Clot formation and fibrinolysis assays reveal functional differences among hemostatic agents in hemophilia A plasma
© 2024 The Author(s)..
Background: Measuring the activity of hemostatic agents used to treat hemophilia A often requires drug-specific assays. In vitro assays show hemophilic clots have abnormal characteristics, including prolonged clotting time and decreased resistance to fibrinolysis. The ability of certain agents to correct these parameters in vitro is associated with hemostatic efficacy in vivo.
Objectives: To compare effects of established and emerging hemostatic agents on clot formation and fibrinolysis in hemophilia A plasma.
Methods: Pooled and individual hemophilia A platelet-poor plasmas were spiked with replacement (recombinant factor VIII [rFVIII], PEGylated rFVIII, polysialylated rFVIII, and porcine rFVIII) or bypassing (emicizumab, rFVIIa, and activated prothrombin complex concentrate) products. Effects on tissue factor-initiated clot formation and fibrinolysis were measured by turbidity.
Results: Compared to normal pooled plasma, hemophilia-pooled plasma showed reduced clot formation and increased fibrinolysis, and all replacement agents improved these characteristics. rFVIII and PEGylated rFVIII produced similar effects at similar concentrations, whereas polysialylated rFVIII produced slightly higher and porcine rFVIII slightly lower effects at these concentrations. Bypassing agents enhanced clot formation and stability, but patterns differed from replacement agents. The clotting rate showed a concentration-response relationship for all agents. High concentrations of all products produced effects that exceeded the normal range in at least some parameters. Responses of individual donors varied, but all agents improved clot formation and stability in all donors tested.
Conclusion: Clotting and fibrinolysis assays reveal hemostatic effects of replacement and bypassing therapies at clinically relevant concentrations. These assays may help characterize hemostatic agents and optimize dosing.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
|---|---|
| Enthalten in: |
Research and practice in thrombosis and haemostasis - 8(2024), 1 vom: 26. Jan., Seite 102337 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Holle, Lori A [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Clot |
|---|
| Anmerkungen: |
Date Revised 02.03.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1016/j.rpth.2024.102337 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369159195 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369159195 | ||
| 003 | DE-627 | ||
| 005 | 20240302232740.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240301s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.rpth.2024.102337 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1314.xml |
| 035 | |a (DE-627)NLM369159195 | ||
| 035 | |a (NLM)38426025 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Holle, Lori A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clot formation and fibrinolysis assays reveal functional differences among hemostatic agents in hemophilia A plasma |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 02.03.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2024 The Author(s). | ||
| 520 | |a Background: Measuring the activity of hemostatic agents used to treat hemophilia A often requires drug-specific assays. In vitro assays show hemophilic clots have abnormal characteristics, including prolonged clotting time and decreased resistance to fibrinolysis. The ability of certain agents to correct these parameters in vitro is associated with hemostatic efficacy in vivo | ||
| 520 | |a Objectives: To compare effects of established and emerging hemostatic agents on clot formation and fibrinolysis in hemophilia A plasma | ||
| 520 | |a Methods: Pooled and individual hemophilia A platelet-poor plasmas were spiked with replacement (recombinant factor VIII [rFVIII], PEGylated rFVIII, polysialylated rFVIII, and porcine rFVIII) or bypassing (emicizumab, rFVIIa, and activated prothrombin complex concentrate) products. Effects on tissue factor-initiated clot formation and fibrinolysis were measured by turbidity | ||
| 520 | |a Results: Compared to normal pooled plasma, hemophilia-pooled plasma showed reduced clot formation and increased fibrinolysis, and all replacement agents improved these characteristics. rFVIII and PEGylated rFVIII produced similar effects at similar concentrations, whereas polysialylated rFVIII produced slightly higher and porcine rFVIII slightly lower effects at these concentrations. Bypassing agents enhanced clot formation and stability, but patterns differed from replacement agents. The clotting rate showed a concentration-response relationship for all agents. High concentrations of all products produced effects that exceeded the normal range in at least some parameters. Responses of individual donors varied, but all agents improved clot formation and stability in all donors tested | ||
| 520 | |a Conclusion: Clotting and fibrinolysis assays reveal hemostatic effects of replacement and bypassing therapies at clinically relevant concentrations. These assays may help characterize hemostatic agents and optimize dosing | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a clot | |
| 650 | 4 | |a factor VIII | |
| 650 | 4 | |a fibrinolysis | |
| 650 | 4 | |a hemophilia | |
| 650 | 4 | |a hemostasis | |
| 700 | 1 | |a Pantazis, Jacob C |e verfasserin |4 aut | |
| 700 | 1 | |a Turecek, Peter L |e verfasserin |4 aut | |
| 700 | 1 | |a Wolberg, Alisa S |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Research and practice in thrombosis and haemostasis |d 2017 |g 8(2024), 1 vom: 26. Jan., Seite 102337 |w (DE-627)NLM277257743 |x 2475-0379 |7 nnns |
| 773 | 1 | 8 | |g volume:8 |g year:2024 |g number:1 |g day:26 |g month:01 |g pages:102337 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.rpth.2024.102337 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 8 |j 2024 |e 1 |b 26 |c 01 |h 102337 | ||