Hereditary Causes for Plasma Clotting Bleeding
Harold R. Schumacher, William A. Rock, Sanford A. Stass in Handbook of Hematologic Pathology, 2019
Diagnosis is made by finding a prolonged bleeding time with a normal platelet count, normal PT, and prolonged PTT due to decreased factor VIII:C levels, usually ranging from 15% to 50%. Factor VIII:C levels are labile in these patients, and assays on specimens taken at different times may need to be performed to detect the nadir of factor VIII functional activity, von Willebrand antigen levels, if measured, are similar to the factor VIII:C level. The diagnosis is confirmed by measuring the von Willebrand factor activity, such as with a Ristocetin-induced platelet aggregation test. Ristocetin, an antibiotic, potentiates the attachment of the vWF to a platelet membrane receptor, glycoprotein Ib/IX. This platelet aggregation test is commercially available. The vWF levels are usually at 15–50%.
Clinical Evidence and Consequences of the Association Between Hemostatic Functions and Malignancies
László Muszbek in Hemostasis and Cancer, 2019
The aggristin (ristomycin) precipitation test is a new tool for the detection of fibrin monomer and fibrin degradation products in plasma, therefore it is useful in the laboratory diagnosis of DIC and in its differentiation from the primary fibrinogenolysis.58,59 The test was based on the observation of Watanabe and Tullis60 that ristocetin in appropriate concentration precipitates fibrin monomers and fibrin degradation products without precipitating fibrinogen and fibrinogen degradation products. They proposed the ristocetin precipitation test.61 Formerly, we studied ristomycin, another member of the vancomycin group of antibiotics, and demonstrated that it is fully capable of replacing ristocetin in the platelet aggregation process and also in the diagnostics of von Willebrand’s disease.62 It seems to be proved that ristomycin has the same properties as ristocetin, also in the precipitation of plasma proteins, and it is able to replace ristocetin in the laboratory diagnosis of intravascular clotting.59 This test proved to be positive in almost all the patients investigated, even when no or only moderate signs of DIC developed. A good correlation with the Thrombo-Wellco test and the poor sensitivity of the ethanol gelation test (EGT) are obvious from Table 8.
Platelet Disorders Douglas Triplett
Genesio Murano, Rodger L. Bick in Basic Concepts of Hemostasis and Thrombosis, 2019
In 1971, Howard and Firkin introduced ristocetin as another tool in the diagnosis of von Willebrand’s syndrome.18 Ristocetin is an antibiotic that was found to aggregate platelets and cause severe thrombocytopenia in vivo.19 Ristocetin was found to induce platelet aggregation in normal patients, but not in patients with von Willebrand’s syndrome. Further study established a defective or reduced plasma component in these patients, which was a necessary cofactor for ristocetin-induced aggregation. The platelets of von Willebrand’s syndrome were entirely normal when this plasma component was added to platelet-rich plasma.20 Subsequently, an assay measuring this plasma factor was reported.21
Clinical pharmacology of caplacizumab for the treatment of patients with acquired thrombotic thrombocytopenic purpura
Published in Expert Review of Clinical Pharmacology, 2019
Maria Laura Sargentini-Maier, Philip De Decker, Claudia Tersteeg, Jan Canvin, Filip Callewaert, Hilde De Winter
The ristocetin platelet aggregation (RIPA) and RICO assays are in vitro assays to evaluate the platelet-binding capacity of vWF present in the blood. The RIPA and RICO assay methodology is based on addition of ristocetin to plasma in the presence of platelets that causes platelet agglutination [35]. The antibiotic ristocetin activates vWF to a similar extent as high shear blood flow conditions, and consequently modulates the binding of vWF to the platelet receptor GP1b. As in vitro platelet aggregation can be blocked by the interaction of caplacizumab with vWF, these methods were selected to evaluate the activity of caplacizumab during treatment in the clinical development program. Full inhibition of vWF mediated platelet adhesion by caplacizumab is indicated by RIPA or RICO activity decreasing below 10% or 20%, respectively. Complete stable target inhibition for at least 24 h was observed after a single subcutaneous dose of ≥10 mg in healthy volunteers. This 10 mg subcutaneous dose, given daily, also elicited full inhibition of vWF-mediated platelet adhesion in patients with aTTP throughout the complete treatment period (Figure 4) [32,33]. In all clinical studies, the RICO activity recovered to baseline values within 7 days upon discontinuation of the study drug.
High shear induces platelet dysfunction leading to enhanced thrombotic propensity and diminished hemostatic capacity
Published in Platelets, 2019
Zengsheng Chen, Nandan K. Mondal, Shirong Zheng, Steven C. Koenig, Mark S. Slaughter, Bartley P. Griffith, Zhongjun J. Wu
Ristocetin- and collagen-induced platelet aggregation capacities of the baseline and sheared blood samples were analyzed using an impedance aggregometer, Multiplate® analyzer (Verum Diagnostica GmbH, Munich, Germany). Ristocetin causes platelet activation and aggregation by enhancing the binding between VWF and platelet surface receptor GPIbα. Collagen can bind directly to the platelet surface integrin α2β1 and GPVI, leading to platelet activation and aggregation. The Multiplate® analyzer is based on the principle that platelets become sticky upon activation, adhere and aggregate onto the metal sensor wires in the Multiplate® test cell, which increases the electrical resistance between the wires. The increase in impedance is expressed in aggregation units (AU) and can be plotted as separate aggregation curves over time. The area under the aggregation curve (AUC, AU*min) was used to indicate ristocetin- or collagen-induced platelet aggregation capacity of the baseline and sheared blood samples. The details of the aggregation experiment can be found in Tóth O’s study [34].
Effect of differently coated silver nanoparticles on hemostasis
Published in Platelets, 2021
Marija Milić, Barbara Vuković, Rinea Barbir, Barbara Pem, Mirta Milić, Vatroslav Šerić, Eleonore Frőhlich, Ivana Vinković Vrček
When no agonists where used, only PLL-AgNPs was able to cause platelet aggregation, similar to the action of PLL alone (Figure S2 in the SI). Indeed, cationic polypeptides have been found to enhance platelet aggregation by neutralizing net negative charge on platelet membrane [32]. These results are consistent with study reported by Jun et al. [15], although Huang et al. [13] reported no AgNPs effect on platelet aggregation. There are two possibilities to explain the findings. In the experiment without agonists, platelet aggregation was measured immediately after addition of AgNPs to whole blood samples, while the measurement of platelet aggregation in experiments with agonists started 30 min after the incubation of whole blood with AgNPs. Thus, if AgNPs induced platelet aggregation alone, there would be less platelets available for activation by agonists, which could result in decreased platelet aggregation. It has been shown that function, for instance of macrophages, is impaired upon exposure to NPs [33] and it is likely that a similar effect may also occur for platelets. The fact that only ristocetin produced this effect may be due to the stronger activating action of this molecule.
Related Knowledge Centers
- Agglutination
- Amycolatopsis
- Platelet
- Von Willebrand Factor
- Blood Plasma
- Thrombocytopenia
- Glycopeptide Antibiotic
- Staphylococcal Infection
- Von Willebrand Disease
- Bernard–Soulier Syndrome