Red Cell-Derived Microparticles (RMP) Correct or Improve Abnormal Coagulation Profiles in TEG in a Variety of Disorders of Different Pathology
Authors: Johansen Max E , Jy Wenche , Horstman Lawrence L , Bidot Carlos , Ahn Yeon S 
Published: October 2019

Abstract
Abstract 2277

Introduction:
Thromboelastography (TEG) reports several viscoelatstic changes during clot formation, giving useful information on multiple parameters, and can give information on effects of therapeutic measures. We previously demonstrated that RMP can improve clotting parameters in selected bleeding disorders, judging by TEG. In this report we characterize the abnormalities seen in TEG in several disease states, and how RMP can modify or correct the abnormal parameters.

Methods: (i)
The following patient groups were studied by TEG: Patients with ITP (n=10), other non immune TP (n=10), thrombocytopenia from aplastic anemia (AA, n=3), antiphospholipid syndrome (APS, n=10), systemic lupus erythmatosus (SLE, n=8), hemophilia (n=3), hemolytic anemia (HA, n=4) and healthy controls (n=84). (ii) RMP were produced from washed, packed RBC by high-pressure extrusion and were added at 1×10E8/mL f.c. to the test samples. (iii) TEG was performed on whole citrated blood, each in presence and absence (+/−) of added RMP. Parameters measured were R (lag time), k (clot formation time), A, angle (initial rate of clot growth), MA (maximum amplitude, or clot strength), G (shear elastic modulus, another measure of clot strength) and CI (coagulation index), a composite measure.

Results:
(1) Baseline findings (absence of RMP). All disease groups except HA had longer R (lag) time than controls (p≤0.03), but only AA, ITP, and SLE had longer k times (p≤0.03). HA had a significantly shorter k time and higher angle A (initial rate) compared to controls, both at p<0.01. Angle A was lower in Hemophilia, TP, ITP, AA and SLE (all p≤0.05 or better). APS did not differ from controls. Finally, MA (amplitude) and G (elastic modulus) were lower in TP, ITP, and AA than controls (p≤0.04), while the other diseases did not differ from controls in this measure. (2) Effect of RMP. The R and k parameters of all disease groups except HA were significantly shortened upon addition of RMP (p≤0.05 or better). RMP also shortened R and k of healthy controls (p<0.01, n=84). TP, ITP, AA, hemophilia APS, and controls also had shorter R+k time, and steeper angle A (p≤0.05 or better for all measures). HA had a shorter R+k time (p<0.05) but angle A remained unaffected. Additionally, modest increases in MA and G were seen in hemophilia and APS in the presence of RMP (p<0.04 or better). (3) Global measures. The CI (coagulation index) was significantly improved (p<0.05 or better) by addition of RMP in TP, ITP, APS, and SLE, indicating a better global coagulation profile in those diseases. (4) Combined groups. When all of the hematologic disorders were combined, significant differences in R, k, R+k, A, and G were observed in the presence of RMP (p≤0.02), but no difference in MA was seen, although it was very close to significance (p=0.051). CI was also markedly improved by RMP (p=0.02). (5) General observation. It is important to add that in nearly all groups, some patients responded strongly to RMP but others weakly or not at all, indicating different status of the disorder, possibly reflecting a state of platelet activation, inflammation, or disease activity.

Conclusions/Discussion:
RMP appear to have broad efficacy in correcting abnormal coagulation profiles in several disorders with differing pathologies. The parameter most strongly affected was time for initial fibrin formation, R. Effect on clot strength (G, MA) was statistically significant but varied among individual patients. RMP could correct abnormal clotting parameters in blood from differing pathologies, although there were individual variations. These data support the hypothesis that RMP can serve as a useful hemostatic agent to reduce bleeding in a variety of conditions of differing etiology. However, the factors responsible for such variations remain unknown. Elucidation of underlying factors influencing the effect of RMP will further improve and refine its therapeutic benefit and indications of its application.

Disclosures:
No relevant conflicts of interest to declare.