Further evaluation of a heparin neutralizer and its effect on factor IX in normal and coumadin-plasma.

Heparsorb, a commercial anion exchange resin capable of removing large amounts of heparin from heparinized plasma, has recently been introduced into the clinical diagnostic laboratory as a useful reagent for the evaluation of blood coagulation in heparinized blood and the evaluation of an unexpected prolongation of global coagulation tests. In this paper data are presented which indicate that Heparsorb has little or no effect on the activities of blood coagulation factors in heparinized plasma, except for a modest (22%) reduction in factor IX-activity. Maximal loss of factor IX-activity was observed after incubation of plasma with Heparsorb for 15 min at room temperature. Prolonged storage of plasma before or after incubation with Heparsorb and changes in plasma pH had no appreciable effect on the extent of factor IX-activity loss. Evidence is presented to substantiate earlier findings that factor IX-activity is not removed by Heparsorb from plasma of patients on coumadin therapy, and to indicate that this lack of effect of Heparsorb on factor IX-activity in coumadin plasma is due to reduced affinity of hypocarboxy-IX for the heparin neutralizing resin.

Loss of 111Indium as indicator of platelet injury.

We previously demonstrated that platelets can be labeled with 111Inoxine with high labeling efficiency and that 111In is not liberated from labeled platelets during the platelet release reaction or prolonged in vitro storage. In view of these findings, we examined the potential usefulness of loss of 111In from labeled platelets as an indicator or platelet damage by comparing the loss of 111In with that of 51Cr and LDH (in some experiments also with platelet factor 3 availability) under different conditions of platelet injury. When washed human platelets labeled with either 51Cr-chromate or 111In-oxine were exposed to increasing concentrations of detergents (Triton X-100, lysolecithin), threshold, rate, and extent of loss of 111In, 51Cr and, LDH were similar. In contrast, when labeled platelets were depleted of metabolic energy by incubation in glucose-free Tyrode albumin solution or glucose-depleted plasma in the presence of antimycin A and 2-deoxy-D-glucose, loss of 51Cr (and PF3a) occurred earlier and progressed at a faster rate than that of 111In or LDH. Similar results were obtained when platelets were exposed to increasing concentrations of PlA1 antibody, causing complement-mediated immune injury. The findings indicate that with certain agents that cause rapid platelet disruption (lysis), different platelet constituents are lost at similar rates. However, under conditions of more subtle or slowly progressive platelet injury, small molecules such as adenine nucleotides (51Cr) may escape earlier and at faster rates than larger molecules such as LDH or 111In-binding platelet protein. Thus, neither 111In loss nor LDH loss appear to be suitable indicators for sublytic or prelytic platelet injury.