Case records of the Massachusetts General Hospital. Case 1-2007. A 40-year-old woman with epistaxis, hematemesis, and altered mental status.
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4-Hydroxycoumarins↗
Biomedical subjects
Elizabeth M Van Cott
Publications and source records attributed to Elizabeth M Van Cott.
Predictors for the development of elevated anti-heparin/platelet factor 4 antibody titers in patients undergoing cardiac catheterization.
A substantial proportion of patients who undergo cardiac catheterization develop antibodies directed against the heparin/platelet factor 4 (PF4) complex after the procedure, which have been implicated in the pathogenesis of heparin-induced thrombocytopenia. This study attempted to identify factors that predicted the development of these antibodies in a prospective cohort study. Antiheparin/PF4 antibody titers were measured at baseline and again 5 +/- 2 days after cardiac catheterization by enzyme-linked immunosorbent assay. A total of 311 patients who underwent cardiac catheterization were included in the analysis. Of these, 25 (8.0%) developed positive antibody levels after catheterization. Patients who had positive antibody test results after catheterization had significantly greater baseline antiheparin/PF4 antibody titers compared with those whose titers remained low (optical density 0.227 vs 0.158, p < 0.001). In a logistic regression model, greater baseline antibody titers, a history of heparin exposure, and a lower platelet count at enrollment were the strongest predictors of conversion to positive antiheparin/PF4 antibody titers after cardiac catheterization. It is possible to identify patients at high risk for developing elevated titers of antiheparin/PF4 antibodies on the basis of their baseline clinical characteristics.
Antibodies↗
Prevalence of heparin-induced thrombocytopenia in patients undergoing cardiac catheterization.
BACKGROUND: Heparin is ubiquitously used in cardiac catheterization but predisposes to the development of heparin-induced thrombocytopenia. The objective was to examine prospectively the prevalence of anti-platelet factor 4 (PF4)/heparin antibodies and heparin-induced thrombocytopenia in the population undergoing cardiac catheterization. METHODS: This is a prospective study of 500 consecutive patients presenting for cardiac catheterization at our institution who were enrolled over the course of 1 year. Anti-PF4/heparin antibodies and concurrent platelet counts were measured at catheterization and 5 days thereafter. Thrombotic complications were assessed 30 days after the procedure via telephone interview. All patients presenting for cardiac catheterization at our institution were screened. Inclusion criteria were (a) males and nonpregnant females with age >18 years and (b) patients scheduled to undergo cardiac catheterization. Patients with a known history of heparin-induced thrombocytopenia, with documented bleeding or hypercoagulability, and those at high risk for bleeding were excluded. RESULTS: Of 500 patients, 15 (3%) had anti-PF4/heparin antibodies before catheterization. After catheterization, the prevalence of anti-PF4/heparin antibodies increased to 10.1% (36 of 357) of the patients. Overall rates of thrombotic complications were low (4 of 445, 0.9%) and did not correlate with anti-PF4/heparin antibody status. Patients with an initial positive test for anti-PF4/heparin antibodies were more likely to have prior coronary disease (73.3% vs 45.2%; P < .05). Patients who developed anti-PF4/heparin antibodies after catheterization were more likely to have increased length of stay (3.7 vs 2.4 days; P = .02). The platelet count at the time of catheterization was lower in the cohort of patients who developed the second positive anti-PF4/heparin antibody test versus patients without a second positive antibody test (mean values of 191,800/microL vs 222,300/microL; P = .008). CONCLUSIONS: The prevalence of antibodies to PF4/heparin is low in the population presenting for cardiac catheterization. However, a significant proportion of patients develop antibodies to PF4/heparin after a small exposure to heparin during catheterization. Clinically significant thrombotic complications were rare and did not correlate with antibody status.
Aged↗
External peer review quality assurance testing in von Willebrand disease: the recent experience of the United States College of American Pathologists proficiency testing program.
The U.S. College of American Pathologists (CAP) has conducted a focused study of the proficiency testing for von Willebrand disease (vWD) analysis from 2003 to 2005. This report summarizes the findings regarding the accuracy and precision of the various assays at different analyte levels, as well as the influence of the reference material used to construct the assay standard curve. The results show that testing of von Willebrand factor (vWF):antigen (vWF:Ag) and ristocetin cofactor activity (vWF:RCo) is reasonably accurate, with all-method mean values falling within 3.2 and 5.6%, respectively, of the International Society on Thrombosis and Haemostasis Secondary Coagulation Standard (lot 2) assigned values. vWF:Ag measurements are reasonably precise (all-method coefficients of variation [CVs] = 10.7 to 15.1%), even at lower levels of vWF. The highest precision was observed for immunoturbidometric assays (CVs, 6.3 to 9.7%). vWF:RCo measurements are less precise (all-method CVs, 23.3 to 30.9%). The reference materials used in the standard curves for immunoturbidometric vWF:Ag assays appear to have accurately assigned vWF values for the majority of commercial suppliers.
Antigens↗
Outcome of postoperative critically ill patients with heparin-induced thrombocytopenia: an observational retrospective case-control study.
INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is described as a decrease in platelet count associated with heparin administration and is an immune-mediated adverse drug reaction that can cause both arterial and venous thromboses. It can be a life-threatening complication of heparin exposure. Little data concerning incidence, predisposing factors, or outcome in critically ill surgical patients are available. METHODS: All critically ill, postoperative patients admitted between January 1, 2000, and December 31, 2001, to a surgical intensive care unit (SICU) who tested positive by an enzyme-linked immunosorbent assay for the HIT antibody (HPIA; Diagnostica Stago, Inc., Parsippany, NJ, USA) were identified. Patient risk factors and outcomes were abstracted retrospectively from the medical record and compared with those from control patients matched for age, gender, diagnosis, severity of illness, and date of SICU admission. RESULTS: Two hundred and ten patients out of 2,046 patients (10%) admitted to the SICU had HIT assays performed. Nineteen patients (0.9% of admissions; 9% of tested individuals) had positive tests. HIT-antibody-positive patients, compared with 19 matched controls, had an increased risk of death or major thrombotic complications (37% versus 10%; P < 0.05) and prolonged length of intensive care unit (ICU) stay (20 days versus 10 days; P < 0.05). Exposure to heparin via intravascular flushes alone was sufficient to generate HIT antibodies in 12 of 19 (63%) patients. Five patients received platelet transfusions after the diagnosis of HIT was known; four of these patients died. CONCLUSION: Heparin flushes were the most common cause of HIT in this study. HIT-antibody-positive patients had an increased risk of death or major complications and a prolonged length of ICU stay. Platelet transfusions often were administered despite a positive HIT test result and were associated with a high mortality rate. Treatment algorithms that minimize exposure to heparin and contraindicate platelet transfusions merit further study.
Adult↗
Effects of marathon running on platelet activation markers : direct evidence for in vivo platelet activation.
We used the ADVIA 2120 Hematology System (Bayer HealthCare, Diagnostics Division, Tarrytown, NY) to study the effects of vigorous exercise on CBC count, WBC differential, RBC fragmentation, and platelet activation parameters in 32 healthy participants in a 26.2-mile (42.2-km) marathon. The runners demonstrated increases in hematocrit and platelet count consistent with dehydration and leukocytosis indicative of demargination of neutrophils or inflammation secondary to tissue destruction (eg, rhabdomyolysis). The number of RBC fragments was increased after the race (P = .008), consistent with exercise-induced hemolysis. The mean platelet component, a measure of platelet granularity, was decreased (P < .0001), and the number of platelet clumps was increased (P = .0026), providing evidence for in vivo platelet activation during the marathon. By using direct measurement of platelet granularity, our study confirms the in vivo activation of platelets by vigorous exercise and establishes the usefulness of automated cell counters for the assessment of platelet activation and of RBC fragmentation in this setting.
Adult↗
Effect of fondaparinux on coagulation assays: results of College of American Pathologists proficiency testing.
CONTEXT: Fondaparinux, a factor Xa inhibitor, is approved for thromboprophylaxis after orthopedic surgery and for treatment of venous thromboembolism. It may also be efficacious, safe, and cost-effective for other patients; thus, more widespread use of fondaparinux is likely. The effect of fondaparinux on coagulation testing needs to be thoroughly examined. OBJECTIVE: To report the effects of fondaparinux on coagulation tests (prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, factor VIII, thrombin time, anti-factor Xa) across diverse methodologies. DESIGN: Samples with different concentrations of fondaparinux (0, 0.4, 0.8, and 2.0 microg/mL) were sent to laboratories participating in the College of American Pathologists Comprehensive Coagulation proficiency survey (N = 898). Laboratory-specific methods were used to assay coagulation parameters. RESULTS: Prophylactic or therapeutic fondaparinux prolonged the prothrombin time by approximately 1 second and the activated partial thromboplastin time by 4 to 5 seconds, and reduced factor VIII from 119% to 107% and 102%, respectively. Supratherapeutic fondaparinux reduced factor VIII to 85%. The activated partial thromboplastin time was prolonged in 19%, 29%, and 52% of laboratories with prophylactic, therapeutic, and supratherapeutic fondaparinux levels, respectively. Fibrinogen, antithrombin, and thrombin time assays did not show clinically significant changes. When measuring fondaparinux concentration using an anti-factor Xa assay, the most accurate results were obtained when fondaparinux was used as the calibrator. CONCLUSIONS: Fondaparinux, even in prophylactic doses, slightly prolongs the prothrombin time and activated partial thromboplastin time and can interfere with factor VIII assays, but it has no clinically relevant effect on fibrinogen, antithrombin, or thrombin time. A fondaparinux standard curve should be used for reporting fondaparinux levels using an anti-factor Xa assay.
Anticoagulants↗
A comparison of glass and plastic blood collection tubes for routine and specialized coagulation assays: a comprehensive study.
CONTEXT: Blood collection tubes made from plastic are beginning to replace glass tubes. Coagulation test results can be influenced easily by preanalytic factors, including exposure to surfaces that activate the clotting cascade. OBJECTIVE: To compare the effects of the blood collection tube material on 22 coagulation assays performed in clinical laboratories. DESIGN: Paired blood samples from 28 healthy volunteers were drawn into BD Vacutainer Glass Citrate Tubes and BD Vacutainer Plus Plastic Citrate Tubes, and the results of coagulation assays were determined in parallel. RESULTS: No statistically significant differences were observed between glass and plastic for 14 assays: prothrombin time (and international normalized ratio); activated partial thromboplastin time; activated protein C resistance; antithrombin activity; factors II, V, VIII, and IX; alpha2-antiplasmin; plasminogen activity; von Willebrand factor antigen; ristocetin cofactor; thrombin time; and reptilase time. Statistically significant differences were found for fibrinogen; chromogenic protein C activity; protein S activity; PTT-LA lupus anticoagulant-sensitive activated partial thromboplastin time; and factors VII, X, XI, and XII. Mean differences ranged from 0.4% to 5.5% and were unlikely to be of clinical significance. CONCLUSIONS: The results of this study suggest that plastic tubes can be used in place of glass tubes for a wide variety of coagulation assays.
Blood Coagulation Tests↗
Protein S assays: an analysis of North American Specialized Coagulation Laboratory Association proficiency testing.
To assess current laboratory practice and the performance of different reagent-instrument combinations for protein S testing, protein S results from the North American Specialized Coagulation Laboratory Association (NASCOLA) proficiency testing surveys for 2002 and the first half of 2003 were analyzed. A written survey of NASCOLA laboratories also was performed to further assess current laboratory practices for protein S testing. The free protein S antigen assays and the Diagnostica Stago Staclot protein S assay were extremely accurate in detecting a heterozygous type I protein S deficiency. Another functional protein S assay and most total protein S assays were less reliable, depending to some extent on the instrument. All assays used by NASCOLA laboratories appropriately identified normal protein S specimens. NASCOLA laboratories performed at least as well as European Concerted Action on Thrombosis laboratories in the proficiency tests. The results suggest that the diagnosis of heterozygous protein S deficiency may be problematic with some currently available assays. Many total protein S antigen assays do not add to the diagnosis and can be unreliable for protein S deficiency subtyping. Better standardization of functional and antigenic assays is needed.
Biological Assay↗
Performance evaluation of the CellaVision DM96 system: WBC differentials by automated digital image analysis supported by an artificial neural network.
We evaluated the CellaVision DM96 (CellaVision AB, Lund, Sweden), an automated digital cell morphology and informatics system for peripheral blood smears. Technologists agreed with 82% of the instrument's preclassifications. Correlation coefficients between final results released from the CellaVision and results obtained by direct microscopy were 0.96 (all neutrophils), 0.94 (lymphocytes), 0.88 (segmented neutrophils), 0.73 (eosinophils), 0.69 (bands), and 0.67 (monocytes). After correction for statistically and clinically insignificant variations, the CellaVision DM96 had 95% sensitivity and 88% specificity for immature myeloid cells. It was 100% sensitive and 94% specific for blasts, and 100% sensitive and 97% specific for unusual WBCs and nucleated RBCs. Advantages of the CellaVision DM96 over direct microscopy include the ability to review slides from a remote location, consultation and quality control on a cell-by-cell basis, and potential labor savings.
Cost-Benefit Analysis↗
Use of the chromogenic factor X assay to predict the international normalized ratio in patients transitioning from argatroban to warfarin.
STUDY OBJECTIVE: To determine the clinical utility of the chromogenic factor X level for conversion from argatroban to warfarin in hospitalized patients. DESIGN: Prospective observational study. PATIENTS: Sixty-two hospitalized patients with indications for anticoagulation in whom the chromogenic factor X assay was used for conversion from argatroban to warfarin. SETTING: University-affiliated hospital. INTERVENTION: From December 2003-May 2004, data for all patients in whom the chromogenic factor X assay was used for conversion from argatroban to warfarin were screened for inclusion. When the chromogenic factor X level was satisfactory, the clinician discontinued the argatroban and a confirmatory international normalized ratio (INR) was obtained. MEASUREMENTS AND MAIN RESULTS: To determine the ability of the chromogenic factor X level to predict the INR free of argatroban influence, we calculated the sensitivity and specificity by using a cutoff chromogenic factor X level of 45% or less, or greater than 45%, which corresponded to an INR of 2 or greater, or less than 2, respectively. We constructed a receiver operating characteristic curve to illustrate various cutoff levels of chromogenic factor X. Of 146 patients screened, 62 had data that met criteria for analysis. An average of 6 +/- 3 doses of warfarin were administered before the confirmatory coagulation studies were obtained. The average time from the chromogenic factor X measurement to obtainment of confirmatory coagulation studies was 9 +/- 4 hours. Use of a chromogenic factor X level of 45% or less to predict an INR of 2 or greater absent of argatroban influence had a sensitivity of 93%, a specificity of 78%, and an accuracy of 89%. The area under the receiver operating characteristic curve was 0.91 (95% confidence interval 0.81-0.99, p<0.0001). CONCLUSION: The chromogenic factor X level is an accurate alternative when converting hospitalized patients from argatroban to warfarin. A chromogenic factor X level of 45% or less is a reliable predictor that the INR will be therapeutic when argatroban therapy is discontinued.
Aged↗
Effects of the blood-collection tube material and long-term storage on platelet activation parameters on the ADVIA 120/2120 hematology system.
The ADVIA 120/2120 Hematology System provides a number of novel parameters of platelet activation. Although the effects of anticoagulant in the blood-collection tube, short-term storage, and ambient temperature on these parameters have been documented in the literature, the effects of long-term storage and the material of the blood-draw tube have not been investigated. We therefore compared platelet activation parameter values obtained with the ADVIA 120 for 50 paired blood samples collected into BD Medical Systems' Vacutainer K(3)EDTA glass tubes and Vacutainer K(2)EDTA Plus plastic tubes and analyzed within 4 hours and after 24 hours following venipuncture. We found a statistically significant but clinically irrelevant decrease (less than 1%) in mean platelet component (MPC) concentration in plastic compared with glass for blood samples analyzed within 4 hours of draw. Reanalysis of the samples after 24 hours showed a clinically and statistically significant increase in mean platelet volume and significant decreases in MPC, platelet component distribution width, and mean platelet mass. These storage-induced changes were of equal magnitude for both tube types. We conclude that the use of plastic versus glass blood-draw tubes should have no clinically significant effect on the parameters of platelet activation on the ADVIA 120/2120 system and that the changes in platelet activation parameters continue to be present at 24 hours.
Anticoagulants↗
Cold-dependent loss of factor VIII von Willebrand factor activities in citrated whole blood is reversed by rewarming.
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Blood Preservation↗
Heparin-induced thrombocytopenia.
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Anticoagulants↗
Prothrombin gene mutation G20210A, homocysteine, antiphospholipid antibodies and other hypercoagulable states in ocular thrombosis.
The purpose of the present study was to determine whether using an extended panel of laboratory tests increases the detection of a hypercoagulable state in patients with ocular thromboses. Twenty consecutive patients with ocular thromboses (vein, artery, or choriocapillaris occlusions) underwent testing for activated protein C resistance/factor V Leiden, prothrombin G20210A, lupus anticoagulant, anticardiolipin antibodies, hyperhomocysteinemia, and deficiencies of protein C, protein S, and antithrombin. For each patient, we selected two age-matched and gender-matched individuals without ocular thromboses as controls. Sixteen of the 20 patients (80%) had one or more laboratory tests that supported a hypercoagulable condition. Prothrombin G20210A (P < 0.02) and hyperhomocysteinemia (P < 0.0006) were significantly more frequent in ocular thrombosis patients compared with controls. The most common condition was antiphospholipid antibody syndrome, present in 40% of patients (confirmed by repeat testing at least 6 weeks later), but this did not reach statistical significance compared with the controls. No patients with ocular thromboses had hereditary abnormalities of protein S, protein C, or antithrombin. In conclusion, an extended panel of laboratory tests improved the detection of a hypercoagulable state in ocular thromboses. Testing for homocysteine, antiphospholipid antibodies, and the prothrombin G20210A mutation should be considered in patients with ocular thromboses.
Activated Protein C Resistance↗
Biphasic activated partial thromboplastin time waveform and adverse events in non-intensive care unit patients.
The purpose of the present study was to determine whether the presence of a biphasic activated partial thromboplastin time (aPTT) waveform (BPW) is associated with adverse clinical outcomes among patients not in an intensive care unit (ICU). Consecutive patients from the emergency department or non-ICU inpatient floors with a BPW (n = 24) were enrolled prospectively, along with 24 matched control subjects with a normal aPTT waveform. Patients with a BPW had a significantly longer hospital stay (mean [median], 16.9 [11] vs 4.9 [2.5] days; P = .011), were more likely to have a positive microbial culture (16/24 [67%] vs 3/24 [13%]; P < .001), were transferred more often to an ICU (6/24 [25%] vs 0/24 [0%]; P = .010), and were more likely to receive an RBC transfusion (11/24 [46%] vs 5/24 [21%]; P = .047) or a fresh frozen plasma transfusion (5/24 [21%] vs 0/24 [0%]; P = .025). Emergency department patients with a BPW were more likely to be admitted (11/11 vs 5/11; P = .018). These results suggest that the BPW is associated with an increased rate of adverse events among non-ICU patients. Further study in this population is warranted.
Adult↗
Physician survey of a laboratory medicine interpretive service and evaluation of the influence of interpretations on laboratory test ordering.
CONTEXT: Complex coagulation test panels ordered by clinicians are typically reported to clinicians without a patient-specific interpretive paragraph. OBJECTIVES: To survey clinicians regarding pathologist-generated interpretations of complex laboratory testing panels and to assess the ability of the interpretations to educate test orderers. DESIGN: Surveys were conducted of physicians ordering complex coagulation laboratory testing that included narrative interpretation. Evaluation of order requisitions was performed to assess the interpretation's influence on ordering practices. SETTING: Physicians ordering coagulation testing at a large academic medical center hospital in Boston, Mass, and physicians from outside hospitals using the academic medical center as a reference laboratory for coagulation testing. OUTCOME MEASURES: Physician surveys and evaluation of laboratory requisition slips. RESULTS: In nearly 80% of responses, the ordering clinicians perceived that the interpretive comments saved them time and improved the diagnostic process. Moreover, the interpretations were perceived by ordering clinicians to help prevent a misdiagnosis or otherwise impact the differential diagnosis in approximately 70% of responses. In addition, interpretations appeared to be able to train the ordering clinicians as to the standard ordering practices. CONCLUSIONS: The results demonstrate physician satisfaction with an innovative information delivery approach that provides laboratory diagnostic interpretation and test-ordering education to clinicians in the context of their daily workflow.
Academic Medical Centers↗
Clinical significance of a borderline titer in a negative ELISA test for heparin-induced thrombocytopenia.
We studied the usefulness of repeated enzyme-linked immunosorbent assay testing for heparin-induced thrombocytopenia (HIT) when the initial test result was negative and sought to determine whether the titer of the initial negative result correlated with the likelihood of obtaining a positive test result in repeated testing. We divided 150 patients who underwent HIT testing into 3 groups (50 patients each): (1) very low titer negative (0.0%-33.3% of the threshold for a positive test); (2) low titer negative (33.4%-66.6% of the threshold); and (3) high titer negative (66.7%-99.9% of the threshold). Among the patients who underwent a repeat test, 5% (1/20) of group 1 patients, 13% (4/32) of group 2 patients, and 43% (13/30) of group 3 patients tested positive in the repeat test (P = .0026). Thus, nearly half of patients with initially negative HIT test results had positive results in the repeat test if the negative titer was 66.7% or more of the threshold. If laboratories report the HIT titer, rather than just negative or positive, the titer might help clinicians predict which patients have HIT despite a negative initial test, and the overall sensitivity for diagnosing HIT might be improved.
Antibodies↗