Viscoelastic measurements of platelet function, not fibrinogen function, predicts sensitivity to tissue-type plasminogen activator in trauma patients.

BACKGROUND: Systemic hyperfibrinolysis is a lethal phenotype of trauma-induced coagulopathy. Its pathogenesis is poorly understood. Recent studies have support a central role of platelets in hemostasis and in fibrinolysis regulation, implying that platelet impairment is integral to the development of postinjury systemic hyperfibrinolysis. OBJECTIVE: The objective of this study was to identify if platelet function is associated with blood clot sensitivity to fibrinolysis. We hypothesize that platelet impairment of the ADP pathway correlates with fibrinolysis sensitivity in trauma patients. METHODS: A prospective observational study of patients meeting the criteria for the highest level of activation at an urban trauma center was performed. Viscoelastic parameters associated with platelet function (maximum amplitude [MA]) were measured with native thrombelastography (TEG), and TEG platelet mapping of the ADP pathway (ADP-MA). The contribution of fibrinogen to clotting was measured with TEG (angle) and the TEG functional fibrinogen (FF) assay (FF-MA). Another TEG assay containing tissue-type plasminogen activator (t-PA) (75 ng mL(-1) ) was used to assess clot sensitivity to an exogenous fibrinolytic stimulus by use of the TEG lysis at 30 min (LY30) variable. Multivariate linear regression was used to identify which TEG variable correlated with t-PA-LY30 (quantification of fibrinolysis sensitivity). RESULTS: Fifty-eight trauma patients were included in the analysis, with a median injury severity score of 17 and a base deficit of 6 mEq L(-1) . TEG parameters that significantly predicted t-PA-LY30 were related to platelet function (ADP-MA, P = 0.001; MA, P < 0.001) but not to fibrinogen (FF-MA, P = 0.773; angle, P = 0.083). Clinical predictors of platelet ADP impairment included calcium level (P = 0.001), base deficit (P = 0.001), and injury severity (P = 0.001). RESULTS AND CONCLUSIONS: Platelet impairment of the ADP pathway is associated with increased sensitivity to t-PA. ADP pathway inhibition in platelets may be an early step in the pathogenesis of systemic hyperfibrinolysis.

Proteomic analysis of the supernatant of red blood cell units: the effects of storage and leucoreduction.

BACKGROUND: Red blood cell (RBC) transfusion is a life-saving intervention for critically ill patients; however, it has been linked to increased morbidity and mortality. We hypothesize that a number of important proteins accumulate during routine storage of RBCs, which may explain some of the adverse effects seen in transfused patients. STUDY DESIGN: Five RBC units were drawn and divided (half prestorage leucoreduced (LR-RBC) and half left as an unmodified control (RBC). The supernatant was separated on days 1 and 42 of storage and proteomic analyses completed with in-gel tryptic digestion and nano-liquid chromatography tandem mass spectrometry. RESULTS: In RBC supernatants, 401 proteins were identified: 203 increased with storage, 114 decreased, and 84 were unchanged. In LR-RBC supernatant, 231 proteins were identified: 84 increased with storage, 30 decreased, and 117 were unchanged. Prestorage leucoreduction removed many platelet- and leucocyte-derived structural proteins; however, a number of intracellular proteins accumulated including peroxiredoxins (Prdx) 6 and latexin. The increases were confirmed by immunoblotting, including the T-phosphorylation of Prdx-6, indicating that it may be functioning as an active phospholipase. Active matrix metalloproteinase-9 also increased with a coinciding decrease in the metalloproteinase inhibitor 1 and cystatin C. CONCLUSION: We conclude that a number of proteins increase with RBC storage, which is partially ameliorated with leucoreduction, and transfusion of stored RBCs may introduce mediators that result in adverse events in the transfused host.

Association between colposcopic findings and histology in cervical lesions: the significance of the size of the lesion.

The relation between eight specific colposcopic diagnostic findings and the histologic grade of a cervical lesion in 896 women was evaluated. The size of the transformation zone (TZ), the size of the lesion, the intensity of the color tone, distinct margins, the pathology of the vessels, and the presence of micropapillae as single findings were highly statistically correlated to the histologic grade (P < 0.0001). By logistic regression analysis the risk for a higher histologic grade when assessed by colposcopy was greatest in women with variation of the acetowhite color (odds ratio (OR) = 16.0; 95% CI, 10.0-26.0) followed by coarse vessels (OR = 10.0; CI, 3.2-34.0). Lesion-size larger than 50% of the visible cervix had an OR of 3.6 (CI, 2.1-6.3). Extention beyond TZ had an OR of 0.4 (CI, 0.2-0.4) and larger TZ had an OR of 0.5 (CI, 0.3-0.9). In conclusion we found that the size of the cervical lesion had some independent predictive value and should be considered in future trials.

Diagnostic accuracy of cytology and colposcopy in cervical squamous intraepithelial lesions.

OBJECTIVE: To evaluate the diagnostic accuracy of cytology and colposcopy in women with an abnormal cervical smear using histology as the 'gold standard'. DESIGN: Survey of consecutively referred women with abnormal smear. SETTING: The out-patient colposcopical clinic of Herning Hospital, Denmark. PATIENTS: 813 women with a median age of 29.0 years (range 15-71 years) with their first abnormal smear. RESULTS: For detecting cervical high-grade lesions (HGL) the sensitivity of cytology was 41% (36-47%), of colposcopy 67% (62-72%) and in combination 75% (70-80%), so at least 25% of HGL were underestimated. Colposcopy underestimated more CIN-2 than CIN-3 lesions and more small lesions and lesions in smaller transformation zones. Cytology underestimated more CIN-2 lesions but equal numbers of small and large lesions and transformation zones. CONCLUSIONS: Colposcopy was a better tool for diagnosing HGL than cytology, but even in combination too many HGL were missed. All women with abnormal cytology should therefore have colposcopical and histological investigation and prospective studies of the natural history of cervical squamous lesions should include histological evidence.

[Status of preventive screening for uterine cervix cancer in Denmark in 1994]. / Status for forebyggende undersøgelser mod livmoderhalskraeft i Danmark 1994.

In 1986 The National Board of Health published guidelines for cervical cancer screening in Denmark. These guidelines recommend organized screening with personal invitations every three years to women in the age group 23-59 years, and in the years to come also invitation of women aged 60-74 years. We studied the organization of cervical cancer screening in Danish counties at the beginning of 1994. Organized screening programmes are running in 15 out of the 16 "counties" (this include the municipalities of København and Frederiksberg). Four counties completely follow the national guidelines. Eight counties follow these guidelines in general, but they do not invite women above the age of 60 years. In total, 72% of women aged 25-74 years are at present invited for cervical cancer screening in Denmark.

[Status of preventive examinations against uterine cervix cancer in Denmark]. / Status for forebyggende undersøgelser mod livmoderhalskraeft i Danmark 1991.

In 1986, The Danish National Board of Health published guidelines for cervical cancer screening. These guidelines recommend organized screening with personal invitations every three years to women in the age group 23-59 years, and in the years to come also invitations to women aged 60-74 years. Five years have now elapsed since publication of these guidelines, and we have therefore studied the present organization of cervical cancer screening in Danish counties. Organized screening programmes are now, medio 1991, running in 11 out of the 16 "counties" (this includes the municipalities of Copenhagen and Frederiksberg). One county follows the national guidelines entirely. Six counties follow these guidelines in general, but they do not invite women over the age of 60 years. In all, 45% of women aged 25-74 years are at present invited for cervical cancer screening in Denmark. Two counties have decided to start organized screening programmes in 1992.

Glassy-cell carcinoma of the cervix: case report with a light and electron microscopy study.

A case of glassy-cell carcinoma of the cervix is reported. In the literature this tumor is regarded as an undifferentiated form of mixed carcinomas of the cervix. At the light microscopic level the tumor cells are characterized by a moderate amount of cytoplasm of ground-glass appearance that stains faintly blue with hematoxylin, a distinct cell wall that stains with eosin or with periodic acid-Schiff (PAS), and large vesiculated nuclei with prominent nucleoli. In the cytoplasm of very few tumor cells, a minute amount of Alcian blue-positive material is demonstrated. At the electron microscopic level the tumor cells show distinct cell borders with interdigitating cytoplasmic projections that contain many desmosomes. Cytoplasmic tonofilaments were demonstrated in few tumor cells. The nuclei show a euchromatic appearance with prominent mesh-basket nucleoli. The cytoplasm contains abundant ribosomes, polyribosomes, and round to oval mitochondria with transverse cristae. Some cells contain a prominent Golgi apparatus with many lysosomelike structures. A very few cells have small intracytoplasmic lumina with microvilli and annulate lamellae. The assumption that the glassy-cell carcinoma of the cervix represents a poorly differentiated adenosquamous carcinoma finds support from our ultrastructural study.