Effect of SSRI Use On Platelet Function Testing and Bleeding Symptoms.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3508-3508
Author(s):  
Neha Rastogi-Chawla ◽  
William Fricke ◽  
Ruth W Kouides ◽  
Peter A. Kouides
Keyword(s):  
Platelet Function ◽  
Whole Blood ◽  
Blood Platelet ◽  
Von Willebrand Disease ◽  
Closure Time ◽  
Clinically Significant ◽  
Bleeding Score ◽  
Von Willebrand ◽  
Function Testing ◽  
Blood Platelet Aggregation

Abstract Abstract 3508 Poster Board III-445 Introduction Selective serotonin reuptake inhibitors (SSRI) are antagonists of the serotonin transporter and lead to a lower concentration of serotonin in platelets. Recently there have been a number of observational studies and case reports highlighting the association of SSRI use with various hemorrhagic complications ranging from gastrointestinal hemorrhage to hemorrhagic stroke and bleeding during orthopedic surgery. On the other hand, there is not enough data on the clinical correlation between the effect of SSRIs on platelet function testing and relation to bleeding symptoms in terms of the bleeding score. Patients and Methods A retrospective, cohort study was done to assess the relationship of bleeding symptoms and laboratory assays of platelet function in patients referred for muco-cutaneous bleeding after von Willebrand disease was ruled out. The cohort was analyzed for the effect of SSRI use on platelet function and bleeding symptoms. Ninety eight patients were studied and their bleeding symptoms were assessed by the European Union Von Willebrand disease bleeding scoring system (EUVWD). Hemostatic tests including whole blood platelet aggregation (Chrono-Log™) and closure time (PFA-100™, Dade/Behring) were assessed. Results 23/98 patients reported SSRI as an active medication. Baseline characteristics were similar with respect to age, sex, race, hematocrit and platelet count among SSRI users and non-users. The majority (96%) were females. The median bleeding score was not statistically different in SSRI users vs. non-users (4 vs. 5). The bleeding symptoms were similar in the two groups with the exception of epistaxis which was more frequent in SSRI non-users. Whole blood platelet aggregation was decreased in 17.4% patients in SSRI users and 4.2% in non-users (p=0.035). Likewise, 52% patients in SSRI users and 29% in non-user had decreased release to any agonist (p=0.04). SSRI users had a higher prevalance of decreased aggregation with low dose collagen, arachidionic acid and ADP. ATP release in response to arachidionic acid and ADP was also lower in SSRI users. PFA-100 closure time with collagen-epinephrine (n=96) was prolonged in SSRI users vs. non users (144.5 vs. 126 sec, p=0.009) while closure time with collagen-ADP (n=22) was 105.5 vs. 108.5 in SSRI users vs. non users (p= 0.94). Conclusions SSRI use is associated with abnormalities in platelet function and this finding probably does warrant testing such patients with a suspected thrombocytopathy off SSRI. Their use, nonetheless, is not associated with a clinically significant difference in bleeding symptoms as assessed by the bleeding score. SSRI users with bleeding symptoms and associated abnormalities in platelet function should be investigated further for the cause of clinically significant bleeding. Bleeding score was assessed using EU-VWD scoring system. The aggregation and release studies were done with whole blood using Chronolog device in 98 patients. Results are represented as percentage abnormal. Closure times were done by PFA-100 (Dade-Behring) and results are expressed in seconds. † CEPI-collagen and epinephrine, CADP-collagen and ADP. Disclosures: No relevant conflicts of interest to declare.

Usefulness of Whole Blood Thromboelastography for the Diagnosis and Characterisation of Von Willebrand Disease.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2274-2274
Author(s):  
Catherine Lambert ◽  
Cedric R. Hermans
Keyword(s):  
Factor Viii ◽  
Whole Blood ◽  
Alpha Angle ◽  
Von Willebrand Disease ◽  
Factor Viii Deficiency ◽  
Closure Time ◽  
Significant Prolongation ◽  
Type 3 ◽  
Von Willebrand

Abstract Whole blood coagulation tests such as thromboelastography and platelet function analyser (PFA-100) are increasingly used for the investigation of haemostatic disorders. These global tests offer the advantages of a simple use and fast results. Although PFA-100 using the ADP cartridge has been validated as a useful tool to assess primary haemostatic disturbancies and has a high sensitivity to detect Von Willebrand disease (VWD), this test is neither specific for, nor predicitve of, any particular disorder of primary haemostasis. On the other hand, the potential usefulness of thromboelastography for the evaluation of VWD has so far not been investigated. The present study was undertaken in order to determine alterations of the thromboelastogram tracing in patients with VWD and evaluate its usefulness in adjunction to PFA-100 for the diagnosis and characterisation of VWD. Thromboelastographic analysis (Pentafarm RoTEM® ) was performed, as previously described by Sorensen et al. (J Thromb Haemost. 2003 Mar;1(3):551–8), over a 36 months period on all consecutive patients referred for bleeding work-up to the Haemostasis and Thrombosis Unit of the Cliniques universitaires Saint-Luc, Brussels, Belgium. Ninety-three patients fulfilling the diagnosis criteria of VWD were analysed (38 ± 18 year, 29 males-64 females). The distribution of VWD types was as follows: type 1 (59), type 2 (31) with subtypes 2A (12), 2M (17), 2B (2) and type 3 (3). The control population included 43 healthy individuals (24 females, 19 males, mean age: 38 ± 10 yr). For each patient, the following tests were performed: closure time measured by PFA-100 using the ADP cartridge, Von Willlebrand factor antigen (VWF:Ag) and activity (VWF:Ac) (collagen binding assay), factor VIII level (one-stage assay) and RoTEM®. The following parameters of the RoTEM® tracing were analysed: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), alpha angle and maximum clot lysis (ML). VWD was associated with a significant prolongation of the CT and the CFT. By contrast, the MCF, the alpha angle and the ML were not significantly different between patients and controls. By multiple regression analysis, the CT and CFT prolongation was found to be influenced only by the reduction of the factor VIII levels. The most important prolongations of the CT and the CFT were found in type 3 VWD reflecting the severe factor VIII deficiency. No significant differences of the RoTEM® parameters were found between type 1, subtypes 2A and 2M, which altogether represent the majority (94%) of the VWD population. CT and CFT prolongation was not correlated with other parameters (closure time, VWF:Ag and VWF:Ac). As expected, the closure time was determined by the level of VWF activity. In conclusion, although we observed a significant prolongation of the CT and the CFT in patients with VWD, RoTEM® appears to be of limited value for the diagnosis and characterization of VWD. Nevertheless, RoTEM® could be used as a screening tool to identify factor VIII deficiency present in a subset of patients with VWD.

The Power of a Standardized Bleeding Score in Diagnosing Pediatric Type 1 Von Willebrand Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1293-1293
Author(s):  
Paul D Marcus ◽  
Kidan G Nire ◽  
Linda Grooms ◽  
Jennifer Klima ◽  
Sarah O'Brien
Keyword(s):  
Platelet Function ◽  
Predictive Value ◽  
Care Setting ◽  
Tertiary Care ◽  
Bleeding Disorder ◽  
Von Willebrand Disease ◽  
The Mean ◽  
Bleeding Score ◽  
Von Willebrand

Abstract Abstract 1293 Poster Board I-315 INTRODUCTION Type I von Willebrand disease (VWD) is the most common inherited bleeding disorder. Repetitive testing of von Willebrand factor (VWF) levels is necessary before the diagnosis can be safely ruled out, as VWF levels fluctuate in response to genetic and environmental factors. A predictive bleeding score (BS) could reveal individuals that may benefit from repetitive testing and those for whom repetitive testing is unlikely to be of benefit. While a standardized questionnaire (the Vicenza score) was developed to evaluate hemorrhagic symptoms, it was never prospectively validated for a pediatric population in a tertiary care setting. SUBJECTS The study targeted children, ages 0 to 17 years, referred to the Hemostasis and Thrombosis Center (HTC) of Nationwide Children's Hospital for a coagulation evaluation as a result of bleeding symptoms, family history of a bleeding disorder and/or abnormal coagulation labs found during pre-operative screening. Children were excluded if they had a previously diagnosed bleeding disorder, if their caregiver did not speak English or if the child did not undergo VWF:Ag and VWF:RCo testing. METHODS Prior to the diagnosis or exclusion of a bleeding disorder in the child, caregivers consented to answer the questionnaire over the telephone. Descriptions of the Vicenza score are available online (http://www.euvwd.group.shef.ac.uk/bleed_score.htm). LABORATORY TESTING A single VWF:Ag or VWF:RCo <30 IU/dL was classified as “Definite Type 1 VWD” while levels from 30-50 IU/dL were classified as “Low VWF” (http://www.nhlbi.nih.gov/guidelines/vwd). Platelet function analysis (PFA-100) screened for platelet function defects, with some patients undergoing follow-up platelet aggregation studies and/or platelet electron microscopy. Laboratory studies from other institutions were excluded from analysis. Patients' medical records were reviewed after hematologic evaluation, and the resultant data was analyzed with STATA 10.1 (Stata Corp., College Station, TX). RESULTS A total of 104 children (52 females and 52 males) with a mean age of 7.53 years (range 1 month to 17 years) were included. At least one hemorrhagic symptom was present in 99 of the 104 children (95%) with the mean number of symptoms being 2.87 (range 0 to 7). The mean Vicenza score was 3.24 (range -1 to 13). Of the 104 children, 8 met criteria for “Definite Type 1 VWD,” 23 met criteria for “Low VWF,” 14 were diagnosed with a “Platelet Function Defect,” and 2 children had bleeding secondary to Ehlers Danlos syndrome. Children with non-bleeding disorders (e.g. Factor XII deficiency) or no laboratory evidence of a bleeding disorder were classified as “No Bleeding Disorder.” In general, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and positive diagnostic likelihood ratio of the bleeding questionnaire demonstrated poor predictive value in our patient population with the exception of high specificity in ruling out “Definite Type 1 VWD” (Table). The NPV was comparably high with both qualitative (>2 bleeding symptoms) and quantitative (BS ≥2) criteria. CONCLUSIONS The Vicenza score, previously validated in adults and in a pediatric primary care setting, appears to have limited predictive value in a pediatric tertiary care setting when evaluating patients with platelet function defects or low VWF levels. While the Vicenza score has a high NPV to exclude “Definite Type 1 VWD,” the use of simpler qualitative criteria is similarly predictive. Disclosures No relevant conflicts of interest to declare.

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.

Preservation of collagen-induced whole blood platelet aggregation by tranexamic acid therapy in primary cardiac valve surgery

Perfusion ◽  
2000 ◽  
Vol 15 (6) ◽  
pp. 507-513 ◽  
Author(s):  
Tetsuya Miyashita ◽  
Takahiko Kamibayashi ◽  
Yoshihiko Ohnishi ◽  
Junjiro Kobayashi ◽  
Masakazu Kuro
Keyword(s):  
Cardiac Surgery ◽  
Platelet Aggregation ◽  
Tranexamic Acid ◽  
Platelet Function ◽  
Whole Blood ◽  
Blood Platelet ◽  
Acid Group ◽  
Valve Surgery ◽  
Control Group ◽  
Blood Platelet Aggregation

Haemostatic disorder is one of the most common complications following cardiac surgery with cardiopulmonary bypass (CPB). Tranexamic acid reduces blood loss and allogeneic blood transfusion requirement in cardiac surgery. It had been thought that tranexamic acid inhibited fibrinolysis alone following CPB. In the present study, the haemostatic effects of tranexamic acid (20 mg/kg body weight bolus after induction of anaesthesia followed by continuous infusion at 2 mg/kg/h), including fibrinolysis and platelet function, were investigated in 22 patients (tranexamic acid group n = 12; control group n = 10) undergoing primary cardiac valve surgery. Fibrinolysis following CPB was reduced significantly in the tranexamic acid group. Following protamine administration, the reduction of collagen-induced whole blood platelet aggregation was mitigated significantly in the tranexamic acid group compared with the control group (36% reduction in the tranexamic acid group vs 58% in the control group; p = 0.011), although platelet counts did not differ between the two groups. In conclusion, tranexamic acid not only inhibits fibrinolysis directly, but also may preserve platelet function following CPB.

Evaluation of the Abnormal Platelet Function in von Willebrand Disease by the Blood Filtration Test

1996 ◽  
Vol 76 (03) ◽  
pp. 460-468 ◽  
Author(s):  
Francesco I Pareti ◽  
Marco Cattaneo ◽  
Luca Carpinelli ◽  
Maddalena L Zighetti ◽  
Caterina Bressi ◽  
...  
Keyword(s):  
Platelet Function ◽  
Relevant Information ◽  
Von Willebrand Disease ◽  
Type I ◽  
Cumulative Number ◽  
Primary Hemostasis ◽  
Normal Platelet ◽  
Filter Test ◽  
Type 3 ◽  
Von Willebrand

SummaryWe have evaluated platelet function in different subtypes of von Willebrand disease (vWD) by pushing blood through the capillarysized channels of a glass filter. Patients, including those with type IIB vWD, showed lower than normal platelet retention and increased cumulative number of blood drops passing through the filter as a function of time. In contrast, shear-induced platelet aggregation, measured in the cone-and-plate viscometer, was paradoxically increased in type IIB patients. Treatment with l-desamino-8-D-arginine vasopressin (DDAVP) tended to normalize the filter test in patients with type I-platelet normal and type I-platelet low vWD, but infusion of a factor VUI/von Willebrand factor (vWF) concentrate lacking the largest vWF multimers was without effect in type 3 patients. Experiments with specific monoclonal antibodies demonstrated that the A1 and A3 domains of vWF, as well as the glycoproteins Ibα and Ilb-IIIa on platelets, are required for platelet retention in the filter. Thus, the test may reflect vWF function with regard to both platelet adhesion and aggregation under high shear stress, and provide relevant information on mechanisms involved in primary hemostasis.

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