Revisiting the Phadia/EliA cut-off values for anticardiolipin and anti-ß2-glycoprotein I antibodies: a systematic evaluation according to the guidelines.

Background Phadia/EliA fluorescence enzyme immunoassays are widely used automated assays for anticardiolipin (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies. To date, cut-off values for these assays have not been evaluated systematically and the evidence behind manufacturer's recommended cut-off values is not clear. Objective To determine Phadia/EliA cut-off values for antiphospholipid antibodies (aPL) according to the procedures suggested by guidelines. Methods A total of 266 blood donors (135 females and 131 males) were included. The pre-handling and analysis of the samples were performed according to the International Society on Thrombosis and Hemostasis (ISTH) guideline for solid phase aPL assays. Cut-off values and corresponding 90% confidence intervals (CI) for each antibody were established and outliers were handled according to the Clinical and Laboratory Standards Institute (CLSI) guideline for reference intervals. Samples from 377 consecutive patients, referred to our thrombophilia center with evidence of thrombosis or pregnancy morbidity were included for aPL testing. Results The in-house 99th (97.5th) percentile cut-off values were 11 (8.7), 12 (6.9) 8.5 (5.0) AU/mL for aß2GPI IgG, IgM and IgA, and 21 (13) GPL-U/mL and 41 (25) MPL-U/mL for aCL IgG and IgM, respectively. The prevalence of positive results (%) defined by these cut-off values in patients with evidence of thrombosis or pregnancy morbidity was 9.5 (12.2), 1.6 (2.9), and 7.0 (9.9), and 0.8 (3.8) for aß2GPI IgG, IgM, and aCL IgG and IgM respectively. The use of in-house 99th percentile cut-off values compared to the manufacturer suggested cut-off values resulted in 1 and 39 fewer samples for aß2GPI and aCL to be classified as positive for aPL, respectively. Conclusions We present Phadia/EliA cut-off values with 90% CI for aPL determined systematically according to the ISTH and CLSI guidelines. These values are different from values previously determined, suggesting variation of aPLs in different populations. Our findings indicate the need for each laboratory to determine/validate assay specific cut-off values for aPL.

[Plasmin-mediated activation of the coagulation system. A study of patients with acute ischemic heart disease treated with recombinant tissue-plasminogen activator]. / Plasminmedieret aktivering af koagulationssystemet. En undersøgelse af patienter med akut iskoemisk hjertesygdom behandlet med rekombinant voevsplasminogenaktivator.

We have studied the response of haemostatic reaction products in peripheral blood of patients with acute ischaemic heart disease receiving combined recombinant tissue type plasminogen activator/heparin therapy. We have found evidence that formation of excessive amounts of plasmin in vivo in relation to such therapy significantly enhances the degradation of fibrin, and of fibrinogen as well as the formation of thrombin. We conclude that excessive plasmin formation by thrombolytic therapy causes systemic effects including activation of coagulation.

The fibrinolysis and coagulation systems in ischaemic heart disease. Risk markers and their relation to metabolic dysfunction of the arterial intima.

This report reviews the major haemostatic deviations associated with the evolution of ischaemic heart disease (IHD) and also such deviations, which might be of importance for the evolution of the acute ischaemic heart syndrome. It is demonstrated that deviation in the t-PA/PAI-1 system indicate endothelial cell dysfunction in patients with IHD. Different factors which have the capability to induce such an endothelial cell dysfunction are proposed, i.e. hyperinsulinemia, mediators of chronic disease phase response, and thrombin. Finally, the intimate interrelation between coagulation and fibrinolysis in patients with IHD is discussed. The experimental and clinical studies reviewed provide good evidence that the endothelial cell response of t-PA and PAI-1 is coupled and that there is an intimate interrelation between generation of thrombin and production/release of t-PA and PAI-1 in IHD patients.

Radial scar in the female breast. A long-term follow-up study of 32 cases.

In a retrospective histologic study of 1862 benign breast tissue specimens, 32 cases were found to have radial scar. The radial scar was multicentric in 44%, and found in breasts with fibrocystic disease and/or duct ectasia. During a follow-up period of 19.5 years (range, 15-24 years), one patient developed breast cancer compared with an expected rate of 0.94. Therefore, local excision of radial scar without further follow-up is sufficient.

Gynecomasty: histological aspects in a surgical material.

In a consecutive and unselected series of 83 patients operated upon for gynecomasty, the histological and related clinical aspects were studied. It was convincingly demonstrated that gynecomasty begins in an active proliferating phase and ends in a fibrous inactive phase. Contrary to previous authors we found it justified that the formation of lobules, indistinguishable from what is seen in the reproduceable age in the female breast, is not necessarily related to the administration of exogenic hormones. In five (6.5%) cases, typical multicentric foci of intraductal epithelial hyperplasia were demonstrated--of the atypical hyperplastic or early intraductal carcinoma type. It was concluded that the clinical significance of such morphological changes must not be overestimated.

Male breast at autopsy.

In a consecutive and unselected series of 100 male autopsies, the breasts were totally extirpated and histologically investigated. Gynecomasty was found in 55 cases, of which 48 were in healed and seven in still active, intermediate phase. All but two cases were bilateral. No clinical evidence of gynecomasty was established in any case. Thus, gynecomasty seems to be very common in men. In seven cases, severe intraductal epithelial hyperplasia was found, three of pagetoid and four of cribriform type. They belonged to the atypical hyperplastic--early intraductal carcinoma type. All cases were incidentally found and without known clinical relevance.

Involvement of the nipple and areola in breast cancer. Value of clinical findings.

In a series of 80 consecutive mastectomies it was investigated histologically, by a horizontal sectioning technique, how often the nipple and/or areola were involved in breast cancer. Such involvement was found in 35 cases (43.8%). In the same series the value of the clinical findings as to involvement of the nipple and/or areola was assessed. Only 6 of the 35 cases had shown clinical changes that could give rise to a suspicion of spread to the nipple and/or areola.