In my last blog concerning the genetic disorder called familial hypercholesterolemia (FH), I mentioned an invasive treatment called LDL apheresis as a potential therapy when medications do not reach target goals. Apheresis is a procedure in which whole blood is withdrawn from a person, run through various filters to remove the desired components from the blood, and then reinfused back into the person. The red blood cells remain relatively intact and functional. It is a procedure similar to hemodialysis for patients who have severe kidney failure. In the case of LDL apheresis, whole blood is removed from the person usually through a venous IV line in the arm. The whole blood is then run through the apheresis system which comprises blood tubing, electrical pumps to push the blood, and a set of separators and filters. Traditionally, whole blood is withdrawn from one IV line and then pumped into a plasma separator. As the name implies, this section separates plasma from red blood cells. The red blood cells are then redirected back into the persons through a second IV line along with some remaining plasma. The filtered plasma is directed to a parallel set of columns that absorb LDL directly from the plasma. The removal process can involve a variety of chemicals such as dextran sulfate or other biological compounds such as sheep antibodies to apolipoprotein B compounds. The net result, however, is removal of LDL and VLDL from the plasma. The LDL depleted plasma is then recombined with the red blood cells and returned back to the person using the second IV line. Some newer systems can remove LDL directly from whole blood and therefore do not require a plasma separator. Blood thinning medications such as heparin are given to prevent clotting in the system, and the system components are sterilized in order to minimize infection risk.
LDL apheresis is quite effective at removing LDL. After a single treatment, plasma LDL levels may fall 60% on average. The catch is that the effect is relatively short lived as the body begins to regenerate LDL. Therefore, repeated treatments are given usually on a weekly or bi-weekly schedule depending on how high the initial LDL is.
The majority of the scientific evidence concerning LDL apheresis has focused on the treatment of familial hypercholesterolemia, both homozygotes and heterozygotes. In the 1990s, a series of coronary angiographic studies were performed to see which therapy would give the best result in stabilizing and preventing future accumulation of atherosclerosis in FH patients: diet, diet+drugs, and diet+drugs+apheresis. Mean reductions of LDL levels were 7, 35, and 53% respectively. The mean percentage of patients showing some progression of their heart disease was 46, 33, and 18% respectively. Thus, it seemed that the lower the LDL by any means was beneficial. In addition, one small non-randomized study suggested that drugs+apheresis reduced cardiovascular events when compared to drug therapy alone.
LDL apheresis is quite safe and well tolerated, but some undesirable effects and adverse reactions can occur. Although the removal of LDL is selective, other important components of the plasma such as HDL, platelets, and vitamin E may be inadvertently removed to a lesser degree. Some red blood cells that are run through the plasma separator may become damaged. This, in turn, may contribute to anemia. The most significant adverse reaction from the treatment is hypotension. Apheresis can withdraw a significant amount of blood volume from a person, and even though most of it is returned, this still may cause a drop in blood pressure. Adequate hydration and the avoidance of blood pressure medication prior to treatment can help minimize this risk. Other more serious events such as a heart attack, air embolism, or death are quite rare.
Given the above information, the Food and Drug Administration has approved the use of LDL apheresis in three categories of patients in the US who have failed both diet and maximum medical therapy: 1) FH homozygotes with LDL >500mg/dl, 2) FH heterozygotes with LDL>300mg/dl, and 3) FH heterozygotes with LDL>200mg/dl and a documented history of heart disease. It is important to remember that apheresis is not a replacement therapy but rather a complement to lifestyle modifications and medicine. Future areas of research include assessing the benefit of this technology in treating those with heart disease and no documented genetic familial hypercholesterolemia.
Published On: February 04, 2009