Viscosity (eta) in a blood suspension is affected by the total hematocrit (HT) as well as by the deformability of the cells. The impact of these combined factors on the rheologic behavior of sickle cell suspensions and on guidelines for transfusion has not been explored fully. Therefore, the eta of mixtures of washed normal (AA) and sickle (SS) red cells was determined in a rotational viscosimeter as a function of the hematocrit level of SS cells (HS), HT, oxygen tension (PO2), and shear rate. The ratio HT:eta can be taken as an index of potential oxygen delivery. The optimal HT (for maximum HT:eta) became progressively higher as the HS or the HS:HT ratio was lowered: at a given HT, HT:eta rose with a decrease in HS, especially at low HS values. These data support the concept that simple transfusion alone is not as beneficial to the patient as exchange transfusion and that substantial benefit can be obtained by bringing the patient to very low HS levels. The finding that eta rose with HT more steeply when the HS:HT ratio rather than HS was held constant suggested that the absolute level of HS may be more useful than the HS:HT ratio as a guide for a transfusion regimen.
The rheological properties of human leukocytes (WBCs) have been studied by micropipette aspiration and filtration tests. A small aspiration pressure applied via a micropipette (diameter approximately equal to 3 micron) causes the WBC to undergo a rapid elastic deformation followed by a slow creep. The data can be analyzed with a viscoelastic model: an elastic element K1 in parallel with a Maxwell element (elastic element K2 in series with viscous element mu). Neutrophils and B lymphocytes are similar in K1, K2, and mu, but these values are higher for T lymphocytes. Treatment of neutrophils with colchicine decreases K2 and mu without changing K1, whereas cytochalasin B decreases all three coefficients; these results indicate the importance of cytoskeletal microtubules and microfilaments in WBC rheology. In the presence of Ca2+, WBCs form protopods which have increased viscoelastic coefficients. Inhibition of protopod formation with pentoxifylline is associated with an increase in WBC deformability. The ruffled surface of the apparently round WBC provides an area about twice that needed to enclose a smooth sphere of the same volume; this geometric feature plays an important role in whole WBC deformability tested through 4-5 micron filter pores or micropipettes. Because of its larger volume and higher cellular viscosity, each WBC is equivalent to approximately 700 erythrocytes in its tendency to block 5-micron channels. The rheology of WBCs has significant implications in their functional behavior, including flow through the microcirculation and interaction with endothelial cells.
Recent revival of interest in the use of vincristine (VCR) for the treatment of idiopathic thrombocytopenic purpura prompted us to evaluate the platelet function of our patients on VCR. Eighteen patients with acute lymphoblastic leukaemia (ALL) in remission, and nine children with solid tumours were studied on 80 occasions at different time intervals after their last VCR dose. A mildly elevated threshold for epinephrine-induced second phase aggregation and a delay in the onset of collagen-induced aggregation was found in patients with ALL not on VCR. Vincristine induced unobtainable second phase aggregation to epinephrine in 67%, 38%, 30% and to ADP in 53%, 13%, 33% of the patients 1 week, 2-3 weeks and 4 weeks respectively after administration. The thrombocytopathy was relative, not absolute, since collagen induced aggregation at all times. Platelet counts, uptake and release of serotonin, bleeding times, clot retractions and release of platelet factor 3 were normal. Platelet adhesion was abnormal in five of 12 patients tested. In vitro platelets are a hundred-fold less sensitive to VCR than in vivo. Cyclic adenosine monophosphate, cyclic guanosine monophosphate and dimethylsulfoxide do not protect platelets from VCR. The exact mechanism by which VCR abolishes second phase aggregation in patients is uncertain. Because of VCR's narrow therapeutic index between thrombocytopenia and thrombocythaemia, the use of VCR should be reserved for life-threatening haematologic disorders when treating non-malignant conditions.
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