Laboratory Analysis of Abnormal Closure Times with Relation to Low Ristocetin Cofactor Versus Other Causes.

Closure times (CTs) have replaced the limitations of the previous testing methods. However, the clinical utility of detecting abnormal CTs remains poorly defined, with the differential diagnosis including von Willebrand’s disease (vWD), aspirin or NSAIDs, uremia, liver disease, or congenital defects. Ristocetin cofactor (RCoF) measures the functional activity of the vW molecule and when low, most often suggests vWD. CTs are frequently done in patients suspected by history of having vWD with some laboratories preferring to perform the collagen/epinephrine (Col/Epi) CT alone, while others additionally include the collagen/ADP (Col/ADP) CT.

METHODS: We analyzed 1480 consecutive CTs from a large reference laboratory done on a PFA-100 (Dade-Behring) and correlated the CTs with RCoF levels done on a BCS analyzer (Dade-Behring). Normal ranges were: Col/Epi CT 84-175 sec.; Col/ADP CT 65-117 sec.; RCoF 0.5-1.5 U/ml. Calculated means for CT of ≥ 300 sec. used a level of 300.

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Of the 260 studies with abnormal closure times, 131 (50%) had normal RCoF values, 47 (18%) were high and 18 (32%) were low. All studies with low RCoFs had at least one abnormal CT with 78/82 (95%) having both CTs prolonged, 2/82 (≫2%) with a long Col/EPI only, and 2/82 (≫2%) with a long Col/ADP only. Mean CTs in patients with low RCoFs and both CTs abnormal were 252 seconds for Col/EPI and 174 seconds for Col/ADP, both well above the upper limits of the normal range. Mean CTs in patients with low RCoFs and one abnormal CT were 180 seconds for Col/EPI and 123 seconds for Col/ADP, both just slightly above the upper limits of the normal range.

CONCLUSIONS: These findings suggest that when RCoF is low, both Col/EPI and Col/ADP CTs are prolonged, usually markedly, and the chances that a low RCoF will be missed is low, particularly if both CTs are used.

RESULTS: Total CTs analyzed: 1480 No.≥ 1 Abnormal CT 260/1480 (18%)