Evaluation of a stroma-free hemoglobin solution for use as a plasma expander.

The preparation of large quantities of a stable, stroma-free hemoglobin solution without coagulant activity is described. Following infusion of this solution into phlebotomized dogs, there is no methemoglobin formation, no adverse effects on vital signs, and no demonstrable activation of blood coagulation. The hemoglobin maintains its oxygen-carrying capacity and liberates oxygen into tissues. Acute and chronic effects on renal function following infusion of this preparation were also studied and no effect on clearance of urea, creatinine, or P.A.H. could be demonstrated. There was no change in urinary output and histological sections revealed no lesions attributable to hemoglobin toxicity. It is concluded that a stroma-free hemoglobin solution may have use as a plasma expander.

Platelet factor 3 in normal subjects and patients with renal failure.

Two tests were used to differentiate abnormalities in release of platelet factor 3 (PF3) from quantitative deficiencies of this factor in normal subjects and in patients with renal failure. The first test was an assay which determined availability of PF3 (PF3-A time) and involved the use of a mixture of patient's platelet-rich plasma (PRP) and normal platelet-poor plasma (PPP) in a fixed ratio (1:8). The second test was similar but used "frozen and thawed" platelets to obtain a quantitative estimate of PF3 (PF3-F time). An abnormal PF3-A time was found in approximately three-quarters of 55 patients with renal insufficiency; 43 of these had chronic and 12 had acute renal failure. This abnormality was present both in patients with and without hemorrhagic manifestations, although it was slightly more common in bleeders. The PF3-F test was abnormal in approximately one-third of the bleeding patients and one-quarter of the non-bleeders. The PF3-A time returned to normal or was significantly shortened 24-48 hr after peritoneal or hemodialysis. Studies on patients who were not dialyzed showed no statistically significant correlations between the PF3-A time and either the serum urea nitrogen, creatinine, calcium, or phosphorus. Furthermore, the PF3-A time was not affected by guanidinosuccinic or guanidinoacetic acids. We therefore conclude that the demonstrable platelet abnormality in patients with uremia is produced by an unknown dialyzable material. The mean plasma clot retraction of uremic patients was also significantly different from the mean plasma clot retraction or normal controls. However, unlike the PF3-A time, the abnormality of plasma clot retraction was not immediately affected by dialysis. Correction of plasma clot retraction did occur after repeated dialyses.

Hemoglobin solution as a plasma expander.

Stroma-free homoglobin solution has received extensive experimental trials in dogs and nonhuman primates. It has been shown to have no coagulant activity and to have no deleterious effect on renal function. Also pathological examination of autopsy and biopsy specimens fails to demonstrate any kidney damage after infusion of large amounts of stroma-free hemoglobin solution. In vivo data would also indicate that the solution can both carry oxygen and liberate it into tissues despite the fact that its in vitro oxygen dissociation curve is shifted to the left. Animals can be maintained with a 3% hematocrit after exchange transfusion with hemoglobin solution, without any significant fall in blood pressure or rise in central venous pressure. This is not true for nonoxygen carrying plasma expanders. Hemoglobin solution has also been shown to have an effect on blood rheology which would tend to increase flow through microcirculation. We conclude that stroma-free hemoglobin solution has potential for use as a plasma expander for treatment of hemorrhagic and possibly other types of shocks, as well as other uses.