Monitoring unfractionated heparin therapy with antifactor Xa activity results in fewer monitoring tests and dosage changes than monitoring with the activated partial thromboplastin time.

STUDY OBJECTIVE: To determine how much more costly it is to monitor unfractionated heparin (UFH) therapy by antifactor Xa heparin activity (HA) than by activated partial thromboplastin time (aPTT). DESIGN: Prospective, randomized, unmasked, cohort, single-center study. SETTING: A 625-bed, adults-only, private teaching hospital. PATIENTS: Two hundred sixty-eight patients with a variety of indications for UFH therapy. INTERVENTIONS: Patients were treated with UFH based on ideal weight (75 U/kg bolus, 20 U/kg initial infusion) and monitored by either HA or aPTT, MEASUREMENTS AND MAIN RESULTS: After adjusting for gender, groups were equivalent in patient characteristics and UFH dosage. The HA group had fewer monitoring tests and dosage changes/24 hours than the aPTT group. These reductions neutralized much of the increased cost of the HA assay itself. CONCLUSION: Monitoring UFH therapy over 96 hours with an HA assay costs $4.37 more than monitoring with aPTT. This modest increase may be acceptable given other advantages of the HA assay.

In unfractionated heparin dosing, the combination of patient age and estimated plasma volume predicts initial antifactor Xa activity better than patient weight alone.

STUDY OBJECTIVE: To determine whether patient factors other than body weight would better predict patients' initial antifactor Xa heparin activity (HA) after start of unfractionated heparin (UFH) therapy. DESIGN: Case series. SETTING: A 625-bed, adults-only, private, tertiary care teaching hospital. PATIENTS: Ninety-two patients requiring UFH therapy. INTERVENTIONS: Patients received initial UFH bolus doses of 72-80 U/kg ideal weight and initial UFH infusions of 19.1-21.2 U/kg ideal weight. MEASUREMENTS AND MAIN RESULTS: Fifty-five percent of the first 6-hour HA measurements were supratherapeutic (> 0.7 U/ml antifactor Xa activity). Patient weight was inferior to a combination of age and estimated plasma volume in predicting initial HA. A predictive model including these two factors accounted for 38.5% of variation in first HA levels compared with 17.7% with actual weight alone. CONCLUSION: Weight-based UFH dosing may frequently result in nontherapeutic initial HA levels. Initial UFH dosing might be improved if protocols based on patient age and estimated plasma volume were developed.

Comparing different lots of activated partial thromboplastin time reagent: analysis of two methods.

This study was conducted to compare the performance of 2 different lots of activated partial thromboplastin time (APTT) reagent from the same manufacturer. Two hundred plasma samples were analyzed for APTT on the same instrument using 2 separate APTT reagent lots. Results were compared with those obtained from duplicate APTT determinations with 1 reagent lot on an additional 267 plasma samples. Regression analysis of paired APTT data was suboptimal because the disagreement of the results increased as the APTT values became higher. A better approach was the use of the Bland and Altman assessment of agreement method on logarithmically transformed data, which showed that the new reagent lot produced values that were 88.9% of the values produced by the old lot. This importantly reduced the APTT therapeutic range for unfractionated heparin (UH). In comparison, duplicate APTT values were 97.6% of a first APTT value. However, 95% limits of agreement for duplicate APTT determinations were +/-10% over the range of values considered therapeutic for UH. The variability of APTT results within and between reagent lots is one reason that APTT may not be optimum for monitoring UH therapy.

Comparison of anti-factor Xa heparin activity and activated partial thromboplastin time in 2,773 plasma samples from unfractionated heparin-treated patients.

This study was conducted to evaluate two methods of determining the "therapeutic range" of the activated partial thromboplastin time (APTT) during unfractionated heparin treatment. Multiple fresh plasma samples from 694 patients treated with unfractionated heparin were tested simultaneously for APTT and anti-factor Xa heparin activity. The data were analyzed by linear regression and by a minimization-of-error technique to determine the more accurate APTT therapeutic range. The best-fit linear regression equation was obtained using logarithmically transformed APTT values. Using this equation, the heparin activity predicted by an APTT value had a 95% limit of agreement of +/- 0.39 U/mL compared with the actual heparin activity. The total clinical error rate of the APTT therapeutic range selected using the best-fit regression equation was 10%. An improvement to 8% was achieved using a method that chose the therapeutic range based on minimizing the APTT errors. Even 8% may be too high an error rate for best clinical results.

The influence of heparin on the prothrombin time.

We studied the effect of known concentrations of heparin on the prothrombin time (PT) in patients receiving warfarin and in controls who were not anticoagulated. Plasma from the subjects and controls was serially diluted with known concentrations of heparin, and PT was measured. Linear regression of heparin concentration versus percentage change in PT resulted in r = 0.86 in the warfarin group and r = 0.72 in the control group. The warfarin group was more sensitive to the effects of heparin than the control group, as manifested by a steeper slope of the regression line (p less than 0.001). Over the therapeutic range of heparin concentration (0.2-0.4 units/ml), the 95% prediction interval of the percentage change in PT was -6-12% at 0.2 units/ml, and 2-20% at 0.4 units/ml in the warfarin group. These results demonstrate a strong relationship between the heparin concentration in plasma and the percentage change in the PT. This effect should be considered when adding warfarin to the regime of patients receiving heparin therapy.

Measurement of canine von Willebrand factor using ristocetin and Polybrene. Diagnosis of canine von Willebrand's disease.

Dogs with VWD provide useful models for the study of the factor VIII complex. However, the study of canine VIIIR:WF has been hampered by the lack of a routine plasma assay for canine RCF, an activity that is usually used as a measure of VIIIR:WF. This study shows that canine plasma can be assayed for RCF with a macroscopic tilt-tube method using formalin-fixed human platelets, ristocetin, and extra canine albumin (5.0 mg/ml) to prevent plasma precipitation. An assay was also developed for canine plasma PBCF, an activity that is closely related to RCF. In 45 normal canine plasmas, VIII:C was not correlated with RCF, PBCF, or VIIIR:AG. However, RCF, PBCF, and VIIIR:AG were well correlated with each other. In 26 canine VWD plasmas, VIII:C was frequently normal, whereas VIIIR:AG, RCF, and PBCF were almost always deficient. The patterns of VIIIR:AG, RCF, and PBCF deficiencies in the canine VWD plasmas suggested that some canine breeds have a "classic" form of VWD whereas other breeds have "variant" forms of disease.

A bleeding disease (von Willebrand's disease) in a Chesapeake Bay Retriever.

A bleeding disease similar to von Willebrand's disease in man was diagnosed in a 6-month-old Chesapeake Bay Retriever with recurrent, protracted gingival hemorrhage that responded rapidly to fresh, whole blood transfusions. The dog had a prolonged bleeding time and low plasma factor VIII coagulant activity (18%). The plasma had no detectable factor VIII-related antigen or von Willebrand factor, as measured by ristocetin-cofactor and polybrene-cofactor activities. The dam of the dog had a plasma factor VIII-related antigen concentration (32%) well below the normal range. The antigen in the sire's plasma was at the low end of the normal range, as was the polybrene-cofactor of both the sire and the dam. These data suggested an inherited basis for von Willebrand's disease in this dog.

Acquired von Willebrand's disease, platelet-release defect and angiodysplasia.

A previously healthy elderly man with gastrointestinal bleeding was found to have criteria for von Willebrand's disease. The late clinical onset of the disorder and negative family studies suggest that the von Willebrand's disease may be acquired. The findings in the patient were similar to the abnormalities reported in the small number of other patients thought to have acquired von Willebrands disease. An inhibitor of factor VIII could not be demonstrated in this patient. This patient also had platelet aggregation abnormalities that are atypical for patients with congenital or acquired von Willebrand's disease. Vascular abnormalities were also found in this patient and in several other previously described patients with von Willebrand's disease.