David Jupe

Accuracy and clinical utility of the CoaguChek XS portable international normalised ratio monitor in a pilot study of warfarin home-monitoring.

Aim: To evaluate the accuracy of the CoaguChek XS international normalised ratio (INR) monitor compared with the laboratory method. Methods: The accuracy and ease of use of the recently marketed CoaguChek XS portable INR monitor was evaluated in 17 patients involved in a trial of warfarin home monitoring. INR results from the monitor were compared with those from the laboratory method. Clinical applicability was measured by discrepant INR values, defined in the literature by expanded and narrow agreement criteria, and by the proportion of INR values differing by >15% and by >20% from those derived by the laboratory method. Results: Participants provided 59 comparison INR measurements for analysis. The paired results were highly correlated (r = 0.91). Expanded and narrow agreement between paired INR values occurred 100% of the time. Only three CoaguChek XS (5.1%) results differed by >15% compared with the laboratory method; no results differed by >20% or were discrepant by >0.5 INR units. Conclusions: In the hands of patients the CoaguChek XS showed good correlation with laboratory determination of INR and compared well with expanded and narrow clinical agreement criteria. Both patients and doctors were highly satisfied with the accuracy and ease of use of the CoaguChek XS.

Short‐term warfarin reversal for elective surgery – using low‐dose intravenous vitamin K: safe, reliable and convenient*

Peri‐procedural management of warfarin reflects an intricate balance between the restoration of haemostasis and appropriate thromboprophylaxis. This prospective single‐arm study assessed the safety and efficacy of a convenient schedule, incorporating low‐dose intravenous vitamin K (vitKIV) for short‐term warfarin reversal prior to elective surgery, as well as vitK‐dependent factor levels (vitK‐Factors) and International Normalized Ratio (INR) pre‐ and post‐vitKIV. One seventy eight patients on long‐term warfarin received 3 mg vitKIV 12–18 h pre‐procedure with no adverse reactions. 167/178 (94%) achieved an INR ≤ 1·5 post‐vitKIV on the day of surgery, while all achieved INR ≤ 1·7. Four patients had procedure‐associated major bleeding, but importantly had achieved a pre‐procedure INR < 1·5 and vitK‐Factors >0·30 iu/ml. No patient suffered a symptomatic thromboembolism during the 6‐week follow‐up. Median days to re‐establish a therapeutic INR were 4 (range 2–11). VitKIV near normalized all vitK‐Factors, with a uniform pattern of depletion and repletion in association with an increase and decrease in INR, respectively; and from the data, INR < 1·5 correlated with vitK‐Factors >0·30 iu/ml. Low‐dose vitKIV for short‐term warfarin reversal was reliable and safe, and successfully lowered the INR to an acceptable level for planned surgery, with no excess of bleeding, thromboembolism, delayed discharge, or resistance to warfarin. The protocol was simple and convenient for both the patients and the healthcare institution.

Functional and phenotypic analysis of a T cell prolymphocytic leukemia

Peripheral blood mononuclear cells obtained from a patient with prolymphocytic leukemia expressed the surface membrane markers characteristic of resting mature T helper lymphocytes. These cells responded to the T cell mitogens PHA and Con A in a blast transformation assay but not the anti-T cell monoclonal antibody Leu 4 and the B cell mitogen, PWM. The concentration of PHA or Con A eliciting maximum blast transformation was less than that required by normal mononuclear cells. The leukemic cells recognised and responded to allogeneic pooled mononuclear cells in a mixed lymphocyte culture. In addition, although they did not express Ia antigens, they served as effective stimulators in the mixed lymphocyte reaction. Consistent with the helper phenotype, the leukemic cells did not produce suppressor factors, but provided help for normal B-enriched lymphocytes to respond to PWM as assessed by both blast transformation and IgG production. T lymphocyte colonies developed when the leukemic cells were treated with PHA during a 20 h liquid culture prior to being seeded into semisolid agar medium containing either PHA or an IL2-containing lymphokine. There was no growth when untreated cells were seeded directly into IL2-containing agar. Analysis of colony formation indicated that, as with normal resting T lymphocytes, proliferation occurred in two distinct steps; activation in response to PHA and replication in response to IL2-like growth factors. These findings demonstrate that in this case the helper T prolymphocytes have the functional capabilities of normal mature T lymphocytes as predicted from their helper phenotype.

Improving clinical outcomes for hospital patients initiated on warfarin

Studies have demonstrated that the risk of warfarin‐related complications is highest in the first 90 days of treatment, while quality audits suggest that warfarin initiation protocols are not always adhered to.

Experience with Recombinant Factor VIla in Australia and New Zealand

Recombinant factor VIIa (rFVIIa; NovoSeventrademark) was availablefor compassionate use in Australia and New Zealand from 1991 to 1994. Over this period there were 18 treatment episodes in 9 patients, age 8-66 years, with haemophilia A and high titre inhibitors cross-reacting with porcine factor VIII. There were no significant adverse effects. Treatment with rFVIIa resulted in a successful outcome in 8 potentially life-threatening (retroperitoneal, subdural, gastro-intestinal) bleeds. Elective cystoscopy, repair of a cranial flap, yttrium synovectomy and inguinal herniotomy were performed successfully, as was surgical decompression of a flexor pollicis longus bleed. Treatment of a patient with an infected haematoma had limited success, attributed to intermittent suboptimal doses. In 2 patients, satisfactory haemostasis was achieved for multiple dental extractions; subsequent oozing was attributed to suboptimal rFVIIa and/or antifibrinolytic therapy.