ПОКАЗАТЕЛИ КОАГУЛЯЦИОННОГО РАВНОВЕСИЯ И АГРЕГАЦИИ ТРОМБОЦИТОВ У ПАЦИЕНТОВ С ИНФЕКЦИЕЙ COVID-19

In 1926, Erik von Willebrand, a Finnish internist andacademic, evaluated and described a 5-year-old girlwith extreme bleeding and bruising due to what hadbeen designated the A˚landic haemorrhagic diseaseby inhabitants of this archipelago island in the Gulfof Bothnia. Hjordis, the propositus, was the ninth of12 children born to a pedigree in which four femalesiblings had already died before the age of 4 withuncontrolled haemorrhage and in which 23 of 66family members, predominantly females, had expe-rienced significant bleeding and bruising complica-tions [1]. In fact, Hjordis herself eventually died atthe age of 13 during her fourth menstrual cycle.Professor von Willebrand mistakenly concluded thatthis bleeding diathesis was an unusual form ofhaemophilia and decided to label the new diseaseas pseudo-haemophilia to differentiate it from thesex-linked recessive haemophilia A. Little did vonWillebrand realize that this disease, eventually tobecomeeponymous[vonWillebranddisease(VWD)],would become the most commonly diagnosed con-genital bleeding disorder, with a prevalence rangingbetween 1 per 10 000 individuals to 1.3% [2]. Type1 VWD is the most common subtype, representingup to 75–80% of all cases while the subtype 3 VWDoccurs in approximately 1 per million population inthe United States and Europe [2]. Determination ofthe exact prevalence of VWD is hindered somewhatby the heterogeneity of clinical and diagnosticlaboratory features. Even Professor von Willebrandappreciated the challenges of diagnosing VWD as hecollaborated with Professor Rudolf Ju¨gens at theBerlin University to examine patients blood sampleswith a newly invented kapilla¨rtrombometer appa-ratus [3]. Although they were technically mistakenwhen they attributed the bleeding manifestations ofVWD to a platelet defect, their observations wereremarkably prescient since it was not until early1970s that the existence of a specific von Willebrandfactor (VWF) glycoprotein separate from factor VIIIwas finally appreciated and demonstrated to supportplatelet adhesion to the subendothelial matrix ofdamaged blood vessels.Over the last 81 years since von Willebranddescribed the bleeding disorder, there have beennumerous attempts and approaches to refine thediagnosis of the disease so that appropriate andefficacious treatment can be delivered. The clinicalphenotype of VWD includes, in part, information onwhether bleeding is spontaneous or related to surgi-cal or physical trauma; family history and inheri-tance pattern; menstrual history in women; age ofonset of bleeding (to distinguish between acquired vs.inherited coagulation disorders); and sites of bleed-ing(mucocutaneousvs.visceral,intra-articular,intra-muscular, or soft tissue locations). Subsequentlaboratory testing is necessary to exclude or confirmthe diagnosis and to further classify the subtype ofVWD. This article will focus on selected vagariesassociated with the ability to utilize clinical pheno-typic information gathered through the history andphysical examination to predict the presence ofVWD. The clinical diagnosis of VWD must be based,however, on more than physician suspicion andintuition. Thus, the need for confirmatory testing inthe laboratory. The frailties of conventional labora-tory testing for diagnosing VWD and the use of anin vitro surrogate of the bleeding time will also be

Repeated Testing Unfolds the Challenge of Diagnosing Von Willebrand Disease: Longitudinal Data from the Vienna Bleeding Biobank

Von Willebrand factor (VWF), a key player in hemostasis and thrombosis, is released from endothelial cells during inflammation. Upon release, VWF is processed by ADAMTS13 into an inactive conformation. The aim of our study was to investigate whether plasma levels of active VWF, total VWF, ADAMTS13, osteoprotegerin (OPG) and the ratios between VWF and ADAMTS13 are risk factors for first ST-segment elevation myocardial infarction (STEMI). We assessed 1026 patients with confirmed first STEMI and 652 control subjects from China, Italy and Scotland, within six hours after their cardiovascular event. Median plasma levels of total VWF, active VWF, OPG and ratios VWF/ADAMTS13 were increased, while plasma levels of ADAMTS13 were decreased in patients compared to controls. The odds ratio (OR) of STEMI in patients with high plasma levels of active VWF was 2.3 (interquartile range (IQR): 1.8-2.9), total VWF was 1.8 (1.4-2.3), ADAMTS13 was 0.6 (05-0.8), OPG was 1.6 (1.2-2.0) and high VWF/ADAMTS13 ratios was 1.5 (1.2-2.0). The OR for total VWF, active VWF and ratios VWF/ADAMTS13 remained significant after adjustment for established risk factors, medical treatment, C-reactive protein, total VWF, ADAMTS13 and OPG. When we adjusted for levels of active VWF, the significance of the OR for VWF and ratios VWF/ADAMTS13 disappeared while the OR for active VWF remained significant. We found evidence that plasma levels of active VWF are an independent risk factor for first STEMI in patients from three different ethnic groups. Our findings confirm the presence of VWF abnormalities in patients with STEMI and may be used to develop new therapeutic approaches.

Type 2 diabetes is known to cause endothelial activation resulting in the secretion of von Willebrand factor (VWF). We have shown that levels of VWF in a glycoprotein Ib-binding conformation are increased in specific clinical settings. The aim of the current study is to investigate whether active VWF levels increase during aging and the development of diabetes within the population of patients suffering from type 2 diabetes. Patients and controls were divided into two groups based on age: older and younger than 60 years of age. VWF antigen, VWF propeptide, VWF activation factor and total active VWF were measured. Patients older than 60 years of age had increased levels of total active VWF, VWF activation factor and VWF propeptide compared to younger patients and controls. All measured VWF parameters were associated with age in diabetic patients. Total active VWF and VWF propeptide correlated with the period of being diagnosed with diabetes. Regression analyses showed that especially the VWF activation factor was strongly associated with diabetes in patients older than 60 years of age. In conclusion, we found that the conformation of VWF could be involved in the disease process of diabetes and that the VWF in a glycoprotein Ib-binding conformation could play a role as risk marker during the development of diabetes in combination with an increase in age. Our study shows that the active quality of VWF was more important than the quantity.

Postpartum Hemorrhage in Women with Von Willebrand Disease after Enhanced Prophylactic Clotting Factor Suppletion: The Pregnancy and Inherited Bleeding Disorders Study (PRIDES)

Factor VIII and von Willebrand factor activity levels during long-term prophylaxis with wilate-Analyses from the WIL-31 study.

Is ≥ 100% the magic number to rule out the laboratory diagnosis of von Willebrand disease based on initial testing?

Modern antithrombotic therapy for acute coronary syndromes rests on a growing body of basic and clinical evidence that rupture or erosion of the surface of a vulnerable plaque sets in motion a sequence of events culminating in thrombus formation in the culprit vessel.1 When the contents of a vulnerable plaque are exposed to the bloodstream, platelets adhere to the subendothelial matrix, release ADP and thromboxane A2, and amplify the generation of thrombin.2 As a result, a platelet aggregate begins to develop. In addition, the coagulation cascade is activated and fibrin strands are formed. Thrombin (factor IIa) plays a pivotal role in the processes described above because of its extensive procoagulant and prothrombotic actions.3 In addition to catalyzing the transformation of soluble fibrinogen into fibrin monomers and activating factor XIII to produce cross-linked fibrin, thrombin promotes clot formation by activating factors V and VIII. It is also one of the most potent agents responsible for platelet adhesion, activation, and aggregation. In vessels with a diseased endothelium, thrombin promotes the release of the vasoconstrictor endothelin 1. Importantly, thrombin also potentiates the proliferative effects of multiple growth factors and is a key mediator of early smooth muscle cell proliferation after arterial injury. There is now abundant evidence that thrombus formation can be prevented by direct or indirect inactivation of thrombin or by inhibition of thrombin production via the intrinsic or extrinsic limbs of the coagulation pathway.3 Unfractionated heparin, the standard antithrombotic agent in clinical practice, is a glycosaminoglycan, consisting of chains of alternating residues of d-glucosamine and uronic acid.4 Although familiar to the vast majority of clinicians, unfractionated heparin has several disadvantages: (1) a variable anticoagulant effect (necessitating frequent monitoring of activated partial thromboplastin time), (2) neutralization by platelet factor 4, (3) less effective inhibition …

Platelet activation and aggregation profile in prolonged external ventricular support

Design of the Von Willebrand Factor in Pregnancy (VIP) Study

VWF and FVIII Levels after Desmopressin Are Associated with the Bleeding Phenotype in Type 1 VWD

Increased von Willebrand factor levels in polycythemia vera and phenotypic differences with essential thrombocythemia

Hemoglobin concentration and body mass index are determinants of plasma von Willebrand factor and factor VIII levels

International audience

Is primary hemostasis involved in bleeding diathesis in patients with type 1 glycogen storage disease?