Summary.  Background: In an effort to improve interlaboratory agreement in the monitoring of unfractionated heparin (UFH), the College of American Pathologists (CAP) recommends that the therapeutic range of the activated partial thromboplastin time (APTT) be defined in each laboratory through correlation with a direct measure of heparin activity such as the factor Xa inhibition assay. Whether and to what extent this approach enhances the interlaboratory agreement of UFH monitoring has not been reported. Objectives: We conducted a cross‐validation study among four CAP‐accredited coagulation laboratories to compare the interlaboratory agreement of the anti‐FXa‐correlated APTT with that of the traditional 1.5–2.5 times the midpoint of normal (1.5–2.5:control) method for defining the therapeutic APTT range. Patients and methods: APTT and FXa inhibition assays were performed in each laboratory on plasma samples from 44 inpatients receiving UFH. Results: Using the anti‐FXa‐correlation method, there was agreement among all four laboratories as to whether a sample was subtherapeutic, therapeutic or supratherapeutic in seven (16%) patient samples. In contrast, consensus was achieved in 23 (52%) samples when the 1.5–2.5:control method was employed. Conclusions: The anti‐FXa‐correlation method does not appear to enhance interlaboratory agreement in UFH monitoring as compared with the traditional 1.5–2.5:control method. Adoption of the anti‐FXa‐correlation method produces considerable disparity in UFH dosing decisions among different centers, although the clinical impact of this disparity is not known.

African Americans with factor VII (FVII) deficiency, as defined by clinical laboratory values, are frequently asymptomatic. To date the genotypes underlying this FVII defect in asymptomatic African Americans have not been established. We show in 3 unrelated African-American patients that the defect is due to a G to A nucleotide change resulting in an arginine to glutamine mutation in Factor VII amino acid 304. This defect results in low FVII coagulant activity levels using rabbit brain thromboplastin but not using human thromboplastin. This report may aid transfusion and hematology specialists evaluate patient results and prevent unnecessary transfusions to treat patients with abnormal laboratory values.

African Americans with factor VII (FVII) deficiency, as defined by clinical laboratory values, are frequently asymptomatic. To date the genotypes underlying this FVII defect in asymptomatic African Americans have not been established. We show in 3 unrelated African-American patients that the defect is due to a G to A nucleotide change resulting in an arginine to glutamine mutation in Factor VII amino acid 304. This defect results in low FVII coagulant activity levels using rabbit brain thromboplastin but not using human thromboplastin. This report may aid transfusion and hematology specialists evaluate patient results and prevent unnecessary transfusions to treat patients with abnormal laboratory values.

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Background: Symptomatology in congenital human FVII deficiency with FVII:C (Factor VII Coagulant Activity) levels < 1% ranges from asymptomatic to severe hemorrhagic problems. Additionally, FVII:C differs markedly depending upon the source of tissue factor (TF) in the thromboplastin utilized for measuring FVII:C. FVII deficiency reported in 1978 in patients from Padua, Italy was later shown to be associated with an arginine (R) to glutamine (Q) mutation at FVII amino acid 304. A study by Triplett et al. from 1985 reported FVII deficiency in 26 patients including 16 Caucasians, 1 Hispanic and 9 blacks. Of these patients, all 9 black patients were asymptomatic whereas the other 17 patients had a clinically relevant bleeding disorder. Since that time there have been no reports describing the genetic cause of FVII deficiency in asymptomatic African American individuals. Methods: Plasma was obtained from patient blood samples obtained in 3.2% sodium citrate. FVII:C levels were performed using one-stage clotting assays with either rabbit brain thromboplastin (Simplastin Excel, Biomerieux, Durham, NC) or lyophilized recombinant human TF (Innovin, Dade Behring, Inc., Newark, DE). Factor VII antigen levels (VII:Ag) were measured using an enzyme-linked immunoabsorbent assay (American Bioproducts Co, Parsippany, NJ). A normal pool was constructed by mixing equal volumes of plasma from greater than 20 healthy control subjects. Results Patient # Prothrombin Time in seconds FVII:C Simplastin Excel FVII:C Innovin FVII:Ag Genotype Phenotype 1-African American 15.6 16% 33% 61% Heterozygote R304Q Minor Nose Bleeds 2- African American Prolonged 26% 54% 67% Heterozygote R304Q Asymptomatic for bleeding 3- African American 14.5 21% 64% NA Heterozygote R304Q Asymptomatic for bleeding Conclusions: We show that FVII deficiency in three asymptomatic African American patients at our specialty laboratory was due to FVII-Padua (R304Q). An additional ten African American patients showed prolonged prothrombin times and FVII:C values consistent with the laboratory phenotype of FVII-Padua. This diagnosis prevented inappropriate blood transfusions prior to surgery in several of these patients.