Platelet Delta Storage Pool Deficiency In Children : A Case Series

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4747-4747
Author(s):  
Shirley M. Abraham ◽  
Koh Boayue ◽  
Ibrahim Ahmed
Keyword(s):  
Electron Microscopy ◽  
Platelet Aggregation ◽  
Family History ◽  
Platelet Function ◽  
Dense Granule ◽  
Antifibrinolytic Agents ◽  
Presenting Symptoms ◽  
Storage Pool ◽  
Mucocutaneous Bleeding ◽  
Platelet Transfusions

Introduction Delta storage pool deficiency (δ-SPD) is a rare group of platelet disorders characterized by a reduction in the number or content of dense granules. δ-SPD causes a mild to moderate bleeding diathesis characterized mainly by mucocutaneous bleeding. A suspected case of δ-SPD can be diagnosed by the patient’s presentation, a family history and suggestive clinical bleeding or preliminary laboratory results such as a typical platelet aggregation pattern, characterized by normal aggregation with ristocetin and lack of second wave of aggregation with ADP or epinephrine. However not all patients have a typical presentation. This is a review of 6 pediatric patients with δ-SPD at our institution. Results We have 3 male and 3 female children with a confirmed diagnosis of δ-SPD. Their current age ranges from 19 months-17 years. Four of the 6 patients are Hispanic and 2 Caucasian. A positive family history of excessive bleeding was obtained in 4 patients. The youngest patient was 2 weeks at diagnosis. Epistaxis was the most common presenting symptom. The youngest patients in the group presented with subdural hematomas before the age of 2. The 17 year old presented with significant menorrhagia and anemia, requiring red cells and platelet transfusions in addition to antifibrinolytic agents and oral contraceptives. The preliminary work up in all patients included a CBC, PT, PTT and platelet function analysis (PFA).PFA was reported as abnormal in only 1 patient and was not accurate in another patient due to platelet clumping. Platelet aggregation studies and Von Willebrand’s panel were done and reported as normal in 5 patients. Platelet count ranged from 248,000- 552,000/mm3. Electron microscopy ranged from 1.69-3.59 dense granule/platelet (normal 4-6 dense granule/platelet). All of the patients were primarily managed by preventive measures and antifibrinolytic agents. Platelet transfusions have been reserved for life threatening bleeds or surgical procedures. Conclusions The presentation of this rare bleeding disorder is not limited to mucocutaneous bleeding. Presenting symptoms in the very young could be limited to an intracranial hemorrhage. Electron microscopy to diagnose this condition should be pursued despite normal platelet function and aggregation studies, especially in patients with a high index of suspicion based on their clinical presentation or family history. Disclosures: No relevant conflicts of interest to declare.

Rab38 Expression in Platelet Dense Granule Storage Pool Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2112-2112
Author(s):  
Ivana Ninkovic ◽  
James G. White ◽  
Kenyatta W. Stephens ◽  
Artur Rangel-Fihlo ◽  
Francsisca C. Wu ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Flow Cytometric Analysis ◽  
Dense Granule ◽  
Bleeding Disorder ◽  
Coding Region ◽  
Platelet Dysfunction ◽  
Granule Formation ◽  
Storage Pool ◽  
Storage Pool Disease

Abstract Platelet dense granule storage pool disease (SPD) is a bleeding disorder characterized by a lack of normal platelet dense granule function, as evidenced by decreased platelet aggregation in response to ADP, epinephrine and collagen. Platelet SPD has been studied most extensively in humans and rodents with Hermansky-Pudlak syndrome (HPS), whose phenotype is a result of defects in granule trafficking, leading to oculocutanous albinism, lysosomal storage diseases, and platelet dysfunction. We have been characterizing the fawn-hooded hypertensive (FHH) rat, which has been previously shown to have a bleeding disorder consistent with a platelet SPD and some of the features of HPS. While the platelets in the FHH rat have normal alpha granules and lysosomes, they lack dense granules as assessed by transmission electron microscopy. Platelet flow cytometric analysis of GPIb and GPIIb indicated that the FHH platelets have normal surface expression of these adhesion proteins. The FHH rat has a mutation in the Rab38 gene at the ATG start site, which is associated with the bleeding disorder. Rab38 is part of a large family of GTPases, which are involved in granule formation and secretion. Western blotting of FHH tissues revealed that there is no expression of Rab38 protein. We have used confocal immunomicroscopy to assess Rab38 in platelet formation and function. In normal rat and human platelets, there was punctate expression of Rab38. There was no Rab38 staining detected in FHH platelets. In human megakaryocytic cell lines, Dami and HEL cells, there was punctate staining of Rab38 that was mainly in the periphery of the cells, with a variable amount of perinuclear staining. There was partial colocalization of Rab38 with serotonin and VWF, and with Lamp-3, a marker of lysosomes. The degree of colocalization varied between cells. There was no clear association of Rab38 with actin and tubulin in megakaryocytes. We also examined a cohort of patients with SPD, but not HPS, for mutations in Rab38. The entire coding region and intron-exon boundaries of the Rab38 gene were sequenced in 18 patient samples collected at Emory University for the CDC Women with Bleeding Disorders and Menorrhagia Study. Ten of the patients had platelet function defects documented by standard platelet aggregation studies, and eight had no identifiable platelet function defect. No mutations in Rab38 were detected. Whereas numerous known polymorphisms were identified and confirmed, there was no association of any of them with platelet function abnormalities. In conclusion, Rab38 is expressed in platelets and megakaryocytes and may interact with other granule proteins during megakaryocyte development. Failure to express Rab38 is associated with platelet dysfunction. Further studies are needed to determine its function in megakaryocytes and platelets, and to determine whether defects in Rab38 are a cause of platelet SPD in humans.

The PFA-100 Does Not Predict Delta-Granule Platelet Storage Pool Deficiencies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2518-2518
Author(s):  
Jonathan L Sladky ◽  
Jennifer Klima ◽  
Linda Grooms ◽  
Bryce A Kerlin ◽  
Sarah H O'Brien
Keyword(s):  
Electron Microscopy ◽  
Family History ◽  
Platelet Function ◽  
Screening Test ◽  
P Value ◽  
Storage Pool ◽  
Platelet Storage ◽  
Platelet Function Disorders ◽  
History Of ◽  
The Relationship

Abstract Abstract 2518 Background: Although delta-granule platelet storage pool deficiencies (δ-PSPDs) are common disorders of platelet function, they are relatively poorly studied and described. One unknown is the relationship between δ-PSPDs and the PFA-100, a screening test originally developed for von Willebrand's disease but now widely used as a general screening test for coagulopathies. Previous studies have suggested that the PFA-100 is less effective in detecting mild platelet function disorders (which include δ-PSPDs) than more severe platelet function disorders. These studies, however, were limited by small numbers of patients with a variety of different platelet function defects. We examined PFA-100 results in a larger pediatric patient population diagnosed specifically with δ-PSPD, and determined the relationship between PFA-100 results and platelet electron microscopy (the standard for diagnosis of δ-PSPDs). Methods: This study is a retrospective medical record review of patients 0 to 18 years of age diagnosed with δ-PSPD at Nationwide Children's Hospital between January 1, 2008 and July 31, 2010. We defined δ-PSPD as patients with an average of fewer than 3.68 delta granules per platelet. We obtained demographic data including age, sex, and family history of bleeding. Lab data was also extracted, including PFA-100 and platelet electron microscopy. We determined the percentage of δ-PSPD patients with an abnormal PFA-100. To examine the correlation between the PFA-100 results and the average number of granules per platelet we used Spearman's Rho as our non-parametric measure of dependence. Results: A total of 88 patients diagnosed with δ-PSPD were included in this study. Of our patient population, 35% were male, and 61% had a first degree family history of easy bruising or bleeding, while only 15% had a family history that was positive specifically for platelet function disorders. The most common symptoms on presentation were easy bruising (56%), epistaxis (39%), oral cavity bleeding (35%) and menorrhagia (30%). Eighty-one of these patients underwent PFA-100 testing, of which 41% had an abnormal CEPI value, 17% had an abnormal CADP value, and 14% had abnormal results for both PFA cartridges. We found no statistical correlation between CEPI closure time and the average number of granules per platelet (rho = 0.0315, p value = 0.7798), nor between CADP closure time and the average number of granules (rho = -0.0095, p value = 0.9328)(Figure). Additionally, the number of bleeding symptoms in each patient was not statistically correlated with CEPI closure times, CADP closure times or platelet EM. Discussion: The PFA-100, which is widely used as a screening test for suspected bleeding disorders, was abnormal in fewer than half of pediatric patients diagnosed with δ-PSPD. We found that PFA-100 results did not correlate with presence or severity of delta-granule platelet storage pool deficiencies as determined by platelet electron microscopy. When evaluating patients with suspected bleeding disorders, PFA-100 testing alone cannot be used to rule out the presence of a δ-PSPD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immature dense granules in platelets from mice with platelet storage pool disease

Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1300-1306 ◽  
Author(s):  
M Reddington ◽  
EK Novak ◽  
E Hurley ◽  
C Medda ◽  
MP McGarry ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Dense Granule ◽  
Mutant Mice ◽  
Normal Numbers ◽  
Group Of Seven ◽  
Dense Granules ◽  
Storage Pool ◽  
Platelet Storage ◽  
Transmission Electron ◽  
Storage Pool Disease

Mepacrine uptake into platelets and bone marrow megakaryocytes was analyzed to further characterize the dense granule defects in a group of seven mouse pigment mutants that have characteristics of platelet storage pool disease (SPD). In contrast to our previous studies using electron microscopy, this method revealed that all mutants had normal numbers of dense granules. However, total mepacrine uptake in all mutant platelets was significantly diminished to less than 50% of normal uptake. Also, the flashing phenomenon observed when normal dense granules are irradiated with ultraviolet light was either greatly diminished or absent when platelets of individual mutants were similarly irradiated. Therefore the principal defect in the mutant platelets is an inability to accumulate dense granule contents rather than an absence of the granules. Mepacrine uptake into megakaryocytes was indistinguishable in normal and mutant mice. This indicates the mutant dense granule defects appear either very late in megakaryocyte development or early in platelet formation in correlation with development of the mature dense granule. By standard transmission electron microscopy we have not been able to detect gross structural or subcellular abnormalities in either platelets or megakaryocytes of mutant mice. It appears all seven mutants produce immature or functionally abnormal dense granules.

scholarly journals Platelet Function Analyzer-100 Shows Poor Predictive Value for Children with Low VWF and Mild Platelet Function Defects

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 28-29
Author(s):  
Megan C. Brown ◽  
Gary Woods
Keyword(s):  
Electron Microscopy ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Chart Review ◽  
Bleeding Disorders ◽  
Platelet Function Testing ◽  
Test Characteristics ◽  
Von Willebrand ◽  
Function Testing

Background: The Platelet Function Analyser (PFA)-100 (Siemens) has proven to be a useful screening tool for primary hemostasis. Studies have demonstrated a pooled sensitivity around 90% for all individuals with Von Willebrand Disease (VWD), however the sensitivity for Type 1 is notably poorer than types 2 and 3. Our institution utilizes the PFA-100 as part of a panel of laboratory studies called the "bleeding screen"; this panel is often used as first line screening for inherited bleeding disorders across the hospital system. As the relative frequency of Type 1 VWD and low VWF (defined as Von Willebrand factor (VWF) levels 30-50%) greatly exceed the frequency of individuals with Type 2 and Type 3, when used as a general screen, the PFA-100 likely has reduced sensitivity than documented in the literature. Methods: To evaluate the utility of the PFA-100 as a screening test for VWD and platelet function defects, we retrospectively examined the ordering practices of PFA-100 in relation to the Von Willebrand panel (VWF:antigen, VWF:ristocetin cofactor, Factor VIII), platelet aggregation studies and platelet electron microscopy. We compared results of the testing with diagnostic codes to characterize the test characteristics of the PFA-100 for the diagnosis of VWD or platelet function defects in a pediatric population. We included all patients tested with the PFA-100 from 2017 to 2018 at any Children's Healthcare of Atlanta facility. Exclusion criteria include age under 30 months (reference range established for those over 30 months), hematocrit <35% or platelets <150,000/uL at time of testing due to impact on PFA-100 results. Demographics, laboratory results, bleeding symptoms and diagnoses were collected via chart review. Bleeding disorders were determined by ICD-9 and ICD-10 codes and confirmed via chart review. Descriptive statistics were calculated with frequency and median (interquartile range); comparative statistics calculated with t-tests, chi-square, Fisher's Exact, Mann-Whitney and Spearman rank tests. Test characteristics for PFA-100 and VWD were determined by correlation between PFA-100 and VWD studies sent concurrently; a ristocetin co-factor <50% was considered positive for VWD in the comparative analysis. Test characteristics determined for platelet function testing were dependent on results of platelet aggregation studies and/or platelet electron microscopy. Results: There were 609 children who met inclusion criteria. Median age was 12.2 years (7.3-15.6). The majority were female (62.4%), white (58.5%) and non-Hispanic (77.0%). The most common reason for testing was epistaxis (28.1%), followed by heavy menstrual bleeding (24.8%) and bruising (18.4%). Almost 30% had no bleeding symptoms documented. The majority of individuals also had a VWD profile sent (91.5%), with 418 having the PFA-100 and VWD Profile sent concurrently. The majority of PFA-100 tests were normal (70.6%). Only 91 (14.9%) had additional platelet evaluation with platelet aggregation studies or electron microscopy. Overall, 170 individuals (27.9%) were found to have a bleeding disorder. VWD was diagnosed in 146 individuals (24.0%), a platelet function defect 14 (2.3%) and 11 individuals had other diagnoses including Factor VII deficiency, Hemophilia A and Hemophilia B. The sensitivity of the PFA-100 for VWD was 60.4% (95%CI 46.9-73.6%) and the sensitivity was 60.0% (26.2-87.4%) for platelet function defects. For those with an abnormal PFA, the results of a VWD profile did not determine the likelihood of a provider sending additional testing with platelet aggregation studies or platelet microscopy. Of the 104 individuals with an abnormal PFA and normal VWD studies, only 31 had platelet aggregation testing. There were no differences in demographics or reported symptoms between the two groups. With normal VWD studies, individuals with an abnormal PFA were about 3 times more likely to have platelet aggregation studies sent (p<0.0001). Conclusion: The PFA-100 has poor sensitivity for VWD and mild platelet function defects in pediatric patients. Most individuals screened with a PFA-100 also had a complete VWD panel sent concurrently indicating that this is used as a screen for platelet function defects in our hospital. Given the poor sensitivity for platelet function defects, advanced platelet function testing should be sent based on clinical concern regardless of PFA-100 results when VWD testing is normal. Disclosures Brown: National Hemophilia Foundation, Takeda Clinical Fellowship: Research Funding. Woods:Takeda: Membership on an entity's Board of Directors or advisory committees.

scholarly journals The response of platelets to epinephrine in storage pool deficiency-- evidence pertaining to the role of adenosine diphosphate in mediating primary and secondary aggregation

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1717-1725 ◽  
Author(s):  
HJ Weiss ◽  
B Lages
Keyword(s):  
Platelet Aggregation ◽  
Receptor Agonist ◽  
Adenosine Diphosphate ◽  
Normal Subjects ◽  
Dense Granule ◽  
Binding Studies ◽  
Dense Granules ◽  
Storage Pool ◽  
Receptor Sites

Abstract Aggregation responses and thromboxane (Tx) formation in ten patients with storage pool deficiency (SPD) specific to the dense granules (delta-SPD) were studied to assess further the role of dense granule adenosine diphosphate (ADP) in mediating platelet aggregation by epinephrine. The ability of epinephrine to elicit secondary aggregation (SA) responses was highly variable in delta-SPD when tested at 5 mumol/L epinephrine, but was consistently abnormal when tested over a range of concentrations. The occurrence of SA in both delta-SPD patients and normal subjects was correlated with the magnitude of the rate of primary aggregation (PA). This PA rate was normal, on average, for the entire patient group but was greater in patients with more consistent SA responses. The PA findings were related to the Kd value obtained in binding studies with 3H-yohimbine, but not with the number of alpha 2-receptor sites. Studies on Tx production (assessed by radioimmunoassay of TxB2) showed that the ability to synthesize Tx from arachidonate was not impaired in delta-SPD, and that there was an absolute positive correlation between epinephrine-induced SA and Tx production. Aggregation in delta-SPD platelets in response to the Tx receptor agonist U44069 was consistently decreased, but could be corrected by addition of ADP. The results of the study suggest that dense granule-derived ADP is not required for PA by epinephrine, but mediates SA as a synergistic agonist with TxA2. This role of ADP in SA may be elucidated more precisely by further studies on platelet activation processes in delta-SPD.

Abnormalities of Epinephrine-Induced Platelet Aggregation and Adenine Nucleotides in Myeloproliferative Disorders

1984 ◽  
Vol 52 (03) ◽  
pp. 292-296 ◽  
Author(s):  
Koichiro Yamamoto ◽  
Eisuke Sekiguchi ◽  
Osamu Takatani
Keyword(s):  
Platelet Aggregation ◽  
Polycythemia Vera ◽  
Chronic Myelogenous Leukemia ◽  
Platelet Function ◽  
Adenine Nucleotides ◽  
Myeloproliferative Disorders ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
Storage Pool ◽  
Percentage Release

SummaryPlatelet aggregation was studied in 18 patients with myeloproliferative disorders, including 14 patients with chronic myelogenous leukemia, 2 with polycythemia vera, 1 with myelofibrosis and 1 with thrombocythemia. Fourteen patients (78%) were abnormal in epinephrine-induced platelet aggregation, while 3 (17%) and 4 (22%) cases showed impaired ADP or collagen induced platelet aggregation, respectively. A significant decrease of total ADP content in resting unstimulated platelets and of the amount released to the medium after aggregation was found in all six patients who were evaluated. ATP and AMP in resting platelets tended to be slightly higher in patients compared with the control group. Released ATP was also significantly less, and the percentage release of ADP and ATP was significantly decreased in patients. A storage pool deficiency of adenine nucleotides was considered to be responsible for abnormal platelet function in patients with myeloproliferative disorders.

scholarly journals Immature dense granules in platelets from mice with platelet storage pool disease

Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1300-1306 ◽  
Author(s):  
M Reddington ◽  
EK Novak ◽  
E Hurley ◽  
C Medda ◽  
MP McGarry ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Dense Granule ◽  
Mutant Mice ◽  
Normal Numbers ◽  
Group Of Seven ◽  
Dense Granules ◽  
Storage Pool ◽  
Platelet Storage ◽  
Transmission Electron ◽  
Storage Pool Disease

Abstract Mepacrine uptake into platelets and bone marrow megakaryocytes was analyzed to further characterize the dense granule defects in a group of seven mouse pigment mutants that have characteristics of platelet storage pool disease (SPD). In contrast to our previous studies using electron microscopy, this method revealed that all mutants had normal numbers of dense granules. However, total mepacrine uptake in all mutant platelets was significantly diminished to less than 50% of normal uptake. Also, the flashing phenomenon observed when normal dense granules are irradiated with ultraviolet light was either greatly diminished or absent when platelets of individual mutants were similarly irradiated. Therefore the principal defect in the mutant platelets is an inability to accumulate dense granule contents rather than an absence of the granules. Mepacrine uptake into megakaryocytes was indistinguishable in normal and mutant mice. This indicates the mutant dense granule defects appear either very late in megakaryocyte development or early in platelet formation in correlation with development of the mature dense granule. By standard transmission electron microscopy we have not been able to detect gross structural or subcellular abnormalities in either platelets or megakaryocytes of mutant mice. It appears all seven mutants produce immature or functionally abnormal dense granules.

scholarly journals Storage pool deficiency in cattle with the Chediak-Higashi syndrome results from an absence of dense granule precursors in their megakaryocytes

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1726-1734 ◽  
Author(s):  
M Menard ◽  
KM Meyers
Keyword(s):  
Electron Microscopy ◽  
Bone Marrow ◽  
Transmission Electron Microscopy ◽  
Membrane System ◽  
Dense Granule ◽  
Virtual Absence ◽  
Dense Granules ◽  
Storage Pool ◽  
Transmission Electron ◽  
Chediak Higashi Syndrome

Abstract Platelets from cattle with the Chediak-Higashi syndrome (CHS) have a storage pool deficiency and virtual absence of platelet dense granules. Megakaryocytes (MKs) from five control (n = 135) and five CHS (n = 133) cattle were evaluated using standard transmission electron microscopy. Osmiophilic dense granules were not observed in control or CHS MKs. In MKs from normal cattle, clear vesicles of 200- to 650-nm diameter bounded by a sharp membrane were observed. They were easily differentiated from the demarcation membrane system, endoplasmic reticulum, and alpha granules. The clear vesicles were virtually absent in MKs from CHS cattle at all stages of maturation. MKs in bone marrow samples from two control (n = 91) and two CHS (n = 61) cattle that had been processed for the uranaffin reaction were also evaluated. The clear vesicles were replaced by uranaffin-positive granules in MKs from control cattle, but positive uranaffin granules were not observed in CHS MKs. These findings indicate that the platelet dense granule storage pool deficiency in CHS cattle results from an anatomic absence of dense granule precursors in maturing and mature CHS MKs.

Diastolic but Not Systolic Heart Failure Is Associated with Multiple Abnormalities on Platelet Aggregation Testing

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1079-1079
Author(s):  
Dharmesh Gopalakrishnan ◽  
Heesun J Rogers ◽  
Paul Elson ◽  
Keith R. McCrae
Keyword(s):  
Heart Failure ◽  
Platelet Aggregation ◽  
Aortic Stenosis ◽  
Platelet Function ◽  
Severe Aortic Stenosis ◽  
Diastolic Heart Failure ◽  
Systolic Heart Failure ◽  
Dense Granule ◽  
Advisory Committees ◽  
Granule Release

Abstract Introduction: The effect(s) of co-morbid medical conditions on platelet function is poorly understood. In this retrospective EMR-based study, we analyzed the influence of various diseases on in vitro measures of platelet function - platelet function analyzer-100 (PFA-100) closure times, platelet aggregation (using light transmission aggregometry (LTA)), platelet dense granule release (using lumi-aggregometry), and platelet flow-cytometry for surface glycoproteins. We also examined their influence on VWF testing. Methods: Four hundred ninety seven patients who had platelet aggregation testing performed using LTA between August 2008 and August 2013 were included in our study. Co-morbidities at the time of testing were recorded. Propensity score matching for each individual disease was used to adjust for relevant covariates. We used a 1:1 nearest neighbor match without replacement, with caliper width set to 0.2 times the standard deviation of the logit of the propensity score. Following matching, Fisher's exact test or Chi square test was used as appropriate to assess the association between categorical variables, while the Mann-Whitney test was used to test the association between categorical and continuous measures. Pearson co-efficient was used to assess the correlation between continuous variables. P < 0.05 was considered significant. Results: 1) Congestive heart failure (n = 44) was associated with impaired platelet aggregation in the presence of arachidonic acid (p = 0.001) and collagen (p = 0.009), as well as impaired dense granule release in the presence of collagen (p = 0.002) and epinephrine (0.012). It was also associated with abnormal aggregation (p = 0.024) and release (p = 0.028) in the presence of ≥ 2 agonists in the respective panels. Diastolic heart failure (n = 25) was found to be associated with impaired aggregation in the presence of ADP (p = 0.007), collagen (p = 0.001), or arachidonic acid (p = 0.007), and to ≥ 2 agonists in the aggregation panel (p = 0.008). Systolic heart failure (n = 26) was not associated with abnormalities in aggregation or release. 2) Severe aortic stenosis (n = 17) was associated with prolonged collagen/ADP (p = 0.003) and collagen/epinephrine (p <0.001) closure times with PFA-100, but not with any abnormalities in the platelet aggregation/release panels. Severe aortic stenosis was associated with a decreased ristocetin cofactor/VWF antigen ratio (0.66±0.17 vs. 0.90±0.37; p = 0.030), but not with any other abnormalities in VWF testing. 3) Diabetes mellitus (n = 65) was associated with impaired platelet aggregation in the presence of collagen (p = 0.034) and impaired platelet release in the presence of epinephrine (p = 0.027). However, glycated hemoglobin level (HbA1C) was not found to correlate with impairments in either aggregation or release in the presence of any agonist. Hypothyroidism (n = 71) or vitamin D deficiency (n = 39) were not found to be associated with abnormalities in any of the platelet function assays. Finally, biochemical parameters reflecting hepatic or renal function did not correlate with any abnormalities in platelet function assays. However, the total number of co-morbidities in any patient correlated with the number of abnormalities in the platelet aggregation as well as release panels. Conclusion: Diastolic heart failure was associated with impaired platelet aggregation in the presence of multiple agonists. Though the mechanism remains unclear, we postulate that this could be related to shear stress to which the platelets are subjected in the non-compliant ventricles. Severe aortic stenosis was associated with prolonged collagen/ADP as well as collagen/epinephrine PFA-100 closure times and with lower ristocetin co-factor/VW antigen ratio suggesting functional impairment of VWF. Though diabetes mellitus was associated with impaired platelet aggregation in the presence of collagen and impaired dense granule release in the presence of epinephrine, no correlation was found between these abnormalities and HbA1C levels, making the significance of the association unclear. Disclosures McCrae: Syntimmune: Consultancy; Momenta: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees; Halozyme: Membership on an entity's Board of Directors or advisory committees.

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