the coagulation profile with or without thrombin stimulation. Most importantly, sheep had a clotting time most similar to humans and could thus be a suitable species for translational coagulation studies. Moreover, our findings confirm the potential usefulness of pigs as an experimental species to study fibrinolytic pathway and support the usefulness of rabbits as a species for examining platelets.

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Generic and Branded Versions of Argatroban Exhibit Differential Anticoagulant Effects In Whole Blood, Plasma Based Assays and Thrombin Generation Assays

Blood ◽

10.1182/blood.v116.21.5129.5129 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5129-5129

Author(s):

Jawed Fareed ◽

Debra Hoppensteadt ◽

Omer Iqbal ◽

Jeanine M. Walenga ◽

Bruce E Lewis

Keyword(s):

Protein Interactions ◽

Whole Blood ◽

Thrombin Generation ◽

Conflicts Of Interest ◽

Anticoagulant Effect ◽

Thrombin Time ◽

Clotting Time ◽

Generic Products

Abstract Abstract 5129 Several generic versions of argatroban) (Mitsubishi; Tokyo, Japan) have been introduced in Japan (Argaron, Gartban, Slovastan). In addition, other generic versions of argatroban are being considered by the European and North American regulatory bodies. While the generic versions of argatroban exhibit similar antithrombin potency (Ki values), because of the differential compositional variations their anticoagulant effects in whole blood systems may differ due to their cellular and plasmatic protein interactions. Branded and generic versions of argatroban may exhibit differential anticoagulant actions in the whole blood and plasma based assays due to their differential interactions with blood cells, platelets and plasma proteins. Three generic versions of argatroban that are commercially available in Japan namely Argaron, Gartban and Slovastan and a powdered version of generic argatroban (Lundbeck) were compared with the branded argatroban. Native whole blood thrombelastographic (TEG) analysis was carried out at 0.1 ug/mL, the Activated Clotting Time (ACT) assay was carried out in a concentration range of 0–10 ug/mL, and such coagulation tests as the PT/INR, aPTT, Heptest, and calcium thrombin time were performed. Plasma retrieved from the supplemented whole blood was also assayed. Ratios of the clotting time test values from whole blood and plasma were calculated. Retrieved plasma samples were also assayed in the thrombin generation assays (TGA). All of the different versions of argatroban produced a concentration dependent anticoagulant effect in the native whole blood TEG and ACT. In the TEG, while argatroban and Slovastan showed a similar effect, Gartban, Argaron and a powdered generic showed weaker effects. Argatroban was also different in the ACT assay. At a concentration of 5 ug/ml the ACTs were, Arg 340+15.2 secs, S 297+10.5 secs, G 292.0+19.1 secs and A 285.2+21.7 secs. In the citrated whole blood systems, all agents produced a concentration dependent anticoagulant effect; however, the generic versions produced a stronger anticoagulant effect in comparison to branded argatroban (p<0.001). In the PT assay at 5 ug/mL, argatroban showed 32 ± 3 sec vs 40–50 sec for the generic products. Similarly in the aPTT, Heptest and thrombin time tests argatroban was weaker than the generic products. Differences among generic versions were also evident. Similar results were obtained in the retrieved plasma, however the ratio of whole blood over plasma varied from product to product. The IC50 of the generic and branded argatrobans in the TGA were also different. These results show that while in the thrombin inhibition assays generic and branded argatroban may show similar effects, these agents exhibit assay dependent differences in the whole blood and plasma based assays. Such differences may be more evident in the in vivo studirs where endothelial cells and other interactions may contribute to product individuality. Therefore, based on the in vitro antiprotease assays, generic argatrobans may not be considered equivalent and require a multi-parametric study. Currently available generic argatrobans may not be equivalent in the in vivo anticoagulant effects. Therefore, clinical validation of the clinical equivalence for these drugs is warranted. Disclosures: No relevant conflicts of interest to declare.

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Coagulation assessment by rotation thrombelastometry in normal pregnancy

Thrombosis and Haemostasis ◽

10.1160/th08-06-0386 ◽

2009 ◽

Vol 101 (04) ◽

pp. 755-761 ◽

Cited By ~ 97

Author(s):

Nicolas Carrabin ◽

Mehdi Benchaib ◽

Oriane Fontaine ◽

Albrice Levrat ◽

Denis Massignon ◽

...

Keyword(s):

Pregnant Women ◽

Point Of Care ◽

Normal Pregnancy ◽

Clot Lysis ◽

Clotting Time ◽

Intrinsic Pathway ◽

Extrinsic Pathway ◽

Coagulation Tests ◽

Maximum Clot Firmness

SummaryWe analysed changes in coagulation during normal pregnancy with a novel point-of-care device based on thrombelastometry (ROTEM®). We compared the results obtained with those of standard coagulation tests in 104 patients: 20 non-pregnant women (controls) and 84 women in the first (T1, n=17), second (T2, n=9) and third (T3, n=58) trimesters of pregnancy. We measured the clotting time (CT), the maximum clot firmness (MCF), the early clot amplitude at 5 and 15 minutes (CA5, CA15) and the clot lysis index (CLI30) with four tests containing specific reagents. (a) The INTEM® test involving ellagic acid activated the intrinsic pathway and (b) the EXTEM® test using tissue factor triggered the extrinsic pathway; (c) The FIBTEM® test based on a platelet inhibitor (cytochalasin D) evaluated the contribution of fibrinogen to clot formation and (d) the APTEM® test was similar to the EXTEM but was based on inhibition in vitro of fibrinolysis by aprotinin. CT and CLI30 were not significantly modified during pregnancy whereas MCF, CA5 and CA15 (INTEM, EXTEM, FIBTEM) increased significantly between the second and third trimesters (e.g. median [interquartile range]: MCF-FIBTEM, 13 [11–16] mm vs. 19 [17–23] mm, respectively, in controls and T3, p< 0.001). EXTEM values were not significantly different from those measured with APTEM. There were significant correlations between the results obtained with ROTEM and those from standard coagulation tests. ROTEM analysis showed a marked increase in coagulability during normal pregnancy. ROTEM values may serve as the basis for future studies in pregnant women.

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Pharmacodynamic markers in the early clinical assessment of otamixaban, a direct factor Xa inhibitor

Thrombosis and Haemostasis ◽

10.1160/th05-05-0347 ◽

2005 ◽

Vol 94 (12) ◽

pp. 1156-1163 ◽

Cited By ~ 16

Author(s):

Marie-Laure Ozoux ◽

Valeria Chu ◽

Kelly Simcox ◽

Vanessa Marks ◽

Geneviève Freyburger ◽

...

Keyword(s):

Thrombin Generation ◽

Plasma Concentrations ◽

Factor Xa ◽

The Novel ◽

Direct Factor ◽

Clotting Time ◽

Pharmacodynamic Markers ◽

High Concentrations ◽

Male Subjects

SummaryThis manuscript reports the assessment of pharmacodynamic (PD) markers of anti-coagulation in the first-in-man study with the novel direct Factor Xa (FXa) inhibitor, otamixaban, with a brief description of safety and pharmacokinetic (PK) findings. The study comprised ten consecutive parallel groups of healthy male subjects (6 active, 2 placebo per group). Eight groups received escalating intravenous doses of otamixaban as 6-hour infusions (1.7 to 183 μg/kg/h) and two groups received a bolus dose (30 or 120 μg/kg) with a 6-hour infusion (60 or 140 μg/ kg/h, respectively). PD markers included anti-FXa activity and clotting time measurements, i.e. activated Thromboplastin Time (aPTT), ProthrombinTime (PT), Heptest® ClottingTime (HCT), and Russell’s Viper Venom-induced clotting Time (RVVT). In addition, Endogenous Thrombin Potential (ETP) was assessed in the bolus-plus-infusion dose groups. Otamixaban was well tolerated. Otamixaban plasma concentrations increased with escalating dose, were maximal at the end-of-infusion (Ceoi), and decreased rapidly as the infusion was stopped. Anti-FXa activity coincided with otamixaban plasma concentrations and clotting time measurements followed the same pattern. Maximal changes from baseline at Ceoi were 1.9 ± 0.2 for aPTT, 2.0 ± 0.2 for PT, 5.1 ± 0.6 for HCT, and 4.5 ± 1.2 for RVVT. Otamixaban inhibited thrombin generation (24% decrease in ETP) and a delay in thrombin generation was noticed in vitro at high concentrations.

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The Inhibitory Effect of Recombinant Human Soluble Thrombomodulin on Initiation and Extension of Coagulation

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614900 ◽

1999 ◽

Vol 82 (12) ◽

pp. 1687-1693 ◽

Cited By ~ 54

Author(s):

Emika Sugimoto ◽

Minako Sata ◽

Toshio Asano ◽

Mitsunobu Mohri

Keyword(s):

Protein C ◽

Thrombin Generation ◽

Anticoagulant Activity ◽

Inhibitory Effect ◽

The Other ◽

Clotting Time ◽

Soluble Thrombomodulin ◽

Factor Va ◽

Recombinant Human Soluble Thrombomodulin

SummaryRecombinant human soluble thrombomodulin (rhsTM) was compared with various anticoagulants for in vitro anticoagulant effects on thrombin generation, clotting time, and thromboelastography. rhsTM as well as APC reduced the level of the peak of the thrombin generation curve, but we did not observe any time-delay to reach the peak. This effect of rhsTM was diminished in PC-deficient plasma and was closely associated with the inhibitory effect on prothrombinase and factor Va. On the other hand, hirudin and argatroban delayed the time to reach the level of the peak, without reducing it. rhsTM and other anticoagulants except for activated protein C (APC) were found to have concentration-dependent anticoagulant activity by conventional clotting tests. However, the concentration of rhsTM for clotting time was slightly affected by anti-protein C antibody. Moreover, the concentration of rhsTM required to inhibit thrombin activity directly was 50 times higher than that needed to inhibit thrombin generation. The effect of rhsTM on clot development was compared with that of other anticoagulants by thromboelastography; rhsTM reduced the growth of the clot but had little effect on the time to activate clotting, while the other anticoagulants had the opposite effect. This effect of rhsTM was completely abolished by the addition of anti-protein C or anti-protein S antibody.These findings suggest that rhsTM attenuates blood clotting by reducing the level of generated thrombin through protein C activation and subsequent factor Va inactivation and prothrombinase inhibition.

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Protein S Regulates Factor IXa in the Absence and Presence of Factor VIIIa Independently of Activated Protein C

Blood ◽

10.1182/blood.v118.21.1197.1197 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1197-1197

Author(s):

Rinku Majumder ◽

Rima Chattopadhyay ◽

Tanusree Sengupta

Keyword(s):

Protein C ◽

Thrombin Generation ◽

Anticoagulant Activity ◽

Activated Protein C ◽

Protein S ◽

Activity Measurement ◽

Clotting Time ◽

Thrombotic Risk ◽

Increased Risk

Abstract Abstract 1197 Coagulation is a finely tuned process. During thrombin formation, several anticoagulant reactions are initiated to prevent systematic activation of coagulation, and impairment of anticoagulant activity causes an increased risk of venous thrombosis. One such anticoagulant factor is protein S, deficiencies of which have been linked to venous and arterial thrombosis. While protein S has been studied for over three decades, the precise role this protein plays in attenuating the hemostatic response is far from clear. Protein S is a vitamin K-dependent plasma protein that functions in feedback regulation of thrombin generation. Protein S was initially identified as a cofactor for activated protein C (APC) but later it was observed that there is only a 3–10 fold increase in APC activity in the presence of protein S. Plasma coagulation assays in the absence of APC suggest that protein S may have other anticoagulant role(s). We report here an anticoagulant activity of Protein S mediated by inhibition of fIXa in the absence and presence of fVIIIa independent of APC. Although an APC-independent anticoagulant activity has been reported for protein S interacting with fVIIIa, no study has shown that the inhibitory effect of protein S is mediated through its interaction with fIXa, thus making our observations novel and significant. Moreover, previous studies that reported an interaction between fVIIIa and protein S were performed with low amounts of phospholipid, a condition that produces activity measurement artifacts due to the presence of active protein S multimers. We used both ex vivo (plasma studies) and in vitro methods at high phospholipid (100–200 micro molar) concentration to determine whether and how the intrinsic pathway of blood coagulation is regulated by protein S. We obtained the following results: 1) activated partial thromboplastin time (aPTT) assays with protein S-supplemented plasma confirmed that protein S prolongs clotting time, and a normal clotting time was restored with addition of anti-protein S antibody, 2) a modified aPPT assay with fIX-deficient plasma confirmed that protein S affects fIX-initiated clotting time, 3) thrombin generation assay through fIXa/fVIIIa pathway, initiated with a limiting amount of tissue factor (TF), was regulated by protein S, 4) in vitro studies with fIXa/fVIIIa and protein S in the presence of phosphatidylserine (PS) vesicles showed ∼40% and ∼65% inhibition in the activity of fIXa in the absence and presence of fVIIIa, respectively, and 5) protein S altered only the KM for fX activation by fIXa but altered both kcat and KM for fX activation by fIXa and fVIIIa. Our findings underscore the central role of protein S in regulation of coagulation. We anticipate these results will unravel important implications for the evaluation of thrombotic risk associated with protein S-deficiency. Disclosures: No relevant conflicts of interest to declare.

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Thrombin generation and rotational thromboelastometry in the healthy adult population

Hämostaseologie ◽

10.5482/hamo-14-08-0033 ◽

2015 ◽

Vol 35 (02) ◽

pp. 181-186 ◽

Cited By ~ 9

Author(s):

T. Schneider ◽

T. Siegemund ◽

R. Siegemund ◽

S. Petros

Keyword(s):

Tissue Factor ◽

Linear Correlation ◽

Thrombin Generation ◽

Alpha Angle ◽

Lag Time ◽

Published Data ◽

Peak Time ◽

Clotting Time ◽

Rotational Thromboelastometry ◽

Maximum Clot Firmness

SummaryPublished data on thrombin generation variables and their correlation with thrombo - elastometry in the healthy population are scarce. This study aimed at assessing thrombin generation in adults and its correlation to classical rotational thromboelastometry (ROTEM).Thrombin generation was measured in platelet-poor plasma from healthy volunteers using the calibrated automated thrombogram (CAT) with 1 and 5 pmol/l tissue factor final concentration. Lag time, thrombin peak, time to thrombin peak and endogenous thrombin potential (ETP) were analyzed. ROTEM was performed without activator (NATEM) and data for clotting time, alpha angle, clot formation time and maximum clot firmness were correlated with those of thrombin generation.Altogether 132 persons (72 men, 60 women; median age: 48.0 years) were included. There was a positive non-linear correlation for age versus lag time (p < 0.001) and time to peak (p = 0.001), and almost linear correlation for age versus thrombin peak (p = 0.024) and ETP (p = 0.001), although with a moderate regression slope. Regarding ROTEM, there was a positive correlation between age and maximum clot firmness and alpha angle (p = 0.001), but a negative correlation between age and clotting time (p = 0.039). Comparing both assays, thrombin peak and ETP measured with a final tissue factor concentration of 5 pmol/l correlated significantly with alpha angle and maximum clot firmness.The age-related changes in CAT and ROTEM variables among adults are not linear. There is a significant correlation, although with a moderate slope, between data from CAT measured with 5 pmol/l tissue factor and ROTEM.

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Large species differences in the pattern of snPI RNA which can distinguish ape from human.

The Journal of Cell Biology ◽

10.1083/jcb.80.3.778 ◽

1979 ◽

Vol 80 (3) ◽

pp. 778-783 ◽

Cited By ~ 4

Author(s):

B J Benecke ◽

S Penman

Keyword(s):

Animal Species ◽

Species Differences ◽

Cell Types ◽

Large Species ◽

Closely Related Species ◽

Precursor Rna ◽

Polymerase I ◽

Ribosomal Precursor ◽

Different Cell Types

The snPI RNA species are a recently described set of molecules whose sizes range from 5S to 10S. They can be labeled in vitro in isolated nuclei and are apparently formed by an RNA polymerase I type of activity. However, in contrast to ribosomal precursor RNA, the usual polymerase I product, they are not found in the nucleolus but rather are located in the nucleoplasm. The snPI RNAs have been found in all mammalian cell types studied. The spectrum seen in gel electrophoresis is unique to each animal species studied but is essentially the same in different cell types within a species. The differences in snPI patterns are quite large between even closely related species and are clearly distinguishable in gorilla and human cells.

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Validation of the Bioequivalence of USP Potency Adjusted Porcine, Ovine, and Bovine Heparins

Blood ◽

10.1182/blood-2020-142861 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 6-6

Author(s):

Nausheen Baig ◽

Ahmed Kouta ◽

Walter Jeske ◽

Debra Hoppensteadt ◽

Jeanine Walenga ◽

...

Keyword(s):

Thrombin Generation ◽

Conflicts Of Interest ◽

Area Under The Curve ◽

Anticoagulant Effect ◽

Clotting Time ◽

Kinetic Assay ◽

Pharmaceutical Ingredients ◽

Biologic Effects ◽

Mass Basis

Introduction: Currently, there is a shortage of porcine heparin due to several factors such as limited availability of porcine mucosa, supply chain issues, and increased usage due to COVID-19. This has warranted the development of heparin from alternate sources such as bovine and ovine mucosa which is abundantly available for this purpose. On a mass basis, commercially available porcine heparins exhibit a similar potency (200 units/mg) to their ovine counterpart (190 units/mg) and a higher potency in contrast to their bovine counterpart (130-150 units/mg). Therefore, at gravimetric levels, the porcine heparins exhibit stronger biochemical and pharmacological effects in various laboratory assays in comparison to bovine heparin and similar effects in comparison to ovine heparins. Since heparin is standardized in biologic units and cross referenced against USP or EP Standard, it is hypothesized that potency equated porcine, ovine, and bovine heparin will exhibit similar biologic activities in laboratory assays carried out in the in vitro setting. The purpose of this study is to compare the biologic properties of the porcine, ovine, and bovine heparin at USP potency equated levels in standardized laboratory assays. Materials and Methods: Active pharmaceutical ingredients (API) of porcine mucosal heparin (200 units/mg) of U.S. origin was commercially obtained from Medefil Inc. (Glendale Heights, IL). Ovine heparin was obtained from Ronnsi Pharmaceutical (Jiangsu, China). Bovine heparin (140 units/mg) was obtained from Kin Master Pharmaceuticals (Posso Fundo, Brazil). All heparins were diluted at a concentration of 100 units/mL in saline. The anticoagulant effect of all heparins were evaluated using the whole blood clotting assays such as the ACT and thromboelastographic methods. Heparins were diluted in citrated human plasma yielding a final concentration range of 0-1 unit/mL. Clot based assays such as aPTT, TT, and prothrombinase induced clotting time (PiCT) were measured. Thrombin generation inhibition assay was carried out using a kinetic assay (CAT system, Diagnositca Stago, Paris, France). Protamine and heparinase neutralization profiles of these agents were also investigated in the plasma-based systems. These assays were then repeated at gravimetric dosages at final concentrations of 0-10 ug/mL. The results collected from these trials were then mathematically converted to units and compared to the results collected from the potency adjusted trials. All results were tabulated and compared, and applicable statistical methods were applied. Results: The USP potency adjusted heparin exhibited comparable anticoagulant effects in both the ACT and TEG assays. At equigravimetric levels porcine and ovine heparins produced comparable anticoagulant effects and bovine heparin produced weaker anticoagulant effect in both assays. In the citrated plasma supplementation studies, all drugs produced similar anticoagulant effects at potency adjusted dosages. In the chromogenic anti-Xa and anti-IIa assays, the behaviors of the agents were also comparable. In the thrombin generation assays, in terms of peak thrombin generation, area under the curve, and lag time, the porcine, ovine, and bovine heparins showed comparable effects. The protamine neutralization profiles of the porcine, ovine, and bovine heparin exhibited variable assay dependent results. Potency adjusted bovine heparin required higher amount of protamine for the complete neutralization of the biologic effects in comparison to the porcine heparin. At gravimetric concentrations, bovine heparins exhibited lower potencies than both the porcine and ovine heparins, which produced similar results. Summary and Conclusion: These results show that at potency adjusted concentrations, the porcine, ovine, and bovine heparin exhibit comparable biochemical and anticoagulant responses in the plasma-based systems. Therefore, the hypothesis that potency equated porcine, ovine, and bovine heparins exhibit comparable biochemical and anticoagulant activities is validated. Thus, the proposed approach to standardize heparins against a common standard in a biologic assay such as the USP method is valid. Furthermore, these results warrant regulatory considerations to fast track the review process for the re-introduction of bovine heparin and approval of bovine heparin as a biosimilar anticoagulant to porcine heparin. Disclosures No relevant conflicts of interest to declare.

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Four-Factor Prothrombin Complex Concentrate (4F-PCC) Effectively Reverses Rivaroxaban Induced Bleeding in a Rabbit Model of Acute Bleeding

Blood ◽

10.1182/blood.v124.21.4220.4220 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4220-4220

Author(s):

Eva Herzog ◽

Jochen Mueller-Cohrs ◽

Franz Kaspereit ◽

Wilfried Krege ◽

Peter Niebl ◽

...

Keyword(s):

Thrombin Generation ◽

Blood Clotting ◽

Prothrombin Complex Concentrate ◽

Rabbit Model ◽

Off Label Use ◽

Clotting Time ◽

Acute Bleeding ◽

Off Label

Abstract Rivaroxaban is an oral, selective direct factor Xa inhibitor approved for several indications in patients at risk of thrombotic events. One limitation of this agent is the lack of data pertaining to its reversal in situations where urgent response is critical (e.g. acute bleeding events or emergency surgery). This study therefore evaluated the effectiveness of a four-factor prothrombin complex concentrate (4F-PCC; Beriplex® P/N, Kcentra®, CSL Behring), for the reversal of rivaroxaban-associated bleeding in an in vivo rabbit model of acute bleeding. In addition, the study evaluated the correlation between in vitro coagulation parameters and haemostasis in vivo in order to gain more information on the predictivity of in vitro markers for effective bleeding reversal. Administration of single intravenous doses of rivaroxaban (150–450 μg/kg) resulted in increased and prolonged bleeding following standardised kidney injury compared to a vehicle treated control group as determined by measurements of total blood loss and time required to achieve full hemostasis. Subsequent treatment with 4F-PCC (25−100 IU/kg) resulted in a dose-dependent reversal of rivaroxaban-associated bleeding signals. Of the in vitro coagulation markers tested, thrombin generation (TGA) and whole blood clotting time (WBCT) correlated well with in vivo measures of PCC-mediated effects. Thrombin generation was highly reagent-dependent, with the assay initiated using tissue factor reagent being most sensitive to the anticoagulant effects induced by Rivaroxaban, while the phospholipid-only reagent being the most predictive of 4F-PCC mediated effective haemostasis in vivo. In summary, in a rabbit model of acute bleeding, 4F-PCC was able to effectively reduce bleeding to control levels following rivaroxaban 150 μg/kg and 300 μg/kg administrations. The 4F-PCC mediated bleeding reversal correlated best with the in vitro endpoints thrombin generation and whole blood clotting time. Disclosures Herzog: CSL Behring GmbH: Employment. Off Label Use: The use of Beriplex P/N for reversal of Rivaroxaban anticoagulation represents off-label use. Mueller-Cohrs:CSL Behring GmbH: Employment. Kaspereit:CSL Behring GmbH: Employment. Krege:CSL Behring GmbH: Employment. Niebl:CSL Behring GmbH: Employment. Doerr:CSL Behring GmbH: Employment. Schulte:CSL Behring GmbH: Employment. Dickneite:CSL Behring GmbH: Employment.

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Peculiar whole blood rotation thromboelastometry (Rotem) profile in 40 sideropenic anaemia patients

Thrombosis and Haemostasis ◽

10.1160/th08-04-0243 ◽

2008 ◽

Vol 100 (12) ◽

pp. 1106-1110 ◽

Cited By ~ 51

Author(s):

Luca Spiezia ◽

Claudia Radu ◽

Paolo Marchioro ◽

Diana Bertini ◽

Valeria Rossetto ◽

...

Keyword(s):

Linear Correlation ◽

Whole Blood ◽

Thrombin Generation ◽

Case Control Study ◽

Study Population ◽

And Gender ◽

Control Study ◽

Maximum Clot Firmness

SummaryThe ROtation ThromboElastoMetry analyser (ROTEM®, Pentapharm, Munich, Germany) is useful for studying whole blood (WB) clot formation and lysis.Reduction of haematocrit (HCT) has been reported to influence traditional thromboelastography parameters without compromising “in vitro” blood coagulation. We performed this case-control study to evaluate ROTEM profiles in sideropenic anaemia patients with different degrees of reduction of HCT levels. Forty consecutively referred patients with sideropenic anaemia were enrolled. A group of 40 healthy age and gender matched subjects acted as a control. The influence of HCT on ROTEM was assessed in the study population and in a model of artificially reconstituted blood with modified HCT values. Cases presented significantly increased levels of maximum clot firmness (MCF) as compared to controls (p<0.001) mimicking a sort of “hypercoagulable profile”. How-ever, thrombin generation tests failed to detect an increase in thrombin generation in cases as compared to controls. A statistically significant inverse linear correlation between HCT and MCF (p<0.0001) was found.In addition,ROTEM profiles following “in vitro” manipulation of HCT confirmed the inverse linear correlation between HCT and MCF found in the study population. In conclusion, the increased clot firmness found by ROTEM in anaemic patients is likely to be related to the method in itself rather than representing a marker of hypercoagulability “in vivo”.Since ROTEM is widely used by anaesthesiologists when deciding the optimisation of products supplementation during surgery,attention should be paid in the case of anaemic patients taking depending on the peculiar thrombo-elastography profile found.

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