Biomedical subjects
Publications and source records attributed to M Barthels.
Von Willebrand disease (VWD) is known for its marked heterogeneity which was already recognized by von Willebrand in 1926. The basis of phenotypic differentiation are quantitative and qualitative or functional differences between the different types and subtypes of VWD. Clinical relevant facts for the practitioner on diagnosis and therapy of von Willebrand disease and von Willebrand syndrome are presented.
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A survey is given on the peculiar characteristics of laboratory methods for analyzing the blood coagulation system with special regard to the pre-analytical, the analytical and post-analytical phase. Routinely used methods are described as well as test combinations for the diagnostic of some characteristic coagulopathies.
A survey is given on pharmacology and indications for the treatment with vitamin K antagonists. The therapeutic handling and self control by the patient is described.
Topics of this survey are the indications and use of plasma-derived and recombinant coagulation factor concentrates. These substitution therapies need to be handled carefully by weighing up their effectiveness against the long and short term side effects in the individual patient.
The analysis of von Willebrand factor (vWF) multimers is an important laboratory tool for distinguishing among the numerous subtypes of von Willebrand disease (vWD). Comparability and reproducibility of this method are insufficient; standardization and external references are pending. Interlaboratory comparison of results therefore may be difficult. We applied densitometry to obtain a reproducible quantification of vWF multimer patterns in healthy donors, patients with vWD variants, and factor VIII/vWF concentrates to improve the reproducibility and comparability of vWF multimer analysis. Multimers were separated and visualized luminographically on x-ray films. Films were scanned and evaluated by densitometry. The variation inherent in vWF multimer analysis and the range of the normal could be quantified. In vWD variants and factor VIII/vWF concentrates, densitometry could quantify and visualize alterations of vWF multimer patterns and facilitate their comparison. Densitometry permits a precise quantitative comparison of sample patterns to a reference plasma. It could be a valuable tool offering reproducible quantification and additional visualization of normal and pathologic vWF multimer patterns, facilitating their comparison and contributing to a standardization of vWF multimer analysis.
Elevation of serum lipoprotein (a) (Lp[a]) is a known risk factor predisposing to cardiovascular and cerebrovascular disease. However, little is known about the role of increased Lp(a) in venous thromboembolism (VTE). This study evaluated the role of Lp(a) among a panel of established hereditary thrombogenic defects in patients with VTE. A total of 685 consecutive patients with at least one episode of VTE and 266 sex- and age-matched healthy controls were screened with regard to activated protein C resistance, protein C, protein S, and antithrombin deficiency, elevated serum levels of Lp(a), and the factor V G1691A, MTHFR C677T, and prothrombin G20210A mutations. Elevated Lp(a) levels above 30 mg/dL were found in 20% of all patients, as compared to 7% among healthy controls (P <.001, odds ratio [OR] 3.2, 95% confidence interval [CI], 1.9-5.3). The coexistence of FV G1691A and elevated Lp(a) was significantly more prevalent among patients with VTE than in the control group (7% versus 0.8%; P <.001, OR 9.8, 95% CI, 2.4-40.7). No other established prothrombotic risk factor was found to be significantly combined with increased Lp(a). These data suggest that Lp(a) concentrations greater than 30 mg/dL are a frequent and independent risk factor for VTE. Furthermore, elevated Lp(a) levels might contribute to the penetrance of thromboembolic disease in subjects being affected by other prothrombotic defects, such as FV G1691A mutation.
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Due to the various reported mechanisms by which tumours may alter haemostasis directly or indirectly, a close relationship between tumour and thrombosis is convincing. As patients with cancer represent a diverse group, the establishment of general treatment guidelines concerning antithrombotic prophylaxis and therapy requires more data than are present to date. However, in cancer patients who are candidates for surgery, chemotherapy, indwelling central venous line, or prolonged immobility, primary prophylaxis is recommended. Patients with manifest thromboembolism should receive immediate treatment and a secondary prophylaxis for more than 3 months or at least as long as the cancer is active. In patients inappropriate for oral anticoagulation, the administration of LMWH is a suitable alternative. More prospective, randomized and larger studies are required to determine the optimally tailored primary prophylaxis, the best time to start and to stop treatment, to determine the best route, dosage and pharmacological antithrombotic, and to define the role of newer anticoagulants as hirudins in the anticoagulative prophylaxis and treatment of patients with cancer.
An overview is given on APCCs and recombinant FVIIa for the treatment of bleeding episodes in hemophiliacs with FVIII or FIX inhibitors or in patients with acquired hemophilia. The initial dose of activated plasma-derived PPCs, mainly FEIBA, is up to 100 U/kg body weight, and the maintenance dosage is up to 100 U/kg body weight twice daily. The single dosage of recombinant FVIIa is about 60-90 microg/kg body weight, which has to be repeated every 2 to 6 hours depending on the bleeding situation.
UNLABELLED: We prospectively evaluated the clinical relevance of genetic risk factors of thrombosis in 137 paediatric patients with solid tumours or leukaemia/lymphoma. The factor V G1691A (FV-L), the prothrombin G20210A (FII-L) and the homozygous MTHFR variant were examined. In addition, protein C, protein S and antithrombin (AT) deficiency were evaluated in patients with ALL or thrombosis. The inter-group incidence of risk factors and thrombotic events was compared. 73 of the 137 patients had ALL and 64 another form of leukaemia, lymphoma or a solid tumour. They were treated according to the established paediatric tumour protocols ALL-BFM, NHL-BFM, COSS, CWS and others. All patients had central venous lines. No patient received heparin or any other anticoagulant. Endpoints of the study were thrombosis, regular completion of chemotherapy or death. Incidence of mutations in the whole group: FV-L (7.3% heterozygous, 0.7% homozygous); FII-L (2.9% heterozygous, no homozygotes); MTHFR (51.8% heterozygous, 10.9% homozygous). Ten patients (7.3%), 6 with ALL and 4 with solid tumours, developed thrombosis. 4 of the 6 patients with ALL and thrombosis (67%) but only 21% of ALL patients without thrombosis had a genetic risk factor (P < 0.013, chi2). No genetic defect was found in the 4 patients with other malignancies and thrombosis. However, besides a tumour, these patients had additional exogenous risk factors including diabetes insipidus and hemiparesis. CONCLUSION: Genetic mutations appear to be additional risk factors for the development of thrombosis in patients with ALL. In contrast, these mutations do not appear to be relevant risk factors for thrombosis in the small number of children with other malignant diseases reported here. This difference may be due to asparaginase and corticosteroids being used in ALL but not in solid tumour protocols.
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The antiphospholipid syndrome (APS) consists clinically of both arterial and venous thrombosis, recurrent fetal loss and thrombocytopenia associated with antiphospholipid antibodies (aPL). Most of these patients were initially found to suffer from systemic lupus erythematosus (SLE). There is an increasing group of patients who exhibit antiphospholipid antibodies and thrombotic complications without clinical features of SLE or related autoimmune disease termed primary antiphospholipid syndrome (PAPS). The case of a 29-year-old woman with thrombosis of the terminal aorta and deep vein thrombosis, recurrent fetal loss, antiphospholipid antibodies and serological support for an underlying connective tissue disease, probably preclinical SLE is reported.
BACKGROUND: It is frequently difficult to disclose covert ingestion of cumarins being the underlying cause of a bleeding disorder. PATIENTS AND METHODS: We report on 16 cases (15 patients) of phenprocoumon (Marcumar) abuse. All patients (9 females, 6 males) were admitted to the hospital because of bleeding and/or prolonged thromboplastin times. Analysis of phenprocoumon in the blood was performed by HPLC. RESULTS AND CONCLUSIONS: The clinical presentation of the bleeding was highly variable. Thromboplastin times ranged from < 5 to 58%. With the exception of two patients with hepatic dysfunctions factor V activity was normal. All but one patient denied the ingestion of Marcumar. One patient died from hemorrhage. Two types of patients emerge from our series: Type I is the young nurse (8 cases), type II the usually male patient formerly treated with phenprocoumon (5 cases). Type I patients had long medical histories and showed autoaggressive behavior including the artificial manipulation of disorders other than hemorrhage. Thromboplastin times however were within or close to the therapeutic range (10 to 25%). Type II patients did not simulate other diseases in addition to hemorrhage. Thromboplastin times were longer than in type I patients. In all instances discrimination between non suicidal and suicidal behaviour was difficult. Psychiatric consultance is indicated.
Idiopathic purpura fulminans usually occurs in young children and is frequently preceded by a preparatory viral or bacterial infection. Following a severe streptococcal pharyngitis, an 8-year-old boy developed purpura fulminans with disseminated intravascular coagulation and severe protein S deficiency (total antigen < 0.05 u/ml). Despite generous plasma infusions, skin necrosis progressed rapidly into compartment syndrome which required fasciotomy and skin grafting and resulted in the loss of three digits of the right foot. Total protein S remained low for over a month despite plasma supplementation and complete normalization of protein C levels. A polyclonal anti-protein S IgG was demonstrated in the patient's plasma, which decreased to 25% of baseline titre after 1 month and was undetectable 6 months after purpura fulminans, when plasma protein S had returned to normal. Transient, isolated and severe deficiencies of protein S have been reported in patients with idiopathic purpura fulminans and a previous preparatory infection. Autoimmune protein S deficiency may play a key role in the aetiopathogenesis of idiopathic purpura fulminans.
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Explore the source record for details and available documents.