Monitoring Haemostatic Response To Factor â…§ In Patients With Hemophilia A Using Thromboelastography

Background:Patients with severe hemophilia A have variable bleeding tendency and different responses to factor replacement therapy. Routine coagulation assays, like activated partial thromboplastin time and factor assay, fail to predict this variability. Thromboelastography is a global haemostatic assay, which mimics the in vivo condition of coagulation by measuring viscoelastic changes of clotting whole blood. Current investigations suggest that TEG parameters are sensitive and dose-dependent to coagulation factor Ⅷ substitution, implying its usefulness in management of hemophilia A. Moreover, TEG may predict the variability in bleeding tendency and response to therapy, thus help tailoring haemostatic treatment to patient requirements.Objective:1To evaluate the usefulness of TEG in the diagnosis and management of hemophilia A by comparing baseline TEG profiles among hemophilia patients.2To evaluate the role of TEG in monitoring routine and perioperative substitution therapy by correlating TEG parameters with FⅧ activity (FⅧ:C) and clinical manifestations.3To investigate the role of TEG as a tool for individualization of therapy based on its inter-individual variation.Methods:38hemohilia A patients without inhibitor were enrolled. Patients in bleeding episodes were infused with different doses of FⅧ concentrates. FⅧ:C and TEG were measured before and15min after the infusion. Some patients were followed up for3months. Perioperative patients were infused with40-50IU/kg FⅧ. FⅧ:C and TEG were measured preinfusion and at nine subsequent time points over48h. FⅧ:C was determined using a One Stage partial thromboplastin time-based assay. FⅧ inhibitor was determined using Bethesda assay. TEG was determined following lab instructions.Results:1Baseline TEG profiles of Hemophilia A patients showed a prolonged R、K、TMRTG and a decreased a、MA、MRTG TEG parameters in severe HA were significantly different from normal controls and mild HA.2Baseline TEG profiles of29severe HA patients showed great inter-individual variability. R correlated negatively with past FⅧ consumption (spearman r=-0.505, P=0.005), but not significantly with the number of target joints or bleeding frequency.3Of the29severe HA patients,6patients receiving prophylactic therapy have a better average baseline TEG profile compared with patients receiving on-demand therapy.415min after the infusion of4-50U/kg FⅧ,R、TMRTG correlated significantly to F Ⅷ:C (Spearman r=-0.811,-0.800). However, there is great inter-patient variability at the same FⅧ:C.5Over48h after the infusion of40-50IU/kg FⅧ, TEG parameters correlated closely to FⅧ:C for each patient.6The improvement in haemostasis was in accordance with the changes in TEG profiles in perioperative substitution. Inter-patient variability in TEG predicted different responses to therapy.Conclusions:1Baseline TEG profiles are abnormal in hemophilia A patients, which can identify severe patients reliably.2There is great inter-patient variability in baseline TEG profiles of severe HA patients, which attributes partly to past FⅧ consumption. Prophylactic therapy can improve baseline TEG profiles. The inter-patient variability in baseline TEG may help optimize therapy for individual severe HA patient.3TEG parameters are dose-independent to FⅧ therapy. R、TMRTG may be effective in monitoring therapy based on their close correlation with FVM:C. There is wide variation between patients but a predictable effect within a patient.4TEG may predict clinical haemostasis and help the individualization of FⅧ therapy to achieve the best haemostasis and cost effectiveness.