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Introduction Measuring factor VIII ( FVIII) activity can be challenging when it has been modified, such as when FVIII is pegylated to increase its circulating half-life. Use of a product-specific reference standard may help avoid this issue. Aim Evaluate the impact of using a product-specific reference standard for measuring the FVIII activity of BAX 855 - a pegylated FVIII - in eight of Switzerland's main laboratories. Methods Factor VIII-deficient plasma, spiked with five different concentrations of BAX 855, plus a control FVIII sample, was sent to the participating laboratories. They measured FVIII activity by using either with a one-stage ( OSA) or the chromogenic assay ( CA) against their local or a product-specific reference standard. Results When using a local reference standard, there was an overestimation of BAX 855 activity compared to the target concentrations, both with the OSA and CA. The use of a product-specific reference standard reduced this effect: mean recovery ranged from 127.7% to 213.5% using the OSA with local reference standards, compared to 110% to 183.8% with a product-specific reference standard, and from 146.3% to 182.4% using the CA with local reference standards compared to 72.7% to 103.7% with a product-specific reference standard. Conclusion In this in vitro study, the type of reference standard had a major impact on the measurement of BAX 855 activity. Evaluation was more accurate and precise when using a product-specific reference standard. [ABSTRACT FROM AUTHOR]

Objectives: Assessing urgency in ectopic pregnancies (ECP) remains controversial since the disorder covers a large clinical spectrum. Severe conditions such as acute abdomen or hemodynamic instability are mostly related to intra-abdominal blood loss diagnosed as free fluid (FF) on transvaginal sonography (TVS). The aims of the current study were to investigate the value of FF and to assess other potentially predictive parameters for judging urgency., Methods: Retrospective cohort analysis on prospectively collected cases of proven ECP (n = 343). Demographics, clinical and laboratory parameters, and findings on TVS and laparoscopy (LSC) were extracted from the digital patient file. FF on TVS and free blood (FB) in LSC were evaluated. Low urgency was defined as FB (LSC) < 100 ml and high urgency as FB (LSC) ≥ 300 ml. The best subset of variables for the prediction of FB was selected and predictors of urgency were evaluated using receiver operator characteristic (ROC) curves., Results: Clinical symptoms, age, β-HCG, hemoglobin (HB) preoperative, and FF were examined in multivariate analysis for the cutoff values of 100 ml and 300 ml. FF was the only independent predictor for low and high urgency; HB preoperative was only significant for high urgency offering marginal improvement. ROC analysis revealed FF as an excellent discriminatory parameter for defining low (AUC 0.837, 95% CI 0.794-0.879) and high urgency (AUC 0.902, 95 % CI 0.860-0.945)., Conclusion: Single assessment of FF on TVS is most valuable for judging urgency. However, the exact cutoff values for a low- and high-risk situation must still be defined., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Thrombophilia testing is controversial, not least because of its high cost. Because comprehensive valid testing requires standardized blood collection close by the specialized laboratory, and interpretation of findings together with clinical data, often only part of the necessary laboratory analyses can be performed in remote central laboratories. Restrictive indications for testing, as have been recommended by previous reviews on the topic, have been based on incomplete analytics, studies with small case numbers, or short observation periods, and on an inappropriate, simple risk stratification for venous thromboembolism (VTE), further subdivided into provoked and unprovoked events., Methods: The authors reviewed four electronic databases for all peer-reviewed and in-press articles about thrombophilia, VTE, obstetric complications, and arterial thrombosis. After confirmation for relevance to the topic, 201 articles were accepted for inclusion in this article. This review summarizes the studies relevant to the evaluation of thrombophilic conditions, and their combination with each other and with clinical risk factors, to stratify individual risk for thromboembolism and obstetric complications., Results: Thrombophilia testing requires highly skilled personnel for laboratory analysis and interpretation. Clinical conditions that influence the results as well as special preanalytical, analytical, and postanalytical aspects must be considered if valid results are to be obtained. Tests involved include the natural anticoagulants antithrombin, protein C, and protein S; the procoagulants fibrinogen (dysfibrinogen), prothrombin (mutation G20210A), factor V (Leiden mutation), factor VIII/von Willebrand factor/blood group ABO, factor IX, and factor XI; the anti-phospholipid antibodies to detect an antiphospholipid syndrome and potentially additional uncertain thrombophilic conditions. The risks of thrombophilic conditions and clinical risk factors for VTE are cumulative or even supra-additive. Scores from thrombophilic conditions and other genetic and nongenetic risk factors permit estimation of risk for first and recurrent VTE. Therapeutic strategies can be derived from this risk stratification., Conclusions: Thrombophilia testing is indicated when the results have potential to influence the type and duration of treatment. Indications include certain patients after VTE; or patients without previous VTE but with positive family history regarding VTE or thrombophilia before major surgery, pregnancy, combined oral contraceptives, or hormone replacement therapy. Whether or not thrombophilia is present should help determine anticoagulation, hormonal contraception, or hormone replacement.

Factor XIII (FXIII) is the final factor in the coagulation cascade. It converts soluble fibrin monomers into a stable fibrin clot, prevents premature degradation of fibrin, participates in wound healing, and helps prevent the loss of the endothelial barrier function. FXIII deficiency is believed to be rare, and this may explain why clinicians do not routinely take it into consideration. Congenital FXIII deficiency is a rare disease with a reported prevalence of 1 per million. However, the prevalence of acquired FXIII deficiency is much higher. Acquired forms have been described in patients with decreased hepatic or bone marrow synthesis, overconsumption and increased degradation by autoantibodies. This review offers guidance on how to suspect and diagnose FXIII deficiency in both the preoperative consultation and different surgical settings. We also analyze current scientific evidence in order to clarify when and why this clinical situation should be suspected, and how it may be treated.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug effect that occurs in 0.1&ndash;5% of heparin treated patients. Management of acute HIT currently involves (1) cessation of heparin exposure, and (2) inhibition of coagulation with an anticoagulant other than heparin. Several anticoagulants can be considered for the treatment of HIT. Anticoagulant monitoring, management of drug-induced adverse events including bleeding, and therapeutic dosing schedules in selected clinical settings represent challenges to the clinician treating HIT patients. Moreover, the fact that not all registered anticoagulants are approved for HIT in Switzerland further complicates the management of HIT. The present recommendations on the anticoagulant treatment of HIT in Switzerland have been elaborated by a panel of Swiss experts belonging to the Working Party Hemostasis (WPH) of the Swiss Society of Hematology (SGH-SSH). They are intended to support clinicians in their decision making when treating HIT patients.

Platelet quality in different platelet concentrates (PCs) has been the subject of several studies. Nonetheless, there is a lack of robust data on the correlation and agreement among platelet function tests as a prerequisite for the association of PC functionality in vitro with platelet function in vivo post PC transfusion. The purpose of our study was to correlate a larger panel of platelet function assays in PCs and to assess whether the methods agree sufficiently and can be used interchangeably. Twelve apheresis platelet concentrates in plasma (APC), 16 pooled platelet concentrates in plasma (PPC), and 12 PPC in T-sol (PPCA) were examined on days 1 and 4 after production. PCs were tested for platelet count, light transmission aggregation (LTA) induced by ADP, collagen, or TRAP; platelet ATP release induced by collagen; and spontaneous and ADP and TRAP-induced increase in CD62P and PAC1 expression measured by flow cytometry. All tests were performed in undiluted platelet-rich plasma, recalcified and mixed with an inhibitor of factor Xa and thrombin. Most platelet function parameters correlated significantly with each other, but agreement among methods was insufficient. A proper inverse correlation was observed between ADP-induced LTA and spontaneous platelet activation assessed by CD62P expression ( r  = -0.61, p  < 0.0001). Spontaneous CD62P correlated also significantly with spontaneous PAC1 ( r  = 0.69, p  < 0.0001) and inversely with TRAP-induced CD62P expression ( r  = -0.86, p  < 0.0001). We found significant correlations among all flow cytometric assays measuring platelet CD62P and PAC1 expression induced by ADP or TRAP. Subsequent Bland Altman analysis revealed insufficient agreement between methods. With one exception (collagen-induced LTA compared with TRAP-induced LTA, percentage error = 16%) the limits of agreement expressed as percentage error exceeded the chosen acceptable difference of 30%. In APC, platelet count was 41% and 44% higher, respectively, than in PPC and PPCA ( p  < 0.0001). Spontaneous CD62P and PAC1 expression were significantly greater, and ADP-induced aggregation and agonist-induced increase in CD62P and PAC1 were significantly lower in PPCA compared to APC and PPC on day 4 of storage. ADP and TRAP-induced CD62P and PAC1 activatability fell significantly during storage between day 1 and day 4 in APC and PPCA, but not in PPC. In conclusion, different platelet function tests capture different aspects of platelet function and do not correlate and agree sufficiently to be used interchangeably.

Essentials Accurate determination of anticoagulant plasma concentration is important in clinical practice. We studied the accuracy and consistency of anti-Xa assays for rivaroxaban in a multicentre study. In a range between 50 and 200 μg L -1 , anti-Xa activity correlated well with plasma concentrations. The clinical value might be limited by overestimation and intra- and inter-individual variation., Summary: Background Determining the plasma level of direct oral anticoagulants reliably is important in the work-up of complex clinical situations. Objectives To study the accuracy and consistency of anti-Xa assays for rivaroxaban plasma concentration in a prospective, multicenter evaluation study employing different reagents and analytical platforms. Methods Rivaroxaban 20 mg was administered once daily to 20 healthy volunteers and blood samples were taken at peak and trough levels (clinicaltrials.gov NCT01710267). Anti-Xa activity was determined in 10 major laboratories using different reagents and analyzers; corresponding rivaroxaban plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). Findings Overall Pearson's correlation coefficient of anti-Xa levels and HPLC-MS results was 0.99 for Biophen ® Heparin (95% CI, 0.99, 0.99), Biophen ® DiXaI (95% CI, 0.99, 0.99) and STA ® anti-Xa liquid (95% CI, 0.99, 1.00). Correlation was lower in rivaroxaban concentrations below 50 μg L -1 and above 200 μg L -1 . The overall bias of the Bland-Altman difference plot was 14.7 μg L -1 for Biophen Heparin, 17.9 μg L -1 for Biophen DiXal and 19.0 μg L -1 for STA anti-Xa liquid. Agreement between laboratories was high at peak level but limited at trough level. Conclusions Anti-Xa activity correlated well with rivaroxaban plasma concentrations, especially in a range between 50 and 200 μg L -1 . However, anti-Xa assays systematically overestimated rivaroxaban concentration as compared with HPLC-MS, particularly at higher concentrations. This overestimation, coupled with an apparent interindividual variation, might affect the interpretation of results in some situations., (© 2017 International Society on Thrombosis and Haemostasis.)

Objectives: Factor V (FV) plays an important role in coagulation. As no purified concentrate is available to restore critical FV levels, the main blood product used to replace FV is plasma. The aim of the present in vitro study was to compare the efficacy of the different available plasma products on the reversal of moderate and severe FV deficiency as assessed by ROTEM® and FV levels., Methods: Five different plasma products (6 batches of each) were compared to determine their effectiveness in replacing FV in plasma moderately or severely deficient in FV. Effectiveness was measured using the ROTEM® EXTEM clotting time (CT) and a factor V assay., Results: FFP, plasma frozen within 24 hours (FP24), Octaplas (solvent/detergent treated pooled plasma), as well as Octaplas and FP24 thawed and stored for 5 days (Octaplas TP and TP), were all used for in vitro replacement of FV. TP was significantly less effective at reversing a prolonged EXTEM CT and FV levels in FV deficient plasma than other tested products. There were no significant differences in EXTEM CT between Octaplas and Octaplas TP, while factor V activity was significantly lower in the Octaplas TP. There was no significant difference between Octaplas and FFP for EXTEM CT or FV activity., Conclusions: Octaplas and Octaplas TP appear to have an equivalent ability to improve the EXTEM CT and could be considered as a treatment alternative to FFP in patients with FV deficiency., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Plasma fibrinogen concentration is important for coagulopathy assessment, and is most commonly measured using the Clauss method. Several factors, including device type and reagent, have been shown to affect results. The study objective was to evaluate performance and repeatability of the Clauss method and to assess differences between measurements performed during and after cardiopulmonary bypass (CPB), by testing plasma samples from patients undergoing cardiac surgery with CPB. Samples were collected from 30 patients before surgery, approximately 20 minutes before weaning from CPB, and 5 minutes after CPB and protamine. Fibrinogen concentration was determined using the Clauss method at six quality-controlled specialised laboratories, according to accredited standard operating procedures. Regarding within-centre agreement for Clauss measurement, mean differences between duplicate measurements were between 0.00 g/l and 0.15 g/l, with intervals for 95% limits of agreement for mean Bland-Altman differences up to 1.3 g/l. Regarding between-centre agreement, some mean differences between pairs of centres were above 0.5 g/l. Differences of up to ~2 g/l were observed with individual samples. Increased variability was observed between centres, with inter-class correlation values below 0.5 suggesting only fair agreement. There were no significant differences in fibrinogen concentration before weaning from CPB and after CPB for most centres and methods. In conclusion, considerable differences exist between Clauss-based plasma fibrinogen measured using different detection methods. Nevertheless, the similarity between measurements shortly before weaning from CPB and after CPB within centres suggests that on-pump measurements could provide an early estimation of fibrinogen deficit after CPB and thus guidance for haemostatic therapy.

Introduction: Rivaroxaban (RXA) is licensed for prophylaxis of venous thromboembolism after major orthopaedic surgery of the lower limbs. Currently, no test to quantify RXA in plasma has been validated in an inter-laboratory setting. Our study had three aims: to assess i) the feasibility of RXA quantification with a commercial anti-FXa assay, ii) its accuracy and precision in an inter-laboratory setting, and iii) the influence of 10mg of RXA on routine coagulation tests., Methods: The same chromogenic anti-FXa assay (Hyphen BioMed) was used in all participating laboratories. RXA calibrators and sets of blinded probes (aim ii.) were prepared in vitro by spiking normal plasma. The precise RXA content was assessed by high-pressure liquid chromatography-tandem mass spectrometry. For ex-vivo studies (aim iii), plasma samples from 20 healthy volunteers taken before and 2 - 3hours after ingestion of 10mg of RXA were analyzed by participating laboratories., Results: RXA can be assayed chromogenically. Among the participating laboratories, the mean accuracy and the mean coefficient of variation for precision of RXA quantification were 7.0% and 8.8%, respectively. Mean RXA concentration was 114±43μg/L .RXA significantly altered prothrombin time, activated partial thromboplastin time, factor analysis for intrinsic and extrinsic factors. Determinations of thrombin time, fibrinogen, FXIII and D-Dimer levels were not affected., Conclusions: RXA plasma levels can be quantified accurately and precisely by a chromogenic anti-FXa assay on different coagulometers in different laboratories. Ingestion of 10mg RXA results in significant alterations of both PT- and aPTT-based coagulation assays., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Systemic treatment with bevacizumab is associated with increased rates of arterial and venous thromboembolism and haemorrhage. In order to investigate the pathophysiological mechanism involved, platelet adhesive and aggregatory functions were tested with a platelet function analyser (PFA-100®) in an in vitro study and in a longitudinal clinical observation study. For the in vitro study, blood from ten healthy volunteers was incubated with different concentrations of bevacizumab (0-1000 μg/ml plasma) and vascular endothelial growth factor (0-500 μg/ml). In the clinical observation study, PFA-100® closure times (CTs) and soluble P-selectin (sP-selectin) serum levels as a serological marker of platelet activation were assessed in 20 patients with metastatic cancer who were treated with bevacizumab in addition to cytotoxic chemotherapy. No significant changes of PFA-100® CTs were observed in the in vitro study. In the clinical observation study, mean PFA-100® CTs after treatment with bevacizumab were unchanged. sP-selectin was decreased after bevacizumab infusion by 18% (p = 0.045), which could suggest an inhibitory action on platelets. Our data do not support the view that increased platelet activation or increased platelet adhesiveness and aggregation by bevacizumab are relevant mechanisms for thrombus formation in clinical practice.

Background: DMSO is routinely infused together with hematopoietic cells in patients undergoing myeloablative therapy and was recently found to inhibit smooth muscle cells proliferation and arterial thrombus formation in the mouse by preventing tissue factor (TF), a key activator of the coagulation cascade. This study was designed to investigate whether DMSO prevents platelet activation and thus, whether it may represent an interesting agent to be used on drug eluting stents., Methods and Results: Human venous blood from healthy volunteers was collected in citrated tubes and platelet activation was studied by cone and platelet analyzer (CPA) and rapid-platelet-function-assay (RPFA). CPA analysis showed that DMSO-treated platelets exhibit a lower adherence in response to shear stress (-15.54+/-0.9427%, n=5, P<0.0001 versus control). Additionally, aggregometry studies revealed that DMSO-treated, arachidonate-stimulated platelets had an increased lag phase (18.0%+/-4.031, n=9, P=0.0004 versus control) as well as a decreased maximal aggregation (-6.388+/-2.212%, n=6, P=0.0162 versus control). Inhibitory action of DMSO could be rescued by exogenous thromboxane A2 and was mediated, at least in part, by COX-1 inhibition., Conclusions: Clinically relevant concentrations of DMSO impair platelet activation by a thromboxane A2-dependent, COX-1-mediated effect. This finding may be crucial for the previously reported anti-thrombotic property displayed by DMSO. Our findings support a role for DMSO as a novel drug to prevent not only proliferation, but also thrombotic complications of drug eluting stents., (Copyright 2009 Elsevier Inc. All rights reserved.)

Question Under Study: In most countries hypersensitivity to vitamin K antagonists (VKA) is considered to be a rare congenital bleeding diathesis. It occurs in patients with FIX propeptide mutations at locus -10. We present a Swiss family with two patients who suffered major bleedings under oral anticoagulant treatment in the presence of therapeutic or subtherapeutic INR levels and abnormally prolonged aPTT. In both patients a mutation in the propeptide of FIX at locus -10 with substitution of alanine by threonine (Ala-10Thr) was found. In one patient FIX clotting activity was found to be severely reduced (2%). The observed bleeding tendency is related to this--compared to the other vitamin K dependent factors (FII, FVII, FX)--excessively and disproportionately low level of FIX. Three generations of this family were tested for propeptide mutations, which are transmitted in an X-chromosomal recessive mode of inheritance. Apart from the two symptomatic male patients we found another male with the mutation who has not been exposed to VKA, six female carriers and four potential male carriers in the fourth generation who have not been tested. A founder effect for this mutation has been previously described for cases in Switzerland and Germany., Conclusion: FIX propeptide mutation-associated hypersensitivity to VKA is a rare occurrence in Switzerland. The severity of associated bleeding complications and the reversible nature of the bleeding diathesis may nonetheless warrant increased awareness on the part of primary care physicians in Switzerland.

Background: High-molecular-weight, low-substituted hydroxyethyl starch (HES) may not affect blood coagulation more than low-molecular-weight, low-substituted HES. The authors assessed in vivo the effect of a lowered C2/C6 ratio on pharmacokinetic characteristics and the impact on blood coagulation of high-molecular-weight, low-substituted HES., Methods: A prospective, randomized, parallel study in 30 pigs compared HES 650/0.42/2.8 with HES 650/0.42/5.6. Before, during, and after infusion of 30 ml/kg body weight HES, blood samples were collected over 630 min to measure HES concentrations and plasmatic coagulation and to assess blood coagulation in whole blood by Thrombelastography (TEG; Haemoscope Corporation, Niles, IL). Pharmacokinetic parameters were estimated using a two-compartment model., Results: The elimination constant was 0.009 +/- 0.001 min(-1) for HES 650/0.42/2.8 and 0.007 +/- 0.001 min(-1) for HES 650/0.42/5.6 (P < 0.001); the area under the plasma concentration-time curve was 1,374 +/- 340 min x g/l for HES 650/0.42/2.8 and 1,697 +/- 411 min x g/l for HES 650/0.42/5.6 (P = 0.026). The measured plasma HES concentrations were not different between HES 650/0.42/2.8 and HES 650/0.42/5.6. Both HES solutions equally affected blood coagulation: Thrombelastographic coagulation index decreased similarly at the end of infusion of HES 650/0.42/2.8 and at the end of infusion of HES 650/0.42/5.6 (P = 0.293). Also, activated partial thromboplastin and prothrombin times increased similarly for HES 650/0.42/2.8 and HES 650/0.42/5.6 (P = 0.831)., Conclusion: Reducing the C2/C6 ratio in high-molecular, low-substituted HES solutions results in a slightly faster HES elimination. However, the blood coagulation compromising effect was unaffected.

The various isoforms of transforming growth factor-beta (TGFbeta) are growth-inhibiting cytokines for cells of epithelial origin. In malignant thyroid tumors, several studies documented a high expression of TGFbeta in the majority of thyroid follicular cells suggesting a possible role as an inhibitor of cell proliferation. In contrast to this uniform pattern of TGFbeta expression in thyroid cancer, scarce and controversial data have been reported on the expression of TGFbeta in benign multinodular goiter. In the present study, we therefore analyzed the expression of TGFbeta1, TGFbeta2, and TGFbeta3 in normal thyroid tissue, multinodular goiters and papillary thyroid carcinomas by immunohistochemistry. In normal thyroid tissue, expression of the 3 TGFbeta isoforms was barely detectable. However, in the carcinomas, almost all epithelial cells displayed immunoreactivity for the three TGFbeta isoforms. In the nodules from multinodular goiters, all 3 isoforms were found to be expressed although the immunolocalization of the 3 proteins was highly variable. TGFbeta-immunostaining was found in scattered clusters of variable size and, its expression pattern was heterogenous among individual cells within single follicles. TGFbeta-positivity was present in spite of immunostaining for proliferating cell nuclear antigen (PCNA), a marker for actively proliferating cells. In conclusion, this study shows that thyroid carcinomas and benign tumors express the TGFbeta1, TGFbeta2, and TGFbeta3 isoforms. In contrast to the abundant and homogeneous expression in differentiated thyroid carcinomas, TGFbeta expression displays a highly variable interfollicular and intrafollicular pattern in multinodular goiters, suggesting an important role of TGFbeta isoforms in tumorigenesis of thyroid cells.

While the multifunctional proteins of the transforming growth factor-beta (TGF-beta) family have a potent antiproliferative effect on thyroid follicular cell growth, increased expression of TGF-beta in proliferating thyroid cells and in thyroid tumours has recently been described, suggesting a secondary counter-regulatory role of these proteins. We have studied further this apparent paradox in vitro using FRTL-5 cells, 5 continuous cell strains from feline multinodular goitres (MNG) and 29 primary cultures prepared from human MNG. While dose dependent inhibition of FRTL-5 cell growth was confirmed, a variable fraction of these cells was naturally resistant towards TGF-beta 1, thus explaining the large interassay variability of growth inhibition (36 to 98% within 2 days, n = 19). After 40 days of continuous exposure, FRTL-5 cells became fully refractory towards TGF-beta 1 inhibition, due to the selective growth of naturally resistant subclones, as demonstrated for example by microscopic observation of three-dimensionally growing collagen-embedded cell clusters. The refractoriness could still be demonstrated even after several cell passages. In addition, 2 out of 5 feline thyroid cell strains obtained from feline MNG and 18 out of 29 primary cultures from human MNG showed a high degree of refractoriness towards TGF-beta. We conclude that constitutively TGF-beta resistant cells may occur in thyroid glands and that persistent TGF-beta refractoriness may secondarily be acquired. Resistant cells may escape regular growth control mechanisms and hence may contribute to the notorious heterogeneity of thyroid growth and to nodular transformation.

In accordance with the available data most authors conclude that epidermal growth factor (EGF) has very little or no effect on FRTL-5 cells. This has been viewed as a serious handicap of this cell line. In the present study we cultivated three strains of FRTL-5 cells from different sources and assessed their response to EGF with regard to proliferation, function and differentiation. Cell proliferation was assessed by counting in a Coulter cell counter after culturing cells at suboptimal conditions in well plates. Cell function was studied by measuring iodide uptake. Cell differentiation was examined immunocytochemically by staining monolayer cultures for thyroglobulin (Tg) and EGF receptor (EGFr) as well as morphologically by microscopical evaluation of monolayer cultures. All three FRTL-5 cell lines investigated express EGFr. In two wild type FRTL-5 cell lines EGF stimulates growth, an effect that is enhanced by the presence of TSH, and partially inhibits iodide uptake. A third mutated strain of FRTL-5 cells does not respond to EGF. Tg expression can be demonstrated immunocytochemically in EGF-treated cells as well as in controls. Morphologically, in monolayer culture EGF-treated cells cannot be distinguished from controls. Contrary to previous reports, these studies demonstrate EGF effects on FRTL-5 cells that are consistent with EGF effects established in other thyroid follicular cells.

Thyroid cell lines have contributed a lot to the understanding of goitrogenesis. The cell lines mostly used in thyroid research are briefly discussed, namely the rat thyroid cell lines FRTL and FRTL-5, the porcine thyroid cell lines PORTHOS and ARTHOS, The sheep thyroid cell lines OVNIS 5H and 6H, the cat thyroid cell lines PETCAT 1 to 4 and ROMCAT, and the human thyroid cell lines FTC-133 and HTh 74. Chinese hamster ovary (CHO) cells and COS-7 cells, stably transfected with TSH receptor cDNA and expressing a functional TSH receptor, are discussed as examples for non-thyroidal cells, transfected with thyroid genes.