Haemostatic effects of polymerized albumin particles carrying fibrinogen γ‐chain dodecapeptide as platelet substitutes in severely thrombocytopenic rabbits

Abstract

Our purpose was to produce a platelet substitute that could enhance haemostatic ability using rabbits with severe thrombocytopenia. We have developed polymerized albumin particles (polyAlb) for treatment of bleeding and focused on a dodecapeptide, HHLGGAKQAGDV (H12), as a useful ligand for activated platelet. This sequence occurs only at the carboxy-terminus of the fibrinogen gamma-chain (gamma 400-411). H12 was conjugated to the surface of polyAlb modified with poly(ethylene glycol) (PEG) chains to produce blood-compatible particles (H12-PEG-polyAlb) that had prolonged blood residence time and enhanced stability in vitro and in vivo. The H12-PEG-polyAlb was administered intravenously to rabbits with severe thrombocytopenia, and the ear bleeding time was measured in order to evaluate the haemostatic effect. The H12-PEG-polyAlb significantly shortened the ear bleeding time of severely thrombocytopenic rabbits and showed no effect on the inhibition or promotion of endogenous and exogenous coagulation activities. Furthermore, we could assess the haemostatic capacity of the H12-PEG-polyAlb, based on the relationship between transfused platelet count and the bleeding time. The H12-PEG-polyAlb may be a suitable candidate for an alternative to human platelet concentrates infused to treat bleeding in patients with severe thrombocytopenia.

Surgical materials: Current challenges and nano-enabled solutions

“…Hemostatic materials with nanofibrous structures have been also developed for clinical applications [112, 113]. For example, Gu et al produced chitosan-based nanofibrous hemostatic mats with no acidic residual by using an electrospinning technique followed by neutralization [112].…”

“…For example, Gu et al produced chitosan-based nanofibrous hemostatic mats with no acidic residual by using an electrospinning technique followed by neutralization [112]. The intrinsic cationic properties of chitosan and its nonspecific binding to cell membrane led to the blood protein adhesion, activation of platelets, and clot formation.…”

“…The blood clotting efficiency of these nanofibrous hemostats, with fiber diameter in the range of 350–440 nm, were then evaluated in vitro . The adhesion of platelets and clot formation were higher on the nanofibrous chitosan mats compared to both Surgicel (an oxidized cellulose-based hemostatic agent) and chitosan sponges [112]. Similarly, Luo et al produced nanofiber hemostatic material based on self-assembling chiral peptide d-EAK16 [113].…”

Neonatal Transfusion Practices

“…The severity of the underlying disease explains the higher probability of death; thrombocytopenia and bleeding is not the cause of excess death rates. 55,57,58 In cases of platelet transfusions it is important to distinguish between alloimmune thrombocytopenia and other causes; first, because newborns with FNAITP, irrespective of prematurity, have a high risk for massive ICH; and second, because HPA-compatible platelets are warranted. The frequency of FNAITP in Caucasian populations is 1:1200 newborns.…”

“…57,58 High dose intravenous immunoglobulin (IVIG) has a role in immune-mediated (early) thrombocytopenia, such as FNAITP and immune thrombocytopenia (ITP) causing (early) thrombocytopenia irrespective of gestational age. Infusions of high dosages of IVIG given weekly to women pregnant with a fetus with FNAITP decrease the risk of intracranial hemorrhage in all infants and induce an increase in the fetal platelet count in 30-85% of these infants.…”