In vitro hemolysis – a potential cause of preanalytical error reviewed

The process of laboratory/point-of-care testing of patient samples comprises three distinct phases: the preanalytical phase, which includes sample collection and transport to the site of testing; the analytical phase; and the postanalytical phase, which includes communication and interpretation of the test result as well the clinical response to the test result in terms of patient management.

Patient safety can be threatened by error at each of these phases but study has clearly shown that most errors in diagnostic testing occur during the preanalytical phase. In vitro hemolysis, which is one of the most common causes of preanalytical error and a common reason for sample rejection, is the focus of this recently published review article.

The authors briefly first review the range of errors that can occur during the preanalytical phase, placing in vitro hemolysis in a wider context. They define hemolysis as the rupture of erythrocytes with release of intracellular contents to plasma and make the important distinction between in vitro hemolysis, which results from poor sample collection/handling, and in vivo hemolysis, a pathological condition. This introductory section includes brief reference to the two methods of detecting hemolysis in centrifuged samples: visual inspection and spectrophotometric analysis. 

The main body of the article is presented under three headings: factors that increase hemolysis; consequences of hemolysis; and finally, management of hemolysis. The authors identify three main stages of the preanalytical process for discussion of factors that increase hemolysis: blood collection, centrifugation of the sample and finally, the process of sample transport.

The authors cite study evidence that there is potential for hemolysis at each of these stages. So for example, they cite evidence that sampling blood via intravenous catheters is associated with greater risk of hemolysis than sampling blood conventionally by venipuncture. The gauge of the needle, characteristics of the collection tube, the site of venipuncture and the use of tourniquet have all been implicated as potential causes of increased hemolysis during blood collection. 

Consideration by the authors of the potential for hemolysis to occur during sample transport is focused almost exclusively on studies investigating the potential hemolyzing effect of pneumatic tube transport. 

Under the main heading, consequences of hemolysis, the authors highlight the analytes particularly susceptible to spurious results as a consequence of in vitro hemolysis. Some, e.g. potassium (K), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) are spuriously raised, whilst others (e.g. glucose, sodium (Na) and chloride (Cl)) are spuriously reduced. 

Under the final main heading, management of hemolysis, the authors discuss the options to be considered when a sample is found to be hemolyzed. This discussion focuses on three options: repeat sample collection; report result with hemolysis warning comment; and report mathematically corrected result based on estimated degree of hemolysis. The authors reflect wider opinion that repeat sampling collection is probably the best (safest) option, but this may not always be possible or appropriate.

In summary, this is an up-to-date non-systematic review of a significant and relatively common source of preanalytical error based on 70 cited references.