TABLE II.
Conditions of the Patient, Blood Sample, and Laboratory Testing Affecting Laboratory Evaluation for von Willebrand Disease (VWD)
| Phlebotomy conditions: An atraumatic blood draw limits the exposure of tissue factor from the site and the activation of clotting factors, minimizing falsely high or low values. Lipemia should be avoided, as it may interfere with photo-optical testing methods, especially some used for VWF:RCo assay. |
| Patient stress level: Undue stress, such as struggling or crying in children or anxiety in adults, may falsely elevate VWF and FVIII levels. Very recent exercise can also elevate VWF levels. |
| Additional conditions in the person: The presence of an acute or chronic inflammatory illness may elevate VWF and FVIII levels, as may pregnancy or administration of estrogen/oral contraceptives. Individuals with blood group O have VWF levels 325% lower than those of other ABO blood groups. African-Americans have higher VWF levels than Caucasians. |
| Sample processing: To prevent cryoprecipitation of VWF and other proteins, blood samples for VWF assays should be transported to the laboratory at room temperature. Plasma should be separated from blood cells promptly at room temperature, and the plasma should be centrifuged thoroughly to remove platelets. If plasma samples will be assayed within 2 hr, they should be kept at room temperature. Frozen plasma samples should be carefully thawed at 37°C and kept at room temperature for <2 hr before assay. |
| Sample storage: Plasma samples that will be stored or transported to a reference laboratory must be frozen promptly at or below −40°C and remain frozen until assayed. A control sample that is drawn, processed, stored, and transported under the same conditions as the tested person’s sample may be helpful in indicating problems in the handling of important test samples. Activity of FVIII typically is 10–20% lower in frozen-thawed plasma than in fresh (nonfrozen) plasma, and can be even lower if blood processing or storage conditions are suboptimal. |
| Laboratory testing: Calibrators for assays of VWF:Ag, VWF:RCo, and FVIII should be referenced to the World Health Organization (WHO) plasma standard. These three tests have relatively high coefficients of variation (CVs of 10–30%), especially the VWF:RCo assay. The quality of laboratory testing also varies considerably among laboratories (high interlaboratory CV). Test results can be reported as international units per deciliter (IU/dL), rather than as a percentage (%) of mean normal, if WHO- linked calibrators are used. Referencing VWF testing results to the population reference range, rather than to ABO-stratified reference ranges, may be clinically useful. |