The Evaluation of Hemostatic Abnormalities Using a CWA-Small Amount Tissue Factor Induced FIX Activation Assay in Major Orthopedic Surgery Patients

Abstract

We analyzed the utility for a clot waveform analysis (CWA) of small tissue factor induced FIX activation (sTF/FIXa) assay in patients with major orthopedic surgery (including total hip arthroplasty [THA] and total knee arthroplasty [TKA]) receiving edoxaban for the prevention of venous thromboembolism (VTE). The sTF/FIXa assay using recombinant human TF in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) was performed using a CWA in the above patients to monitor the efficacy of edoxaban administration. Of 147 patients (109 THA and 38 TKA), 21 exhibited deep vein thrombosis (DVT), and 15 had massive bleeding. Increased peak heights of the CWA-sTF/FIX were observed in almost patients after surgery and prolonged peak heights of the CWA-sTF/FIX were observed in almost patients treated with edoxaban. The peak heights and times of the CWA-sTF/FIX were significantly higher and shorter, respectively, in PRP than in PPP. There were no significant differences in parameters of the CWA-sTF/FIXa between the patients with and without DVT or between those with and without massive bleeding. The peak time of CWA-sTF/FIXa were significantly longer in TKA patients than in THA patients on day 1 after surgery. The second derivative peak height of the CWA-sTF/FIXa was significantly lower in TKA patients than in THA patients on day 4. The CWA-sTF/FIX reflected hemostatic abnormalities after surgery and the administration of edoxaban, and the results were better in PRP than PPP. Further studies separately analyzing the THA and TKA subgroups should be conducted.

A Clot Waveform Analysis Showing a Hypercoagulable State in Patients with Malignant Neoplasms

“…The prolongation of peak times in patients with malignant neoplasm reflect with anticoagulants. The prolongation of peak time in CWA-APTT and sTF/FIXa due to anticoagulant were previously reported in major orthopedic surgery [17]. The peak time CWA-APTT or -sTF/FIXa may reflect with anticoagulant, and the peak height may reflect physiological clotting activity.…”

“…Although elevated D-dimer is useful for detecting thrombosis in patients with cancer [14,15], there are no routine test for hypercoagulability. Recently, a clot waveform analysis (CWA) to activated partial thromboplastin time (APTT) has been developed to analyze to evaluate hemostatic abnormalities in patients with bleeding tendency and to monitor anticoagulant therapy [16,17]. Furthermore, the use of the small amount of TF induced FIX activation assay (sTF/FIXa) assay can evaluate the hemostatic abnormalities including platelet abnormalities [18].…”

The Reevaluation of Thrombin Time Using a Clot Waveform Analysis

“…This thrombin activates not only fibrinogen, but also FV, FVIII, FIX, FX, and FXI, with the activation cycle from thrombin to FXI continuing for a short time thereafter [ 14 ]. The CWA-sTF/FIXa with a 2000-fold diluted PT reagent (recombinant TF) [ 24 , 25 ] was developed to evaluate physiological coagulation, and was shown to be capable of measuring the FVIII concentration. As a cross-mixing test of the CWA-TT between calibration plasma and FVIII-deficient plasma showed a good dose-response curve, the CWA-TT may be able to measure the FVIII concentration.…”

“…However, most APTT reagents have some contact activation substance, and cannot demonstrate physiological coagulation [ 15 ]. Therefore, an sTF/FIXa assay [ 15 , 24 ] uses PRP as a physiological phospholipid instead of commercial APTT reagents. The CWA-TT also showed that the peak height, especially the 1st DPH-2, was higher in PRP than in PPP.…”

Clot Waveform Analysis Demonstrates Low Blood Coagulation Ability in Patients with Idiopathic Thrombocytopenic Purpura

“…The clot waveform analysis (CWA)-APTT method [6] is capable of measuring very low coagulation factor VIII (FVIII) activities in hemophilia A [7] and to detect early disseminated intravascular coagulation (DIC) using biphasic waveforms [8]. Furthermore, CWA-APTT [6] is reported to be useful for the diagnosis of lupus anticoagulant, liver dysfunction, DIC, hemophilia, and factor VIII inhibitor [9][10][11][12], and for the monitoring of bypass therapy in patients who are positive for FVIII inhibitor or for anticoagulant therapy [13][14][15]. The CWA-APTT [6,15] and sTF/FIXa assays [5,14] are routine assays that are able to express the peak times and peak heights of the clotting curve or its derivative curve, easily when evaluating the thrombin burst.…”