Carolyn M. Chesney

Stability of prostaglandin I2 in human blood

Prostaglandin I2 (PGI2) is hydrolyzed more slowly in human plasma than in buffer at the same pH; this stabilization appears to be due to binding of PGI2 to albumin. The stability of the antiaggregatory potency of PGI2 is similar in human blood and in plasma buffered to pH 7.55. No measurable conversion of [3H]-PGI2 to radioactive or nonradioactive metabolites occurred during incubation with blood.

Altered von Willebrand factor molecule in children with thrombosis following asparaginase-prednisone-vincristine therapy for leukemia.

Eleven consecutive leukemia patients with thrombosis induced by asparaginase-prednisone-vincristine therapy were studied to gain insight into the pathogenesis of this complication. Measurement of anti-thrombin III, plasminogen, factor V, and fibrin degradation products as well as platelet aggregation sensitivity to adenosine diphosphate disclosed no consistent abnormalities that would explain pathologic thrombus formation. A decrease in platelet counts observed in nine of 11 patients, prompted us to investigate the possible involvement of factor VIII in this disorder. Levels of factor VIII procoagulant activity, von Willebrand factor (vWF) and ristocetin cofactor were similar to findings for an identically treated comparison group who remained free of thrombotic complications. However, qualitative examination of vWF by crossed immunoelectrophoresis (CIE) revealed a distinct right shift of the immunoprecipitin lines in each of three thrombotic patients tested, whereas a normal profile was found in three similarly treated patients without the complication. This altered pattern had reverted to normal when CIE was repeated 2 to 7 months later. We postulate that the abnormal vWF is related to the development of thrombosis.

Lack of pathogenetic role of proteins C and S in thrombosis associated with asparaginase‐prednisone‐vincristine therapy for leukaemia

Summary. Plasma levels of protein C and protein S antigens were measured in eight children who developed thrombosis following asparaginase‐prednisone‐vincristine treatment for acute lymphoblastic leukaemia and in nine similarly treated children without this complication. Protein C antigen levels were below normal in three of the eight patients with thrombosis and in three of the nine patients without the complication (P= 0‐38). Low protein S antigen levels were found in five of six patients with thrombosis and in two of seven patients without thrombosis (P=0‐10). Plasma factor IX and factor X antigen levels, other vitamin K dependent factors, were also measured in the two groups of patients. In general, reduced levels of protein C, protein S or both antigens (anticoagulant vitamin K dependent proteins) were associated with reduced levels of factor IX, factor X, or both of these factors (procoagulant vitamin K dependent clotting proteins). The ratios of protein C and protein S antigens to each other and to factor IX and factor X antigens did not differ between the two groups. Thus, there is no clear evidence that reduced levels of protein C and (or) protein S cause thrombosis in leukaemia patients treated with this drug combination.

Effect of synthetic estrogen on platelet aggregation and vascular release of PGI2-like material in the rabbit

Treatment of adult female New Zealand white rabbits with ethinyl estradiol, the synthetic estrogen used in many oral contraceptives, results in a significant increase in in vivo aggregation. This alteration in platelet behavior is accompanied by diminished vascular release of antiaggregatory PGI2 (prostacyclin)-like material. Addition of a progestin prevents the change in platelet aggregation seen with the estrogen alone. Diminished vascular PGI2 release may be an important factor in the pathogenesis of thrombotic occurrences experienced by some oral contraceptive users. In vivo platelet aggregation may be of value in identifying individuals at risk of developing thrombotic disturbances while taking oral contraceptives.

The role of the telopeptide region of collagen in the platelet-collagen interaction.

Abstract Removal of the telopeptide regions by pepsin inhibits platelet aggregation and release by monomeric collagen in PRP. This inhibitory effect appears to be due to the inability of pepsin modified collagen to form fibrils in plasma, since fibrils formed in buffer cause aggregation and [ 14 C] serotonin release in PRP. Fibrils formed from pepsin modified collagen appear to be quantitatively more effective in causing platelet aggregation and serotonin release than normal fibrils. When pepsin modified collagen is studied as a function of time of digestion, there is a dissociation between platelet aggregation and release. Fibrils formed from pepsin modified collagen become quantitatively more effective the longer the duration of digestion. Platelet aggregation but not release by fibrillar collagen can be inhibited by a 14 fold excess of pepsin soluble collagen. This effect can be overcome by increasing the concentration of fibrillar collagen. Pepsin modified soluble collagen appears to cause serotonin release of gel filtered platelet but not aggregation. These data suggest that the telopeptide regions play a role in collagen quaternary structure and that the atelopeptide tropocollagen may bind to the platelet but is not sufficient to produce platelet aggregation.