Association Between Compliance with Triage Directions from an Organized State Trauma System and Trauma Outcomes.

BACKGROUND: The Louisiana Emergency Response Network (LERN), a statewide trauma system, has a single communication center with real-time data on hospital capacity across the state. With these data, scene information, and a standardized triage protocol, prehospital providers are directed to the most appropriate hospital. The purpose of our study was to compare outcomes between those patients who complied with the LERN communication center direction and those who did not. STUDY DESIGN: Trauma patients directed by LERN from the field in 2014 were included. Patients who followed the LERN communication center direction were considered the compliant group. Patients brought to a hospital inconsistent with the LERN direction were considered the noncompliant group. Chi-square analysis was used to compare differences between groups and a p value of <0.05 was considered statistically significant. RESULTS: During the study period, LERN directed 14,071 patients to a destination hospital. Prehospital providers were compliant with the LERN direction in 13,037 (92.7%) patients and noncompliant in 1,034 (7.3%) patients. There were fewer patients in the compliant group (570 of 13,037 [4.3%]) requiring transfer to a second hospital than in the noncompliant group (312 of 1,034 [30.2%]) (p < 0.01). The mortality rate was lower in the compliant group (81 of 13,037 [0.6%]) than in the noncompliant group (21 of 1,034 [2.03%]) (p < 0.01). CONCLUSIONS: Following direction from a central communication center with real-time hospital capacity data yielded a 6-fold decrease in secondary transfer and a 3-fold decrease in mortality. These data emphasize the value of an organized statewide trauma network that routes patients to the appropriate facilities.

Impact of Prehospital Transportation on Survival in Skiers and Snowboarders with Traumatic Brain Injury.

INTRODUCTION: Prehospital helicopter use and its impact on outcomes in snowboarders and skiers incurring traumatic brain injury (TBI) is unknown. The present study investigates the association of helicopter transport with survival of snowboarders and skiers with TBI, in comparison with ground emergency medical services (EMS), by using data derived from the National Trauma Data Bank (2007-2014). METHODS: Primary and secondary endpoints were defined as in-hospital survival and absolute risk reduction based upon number needed to transport (treat) respectively. Multivariable regression models including traditional logit model, model fitted with generalized estimating equations, and those incorporating results from propensity score matching methods were used to investigate the association of helicopter transport with survival compared with ground EMS. RESULTS: Of the 1018 snowboarders and skiers who met the criteria, 360 (35.4%) were transported via helicopters whereas 658 (64.6%) via ground EMS with a mortality rate of 1.7% and 1.5%, respectively. Multivariable log-binomial models demonstrated association of prehospital helicopter transport with increased survival (odds ratio 8.58; 95% confidence interval 1.09-67.64; P = 0.041; absolute risk reduction: 10.06%). This finding persisted after propensity score matching (odds ratio 24.73; 95% confidence interval 5.74-152.55; P < 0.001). The corresponding absolute risk reduction implies that approximately 10 patients need to be transported via helicopter to save 1 life. CONCLUSIONS: Based on our robust statistical analysis of retrospective data, our findings suggest prehospital helicopter transport improved survival in patients incurring TBI after snowboard- or ski-related falls compared with those transported via ground EMS. Policies directed at using helicopter services at remote winter resorts or ski or snowboarding locations should be implemented.

Distance of the internal central venous catheter tip from the right atrium is positively correlated with central venous thrombosis.

Central venous catheters (CVCs) are associated with occlusive, infectious, and thrombotic complications. The aim of this study was to determine if internal CVC tip position was correlated with subsequent complications. This was an institutional review board approved single-center retrospective review of 169 consecutive patients who underwent placement of 203 semipermanent CVCs. Using post-placement chest X-rays, a de novo scale of internal catheter tip position was developed. Major complications were recorded. A logistic regression analysis was used to determine if catheter tip position predicted subsequent complications. There were 78 men and 91 women with a mean age of 48 ± 11 years. There were 21 catheter tips placed in the subclavian/innominate veins, 32 in the upper superior vena cava, 113 in the atriocaval junction, and 37 in the right atrium. There were 83 complications occurring in 61 (36.1 %) patients, including sepsis in 40 (23.7 %), venous thrombosis in 18 (10.7 %), catheter occlusion in 16 (9.5 %), internal catheter repositioning in 6 (3.6 %), pneumothorax in 2 (1.2 %), and death in 1 (0.6 %). An internal catheter tip position peripheral to the atriocaval junction resulted in a catheter that was more likely to undergo internal repositioning (p < 0.001) and venous thrombosis (p < 0.001). Patients with femoral catheters were more likely to develop sepsis (45 %) than patients whose catheters were inserted through the upper extremity veins (18 %) (p < 0.01). In conclusion, to reduce catheter-associated morbidity and potentially mortality, the internal catheter tip should be positioned at the atriocaval junction or within the right atrium and femoral insertion sites should be avoided whenever possible.

Does a Negative Emergency Celiotomy Exclude the Possibility of Significant Diaphragmatic Injury? A Case Report and Review of the Literature.

INTRODUCTION: Diaphragmatic rupture (DR) is an uncommon, potentially serious complication following blunt or penetrating abdominal trauma. Even with a high index of suspicion, the diagnosis of DR can easily be missed for a long period post injury. Delayed or missed diagnosis [delayed diagnosis of diaphragmatic rupture (DDDR)] and delayed diaphragmatic rupture (DDR) are possible explanations in cases where the initial operative exploration fails to show the diaphragmatic damage. CASE PRESENTATION: Here we present a patient with suspected DR that was not seen on initial open abdominal exploration, but was suggested by subsequent serial imaging. This injury was ultimately identified on laparoscopic exploration. The procedure was converted to open (celiotomy) due to poor tolerance of the pneumoperitoneum required for laparoscopy, and the laceration was primarily repaired. We propose that DDR and DDDR be considered as a differential diagnosis in patients with a previous thoraco-abdominal trauma when presenting with radiologic/clinical signs suspicious for DR, even when the immediate post traumatic exploration failed to demonstrate a DR. CONCLUSIONS: A high index of suspicion is essential for early detection of DDR and DDDR. Patients with high impact injuries or surrounding organ damage should be followed with serial clinical examinations, follow-up radiologic assessments, and even re-exploration in situations highly suspicious for diaphragmatic injuries.

Usefulness of optical density values from heparin-platelet factor 4 antibody testing and probability scoring models to diagnose heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a complication caused by antibodies directed to the heparin-platelet factor 4 (PF4) complex with a seemingly paradoxical high risk of thrombosis. Discontinuation of heparin and administration of an alternative anticoagulant is important in prevention of catastrophic thrombosis. Diagnosis is challenging and based on clinical probability models (Warkentin 4 Ts and Chong scale) and, to a lesser degree, laboratory testing. Enzyme-linked immunosorbent assay (ELISA) measurement of heparin-PF4 antibodies is commonly used but has low predictive values for thrombosis. We analyzed 105 cases of suspected HIT and compared optical density values and the Warkentin 4 Ts for sensitivity, specificity, positive predictive value, and negative predictive value (NPV). The predictive value of ELISA alone was inferior to the Warkentin 4 Ts score. The sensitivity and NPV of the clinical score was improved by incorporating ELISA results. The combination of a negative ELISA result with low probability 4 Ts resulted in an NPV of 94%.

Leukoreduction of blood transfusions does not diminish transfusion-associated microchimerism in trauma patients.

BACKGROUND: Transfusion of trauma patients can result in long-term survival of donor white blood cells (WBCs) or "transfusion-associated microchimerism" (TA-MC). The aim was to determine whether leukoreduction of blood transfusions, advocated to reduce the immunomodulatory effect of transfusion, decreases the likelihood of developing TA-MC. STUDY DESIGN AND METHODS: A subgroup of trauma patients from a randomized trial was examined, evaluating the risk of infection following leukoreduced versus nonleukoreduced blood transfusion. Patients' blood was sampled at least 1 month after hospital discharge, and TA-MC was assessed with quantitative allele-specific polymerase chain reaction detection of differences at the HLA-DR locus or a panel of insertion-deletion polymorphism loci distributed throughout the chromosomal complement. At the time of blood sampling, a scripted interview was used to ascertain symptoms suggestive of chronic graft-versus host disease (cGVHD). RESULTS: For 67 patients evaluated, the mean age was 43 +/- 17 years and mean Injury Severity Score was 24 +/- 12. Median time from injury to blood sampling for TA-MC was 240 (interquartile range, 116-360) days. Nine of 32 patients (28%) in the nonleukoreduced transfusion group developed TA-MC compared to 13 of 35 patients (37%) in the leukoreduced group (p = 0.43). Subjects with TA-MC were no more likely than subjects without TA-MC to have at least one symptom suggestive of cGVHD (64% vs. 76%, respectively). CONCLUSIONS: TA-MC seems to be a prevalent condition among injured patients at the second of two regional trauma centers evaluated, suggesting that it is a common phenomenon after transfusion in the setting of injury. Although leukoreduction removes greater than 99.9 percent of donor WBCs, it fails to prevent or even substantially reduce the likelihood of developing TA-MC. TA-MC does not appear to be strongly associated with symptoms suggestive of cGVHD several months after transfusion.

Enhanced ascertainment of microchimerism with real-time quantitative polymerase chain reaction amplification of insertion-deletion polymorphisms.

BACKGROUND: The characterization of microchimerism (MC) by gene amplification has been limited by few allogeneic markers, ascertainment bias, and assay analytic performance. To address this, a panel of 12 MC assays based on insertion-deletion (InDel) polymorphisms had been optimized. STUDY DESIGN AND METHODS: The InDel assays were validated with comprehensive in vitro spiking studies at the stochastic limit of detection. Their ability was also determined to ascertain MC of unknown source genotype with both theoretical and actual donor-recipient pairs, and the assays were applied to a clinical population of 73 trauma patients who received transfusions where MC was previously characterized by HLA-based assays alone. RESULTS: In the stochastic spiking experiments, all assays were sensitive to a single copy of target DNA, and no false-positive amplification occurred among 1128 samples studied. Among 219 theoretical donor-recipient pairs, informative alleles existed for 99.5 percent with both InDel and HLA compared to 91.3 percent with HLA alone. In the clinical population, 33 cases of MC were detected (9 more cases than by HLA-DR alone) in the nonleukoreduced (non-LR) group and 8 cases (1 more case than by HLA-DR) in the LR group for the short-term follow-up. Among 27 long-term follow-up samples, 8 cases were detected overall (3 more cases than by HLA-DR alone). CONCLUSION: It is concluded that an InDel-based assay panel has excellent technical performance characteristics while also allowing for ascertainment of some MC cases not detectable with HLA alone. The tandem use of both the InDel and the HLA provides a powerful tool for the enhanced ascertainment of MC.

Laboratory comparison of the VisuLize IX antigen assay with the Asserachrome IX antigen assay.

Factor IX antigen levels are used primarily to assess factor IX levels in patients with liver insufficiency or who are receiving oral vitamin K antagonist therapy. We evaluated the test performance of a new factor IX antigen enzyme-linked immunoassay kit and compared it to our currently used enzyme-linked immunoassay method. Samples from normal donors and patients with known hemophilia B of varying severity were tested by using a predicate factor IX antigen method (Asserachachrome IX:Ag) and a new factor IX antigen method (VisuLize IX Antigen). The 2 methods were evaluated for performance, correlation, differences, and bias. Test samples included 46 normal donors, 14 commercial products, and 16, 18, and 15 severe, moderate, and mildly deficient factor IX deficient plasmas, respectively. The 2 methods correlated well using regression analysis. However, there were significant differences using the paired t test with bias plots indicating higher absolute values for the VisuLize IX antigen method in the severe and moderate deficiency range, but not the normal range. Testing commercially prepared survey material, the Asserachrome method demonstrated a consistently lower result than expected. The VisuLize factor IX is a new method for determining antigenic levels in human plasma. This method has a much shorter incubation time and demonstrates good correlation with current factor IX antigenic methods.

High-level long-term white blood cell microchimerism after transfusion of leukoreduced blood components to patients resuscitated after severe traumatic injury.

BACKGROUND: Long-term white blood cell (WBC) microchimerism (MC), of at least 2 years, has been reported in trauma patients receiving fresh nonleukoreduced (non-LR) blood. It is unknown, however, whether this occurs with LR blood products that are nearly devoid of WBCs. Twenty-seven patients transfused with LR and non-LR blood products were studied after severe traumatic injury. A secondary aim was to explore donor-recipient mixed lymphocyte reactivity in vitro. STUDY DESIGN AND METHODS: To quantify MC, allele-specific real-time polymerase chain reaction assays were developed targeting HLA Class II sequence polymorphisms. Extensive validation showed that these assays reliably detect a single copy of target sequence in a complex allogeneic background without false positivity. RESULTS: At a median follow-up of 26 months (range, 24-39 months), long-term MC was observed in 3 of 20 patients (15%) who received non-LR blood products and 2 of 7 (29%) who received LR blood products. The maximum MC ranged from 0.40 to 4.90 percent of circulating WBCs and appeared, by Class II genotype analysis, to be attributable to a single donor. CONCLUSION: It is concluded that robust levels of long-term MC, apparently traceable to a single donor, occur at similar frequency despite leukoreduction of transfused blood products. Exploratory analysis of donor-recipient mixed lymphocyte reactivity suggests that long-term MC may require a state of bidirectional tolerance before transfusion.

Microchimerism in transfused trauma patients is associated with diminished donor-specific lymphocyte response.

BACKGROUND: Blood transfusion can result in long-term survival of donor leukocyte subpopulations, or microchimerism, in the peripheral blood of injured patients. Neither injury severity nor the number of transfusions is associated with its occurrence. We sought to determine whether changes in general or antigen-specific lymphocyte activation may be associated with the subsequent development of microchimerism. METHODS: We evaluated 63 transfused trauma patients, which we compared with 10 non-transfused trauma patients and 10 healthy control subjects. Of the 63 transfused patients, 31 were known to have evidence of microchimerism at hospital discharge with real-time quantitative PCR for non-recipient HLA DR alleles. We assessed lymphocyte response to phytohemagglutinin (PHA) using blood sampled upon arrival to the hospital (before transfusion) and at discharge. We performed one-way mixed leukocyte cultures (MLC) with pre-transfusion recipient specimens to assess recipient lymphocyte response to mitomycin-C treated donor cells and vice versa. RESULTS: Lymphocyte response to PHA in microchimeric transfusion recipients was lower at admission (before transfusion) and discharge than in non-microchimeric recipients. Lymphocytes from microchimeric patients had less response to donor cells than did lymphocytes from non-microchimeric patients. Microchimeric patients also more frequently had diminished lymphocyte response to a single blood donor on MLC. CONCLUSIONS: Transfusion-associated microchimerism is correlated with diminished response to mitogen challenge as well as to specific alloantigenic challenges. This microchimerism is predated by diminished lymphocyte response to a specific blood donor in many instances. The blood donor associated with this diminished alloantigenic lymphocyte response may be the source of microchimeric cells present in the recipient.

Comparison of samples obtained from 3.2% sodium citrate glass and two 3.2% sodium citrate plastic blood collection tubes used in coagulation testing.

We sought to compare coagulation test results obtained from patients using 2 plastic blood collection tubes and the traditional glass blood collection tube. Blood specimens were obtained from 241 patients in 3.2% buffered sodium citrate using standard glass tubes, in 3.2% buffered sodium citrate in plastic tubes, and in 3.2% sodium citrate "sandwich" tubes (plastic within plastic). All samples were obtained and processed contemporaneously and tested for prothrombin time (PT) and activated partial thromboplastin time (aPTT). Residual plasma was frozen at -70 degrees C for future testing, including fibrinogen, antithrombin, plasminogen, protein C and protein S (functional and antigenic), dilute Russell viper venom time (DRVVT), ristocetin cofactor, factor XIII, D dimer, anti-Xa activity, and prothrombin fragment. Although paired t test analysis revealed statistically significant differences (P < .05) between glass and plastic for PT, aPTT, fibrinogen, protein C (functional and antigenic), functional protein S, DRVVT and confirmation method, antithrombin, and factor XIII, these differences were not considered clinically significant.

Blood transfusion is associated with donor leukocyte microchimerism in trauma patients.

INTRODUCTION: Blood transfusion can result in survival of donor leukocyte subpopulations in the recipient. Persistence of donor leukocytes in the transfusion recipient is termed microchimerism. Microchimerism likely reflects engraftment of the recipient with donor hematopoietic stem cells and is very uncommon with transfusion for elective surgery, sickle cell anemia, thalassemia, and HIV. We have found, however, that microchimerism may be more common in trauma patients. OBJECTIVE: To determine how frequently transfusion after trauma is associated with microchimerism. METHODS: We prospectively enrolled 45 trauma patients who were transfused > or =2 units of PRBCs. We sampled blood before hospital discharge and determined microchimerism by polymerase chain reaction (PCR) analysis of specimens using quantitative allele-specific HLA DR assays to detect non-recipient alleles. Data are expressed as median with interquartile range. RESULTS: Patients had a median age of 38 (interquartile range 25, 58) years, ISS of 19 (13, 29), and mortality of 7%. Seventy-eight percent were men, and 84% had blunt trauma. Patients received a median of 6 (4, 16) (range 2, 87) units of PRBCs. Of the 45 patients, 24 (53%) had evidence of microchimerism. Compared with patients without evidence of microchimerism, these patients had no difference in mean age, gender, ISS, units of PRBCs transfused, time from transfusion to blood sampling, or proportion that underwent splenectomy. Twenty-one of the 24 patients with microchimerism had only 1 or 2 non-recipient DR alleles identified by PCR. CONCLUSIONS: Transfusion after trauma is associated with over half of recipients having evidence of microchimerism. Age, sex, ISS, and splenectomy of the recipient and the number of transfused units did not correlate with microchimerism. Because the median time from transfusion to sampling for PCR analysis was not longer in the group without microchimerism, it is unlikely microchimerism is due merely to failure of the recipient to clear transfused donor leukocytes.

Effects of pentasaccharide (fondaparinux) and direct thrombin inhibitors on coagulation testing.

CONTEXT: Direct thrombin inhibitors (DTIs) and fondaparinux represent a new class of anticoagulants. The effects of DTIs on activated partial thromboplastin time and prothrombin time measurements have been reported previously, but there are limited data on the impact of these anticoagulants on other coagulation tests. OBJECTIVE: To determine the effects of fondaparinux and 3 DTIs (argatroban, bivalirudin, and lepirudin) on miscellaneous coagulation tests. DESIGN: Bivalirudin, lepirudin, argatroban, and fondaparinux were added to pooled normal plasma and tested for fibrinogen, antithrombin (thrombin and Xa substrate methods), plasminogen, protein C (clot and chromogenic methods), protein S, von Willebrand factor, D-dimer, lupus anticoagulant testing (dilute Russell viper venom test [DRVVT] with ratio), and factors II, IX, and X activities. RESULTS: We found no drug interference on antithrombin, plasminogen, chromogenic protein C, von Willebrand factor, or D-dimer results. All DTIs falsely decreased fibrinogen values, while falsely increasing protein C and protein S levels. All DTIs prolonged the DRVVT, and only argatroban yielded DRVVT ratios less than 1.2. Lepirudin demonstrated no effect on factor II activity, and only argatroban demonstrated decreased factor X activity. All DTI samples demonstrated a linear, dose-dependent, false decrease of factor IX activity. CONCLUSIONS: Using in vitro methods, we demonstrated DTI effects on numerous clot-based assays, but we found no interference with latex agglutination, chromogenic, or platelet aggregation methods. Fondaparinux only affected measurement of protein S activity. Caution must be used when interpreting coagulation test results on patients receiving these drugs.

Comparing direct thrombin inhibitors using aPTT, ecarin clotting times, and thrombin inhibitor management testing.

BACKGROUND: Patients with heparin-induced thrombocytopenia and thrombosis may be acutely anticoagulated with direct thrombin inhibitors (DTIs). The anticoagulation is typically monitored using the activated partial thromboplastin time (aPTT) or ecarin clotting time (ECT). OBJECTIVE: To compare 14 methods for measuring aPTT, as well as ECT and thrombin inhibitor management test (TIM), in samples containing DTIs. METHODS: DTIs were added to pooled normal plasma to achieve low (0.1-1.2 microg/mL) and high (1.5-8.0 microg/mL) drug concentrations. Each low-concentration DTI sample was tested using all aPTT reagents, while each low- and high-concentration DTI was tested using the ECT and TIM. RESULTS: All aPTT reagents had a significant dose-dependent correlation with drug concentration. Only Actin FSL and APTT-S demonstrated equivalent aPTT ratios obtained from any DTI. The TAS-aPTT was the most sensitive aPTT reagent to argatroban, with the aPTT ranging from 52.7 to 121.2 seconds corresponding to 0.1 to 1.2 microg/mL of drug concentration. The TAS-aPTT and Pathromtin were the most sensitive aPTT reagents to bivalirudin, with aPTTs of 87.4 seconds and 101.5 seconds, respectively, at 1.2 microg/mL of drug. Pathromtin was the most sensitive aPTT reagent to lepirudin, with a maximum aPTT of 108.9 seconds at 1.2 microg/mL of drug. There was no statistically significant difference between the TIM and ECT clotting times for each DTI. Lepirudin and bivalirudin ECT and TIM clotting times were equivalent. CONCLUSIONS: There are unique differences between reagent manufacturers in the monitoring of DTIs. Acceptable alternatives to aPTT monitoring of DTI anticoagulation include the ECT and TIM.

Argatroban therapy for antithrombin deficiency and mesenteric thrombosis: case report and review of the literature.

Antithrombin deficiency is a hypercoagulable state that can increase the risk for thrombosis, especially in the presence of other procoagulant triggers. Unfractionated heparin and low-molecular-weight heparins may not provide effective anticoagulation since they require antithrombin for activity. Direct thrombin inhibitors, however, work independently of antithrombin. A 21-year-old man with a history of heavy alcohol consumption had thrombosis of the superior mesenteric vein. Infusion with unfractionated heparin was started, and despite repeated boluses and increases to 21 U/kg/hour, the maximum activated partial thromboplastin time reached was 39 seconds. The unfractionated heparin was discontinued, and the direct thrombin inhibitor argatroban was infused at rates of 0.4-0.5 microg/kg/minute. Over the course of several weeks, the patient had numerous operations to remove and repair necrotic bowel. When no further surgery was anticipated, warfarin therapy was started; the argatroban infusion was discontinued when the patient reached the therapeutic target international normalized ratio with warfarin. No recurrent thrombosis or major bleeding occurred. Direct thrombin inhibitors, such as argatroban, seem to be suitable alternatives for acute anticoagulation in patients with antithrombin deficiency.

Effect of direct thrombin inhibitors, bivalirudin, lepirudin, and argatroban, on prothrombin time and INR values.

Direct thrombin inhibitors (DTIs) represent a new class of promising anticoagulation agents. The DTIs frequently are used to provide initial anticoagulation, with long-term therapy requiring eventual transition to coumarins. Unfortunately, DTIs not only prolong the activated partial thromboplastin time but also can affect international normalized ratio (INR) values. We approximated the DTI effect on INRs by each drug to pooled plasma at concentrations between 0.1 and 1.2 microg/mL. We then concurrently tested these samples using 14 prothrombin time (PT) reagents. By using repeated measures analysis of variance, we found significant differences (P < .05) between the median INRs for lepirudin and argatroban for all PT reagents, between lepirudin and bivalirudin for all reagents except PT-Fibrinogen HS Plus (P = .07), and between bivalirudin and argatroban for all reagents except Thromborel S (P = .05). The DTI effect on INRs was dependent on drug, drug concentration, and reagent. Argatroban had the most effect on INRs, while lepirudin had the least effect. Reagents with a lower international sensitivity index were less affected by DTI; ThromboMax HS was the least sensitive PT reagent to any DTI.

Lepirudin in heparin-induced thrombocytopenia and extracorporeal membranous oxygenation.

OBJECTIVE: To report a case of intermediate-probability suspected heparin-induced thrombocytopenia (HIT) treated with lepirudin in a patient requiring continuous extracorporeal membranous oxygenation (ECMO). CASE SUMMARY: A 17-year-old girl was admitted with multiple traumatic injuries including severe bilateral pulmonary contusions. Within 48 hours, she developed progressive pulmonary failure despite mechanical ventilation, and was placed on ECMO. Anticoagulation of the ECMO circuit was facilitated by unfractionated heparin (UFH). The platelet count of 116 x 10(3)/mm(3) after initiation of ECMO gradually decreased over 5 days to 44 x 10(3)/mm(3). On ECMO day 5, a highly positive enzyme-linked immunosorbent assay for HIT antibodies was reported, and the UFH infusion was discontinued. Lepirudin was immediately started with a bolus of 0.1 mg/kg, followed by an infusion of 0.12 mg/kg/h, with a target activated partial thromboplastin time (aPTT) ratio approximately 2 times control. The ECMO circuit was maintained without any unexpected bleeding complications or thrombosis for 6 additional days until the patient died secondary to pulmonary failure after ECMO was removed. DISCUSSION: Use of ECMO typically requires continuous infusion of UFH to keep the circuit from clotting. In patients with HIT, alternative anticoagulation using a direct thrombin inhibitor may be warranted. Lepirudin was effectively used to maintain the circuit despite continued presence of heparin molecules impregnated into the ECMO circuit tubing. The aPTT was successfully used to monitor and adjust the lepirudin infusion. CONCLUSIONS: In patients requiring ECMO in the presence of HIT, anticoagulation of the ECMO circuit may be accomplished using a continuous infusion of a direct thrombin inhibitor such as lepirudin.

Variability of plasma anti-Xa activities with different lots of enoxaparin.

BACKGROUND: Previous studies have indicated the variability of anti-Xa activity in different sources of heparin and the variability of different methods used for measuring anti-Xa activity. Manufacturers of low-molecular-weight heparins (LMWHs) determine each lot's anti-Xa activity against the World Health Organization standard, but little information is known about anti-Xa activity variation between lots of LMWH and the impact on reported anti-Xa activity in patient samples. OBJECTIVE: To determine the variation of plasma anti-Xa activity in patients receiving enoxaparin when different lots of enoxaparin are used for test calibration. METHODS: We obtained 7 lots of enoxaparin containing approximately 10,000 IU/mL and one lot containing approximately 15,000 IU/mL of anti-Xa activity. For each lot, a 2.0 anti-Xa IU/mL dilution was prepared and a calibration curve performed using a chromogenic method. To test the variation in reported results between the different calibration lots, 20 patient samples were tested. Nineteen patients receiving enoxaparin and one patient not receiving enoxaparin (negative control) were tested in a blinded fashion, and the changes in light absorbance recorded. Anti-Xa activity results from tested plasmas were then extrapolated from each enoxaparin lot calibration curve. RESULTS: Using Student's paired t-test, there were statistically significant differences between the plasma anti-Xa activities generated from the various enoxaparin lots. In the range of 0.5-1.0 IU/mL of anti-Xa activity, 3 (4.2%) samples had a >0.2 IU/mL difference (maximum difference 0.33 IU/mL) in anti-Xa activity between 2 lots of enoxaparin. For samples that had supratherapeutic anti-Xa activities (1.0-1.5 IU/mL anti-Xa activity), there was a wider variation (>0.2 IU/mL) in anti-Xa activity, which may have resulted in a dosing change. CONCLUSIONS: The statistical differences in plasma anti-Xa activities noted between enoxaparin lots are not clinically significant. However, anti-Xa activities in the upper therapeutic and supratherapeutic ranges (>1.0 IU/mL of anti-Xa activity) resulted in a deviation of >0.3 IU/mL in reported anti-Xa activity, which may result in dosing changes.

Anti-Xa stability of diluted enoxaparin for use in pediatrics.

BACKGROUND: The use of enoxaparin in low-weight pediatric patients is becoming common practice. Anti-Xa stability of unit-dose syringes prepared after dilution beyond one day is presently unknown. OBJECTIVE: To evaluate the anti-Xa stability of diluted enoxaparin stored in glass vials and tuberculin syringes. METHODS: Four separate batches of enoxaparin were diluted with sterile water to a final concentration of 20 mg/mL (2000 IU/mL) and aliquoted into plastic 1-mL syringes containing 6 mg (0.3 mL) or maintained in the glass vial. Syringes were stored at room temperature or under refrigeration. The glass vial used for diluting was stored at room temperature. The anti-Xa activity was measured on the date of preparation to 4 weeks. Statistical comparisons determined whether differences in anti-Xa activity in diluted enoxaparin are affected by the storage medium or temperature. A paired t-test was used to determine any significant differences between the anti-Xa activity on date of preparation (baseline) and subsequent time periods, with p < 0.05 considered statistically significant. RESULTS: The mean baseline anti-Xa activity was 2607 IU/mL (95% CI 2300 to 2914). No measurable decrease occurred in diluted enoxaparin anti-Xa activity in the glass vial maintained over the 4-week period. Compared with the glass vial, room temperature and refrigerated syringe samples had trending decreases of anti-Xa activity at weeks 3 and 4, but did not reach statistical significance. CONCLUSIONS: A nonsignificant decrease in anti-Xa activity occurred starting at day 22 for the diluted enoxaparin in tuberculin syringes, regardless of storage temperature. Storage up to 4 weeks of diluted enoxaparin in glass or prefilled syringes does not result in a statistically significant loss of anticoagulant potential, as measured by anti-Xa activity.

Comparison of six D-dimer methods in patients suspected of deep vein thrombosis.

We evaluated six D-dimer methods to determine their sensitivity, specificity, and negative predictive values (NPV) in symptomatic patients suspected of deep vein thrombosis (DVT). In patients suspected of DVT a whole blood D-dimer test (SimpliRED, Agen) was performed, and then tested using enzyme-linked immunosorbent assay (VIDAS D-Dimer, BioMerieux; Asserachrome D-Di, Stago International; Dimertest Gold, Agen) and automated immunoturbidometric methods (Advanced D-Dimer, Dade Behring; MiniQuant, Biopool). Each D-dimer method was independently compared with radiographic results to determine sensitivity and NPV. There were 151 patients enrolled in the study. Thirty-five (23.2%) patients had a positive Doppler ultrasound, with 26 proximal, eight distal, and one patient with both proximal and distal thrombus. Two patients (1.3%) had inconclusive studies and were excluded from the analyses. For all patients, the sensitivities for the rapid D-dimer methods were: SimpliRED, 82.3% [95% confidence interval (CI), 80.3-84.3%]; VIDAS D-Dimer, 91.4% (95% CI, 89.9-92.9%); MiniQuant D-Dimer, 96.3% (95% CI, 95.1-97.5%); and Advanced D-Dimer, 97.1% (95% CI, 96.3-97.9%). The sensitivity improved for SimpliRED (86.4%; 95% CI, 83.3-89.4%), VIDAS D-Dimer (95.5%; 95% CI, 85.0-100%), MiniQuant D-Dimer (100%; 95% CI, 96.9-100%) and Advanced D-Dimer (100%; 95% CI, 98.9-100%) in the inpatient population. The automated immunoturbidometric methods, the MiniQuant D-Dimer and Advanced D-Dimer, demonstrated comparable sensitivities and NPV with the VIDAS D-Dimer method in symptomatic patients suspected of DVT, which would suggest that these newer D-dimer methods could be used as part of the diagnostic algorithm for patients suspected of DVT.