Inge Scharrer

University of Texas Health Science Center at San Antonio | UT HSC

Objective: Although several risk factors for retinal vein occlusion (RVO) are known, what triggers RVO is unclear in many cases. We aimed to evaluate the relevance of multiple risk factors in patients with RVO. Methods: The Gutenberg RVO Study is an observational case-control study that assessed thrombophilic, cardiovascular, ophthalmic, and dru...

Von Willebrand factor (VWF) is secreted as an acute phase protein during inflammation. ADAMTS-13 regulates the size and prothrombotic activity of VWF by it’s specific proteolytic activity. To determine the relevance of this regulatory pathway for the innate inflammatory response by polymorphonuclear neutrophils (PMN), we employed a mouse model of i...

We describe cardiac and cerebral manifestations in 27 patients with the antiphospholipid syndrome and give a review of the literature. Patients and methods We studied 27 patients with either cardiac, cerebral or both manifestations, who also were diagnosed with the antiphospholipid syndrome (APS). All patients fulfilled the proposed classification...

Unlabelled: We report on our patient (case 2) who experienced a first acute episode of thrombotic thrombocytopenic purpura (TTP) at the age of 19 years during her first pregnancy in 1976 which ended in a spontaneous abortion in the 30th gestational week. Treatment with red blood cell concentrates was implemented and splenectomy was performed. Afte...

Introduction Thromboelastography (TEG), a widely used clinical point of care coagulation test, is poorly understood. To investigate its fibrin determinants we used normal and variant fibrinogen isolates. Materials and Methods We focused mainly on the TEG maximum signal amplitude (MA), a shear modulus and clot stiffness indicator. Isolates included...

Unlabelled: We report on 21 patients with idiopathic thrombotic thrombocytopenic purpura (TTP) whose courses of disease have been followed from the respective diagnosis until now. They had a documented ADAMTS13 activity below 5%, a high autoantibody titer and detectable ultralarge von Willebrand factor (VWF) multimers during their episodes. The in...

An adequate number of qualified haemophilia centres is an essential requirement for effective and cost-efficient haemophilia care. During a reassessment of the delivery of haemophilia care in Germany a broad range of criteria relating to structure and quality of the centres were defined and a questionnaire was developed. Results: Of 137 doctors who...

Unlabelled: 76 German patients suffering from thrombotic thrombocytopenic purpura (TTP) were interrogated about the prevalence of co-occurring autoimmune disorders. In order to analyze a possible association of TTP with the questioned diseases, a comparison of prevalence rates between the patient group and the general population has been made for...

Unlabelled: An adequate number of qualified haemophilia centres is an essential requirement for effective and cost-efficient haemophilia care. During a reassessment of the delivery of haemophilia care in Germany a broad range of criteria relating to structure and quality of the centres were defined and a questionnaire was developed. Results: Of...

The anti-phospholipid syndrome (APS) is characterized by recurrent thrombosis and occurrence of anti-phospholipid antibodies (aPL). aPL are necessary, but not sufficient for the clinical manifestations of APS. Growing evidence suggests a role of innate immune cells, in particular polymorphonuclear neutrophils (PMN) and Toll-like receptors (TLR) to...

Induction of oxidative burst is dependent on aPL concentration. Human PMN (2×105 cells per well) were incubated with LPS (100 ng/ml) together with medium or titrated hIgG or aPL (10 µg/ml, 1 µg/ml, 0.1 µg/ml). Detection of specific fluorescence index (SFI) over time was calculated by subtraction of the background fluorescence of labelled cells incu...

Stimulation of PMN with aPL has no impact on induction of apoptosis. Human PMN (2×105 cells per well) were incubated with LPS (100 ng/ml) with or without the addition of aPL or hIgG (10 µg/ml) Apoptotic cells were quantified by detection of DNA fragmentation via FACS. Data shown are from one representative experiment out of 3 independent with 2 rep...

Exudative age-related macular degeneration (ARMD) is one of the conditions which has been shown to be associated with a risk of massive subretinal hemorrhage. Patients with thick submacular hemorrhage complicating ARMD typically have a poor visual prognosis. Antiplatelet therapy with aspirin, clopidogrel or ticlopidine has significant benefits in t...

Als häufigste Ursache der subretinalen Massenblutungen gilt die neovaskuläre altersbedingte Makuladegeneration (AMD), die eine Erkrankung des fortgeschritteneren Lebensalters darstellt. Diese Altersgruppe hat jedoch nicht nur ein erhöhtes AMD-Risiko, sondern weist darüber hinaus zahlreiche kardiovaskuläre Begleiterkrankungen auf, die eine vorüberge...

Hintergrund Ziel unserer prospektiven Analyse war zu zeigen, wie häufig Gerinnungsstörungen in dem Patientenkollektiv einer Tonsillektomie vorkommen und wie häufig Gerinnungsstörungen die Ursache für Nachblutungen sind. Patienten und Methoden In die Studie eingeschlossen wurden alle 92 konsekutiven Fälle, die im Zeitraum vom 01.01.2007 bis 31.12.2...

The aim of our prospective analysis was to show the incidence of bleeding disorders among a tonsillectomy patient population and in case of bleeding disorders. This study comprised 92 consecutive patients who underwent tonsillectomies from 1 January 2007 to 31 December 2007 at the Department of Otorhinolaryngology, University Medical Center Mainz....

An adequate number of qualified haemophilia centres is an essential requirement for effective and cost-efficient haemophilia care. During a reassessment of the delivery of haemophilia care in Germany a broad range of criteria relating to structure and quality of the centres were defined and a questionnaire was developed. Results: Of 137 doctors who...

Fifty-four adult German patients suffering from idiopathic thrombotic thrombocytopenic purpura (TTP) have been examined for HLA class II. All patients presented autoantibodies against ADAMTS13 and ADAMTS13 activity levels <5%. Blood samples have been analyzed for HLA-DRB1 and DQB1 alleles using sequence-specific primer PCR and sequence-specific oli...

Epistaxis can have a variety of different local or systemic causes. It is the cardinal symptom of von Willebrand disease (VWD), the most frequent congenital bleeding disorder with a prevalence of approximately 1%. The usual routine coagulation screening tests (PT, APTT, platelet count) are not sufficient to diagnose VWD, factor XIII (FXIII)-deficie...

Over the past years there has been a dramatic increase in the number of identifiable causes of thrombophilia. However, as retinal vein occlusions (RVO) have a strong pathogenic correlation with the presence of hypertension or arteriosclerosis and the average age of affected patients is usually within the sixth or seventh decade of life, thrombophil...

Over the past years there has been a dramatic increase in the number of identifiable causes of thrombophilia. However, as retinal vein occlusions (RVO) have a strong pathogenic correlation with the presence of hypertension or arteriosclerosis and the average age of affected patients is usually within the sixth or seventh decade of life, thrombophil...

The main aim of this study was to investigate the influence of perioperative anticoagulation on the clinical course and outcome of 144 patients who underwent surgery for chronic subdural hematoma (CSDH). The outcome was categorized according to the modified Rankin Scale (mRS), Barthel Index and postoperative quality of life (QoL) scale. There was a...

The aetiology of anti-factor VIII (FVIII) autoantibody formation in acquired haemophilia remains unknown. We hypothesised that encounter of antigenically different, allogeneic FVIII may challenge inhibitor formation after presentation on MHC class II. Eighteen consecutive cases with acquired haemophilia were enrolled (nine females, nine males). A c...

Acquired haemophilia A (AH) is a rare bleeding disorder caused by an auto-antibody to coagulation factor VIII. It is associated with various autoimmune diseases, pregnancy, cancer or drug ingestion; however, in 50% of patients, no underlying disorder is found. In the present study, we investigated the association of HLA class I (A, B and Cw) and cl...

Severe factor XIII (FXIII) deficiency is a rare autosomal recessive coagulation disorder affecting one in two million individuals. The aim of the present study was to screen for and analyse F13B gene defects in the German population. A total of 150 patients presenting with suspected FXIII deficiency and one patient with severe (homozygous) FXIII de...

Over the past years, there has been a dramatic increase in the number of identifiable causes of thrombophilia. However, to date, there are no large, prospective studies to assess an optimal, cost-effective approach with regard to screening and case finding for thrombophilic risk factors in patients presenting with retinal vessel occlusion. Two hund...

The use of factor VIII (FVIII) concentrates in the treatment of hemophilia A has raised important safety issues, historically of pathogen transmission and increasingly of inhibitor development to FVIII treatment. While manufacturing processes of current recombinant FVIII products have been shaped entirely around preventing pathogen transmission, th...

Hereditary dysfibrinogenemia is a rare clotting disorder, which results from mutations in at least one of the three fibrinogen genes. We examined the frequency of hemostatic clinical and laboratory anomalies at presentation of 37 probands from 12 unrelated families with five different defects (Aalpha R16C, gamma A357T, gamma318-319 del, gamma M310T...

Data on changes of haemostatic parameters at altitudes above 5000 m are very limited. So far it is unknown, whether altered coagulation could contribute to the development of acute mountain sickness. Thirty four healthy mountaineers were randomised to two acclimatisation protocols and undertook an expedition on Muztagh Ata (7549 m) in China. Tests...

BACKGROUND: The potential impact of coagulation abnormalities on retinal vascular occlusive diseases, individually and in combination with cardiovascular risk factors, remains unclear. PATIENTS AND METHODS: In a prospective case-control study a cohort of 74 young patients with central, hemicentral or branch retinal vein occlusion (RVO) (≤ 45 years...

To investigate the efficacy of intravenous thrombolysis with low-dose recombinant tissue plasminogen activator (rt-PA) in recent-onset central retinal vein occlusion (CRVO) or branch retinal vein occlusion. This was a prospective, randomized, controlled multicenter trial in patients with CRVO or branch retinal vein occlusion, best-corrected visual...

Dysfibrinogenemia is caused by a variety of structural abnormalities in the fibrinogen molecule, which results in a tendency for bleeding and thrombosis as well as obstetric complications. The obstetric complications of dysfibrinogenemia include first-trimester pregnancy loss, hemorrhage, placental abruption, and thrombosis. We conducted a retrospe...

The potential impact of coagulation abnormalities on retinal vascular occlusive diseases, individually and in combination with cardiovascular risk factors, remains unclear. In a prospective case-control study a cohort of 74 young patients with central, hemicentral or branch retinal vein occlusion (RVO) (<or= 45 years at the time of the RVO or a pre...

The potential impact of coagulation abnormalities on non-arteritic ischaemic optic neuropathy (NAION), individually and in combination with cardiovascular risk factors, remains unclear. In a prospective case-control study a cohort of 26 NAION patients < 60 years at the time of the NAION or a previous thromboembolic event and 50 subjects matched for...

Hintergrund: Die Bedeutung thrombophiler Gerinnungsstörungen für die Entstehung der nichtarteriitischen anterioren ischämischen Optikusneuropathie (NAION) wurde bisher wenig untersucht. Patienten und Methoden: In einer prospektiven Fallkontrollstudie untersuchten wir 26 Patienten mit NAION < 60 Jahre zum Zeitpunkt der NAION oder eines vorangegangen...

To date, the question whether there is a relationship between thrombophilic disorders and the development of nonarteritic ischemic optic neuropathy (NAION) remains controversial. We sought to investigate the prevalence of various coagulation defects among NAION patients <65 years of age, and to provide clinical guidelines for a selective thrombophi...

To evaluate the beneficial effect of intravenous thrombolysis aiming at rapid restoration of blood flow during the early hours of a central retinal artery occlusion (CRAO). Interventional case series. In the present study, we prospectively evaluated the visual outcome after thrombolytic treatment with low-dose (50 mg) rt-PA (recombinant tissue plas...

Co-morbidities of haemophilia, such as arthropathy and blood-borne infections, can adversely affect the quality of life of adult patients with haemophilia. The purpose of this study was to develop and validate a haemophilia-specific health-related quality of life questionnaire for adults (HAEMO-QoL-A). Subjects with varying severities of haemophili...

Patients with von Willebrand disease (VWD) and haemophilia A (HA) lack, to varying degrees, the von Willebrand factor (VWF) and coagulation factor VIII (FVIII) that are critical for normal haemostasis. These conditions in turn make patients prone to uncontrolled bleeding. Historically, patients with severe forms of VWD or HA were crippled before ad...

Acquired haemophilia (AH) is an autoimmune disorder characterized by autoantibodies against endogenous factor VIII (FVIII). Half of the patients present with an underlying disease known to cause the FVIII autoantibodies whereas in the other half the disease is of idiopathic nature. Recently, it has been shown that variants of the polymorphic cytoto...

FXIII deficiency is a rare autosomal recessive disorder affecting approximately 1 out of 1–3 million inhabitants. The disease is characterized by bleeding, impaired wound repair and spontaneous abortions in females. Extracellular FXIII molecule has a tetramer structure composing of two catalytic A-subunits and two B-subunits that act as a carrier m...

Since October 2005 the central laboratory of the university hospital in Mainz offers the diagnostic assay for thrombotic thrombocytopenic purpura (TTP).

Patients with hemophilia were at high risk of acquiring blood-borne infections transmitted by factor VIII or factor IX concentrates which were not virus inactivated before 1986.

Hepatitis C virus (HCV) infection is often observed in hemophilic patients who were treated with non-virus inactivated clotting factor concentrates prior to the mid 1980s. HCV infection is an important cause of morbidity and mortality in patients with hereditary bleeding disorders. Current studies suggest that up to 5% of HCV infected patients deve...

Modern plasma-derived factor VIII and IX concentratesRecombinant factor concentrates

Mitomycin C-associated thrombotic microangiopathy (TMA) has a poor prognosis with limited therapeutic options. Most patients die within 4 months of diagnosis due to pulmonary or renal failure. Here, a patient resistant to total plasma exchange (TPE) and immunosuppressive therapy with glucocorticoids, rituximab, vincristine, and splenectomy who was...

We report our clinical experience in the immune tolerance (IT) therapy of 21 paediatric haemophiliacs with FVIII inhibitor: high responders (16HR) received initially FVIII twice daily at a dosage of 50–300 U/kg/day, 11/16 received a concomitant treatment with activated prothrombin complex concentrate (100–200 U/kg/day). Low responders (five LR) rec...

A plasma-derived von Willebrand factor (VWF) concentrate with low factor VIII (FVIII) content was specifically developed to treat von Willebrand disease (VWD). Efficacy and safety were investigated by merging the results of two comparable protocols conducted prospectively in 5 European and 12 French centers. Fifty patients with clinically severe VW...

Treatment of relapsed or refractory autoimmune mediated haemolytic syndromes, such as autoimmune haemolytic anaemia (AIHA) and thrombotic thrombocytopenic purpura (TTP), represents a therapeutic challenge. Here we report on our experience with the monoclonal anti-CD20 antibody rituximab (R) compared to standard treatment in these diseases. Patients...

Arthropathy of the hip is moderate in frequency in haemophiliac patients, but is less common than ankle, knee or elbow arthropathy. We report about our experience with total hip replacement in patients with severe bleeding disorders over a period of 30 years. Between July 1972 and 2002, 15 hips in 13 patients were replaced. The main bleeding disord...

Heterogeneity in the mechanisms of coagulation may contribute to an increased thrombotic risk for patients with malignancies. The coincidence of malignancies and antiphospholipid antibodies (aPL) have been described in several important epidemiological studies. The pathological significance of aPL in patients with malignancies is, however, still un...

The finding of 16 bleeding complications in 173 surgical interventions is low (9.2%). Most bleeding complications were seen in patients with vWD type 2B and 3. Patients who underwent major surgery and who received only Minirin had more often bleeding complications. Our evaluation of bleeding incidents in the context of surgery in vWD patients revea...

The congenital dysfibrinogenemia is a rare clotting disorder which is based on a structural defect in the fibrinogen molecule. Fibrinogen is a 340-kDa glycoprotein circulating in plasma at a concentration of 150-450 mg/dl, with half life of about four days. The 340 kD-fibrinogen molecule is composed of two identical subunits, each comprising three...

Background Major orthopedic procedures (hip and knee replacement) and the presence of thrombophilia are risk factors of thrombotic events. Besides the FV G1691A mutation and the FII G20210A variant, high levels of factor VIII above 150% are associated with a 5 fold risk for venous thrombosis. In absence of any prophylaxis, the incidence of venograp...

Acquired hemophilia A is caused by inhibitory autoantibodies to factor VIII (FVIII). Inhibitors block interaction of FVIII and its interacting molecules including factor IX or von Willebrand factor. In acquired hemophilia the knowledge on inhibitor epitopes is limited. Epitopes that have been located so far cluster in the A2 or in the C2 domain of...

Treatment of hemophilic patients requires systematic record keeping of specific patient related data. In the past few years the technical development like personal computers, databases and the Internet brought considerable advantages. The possibility of managing and analyzing patient data by database driven application offers new opportunities to a...

The presence of antiphospholipid antibodies has been reported in a large variety of patients with malignancies. Many case reports and reviews have appeared indicating that the presence of the antiphospholipid antibodies is related to thrombotic associations with the antiphospholipid syndrome (APS) in a proportion of these patients. We investigated...

FVIII therapy for haemophilia A is safe and effective, with the problem of individually sufficient efficacy unsettled. Routine one-stage clotting assays and tests employing chromogenic substrates poorly detect individual haemostatic effects of FVIII due to artificial test conditions. In particular, the use of cell-free and diluted plasma samples ne...

To describe a novel missense mutation in the antithrombin gene associated with antithrombin deficiency type I in a 40-year-old man with retinal vein occlusion. Investigational case report. Ophthalmoscopy of the right eye showed hemicentral retinal vein occlusion. The patient's medical history was negative for glaucoma or cardiovascular risk factors...

OBJECTIVE AND PURPOSE: Neurological involvement is a common feature of the antiphospholipid syndrome (APS). A variety of thrombotic and non-thrombotic manifestations may accompany the presence of antiphospholipid antibodies (aPL). We retrospectively reviewed the prevalence of aPL in a cohort of over 350 unselected patients from a neurological clini...

This study investigates the effect of pre-analytic storage conditions on the laboratory evaluation of von Willebrand disease (VWD) and haemophilia. Samples from healthy controls and patients with VWD were stored as whole blood and as separated plasma, both at room temperature and on crushed ice, for two different time periods (3 or 6 h). In samples...

Routine molecular genetic analysis identified the causative mutations in most of the HAE families. It is very important in diagnosing HAE carriers in affected families prior to clinical manifestation thus allowing the identification of high risk patients for developing acute and life threatening edema.

Despite FVIII prophylaxis and better joints in hemophilic patients this group of patients will get older and arthritis of the hip is an increasing problem in the older generation. Regardless hemophilic arthropathy patients will develop hip and knee arthritis and the need for surgery will increase. We conclude after more than 30 years of experience...

- The therapy with Rituximab shows high response rates and appears to be effective in the elimination of inhibitors. - Whether the success of the inhibitor elimination by Rituximab correlated to the inhibitor titer is unknown. - Further studies are needed to confirm whether Rituximab has a role in the first line therapy compared with other therapy...

High-sensitive C-reactive protein (hs-CRP) is a marker of inflammation which has been shown in several prospective studies to independently predict myocardial infarction, stroke and peripheral artery disease. Patients with antiphospholipid antibodies (aPL) are at increased risk of recurrent thromboembolic events, but the possibility of predicting t...

We report a 36-year-old woman with the occurrence of painful focal seizures of her left hand and the left leg. She also had focal motor seizures at the left corner of her mouth. The duration and frequency of the episodes increased over four days from a few seconds once a day to frequent intervals lasting more than four hours at a time. The symptoms...