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Objective: To make recommendations regarding the appropriate evaluation for the prothrombin G20210A mutation, as reflected by published evidence and the consensus opinion of recognized experts in the field. DAT SOURCES: Review of the medical literature, primarily since 1996., Data Extraction and Synthesis: After an initial assessment of the literature, key points defining the condition, and review of the clinical study design, a draft manuscript was prepared and circulated to every participant in the College of American Pathologists Conference on Diagnostic Issues in Thrombophilia before the meeting. Each of the key points and associated recommendations were then presented for discussion at the conference. Recommendations were accepted if a consensus of 70% of experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form., Conclusions: Consensus was reached on several recommendations concerning the criteria for testing for the prothrombin G20210A mutation and for the method of testing. First, a major point of consensus was that the prothrombin G20210A mutation is a significant risk factor for venous thromboembolism (VTE) and that testing should be considered in the initial evaluation of suspected inherited thrombophilia. Second, although several analytic methods are commonly used for genetic testing for the prothrombin mutation, all are generally robust and reliable. The recommendations for testing for the prothrombin mutation parallel those for the factor V Leiden mutation and include patients with a history of recurrent VTE, a first episode of VTE before the age of 50 years, a history of an unprovoked VTE at any age, thromboses in unusual anatomic sites, or an affected first-degree relative with VTE. A history of VTE related to pregnancy or estrogen use and unexplained pregnancy loss during the second or third trimesters were also considered to be indications for testing. Other scenarios remain controversial or not recommended, including general population screening.

Objective: To review the role of an elevated total plasma homocysteine level (hyperhomocyst[e]inemia) in patients with venous or arterial thrombosis, as reflected by the medical literature and the consensus opinion of recognized experts in the field., Data Sources: Review of the medical literature, primarily from the last 10 years., Data Extraction and Synthesis: The literature was reviewed to identify key points defining the condition, and the clinical study design of each article was examined. A draft manuscript was prepared and circulated prior to the conference to every participant in the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia. Each of the key points and associated recommendations was then presented for discussion at the conference. Recommendations were accepted if a consensus of the 70% of the experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form., Conclusions: Consensus was reached on 9 recommendations concerning the criteria for diagnosis, the method of testing, and the approach for clinical management. A major point of consensus was that no causal role of hyperhomocyst(e)inemia in venous or arterial thrombosis is yet established. Testing methods used to measure homocysteine directly are sensitive and reliable, and provide more information than does genotyping for markers linked to abnormal plasma homocysteine.

A retrospective autopsy study during 1957 to 1983 of patients with clinically documented cystic fibrosis (CF) who were at least 15 years old at the time of death (33 patients) revealed that 11 (33%) had amyloid deposits in multiple organs. The spleen, liver, and kidneys were the principally affected organs, with microscopic deposits mainly restricted to blood vessels. Only one patient had overt clinical manifestations of organ dysfunction secondary to the presence of amyloid. No differences were noted between the groups with (11 patients) and without (22 patients) amyloidosis with respect to age at diagnosis of CF; number, severity, and types of infections; and longevity. Our data demonstrate that amyloidosis is more common in patients with CF than previously reported, and this purported increase parallels the longer life span of these patients. Those patients who are older than 15 years of age constitute the particular group at risk, and they should be evaluated for amyloidosis if unusual clinical findings emerge to suggest it. Clinically evident amyloidosis is uncommon, however, in patients with CF and amyloid deposits at this time. It is likely that clinically relevant amyloidosis will become more of a complicating factor in the future as the life span of these patients continues to increase.