Distinguishing between in vitro and in vivo release of platelet specific proteins has led to problems in interpretation of clinical studies with PF4, and with BTG.As part of a prospective study of peripheral occlusive arterial disease in diabetes mellitus PF4 and BTG were measured together by specific radioimmunoassay in four groups of subjects age 50-70 years. Groups included (1) 106 normal subjects (NC); (2) 126 with clinical and objective evidence (transcutaneous doppler ultrasound and treadmill exercise) of peripheral arterial occlusive disease (ASO); (3) 244 with diabetes mellitus without ASO and (4) 101 with both diabetes mellitus and ASO.PF4 did not distinguish among the four groups: NC vs ASO p=. 18, NC vs DM p=.52, NC vs DM+ASO p=.73, NC vs all diabetics p=.61, and NC vs all ASO p=.46. However, BTG did distinguish the groups with vascular disease from NC: NC vs ASO p=.02, NC vs DM+ASO p<.001, NC vs DM p=.32, DM vs DM+ASO p<.01, all ASO vs all nonASO p<.001.Normal range for PF4 is 0-13 ng/ml with a median of 3.0 ng/ml, a mean of 3.0 ng/ml, and SD 1.97. Normal range for BTG is 14-46 ng/ml with a median of 26 ng/ml, a mean of 27.2 ng/ml, and SD 10.3. When PF4 and BTG are correlated (all groups included) r=.41 p<.001.PF4 and BTG levels should be performed together. When done together low PF4 levels support the absence of in vitro platelet release due to sample collection and handling. BTG levels are significantly increased in subjects with peripheral arterial disease, supporting the active role of platelets in thrombotic occlusive arterial disease.
Significant hemostatic abnormalities can occur during orthotopic liver transplantation (OLT). This study addressed three goals: 1)evaluation of the hemostatic mechanism at each stage of the OLT; 2) the relationship of the coagulation process with the thrombelastograph (TEG); and 3) comparison of results in patients requiring retransplantation or who died, with the overall pattern. To evaluate hemostasis during 50 consecutive OLTs, a detailed coagulation and TEG study was done. The surgical procedure was divided into the following stages: Stage I--induction of anesthesia to occlusion of blood flow to the patient’ s diseased liver; Stage II—occlusion of blood flow to the patient’ s diseased liver to reperfusion of the patient’ s new liver; and Stage III—reperfusion of the new liver until skin closure. 28 ml of arterial blood were sampled at the beginning and end of each stage and up to five days posttransplantation for the following: platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, prothrombin, factors V, VII, IX, and X, plasminogen, antiplasmin, antithrombin III (functional and immunologic), fibrinolytic split products, and TEG. The patient’ s core temperature and amount of blood products transfused were obtained intraoperatively during each of the six data times. The ischemia time of the donor liver was recorded. Significant hemostatic abnormalities developed during each of the 50 OLTs, especially during reperfusion of the donor liver. In some instances, this was corrected within one hour, but platelet counts continued to fall, and a number of coagulation factors rebounded only partially. The TEG values correlated with laboratory data and blood loss, but the correlations were not strong. The patient’ s requirement for red cells varied with the operative drop in temperature; however, the donor liver ischemia time and length of Stage II made no significant difference. It is concluded that 1) significant deterioration of coagulation factors occurs during OLT, 2) the TEG is an effective screening test that affords prompt information, 3) aggressive measures should be taken to maintain the patient’ s body temperature at 37°C, 4) patient outcome was not predicted by intraoperative hemostatic evaluation.
An automated method for specific factor assays has been developed using a novel thrombin-specific chromogenic substrate (developed by A. Aiyappa, Ph. D., Abbott Labs). For factors VIII, IX, XI and XII, the test system includes an ellagic acid activator and brain phospholipid in a calcium containing tris buffer pH 7.4. These are mixed with a plasma sample consisting of a mixture of specific factor deficient substrate and test plasma for 5 minutes and then the chromogenic substrate is added. After another 5 minutes the increase in optical density ΔOD is recorded. Normal plasma serially diluted in specific factor deficient substrate is used to construct a standard graph and test plasma results are interpolated from this.Fifty-four comparative assays have been done for factors VIII and IX and correlated with the results obtained from conventional clotting assays. For factor VIII the correlation coefficient (r)=0.935 (N=35) and for factor IX r=0.941 (N=19). While insufficient data exists to date for factors XI and XII, these assays appear to be comparable to the VIII and IX results.The assays for factors V, VII and X use a simplified system in that the chromogenic substrate and phospholipid are added together. The ΔOD is again recorded after 5 minutes. Test plasma results are interpolated from a standard graph constructed using serially diluted normal plasma as before. To date only the factor V assay has enough data to do a correlation with the clotting assays and r=0.953 (N=13) which is similar to the r value for the VIII and IX assays.Because of the widespread availability of the automated analyzer used in the assay and the standardization of end point determination it provides, specific factor assays might be made more widely available outside specialized coagulation centers.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.