An alternative extrinsic pathway of human blood coagulation

To study the interrelationships of the major human coagulation pathways, factor X activation in normal and various deficient human plasmas was evaluated when clotting was triggered by dilute rabbit or human thromboplastin. Various dilutions of thromboplastin were added to plasma samples containing 3H-labeled factor X, and the time course of factor X activation was determined. At a 1/250 dilution of rabbit brain thromboplastin the rate of factor X activation in factor VIII or factor IX deficient plasma was only 10% of the activation rate seen for normal or factor XI deficient plasma. Reconstitution of the deficient plasmas with factors VIII or IX, respectively, restored normal factor X activation. Similar results were obtained when various dilutions of human thromboplastin replaced the rabbit thromboplastin. From these experiments, it is inferred that normal activation of factor X in plasma due to dilute thromboplastin requires factors VII, IX and VIII. An alternative extrinsic pathway that involves factors VII, IX, and VIII may be a major physiologic extrinsic pathway, and this pathway may help to explain the clinical observations of bleeding diatheses in patients deficient in factors IX or VIII.     

Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study

Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.     

Ca2+ transport systems mediating the high K+/low Na+-induced uptake of Ca2+ into rat atrium

The effect of high K+/low Na+-Tyrode's solution on Ca2+ uptake into neonatal rat atrium was studied using 45Ca2+. Substitution of 60-129 mM Na+ in Tyrode's solution by equimolar concentrations of K+ or choline, significantly (with the exception of 60 mM choline substitution) increased Ca2+ uptake above control. Furthermore, the Ca2+ uptake stimulated by K+ substitution was significantly greater than that stimulated by choline substitution at the corresponding concentrations. The choline/low Na+-induced Ca2+ uptake (i.e. that above the Ca2+ uptake measured in normal Tyrode's solution) was increased by pre-exposure to either ice-cold Tyrode's solution for 1 h (approximately 36% increase) or to K+-free Tyrode's solution for 3 h (approximately 100% increase). The choline/low Na+-induced Ca2+ uptake was abolished by the hypertonic addition of NaCl (returning the bathing Na+ concentration to normal), increased (approximately 140%) by the addition of 1.8 mM PO4(3-)-free Hepes buffered choline/low Na+ media, but unaffected by 0.2 mM cadmium. The high K+/low Na+-induced Ca2+ uptake (i.e. that above the Ca2+ uptake measured in normal Tyrode's solution) was relatively insensitive to pre-exposure to cold (0% change) or K+-free media (11% increase) and only 50% inhibited by the hypertonic addition of NaCl (returning the bathing Na+ concentration to normal). However, the high K+/low Na+-induced Ca2+ uptake was 57% inhibited by 0.2 mM cadmium and approximately 30% inhibited by the addition of 1.8 mM PO4(3-) to HCO3-/PO4(3-)-free Hepes buffered high K+/low Na+ media.(ABSTRACT TRUNCATED AT 250 WORDS)     

Factor V deficiency in Philadelphia-positive chronic myelogenous leukemia

Factor V deficiency has been identified in 8 of 8 patients 7--20 yr of age, with Philadelphia-positive (Ph1+) chronic myelogenous leukemia (CML). In these 8 patients, factor V deficiency was not due to hepatic dysfunction, factor V inhibitors, or disseminated intravascular coagulation. In 3 patients, factor V activity rose 10%--12% (0.10--0.12 U/ml) after the infusion of 28--31 ml/kg body weight of fresh frozen plasma (FFP). The rise persisted less than 14 hr. The mean measured postinfusion rise in factor V was 18% of the expected rise calculated from the volume of FFP infused in the patients' plasma volume. In 4 patients, a small transient rise in factor V activity occurred after splenectomy or plateletpheresis. Factor V deficiency was completely corrected after a marked reduction in bone marrow cellularity in 2 patients with Ph1+ CML treated with extensive chemotherapy, total body irradiation, and bone marrow transplantation. Factor V deficiency was retrospectively observed in 6 of 20 patients, ages 20--80 yr, with Ph1+ CML and 3 of 6 patients with other myeloproliferative disorders. The factor V deficiency appears to be associated with the large myeloid- megakaryocytic cell mass characteristic of CML and other myeloproliferative disorders.     

Repeat liver resection after a hepatic or extended hepatic trisectionectomy for colorectal liver metastasis

Objective: A right and left hepatic trisectionectomy and an extended trisectionectomy are the largest liver resections performed for malignancy. This report analyses a series of 23 patients who had at least one repeat resection after a hepatic trisectionectomy for colorectal liver metastasis (CRLM).Methods: A retrospective analysis of a single-centre prospective liver resection database from May 1996 to April 2009 was used for patient identification. Full notes, radiology and patient reviews were analysed for a variety of factors with respect to survival.Results: Twenty-three patients underwent up to 3 repeat hepatic resections after 20 right and 3 left hepatic trisectionectomies. In 18 patients the initial surgery was an extended trisectionectomy. Overall 1-, 3- and 5-year survival rates after a repeat resection were 100%, 46% and 32%, respectively. No factors predictive for survival were identified.Conclusion: A repeat resection after a hepatic trisectionectomy for CRLM can offer extended survival and should be considered where appropriate.