Deep vein thrombosis: prevalence and risk factors in rehabilitation admissions with brain injury.

OBJECTIVE: To determine the prevalence and risk factors of deep vein thrombosis (DVT) among neurorehabilitation admissions with acquired brain injury (BI). METHODS: In this prospective, sequential case series, 709 consecutive initial neurorehabilitation patients with BI < 120 days-including traumatic brain injury (TBI; n = 360), intracranial hemorrhage (ICH; n = 213), primary brain tumor (n = 66), and hypoxia/other BI (n = 70)--were screened for evidence of DVT with lower extremity venous duplex ultrasonography (VDU). The admission screening protocol combined VDU and a commercial d-dimer (Dimertest [DDLx]) latex agglutination assay. DVT was considered present based upon VDU results only. RESULTS: DVT prevalence was 11.1%, and was higher with brain tumor (21.2%) and ICH (16%) than with TBI (6.7%) (chi2 test; p = 0.001). DVT risk factors identified by multivariable logistic regression analysis in the overall sample included older age (p = 0.002), type of BI (p = 0.04), DDLx (p = 0.0001), and greater postinjury duration (p = 0.0001), with a trend observed regarding lower Functional Independence Measure (FIM) locomotion (FIM-Loco) subscale score (p = 0.07). However, risk factors also varied with type of BI. Among patients with TBI, only DDLx (p = 0.001) and greater postinjury duration (p = 0.001) were associated with DVT. CONCLUSIONS: Admission venous duplex ultrasonography revealed occult proximal lower extremity deep vein thrombosis in 11% of neurorehabilitation patients with acquired brain injury. Deep vein thrombosis risk is multifactorial in this heterogenous patient population, with relative factor risk influenced by type of acquired brain injury. Semiquantitative d-dimer latex agglutination assay correlated significantly with presence of deep vein thrombosis.

Managing anemia and blood loss in elective gynecologic surgery patients.

Hysterectomy is the second-most-common surgical procedure among premenopausal women. The conditions that lead to the need for a hysterectomy often are accompanied by chronic blood loss that can lead to anemia. Moreover, hysterectomy and myomectomy may result in significant blood loss, which exacerbates the anemia. The presence of fatigue associated with anemia has a substantially negative impact on quality of life and the ability to perform activities of daily living. Options for alleviating perioperative anemia include minimizing surgical blood loss, blood transfusion, supplementation with hematinics, such as iron and folic acid, and treatment with recombinant human erythropoietin. Treating preoperative anemia is expected to help correct anemia prior to surgery and may have a positive impact on anemia-related symptoms and surgical outcomes.

The preoperative bleeding time test lacks clinical benefit: College of American Pathologists' and American Society of Clinical Pathologists' position article.

The major conclusions of this position article are as follows: (1) In the absence of a history of a bleeding disorder, the bleeding time is not a useful predictor of the risk of hemorrhage associated with surgical procedures. (2) A normal bleeding time does not exclude the possibility of excessive hemorrhage associated with invasive procedures. (3) The bleeding time cannot be used to reliably identify patients who may have recently ingested aspirin or nonsteroidal anti-inflammatory agents or those who have a platelet defect attributable to these drugs. The best preoperative screen to predict bleeding continues to be a carefully conducted clinical history that includes family and previous dental, obstetric, surgical, traumatic injury, transfusion, and drug histories. A history suggesting a possible bleeding disorder may require further evaluation; such an evaluation may include performance of the bleeding time test, as well as a determination of the platelet count, the prothrombin time, and the activated partial thromboplastin time. In the absence of a history of excessive bleeding, the bleeding time fails as a screening test and is, therefore, not indicated as a routine preoperative test.

Randomized blinded study of aprotinin infusion for liver crush injuries in the pig model.

Repeat exploratory laparotomies for intra-abdominal bleeding in patients who sustain severe blunt intra-abdominal trauma are common. Reexploration usually reveals no single site of bleeding and the abdomen is closed with laparotomy pad packing, with a presumed diagnosis of coagulopathy. These postoperative coagulational defects may be the result of dilution, consumption, dysfunction, or acquired defects of either the coagulation, fibrinolytic, or platelet systems. The liver plays a major role in the balance of hemostatic systems, and this balance is disrupted by liver trauma. This study investigates the use of intravenous aprotinin, a naturally occurring serine protease inhibitor, in a pig liver crush model to evaluate its effectiveness in reducing intra-abdominal bleeding in experimentally induced shock and non-shock states.

Remote umbilical arterial blood pH analysis: accuracy, utility, and limitations.

It is not always possible or feasible to perform routine umbilical artery blood sampling at birth. This study was undertaken to assess the accuracy of selective remote umbilical arterial blood analysis to retrospectively predict the original birth pH of any newborn. Umbilical arterial blood samples were obtained in two preheparinized syringes immediately following 1007 deliveries. One sample was analyzed within 60 minutes of delivery. The other was placed on ice and later analyzed at variable time intervals up to 180 hours postpartum. The results of each remote analysis were adjusted using a previously published regression equation to accurately identify which newborns had pH values < 7.00, < or = 7.10, or < 7.20 at birth. Among the 1007 newborns, there were 14 (1.3%), 44 (4.3%), and 187 (18.5%) who had pH values < 7.00, < or = 7.10, and < 7.20, respectively, at birth. Remote umbilical arterial samples analyzed within 72 hours of delivery correctly identified newborns with an original pH < 7.00, < or = 7.10, or < 7.20 with: (1) a sensitivity of 100, 82, and 84%, respectively; (2) positive predictive values of 100, 93, and 66%, respectively; and (3) a test efficiency of 100, 99, and 89%, respectively. Up to 72 hours after delivery, remote umbilical arterial blood pH analysis can be reliably used to accurately identify the newborn that was acidotic at birth.

The effect of levenogesterol (Norplant) contraception on coagulation as measured by antithrombin-III levels.

PURPOSE: To determine the effect of contraception given immediately postpartum on coagulation as measured by antithrombin III. STUDY DESIGN: In this prospective study, parturients (n = 85) self selected three means of postpartum contraception: levenorgesterol implants, oral contraceptives, or a barrier method. RESULTS: Baseline coagulation was assessed by antithrombin-III levels in each of the 85 women within 48 hours of delivery (100.35 +/- 1.61%) and at one (109.1 +/- 1.89%) and six (105.51 +/- 1.71%) weeks postpartum. There was a rise in antithrombin-III after delivery but there were no significant differences between the groups. CONCLUSION: The levenorgesterol implant system did not cause a decrease in antithrombin-III in normal parturients.

PIP: The effect of postpartum Norplant implant use on coagulation factors was investigated in a prospective study conducted in Mississippi, US. 85 postpartum women were given a choice of 3 contraceptive methods: levonorgestrel implants (n = 25), oral contraceptives (n = 38), or a barrier method (n = 22). Antithrombin-III (AT-III) levels were measured on the day of discharge from the hospital after delivery, 7 days after delivery, and 6 weeks after delivery. There was no significant difference between groups in the initial AT-III level (mean, 100.35 +or- 1.61%). At the end of the first postpartum week, AT-III levels rose significantly to 109.1 +or- 1.89%, but again, there were no significant differences according to contraceptive method. By the 6-week follow-up, AT-III levels had stabilized at a mean of 105.51 +or- 1.71%, with no significant between-group differences. AT-III levels in pill users declined more markedly between the first and sixth postpartum weeks than those in the 2 other groups. These findings indicate that subdermal implant use does not affect coagulation, and these devices can be inserted safely during the postpartum period.

Maternal serum creatine kinase does not predict tubal pregnancy.

PURPOSE: Our purpose was to validate prospectively the predictive value of maternal serum creatine kinase in the evaluation of ectopic pregnancy. METHODS: Fifty-one consecutive pregnant first-trimester patients who presented for suspected abnormal pregnancy were enrolled. Maternal serum samples were obtained and assayed for creatine kinase. Patients were subsequently evaluated for abnormal pregnancy by serial quantitative hCG levels, transvaginal ultrasonography, and surgery when appropriate. A receiver operating characteristic (ROC) curve was generated comparing intrauterine to extrauterine (ectopic) pregnancy. RESULTS: Of 51 patients, 18 had an ectopic pregnancy, 16 had a spontaneous abortion, and 17 had an ongoing intrauterine pregnancy. The ROC curve revealed that maternal serum creatine kinase had no ability to predict ectopic pregnancy. CONCLUSIONS: Maternal serum creatine kinase is not a reliable predictor of tubal pregnancy.

Performance characteristics of fibrinogen assays. Results of the College of American Pathologists Proficiency Testing Program 1988-1991.

Plasma fibrinogen concentration appears to be an important risk factor for the development of atherosclerotic cardiovascular disease of a similar magnitude to cholesterol. The quality control of plasma fibrinogen assays has taken on new importance as a consequence of this potential role as an atherosclerotic risk factor. This article reviews the performance characteristics of 40,000 fibrinogen assays comprising the College of American Pathologists Proficiency Testing Program from 1988 through 1991. Instrument and reagent variables both play roles in the poor interlaboratory reproducibility documented by this study. The absence of either a national or international standard for plasma fibrinogen assays has been a major source of reagent variability. The validation and calibration of the College of American Pathologists lyophilized plasma reference preparation for fibrinogen determination is also reported in this study. The availability of this validated reference plasma should markedly improve interlaboratory reproducibility.

Factors affecting the performance of factor VIII coagulant activity assays. Results of proficiency surveys of the College of American Pathologists.

To evaluate sources of interlaboratory variation in factor VIII coagulant assays and the effects of uniform calibration on it, data were analyzed from Survey Set H2-C, 1987, of the College of American Pathologists, Northfield, Ill, into which the College of American Pathologists Reference Preparation for Factor VIII was incorporated. Peer group performance and its improvement by uniform calibration were evaluated by comparing means, precisions, and numbers of acceptable survey scores. Results showed a poorer performance by less experience laboratories and by those that used undesirable calibrators. Substantial improvement was seen with uniform calibration, especially among laboratories that had employed poorer calibrators. Although variance component analysis showed that the type of calibrator was the most important contributor to interlaboratory variation, it accounted for only 10% of total variability. Participant summaries and questionnaires that spanned several years revealed steady improvement in methodology but no striking changes in interlaboratory variation.

Coagulation changes after an experimental missile wound to the brain in the cat.

Platelet studies (total number and platelet aggregation) and coagulation assays (fibrinogen, factor VIII, and anti-thrombin III) were performed on systemic arterial blood of four control and four experimental adult cats that sustained a penetrating missile injury to the brain. Among the brain-wounded, a significant decrease in the total number of platelets and aggregates occurred 120 minutes after injury. Fibrinogen levels decreased significantly in the brain-wounded animals by 240 minutes after injury and continued declining until the end of the 6-hour experiment. No significant changes occurred in factor VIII and antithrombin III levels in wounded as compared with control animals. These results indicate that blood coagulation factors are altered following a missile wound to the brain. These alterations may, occasionally, lead to clinically manifested bleeding disorders, specifically disseminated intravascular coagulation. Thus, early analysis and control of the coagulation system in the brain-wounded patient should be considered to prevent and treat bleeding disorders in the setting of penetrating head injury.

Effect of lupus anticoagulants on the activated partial thromboplastin time. Results of the College of American Pathologists survey program.

Lupus anticoagulants are antibodies that interfere with in vitro phospholipid-dependent coagulation reactions. In vivo, they have been associated with a variety of thromboembolic problems. Samples from patients with lupus anticoagulants were included in the 1986 and 1987 College of American Pathologists proficiency survey program. Participant performance on these samples demonstrated significant variation in the responsiveness of different activated partial thromboplastin reagents to lupus anticoagulants. The level of factor VIII in these samples reported by the participants also varied with the reagent used. Follow-up studies demonstrated striking reagent-dependent differences in the dilutional effect on apparent factor VIII, IX, XI, and XII activity. These results point out the importance of selecting sensitive and responsive reagents for appropriate identification of lupus inhibitors. In addition, the results indicate that the choice of reagent used for factor assays can affect the apparent factor activity as well as whether a dilutional effect is noted when a lupus anticoagulant is present in the test sample, an important consideration when trying to distinguish a lupus anticoagulant from a specific factor inhibitor.

Evaluation of APTT reagent sensitivity to factor IX and factor IX assay performance. Results from the College of American Pathologists Survey Program.

Hereditary factor IX deficiency (hemophilia B) is among the more common hereditary bleeding disorders and factor IX assays are among the more common specific factor assays performed by coagulation laboratories. To assess the sensitivity of various reagents used for performance of activated partial thromboplastin times and factor IX assays, a series of samples with varying levels of factor IX were included in the 1988 College of American Pathologists Survey Program. We found significant differences in the sensitivity of reagents to factor IX deficiency. Surprisingly, the least sensitive reagents were among the most commonly used reagents. Significant differences in the classification of activated partial thromboplastin times as abnormal were noted between H1 and H2 survey participants. As with factor VIII assays, significant differences in the dose-response curves for factor IX deficiency were noted between reagents, with more responsive reagents giving more precise results for factor IX assays. Comparison of factor IX assay performance in 1988 with 1980 performance indicates a substantial improvement in assay precision. However, a further improvement in assay performance could be expected if current recommendations were followed.

Factor VIII assays. Assessment of variables.

Factor VIII assays are the most common specific coagulation factor assay performed in the United States. Interlaboratory proficiency studies have documented persistent problems with variation in results between laboratories. The Coagulation Resource Committee of the College of American Pathologists conducted a workshop to analyze variables that may affect performance of the one-stage factor assay. The results indicate that accuracy of the assay can be improved by uniform standardization of reference plasma samples and that reproducibility can be enhanced through appropriate choice of reagents and instruments. Optimizing performance of this assay should lead to more reproducible interlaboratory results.

The effects of heparin on the activated partial thromboplastin time of the College of American Pathologists Survey specimens. Responsiveness, precision, and sample effects.

Heparinized survey samples from the College of American Pathologists from 1981 through 1984 were reviewed to assess effects of the various reagents and instrumentation on the performance of the activated partial thromboplastin time (aPTT) in response to heparin. Responsiveness of the aPTT to the concentration of heparin as well as its sensitivity to the detection of heparin in the therapeutic range was most affected by choice of reagents. Precision was most affected by choice of instruments with photo-optical devices being roughly comparable. A previously described effect of calcium vs sodium salts of heparin was not supported by these data. Survey results were compared with results from fresh plasma samples from patients who had received heparin therapeutically and with response curves obtained from specimens heparinized ex vivo. The pattern of reagent dose responsiveness to the heparinized patient samples differed from that seen with survey samples and with the ex vivo heparinized fresh plasma samples. In addition, intrinsic characteristics of the individual specimens exerted substantial effects on the test results for all specimen types. Therefore, one cannot automatically assume that phenomena that hold for one form of plasma preparation are applicable to another. The nature and source of the heparinized plasma specimen must be taken into account when interpreting aPTT results.

In vitro aggregation of normal platelets: a hypothetical first-approximation model for light extinction in platelet-rich plasma.

Aggregometer tracings of light transmission through platelet-rich-plasma are routinely used for the clinical evaluation of platelet function. The analytical relation between the changing aggregometer curve tracings of the light extinction and the aggregation process remains unknown. A first-approximation equation for this relation is proposed, based upon a highly simplified view of the in vitro aggregation process for normal platelets. The model described is capable of generating curves which show strong resemblance to those predicted by light scattering theory as well as those observed experimentally, including biphasic structures.

Coronary heart disease in young black and white males in New Orleans: Community Pathology Study.

The biracial population of New Orleans has a high overall mortality rate, high coronary heart disease (CHD) mortality rate, and high autopsy rate. In the New Orleans Community Pathology Study we investigated atherosclerosis and CHD in all deceased males aged 25 to 44 years, with major focus on the 52% of subjects from whom heart and arterial specimens were collected and evaluated according to standardized procedures. Morphologic correlates of CHD are the same in young black and white males. CHD mortality and mortality from cerebral hemorrhage, hypertensive heart disease, chronic renal disease, and diabetes are greater in young black males than young white males. Age, serum cholesterol, and hypertension were identified as important associated factors in the atherosclerotic process, as well as in CHD. The extent of coronary lesions seems to have decreased between 1960-1964 and 1969-1978 in young white males but not in blacks. Racial differences in coronary lesion involvement in non-CHD deaths are smaller than in our earlier studies.

Laboratory assessment of coagulation disorders in liver disease.

Coagulation disorders in liver disease (cirrhosis or acute hepatic necrosis) may be assessed by the laboratory evaluation of factors V, VII, VIII and IX, and fibrinolysis. Tests of platelet and vascular function do not significantly contribute to this assessment. The response of the factors to vitamin K and to fresh frozen plasma contribute to the assessment of bleeding potential and prognosis.

Detection of abnormal cells in white cell differentials: comparison of the HEMATRAK automated system with manual methods.

Automated differential systems can rapidly count larger numbers of cells compared with the standard manual procedure. When a fixed number of abnormal cells are interspersed randomly with a large number of normal cells, it can be shown mathematically that counting more cells increases the chances of detecting at least one abnormal cell. To test this hypothesis in a clinical setting, the authors compared 200-cell and 400-cell automated differentials obtained via the HEMATRAK Model 360 system with results of 100-cell differentials performed either manually or automatically for a group of 141 blood smears. Manual 100-cell differentials also were performed in a reference laboratory for comparison. In close agreement with theoretical expectation, both 200-cell and 400-cell differentials detected significantly more abnormal cells than did either the manual or automated 100-cell differential. Results of the latter two were not significantly different. Eighty-seven per cent of the slides that, according to the 100-cell manual differential, were without abnormal cells were found to have such cells on the 400-cell automated differential. Atypical lymphocytes and nucleated red blood cells were the abnormal cells most frequently identified.

Demand v need v physician prerogatives in the use of the WBC differential.

The clinical use of the WBC differential was investigated before and after it was made available on demand. The results indicate that no consistent policy existed in our hospital for the ordering of a differential. When differentials were made available on demand, the number of differentials did not increase compared with earlier periods. The demand for differentials may have been caused more by the denial of a physician's prerogative to order a differential rather than by its requirement for patient care.