A 17-month old child suffered a stroke in July of 2010. The results of a specimen collected ten days after the event showed that his protein C and protein S activities were 54% and 40%. Reference intervals for a child over 1 year old are the same as adults: 65% to 140% for protein C and 70% to 140% for protein S. An MRI revealed a previous stroke and the neurologist concluded the child had combined inherited protein C and protein S deficiencies. However, repeat assays performed one month after the stroke were 79% and 74%. What happened?
The prevalence of hereditary protein C deficiency in the community is 1 in 300, and protein S, 1 in 1000, so the likelihood of a patient possessing both deficiencies is 1 in 300,000. In 2004, however, Dr. Marisa Marques and I reviewed five years of laboratory data and found that nearly 20% of thrombophilia profiles turn up a combined protein C and protein S deficiency. This is an error of timing, and illustrates the need for education that helps us avoid an erroneous diagnosis. Laboratory practitioners know that proteins C and S are vitamin K-dependent, and that their activity is reduced in warfarin therapy. They also drop during or following a thrombotic event, and protein S activity at least, is low during inflammation and pregnancy.
laboratory directors regularly remind physicians that specimens for proteins C and S and for antithrombin activity and antigen assays must be collected at least ten days after warfarin is discontinued and at least ten days after resolution of a clotting episode to accurately identify a genetic deficiency. Positive results should be repeated once after a period of several weeks, and first-degree relatives should be tested to confirm the deficiency is hereditary.
Can you provide anecdotes about situations you have experienced in which a patient believes they have a combined protein C and S deficiency? Please respond in our comments section. Geo.
