Congenital factor VII deficiency presenting as delayed bleeding following dental extraction. A review of the role of factor VII in coagulation.

Recent updated models of the coagulation mechanism suggest that factor VII/thromboplastin complex is the main initiator or trigger of coagulation. Factor VII activation of factor IX is likely to be an important activation pathway. Inhibition of factor VII by tissue factor pathway inhibitor may have a regulatory role in the initiation of coagulation. Defining factor VII's interactions in coagulation physiology may lead to answers for some clinical problems in both hemostasis and thrombosis. We describe a 15-year-old Chinese boy with factor VII deficiency and a factor VII level of 0.08 U/ml. His symptoms were recurrent epistaxis and moderate delayed bleeding post-dental extraction. Such specific symptoms have been reported previously in a study of 40 European patients. It is one diagnosis to consider if a patients main symptom is significant post-dental bleeding. It is possible that there is requirement for higher levels of factor VII at these anatomical sites making them the common sites for symptoms in patients with moderate deficiency. Case reports of rare clotting factor deficiencies will illustrate what may be important in vitro functions of clotting proteins. Therefore reporting should be encouraged, especially during review and reconsideration of models of the coagulation mechanism.

Transient myeloproliferative disorder in a Down's neonate with rearranged T-cell receptor beta gene and evidence of in vivo maturation demonstrated by dual-colour flow cytometric DNA ploidy analysis.

Neonates with Down's syndrome may develop a transient myeloproliferative disorder (TMPD) which on presentation is indistinguishable from acute leukemia, with the difference manifest only on follow-up. The clinical course is one of spontaneous remission in TMPD and relentless progression in leukemia. We describe a Down's neonate presenting with hyperleucocytosis and circulating blasts which were positive for CD34, myeloid (CD33), megakaryocytic (CD41, CD42b, CD61), and T-lineage (CD3, CD7), but not B-lineage, associated antigens. Clonal rearrangement of the T-cell receptor beta (TCR beta) gene was found, with the immunoglobulin heavy chain gene in germline configuration, showing the disease to be a clonal proliferation of a multipotential stem cell involving the myeloid and T lineages. Dual-colour flow cytometric DNA ploidy analysis of CD41 positive blasts showed initially a predominant 2N population, but polyploidization to 6N and 8N cells was found on follow-up, concomitant with a progressive decrease in circulating blasts, suggesting maturation of the abnormal clone and a provisional diagnosis of TMPD. This was shown by the eventual resumption of normal haemopoiesis with the disappearance of blasts and the clonally rearranged TCR beta gene.

Dual-color flow cytometric analysis of megakaryocytic DNA ploidy in the investigation of blastic phase chronic myelogenous leukemia with rearrangement of 3q26.

A patient is described with chronic myelogenous leukemia in blastic crisis, in whom numerous circulating platelet fragments and megakaryocytic nuclei were present, with 50% blasts and 50% micromegakaryocytes in the marrow. The blasts expressed myeloid-associated antigens CD34, CD33, and CD13, whereas the micromegakaryocytes were positive for CD41, CD42b, and CD61. These findings suggested a myeloblastic transformation with a possible megakaryoblastic component. Cytogenetic analysis showed rearrangement of 3q26 in the form of t(2;3) (p13;q26), in addition to t(9;22) (q34;q11). Dual-color flow cytometric analysis of DNA content of CD42b-positive cells showed that the micromegakaryocytes were predominantly 2N, indicating a maturation block before nuclear endoreplication and polyploidization. These findings confirmed a combined myeloblastic and megakaryoblastic transformation. It is concluded that dual-color flow cytometric DNA analysis is a useful method for the investigation of abnormal megakaryocytopoiesis in hematologic malignancies.

Use of technicon H*1 technology in routine thalassaemia screening.

In a retrospective study of 36 cases of alpha-thalassaemia trait, 43 cases of beta-thalassaemia trait and 45 cases of iron deficiency, we have assessed the performance of the Technicon H*1 erythrogram, the hypochromia minus microcytosis (H-M) index, and the discriminant function (DF). The diagnostic accuracy of the erythrogram pattern was 83.3% for alpha-thalassaemia trait and 95.3% for beta-thalassaemia trait. The diagnostic accuracy for the H-M index was 19.4% for alpha-thalassaemia trait, 72.1% for beta-thalassaemia trait and 91.1% for iron deficiency. By comparison, the DF gave a diagnostic accuracy of 75.0% for alpha-thalassaemia trait, 81.4% for beta-thalassaemia trait and 88.9% for iron deficiency when using a locally derived value for the constant (k) = 19.2. Our study shows that the H*1 erythrogram pattern, the H-M index and the DF are useful predictive indicators in routine laboratory screening for thalassaemia.

An evaluation of leucocyte analysis on the Coulter STKS.

The performance of leucocyte analysis on the Coulter STKS (Coulter, Hialeah, FL, USA) was evaluated for accuracy, precision and reliability. The results were compared with those obtained from visual examination of a Romanowsky stained blood film together with the automated WBC-diff. from the Technicon H*1 (Technicon, Tarrytown, NY, USA). The relationship between the number of cells counted per WBC-diff. and the WBC count of the sample was established. Precision of the STKS WBC-diff. was acceptable on blood samples with normal and low WBC counts. Correlation with an 800 cell manual WBC-diff. (n = 104) was excellent (r = 0.97, 0.97, 0.83, 0.98 and 0.53 for neutrophils, lymphocytes, monocytes, eosinophils and basophils respectively). Blood specimens, collected into dipotassium EDTA, could be stored at 20-25 degrees C for at least 8 h with no significant effect on the STKS WBC-diff. In a study of 513 patient samples, the BLASTS suspect flag gave 5.4% false positives and zero false negatives, the VARIANT LYMPHS flag gave 1.5% false positives and 0.4% false negatives, and the IMM GRANS/BANDS flag gave 30.8% false positives and 2.3% false negatives. Several instrument and sample related problems were encountered during this study. Despite these limitations, the STKS can provide efficient 5 part WBC-diffs. and effective screening for WBC abnormalities.

Comparison of anticoagulants for the preservation of prothrombin time specimens.

The value of different anticoagulants as preservatives of specimens for prothrombin time ratios is evaluated and discussed. An increase in the ratio was demonstrated with all anti-coagulants after 24 hours and this was significant when coagulometer error was taken into account. Both solid and liquid sodium citrate were superior to sodium oxalate as preservatives at 24 hours after taking off samples, but differences were slight and were not significant when coagulometer error was considered. It was concluded that for routine clinical practice, where a range of the prothrombin time ratio of 1.8/1 to 2.5/1 is allowable, there would be no significant advantage in any of the anticoagulants considered.