Value of Platelet Esoteric Testing in Laboratory Diagnosis of Platelet Disorders: A Single Center Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1061-1061 ◽  
Author(s):  
Juliana Perez Botero ◽  
Deepti M. Warad ◽  
Rong He ◽  
Rajiv K. Pruthi ◽  
Dong Chen
Keyword(s):  
Flow Cytometry ◽  
Assessment Tool ◽  
Light Transmission ◽  
Conflicts Of Interest ◽  
Postoperative Bleeding ◽  
Retrospective Chart Review ◽  
Dense Granule ◽  
Platelet Glycoprotein ◽  
Molecular Testing ◽  
Platelet Disorders

Introduction Patients with inherited and acquired platelet disorders (PD) frequently present with thrombocytopenia and/or mucocutaneous bleeding. Diagnosis of PDs relies on both clinical and laboratory investigation, which encompasses both routine and esoteric platelet testing. The former includes platelet indices, light transmission aggregation (LTA) and platelet function analyzer (PFA-100). The latter includes platelet glycoprotein (GP) assessment by flow cytometry and platelet transmission electron microscopy (PTEM). Several recent studies have demonstrated limited sensitivities of routine platelet testing. It is uncertain if a combination of both routine and esoteric testing can vastly improve the sensitivity. Our goal is to assess the value of platelet esoteric testing and the ultimate sensitivity of laboratory platelet testing in diagnosing PDs. Methods Patients (between year 2012 and 2015) with a known or suspected inherited or acquired platelet disorders were recruited for platelet routine and esoteric testing. Patients' clinical features including ISTH bleeding assessment tool (BAT) scores, platelet count, LTA, PFA-100 ADP (CADP) and epinephrine (CEPI) cartridge closure times, GP expression by flow cytometry and PTEM were performed. All clinical and laboratory variables were collected and statistically analyzed. Results A total of 69 patients (51 females; median age 40 years; range: 8 months to 76 years) were enrolled to this cohort study. By retrospective chart review, 34 patients (49%) had a positive ISTH-BAT score (range 0 to 16). The most common bleeding manifestations (on any degree of severity) were cutaneous bleeding present in 53% of patients (n=37), menorrhagia in 47% of females (n=24), epistaxis in 36% (n=25) and postoperative bleeding in 35% (n=24). Joint, muscle and CNS hemorrhage were the least frequent with 7%, 6% and 1% of patients reporting bleeding in these sites. A total of 22 patients (32%) had thrombocytopenia at the time of their evaluation. Fifty-eight patients (84%) had platelet aggregation studies and of those 15 (26%) had an abnormal study. PFA-100 was performed in 57 patients (83%) of whom 42% (n=24) had prolonged closure times with either ADP or epinephrine. PTEM was performed on all samples. Twenty-seven patients (39%) had abnormal platelet structure including 17 patients who had dense granule deficiency. GP by flow cytometry was performed in 41 patients (59%) and abnormal glycoprotein expression was detected in 6 patients (15%). Of the 55 patients who had all tests performed, 22 patients (40%) had completely normal results. Of the routine tests, only PFA-CEPI or -CADP prolongation is associated with the likelihood of a PTEM abnormality (P<0.005). With the assistance of molecular testing, there were 2 cases of MYH-9 mutation-related platelet disorders, one of RUNX1 mutation-associated thrombocytopenia, one of York platelet syndrome, two of Bernard Soulier variants, one of Quebec syndrome and three of gray platelet syndrome or variants. Bleeding scores showed no statistically significant association with severity of any laboratory abnormalities. Conclusion In this cohort, the sensitivity of routine platelet testing in clinically suspected PDs is about 30-40%. Addition of platelet esoteric testing improves the sensitivity to 60%. However, the degree of platelet laboratory abnormalities do not predict severity of bleeding. The findings of this cohort underscore the importance of clinical assessment and both platelet routine and esoteric testing in investigation of patients with suspected PDs. Disclosures No relevant conflicts of interest to declare.

Fucosyltransferase VI Induces Platelet Activation: A Novel Property of a Plasma Glycosyltransferase.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4016-4016
Author(s):  
José-Tomás Navarro ◽  
Shwan Tawfiq ◽  
Roland Wohlgemuth ◽  
Karin M. Hoffmeister ◽  
Robert Sackstein
Keyword(s):  
Flow Cytometry ◽  
Platelet Aggregation ◽  
Platelet Activation ◽  
Light Transmission ◽  
Conflicts Of Interest ◽  
Platelet Rich Plasma ◽  
Surface Protein ◽  
Surface Flow ◽  
Platelet Surface ◽  
Biochemical Studies

Abstract Abstract 4016 Poster Board III-952 A number of glycosyltransferases are present in human plasma with the α(1→3) fucosyltransferase, Fucosyltransferase VI (FTVI), having the highest plasma concentration. Notably, elevated plasma levels of FTVI are associated with a variety of cancers and correlate with tumor load/progression. The well-known association of neoplasia with thromboembolic complications prompted us to examine whether FTVI has direct effect(s) on platelet function. We obtained human platelets from blood of healthy donors and separated from platelet-rich plasma by differential centrifugation. Freshly isolated platelets (x108/ml) were stirred and exposed at 37°C to varying concentrations (20, 40, 60 and 80 mU/mL) of glycosyltransferases FTVI, β-1-4-galactosyltransferase-I (βGalT-I), or α,2-3-N-sialyltransferase (α2,3-N-ST), or to 1 U/mL thrombin. Platelet aggregation and activation was assessed by aggregometry (light transmission) or by flow cytometry of FSC/SSC characteristics and of surface expression of P-Selectin, respectively. FT-VI reproducibly induced platelet aggregation and activation, whereas other glycosyltransferases (β4GalT-I and α2,3-N-ST) had no effect on platelets. FTVI activation of platelets was concentration-dependent, and the aggregation curve for FTVI was one wave, similar to that for thrombin. FTVI-induced platelet activation was independent of catalytic conversion of surface glycans, but was inhibited by FTVI denaturation, indicating that FTVI-induced platelet activation is a lectin-mediated process. To determine the membrane target(s) mediating FTVI-induced platelet activation, biochemical studies were performed after catalytic exofucosylation of the platelet surface. Flow cytometry after platelet exofucosylation showed formation of the carbohydrate structure sLex, detected by the mAb Heca452, but no formation of Lex (CD15). Western blot showed that enforced fucosylation induced sLex on a single platelet surface protein, and further biochemical studies revealed that this protein is GPIbα. These findings unveil a previously unrecognized property of FTVI as an activator of platelets, mediated via a specific lectin/carbohydrate interaction on GP1ba, and offer novel perspectives on the pathobiology of tumor-associated thrombogenesis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Flow Cytometric Analysis of Platelet Function in Patients on Antiplatelet Therapy and Suspected Thrombocytopathy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1161-1161
Author(s):  
Dana Huskens ◽  
Mark Roest ◽  
Lisa Florin ◽  
Bas De Laat ◽  
Katrien Devreese
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Assessment Tool ◽  
Light Transmission ◽  
Conflicts Of Interest ◽  
Flow Cytometric Analysis ◽  
Blood Platelet ◽  
Flow Cytometric ◽  
Healthy Donors ◽  
Bleeding Score

Abstract Background: Light transmission aggregometry (LTA) is still the most used test for the identification and diagnosis of platelet function defects (PFD). Disadvantages of LTA include its laborious nature, the large volumes of blood required and the relative insensitivity to small changes in platelet function. We investigated if the flow cytometry-based whole blood platelet activation test (WB-PACT) correlates with LTA or could be used as a complimentary test. Methods: WB-PACT quantifies αIIbβ3 activation and P-selectin expression in response to 3 agonists and VWF binding to platelets in response to ristocetin. In total, 212 patients (51 on dual antiplatelet therapy (acetylsalicylic acid and ADP receptor antagonist), 161 suspected for bleeding diathesis) were tested. For WB-PACT parameters, the 2.5th, 10th and 25th percentiles were determined in 56 healthy donors to score the patient samples. For LTA, maximal aggregation, disaggregation and prolongation of the lagtime in response to 4 agonists and ristocetin was scored. Patients with at least one parameter lower than the 10th percentile measured with WB-PACT in healthy donors or at least one value deviating from the normal range measured with LTA were diagnosed with PFD. A bleeding score (BS) was calculated with the ISTH/SSC bleeding assessment tool (Rodeghiero et al., JTH, 2010). Results: A moderate correlation between LTA versus WB-PACT was found with a R of 0.60 (Figure 1). In total, 95 patients were diagnosed with PFD by both tests (κ=0.40, Table 1) and BS were recorded for 28/95 patients. Of these 28 patients, 25% had an elevated BS (adapted according to gender and age: >5 in women, >3 in men and >2 in children) and 36% had a BS>3. BS were recorded for 30/38 and 22/24 patients who were diagnosed with PFD according to WB-PACT only and LTA only, respectively. Interestingly, 27% of patients with PFD according to WB-PACT had an elevated BS and 40% had a BS>3. For LTA, only 13% of patients with PFD had an elevated BS and 13% had a BS>3. Conclusions: Flow cytometric analysis of platelet function by WB-PACT gives additional value to LTA to determine PFD. Disclosures No relevant conflicts of interest to declare.

Impact Of Dedicated CML Clinic On The Outcome Of Patients With Newly Diagnosed CML: Experience Of a Single Canadian Center

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5186-5186
Author(s):  
Moussab Damlaj ◽  
Yury Monczak ◽  
Sarit Assouline
Keyword(s):  
Conflicts Of Interest ◽  
Blast Crisis ◽  
Retrospective Chart Review ◽  
Rank Test ◽  
Molecular Testing ◽  
Inadequate Response ◽  
Rt Pcr ◽  
Molecular Responses ◽  
Sokal Score

Abstract Background The outcome of patients with CML has improved significantly since the introduction of imatinib (O’Brien et al 2003). In the landmark IRIS trial, the rate of complete cytogenetic response (CCyR) was 69% by 12 months and 87% by 60 months and 7% of patients progressed to accelerated or blast crisis (Druker et al 2006). Multiple studies show that bcr-abl transcript level at 3 months can predict outcome and can be used to guide therapeutic strategies (Marin et al 2012). Additionally, patients achieving CCyR within 2 years on imatinib were projected to have a normal life expectancy (Gambacorti-Passerini et al 2011). Surprisingly, a survey of the CML World Registry involving over 1800 patients revealed that only 10% and 15% of patients had cytogenetic and molecular evaluation at 3 months, respectively. At our institution, we have a dedicated, multidisciplinary CML clinic with RT-PCR assay in house. We sought to determine how the outcome of our CP-CML patients, followed every 3 months and according to the ELN (European Leukemia Network) guidelines compares to clinical trial results. Methods Patients with CP-CML treated with imatinib first line between January 2004 and December 2012 were included in this retrospective chart review. Diagnosis was based on bone marrow aspirate with blast count and cytogenetic and/or FISH, and bcr/abl transcript RT-PCR using the IS method. Patients presenting in AP or BP, or those having previous lines of therapy except hydroxyurea or anagrelide were excluded. Baseline demographic, medical history, Sokal score at presentation and monitoring frequency for hematologic, cytogenetic and molecular responses were extracted. Definitions of cytogenetic and molecular responses were in accordance with the ELN guidelines. Cumulative rates of cytogenetic and molecular responses were estimated using the Kaplan–Meier method. Data for patients not achieving an adequate response were censored at the last follow up visit. Differences between groups were calculated by log rank test. The study received IRB approval at our institution. Results 55 eligible patients were identified. Median age was 53 years (17-92) and 33 (60%) were male. Distribution of Sokal score was low in 28 (50.9%), intermediate in 22 (40%) and high in 5 (9%). Median follow up duration was 53 months (range 3-106). Seven patients (12.7%) required switching to second line TKI, six for inadequate response, one for intolerance and one patient required switch to third line TKI for inadequate response. Molecular testing at 3 and 18 months post start of imatinib was performed in 48 pts (87.3%) and 53 (96.4%), respectively. At 12 months, 49 (89.1%) had cytogenetic evaluation. Estimated rates of CCyR at 6 months, 12 months, 18 months and 24 months were 46.6%, 69.2%, 78.7% and 88.2%, respectively. Estimated rates of MMR at 6 months, 12 months, 18 months and 24 months were 23.9%, 41.2%, 58.8% and 70.6%, respectively. When stratified by Sokal score, rate of CCyR at 12 months was 82.1%, 72.7% and 60% (p 0.8840) for low, intermediate and high scores, respectively. Conclusions CP-CML patients followed in a dedicated CML clinic receive more rigorous follow-up and monitoring and achieve response rates similar to that of clinical trials. Additionally, in this small cohort of patients, discontinuation rate of imatinib was substantially lower than previously reported. Disclosures: No relevant conflicts of interest to declare.

Bleeding Risks Associated with Confirmed Platelet Dense Granule Deficiency and/or Impaired Aggregation Responses

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3728-3728
Author(s):  
Janaki Iyer ◽  
Matthew Badin ◽  
Lucas Graf ◽  
Georges E. Rivard ◽  
A. D. Paterson ◽  
...  
Keyword(s):  
General Population ◽  
Platelet Function ◽  
Assessment Tool ◽  
Family Members ◽  
Dense Granule ◽  
Medical Attention ◽  
Excessive Bleeding ◽  
Platelet Function Disorders ◽  
Platelet Disorders ◽  
Population Controls

Abstract Platelet function disorders represent a heterogeneous group of bleeding disorders with diverse molecular causes that are frequently associated with platelet dense granule deficiency and/or impaired aggregation responses. With the exception of Quebec platelet disorder (QPD), bleeding risks for common platelet disorders have not been estimated. This led us to study a Canadian cohort with uncharacterized platelet function disorders and confirmed abnormalities in validated assays for platelet dense granule deficiency and/or light transmission aggregometry (reduced aggregation with ≥2 agonists). Subjects were assessed using: (i) the International Society for Thrombosis and Haemostasis bleeding assessment tool (ISTH-BAT) to determine scores and categorize symptom severity, and (ii) CHAT-P, a clinical history assessment tool for assessment of platelet disorders that included questions about general health and bleeding symptoms/problems and questions previously used to assess bleeding risks for QPD. CHAT-P was completed by subjects (or parent in the case of young children) before review by a hematologist. Participants included: 29 individuals with confirmed platelet function disorders of unknown cause (from 7 families, 10 "sporadic" cases), 12 unaffected relatives and 60 general population controls. A one-way ANOVA was used to compare the overall ISTH-BAT scores between the affected individuals, unaffected relatives and healthy controls. Bleeding risks were estimated as odds ratio (OR) with 95% confidence intervals (CI) using CHAT-P data for general population controls as the comparison group. The total number of affected subjects reporting a bleeding problem/symptom from the group of affected individuals was added up and compared with the corresponding numbers of responses for general population controls and unaffected relatives using ANOVA. Summative bleeding scores for CHAT-P items with OR>1 were used to compare the number and range of abnormal bleeding symptoms experienced by subjects. Individuals with confirmed platelet abnormalities had higher ISTH-BAT scores (median: 9, range: 0-18) than unaffected family members (median: 0, range: 0-1) and general population controls (median: 0, range: 0-6) (p < 0.01), and their most severe symptom scores were for: epistaxis, cutaneous bleeding, menorrhagia, bleeding from dental extractions, surgery and a subdural hematoma at birth. Affected individuals had higher risks for bleeding (OR, 95% CI, p value) including: bleeding from minor cuts/wounds lasting >1 hour (56, 3.1-1000, p<0.01); abnormal bruising (15-65, 1.8-140 to 3.7-1200, p<0.01); prolonged nosebleeds (23, 5.9-92, p<0.01) and nosebleeds requiring medical attention (40, 1.5-520, p<0.01), packing (33, 1.8-620, p<0.01) or cautery (27, 1.5-510, p<0.01); wound healing problems (13, 3.4-53, p<0.01); excessive bleeding from injuries/trauma (9.5, 1-87, p=0.03), oral/dental challenges (44, 5.3-370, p<0.01) and surgery (17, 4.1-68, p<0.01). Affected females reported: bleeding interfering with their sex life (6.5, 1.1-38, p=0.04); menses >7 days (11, 2.5-49, p<0.01); flooding/gushing accidents (3.8, 1.2-12, p=0.04 ) and/or clots with menses (13, 2.6-63, p<0.01); menses requiring treatment (7.8, 2.1-29, p<0.01); and excessive bleeding during childbirth (17, 2.7-105, p<0.01), sometimes requiring surgical intervention (41, 2-810, p<0.01). Affected individuals reported more of these bleeding symptoms (median: 15, range: 0-24) than unaffected family members (median: 2, range: 0-6; p<0.01) and general population controls (median: 1, range: 0-14, p<0.01), although there was overlap. Our study illustrates that uncharacterized platelet function disorders are associated with significantly increased bleeding risks and mild rather than severe bleeding problems. It will be important to translate our study findings for patients and healthcare providers to promote evidence-based care of individuals with confirmed dense granule deficiency and/or impaired aggregation responses, which are common amongst individuals tested for bleeding problems. Disclosures No relevant conflicts of interest to declare.

scholarly journals Platelet-Associated Antibodies By Flow Cytometry in Adult Patients with Immune Thrombocytopenia before and after Splenectomy

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-5
Author(s):  
Kseniya A. Nikiforova ◽  
Elena K. Egorova ◽  
Yuliya O. Davydova ◽  
Nikolay M. Kapranov ◽  
Elena I. Pustovaya ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Peripheral Blood ◽  
Immune Thrombocytopenia ◽  
Conflicts Of Interest ◽  
Polyclonal Antibodies ◽  
Fluorescein Isothiocyanate ◽  
Platelet Glycoprotein ◽  
Rank Test ◽  
Severe Thrombocytopenia ◽  
Becton Dickinson

Introduction Immune thrombocytopenic purpura (ITP), or primary immune thrombocytopenia is an autoimmune disease characterized by isolated thrombocytopenia (number of platelets in peripheral blood is less than 100×109/L) and splenic production of antibodies against platelet glycoprotein complexes and megakaryocytes, resulting in hemorrhagic syndrome. Circulating platelets attached by autoantibodies that leads to accelerated removal of these cells by spleen macrophages. The therapy for patients with newly diagnosed ITP with hemorrhagic syndrome and/or severe thrombocytopenia (number of platelets in peripheral blood &lt;10-20×109/L) includes corticosteroids and characterized by a low rate of remission (just around 20-30%). For cases of ITP resistant to corticosteroid therapy recommends one of the second-line method of treatment - splenectomy (SE). Approximately 60-80% of the patients achieve complete remission after splenectomy. There is a technique for assessment of platelet-associated antibodies (PAA) classes IgG, IgM and IgA on platelets by flow cytometry. This method is a commodious, easy, quick, and relatively cheap and applied to estimate autoimmunity status of patients with thrombocytopenia. However, this method characterized by low specificity. Aim The aim of the study was to determine the correlation between level of PAA of IgG, IgM, and IgA classes in the peripheral blood of adults with ITP before SE, 5-7 days and 3 months after SE. Patients and methods The study included 21 patients with ITP (4 cases of persistent ITP and 17 cases with chronic form). Median age was 36.9 years, M:F ratio was 1: 4.25 (men was older than women - 46.0 years old versus 34.7). All patients underwent from 1 to 3 lines of therapy and were recommended for SE due to resistance to treatment. The PAA level was measured at three time points (before SE, 5-7 days, and three months after SE) by flow cytometry (Becton Dickinson FACS Canto II). Goat polyclonal antibodies against human IgG, IgM, IgA labeled with fluorescein isothiocyanate (FITC) (Cedarlane) were used to determine antibodies of various classes. Anti-CD41a labeled with phycoerethrin (Becton Dickinson) was used to determined platelets. PAA level was assessed based on the mean of fluorescence intensity (MFI) of the FITC-channel. Statistic analysis was carried out using GraphPad Prism 6.01. Wilcoxon signed-rank test had been used for pair comparison. The value of 0.05 had been taken as reliable. Results MFI levels of PAA IgA (391 vs 198, p = 0.005) and IgM (275 vs 142, p&lt;0.0001) significantly decreased in patients after SE compared with the initial level (level before SE). Level of MFI PAA IgM also remained reduced (275 vs 138, p=0.0084) three months after SE (Fig. 1). MFI levels of PAA IgG did not change. Conclusions Using of flow cytometry to determinate platelet-associated immunoglobulins for diagnostic of ITP remains controversial. Despite the fact, this test can be recommended for monitoring of PAA from patients with ITP after SE. In addition, the results confirm the fact that most cells producing antiplatelet antibodies seems to be residing in a spleen. Disclosures No relevant conflicts of interest to declare.

scholarly journals Platelet Transmission Electron Microscopy and Flow Cytometry in the Diagnosis of Congenital/Hereditary Qualitative or Quantitative Platelet Disorders

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3476-3476
Author(s):  
Juliana Perez Botero ◽  
Laynalee K Cardel ◽  
Aneel A. Ashrani ◽  
John A. Heit ◽  
Rong He ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Flow Cytometry ◽  
Platelet Aggregation ◽  
Dense Granule ◽  
Glanzmann Thrombasthenia ◽  
Transmission Electron ◽  
Gray Platelet Syndrome ◽  
Platelet Disorders ◽  
Bleeding History

Abstract Background Congenital/hereditary qualitative platelet disorders (CQPD) can be classified by platelet count (eg, normal or decreased) and platelet size as well as by functional defect. Based on mean platelet volume (MPV), congenital thrombocytopenias (CT) are classified as macro-thrombocytopenias (eg, Bernard-Soulier syndrome [BSS], MYH-9 [myosin heavy chain 9, non-muscle]-associated thrombocytopenias, gray platelet syndrome [GPS], etc.); microthrombocytopenias (eg, Wiskott-Aldrich syndrome and variants); and those with normal platelet size. CQPDs with normal platelet count include Glanzmann thrombasthenia (GT), dense granule storage pool disorders (DG-SPD) including Hermansky-Pudlak syndrome (HPS), platelet secretion disorders and many others. Diagnosis has relied on platelet counting and sizing, blood smear light microscopy, platelet aggregation (agg) and platelet function analyzer (PFA-100) studies. Platelet transmission electron microscopy (PTEM) and flow cytometry can provide supplementary information and molecular analysis is also evolving. The objective of this study was to determine the roles of platelet transmission electron microscopy (PTEM) and flow cytometry in the diagnosis of CQPD and CT. Methods In this retrospective cohort study, after IRB approval, the electronic medical record system was queried for patients (pt) with a confirmed CQPD or CT seen at Mayo Clinic between 2000 and 2015. A detailed chart review was undertaken. Results 54 pt (64% female) met our study criteria; median age was 32 years (range 1 day to 81 years). 18/54 (33%) pt had macrothrombocytopenia: BSS 4 (7%); MYH-9 10 (19%); gray platelet syndrome 4 (7%). 36/54 (66%) had normal MPV: Glanzmann thrombasthenia 6 (11%); storage pool disorders including DG-SPD 10 (19%) and HPS 2 (3%), mild alpha granule deficiency 3 (6%) and York platelet syndrome 4 (7%); platelet secretion disorders 4 (7%); ANKRD26 mutation 3 (6%); congenital amegakaryocytic thrombocytopenia 1 (2%); GATA-1 mutation 1 (2%); RUNX-1 mutation 1 (2%); and Jacobsen syndrome 1 (2%). 44 pt (81%) had a positive bleeding history: epistaxis 52%, cutaneous bleeding 57%, gastrointestinal bleeding 21% and menorrhagia 54%; 10 pt (19%) had a negative bleeding history. Results of standard and esoteric platelet testing are summarized in Table 1. Diagnosis in the 10 pt with glycoprotein deficiency (BSS or GT) was established by agg; flow cytometry was confirmatory but not necessary. Of the 23 pt with SPD, 5 had a negative bleeding history; 4 pt had normal agg and PFA-100 and were diagnosed exclusively by PTEM. In this group, the abnormalities on platelet aggregation and PFA were variable and PTEM allowed for a better definition of the specific abnormalities. For MYH-9 patients, PTEM confirmed leukocyte inclusions that had already been identified on light microscopy. PTEM was the only diagnostic modality able to identify the abnormality in York platelet syndrome. In 5/54 (9%) genetic testing was necessary for diagnosis (GATA-1, ANKRD26 and RUNX-1) Conclusion In this cohort, standard platelet assays established the diagnosis in the large majority of CQPD and CT. PTEM was essential for confirmation in DG-SPD, mild alpha granule deficiency and York platelet syndrome and useful in combination with molecular testing to establish a diagnosis in selected cases. Guidance on selection of patients for such specialized testing requires further study. Table 1. Results of standard and esoteric platelet testing for 54 patients with congenital qualitative platelet disorders and/or thrombocytopenia Disorder n (%) Platelet aggregation PFA PTEM Flow cytometry Confirmation by genetics Done Abnormal Done Abnormal Done Abnormal Done Abnormal Glanzmann thrombasthenia 6 (11) 6 6 5 5 1 0 3 3 0 Bernard-Soulier syndrome & variants 4 (7) 4 4 4 4 3 0 4 4 0 MYH-9 related disorders 10 (19) 7 2 8 3 5 5 4 2 5 Dense granule deficiency and HPS 12 (22) 12 8 12 8 12 12 4 0 0 Alpha granule deficiency* 7 (13) 7 4 7 6 7 7 4 4 1 York platelet syndrome 4 (7) 1 0 1 1 4 4 1 1 0 TXA2 or PG synthesis/receptor defect 4 (7) 4 4 4 3 3 0 3 0 0 CATM 1 (2) 0 - 0 - 0 - 0 - 1 ANKRD26 3 (6) 3 3 3 2 3 3 3 3 3 GATA-1 1 (2) 0 - 1 1 1 1 1 1 1 RUNX-1 1 (2) 1 0 1 1 0 - 0 - 1 Jacobsen syndrome 1 (2) 1 0 1 1 1 1 1 0 1 MYH-9: myosin heavy chain 9, non-muscle (MHY-9) associated thrombocytopenia, HPS: Hermansky-Pudlak Syndrome, TXA2: thromboxane A2, PG: prostaglandin CATM: congenital amegakaryocytic thrombocytopenia. * Includes gray platelet syndrome Disclosures Pardanani: Stemline: Research Funding.

A Monoclonal Antibody to the Human Platelet Glycoprotein II b/III a Complex Induces Platelet Activation

1988 ◽  
Vol 60 (01) ◽  
pp. 068-074 ◽  
Author(s):  
Piet W Modderman ◽  
Han G Huisman ◽  
Jan A van Mourik ◽  
Albert E G Kr von dem Borne
Keyword(s):  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Dense Granule ◽  
Platelet Glycoprotein ◽  
Activated Platelets ◽  
Complex Functions ◽  
Slow Aggregation ◽  
Irreversible Aggregation ◽  
Platelet Release ◽  
Aggregation Of Platelets

SummaryThe platelet glycoprotein (GP) IIb/IIIa complex functions as the receptor for fibrinogen on activated platelets. The effects of two anti-GPIIb/IIIa monoclonal antibodies on platelet function were studied. These antibodies, 6C9 and C17, recognized different epitopes, which were exclusively present on the undissociated GPIIb/IIIa complex. Whereas C17 inhibited the binding of fibrinogen to platelets and platelet aggregation induced by adenosine diphosphate (ADP) or collagen, 6C9 caused irreversible aggregation of platelets, both in the presence and absence of extracellular fibrinogen. When incubated with unstirred (nonaggregating) platelets, 6C9 induced release of alpha and dense granule-constituents as well as binding of 125I-fibrinogen to platelets. The latter was evidently mediated in part by platelet-derived ADP, since it was inhibited to a large extent by apyrase, the ADP-hydrolyzing enzyme. F(ab’)2 fragments of 6C9 did not induce platelet-release reactions but caused (slow) aggregation of platelets in the presence of extracellular fibrinogen.These results indicate that binding of an antibody to a specific site on the platelet GPIIb/IIIa complex may cause fibrinogen-mediated aggregation. The Fc part of the platelet-bound antibody appears to be involved in the induction of platelet release.

scholarly journals The ISTH bleeding assessment tool as predictor of bleeding events in inherited platelet disorders: Communication from the ISTH SSC Subcommittee on Platelet Physiology

2021 ◽  
Vol 19 (5) ◽  
pp. 1364-1371
Author(s):  
Paolo Gresele ◽  
Emanuela Falcinelli ◽  
Loredana Bury ◽  
Alessandro Pecci ◽  
Marie‐Christine Alessi ◽  
...  
Keyword(s):  
Assessment Tool ◽  
Bleeding Events ◽  
Platelet Disorders ◽  
Platelet Physiology

PS01.168: IS IT POSSIBLE TO PREVENT GASTRIC TUBE NECROSIS FOLLOWING ESOPHAGECTOMY?

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 97-97
Author(s):  
Katsunori Nishikawa ◽  
Yujiro Tanaka ◽  
Yuichiro Tanishima ◽  
Shunsuke Akimoto ◽  
Fumiaki Yano ◽  
...  
Keyword(s):  
Gastric Tube ◽  
Assessment Tool ◽  
Imaging System ◽  
Conflicts Of Interest ◽  
Tissue Perfusion ◽  
Early Postoperative Period ◽  
Partial Replacement ◽  
Full Thickness ◽  
Intraoperative Assessment ◽  
Vascular Insufficiency

Abstract Background Gastric tube necrosis (GN) following esophagectomy is a rare, but critical and life threatening complication. Unlike anastomotic leakage due to local ischemia, GN involves extensive full thickness ischemia resulting from vascular insufficiency. Most cases of GN need total or partial replacement of gastric tube. Although quantitative assessment of tissue perfusion during esophageal surgery contributed to reduce the incidence of postoperative anastomotic complications, GN remains a serious complication to be solved. Methods Data were collected retrospectively from 271 patients who underwent esophagectomy and gastric tube reconstruction at a single center between 2008 and 2018, in which cases of GN were identified. Gastric mobilization was mainly performed laparoscopically using a hand-assisted maneuver. The short gastric and left gastric arteries were divided, and the right gastric and gastroepiploic arteries were both preserved. The gastric tube 3.5 cm in width was created along the greater curvature. Intraoperative assessment of perfusion of the gastric tube was performed using our novel Thermal Imaging System (TIS) in all patients. Quantitative tissue perfusion scores defined as anastomotic viability index (AVI) were calculated at various points from the anastomosis. Results The inpatient mortality rate was 1.8% (n = 5). Anastomotic leak (AL) developed in 8.8% (n = 24) of the study group. The mean AVI score of cases with AL was 0.58, which was significantly lower than that without AL (0.71, P < 0.001). GN occurred in two patients (0.7%). The AVI score of the both GN cases were relatively high at 0.74 and 0.82. In one of the cases, circumferential full thickness ischemia 10 cm in length from the esophagogastric anastomosis was revealed by contrast CT scans and endoscopy, which was later identified to be due to severe vascular impairment. Conclusion TIS can be used as a reliable intraoperative assessment tool for perfusion of the gastric tube. We assume that most AL would be caused by delayed anastomotic healing due to poor vascularization of the gastric tube. On the other hand, obvious difference in AVI scores between AL and GN may indicate the involvement of different etiology. Given that development of GN seemed to be caused by acute failure in vascularization during the early postoperative period. Disclosure All authors have declared no conflicts of interest.

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