COVID-19 infections are associated with a high prevalence of venous thromboembolism, particularly pulmonary embolism (PE). It is suggested that COVID-19 associated PE represents in situ ...immunothrombosis rather than venous thromboembolism, although the origin of thrombotic lesions in COVID-19 patients remains largely unknown.
In this study, we assessed the clinical and computed tomography (CT) characteristics of PE in 23 consecutive patients with COVID-19 pneumonia and compared these to those of 100 consecutive control patients diagnosed with acute PE before the COVID-19 outbreak. Specifically, RV/LV diameter ratio, pulmonary artery trunk diameter and total thrombus load (according to Qanadli score) were measured and compared.
We observed that all thrombotic lesions in COVID-19 patients were found to be in lung parenchyma affected by COVID-19. Also, the thrombus load was lower in COVID-19 patients (Qanadli score −8%, 95% confidence interval 95%CI −16 to −0.36%) as was the prevalence of the most proximal PE in the main/lobar pulmonary artery (17% versus 47%; −30%, 95%CI −44% to −8.2). Moreover, the mean RV/LV ratio (mean difference −0.23, 95%CI −0.39 to −0.07) and the prevalence of RV/LV ratio >1.0 (prevalence difference −23%, 95%CI −41 to −0.86%) were lower in the COVID-19 patients.
Our findings therefore suggest that the phenotype of COVID-19 associated PE indeed differs from PE in patients without COVID-19, fuelling the discussion on its pathophysiology.
•COVID-19 pneumonia is associated with high incidence of pulmonary embolism (PE).•The origin of COVID-19 associated PE is debated.•We compared radiological PE parameters in COVID-19 patients with control patients.•In COVID-19 patients, thrombus load and prevalence of RV dysfunction was lower.•Our findings support the concept of in situ immunothrombosis in COVID-19 patients
Von Willebrand disease (VWD) is the most common inherited bleeding disorder but its diagnosis can be challenging due to the heterogeneity of the disease. VWD is mainly associated with mild ...mucocutaneous bleeding, although there are more severe phenotypes with bleeding from the gastrointestinal tract or even the joints. Also, surgical interventions and trauma may lead to critical bleeding events. These bleeding episodes are all related to quantitative or qualitative defects of von Willebrand factor (VWF), a multimeric glycoprotein produced by endothelial cells and megakaryocytes, which mediates platelet adhesion and aggregation and binds factor VIII (FVIII) in the circulation. This review describes the diagnostic procedures required for correct diagnosis. Accurate diagnosis and classification is required for proper treatment and counseling. Assessment of bleeding starts with the medical history. After a positive bleeding or family history, subsequent laboratory investigations will start with a panel of standard screening tests for hemostatic defects. Patients suspected of having VWD will be tested for plasma VWF antigen levels, the ability of VWF to bind platelets and FVIII activity. When VWD is confirmed, a set of subtyping tests can classify the patients as VWD types 1, 2 (A, B, M or N) or 3. The performance of some additional assays and analyses, such as VWF propeptide measurement or genetic analysis, may help in identifying the pathological mechanism behind certain defects or can guide in the choice of treatment.
von Willebrand disease (VWD) is a bleeding disorder caused by inherited defects in the concentration, structure, or function of von Willebrand factor (VWF). VWD is classified into three primary ...categories. Type 1 includes partial quantitative deficiency, type 2 includes qualitative defects, and type 3 includes virtually complete deficiency of VWF. VWD type 2 is divided into four secondary categories. Type 2A includes variants with decreased platelet adhesion caused by selective deficiency of high-molecular-weight VWF multimers. Type 2B includes variants with increased affinity for platelet glycoprotein Ib. Type 2M includes variants with markedly defective platelet adhesion despite a relatively normal size distribution of VWF multimers. Type 2N includes variants with markedly decreased affinity for factor VIII. These six categories of VWD correlate with important clinical features and therapeutic requirements. Some VWF gene mutations, alone or in combination, have complex effects and give rise to mixed VWD phenotypes. Certain VWD types, especially type 1 and type 2A, encompass several pathophysiologic mechanisms that sometimes can be distinguished by appropriate laboratory studies. The clinical significance of this heterogeneity is under investigation, which may support further subdivision of VWD type 1 or type 2A in the future.
Von Willebrand's Disease Leebeek, Frank W G; Eikenboom, Jeroen C J
The New England journal of medicine,
11/2016, Letnik:
375, Številka:
21
Journal Article
The aim of this study was the validation of the criteria defining a significant mucocutaneous-bleeding history in type 1 von Willebrand disease (VWD).
To avoid selection bias, 42 obligatory carriers ...(OC) of type 1 VWD were identified from a panel of 42 families with type 1 VWD enrolled by 10 expert centers. OC were identified by the presence of an offspring and another first degree relative with type 1 VWD (affected subjects, AFF). A standardized questionnaire was administered to evaluate hemorrhagic symptoms at the time of first examination, using a bleeding score ranging from 0 (no symptom) to 3 (hospitalization, replacement therapy, blood transfusion). Sensitivity, specificity, diagnostic likelihood ratios, positive and negative predictive values for the diagnosis of type 1 VWD were calculated from the data collected in OC and in 215 controls.
Having at least three hemorrhagic symptoms or a bleeding score of 3 in males and 5 in females was very specific (98.6%) for the bleeding history of type 1 VWD, although less sensitive (69.1%). None of the misclassified OC had life-threatening bleeding episodes after diagnosis.
We suggest that the use of a standardized questionnaire and bleeding score may be useful for the identification of subjects requiring laboratory evaluation for VWD.
Quantitative bleeding assessment tools (BATs) have been used to describe the severity of the bleeding phenotype in patients with von Willebrand disease.
To evaluate the clinical usefulness of a BAT ...for the diagnosis of mild bleeding disorders (MBDs) in previously undiagnosed patients.
We prospectively assessed 215 patients who were consecutively referred for evaluation of bleeding symptoms (n=71), abnormal laboratory clotting test results (n=105) or family investigation (n=39) at two second-level centers. The bleeding history was assessed by a young investigator who administered the BAT instrument, and also by a senior physician who independently evaluated the patient and made the final diagnoses. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were computed for a predefined bleeding score (BS) cut-off (BS of >3). Receiver operating characteristic curves were used to establish a diagnostic prediction rule.
Assuming the prevalence of MBD in the general population to be ∼1%, a normal BS (≤3) had a very high NPV (99.2%). The PPVs in patients referred for hemostatic or family evaluation at second-level clinics were estimated to be 71.0% and 77.5% (assuming MDB prevalences of 20% and 50%, respectively, in these settings). Measurement of BS in addition to activated partial thromboplastin time significantly increased the diagnostic efficiency of the BAT instrument (NPV of 99.6%).
BAT use improves the evaluation of patients with suspected MBD, and we propose its use in a clinical prediction guide based on BAT and activated partial thromboplastin time for the exclusion of patients with suspected MBD in a low-prevalence setting.
Weibel-Palade bodies (WPBs) are the storage organelles for von Willebrand factor (VWF) in endothelial cells. VWF forms multimers that assemble into tubular structures in WPBs. Upon demand, VWF is ...secreted into the blood circulation, where it unfolds into strings that capture platelets during the onset of primary hemostasis. Numerous mutations affecting VWF lead to the bleeding disorder von Willebrand disease. This review reports the recent findings on the effects of VWF mutations on the biosynthetic pathway of VWF and its storage in WPBs. These new findings have deepened our understanding of VWF synthesis, storage, secretion, and function.
Background The absolute risk of recurrences among patients using aspirin for prevention of cardiovascular events remains high. Persistent platelet reactivity despite aspirin therapy might explain ...this in part. Reported prevalences of this so-called aspirin resistance vary widely, between 0% and 57%. Objectives The aim of the study was to systematically review all available evidence on prevalence of aspirin resistance and to study determinants of reported prevalence. Methods Using a predefined search strategy, we searched electronic databases MEDLINE, EMBASE, CENTRAL, and Web of Science. To be included in our analysis, articles had to contain a laboratory definition of aspirin resistance, use aspirin as secondary prevention, and report associated prevalence. Results We included 34 full-text articles and 8 meeting abstracts. The mean prevalence of aspirin resistance was 24% (95% CI 20%-28%). After adjustment for differences in definition, used dosage, and population, a statistically significant higher prevalence was found in studies with aspirin dosage ≤100 mg compared with ≥300 mg (36% 95% CI 28%-43% vs 19% 95% CI 11%-26%, P < .0001). Studies measuring platelet aggregation using light aggregometry with arachidonic acid as an agonist had a pooled unadjusted prevalence of 6% (95% CI 0%-12%). In studies using point-of-care platelet function–analyzing devices, the unadjusted prevalence was significantly higher, at 26% (95% CI 21%-31%). Conclusions Prevalences widely differ between studies reporting on aspirin resistance. Both aspirin dosage and the method of defining aspirin resistance strongly influence estimated prevalence, which explains found heterogeneity among studies. On average, it appears that about 1 in 4 individuals may express biochemically defined aspirin resistance.
PDF
