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A ROTEM method using APTT reagent and tissue factor as the clotting activators may better define bleeding heterogeneity in moderate or severe haemophilia A (part I: Study in plasma samples).
Thromb Res 2018; 171:7-13TR

Abstract

Bleeding heterogeneity observed in haemophilia A (HA) may attribute to that the available monitoring methods cannot appropriately reflect the coagulation profile. The present study aimed to develop a global approach by changing the clotting initiation way in rotational thromboelastometry (ROTEM) assay. ROTEM was run in Factor VIII (FVIII)-immune-depleted plasma to which different concentrations of recombinant VIII (rFVIII) had been added, and also in 31 patients with HA. The clotting activators were APTT reagent (1.2 × 10-3 of the dose used in the original APTT method) and recombinant tissue factor (0.02 pmol/L). In FVIII-immune-depleted plasma spiked with rFVIII, maximum velocity of coagulation reliably mirrored the rFVIII levels. This dose-response disappeared after the samples were pre-incubated with an antibody against TFPI, protein S, activated prothrombin complex concentrate or rFVIIa known to favour the extrinsic activation. In the HA patients with FVIII 0-0.21 IU/mL, APTT and ROTEM outcomes varied in significant correlations to FVIII activity; however, this correlation became non-significant when only samples with FVIII 0-0.05 IU/mL were included.

Conclusions:

The decreased coagulation in HA mostly result from deficiency/absence of FVIII; other pro-/anti-thrombotic proteins are also influential. The multiple effects may cause a mismatch between bleeding phenotype and FVIII concentrations. The ROTEM assay with the clotting activators i.e., tiny doses of APTT reagent and TF are more effective than the original APTT method as regards the assay sensitivity to influence by VIII activity and also to that by other pro-/anti-thrombotic proteins, showing the whole coagulation picture behind the phenotypic heterogeneity in HA.

Authors+Show Affiliations

Dept. of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. Electronic address: heshu9999@gmail.com.Coagulation Unit, Haematology Centre, Karolinska University Hospital, Dept. of Medicine, Karolinska Institutet, Stockholm, Sweden.Paediatric Coagulation Unit, Dept. of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.Dept. of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.Dept. of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.Dept. of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.Dept. of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden; Coagulation Research Unit, Dept. of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.Coagulation Unit, Haematology Centre, Karolinska University Hospital, Dept. of Medicine, Karolinska Institutet, Stockholm, Sweden.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30216822

Citation

He, Shu, et al. "A ROTEM Method Using APTT Reagent and Tissue Factor as the Clotting Activators May Better Define Bleeding Heterogeneity in Moderate or Severe Haemophilia a (part I: Study in Plasma Samples)." Thrombosis Research, vol. 171, 2018, pp. 7-13.
He S, Eelde A, Petrini P, et al. A ROTEM method using APTT reagent and tissue factor as the clotting activators may better define bleeding heterogeneity in moderate or severe haemophilia A (part I: Study in plasma samples). Thromb Res. 2018;171:7-13.
He, S., Eelde, A., Petrini, P., Wallen, H., Gabrielsson, L., Svensson, J., ... Holmström, M. (2018). A ROTEM method using APTT reagent and tissue factor as the clotting activators may better define bleeding heterogeneity in moderate or severe haemophilia A (part I: Study in plasma samples). Thrombosis Research, 171, pp. 7-13. doi:10.1016/j.thromres.2018.09.041.
He S, et al. A ROTEM Method Using APTT Reagent and Tissue Factor as the Clotting Activators May Better Define Bleeding Heterogeneity in Moderate or Severe Haemophilia a (part I: Study in Plasma Samples). Thromb Res. 2018;171:7-13. PubMed PMID: 30216822.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A ROTEM method using APTT reagent and tissue factor as the clotting activators may better define bleeding heterogeneity in moderate or severe haemophilia A (part I: Study in plasma samples). AU - He,Shu, AU - Eelde,Anna, AU - Petrini,Pia, AU - Wallen,Håkan, AU - Gabrielsson,Lena, AU - Svensson,Jan, AU - Blombäck,Margareta, AU - Holmström,Margareta, Y1 - 2018/09/05/ PY - 2018/05/16/received PY - 2018/08/29/revised PY - 2018/09/04/accepted PY - 2018/9/15/pubmed PY - 2019/1/15/medline PY - 2018/9/15/entrez KW - Bleeding heterogeneity KW - Clotting activator KW - Coagulation profile KW - Haemophilia A KW - ROTEM SP - 7 EP - 13 JF - Thrombosis research JO - Thromb. Res. VL - 171 N2 - Bleeding heterogeneity observed in haemophilia A (HA) may attribute to that the available monitoring methods cannot appropriately reflect the coagulation profile. The present study aimed to develop a global approach by changing the clotting initiation way in rotational thromboelastometry (ROTEM) assay. ROTEM was run in Factor VIII (FVIII)-immune-depleted plasma to which different concentrations of recombinant VIII (rFVIII) had been added, and also in 31 patients with HA. The clotting activators were APTT reagent (1.2 × 10-3 of the dose used in the original APTT method) and recombinant tissue factor (0.02 pmol/L). In FVIII-immune-depleted plasma spiked with rFVIII, maximum velocity of coagulation reliably mirrored the rFVIII levels. This dose-response disappeared after the samples were pre-incubated with an antibody against TFPI, protein S, activated prothrombin complex concentrate or rFVIIa known to favour the extrinsic activation. In the HA patients with FVIII 0-0.21 IU/mL, APTT and ROTEM outcomes varied in significant correlations to FVIII activity; however, this correlation became non-significant when only samples with FVIII 0-0.05 IU/mL were included. Conclusions: The decreased coagulation in HA mostly result from deficiency/absence of FVIII; other pro-/anti-thrombotic proteins are also influential. The multiple effects may cause a mismatch between bleeding phenotype and FVIII concentrations. The ROTEM assay with the clotting activators i.e., tiny doses of APTT reagent and TF are more effective than the original APTT method as regards the assay sensitivity to influence by VIII activity and also to that by other pro-/anti-thrombotic proteins, showing the whole coagulation picture behind the phenotypic heterogeneity in HA. SN - 1879-2472 UR - https://www.unboundmedicine.com/medline/citation/30216822/A_ROTEM_method_using_APTT_reagent_and_tissue_factor_as_the_clotting_activators_may_better_define_bleeding_heterogeneity_in_moderate_or_severe_haemophilia_A__part_I:_Study_in_plasma_samples__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0049-3848(18)30525-5 DB - PRIME DP - Unbound Medicine ER -