Abstract Number: PB1183
Meeting: ISTH 2020 Congress
Background: Patients with a significant bleeding history and normal routine laboratory tests are labelled as having unclassified bleeding disorder (UBD). We have shown previously that enzymatically oxidised phosphatidylcholine
(12-HETE-PC), produced rapidly on platelet activation, supports thrombin generation whereas native PC does not.
Aims: We investigated whether the bleeding phenotype could be explained by the ability of platelets or microparticles (MP) to support thrombin generation (TG) mediated by phospholipids (PL) in the platelet membrane.
Methods: Washed platelets (WP) from healthy controls (HC) (n=27) and UBD patients (n=20) were isolated and activated with thrombin. TG on platelets and MPs, resuspended in standardised platelet poor plasma were activated using liposomes containing tissue factor (10pM) and phospholipid (0.5µM). 12-HETE-PL and externalised phosphatidylserine (PS) were measured using mass spectrometry. In 3 UBD patients, samples were collected pre and post DDAVP.
Results: Peak TG supported by washed platelets and MPs was reduced in UBD patients (p < 0.05) (Figure 1). There was no difference in externalised PS in UBD patients and HC. 12-HETE-PC was markedly lower in UBD 9.5 (3.5-18.9) vs 30.7 (13.8-41.8) ng/2x107 platelets, p=0.01 (Figure 2). In 3 UBD patients treated with DDAVP for invasive procedures there was increased externalisation of all species of PS (p< 0.04) and a trend towards increased peak TG on washed platelets.
Conclusions: In UBDs, a reduced ability of platelets and MPs to support TG may, in part, explain the bleeding phenotype. The reduction in TG was associated with a decreased ability of activated platelets to make procoagulant 12-HETE-PC. This suggests the PL composition of the platelet membrane may be implicated in UBD. DDAVP is effective in UBD and we suggest that this may be because it increases externalised PS and better supports TG. Further studies in independent cohorts of patients with UBD are required to confirm these findings.
To cite this abstract in AMA style:Obaji SG, Slatter DA, Tyrrell VJ, Jenkins PV, O'Donnell VB, Collins PW. Uncharacterised bleeding Disorders Are Associated with Reduced Platelet and Microparticle Thrombin Generation and Decreased Procoagulant Oxidised Phosphatidylcholine [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/uncharacterised-bleeding-disorders-are-associated-with-reduced-platelet-and-microparticle-thrombin-generation-and-decreased-procoagulant-oxidised-phosphatidylcholine/. Accessed October 1, 2023.
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