Hb Dartmouth [alpha66(E15)Leu-->Pro (alpha2) (CTG-->CCG)]: a novel alpha2-globin gene mutation associated with severe neonatal anemia when inherited in trans with Southeast Asian alpha-thalassemia-1.

We report a novel mutation at alpha66(E15)Leu-->Pro (alpha2) (CTG-->CCG), that we have named Hb Dartmouth for the medical center at which the patients were cared for, in monozygotic twins who also inherited the Southeast Asian alpha-thalassemia-1 deletion. The mother, of Khmer ancestry, is heterozygous for alpha-thalassemia-1. The father, who is of Scottish-Irish ancestry, is a silent carrier of the codon 66 mutation. The twins had severe neonatal anemia requiring transfusion.

A method for proficiency testing of small peer groups in the College of American Pathologists Coagulation Surveys.

OBJECTIVE: To develop a grading scheme for the proficiency testing of small peer groups of fewer than 10 members for the prothrombin time (PT) and activated partial thromboplastin time (APTT). METHODS: A modified target value for small peer groups was derived based on the assumption that measurement variability in the PT and APTT is more greatly influenced by variations in reagents than in instruments. Criteria for grading were established by statistical simulation to achieve misclassification errors of less than 5% for both incorrectly passing and failing participants. College of American Pathologists Coagulation Survey data were analyzed to determine the number of additional laboratories graded using the proposed scheme, as well as the failure rates among participants in the small peer groups. RESULTS: The modified target value for small peer groups is a weighted average between the mean of the peer group and the mean of all participants using the same reagent (reagent group). Peer groups with as few as 4 members can be graded provided that specific criteria are satisfied: there must be at least 5 peer groups for the same reagent, at least 3 of these 5 peer groups must have more than 3 members, and the coefficient of variation for the reagent group must be less than 10%. This proposed grading scheme decreased the number of ungraded laboratories by 44% to 46% for the PT and 42% to 55% for the APTT. The percentage of failing grades among participants in the small peer groups ranged from 1.3% to 4.1% for the PT and 1.4% to 7.2% for the APTT. These failure rates were 2.8- to 13.0-fold higher than the failure rates in large peer groups (P < or = .05). CONCLUSIONS: The proposed small peer group grading scheme can improve the effectiveness of College of American Pathologists proficiency testing for the PT and APTT and may also be generally applicable to other test methods and analytes.

College of American Pathologists Conference XXXI on laboratory monitoring of anticoagulant therapy: laboratory monitoring of oral anticoagulant therapy.

OBJECTIVE: To review the state of the art of laboratory monitoring of oral anticoagulant therapy, as reflected by the medical literature and the consensus opinion of recognized experts in the field, and to make recommendations for improvement in laboratory monitoring of oral anticoagulant therapy. DATA SOURCES: Review of the medical literature, primarily from the last 10 years, and current laboratory practices by a panel of 8 international experts in the field of oral anticoagulant monitoring. DATA EXTRACTION AND SYNTHESIS: After an initial assessment of the literature, key points were identified. Experts were assigned to do an in-depth review of the literature and current practices relevant to each of the key points and to prepare a summary of their findings and recommendations. A draft manuscript was prepared and circulated to every participant in the College of American Pathologists Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy prior to the conference. Each of the key points and associated recommendations was then presented for discussion at the Conference. Recommendations were accepted if a consensus of the 26 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 12 recommendations concerning the laboratory monitoring of oral anticoagulant therapy. Detailed discussion of the rationale for each of these recommendations is found in the text of this article. Discussion of points on which consensus was not reached is also included in the text. It is hoped that widespread adoption of these recommendations will further improve the laboratory monitoring of oral anticoagulant therapy.

The preoperative bleeding time test lacks clinical benefit: College of American Pathologists' and American Society of Clinical Pathologists' position article.

The major conclusions of this position article are as follows: (1) In the absence of a history of a bleeding disorder, the bleeding time is not a useful predictor of the risk of hemorrhage associated with surgical procedures. (2) A normal bleeding time does not exclude the possibility of excessive hemorrhage associated with invasive procedures. (3) The bleeding time cannot be used to reliably identify patients who may have recently ingested aspirin or nonsteroidal anti-inflammatory agents or those who have a platelet defect attributable to these drugs. The best preoperative screen to predict bleeding continues to be a carefully conducted clinical history that includes family and previous dental, obstetric, surgical, traumatic injury, transfusion, and drug histories. A history suggesting a possible bleeding disorder may require further evaluation; such an evaluation may include performance of the bleeding time test, as well as a determination of the platelet count, the prothrombin time, and the activated partial thromboplastin time. In the absence of a history of excessive bleeding, the bleeding time fails as a screening test and is, therefore, not indicated as a routine preoperative test.

Complex t(1;15;17) in acute promyelocytic leukemia with duplication of RAR alpha and PML sequences.

A 46-year-old white male presented with a two-week history of a flu-like illness and bleeding gums. A diagnosis of acute promyelocytic leukemia was made on bone marrow examination with accompanying DIC. All cytogenetically abnormal cells (28/30 at intake and 30/30 at two weeks post-induction) represented a single clone with apparent deletion of 1(p22) and 3(p25), and with a large, derivative chromosome 17. By conventional G- and C- banded analysis, the monocentric der(17) appeared to be disrupted distal to the typical (17q21) APL breakpoint, chromosome 15 did not demonstrate gross rearrangement, and the source of the additional material on the der(17) was unknown. Fluorescence in situ hybridization (FISH) with t(15;17), RAR alpha, and 17qter probes and with chromosome 1, 15, and 17 paints demonstrated that the der(17) consisted of a complex rearrangement with duplication of both RAR alpha and PML, insertion of chromosome 1 sequences, and double insertion of chromosome 15 sequences. The fusion of RAR alpha and PML consistent with APL appears to have occurred at the distal juxtaposition of these sequences in the derivative chromosome.