EXTRACORPOREAL SYSTEM THAT MODIFIES HEMOGLOBIN IN PATIENTS WITH SICKLE-CELL ANEMIA

The authors have developed an extracorporeal device, the Sickle Cell Machine (SCM), which adds sodium cyanate to the blood, allows time for irreversible reaction with hemoglobin (carbamylation), removes the excess free cyanate by dialysis and monitors the flowing blood to prevent excess free cyanate from returning to the patient. In vivo trials on sheep confirmed the safety and reliability of the SCM and performance criteria for the three disposable components in the extracorporeal circuit: 1) the Hemo‐Reactor, in which sodium cyanate reacts predominantly with NHAerminal valine on hemoglobin chains; 2) the Hemo‐Detoxifier, which is a specially designed hollow fiber dialyzer with an extraction efficiency of 97% or more at Qsbb/sb> = 20–40 ml/min and Qsbd/sb> = 500 ml/min; and 3) the Hemo‐Analyzer, which is a small hollow fiber dialyzer for continuous on‐line analysis of the concentration of free (unreacted) sodium cyanate in blood returned continuously to the patient during a treatment. For a 70‐Kg patient at steady state, the average degree of carbamylation following one 4‐hr treatment will be about 1.8 moles cyanate/mole sickle cell hemoglobin tetramer and will drop to about 1.2 at the end of a two‐to‐three‐week intertreatment period. The postcarbamylation distribution will be such that about 90% of the red cells will have been treated whereas the precarbamylation distribution will be such that 55% will still be carbamylated. The system described herein can be modified to continuously treat whole blood with any chemical agent that binds to blood components and then remove the unreacted chemical before it is returned to the patient. A special on‐line monitor continuously measures the concentration of the residual drug in the blood before it is returned. It then compares by computer both the rate and total amount of drug returned with respect to pre‐set limits and automatically isolates the patient from the extracorporeal circuit if these limits are exceeded. The first clinical trials of the SCM will begin soon. It is important to understand that, whereas the machine is safe to use on patients, there is no conclusive evidence that cyanate will indeed prevent sickle cell crises. It is anticipated that it will take several years to determine whether or not cyanate treatment of sickle cell blood with the SCM will prove of benefit to patients with sickle cell disease. © 1979 International Center for Artificial Organs and Transplantation