No approved-drug candidate for platelet-type bleeding disorder 11 is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
RCSB Protein Data Bank · entry 5OU7 · 1.9 Å · ligand 1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE (PG6). Experimental structure, not a prediction.
The AABB guideline on platelet transfusion, based on a systematic review of trials up to 2014, recommends prophylactic transfusion for hospitalised adults with therapy-induced hypoproliferative thrombocytopenia when the platelet count is 10 × 10⁹ cells/L or less. For elective central venous catheter placement the suggested threshold is below 20 × 10⁹ cells/L, and for lumbar puncture or major non-neuraxial surgery below 50 × 10⁹ cells/L. The guideline recommends against routine prophylactic transfusion for non-thrombocytopenic patients having cardiac surgery with bypass, and makes no recommendation for or against transfusion in patients on antiplatelet therapy who have intracranial haemorrhage. The evidence for several of these recommendations is graded as low or very low quality.
A 2007 review of immune thrombocytopenic purpura in adults states that most patients tolerate the disease well with little morbidity. Splenectomy remains the best curative treatment for chronic disease after at least six months of follow-up. Treatments such as anti-D, rituximab or dexamethasone may allow splenectomy to be postponed indefinitely if a haemostatic platelet count is achieved. Mortality from bleeding may be relevant only in patients refractory to splenectomy. The review notes that an aggressive approach is justified only when platelet counts fall below 20 × 10⁹/L and in splenectomy-refractory patients.
A 2021 cross-sectional study using the ATHNdataset identified 2767 patients with platelet function disorders (PFDs) from 140 US treatment centres between 2010 and 2020. Of 1271 patients who underwent at least one procedure, 3252 procedures were recorded. Surgery-associated bleeding episodes (intraoperative or postoperative) occurred with 69 procedures (2.1 percent): intraoperative bleeds in 18 procedures (0.5 percent) and postoperative bleeds in 51 (1.6 percent). In patients with Glanzmann thrombasthenia, bleeding episodes followed 9 of 22 dental procedures (41 percent), 1 of 4 circumcisions (25 percent), and 11 of 60 other procedures (18.3 percent). In Bernard Soulier syndrome, no bleeding episodes were reported among 6 procedures. In storage pool deficiency, bleeding followed 26 of 1688 dental procedures (1.5 percent) and 62 of 1688 other surgeries (3.67 percent). No intraoperative or postoperative mortality was reported. Among 646 patients who received haemostatic treatment before, during or after a procedure, 49 percent of treatment exposure days were before the procedure, 0.7 percent during, and 49.5 percent after.
A 2006 report describes a family with congenital bleeding diathesis due to P2Y12 receptor deficiency. Two sisters had a severe defect from a single base-pair deletion (378delC) causing a frameshift and truncated protein. The 13-year-old son of one sister had a moderately prolonged bleeding time (13 minutes) and a partial platelet defect. Quantitative PCR and Southern blotting showed that the son, his mother, and his aunt each had only one intact P2Y12 allele. The son’s remaining allele was normal, while the mother and aunt each had a mutant allele, explaining the milder phenotype in the son. This is a description of haploinsufficiency in a single family; no treatment or outcome data beyond the laboratory and clinical phenotype are provided.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Internal Medicine · 2014 · 989 citations
Platelet Transfusion: A Clinical Practice Guideline From the AABB
AbstractBACKGROUND: The AABB (formerly, the American Association of Blood Banks) developed this guideline on appropriate use of platelet transfusion in adult patients. METHODS: These guidelines are based on a systematic review of randomized, clinical trials and observational studies (1900 to September 2014) that reported clinical outcomes on patients receiving prophylactic or therapeutic platelet transfusions. An expert panel reviewed the data and developed recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RECOMMENDATION 1: The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 2: The AABB suggests prophylactic platelet transfusion for patients having elective central venous catheter placement with a platelet count less than 20 × 109 cells/L. (Grade: weak recommendation; low-quality evidence). RECOMMENDATION 3: The AABB suggests prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 4: The AABB suggests prophylactic platelet transfusion for patients having major elective nonneuraxial surgery with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 5: The AABB recommends against routine prophylactic platelet transfusion for patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass. The AABB suggests platelet transfusion for patients having bypass who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 6: The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous). (Grade: uncertain recommendation; very-low-quality evidence).
https://doi.org/10.7326/m14-1589Current Opinion in Hematology · 2007 · 86 citations
Immune thrombocytopenic purpura in adults
AbstractPURPOSE OF REVIEW: A review of recent studies was conducted to determine if guidelines promulgated by the American Society of Hematology and the British Committee for Standards in Haematology need to be updated as these were based mainly on expert opinion rather than outcomes derived from clinical trials. RECENT FINDINGS: Recent studies suggest that most patients with immune thrombocytopenic purpura have a disease that is generally well tolerated, with little morbidity. Splenectomy remains the best 'curative' treatment for adults with chronic disease (at least 6 months of follow up). Other treatments such as anti-D, rituximab or dexamethasone may allow the decision of splenectomy to be postponed, possibly indefinitely, if hemostatic platelet count is attained. Mortality from bleeding may be relevant only in patients refractory to splenectomy. Cytotoxic agents should be reserved for patients with bleeding refractory to other treatments. SUMMARY: Patients with platelet counts less than 30 x 10(9)/l or bleeding have to be treated but management decisions should also be based on lifestyle, age, and other medical conditions that may contribute to the risk of serious bleeding. An aggressive therapeutic approach is justified only in patients with platelet counts below 20 x 10(9)/l and those refractory to splenectomy. Newer therapies may be more targeted in their action.
https://doi.org/10.1097/moh.0b013e3282b9748fAnesthesia & Analgesia · 2001 · 32 citations
Bleeding in a Patient Receiving Platelet Aggregation Inhibitors
AbstractPlatelet receptor glycoprotein (GP) IIb/IIIa antagonists (abciximab, eptifibatide) are antithrombotic agents that provide comprehensive blockade of receptors necessary for the final common pathway of platelet aggregation. Perioperative bleeding, a concern whenever platelet function is inhibited, has been described in surgical patients after treatment with abciximab (1,2). To allow recovery of platelet function and to prevent bleeding, the infusion of abciximab should be discontinued 12–24 h before surgery (3). For eptifibatide, with an elimination half-life of 2.5 h, this interval is even shorter. We report a patient who preoperatively received several antiplatelet drugs (aspirin, clopidogrel, abciximab, and eptifibatide) and consequently experienced massive perioperative bleeding although surgery was performed at a time when, according to pharmacodynamic and pharmacokinetic properties of individual drugs, the antiplatelet action should have been terminated. This case illustrates a need to preoperatively assess resolution of platelet function after exposure to these antiplatelet drugs. In addition, this case indicated that Sonoclot® (SNC; Sienco, Wheat Ridge, CO) might detect platelet dysfunction in the presence of an apparently normal Thrombelastograph® (TEG®; Haemoscope, Skokie, IL) tracing. This led us to conduct the in vitro study to examine the sensitivity of these two methods for detecting platelet dysfunction in the presence of the GP IIb/IIIa inhibitor, eptifibatide, which was the last antiplatelet drug our patient received before surgery. Case Report A 70-yr-old, 75-kg woman was scheduled for repair of a 9-cm abdominal aortic aneurysm. She had a history of coronary artery disease, congestive heart failure, hypertension, and carotid artery stenosis. Eight days before the abdominal aortic aneurysm repair, she underwent internal carotid artery stenting and was treated with the GP IIb/IIIa inhibitor abciximab (ReoPro®; Eli Lilly, Indianapolis, IN) (0.125 μg · kg · min−1 for 12 h) followed by two antiplatelet medications, clopidogrel (Plavix®; Bristol-Myers Squibb, New York, NY) (75 mg daily for 2 days) and aspirin (325 mg daily for 2 days). After carotid artery stenting, her serum creatinine concentration increased from 0.9 mg/dL to 2.1 mg/dL. Five days before the abdominal aortic aneurysm surgery, the patient was treated with a second GP IIb/IIIa inhibitor, eptifibatide (Integrilin®; Key Pharmaceuticals, Kenilworth, NJ) (2 μg · kg · min−1 on the first day; then the rate was reduced to 1 μg · kg · min−1 in view of the increased serum creatinine concentration), which was discontinued 8 h before surgery. The preoperative platelet count was 1.25 × 105/μL, prothrombin time was 13.8 s, international normalized ratio was 1.21, and activated partial thromboplastin time was 25 s. Platelet function was not preoperatively assessed. During surgery, the patient lost 1500 mL of blood from “capillary bleeding” before aortic cross-clamping. To assess coagulation abnormality in the operating room we tested the patient’s blood with TEG® and SNC®. TEG® tracing appeared to be in the normal range (maximal amplitude [MA] was 62 mm) (Fig. 1A). At the same time SNC® signature was consistent with slow clot retraction of the fibrin gel, i.e., consistent with poor platelet function (time to peak was delayed to 23 min, normal is approximately 12 min) (Fig. 1B, dashed superimposed curve represents a normal SNC® signature obtained from the same patient 4 days later). Four platelet and two fresh-frozen plasma units were given without adequate hemostasis or significant change in SNC® signature. As the aortic cross-clamp had not been applied, the surgery was aborted. That night, the patient received multiple blood and platelet transfusions and was taken back to surgery for evaluation of the continuing bleeding (continuous decrease in hemoglobin levels). Before the repeat surgery, a coagulation profile was performed which showed no evidence of disseminated intravascular coagulation (prothrombin time 12.3 s, activated partial thromboplastin time 25.7 s, international normalized ratio 1.08, and fibrinogen 286 mg/dL). Exploratory surgery revealed a large retroperitoneal hematoma and no signs of active surgical or microcapillary bleeding. She was taken back to the intensive care unit where she remained for the next 24 h before being discharged to a regular nursing floor.Figure 1: Upper panel, Thrombelastogram® tracing from our patient (case report) consistent with normal platelet function. Lower panel, Sonoclot® signature from the same patient is consistent with platelet dysfunction (clot retraction is slow and time-to-peak is delayed to 23 min). Dashed superimposed curve represents normal Sonoclot® signature.Assessment of Platelet-Inhibiting Effects of Eptifibatide with Thrombelastograph® and Sonoclot® Because our bleeding patient had an apparently normal TEG® and an abnormal SNC® signature, we designed this in vitro study to quantify the effect of the GP IIb/IIIa receptor inhibitor, eptifibatide, with TEG® and SNC®. We believe that the eptifibatide was responsible for the bleeding in our patient because it was the last antiplatelet drug administered before surgery. Methods After IRB approval and written consent, 10 mL of blood was drawn from 12 volunteers. These volunteers had been asked to take no antiplatelet drugs and herbal supplements for 14 days before blood sampling. In addition, they had nothing by mouth for 12 h before the blood draw. The whole blood samples were collected into siliconized Vacutainer glass tubes containing 3.8% trisodium citrate with a sodium citrate/blood ratio maintained at 9:1 (vol/vol). The eptifibatide stock solution was prepared by diluting it with 0.9% normal saline. We added 10 μL of this stock solution to each blood sample (350 μL) in disposable TEG® or SNC® cuvettes. The final eptifibatide concentrations in the cuvettes was 4 μg/mL (0.5 × therapeutic clinical concentration), 8 μg/mL (1.0 × therapeutic plasma concentration), and 18.5 μg/mL (2.2 × therapeutic plasma concentration). A 0.9% saline solution (10 μL) was used as a control. Collected citrated whole blood was incubated for 5 min at 37°C before analyses. Before each test, the blood sample was recalcified with 0.013 mL of 0.2 M CaCl2. The analysis of the following TEG® ratio variables was performed: R (reaction time, time from sample placement in the cuvette until TEG® tracing amplitude reaches 2 mm; represents the rate of initial fibrin formation), K, clot formation time (measured from R time to the point when the amplitude of the tracing reaches 20 mm; represents the time for development of fixed degree of viscoelasticity during clot formation), α angle (α°) (angle formed by the slope of the initial TEG® tracing; denotes speed at which solid clot forms, MA (the greatest amplitude of the TEG® tracing and is a reflection of the absolute strength of the fibrin clot, i.e., reflects platelet function). The following SNC® variables were recorded: sonACT, Sonoclot activated clotting time (liquid phase or onset of clot formation, may be compared to the R interval in TEG®), clot rate (slope of the SNC® signature, characterizes fibrin gel formation and correlates with the TEG® α°, and Platelet Function (a number calculated from an algorithm that takes into account elements of clot retraction from the SNC® signature; it can be compared to the TEG® MA variable). We also measured SNC® time-to-peak (this variable represents the amount of time SNC® signature reaches the peak; it places great emphasis on how fast it takes to activate platelets rather than how much the platelets contribute to the clot retraction). Comparisons between TEG® and SNC® variables (only those that reflect platelet function) were made for each of the above three concentrations of eptifibatide. MA and SNC® platelet function values decreased while time-to-peak increased in the presence of eptifibatide. For statistical analysis we compared relative changes of each test regardless of the direction of that change. Statistical analysis was performed by repeated-measures analysis of variance, and differences were considered statistically significant at P < 0.05. All variables were expressed as mean and sd. A coefficient of variation for both methods was performed by repeatedly (n = 5) measuring SNC® Platelet Function and TEG® MA on a blood sample from a single patient. Results Figure 2 shows the TEG® and SNC® dose-response tracings to eptifibatide. The eptifibatide effect on SNC® signature clot retraction is characteristic; in all studied concentrations eptifibatide only delayed clot retraction, but it never inhibited it completely. Figure 3 compares relative changes of TEG® MA, and SNC® Platelet Function and time-to-peak. At lower levels of platelet GP IIb/IIIa receptor blockade (4 μm/mL eptifibatide), the TEG® MA and SNC® Platelet Function were reduced 16 ± 9% and 28 ± 14% from baseline, respectively (P <0.03), while time-to-peak increased 45% above the baseline. At normal therapeutic range (8 μg/mL) and above the therapeutic range (18.5 μg/mL) SNC® Platelet Function and TEG® MA exhibited similar reductions (approximately 40% and 60%, respectively) (P = 0.9). At any concentration of eptifibatide studied, SNC® time-to-peak variable changed the most. Table 1 shows absolute values of TEG® and SNC® variables before and after addition of eptifibatide. There was an 18% to 20% variability in baseline values between the patients. Coefficient of variation for TEG® MA and SNC® Platelet Function was 1.6% and 2.6%, respectively (n = 5 each).Figure 2: Response to eptifibatide assessed by Thrombelastography® (upper panel) and Sonoclot® (lower panel).Figure 3: Relative decrease in maximal amplitude (Thromboelastogram®) (TEG-MA) and Sonoclot® (SNC) Platelet Function and increase in Sonoclot® (SNC) time-to-peak interval in response to increasing concentration of eptifibatide. All values are mean ± sd; *P < 0.03; **P < 0.04, ***P < 0.02.Table 1: Absolute Values of Thrombelastogram® and Sonoclot® Variables at Different Eptifibatide ConcentrationsDiscussion Antiplatelet drugs are administered to reduce myocardial infarction and mortality associated with unstable angina, percutaneous transluminal coronary angioplasty, and after placement of vascular stents. We described a patient who received several antiplatelet medications after carotid artery stenting but developed severe bleeding during consequent surgery for aortic aneurysm repair. It appears that the residual antiplatelet effects of the multiple medications this patient received may have contributed to the bleeding. Aspirin and clopidogrel taken 6 days before the surgery might have had lingering antiplatelet action (10 to 15 days). Eptifibatide has primarily renal excretion; therefore, its prolonged elimination might be seen in patients with renal insufficiency (3). Typically, eptifibatide effects are abated if the drug is stopped eight hours before surgery; however, this might not be true if the patient’s serum creatinine is increased, as in our patient. The activated form of GP IIb/IIIa mediates the final common pathway of platelet aggregation. The reversibility of platelet inhibition and the rate of plasma clearance are largely a function of GP IIb/IIIa pharmacokinetic and pharmacodynamic properties (4). Clopidogrel is an antiplatelet drug that inhibits the binding of adenosine 5′-diphosphate to its platelet receptor, which leads to direct inhibition of the binding of fibrinogen to the GP IIb/IIIa receptor. The antiplatelet effect of clopidogrel lasts about 10 days, which corresponds to the life span of the platelet (5). Abciximab, a direct high-affinity GP IIb/IIIa receptor antagonist, has a biologic half-life of eight hours (6,7). Abciximab can be detected on the surface of circulating platelets for at least two weeks after discontinuation of the drug (8). Eptifibatide has a higher specificity and a lower affinity for GP IIb/IIIa receptors resulting in a biological half-life of 2.5 hours and a rapidly reversible antiplatelet effect (4). A substantial recovery of platelet aggregation is apparent within four hours of completion of eptifibatide infusion, whereas the bleeding time returns to baseline within one hour (9). In our patient, a SNC® signature performed more than 12 hours after discontinuation of eptifibatide therapy clearly showed poor platelet function, suggesting that we should not assume the cessation of the effects of antiplatelet drugs based on their individual pharmacokinetic principles. At the same time, a TEG® tracing appeared within normal limits (Fig. 1), which suggests that TEG® and SNC® may have different sensitivities in detecting changes in the viscoelastic properties of blood treated with antiplatelet drugs. One of the problems in accurately assessing the level of platelet dysfunction with TEG® and SNC® is the wide range of normal values (Table 1) that is caused by person-to-person variability; i.e., differences in platelet counts, fibrinogen concentrations, and variability in number of GP IIb/IIIa receptors and its ligand-binding function (10). We have demonstrated that in healthy individuals who were not on antiplatelet medications, normal values of TEG® and SNC® varied up to 20%. At the same time, the small dose of eptifibatide decreased platelet function (as represented by the change in test values) an average of 15% for TEG® and 28% for SNC®. Therefore, for both methods, there may be an overlap of values from either normal blood or blood treated with antiplatelet drugs. This may be more true for the TEG® MA that changes less than SNC® Platelet Function at low levels of platelet GP IIb/IIIa receptor blockade. In other words, TEG® MA may still be in a “normal” range despite the presence of moderate platelet inhibition, and in the absence of a baseline tracing it may be difficult to interpret the results. Unfortunately, there is a problem because we typically do not have a baseline TEG® or SNC® tracings performed before antiplatelet therapy was instituted. This study showed that at smaller clinical concentrations of eptifibatide (4 μg/mL), SNC® was a more sensitive monitor of inhibited platelet activation than TEG®. At normal (8 μg/mL) and large (18.5 μg/mL) clinical concentrations, both SNC® and TEG® measured decreases in platelet activation with equal sensitivity. At any used eptifibatide concentration, SNC® time-to-peak was affected more than the TEG® MA was (Fig. 3). It is equally important to note that eptifibatide in the studied concentrations never completely inhibited SNC® time-to-peak; therefore, this variable was always available for qualitative visual assessment. Also, this indicates a very specific action of eptifibatide on platelet GP IIb/IIIa receptors: clot retraction is always present, albeit prolonged. This visual qualitative assessment of the SNC® signature might be useful because the sharp, well-defined peak indicates strong clot retraction (good platelet function) whereas a poorly defined peak and its delayed onset indicate weak and slow clot retraction (poor platelet function). Therefore, even in the absence of a baseline reference the configuration of SNC® signature will be visibly altered when platelet dysfunction is present, and we believe that exactly this characteristic of SNC® signature represents an advantage over any other numerical value. In conclusion, patients treated with GP IIb/IIIa antagonists should be evaluated before surgery with platelet function tests, and adequate platelet function should not be assumed based on the drugs’ pharmacokinetic profiles. TEG® and SNC® can be used as bedside monitors for assessment of platelet activation; however, baseline values before an antiplatelet drug is given are necessary to quantify the extent of antiplatelet action. In the absence of a reference tracing (baseline), the changes in SNC® signature configuration might be more indicative of platelet dysfunction compared with the TEG® tracing. This might be especially true at the lower levels of platelet GP IIb/IIIa receptor inhibition.
https://doi.org/10.1097/00000539-200110000-00015Current Opinion in Cardiology · 2009 · 10 citations
A new generation of antiplatelet agents
AbstractPURPOSE OF REVIEW: Since the development and market entry of clopidogrel, a platelet ADP blocker, physicians have had few new antiplatelet options available to them for the treatment of acute and chronic coronary disease, specifically in the setting of acute coronary syndromes, percutaneous coronary intervention, and chronic stent management. Over the years, limitations of current antiplatelet regimens have emerged, establishing a need for novel antiplatelet drugs. This article discusses potential new targets for platelet inhibition and reviews innovative antiplatelet therapies under investigation. RECENT FINDINGS: There are five main categories of antiplatelet therapies currently undergoing clinical study, consisting of the thienopyridines (P2Y12 receptor antagonists), cyclopentyltriazolopyrimidines (P2Y12 receptor antagonists), anti-von Willebrand factor aptamers, thrombin receptor (protease-activated receptor-1) antagonists, and thromboxane receptor antagonists. Early studies of these agents are discussed. SUMMARY: Each of these new antiplatelet therapies has a unique profile that is aimed at improving clinical response with hopes of incremental efficacy and decreased complications, specifically bleeding.
https://doi.org/10.1097/hco.0b013e32832e2b44Sang thrombose vaisseaux · 2017 · 1 citations
Management of invasive procedures in patients with platelet disorders or thrombocytopenia Guidelines by French expert group on inherited platelet diseases
AbstractInherited platelet disorders (thrombocytopenia, functional defects or both) are rare and extremely heterogeneous with variable risk of spontaneous bleeding, but they are frequently diagnosed after haemorrhages following a surgical procedure or a trauma. Clinical studies focusing on these disorders are scarce due to their paucity, and thus they did not allow defining strong recommendations on the haemostasis treatment of these patients. On the basis of literature review and the experience of his members, the Reference Centre on inherited platelet disorders in France provides practical recommendations on the perioperative management, according to the type of underlying disease, to the bleeding risk associated to the invasive procedure, and to the clinical history of the patient. The indication and use of platelet concentrates and of various drugs i.e. tranexamic acid, desmopressin, recombinant factor VIIa, von Willebrand factor concentrates, and thrombopoietin receptor agonists are discussed in this text.
https://doi.org/10.1684/stv.2017.0980Blood · 2021 · 0 citations
Surgery-Associated Bleeding Risk in Patients with Platelet Function Disorders - a Cross Sectional Study with the American Thrombosis and Hemostasis Network Dataset (ATHNdataset)
AbstractAbstract Introduction: Platelet function disorders (PFDs) are a group of heterogenous bleeding disorders with varying bleeding phenotype. Intraoperative and post-operative bleeding are serious complications among patients with PFDs undergoing surgery. There are very few studies in literature that have specifically investigated surgery associated bleeding complications in PFDs. The aim of this study was to utilize a large national dataset to describe surgeries performed in patients with PFD, characterize the bleeding associated with these surgical procedures and outline the therapeutic approaches adopted. Methods: In this retrospective study, the ATHNdataset was queried for demographic data, PFD diagnosis, surgeries among patients with PFD, intraoperative and post-operative bleeding episodes and treatment. Descriptive statistics were used. The ATHNdataset captures information from patients with bleeding and clotting disorders from over 140 federally funded hemophilia and thrombosis treatment centers (HTCs) in the US. Patients authorize inclusion of their demographic and clinical information in this de-identified Health Insurance Portability and Accountability Act (HIPAA)-compliant data set. Results: From January 2010 to March 2020, the ATHNdataset captured 2767 patients with PFDs, of which 1769 (63.93%) were female and 998 (36.1%) were male, with 1393 patients between 0-18 years (50%) and 1374 (50%) adults &gt;18 years. PFDs identified include 32 patients with Bernard Soulier syndrome (1.16%), 131 patients with Glanzmann thrombasthenia (4.7%), 4 patients with Gray platelet syndrome (0.14%), 29 patients with Hermansky Pudlak syndrome (1%), 1548 patients with storage pool deficiency (55.9%), and 1023 patients diagnosed as PFD (36.9%). A total of 3252 procedures were reported between 2010 and 2020; 1271 patients (46%) patients with at least one documented procedure. Figure 1 shows common procedures among patients with PFDs. Surgery-associated bleeding episodes (includes intraoperative and post-operative bleeds) were reported with 69 procedures (2.1%), which included intraoperative bleeds reported for 18 procedures (0.5%) and post-operative bleeds reported for 51 procedures (1.6%). Of the 60 procedures in patients with Glanzmann thrombasthenia, surgery-associated bleeding episodes were reported after 9 dental procedures (41%), 1 circumcision (25%) and 11 other surgeries/procedures (18.3%). Of the 6 procedures in patients with Bernard Soulier syndrome, no intraoperative or post-operative bleeding episodes were reported. Of 1688 procedures in patients with storage pool deficiency, surgery-associated bleeding episodes were reported after 26 dental procedures (1.5%) and 62 other surgeries/procedures (3.67%). No intraoperative or post-operative mortality was reported among these patients. Of 1272 patients who underwent at least 1 procedure, 646 patients (50.7%) received some form of treatment before/during/after a procedure. Among these 646 patients, 2794 exposure days of hemostasis medications were used before/during/after procedures. Among these, 49% were prior to the procedure, 0.7 % during the procedure and 49.5% after the procedure. Treatments used are shown in figure 2. Conclusion: Our study shows that patients with PFDs have a substantial risk of bleeding associated with surgery. Identifying the risk of bleeding by type and providing appropriate pre-surgical prophylaxis can decrease rates of surgery-associated bleeding in PFDs. Figure 1 Figure 1. Disclosures Sidonio: Sanofi, Takeda, Octapharma, Bayer, Biomain, Grifols, Kedrion, Genentech. Catalyst, Guardian Therapeutics, Novo Nordisk, Hema Biologics, Uniqure.: Consultancy, Honoraria. Ahuja: Genentech: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: DSMB member ; XaTek, Inc: Patents & Royalties; Sanofi: Membership on an entity's Board of Directors or advisory committees.
https://doi.org/10.1182/blood-2021-148753Blood · 2006 · 0 citations
Haploinsufficiency of the Platelet P2Y12 Gene in a Family with Congenital Bleeding Diathesis.
AbstractAbstract Two related patients (sisters) with a congenital bleeding diathesis associated with a severe defect of the platelet ADP receptor, P2Y12, have been described (Cattaneo et al, ATVB2000;20:883). Platelets from these patients are severely defective in ADP-dependent aggregation and in Gi-coupled ADP-mediated responses, but are normal in Gq-coupled ADP-mediated responses. Molecular analysis of the P2Y12 gene of each sister revealed an identical single base pair (bp) deletion (378delC) occurring just beyond the coding sequence for the third transmembrane domain in P2Y12. The mutation results in a frame shift (Thr126 frame shift X34) and premature truncation of the protein (Conley et al, Blood2001; 98:43b). In the present study, we focused on a 13-year old son (GL) of one of the affected sisters. GL has not suffered spontaneous bleedings; his bleeding time is moderately prolonged (13 min). His platelets display a phenotype that is compatible with partial defect of the platelet P2Y12 receptor: abnormal aggregation and ATP secretion induced by several agonists, moderate deficiency of platelet-binding sites for [33P]2MeS-ADP, and partial impairment of inhibition of adenylate cyclase by ADP. PCR analysis of GL’s P2Y12 gene revealed only normal DNA sequence. Therefore, we hypothesized that the abnormal platelet phenotype of GL is due to haploinsufficiency of his P2Y12 gene, and, accordingly, his mother and aunt suffer from P2Y12 deficiency owing to haploinsufficiency and the previously described single base mutation in their remaining P2Y12 allele. In order to test our hypothesis, we analyzed genomic DNA from the family by Southern blotting and real time quantitative PCR. The Southern blot results suggested that GL had one P2Y12 allele only, which he inherited from his father. Our P2Y12 gene quantification strategy was based on SYBR Green detection and normalization using two reference genes with a normal copy number, ZNF 80 (3q13.31) and GPR15 (3q12.1). P2Y12 gene copy numbers, calculated by use of a comparative Ct method, revealed that GL, his mother, and aunt each contained a single intact P2Y12 allele. Thus, GL, his mother, and aunt suffer from haploinsuffiency in their P2Y12 alleles. However, GL’s remaining allele is normal, while his mother and aunt each have a remaining mutant allele. This explains the differences in clinical phenotypes between GL and his mother and aunt. The quantitative PCR result, supported by Southern blotting results, supports our hypothesis and illustrates the platelet phenotype associated with P2Y12 haploinsufficiency.
https://doi.org/10.1182/blood.v108.11.1100.1100ANZ Journal of Surgery · 2013 · 0 citations
Perioperative management of anticoagulation in elective surgery
AbstractSurgeons commonly need to treat patients receiving anticoagulant and anti-platelet therapy. This requires risk assessment and management to balance minimization of bleeding complications and avoidance of further ischaemic or thrombotic events. This review considers the evidence available to guide management of patients on anti-platelet and anticoagulant therapy, including some of the new classes of anti-platelets and anticoagulants which clinicians may be less familiar with.
https://doi.org/10.1111/ans.12170Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
