Florian Langer

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

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Publications (45)127.74 Total impact

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    ABSTRACT: Background: Tissue factor (TF), the principal initiator of the extrinsic coagulation pathway, is expressed by many tumors and can be released into the bloodstream on plasma microparticles (MPs). Experimental studies indicate that TF may facilitate hematogenous metastasis by promoting tumor cell-induced microvascular thrombosis, but clinical data supporting this hypothesis is sparse. Case reports: Here, we report 2 unusual cases of rapidly progressive solid malignancies (gastric and urothelial carcinoma). In both patients, cancer cell dissemination with diffuse bone marrow involvement was either strongly suggested by leukoerythroblastic changes on peripheral blood smear or directly proven by positive findings on aspiration cytology. Furthermore, laboratory evidence of thrombotic microangiopathy (TMA) and disseminated intravascular coagulation was accompanied by new-onset severe pulmonary hypertension and a hemolytic uremic syndrome-like disorder in the gastric and the urothelial carcinoma patient, respectively. TF-specific procoagulant activity of isolated plasma MPs, as assessed by single-stage clotting assay, was dramatically increased in both patients compared to healthy controls (21- and 55-fold), and primary tumor samples stained strongly positive for TF by immunohistochemistry. Conclusion: TMA was likely caused by TF-triggered tumor cell embolization in both patients. Further clinical evidence is thus provided that TF directly links coagulation activation to cancer cell dissemination.
    Oncology Research and Treatment 09/2015; 38(9):449-452. DOI:10.1159/000433501
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    ABSTRACT: In acute myeloid leukemia (AML), disseminated intravascular coagulation (DIC) contributes to morbidity and mortality, but the underlying pathomechanisms remain incompletely understood. We conducted a prospective study on 69 patients with newly diagnosed AML to further define the correlates of systemic coagulation activation in this hematological malignancy. Tissue factor procoagulant activity (TF PCA) of isolated peripheral blood mononuclear cells (PBMCs) and TF expression by circulating microparticles (MPs) were assessed by single-stage clotting and thrombin generation assay, respectively. Soluble plasma TF antigen and secretion of vascular endothelial growth factor (VEGF) by cultured PBMCs were measured by ELISA. Cell-free plasma DNA was quantified by staining with a fluorescent dye. TF PCA of PBMCs was significantly increased in AML patients as compared to healthy controls. Furthermore, TF PCA was significantly associated with decompensated DIC at presentation, as defined by a plasma fibrinogen level of ≤1 g/L (n = 11). In addition to TF PCA and circulating blasts, serum lactate dehydrogenase, a surrogate marker for leukemic cell turnover, correlated with plasma D-Dimer in the total patient cohort and was significantly increased in DIC patients, suggesting a role for myeloblast apoptosis/necrosis in activation of the TF-dependent coagulation pathway. Consistently, TF-bearing plasma MPs were more frequently detected and levels of soluble TF antigen were significantly higher in DIC vs. non-DIC patients. No association was found between TF PCA expression and VEGF secretion by isolated PBMCs, but significantly increased levels of cell-free plasma DNA pointed to a contribution of the intrinsic contact pathway to systemic coagulation activation in the total patient cohort and in patients with lower TF PCA expression. While PBMC-associated TF PCA had no effect on long-term survival, DIC occurrence at presentation increased the risk of early mortality. In newly diagnosed AML, TF expression by PBMCs and shedding of TF-bearing plasma MPs are central to the pathogenesis of DIC, but additional pathways, such as DNA liberation, may contribute to systemic coagulation activation.
    08/2015; 4(1):22. DOI:10.1186/s40164-015-0018-x
  • K Holstein · S von Mackensen · C Bokemeyer · F Langer ·
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    ABSTRACT: In haemophilia, clinical outcomes are mainly determined by the severity of clotting factor deficiency, treatment regimen, availability of clotting factor concentrate and age. Information about the relevance of patient-related factors such as education, social status or impact of the disease on the patient's life is scarce. To assess the impact of social status and disease-related impairment of certain aspects of the patient's life on clinical and psychosocial outcomes in patients with inherited bleeding disorders (PWBD). Consecutive patients of a single centre were assessed by questionnaires on social status and quality of life (SF-36). Social status was defined by school and professional education, employment and financial income of patients as well as school education of their parents. Fifty-seven PWBD (mean age, 38 ± 16 years) were enrolled, 60% were treated on-demand; PWBD had a median number of 2.5 (0-34) annual bleeds and a median orthopaedic joint score of 6 (0-38). No significant differences were found for clinical and psychosocial outcomes across social status groups. More than half of the patients reported that haemophilia had an impact on their school education, childhood and leisure activities. Patients with a high impact of haemophilia on their lives were less satisfied with their lives (P < 0.002), reported worse quality of life in all domains of the SF-36, had a worse joint score (P < 0.024) and reported more pain (P < 0.013). The perceived impact of haemophilia on patients' lives seems to have a stronger impact on clinical and psychosocial outcomes than patients' actual social status. © 2015 John Wiley & Sons Ltd.
    Haemophilia 07/2015; DOI:10.1111/hae.12760 · 2.60 Impact Factor
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    ABSTRACT: Patients with germ cell tumors (GCTs) receiving cisplatin-based chemotherapy are at increased risk of thrombosis, but the underlying cellular and molecular mechanisms remain obscure. To study baseline tissue factor (TF) expression by GCT cell lines and its modulation by cisplatin treatment. TF expression was assessed by single-stage clotting and thrombin generation assay, flow cytometry, ELISA, and Western blot analysis. Cell cycle analysis and detection of phosphatidylserine (PS) membrane exposure were carried out by flow cytometry. TF mRNA was analyzed by quantitative RT-PCR. Significant expression of TF-specific procoagulant activity (PCA) was detected on three non-seminoma (NT2, 2102Ep, NCCIT) and one seminoma cell line (TCam-2). Treatment with 0.4μM cisplatin (corresponding to the IC50) for 48hrs increased TF PCA on NT2 cells 3-fold, an effect that was largely independent of PS exposure and that could not be explained by translocation of active TF from intracellular storage pools. Cisplatin-induced TF PCA expression in NT2 cells did not occur before 12hrs, but was steady thereafter and accompanied by a 2-fold increase in total and surface-located TF antigen. Importantly, increased TF gene transcription or production and release of an intermediate factor were not involved in this process. Cell cycle analysis suggested that cisplatin-induced G2/M arrest resulted in an accumulation of procoagulant TF on the membrane surface of NT2 cells. In addition to induction of apoptosis/necrosis with PS-mediated activation of preformed TF, cisplatin may alter the procoagulant phenotype of GCT cells through an increase in total cellular TF antigen. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Thrombosis Research 07/2015; 136(3). DOI:10.1016/j.thromres.2015.07.002 · 2.45 Impact Factor
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    ABSTRACT: Cancer is a leading cause of thrombosis. We identify a new procoagulant mechanism that contributes to thromboembolism in prostate cancer and allows for safe anticoagulation therapy development. Prostate cancer-mediated procoagulant activity was reduced in plasma in the absence of factor XII or its substrate of the intrinsic coagulation pathway, factor XI. Prostate cancer cells and secreted prostasomes expose long chain polyphosphate on their surface that co-localized with active factor XII and initiated coagulation in a factor XII-dependent manner. Polyphosphate content correlated with the procoagulant activity of prostasomes. Inherited deficiency in factors XI, XII or high molecular weight kininogen, but not plasma kallikrein, protected mice from prostasome-induced lethal pulmonary embolism. Targeting polyphosphate or factor XII conferred resistance to prostate cancer-driven thrombosis in mice, without increasing bleeding. Inhibition of factor XII with recombinant 3F7 antibody reduced the increased prostasome-mediated procoagulant activity in patient plasma. The data illustrate a critical role for polyphosphate/factor XII-triggered coagulation in prostate cancer-associated thrombosis with implications for anticoagulation without therapy-associated bleeding in malignancies. Copyright © 2015 American Society of Hematology.
    Blood 07/2015; 126(11). DOI:10.1182/blood-2015-01-622811 · 10.45 Impact Factor
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    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 · 1.60 Impact Factor
  • Minna Voigtlaender · Lenard Conradi · Andrea Hinsch · Florian Langer ·

    04/2015; DOI:10.1055/s-0035-1549841
  • 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 · 1.60 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 · 1.60 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 · 1.40 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(1):21. DOI:10.1186/2162-3619-3-21
  • Katharina Holstein · Barbara Eifrig · Florian Langer ·
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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; 134. DOI:10.1016/j.thromres.2013.10.012 · 2.45 Impact Factor
  • Florian Langer · Wolfram 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 · 4.98 Impact Factor

  • Thrombosis and Haemostasis 12/2013; 111(4). DOI:10.1160/TH13-06-0462 · 4.98 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.
    Onkologie 11/2013; 36(11):663-8. DOI:10.1159/000355652 · 0.86 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 10/2013; 33 Suppl 1:S50-4. · 1.60 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; 24(5). DOI:10.1097/MBC.0b013e32835e63b7 · 1.40 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 · 10.45 Impact Factor
  • K Holstein · G Marx · B Lentz · C Bokemeyer · F Langer ·
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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 35 IU/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 <0.4 BU 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 09/2012; 32 Suppl 1:S48-51. · 1.60 Impact Factor

  • Thrombosis Research 04/2012; 129:S169. DOI:10.1016/S0049-3848(12)70070-1 · 2.45 Impact Factor

Publication Stats

461 Citations
127.74 Total Impact Points


  • 2003-2015
    • University Medical Center Hamburg - Eppendorf
      • • Bone Marrow Transplantation Unit
      • • Department of Hepatobiliary and Transplant Surgery
      Hamburg, Hamburg, Germany