| 1. |
- Badimon, Lina, et al.
(author)
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Atherothrombotic risk in obesity
- 2013
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In: Hämostaseologie. - 0720-9355. ; 33:4, s. 259-268
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Journal article (peer-reviewed)abstract
- A link between obesity and coronary artery disease development has been repeatedly proposed, possibly in part due to the development of a proinflammatory and prothrombotic state in obese subjects. Adipocytes secrete numerous hormones and cytokines (adipokines) which influence gene expression and cell functions in endothelial cells, arterial smooth muscle cells, and monocytes/macrophages favouring the development of an atherosclerotic vulnerable plaque. Moreover, the release of such biologically active molecules also promotes endothelial function impairment, disturbs the haemostatic and fibrinolytic systems, and produces alterations in platelet function affecting the initiation, progression, and stabilization of thrombus formation upon atherosclerotic plaque rupture. In this review we will discuss the pathophysiological mechanisms by which obesity contributes to increase atherothrombosis paying special attention to its effects over thrombosis.
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| 2. |
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| 3. |
- Berntorp, Erik
(author)
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Plasma-derived versus recombinant factor concentrates in PUPs : A never ending debate?
- 2017
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In: Hämostaseologie. - 0720-9355. ; 37:1, s. 53-57
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Journal article (peer-reviewed)abstract
- Inhibitor development in haemophilia is a serious complication to treatment with factor concentrates. Since the advent of more pure products, especially developed using recombinant DNA technology, some studies have shown an increased incidence of inhibitors in previously untreated patients (PUPs) receiving recombinant products whereas plasmaderived concentrates sometimes have been claimed to have a protective role, probably due to the content of von Willebrand factor (VWF). In fact, experiments indicate that the VWF may block uptake of factor VIII into macrophages for further processing to the immune system. Also, a competition between VWF and inhibitor binding to the C2 domain of factor VIII has been suggested. Recently, large cohort and surveillance studies have created a vigorous debate about the role of product class for inhibitor development as results have been conflicting. The only randomised prospective study, the SIPPET study, was published in 2016, and substantiated previous reports claiming that plasma derived concentrates give less inhibitors in patients with severe haemophilia A, previously not exposed to factor VIII. The debate will continue.
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| 4. |
- Dahlback, Björn
(author)
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Advances in understanding mechanisms of thrombophilic disorders
- 2020
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In: Hämostaseologie. - : Georg Thieme Verlag KG. - 0720-9355 .- 2567-5761. ; 40:1, s. 12-21
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Research review (peer-reviewed)abstract
- Venous thromboembolism constitutes a major medical problem afflicting millions of individuals worldwide each year. Its pathogenesis is multifactorial, involving both environmental and genetic risk factors. The most common genetic risk factor known to date is a mutation in the factor V (FV) gene (R506Q or FV Leiden), which impairs the normal regulation of FV by activated protein C (APC). APC is an important regulator of blood coagulation, cleaving and inactivating not only FV/FVa but also activated factor VIII (FVIIIa). In FVa, APC cleaves several sites, Arg506 (R506) being one of them. The R506Q mutation results in the APC resistance phenotype and a lifelong hypercoagulable state. A prothrombin gene mutation is another relatively frequent thrombosis risk factor, whereas deficiencies of the anticoagulant proteins antithrombin, protein C, or protein S are less common. As a result of the high prevalence of FV and prothrombin mutations in the general population, combinations of genetic defects are relatively common. Such individuals have highly increased risk of thrombosis.
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| 5. |
- Dahlbäck, Björn
(author)
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Early days of APC resistance and FV Leiden.
- 2008
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In: Hämostaseologie. - 0720-9355. ; 28:3, s. 103-103
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Journal article (peer-reviewed)abstract
- Venous thrombosis is a major medical problem annually affecting millions of individuals worldwide. It is a typical multifactorial disease, the pathogenesis involving both environmental and genetic risk factors. A single point mutation in the gene of coagulation factor V (FV), which results in the replacement of Arg506 with a Gln (FV Leiden) is the most common genetic risk factor known to date. The anticoagulant activated protein C (APC) regulates the activity of FVa by cleaving several sites in FVa, and the Arg506 is one of them. APC resistance, which is the consequence of the FV Arg506Gln mutation, results a lifelong hypercoagulable state that increases the risk of thrombosis. APC resistance was discovered in my laboratory and the first paper was published in 1993. This was the starting point for an avalanche of research in many laboratories and several thousands of articles have been published since on this topic. The medical community amazingly quickly accepted the concept of APC resistance/FV Leiden as a major risk factor for thrombosis and millions of individuals are today tested for this condition. This review is a personal historical annotation about the early days of APC resistance.
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| 6. |
- Edvardsson, Maria, et al.
(author)
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Type 2 Diabetes: Platelets and Long-Term Metabolic Control as Estimated from Glycosylated Haemoglobin (HbA1c)
- 2024
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In: Hämostaseologie. - : GEORG THIEME VERLAG KG. - 0720-9355.
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Journal article (peer-reviewed)abstract
- In type 2 diabetes, platelets are likely affected by impaired long-term glycaemic control, but such pathophysiological links are poorly understood. This study thus compares platelet reactivity (i.e. agonist-evoked platelet reactions) in vitro with glycosylated haemoglobin (HbA1c), a measure commonly used for monitoring long-term metabolic control of type 2 diabetes. Elders with type 2 diabetes ( n = 35) were divided according to HbA1c into groups (HbA1c-low and high) consisting of 17 and 18 subjects, respectively. For estimating mitochondria disintegration, a flow cytometer determined mitochondrial transmembrane potentials after whole blood agonist stimulation. The activating agents used were alpha-thrombin (10 mu M) and collagen (0.15 mu g/mL). The same apparatus analysed the fibrinogen receptor activity, lysosomal exocytosis (surface lysosomal-associated membrane protein 1), and platelet procoagulant characteristics (membrane-attached annexin V) after stimulation. In type 2 diabetes, after in vitro agonist stimulation, platelet mitochondria injury was higher in the HbA1c-high group. The fibrinogen receptor, lysosomal secretion, and the creation of procoagulant platelets proved to be uninfluenced by HbA1c.
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| 7. |
- Gautam, G, et al.
(author)
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How to Differentiate Recurrent Deep Vein Thrombosis from Postthrombotic Syndrome
- 2020
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In: Hamostaseologie. - : Georg Thieme Verlag KG. - 2567-5761. ; 40:033, s. 280-290
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Journal article (peer-reviewed)abstract
- Venous thromboembolism (VTE) is associated with significant morbidity and mortality. Accuracy of diagnosis is thus of vital importance. Failure to diagnose VTE increases the risk of progression and complications. Conversely, anticoagulation as a result of an incorrect diagnosis exposes patients to the associated hazards of bleeding. The diagnostic management of recurrent deep vein thrombosis (DVT) and postthrombotic syndrome (PTS) is especially challenging due to the lack of well-established diagnostic standards. Particularly, the differentiation between the two is notoriously difficult as symptoms, clinical signs, and diagnostic test findings largely overlap. This review highlights the current diagnostic and management strategies for recurrent DVT and PTS with a focus on clinical findings and imaging modalities. We also discuss current open questions for clinicians in the field, anticipating future directions and predictions for the year 2050.
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| 8. |
- Karpman, Diana, et al.
(author)
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Complement activation in thrombotic microangiopathy.
- 2013
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In: Hämostaseologie. - 0720-9355. ; 33:2, s. 96-104
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Research review (peer-reviewed)abstract
- The endothelium lining the vascular lumen is continuously exposed to complement from the circulation. When erroneously activated on host cells, complement may generate a deleterious effect on the vascular wall leading to endothelial injury, exposure of the subendothelial matrix and platelet activation.In this review the contribution of complement activation to formation and maintenance of the pathological lesion termed thrombotic microangiopathy (TMA) is discussed. TMA is defined by vessel wall thickening affecting mainly arterioles and capillaries, detachment of the endothelial cell from the basement membrane and intraluminal thrombosis resulting in occlusion of the vessel lumen. The TMA lesion occurs in haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). HUS is further sub-classified as associated with Shiga toxin-producing Escherichia coli (STEC-HUS) or with complement dysregulation (atypical HUS) as well as other less common forms. The contribution of dysregulated complement activation to endothelial injury and platelet aggregation is reviewed as well as specific complement involvement in the development of HUS and TTP.
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| 9. |
- Lubenow, Norbert, et al.
(author)
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[Hirudins in the treatment of heparin-induced thrombocytopenia and in thrombosis prophylaxis].
- 2002
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In: Hämostaseologie. - 0720-9355. ; 22:3, s. 44-54
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Journal article (peer-reviewed)abstract
- Approved indications for the recombinant hirudins lepirudin (Refludan(R)) und desirudin (Revasc(R)) are therapy of heparin-induced thrombocytopenia (HIT) and thrombosis prophylaxis following knee or hip replacement surgery. Kidney function dependent pharmacokinetics and their capability of inducing antibodies directed against hirudin are characteristic of this class of drugs. However, close dose-monitoring allows safe and effective use of both compounds. While lepirudin is used widely, besides danaparoid, for treatment of HIT, desirudin has not yet been widely accepted for thrombosis prophylaxis following knee or hip replacement surgery.
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| 10. |
- Sacco, Clara, et al.
(author)
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Lemierre Syndrome : Clinical Update and Protocol for a Systematic Review and Individual Patient Data Meta-analysis
- 2019
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In: Hämostaseologie. - : Georg Thieme Verlag KG. - 0720-9355 .- 2567-5761. ; 39:1, s. 76-86
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Research review (peer-reviewed)abstract
- Lemierre syndrome usually affects otherwise healthy adolescents or young adults and occurs at an overall rate of 1 to 10 cases per million person-years with an estimated fatality rate of 4 to 9%. Diagnostic criteria remain debated and include acute neck/head bacterial infection (often tonsillitis caused by anaerobes at high potential for sepsis and vascular invasion, notably Fusobacterium necrophorum) complicated by local vein thrombosis, usually involving the internal jugular vein, and systemic septic embolism. Medical treatment is based on antibiotic therapy with anaerobic coverage, anticoagulant drugs and supportive care in case of sepsis. Surgical procedures can be required, including drainage of the abscesses, tissue debridement and jugular vein ligation. Evidence for clinical management is extremely poor in the absence of any adequately sized study with clinical outcomes. In this article, we illustrate two cases of Lemierre syndrome not caused by Fusobacterium necrophorum and provide a clinically oriented discussion on the main issues on epidemiology, pathophysiology and management strategies of this disorder. Finally, we summarize the study protocol of a proposed systematic review and individual patient data meta-analysis of the literature. Our ongoing work aims to investigate the risk of new thromboembolic events, major bleeding or death in patients diagnosed with Lemierre syndrome, and to better elucidate the role of anticoagulant therapy in this setting. This effort represents the starting point for an evidence-based treatment of Lemierre syndrome built on multinational interdisciplinary collaborative studies.
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