scholarly journals A Shear Micro-Gradient Microfluidic to Monitor Platelet Aggregation Dynamics in the Context of Von Willebrand Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3753-3753
Author(s):  
Harshal Nandurkar ◽  
Warwick Nesbitt ◽  
Rose Brazilek ◽  
Francisco Tovar-Lopez ◽  
Angus Wong ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Shear Rate ◽  
Whole Blood ◽  
Von Willebrand Disease ◽  
Screening Tools ◽  
Small Scale ◽  
Blood Samples ◽  
Microfluidic Platform ◽  
Significant Difference ◽  
Von Willebrand

Abstract Background: Virchow's triad identifies the three principle parameters driving haemostasis and thrombosis as: i. Changes in vessel wall properties and exposure of subendothelial matrix proteins; ii. Presentation of blood borne chemical activators (hypercoaguability); and iii.Blood-flow dependent mechanical factors (haemodynamics). Studies identifying a key role for micro-scale shear gradients in driving the earliest stages of platelet thrombus formation have informed the development of a novel set of microfluidic devices that have potential utility as rapid and efficient screening tools of shear dependent platelet function. Aim: The aim of this project was to undertake a small scale clinical and laboratory based characterisation study of a microfluidic platform designed by us and to assess its ability to identify differences in platelet aggregation dynamics in citrated whole blood taken from control subjects and subjects with clinically diagnosed or undiagnosed von Willebrand disease (Types 1, 2 and 3). Method: Patients with VWD were recruited from the haemophilia outpatient clinic, Alfred hospital. Whole blood samples (250mL) or samples treated ex vivo to block the canonical platelet amplification loop pathways were perfused at a defined flow rate (45ml/mL) through a set of well defined micro-shear gradient geometries pre-coated with purified VWF to initiate platelet capture. Microfluidic geometries were characterised by an entry shear rate of 1,800.s-1, that was accelerated to a peak shear rate of either 45,000.s-1 or 150,000.s-1, returning to an exit shear rate of 1,800.s-1. The rate of initial shear acceleration was varied using a series of geometries with contraction entry angles varying from 15 - 85o. Results: The microfluidic platform was able to identify patients with Types 1 (VWF antigen < 30%), 2A and 3 VWD. ROC analysis of control versus VWD samples determined that the device sensitivity approached 94.4%, with a specificity of 100% for VWD. A statistically significant difference (p< 0.05) was observed when comparing control blood samples to type 1VWD (p< 0.001) and type 2A VWD samples (p=0.004), with both subtypes showing minimal to no platelet aggregation in the device. Patients presenting with bleeding symptoms but found not to have VWD (normal VWF:Ag levels) showed no significant difference (p=0.907) to controls. Furthermore, exogenous titration of Type 3 (n=2) VWD blood samples with purified VWF (10 - 100mg/mL) recapitulated platelet aggregation in a concentration dependent manner. Head to head comparison with standard laboratory based tests including, VWF:Ag, VWF:CB and VWF:RCo demonstrated a strong linear correlation with device output. In addition, time-course (0, 2 and 4 Hrs) trials demonstrate that the device is a sensitive measure of DDAVP treatment of VWD. Conclusion: The Studies presented demonstrate that haemodynamically sensitive platelet aggregation within our prototype platform is critically dependent on blood VWF antigen levels and demonstrates good proof-of-concept that the microfludic can selectively identify VWD dependent defects in whole blood platelet aggregation. Taken together these data suggest that a microfluidic platform with discrete haemodynamic control can operate as a sensitive screen for VWD. Future studies will focus on defining the particle and key haemodynamic parameters that shift both device selectivity and sensitivity. Disclosures No relevant conflicts of interest to declare.

scholarly journals Glycoprotein Ib, von Willebrand factor, and glycoprotein IIb:IIIa are all involved in platelet adhesion to fibrin in flowing whole blood

Blood ◽  
1990 ◽  
Vol 76 (2) ◽  
pp. 345-353 ◽  
Author(s):  
RR Hantgan ◽  
G Hindriks ◽  
RG Taylor ◽  
JJ Sixma ◽  
PG de Groot
Keyword(s):  
Platelet Aggregation ◽  
Shear Rate ◽  
Von Willebrand Factor ◽  
Whole Blood ◽  
Platelet Adhesion ◽  
Thrombus Formation ◽  
Shear Rates ◽  
Wall Shear ◽  
Von Willebrand ◽  
Willebrand Factor

We have investigated the molecular basis of thrombus formation by measuring the extent of platelet deposition from flowing whole blood onto fibrin-coated glass coverslips under well-defined shear conditions in a rectangular perfusion chamber. Platelets readily and specifically adhered to fibrin-coated coverslips in 5 minute perfusion experiments done at either low (300 s-1) or high (1,300 s-1) wall shear rates. Scanning electron microscopic examination of fibrin-coated coverslips after perfusions showed surface coverage by a monolayer of adherent, partly spread platelets. Platelet adhesion to fibrin was effectively inhibited by a monoclonal antibody (MoAb) specific for glycoprotein (GP) IIb:IIIa. The dose-response curve for inhibition of adhesion by anti-GPIIb:IIIa at both shear rates paralleled that for inhibition of platelet aggregation. Platelet aggregation and adhesion to fibrin were also blocked by low concentrations of prostacyclin. In contrast, anti- GPIb reduced adhesion by 40% at 300 s-1 and by 70% at 1,300 s-1. A similar pattern of shear rate-dependent, incomplete inhibition resulted with a MoAb specific for the GPIb-recognition region of von Willebrand factor (vWF). Platelets from an individual with severe von Willebrand's disease, whose plasma and platelets contained essentially no vWF, exhibited defective adhesion to fibrin, especially at the higher shear rate. Addition of purified vWF restored adhesion to normal values. These results are consistent with a two-site model for platelet adhesion to fibrin, in which the GPIIb:IIIa complex is the primary receptor, with GPIb:vWF providing a secondary adhesion pathway that is especially important at high wall shear rates.

A Ristocetin-Independent ELISA for the Measurement of VWF Activity.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1411-1411
Author(s):  
Michelle Stapleton ◽  
Jeffery Bub ◽  
Suzette Chance
Keyword(s):  
Platelet Aggregation ◽  
Comparative Method ◽  
Method Comparison ◽  
Von Willebrand Disease ◽  
Small Scale ◽  
Activity Measurement ◽  
Plasma Samples ◽  
Data Set ◽  
Platelet Surface ◽  
Von Willebrand

Abstract Abstract 1411 Von Willebrand Disease (VWD) is a relatively common bleeding disorder characterized by both quantitative and qualitative deficiencies in von Willebrand Factor. The correct diagnosis and classification of VWD is made on the basis of a personal and family bleeding history and the results of a panel of laboratory tests. Evaluations of both VWF antigen level and function are required. Most commonly VWF function is evaluated based on VWF binding to platelets through the platelet surface glycoprotein GPIba in a platelet aggregation assay (VWF:RCo). The VWF:RCo assay requires the use of the antibiotic ristocetin to induce a conformational change in VWF which allows VWF to bind to GPIba on the surface of fresh or fixed platelets in the absence of VWF denaturation. When evaluating 172 normal controls, Flood et. al. (Blood, 2010) elegantly demonstrated that 63% of African-American controls and 17% of Caucasian controls had a single nucleotide polymorphism, D1472H, which altered the ability of these individuals to bind ristocetin and resulted in abnormal VWF:RCo results in the absence of any bleeding abnormalities. GTI Diagnostics, Inc. (Waukesha, Wisconsin) has developed a ristocetin-independent fluorescent ELISA for the quantitative measurement of VWF activity in plasma, specifically VWF binding to immobilized GPIba. This VWF activity ELISA, referred to as the GTI IbCo Assay, uses microwells coated with recombinant GPIba containing two “gain-of-function” mutations. The mutant GPIba is capable of spontaneous binding to VWF in the absence of ristocetin or VWF denaturation (Flood et. al, Blood, 2010). A brief description of the assay follows. In the absence of ristocetin, calibrators, controls, and samples are added to the microwells and VWF binding to GPIba is allowed to take place. Unbound material is washed from the wells and a biotinylated anti-VWF detection antibody is added to the wells. The microwells are washed to remove any unbound detection antibody. A streptavidin-labeled horseradish peroxidase conjugate is added to the microwells and incubated. After a final wash step, a fluorescent peroxidase substrate is added to the wells. The reaction is quenched after 30 minutes and the fluorescence is read using an excitation wavelength between 315 and 340 nm and an emission wavelength between 370 and 470 nm. The reportable result (U/dL) of VWF binding to GPIba is determined from the standard curve. All assay incubation steps are 30 minutes and conducted at room temperature, therefore the assay can be completed in < 3 hours. A small scale method comparison study was conducted on 11 plasma samples purchased from George King Bio-Medical, Inc. The plasma samples are Factor Assay ConTrol (FACT) samples and extensively characterized by George King Bio-Medical, Inc for 25 different coagulation parameters including VWF:RCo using a Chrono-Log platelet aggregometer and Helena Laboratories lyophilized platelets. The 11 samples were tested in the GTI IbCo Assay and the results obtained were compared to those obtained with the comparative method, in this case the VWF:RCo values provided by the supplier. For standardization of the GTI IbCo Assay, a IbCo value of 100 U/dL was assigned to the ISTH Secondary Coagulation Standard Lot #3. As illustrated in the table below, the samples tested included samples with varying levels VWF:RCo activity. When the results were compared, there was good correlation and agreement between the two methods. Larger method comparison studies will be conducted. Based on this limited data set the GTI IbCo Assay demonstrated good correlation and agreement with the “gold standard” Ristocetin Cofactor Assay by platelet aggregation. The GTI IbCo Assay is able to measure the functional activity of VWF, specifically in regards to VWF binding to GPIba in the absence of ristocetin in a simple ELISA format. The GTI IbCo Assay removes the need for fresh or lyophilized platelets from the traditional assay and also eliminates the ristocetin dependence from the VWF activity measurement. By removing any dependence on ristocetin to induce the VWF to GPIba interaction we have also removed any possible assay discrepancies based on a patient's inability to interact with ristocetin. Disclosures: Stapleton: GTI Diagnostics: Employment. Bub:GTI Diagnostics: Employment. Chance:GTI Diagnostics, Inc: Employment.

Whole Blood Impedance Aggregometry: A New Tool for Severe Inherited Platelet Disorder Diagnosis?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5266-5266 ◽  
Author(s):  
Celine Desconclois ◽  
Vincent Valarche ◽  
Tewfik Boutekedjiret ◽  
Martine Raphael ◽  
Marie Dreyfus ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Whole Blood ◽  
Von Willebrand Disease ◽  
Fast Method ◽  
Normal Ranges ◽  
Platelet Function Disorders ◽  
Platelet Disorder ◽  
Platelet Disorders ◽  
Von Willebrand

Abstract Abstract 5266 Diagnosis and characterization of platelet function disorders may be challenging. It requires multiple laboratory data including the assessment of platelet functions. Platelet function analysis is most commonly performed using light transmission aggregometry (LTA). LTA is a time-consuming method requiring centrifugation steps and large blood volumes. It is difficult to perform in children and in cases of thrombocytopenia. In contrast, platelet aggregation in whole blood using impedancemetry (WBI) is a fast method, allows omission of centrifugation steps and performance of platelet function studies under more physiological conditions with small samples size. It is based on the change of resistance proportional to the amount of platelets sticking to two electrodes where an alternating current is applied. Multiplate® (for “multiple electrode aggregometry”, Dynabite Medical) is a new generation of WBI aggregometer using diluted blood and single-use test cells containing twin electrodes that reduce the variation of results. We have already showed the good Multiplate® performance concerning ristocetin-induced platelet aggregation in a population of 30 patients with characterized von Willebrand disease (Valarche et al, 2011). Our aim in this ongoing study was to assess the performance of WBI in patients with inherited platelet function disorders. We tested 8 patients including 2 unrelated patients with Glanzmann Thrombasthenia (GT), 2 unrelated patients with Bernard-Soulier Syndrome (BSS), 1 patient with Gray Platelet Syndrome (GPS) and 3 patients from the same family with a platelet type von Willebrand disease (PTVWD). GT, BSS, and PTVWD diagnosis were confirmed using genotyping. BSS and GPS patients had chronic thrombocytopenia. GT, BSS, GPS and 1/3 PTVWD had platelet function tests with LTA in parallel. WBI was performed on heparinized whole blood diluted at ½ in NaCl at 37°C and triggered using high (0.77 mg/mL, WBI RH) and low (0.5 mg/mL, WBI RL) final ristocetin concentrations, ADP (6.5 Âμ Mol, WBI ADP) and collagen (3.2 Âμg/mL, WBI Coll). Results were expressed in arbitrary unit (AU) corresponding to the area under the aggregation curve observed during 6 min. Normal ranges indicated in brackets were based on the mean +/− 2 SD of 30 healthy volunteers' results. Results highlighted in grey are those out of the normal ranges (Table 1).Table 1:Results of the 8 patients with inherited platelet disorders.PatientsPlatelet count (109/L)WBI RH (AU) [>500]WBI RL (AU) [<150]WBI ADP (AU) [>550]WBI Coll (AU) [>500]GT 116923441443GT 224955417ND7BSS 134371119129BSS 230254733582GPS7916217ND42PTVWD22099493ND338PTVWD231116560ND1092PTVWD2341174168ND852 All patients except those with PTVWD had decreased results with WBI. However, as expected, patients with GT had flat traces using WBI ADP and WBI Coll but normal or only decreased curves (234 – 554 AU) using WBI RH. On the opposite, BSS patients had flat traces using WBI RH but detectable curves using WBI ADP (191 – 335 AU) despite decreased platelet count. The thrombocytopenic GPS patient has a flat trace using WBI Coll and decreased WBI RH (162 AU). Members of the PTVWD family had normal results except a slightly increased result with WBI RH in 1/3 patients. Finally, LTA results performed in 6/8 patients were all in accordance with those of the WBI. In conclusion, in 8 patients with well characterized inherited platelet disorders, WBI was able to detect all abnormalities except PTVWD. In such cases, different ristocetin concentrations use might be critical to increase sensitivity. In our hands, WBI was able to discriminate disorders involving platelet glycoprotein (GP) IIb-IIIa from GP Ib-IX-V: GT patients exhibited flat traces using WBI ADP and WBI Coll, whereas patients with BSS exhibited flat traces with ristocetin. These preliminary results need to be confirmed on a larger population of patients with various characterized platelet function disorders. They suggest that WBI using the Multiplate® analyzer, which is a fast, easy and blood-preserving test, could be a valuable extra step before or in addition to the classic LTA for the diagnosis of severe inherited platelet disorders. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Glycoprotein Ib, von Willebrand factor, and glycoprotein IIb:IIIa are all involved in platelet adhesion to fibrin in flowing whole blood

Blood ◽  
1990 ◽  
Vol 76 (2) ◽  
pp. 345-353 ◽  
Author(s):  
RR Hantgan ◽  
G Hindriks ◽  
RG Taylor ◽  
JJ Sixma ◽  
PG de Groot
Keyword(s):  
Platelet Aggregation ◽  
Shear Rate ◽  
Von Willebrand Factor ◽  
Whole Blood ◽  
Platelet Adhesion ◽  
Thrombus Formation ◽  
Shear Rates ◽  
Wall Shear ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract We have investigated the molecular basis of thrombus formation by measuring the extent of platelet deposition from flowing whole blood onto fibrin-coated glass coverslips under well-defined shear conditions in a rectangular perfusion chamber. Platelets readily and specifically adhered to fibrin-coated coverslips in 5 minute perfusion experiments done at either low (300 s-1) or high (1,300 s-1) wall shear rates. Scanning electron microscopic examination of fibrin-coated coverslips after perfusions showed surface coverage by a monolayer of adherent, partly spread platelets. Platelet adhesion to fibrin was effectively inhibited by a monoclonal antibody (MoAb) specific for glycoprotein (GP) IIb:IIIa. The dose-response curve for inhibition of adhesion by anti-GPIIb:IIIa at both shear rates paralleled that for inhibition of platelet aggregation. Platelet aggregation and adhesion to fibrin were also blocked by low concentrations of prostacyclin. In contrast, anti- GPIb reduced adhesion by 40% at 300 s-1 and by 70% at 1,300 s-1. A similar pattern of shear rate-dependent, incomplete inhibition resulted with a MoAb specific for the GPIb-recognition region of von Willebrand factor (vWF). Platelets from an individual with severe von Willebrand's disease, whose plasma and platelets contained essentially no vWF, exhibited defective adhesion to fibrin, especially at the higher shear rate. Addition of purified vWF restored adhesion to normal values. These results are consistent with a two-site model for platelet adhesion to fibrin, in which the GPIIb:IIIa complex is the primary receptor, with GPIb:vWF providing a secondary adhesion pathway that is especially important at high wall shear rates.

Platelet Activation and Aggregation Induced by Recombinant von Willebrand Factors Reproducing Four Type 2B von Willebrand Disease Missense Mutations

1998 ◽  
Vol 79 (01) ◽  
pp. 211-216 ◽  
Author(s):  
Lysiane Hilbert ◽  
Claudine Mazurier ◽  
Christophe de Romeuf
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Von Willebrand Disease ◽  
Platelet Glycoprotein ◽  
Missense Mutations ◽  
Inhibit Platelet Aggregation ◽  
Wild Type ◽  
A1 Domain ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryType 2B of von Willebrand disease (vWD) refers to qualitative variants with increased affinity of von Willebrand factor (vWF) for platelet glycoprotein Ib (GPIb). All the mutations responsible for type 2B vWD have been located in the A1 domain of vWF. In this study, various recombinant von Willebrand factors (rvWF) reproducing four type 2B vWD missense mutations were compared to wild-type rvWF (WT-rvWF) for their spontaneous binding to platelets and their capacity to induce platelet activation and aggregation. Our data show that the multimeric pattern of each mutated rvWF is similar to that of WT-rvWF but the extent of spontaneous binding and the capacity to induce platelet activation and aggregation are more important for the R543Q and V553M mutations than for the L697V and A698V mutations. Both the binding of mutated rvWFs to platelets and platelet aggregation induced by type 2B rvWFs are inhibited by monoclonal anti-GPIb and anti-vWF antibodies, inhibitors of vWF binding to platelets in the presence of ristocetin, as well as by aurin tricarboxylic acid. On the other hand, EDTA and a monoclonal antibody directed against GPIIb/IIIa only inhibit platelet aggregation. Furthermore, the incubation of type 2B rvWFs with platelets, under stirring conditions, results in the decrease in high molecular weight vWF multimers in solution, the extent of which appears correlated with that of plasma vWF from type 2B vWD patients harboring the corresponding missense mutation. This study supports that the binding of different mutated type 2B vWFs onto platelet GPIb induces various degrees of platelet activation and aggregation and thus suggests that the phenotypic heterogeneity of type 2B vWD may be related to the nature and/or location of the causative point mutation.

scholarly journals Platelet von Willebrand factor: evidence for its involvement in platelet adhesion to collagen

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1214-1217
Author(s):  
E Fressinaud ◽  
D Baruch ◽  
C Rothschild ◽  
HR Baumgartner ◽  
D Meyer
Keyword(s):  
Shear Rate ◽  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Von Willebrand Disease ◽  
High Shear ◽  
Shear Rates ◽  
High Shear Rates ◽  
Von Willebrand ◽  
Willebrand Factor

Although it is well established that plasma von Willebrand Factor (vWF) is essential to platelet adhesion to subendothelium at high shear rates, the role of platelet vWF is less clear. We studied the respective role of both plasma and platelet vWF in mediating platelet adhesion to fibrillar collagen in a parallel-plate perfusion chamber. Reconstituted blood containing RBCs, various mixtures of labeled washed platelets and plasma from controls or five patients with severe von Willebrand disease (vWD), was perfused through the chamber for five minutes at a shear rate of 1,600 s-1. Platelet-collagen interactions were estimated by counting the radioactivity in deposited platelets and by quantitative morphometry. When the perfusate consisted of normal platelets suspended in normal plasma, platelet deposition on the collagen was 24.7 +/- 3.6 X 10(6)/cm2 (mean +/- SEM, n = 6). Significantly less deposition (16 +/- 2.3) was observed when vWD platelets were substituted for normal platelets. In mixtures containing vWD plasma, significantly greater deposition (9 +/- 2.2) was obtained with normal than with vWD platelets (1 +/- 0.4) demonstrating a role for platelet vWF in mediating the deposition of platelets on collagen. Morphometric analysis confirmed these data. Our findings indicate that platelet, as well as plasma, vWF mediates platelet-collagen interactions at a high shear rate.

scholarly journals Aggregation activity of blood formed elements in patients with type 1 and type 2 diabetes mellitus

2012 ◽  
Vol 15 (2) ◽  
pp. 49-53
Author(s):  
Boris Il'ich Kuznik ◽  
Yury Antonovich Vitkovskiy ◽  
Marina Yur'evna Zakharova ◽  
Natalya Nikolaevna Klyuchereva ◽  
Olga Sergeevna Rodnina ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Platelet Aggregation ◽  
Blood Samples ◽  
Significant Difference ◽  
Erythrocyte Adhesion ◽  
T1 And T2 ◽  
Aggregation Activity ◽  
Spontaneous Platelet Aggregation

Aims. To assess differences in blood formed elements aggregation activity in patients with type 1 (T1) and type 2 (T2) diabetes mellitus(DM). Materials and methods. We studied blood samples from 88 patients with T1 and T2 DM. Platelet aggregation activity was assessed bymeans of ?Biola? aggregometer; we also determined platelet-lymphocyte and leucocyte-erythrocyte adhesion intensity. Results. We show that spontaneous platelet aggregation is markedly increased in patients with T1DM but remains normal or slightlyelevated in case of T2DM. In blood from patients with T2DM platelet aggregation in response to ADP, epinephrine, ristomycineand contact with collagen was generally increased, whereas in T1DM we often observed its secondary reduction. Data on plateletlymphocyteadhesion in T1DM is controversial, but in T2DM this process seems to be significantly suppressed. Quantity of leucocyteerythrocyteaggregates was sharply increased in both T1DM and T2DM. Conclusion. We've determined significant difference in blood formed elements aggregation activity between patients with T1 and T2 DM.

Effect of recombinant von Willebrand factor reproducing type 2B or type 2M mutations on shear-induced platelet aggregation

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3796-3803 ◽  
Author(s):  
Nadine Ajzenberg ◽  
Anne-Sophie Ribba ◽  
Ghassem Rastegar-Lari ◽  
Dominique Meyer ◽  
Dominique Baruch
Keyword(s):  
Platelet Aggregation ◽  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
High Shear ◽  
Shear Rates ◽  
High Shear Rates ◽  
Consistent Increase ◽  
A1 Domain ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract The aim was to better understand the function of von Willebrand factor (vWF) A1 domain in shear-induced platelet aggregation (SIPA), at low (200) and high shear rate (4000 seconds-1) generated by a Couette viscometer. We report on 9 fully multimerized recombinant vWFs (rvWFs) expressing type 2M or type 2B von Willebrand disease (vWD) mutations, characterized respectively by a decreased or increased binding of vWF to GPIb in the presence of ristocetin. We expressed 4 type 2M (-G561A, -E596K, -R611H, and -I662F) and 5 type 2B (rvWF-M540MM, -V551F, -V553M, -R578Q, and -L697V). SIPA was strongly impaired in all type 2M rvWFs at 200 and 4000 seconds-1. Decreased aggregation was correlated with ristocetin binding to platelets. In contrast, a distinct effect of botrocetin was observed, since type 2M rvWFs (-G561A, -E596K, and -I662F) were able to bind to platelets to the same extent as wild type rvWF (rvWF-WT). Interestingly, SIPA at 200 and 4000 seconds-1 confirmed the gain-of-function phenotype of the 5 type 2B rvWFs. Our data indicated a consistent increase of SIPA at both low and high shear rates, reaching 95% of total platelets, whereas SIPA did not exceed 40% in the presence of rvWF-WT. Aggregation was completely inhibited by monoclonal antibody 6D1 directed to GPIb, underlining the importance of vWF-GPIb interaction in type 2B rvWF. Impaired SIPA of type 2M rvWF could account for the hemorrhagic syndrome observed in type 2M vWD. Increased SIPA of type 2B rvWF could be responsible for unstable aggregates and explain the fluctuant thrombocytopenia of type 2B vWD.

WHOLE BLOOD AGGREGOMETER IN THE ASSESSMENT OF PLATELET HYPER-AGGREGABILITY

1987 ◽  
Author(s):  
R Abbate ◽  
M Boddi ◽  
S Favilla ◽  
G Costanzo ◽  
R Paniccia ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Vascular Complications ◽  
Thromboembolic Complications ◽  
Significant Difference ◽  
Platelet Number ◽  
Patient Groups ◽  
Clinical Conditions ◽  
Selection Of

The aim of this study has been to investigate the reliability of platelet aggregation in whole blood in some clinical conditions associated to thromboembolic complications.18 healthy subjects, 15 patients affected by ischemic heart disease (IHD) and 15 patients affected by insulin independent diabetes, free of vascular complications, were studied. Collagen induced (2.5 mg/L f.c.) platelet aggregation was evaluated both in whole blood (WB) by using impedance whole blood aggregometer (Chrono-Log) and in platelet rich plasma (PRP) by Born aggregometer. Aggregation was significantly higher in whole blood than in PRP in all the groups investigated (p < 0.01). No significant difference was found in PRP aggregation among the three groups, whereas WB aggregation was significantly higher in the two patient groups (IHD 79.5 + 14.2%, Diabetes 81.3 + 17.6%) than in controls (64.8 ± 14.1%) (p < 0.01 for both comparisons). No relationship was found between WB aggregation and Hct or platelet number in any of the groups studied. A slight relationship was found between megathrombocyte count and WE aggregation values (r=0.31, p < 0.05).Collagen platelet aggregation in WB seems to be provided with higher sensibility than PRP aggregation in detecting hyper-aggregability, probably because it does not imply the selection of platelet populations with loss of larger platelets and of other blood cells.

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