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Published in Samar Razaq, Difficult Cases in Primary Care, 2021
Haemophilia A, also known as classical haemophilia, is among the commonest of the bleeding disorders and is caused by an absence or low levels of factor VIIIc. Haemophilia B, or Christmas disease, is caused by a deficiency of factor IX. The two conditions present in a similar fashion clinically. Both are X-linked recessive disorders and a good family history enables a diagnosis to be made. Unexplained bruising and haemarthrosis, when the child is mobile, occasionally raise concerns regarding non-accidental injury. Von Willebrand’s disease is caused by a deficiency or abnormal function of von Willebrand factor and its most common form is inherited in autosomal dominant fashion. Epistaxis can be a recurring problem in this condition. Idiopathic thrombocytopaenic purpura is the commonest of the immune thrombocytopaenias in which there is an increased destruction of platelets. Bernard–Soulier’s syndrome is a congenital disorder in which there is a failure of platelet production.
Altered Regulation of Fibrinolysis in Scleroderma and Potential for Thrombolytic Therapy
Published in Pia Glas-Greenwalt, Fibrinolysis in Disease Molecular and Hemovascular Aspects of Fibrinolysis, 2019
Marvin J. Fritzler, David A. Hart
Coagulation abnormalities have been observed in patients with scleroderma.68,89,90 Such patients have increased frequency of thrombotic episodes, increased rate of fibrinogen breakdown, fibrin deposition in tissues, endothelial cell aberrations, and elevated levels of factor VIII.91,92 These vascular changes may lead to pulmonary hypertension and, in some cases, progressive pulmonary fibrosis. Compromise of the peripheral vascular system can lead to amputation of digits. Abnormalities of PA/PAI regulation are likely not central to the circulatory alterations, since t-PA/PAI-1 levels in most patients have not been reported to be markedly abnormal.93 A study by Martucci-Cerinic et al.94 demonstrated that cutaneous and plasma plasmin levels were normal in patients with scleroderma. These authors did, however, provide evidence that plasma von Willebrand factor levels were elevated. Likewise, Munkvad et al.95 reported that plasma t-PA levels were normal in scleroderma patients, but u-PA levels were depressed. Lotti et al.96 reported that cutaneous fibrinolytic activity following histamine challenge was normal in 3/5 patients and decreased in 2/5 patients. Such data indicate that heterogeneity exists in these patient populations which precludes making general statements regarding the status of the PA/PAI system.
Hereditary Causes for Plasma Clotting Bleeding
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
As the understanding of the vWF genetics, structure and function has increased, so has the subclassification of the types of von Willebrand’s disease. As many as 28 subtypes were described until, in 1993, a revised classification was developed and endorsed by the Subcommittee on von Willebrand Factor of the International Society on Thrombosis and Haemostasis (ISTH) (23,25). In essence, there are three main types of vWD, based on the pattern of molecular weight (M.Wt.) multimer bands of the plasma vWF detected after electrophoresis on SDS-agarose gel electrophoresis. Normal vWF in plasma separates into many bands of high, intermediate, and low M.Wt. The larger vWF multimers bind platelets to subendothelial collagen.
Gastrointestinal bleeding in von Willebrand patients: special diagnostic and management considerations
Published in Expert Review of Hematology, 2023
Edwin Ocran, Nicholas L.J. Chornenki, Mackenzie Bowman, Michelle Sholzberg, Paula James
Von Willebrand Disease (VWD) is the most prevalent-inherited bleeding disorder. The disease is autosomally inherited and is caused by a deficiency or dysfunction of von Willebrand Factor (VWF), resulting in impaired blood clotting. The trait may occur in about 1% of the general population, with a symptomatic prevalence of 1 in 1000 [1]. VWF plays essential roles in normal hemostasis including the protection of coagulation factor VIII (FVIII) from early degradation, the binding to exposed subendothelial collagen at sites of vascular injury, and the binding to platelet surface glycoproteins, which leads to platelet adhesion and subsequent platelet aggregation under high shear stress [2,3]. Recently, VWF has been linked to other non-hemostatic roles including inflammation, cell proliferation and angiogenesis, as discussed by Rauch et al. [3].
Contributions of von Willebrand factor to clinical severity of sickle cell disease: a systematic review and metanalysis
Published in Hematology, 2022
T. U. Nwagha, Martins Nweke, E. D. Ezigbo
VWF is a glycoprotein that is known to mediate platelet adhesion, increased platelet adhesion and aggregation, and impaired fibrinolytic activity, all of which contribute to a state of hypercoagulable and prothrombotic disease [5]. VWF is a large sticky multimeric protein that contributes to vascular hemostasis and functions as a marker of endothelial dysfunction [6]. The larger the protein, the more adhesive it is to function. A VWF deficiency or defect can result in von Willebrand disease and bleeding. On the other hand, an increase in VWF can promote thrombosis by creating a favourable environment [7]. Hypercoagulability has been linked to a variety of clinical symptoms, including severe vasoocclusive crises, hemolytic anemia, and oxidative stress [3,5]. In SCD, a similar relationship has been discovered between an elevated level of extracellular hemoglobin (Hb) and the development of the disease. Extracellular Hb binds to VWF and inhibits its cleavage by ADAMTS-13, resulting in the accumulation of ultra-large VWF multimers in the circulation and in the endothelium, as well as the stimulation of prothrombotic events [8].
Chronic thromboembolic pulmonary hypertension: a review of risk factors, management and current challenges
Published in Expert Review of Cardiovascular Therapy, 2022
John E Cannon, David P Jenkins, Stephen P Hoole
Despite its association with acute PE, classical hereditary risk factors for VTE including Protein C, Protein S and antithrombin deficiencies and mutations of factor V and factor II are not risk factors for the development on CTEPH. In contrast, antiphospholipid antibody syndrome is a recognized risk factor for developing acute PE and CTEPH [18]. There are a few thrombophilic factors that are implicated in CTEPH pathogenesis including an elevated factor VIII level [19]. Von Willebrand factor (vWF) plays an important role in platelet recruitment mediating the adhesion of platelets to the endothelium and is also a carrier protein for the pro-coagulant blood clotting factor VIII. vWF is noted to be elevated in patients with CTEPH and the vWF-cleavage protein ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), which regulates vWF-activity is also reduced. Together, ADAMTS13–VWF axis dysregulation appears to be important in CTEPH pathogenesis. The linkage of the ADAMTS13 gene and ABO genetic locus may also explain why CTEPH is more common in patients with non-O blood group [20,21].