Florian Langer

University Medical Center Hamburg - Eppendorf, Hamburg, Hamburg, Germany

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Publications (39)115.46 Total impact

  • F Langer
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    ABSTRACT: The clinical link between cancer and thrombosis has been recognized by Armand Trousseau in 1865. It has become clear that activation of coagulation and fibrinolysis plays an important role not only in the pathophysiology of Trousseau's syndrome, but also in the progression of solid malignancies. In particular, tissue factor is critical for both primary tumour growth and haematogenous metastasis. Haemostatic perturbations in cancer patients are, at least in part, controlled by defined genetic events in molecular tumourigenesis, including activating and inactivating mutations of oncogenes and tumour suppressor genes, respectively. While long-term treatment with low-molecular-weight heparin (LMWH) is considered standard therapy for established venous thromboembolism (VTE), pharmacological VTE prophylaxis in ambulatory cancer patients and the management of complex systemic coagulopathies remain a challenge and have to be decided on an individual basis and in a risk-adapted manner. Experimental and preclinical studies further suggest that LMWH may be beneficial in cancer therapy, but this innovative concept has not yet been proven beyond doubt in rigorously designed clinical trials.
    Hamostaseologie 05/2015; 35(2):152-64. DOI:10.5482/HAMO-14-11-0057 · 1.59 Impact Factor
  • C Dicke, F Langer
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    ABSTRACT: Clinically relevant clotting abnormalities in cancer patients are referred to as Trousseau's syndrome. While thrombotic complications such as venous thromboembolism are most frequent in every day's practice, cancer patients may also experience severe bleeding symptoms due to complex systemic coagulopathies, including disseminated intravascular coagulation, haemolytic thrombotic microangiopathy, and hyperfibrinolysis. The pathophysiology of Trousseau's syndrome involves all aspects of Virchow's triad, but previous basic research has mainly focused on the cellular and molecular mechanisms underlying blood hypercoagulability in solid cancers and haematological malignancies. In this regard, over-expression of tissue factor (TF), the principal initiator of the extrinsic coagulation pathway, by primary tumour cells and increased shedding of TF-bearing plasma microparticles are critical to both thrombus formation and cancer progression. However, novel findings on intrinsic contact activation in vivo, such as the release of polyphosphates or DNA by activated platelets and neutrophils, respectively, have pointed to additional pathways in the complex pathophysiology of Trousseau's syndrome.
    Hamostaseologie 11/2014; 35(1). DOI:10.5482/HAMO-14-08-0037 · 1.59 Impact Factor
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    ABSTRACT: Immune tolerance induction (ITI) in patients with haemophilia B and inhibitors may be complicated by anaphylactic reactions and nephrotic syndrome with lower success rates than in haemophilia A (25% vs. 50-90%). According to case reports, immunosuppressive therapy in addition to high doses of factor IX (FIX) appears to be promising. We report an 18-year-old patient with severe haemophilia B and a FIX inhibitor with a maximum titre of 2.6 Bethesda units and allergic skin reactions to FIX infusions. At 5 years of age, this patient already had a FIX inhibitor with allergic reactions to FIX and activated prothrombin complex concentrate. ITI at 11 years of age with high-dose FIX, dexamethasone, rituximab, mycophenolate mofetil and intravenous immunoglobulins had induced a sustained response until the current presentation. The patient was restarted on the same ITI regimen with aforementioned immunosuppressants, which were initiated one week before high-dose FIX. No allergic reactions, nephrotic syndrome or serious infection occurred during ITI. The FIX inhibitor was undetectable after five weeks of treatment and remained so until 19 months of follow-up.
    Hamostaseologie 11/2014; 34 Suppl 1(4A):S5-8. DOI:10.5482/HAMO-14-01-0010 · 1.59 Impact Factor
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    ABSTRACT: The management of patients with acquired factor V inhibitors is challenging, because their bleeding risk is highly variable and only poorly correlated with routine coagulation tests. Furthermore, there is no standardized treatment for bleeding control or inhibitor eradication. An 84-year-old white man underwent uneventful surgery for a ruptured intracerebral haemangioma. There were no perioperative coagulation abnormalities. Eight weeks after surgery, however, the prothrombin and the activated partial thromboplastin times were found to be maximally prolonged without signs of acute haemorrhage. A factor V inhibitor of 212 Bethesda units was diagnosed. We used a fluorogenic real-time thrombin generation assay with low concentrations of tissue factor (TF) to analyse the factor V inhibitor for interference with coagulation in platelet-poor plasma. Compared with three bleeding patients with acquired haemophilia A and severely deficient thrombin generation, total thrombin generation capacity was similar in the patient and healthy controls. However, the lag phase was significantly prolonged, suggesting a defect in the initiation/amplification, but not in the propagation phase of TF-triggered thrombin generation. This defect could be fully reproduced by purified patient IgG and largely corrected by ex-vivo addition of activated prothrombin complex concentrate, but not recombinant human FVIIa. Addition of normal platelets to the patient's plasma resulted in a pronounced shortening of the lag phase, suggesting that platelet-derived factor V can escape the inhibitor. Our findings offer an explanation for the absence of spontaneous bleeding in this patient and support the concept of platelet transfusions for the management of acute haemorrhages in patients with acquired factor V inhibitors.
    Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 08/2014; 26(1). DOI:10.1097/MBC.0000000000000181 · 1.38 Impact Factor
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    ABSTRACT: Acquired hemophilia A (AHA) and acquired von Willebrand Syndrome (AVWS) are both rare bleeding disorders that can be associated with lymphoproliferative or autoimmune diseases. AHA is uniformly caused by inhibitory autoantibodies against coagulation factor VIII (FVIII), while the pathophysiology of AVWS comprises several distinct mechanisms, including reduced synthesis, accelerated clearance, or increased proteolysis. In this regard, autoantibodies to von Willebrand factor (VWF) have been described in patients with systemic lupus erythematosus (SLE) or monoclonal gammopathy. Here, we report the case of a 71-year-old patient with a recent onset of spontaneous mucocutaneous and soft-tissue bleeding due to severely decreased FVIII and VWF. While there was no evidence for monoclonal gammopathy, specific IgG antibodies against both FVIII and VWF were detected. Furthermore, VWF multimer analysis revealed the presence of ultralarge plasma multimers and absence of the typical multimeric triplet structure, a finding consistent with decreased proteolytic processing of massively released, but rapidly cleared VWF. Both FVIII and VWF readily responded to immunosuppressive therapy with prednisolone. Interestingly, clinical and laboratory findings established the diagnosis of "late-onset SLE" in our patient. Thus, about 45 years after the first description of AVWS in a 12-year-old boy with SLE, we present another unusual case of concomitant autoimmune-mediated AHA and AVWS in an elderly SLE patient, which, to the best of our knowledge, has not been reported so far.
    08/2014; 3:21. DOI:10.1186/2162-3619-3-21
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    ABSTRACT: The impact of haemophilia and its treatment on social status has not been well studied, although research into the quality of life of patients with haemophilia has shed some light on aspects of social and role functioning. Studies conducted before the advent of safe and effective coagulation factor replacement therapy suggest that the haemophilia population was predominantly of low socioeconomic status with many social disadvantages, including high rates of disability and unemployment and low rates of marriage. Since the availability of purified factor VIII concentrates that could be used in a home-care setting and as prophylaxis, most research suggests that social status and well-being amongst children, adolescents, and adults with haemophilia is not compromised, and is comparable to that of the general population. Children and adolescents with haemophilia do not generally feel disadvantaged, although haemophilia-related issues at school and amongst peer groups do arise. Recent studies in adults show higher than average rates of marriage and cohabitation and the attainment of a generally good educational status, but, as in the past, employment rates remain comparatively lower. Social status amongst the elderly with haemophilia who may have developed severe disability as a result of their condition is poorly defined and has never been formally studied. Additional research is recommended.
    Thrombosis Research 04/2014; DOI:10.1016/j.thromres.2013.10.012 · 2.43 Impact Factor
  • F Langer, W Ruf
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    ABSTRACT: Tissue factor (TF), the cellular receptor and cofactor for factor VII/VIIa, initiates haemostasis and thrombosis. Initial tissue distribution studies suggested that TF was sequestered from the circulation and only present at perivascular sites. However, there is now clear evidence that TF also exists as a blood-borne form with critical contributions not only to arterial thrombosis following plaque rupture and to venous thrombosis following endothelial perturbation, but also to various other clotting abnormalities associated with trauma, infection, or cancer. Because thrombin generation, fibrin deposition, and platelet aggregation in the contexts of haemostasis, thrombosis, and pathogen defence frequently occur without TF de novo synthesis, considerable efforts are still directed to understanding the molecular events underlying the conversion of predominantly non-coagulant or cryptic TF on the surface of haematopoietic cells to a highly procoagulant molecule following cellular injury or stimulation. This article will review some of the still controversial mechanisms implicated in cellular TF activation or decryption with particular focus on the coordinated effects of outer leaflet phosphatidylserine exposure and thiol-disulfide exchange pathways involving protein disulfide isomerase (PDI). In this regard, our recent findings of ATP-triggered stimulation of the purinergic P2X7 receptor on myeloid and smooth muscle cells resulting in potent TF activation and shedding of procoagulant microparticles as well as of rapid monocyte TF decryption following antithymocyte globulin-dependent membrane complement fixation have delineated specific PDI-dependent pathways of cellular TF activation and thus illustrated additional and novel links in the coupling of inflammation and coagulation.
    Thrombosis and Haemostasis 01/2014; 111(3). DOI:10.1160/TH13-09-0802 · 5.76 Impact Factor
  • Thrombosis and Haemostasis 12/2013; 111(4). DOI:10.1160/TH13-06-0462 · 5.76 Impact Factor
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    ABSTRACT: Background: Germ cell tumor (GCT) patients are at risk of venous thromboembolic events (VTEEs). A higher incidence of VTEEs has been reported in GCT patients undergoing cisplatin-based chemotherapy. Patients and Methods: A retrospective analysis of the incidence of and risk factors for VTEEs in 193 GCT patients receiving platinum-based chemotherapy in Hamburg, Germany, between 2000 and 2009 was performed. Results: VTEEs occurred in 22 patients (11%). In only 4 patients, the VTEEs occurred during cisplatin-based chemotherapy, while 18 patients (81%) experienced VTEEs prior to initiation of chemotherapy. Pure seminoma, 'intermediate risk' (International Germ Cell Cancer Collaborative Group (IGCCCG)), retroperitoneal or supraclavicular lymph node metastases, elevated lactate dehydrogenase (LDH) levels, a central venous catheter (CVC), arterial hypertension, application of granulocyte colony-stimulating factor (G-CSF) and of ≥ 3 cycles of cisplatin-based chemotherapy could be identified as risk factors. 2 risk groups could be described: (i) VTEEs manifesting before chemotherapy in patients with seminoma, retroperitoneal tumor masses, and elevated LDH levels, and (ii) VTEEs occurring during chemotherapy applied via CVC in patients with supraclavicular lymph node metastases. Conclusions: The incidence of VTEEs in GCT patients was 11%, but in the majority of patients, the VTEEs occurred before the initiation of platinum-based chemotherapy. Supraclavicular lymph node metastases and use of a CVC are risk factors for VTEEs during chemotherapy. © 2013 S. Karger GmbH, Freiburg.
    Onkologie 11/2013; 36(11):663-8. DOI:10.1159/000355652 · 0.84 Impact Factor
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    ABSTRACT: Preoperative evaluation of patients presenting with ovarian masses is challenging, partly due to shortcomings with the commonly used marker, CA-125. Ovarian cancer is associated with systemic coagulation activation. Measurement of D-dimer, serum tissue factor (TF), and the coagulation process as a whole are considered candidates for improving discrimination between benign and malignant ovarian masses. We therefore sought to identify possible benefits by analyzing preoperative coagulation status in conjunction with CA-125 in patients with ovarian masses. Preoperative blood from 95 patients with ovarian masses (75 benign, 20 malignant) and 30 controls was analyzed, prospectively. Thromboelastography served for global hemostatic assessment. Plasma TF antigen and D-dimer were measured by ELISA and microparticle-associated TF activity by thrombin generation assay. TF microparticles were enumerated by flow cytometry. Time to clot formation by thromboelastography was similar between patients having either benign or malignant ovarian tumors. Clot formation rate, clot strength, and coagulation index were significantly increased in patients having malignant versus benign tumors, indicating that thromboelastography differentiated malignant from benign tumors. D-dimer alone differentiated malignant from benign ovarian tumors and also improved differentiation when combined with CA-125. Circulating TF antigen, activity, and TF microparticle numbers, however, failed to differentiate benign from malignant tumors. Significant coagulation activation occurs in women with ovarian malignancies. Plasma D-dimer may help discriminate between patients with benign and malignant tumors. Thromboelastography may also contribute meaningfully when combined with CA-125 in the preoperative evaluation of ovarian masses. Larger studies are needed to assess these possibilities.
    Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 02/2013; DOI:10.1097/MBC.0b013e32835e63b7 · 1.38 Impact Factor
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    ABSTRACT: Lymphocyte depletion with antithymocyte globulin (ATG) can be complicated by systemic coagulation activation. We found that ATG activated tissue factor procoagulant activity (TF PCA) on monocytic cells more potently than other stimuli that decrypt TF, including cell disruption, TFPI inhibition or calcium ionophore treatment. Induction of TF PCA by ATG was dependent on lipid raft integrity and complement activation. We showed that ATG-mediated TF activation required complement activation until assembly of the C5b-7 membrane insertion complex, but not lytic pore formation by the membrane attack complex C5b-9. Consistently, induction of TF PCA by ATG did not require maximal phosphatidylserine membrane exposure and was not correlated with the magnitude of complement-induced lytic cell injury. Blockade of free thiols, an inhibitory monoclonal antibody to protein disulfide isomerase (PDI) and the small-molecule PDI antagonist quercetin-3-rutinosid prevented ATG-mediated TF activation, and C5 complement activation resulted in oxidation of cell surface PDI. This rapid and potent mechanism of cellular TF activation represents a novel connection between the complement system and cell surface PDI-mediated thiol-disulfide exchange. The delineation of this clinically relevant mechanism of activation of the extrinsic coagulation pathway during immunosuppressive therapy with ATG may have broader implications for vascular thrombosis associated with inflammatory disorders.
    Blood 01/2013; 121(12). DOI:10.1182/blood-2012-10-460493 · 10.43 Impact Factor
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    ABSTRACT: BACKGROUND: Acquired factor XIII (FXIII) deficiency is associated with reduced clot firmness and increased bleeding in patients undergoing major surgery. In contrast, only limited information is available on the haemostatic relevance of acquired FXIII deficiency in non-surgical patients. CASE REPORT: An 81-year-old patient, who had experienced acute type-A dissection of the aorta eight years earlier, presented with a 3-year history of progressive mucocutaneous and soft-tissue bleeding. Diagnostic work-up was unremarkable for global coagulation tests, but FXIII and alpha2-antiplasmin were decreased to 33% and 27%, respectively, while plasma D-dimer was elevated to > 35 mg/l. A FXIII inhibitor was excluded by mixing studies. CT scanning revealed a massively elongated and progressively dilated aorta with a false lumen reaching from the left carotid artery to the iliac bifurcation. Bleeding control was achieved by single doses of FXIII at 20-30 IU/kg body weight and tailored oral tranexamic acid. CONCLUSION: Acquired FXIII deficiency with activity levels of 30-35% may confer a severe bleeding tendency in non-surgical patients, especially in the context of increased thrombin an fibrin generation.
    Hamostaseologie 01/2013; 33 Suppl 1:S50-4. · 1.59 Impact Factor
  • Thrombosis Research 04/2012; 129:S169. DOI:10.1016/S0049-3848(12)70070-1 · 2.43 Impact Factor
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    ABSTRACT: Background: Development of FVIII inhibitors represents a major challenge in patients with mild haemophilia A (HA), because they tend to occur at an older age and classical immune tolerance induction appears to be less effective. Case report: A man (age: 60 years) with mild HA due to the missense mutation, Leu1929Arg, received a single dose of rFVIII at 35IU/kg prior to routine colonoscopy, totalling 25 lifetime exposure days. Two months later, rFVIII was infused for a traumatic hip haematoma. However, FVIII recovery was inappropriate, and a FVIII inhibitor of 19 BU with type-2 kinetics was detected, resulting in FVIII:C of <1%. Two weeks later, the patient experienced spontaneous iliopsoas bleeding. Parallel to bypassing therapy, we started single-agent immunosuppression with prednisolone at 1.5mg/kg. FVIII:C "normalized" at 10.2% after four weeks. After five months, the inhibitor titre fell to <0.4BU with sustained remission after one year of follow-up. Conclusion: In mild HA, FVIII inhibitors may share characteristic features with FVIII autoantibodies commonly observed in acquired HA. Therefore, immunosuppressive therapy alone could be successful at least in a subset of patients.
    Hamostaseologie 01/2012; 32 Suppl 1:S48-51. · 1.59 Impact Factor
  • F Langer, C Bokemeyer
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    ABSTRACT: Cancer is characterized by bidirectional interrelations between tumour progression, coagulation activation, and inflammation. Tissue factor (TF), the principal initiator of the coagulation protease cascade, is centrally positioned in this complex triangular network due to its pleiotropic effects in haemostasis, angiogenesis, and haematogenous metastasis. While formation of macroscopic thrombi is the correlate of cancer-associated venous thromboembolism (VTE), a major healthcare burden in clinical haematology and oncology, microvascular thrombosis appears to be critically important to blood-borne tumour cell dissemination. In this regard, expression of TF in malignant tissues as well as shedding of TF-bearing microparticles into the circulation are thought to be regulated by defined genetic events relevant to pathological cancer progression, thus directly linking Trousseau's syndrome to molecular tumourigenesis. Because pharmacological inhibition of the TF pathway in selective tumour types and patient subgroups would be in line with the modern concept of individualized, targeted anti-cancer therapy, this review will focus on the role of TF in tumour biology and cancer-associated VTE.
    Hamostaseologie 07/2011; 32(2):95-104. DOI:10.5482/ha-1160 · 1.59 Impact Factor
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    ABSTRACT: High on-treatment platelet reactivity has been associated with adverse cardiovascular events in patients receiving anti-platelet agents, but the molecular mechanisms underlying this phenomenon remain incompletely understood. Succinate, a citric acid cycle intermediate, is released into the circulation under conditions of mitochondrial dysfunction due to hypoxic organ damage, including sepsis, stroke, and myocardial infarction. Because the G protein-coupled receptor (GPCR) for succinate, SUCNR1 (GPR91), is present on human platelets, we hypothesized that succinate-mediated platelet stimulation may counteract the pharmacological effects of cyclooxygenase-1 and ADP receptor antagonists. To test this hypothesis in a controlled in-vitro study, washed platelets from healthy donors were treated with acetylsalicylic acid (ASA) or small-molecule P2Y(1) or P2Y(12) inhibitors and subsequently analyzed by light transmittance aggregometry using arachidonic acid (AA), ADP and succinate as platelet agonists. Aggregation in response to succinate alone was highly variable with only 29% of donors showing a (mostly delayed) platelet response. In contrast, succinate reproducibly and concentration-dependently (10-1000 µM) enhanced platelet aggregation in response to low concentrations of exogenous ADP. Furthermore, while succinate alone had no effect in the presence of platelet inhibitors, responsiveness of platelets to ADP after pretreatment with P2Y(1) or P2Y(12) antagonists was fully restored, when platelets were co-stimulated with 100 µM succinate. Similarly, succinate completely (at 1000 µM) or partially (at 100 µM) reversed the inhibitory effect of ASA on AA-induced platelet aggregation. In contrast, succinate failed to restore platelet responsiveness in the presence of both ASA and the P2Y(12) antagonist, suggesting that concomitant signaling via different GPCRs was required. Essentially identical results were obtained, when flow cytometric analysis of surface CD62P expression was used as a different readout for platelet activation. In summary, extracellular succinate may have a co-stimulatory role in platelet aggregation and, by (partially) antagonizing the effects of platelet inhibitors, may contribute to the inter-individual variability frequently observed in platelet function testing.
    Platelets 07/2011; 23(1):60-8. DOI:10.3109/09537104.2011.590255 · 2.63 Impact Factor
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    ABSTRACT: Anti-CD40L immunotherapy in systemic lupus erythematosus patients was associated with thromboembolism of unknown cause. We previously showed that monoclonal anti-CD40L immune complexes (ICs) activated platelets in vitro via the IgG receptor (FcgammaRIIa). In this study, we examined the prothrombotic effects of anti-CD40L ICs in vivo. Because mouse platelets lack FcgammaRIIa, we used FCGR2A transgenic mice. FCGR2A mice were injected i.v. with preformed ICs consisting of either anti-human CD40L mAb (M90) plus human CD40L, or a chimerized anti-mouse CD40L mAb (hMR1) plus mouse CD40L. ICs containing an aglycosylated form of hMR1, which does not bind FcgammaRIIa, were also injected. M90 IC caused shock and thrombocytopenia in FCGR2A but not in wild-type mice. Animals injected with hMR1 IC also experienced these effects, whereas those injected with aglycosylated-hMR1 IC did not, demonstrating that anti-CD40L IC-induced platelet activation in vivo is FcgammaRIIa-dependent. Sequential injections of individual IC components caused similar effects, suggesting that ICs were able to assemble in circulation. Analysis of IC-injected mice revealed pulmonary thrombi consisting of platelet aggregates and fibrin. Mice pretreated with a thrombin inhibitor became moderately thrombocytopenic in response to anti-CD40L ICs and had pulmonary platelet-thrombi devoid of fibrin. In conclusion, we have shown for the first time that anti-CD40L IC-induced thrombosis can be replicated in mice transgenic for FcgammaRIIa. This molecular mechanism may be important for understanding thrombosis associated with CD40L immunotherapy. The FCGR2A mouse model may also be useful for assessing the hemostatic safety of other therapeutic Abs.
    The Journal of Immunology 08/2010; 185(3):1577-83. DOI:10.4049/jimmunol.0903888 · 5.36 Impact Factor
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    ABSTRACT: It is established that experimental metastasis requires platelet activity. CD154 expressed on and released from activated platelets induces an inflammatory response in endothelial cells and monocytes, including tissue factor production. CD154 has also been shown to activate platelets in vitro and promote thrombus stability in vivo. These CD154 effects may be mediated, at least in part, by CD40 signaling on platelets and vascular endothelial cells. We have previously demonstrated prolonged bleeding and PFA-100 closure times in mice deficient for Cd154 or its receptor Cd40. In the present study, we hypothesized that Cd40 and Cd154 promote lung tumor formation in experimental metastasis in mice. We created mice doubly deficient in Cd40 and Cd154 (Dbl KO) and found them to be both fertile and viable. Injected tumor cells seeded poorly in mice deficient in Cd40 or Cd154, as well as Dbl KO, compared to wild-type mice. We sought to determine whether blood-borne Cd40 versus endothelial Cd40 contribute differentially to reduced experimental lung metastasis, as observed in Cd40 deficient mice. By bone marrow transplantation, we created mice deficient for Cd40 either in the blood compartment but not in the endothelium, or vice versa. We found that mice deficient in blood compartment Cd40 had fewer lung nodules compared to wild-type mice and mice deficient in endothelial Cd40. Our findings suggest an important contribution of the Cd40-Cd154 pathway to experimental lung metastasis. Furthermore, the data points to a selective role for peripheral blood cell Cd40 in this process.
    Clinical and Experimental Metastasis 10/2009; 26(7):829-837. DOI:10.1007/s10585-009-9282-7 · 3.73 Impact Factor
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    ABSTRACT: Tissue factor (TF) plays a critical role in tumour growth and metastasis, and its enhanced release into plasma in association with cellular microparticles (MPs) has recently been associated with pathological cancer progression. We have previously demonstrated significantly elevated levels of plasma TF antigen as well as systemic coagulation and platelet activation in patients with localised prostate cancer. In this prospective study, we used a highly sensitive one-stage clotting assay to measure preoperative TF-specific procoagulant activity (PCA) of plasma MPs in 68 consecutive patients with early-stage prostate cancer to further explore the relevance of circulating TF in this tumour entity. Automated calibrated thrombography was used to monitor thrombin generation in cell-free plasma samples in the absence of exogenous TF or phospholipids. Compared to healthy male controls (n=20), patients had significantly increased levels of both D-dimer and TF-specific PCA of plasma MPs (p<0.001). Furthermore, MP-associated TF PCA was higher in patients with (n=29) than in those without (n=39) laboratory evidence of an acute-phase reaction (p=0.004) and decreased to normal levels within one week after radical prostatectomy. Overall, we found a significant correlation between TF-specific PCA of plasma MPs and plasma D-dimer (p=0.002), suggesting that plasma MPs contributed to in-vivo coagulation activation in a TF-dependent manner. Thrombin generation in plasma was also significantly increased in patients compared to controls (p<0.01). Collectively, our findings suggest that TF-specific PCA of plasma MPs contributes to intravascular coagulation activation in patients with early-stage prostate cancer and may represent a potential link between hypercoagulability, inflammation, and disease progression.
    Thrombosis and Haemostasis 06/2009; 101(6):1147-55. DOI:10.1160/TH08-10-0654 · 5.76 Impact Factor
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    ABSTRACT: Krebspatienten haben ein erhöhtes Risiko für thromboembolische Komplikationen, die gemeinhin unter dem Begriff des Trousseau-Syndroms zusammengefasst werden. Neben der malignen Grunderkrankung, die mit dramatischen Veränderungen von systemischer Blutgerinnung und Fibrinolyse einhergehen kann, spielen Supportivmaßnahmen und spezifische Krebstherapien wie Operation oder Chemotherapie in der Pathophysiologie der tumorassoziierten venösen Thromboembolie (VTE) eine bedeutende Rolle. Klinische Studien haben gezeigt, dass in der medikamentösen Therapie der tumorassoziierten VTE eine Langzeitbehandlung mit niedermolekularem Heparin (NMH) einer Sekundärprophylaxe mit Vitamin-K-Antagonisten überlegen ist. Welche Krebspatienten am ehesten von einer primären Thromboseprophylaxe mit NMH profitieren, ist dagegen nicht abschließend geklärt. Diesbezüglich muss das individuelle Risikoprofil, das in erheblichem Maße durch den Allgemeinzustand des Patienten und etwaige Begleiterkrankungen mitbestimmt wird, berücksichtigt werden. Experimentelle und klinische Studien legen nahe, dass NMH über eine multifaktorielle Beeinflussung der Tumorbiologie auch in der Krebstherapie von Nutzen sein könnte. Cancer patients are at increased risk of thromboembolic complications, which are commonly referred to as Trousseau’s syndrome. Besides the potentially dramatic effects of the tumor on the coagulation and fibrinolytic systems, various supportive measures and more specific cancer treatments, such as surgery or chemotherapy contribute to the pathophysiology of cancer-associated venous thromboembolism (VTE). Clinical trials have shown that long-term therapy with low-molecular-weight heparin (LMWH) is superior to secondary prophylaxis with vitamin K antagonists in the treatment of patients with cancer-associated VTE. Based on currently available clinical evidence it is not clear which cancer patient should be offered primary thromboprophylaxis with LMWH. In this respect, the individual risk profile which is substantially influenced by the general condition of the patient and possible co-morbidities have to be taken into account. Recent experimental and clinical studies have suggested that LMWH affects tumor biology at various levels and may thus be potentially beneficial as an adjunct in cancer therapy.
    Der Onkologe 02/2009; 15(2):150-156. DOI:10.1007/s00761-008-1552-5 · 0.13 Impact Factor

Publication Stats

369 Citations
115.46 Total Impact Points


  • 2003–2014
    • University Medical Center Hamburg - Eppendorf
      • • Bone Marrow Transplantation Unit
      • • Department of Hepatobiliary and Transplant Surgery
      Hamburg, Hamburg, Germany
  • 2004–2013
    • Florida Hospital Cancer Institute
      Orlando, Florida, United States