The Role of Plasmapheresis in Critical Illness

Objectives

This chapter will:

1.
Review the techniques of plasmapheresis.
2.
Review the indications and evidence for plasmapheresis and therapeutic plasma exchange in critical illness.

Extracorporeal blood purification by plasmapheresis has been more streamlined and gained more interest by intensivists during the past decade. A useful document is the regularly updated “Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—Evidence-Based Approach” published by the American Society for Apheresis in 2007.

Plasmapheresis is a method that separates and removes the plasma component from the blood of a patient. Blood has four major components: red blood cells, white blood cells, platelets, and plasma. When the soluble plasma molecules are thought to cause harm to a patient, clinicians can employ plasmapheresis to remove the harmful substances from the patient's plasma.

Techniques of Plasmapheresis

Currently, clinicians can use two main techniques to perform plasmapheresis: centrifugation and filtration. With centrifugation technique, whole blood is spun such that the four blood components of red blood cells, white blood cells, platelets, and plasma are separated into layers according to their different densities. The plasma layer then is withdrawn and discarded. With filtration technique, whole blood passes through a filter to separate the plasma component from the larger cellular component of red and white blood cells and platelets.

Plasmapheresis by centrifugation is performed commonly by blood bankers. The advantage of using centrifugation is that there is no limit on the size of the molecules being removed. The disadvantage is that this requires an extra resource with consultation to the blood bank service. Plasmapheresis by filtration is performed commonly by nephrologists and intensivists. The advantage of using this technique is that a large filter can be added easily onto an existing continuous venovenous renal replacement therapy circuit. The disadvantage of using filtration is that there is a limit on the size of the molecules being removed, which is dependent on the pore size of the filter. The efficiency of removing plasma molecules with a standard 1 to 1.5 plasma volume exchange ranges from 63% to 83%. For example, if a patient has 100 harmful molecules in the plasma, after a standard 1 to 1.5 volume exchange, there will be from 37 to 17 harmful molecules left in the plasma.

Replacement Fluid

Currently, there is no consensus on which type of replacement fluid to use during plasmapheresis. The more common options are albumin and fresh frozen plasma. The goals of the replacement fluid are to (1) prevent hypovolemia, (2) maintain appropriate plasma oncotic pressure, (3) maintain appropriate levels of coagulation factors, and (4) replenish depleted beneficial plasma substances. For example, if the pathophysiologic processes can be narrowed down to the presence of a few substances such as autoantibodies to the peripheral nerve myelin in Guillain-Barré syndrome, then the replacement fluid can be albumin. However, if the intensity and frequency of plasmapheresis is high, then after a couple of plasmapheresis sessions with albumin, fresh frozen plasma should be used as a replacement fluid to prevent significant dilutional coagulopathy. However, more often, because the pathophysiologic processes of critical illness involve multiple complex and interrelated pathways, there is an accumulation and deficiency of harmful and beneficial substances respectively in the patient's plasma. Sepsis-induced multiple organ failure is an example of such a complex pathology. In these cases, a strategy of removing harmful substances and replacing beneficial substances often is recommended. Therapeutic plasma exchange (TPE) is the commonly used term to indicate plasmapheresis followed by replacement with fresh frozen plasma infusion.

Indications and Evidence of Plasmapheresis and Therapeutic Plasma Exchange in Critical Illness

In the latest version of the “Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—Evidence-Based Approach” published by the American Society for Apheresis (ASFA), the recommendations are divided into four categories:

Category I: Disorders for which apheresis is accepted as first-line therapy, either as a primary stand-alone treatment or in conjunction with other modes of treatment
Category II: Disorders for which apheresis is accepted as second-line therapy, either as a stand-alone treatment or in conjunction with other modes of treatment
Category III: Optimum role of apheresis therapy is not established. Decision making should be individualized.
Category IV: Disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful. Institutional Review Board (IRB) approval is desirable if apheresis treatment is undertaken in these circumstances.

The ASFA document gives an extensive review of the literature on the rationale for plasmapheresis in 72 diseases, including technical recommendations such as duration and types of replacement fluid. In this chapter, we briefly review diseases in critically ill patients for whom plasmapheresis/TPE is recommended as first-line therapy by the ASFA. We can group these recommendations into thrombotic microangiopathies, acute liver failure, neurologic disorders, renal disorders, and ABO-incompatible solid organ transplantation. We also discuss the current evidence and research for TPE in sepsis-induced multiple organ failure, because this still has a high mortality rate without specific therapeutic strategy other than support care.

Thrombotic Microangiopathies

Thrombotic microangiopathies (TMA) are a family syndrome associated with disseminated microvascular thromboses. The clinical features include microangiopathic hemolytic anemia, thrombocytopenia, and if untreated, MOF. The ASFA gives a category I recommendation to use TPE for thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) resulting from factor H autoantibodies, and ticlopidine-mediated TMA.

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