scholarly journals Low Neonatal Circumcision Bleeding Rate in Patients Diagnosed with Delta-Storage Pool Deficiency Later in Life

2021 ◽  
Author(s):  
Hebah Al Absi ◽  
Stein Dagmar
Keyword(s):  
Medical Records ◽  
Postoperative Bleeding ◽  
Newborn Period ◽  
Common Procedure ◽  
Intraoperative Bleeding ◽  
Bleeding Rate ◽  
Dense Granules ◽  
Storage Pool ◽  
Storage Pool Disease ◽  
Male Subjects

Introduction male circumcision is a common procedure, generally performed during the newborn period. Few reports have described circumcision in patients with bleeding disorders. Aim to determine bleeding rate after circumcision in neonatal male subjects who were diagnosed later in life with delta-storage pool disease (SPD). Methods we retrospectively reviewed the medical records of male subjects (<18 years of age) who were diagnosed with SPD later in life and were circumcised at birth without hemostatic prophylaxis due to lack of family history at that time from 2000-2020. Intraoperative/postoperative bleeding and bleeding severity were the main outcomes evaluated. Results 153 male subjects were included. Circumcision was performed at a median age of 2 days (range, 1 day-4 months). The main indication for circumcision was parental request. Median severity of granule deficiency was 2.76 dense granules/platelet (range, 1.12-3.82 DG/Plt). None of the subjects had intraoperative bleeding. Three subjects (2%) had postoperative bleeding and only one (0.65%) required ER intervention to stop bleeding. Conclusion the overall incidence of bleeding in our subjects with SPD who were undiagnosed and untreated at circumcision, is comparable to that reported for patients without a bleeding disorder.

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 Content and thrombin-induced release of acid hydrolases in gel-filtered platelets from patients with storage pool disease

Blood ◽  
1975 ◽  
Vol 46 (1) ◽  
pp. 131-142 ◽  
Author(s):  
H Holmsen ◽  
CA Setkowsky ◽  
B Lages ◽  
HJ Day ◽  
HJ Weiss ◽  
...  
Keyword(s):  
Acid Phosphatase ◽  
Normal Subjects ◽  
Acid Hydrolases ◽  
Release Reaction ◽  
Dense Granules ◽  
Storage Pool ◽  
Low Concentrations ◽  
Storage Pool Disease ◽  
Beta Galactosidase

Abstract The levels of four acid hydrolases, beta-N-acetyl glucosaminidase, beta- glucuronidase, beta-galactosidase, and acid phosphatase, and the extent of their release (release II) by thrombin was determined in platelets from nine normal subjects, nine patients with storage pool disease, and in normal platelets which had been exposed to aspirin. The levels of all four hydrolases were normal in patients with SPD. However, release of three of these hydrolases (acid phosphatase was an exception) by low concentrations of thrombin (0.015 and 0.04 U/ml) was decreased in the patients as a group, although considerable variation in the extent of release of each enzyme was noted. In contrast, aspirin failed to inhibit release II in normal platelets (except for a slight impairment in the release of beta-N-acetyl glucosaminidase), although release I (serotonin, ATP and ADP) was inhibited. All release defects could be overcome by using higher concentrations of thrombin (0.2 U/ml). The normal levels of acid hydrolases in the platelets of patients with SPD (who are deficient in the platelet dense granules) suggest that these enzymes are not normally stored in the dense granules, but rather in alpha-granules. The findings also support the conclusions of previous studies that the release reaction is impaired in SPD. This release defect appears to be different from that seen in normal platelets after exposure to aspirin.

scholarly journals Content and thrombin-induced release of acid hydrolases in gel-filtered platelets from patients with storage pool disease

Blood ◽  
1975 ◽  
Vol 46 (1) ◽  
pp. 131-142 ◽  
Author(s):  
H Holmsen ◽  
CA Setkowsky ◽  
B Lages ◽  
HJ Day ◽  
HJ Weiss ◽  
...  
Keyword(s):  
Acid Phosphatase ◽  
Normal Subjects ◽  
Acid Hydrolases ◽  
Release Reaction ◽  
Dense Granules ◽  
Storage Pool ◽  
Low Concentrations ◽  
Storage Pool Disease ◽  
Beta Galactosidase

The levels of four acid hydrolases, beta-N-acetyl glucosaminidase, beta- glucuronidase, beta-galactosidase, and acid phosphatase, and the extent of their release (release II) by thrombin was determined in platelets from nine normal subjects, nine patients with storage pool disease, and in normal platelets which had been exposed to aspirin. The levels of all four hydrolases were normal in patients with SPD. However, release of three of these hydrolases (acid phosphatase was an exception) by low concentrations of thrombin (0.015 and 0.04 U/ml) was decreased in the patients as a group, although considerable variation in the extent of release of each enzyme was noted. In contrast, aspirin failed to inhibit release II in normal platelets (except for a slight impairment in the release of beta-N-acetyl glucosaminidase), although release I (serotonin, ATP and ADP) was inhibited. All release defects could be overcome by using higher concentrations of thrombin (0.2 U/ml). The normal levels of acid hydrolases in the platelets of patients with SPD (who are deficient in the platelet dense granules) suggest that these enzymes are not normally stored in the dense granules, but rather in alpha-granules. The findings also support the conclusions of previous studies that the release reaction is impaired in SPD. This release defect appears to be different from that seen in normal platelets after exposure to aspirin.

Inherited Platelet δ-Storage Pool Disease in Dogs Causing Severe Bleeding: An Animal Model for a Specific ADP Deficiency

1995 ◽  
Vol 74 (03) ◽  
pp. 949-953 ◽  
Author(s):  
Mary Beth Callan ◽  
Joel S Bennett ◽  
Deborah K Phillips ◽  
Mark E Haskins ◽  
James E Hayden ◽  
...  
Keyword(s):  
Adenine Nucleotide ◽  
Bleeding Disorder ◽  
Serotonin Uptake ◽  
Severe Bleeding ◽  
Minor Trauma ◽  
Dense Granules ◽  
Storage Pool ◽  
Normal Number ◽  
Platelet Disorder ◽  
Storage Pool Disease

SummaryThe nature of a disorder producing moderate to severe bleeding after minor trauma, venipuncture, and surgery was studied in 3 families of American cocker spaniel dogs. In the 5 affected dogs tested, platelet counts and measurements of plasma coagulant function and von Willcbrand factor were normal. However, bleeding times were prolonged in 4 of the 5 affected dogs tested, and platelet aggregation in response to ADP and collagen was consistently abnormal in 3, suggesting that the bleeding disorder was due to abnormal platelet function. Measurements of 14C-serotonin uptake and retention by the affected platelets were normal. However, their ADP content was decreased, while their ATP content was normal, resulting in a mean ATP/ADP ratio of 8.32, compared to a mean ratio of 1.9 in normal canine platelets. Electron microscopy revealed that the number and appearance of the dense granules in the affected platelets were indistinguishable from those of normal controls. These studies suggest that this bleeding disorder results from a deficient δ-granule storage pool of ADP; given the normal serotonin uptake and retention by affected platelets and the apparently normal number of dense granules, the ADP deficiency may be the consequence of a selective defect in δ-granule ADP transport. Additional studies of this unique platelet disorder will provide an opportunity to understand the mechanism of adenine nucleotide storage in platelet δ granules.

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 The mouse pale ear pigment mutant as a possible animal model for human platelet storage pool deficiency

Blood ◽  
1981 ◽  
Vol 57 (1) ◽  
pp. 38-43 ◽  
Author(s):  
EK Novak ◽  
SW Hui ◽  
RT Swank
Keyword(s):  
Animal Model ◽  
Human Platelet ◽  
Dense Granule ◽  
Subcellular Organelles ◽  
Dense Granules ◽  
Storage Pool ◽  
Platelet Protein ◽  
Platelet Storage ◽  
Storage Pool Disease ◽  
Experimental Injury

Abstract The mouse pigment mutant pale ear, ep/ep, which has a defect in kidney lysosomal enzyme secretion, had prolonged bleeding on experimental injury. Platelet counts and platelet protein did not differ from normal. There was, however, a deficiency in the platelet dense granule contents, serotonin, ATP, and ADP. Furthermore, a marked reduction of platelet dense granules was observed by electron microscopy. The results suggest that pale ear is a useful animal model in the study of platelet storage pool disease. Studies on this mutant and other pigment mutants have established that one gene can regulate at least three subcellular organelles, including the melanosome, the lysosome, and the platelet dense granule.

scholarly journals The mouse pale ear pigment mutant as a possible animal model for human platelet storage pool deficiency

Blood ◽  
1981 ◽  
Vol 57 (1) ◽  
pp. 38-43 ◽  
Author(s):  
EK Novak ◽  
SW Hui ◽  
RT Swank
Keyword(s):  
Animal Model ◽  
Human Platelet ◽  
Dense Granule ◽  
Subcellular Organelles ◽  
Dense Granules ◽  
Storage Pool ◽  
Platelet Protein ◽  
Platelet Storage ◽  
Storage Pool Disease ◽  
Experimental Injury

The mouse pigment mutant pale ear, ep/ep, which has a defect in kidney lysosomal enzyme secretion, had prolonged bleeding on experimental injury. Platelet counts and platelet protein did not differ from normal. There was, however, a deficiency in the platelet dense granule contents, serotonin, ATP, and ADP. Furthermore, a marked reduction of platelet dense granules was observed by electron microscopy. The results suggest that pale ear is a useful animal model in the study of platelet storage pool disease. Studies on this mutant and other pigment mutants have established that one gene can regulate at least three subcellular organelles, including the melanosome, the lysosome, and the platelet dense granule.

scholarly journals Metal ion contents of gel-filtered platelets from patients with storage pool disease

Blood ◽  
1975 ◽  
Vol 46 (1) ◽  
pp. 119-130
Author(s):  
B Lages ◽  
MC Scrutton ◽  
H Holmsen ◽  
HJ Day ◽  
HJ Weiss
Keyword(s):  
Metal Ion ◽  
Gel Filtration ◽  
Direct Determination ◽  
Dense Granules ◽  
Control Subjects ◽  
Storage Pool ◽  
Suspension Medium ◽  
Ion Contents ◽  
Storage Pool Disease

Platelets from nine patients with storage pool disease (SPD) and from ten control subjects were isolated by gel filtration into a suspension medium permitting the direct determination of platelet Mg-2+, Ca-2+, and K+ levels. The total intracellular levels of ATP and ADP, as well as the incorporation patterns of 14-C-adenine into the metabolic nucleotide pool, were also determined in these platelet suspensions. The gel-filtered platelets (GFP) from SPD patients exhibited slightly lowered levels of ATP and substantially reduced amounts of ADP, in agreement with previous studies using PRP suspensions. Diminished aggregation responses to ADP, epinephrine, and to collagen in particular, similar to those observed previously in PRP, were obtained in GFP from SPD patients. However, GFP from the patients exhibited more variable aggregation responses to addition of ADP and epinephrine than did GFP from the control subjects. Increases in the extent of radioactive hypoxanthine formation, observed previously in normal platelets as a result of isolation into the suspension medium used in these studies, were significantly reduced in the GFP from SPD patients. The levels of platelet Mg-2+ and K+ determined in GFP from the patients were not significantly different from the levels of these ions in GFP from control subjects. However, substantial reductions in platelet Ca- 2+ were found in the SPD platelets. A strong correlation was obtained between this reduction in platelet Ca-2+ and the reduction in ADP in these platelets. No such correlation was apparent between the ATP and Ca-2+ deficiencies. These results suggest that a major portion of platelet Ca-2+ may be located in the dense granules and support previous hypotheses that granular ADP and/or Ca-2+ may play a role in the release reaction. The finding of normal levels of platelet Mg-2+ and K+ in SPD platelets, however, suggests that these latter ions are not located in the dense granules.

Decreased ATP, ADP and Serotonin in Young Platelets of Fawn-Hooded Rats with Storage Pool Disease

1974 ◽  
Vol 32 (02/03) ◽  
pp. 670-677 ◽  
Author(s):  
Th B. Tschopp ◽  
H. J Weiss
Keyword(s):  
Bone Marrow ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Recovery Phase ◽  
Bleeding Diathesis ◽  
Serotonin Content ◽  
Dense Granules ◽  
Storage Pool ◽  
Storage Pool Disease ◽  
Premature Release

SummaryThe bleeding diathesis and abnormalities of platelet aggregation in the Fawn-Hooded (FH) rat, as in human patients with storage pool disease, have been attributed to decreased amounts of adenine nucleotides that are ordinarily stored with serotonin in the platelet dense granules. This study was undertaken in order to establish whether the platelet defect of the FH rat was present in young platelets, newly emerged from the bone marrow, or whether the platelets acquired this abnormality (possibly by a premature release reaction) during their circulation in the blood. FH and Wistar rats were made thrombocytopenic with one injection of anti-platelet serum (APS) and platelets were harvested during the recovery phase. The ATP content of “young” FH platelets harvested two days after injection of APS, was higher than that of platelets obtained from untreated FH rats, but was still only 50% of that found in “young” Wistar platelets. In addition, the adenine nucleotide content of FH platelets did not change during treatment with aspirin. “Young” FH platelets were also deficient in serotonin and, unlike Wistar platelets, their serotonin content did not increase appreciably with the increasing platelet age. The results of the study strongly suggest that the defect in FH platelets is present in platelets newly emerged from the bone marrow and is not due to premature release of the “storage” contents during their circulation in the blood.

scholarly journals Platelet δ-Storage Pool Disease: An Update

2020 ◽  
Vol 9 (8) ◽  
pp. 2508 ◽  
Author(s):  
Arnaud Dupuis ◽  
Jean-Claude Bordet ◽  
Anita Eckly ◽  
Christian Gachet
Keyword(s):  
Light Transmission ◽  
Blood Platelets ◽  
Direct Determination ◽  
Oculocutaneous Albinism ◽  
Dense Granules ◽  
Storage Pool ◽  
Light Transmission Aggregometry ◽  
Immune Deficiencies ◽  
Storage Pool Disease

Platelet dense-granules are small organelles specific to the platelet lineage that contain small molecules (calcium, adenyl nucleotides, serotonin) and are essential for the activation of blood platelets prior to their aggregation in the event of a vascular injury. Delta-storage pool diseases (δ-SPDs) are platelet pathologies leading to hemorrhagic syndromes of variable severity and related to a qualitative (content) or quantitative (numerical) deficiency in dense-granules. These pathologies appear in a syndromic or non-syndromic form. The syndromic forms (Chediak–Higashi disease, Hermansky–Pudlak syndromes), whose causative genes are known, associate immune deficiencies and/or oculocutaneous albinism with a platelet function disorder (PFD). The non-syndromic forms correspond to an isolated PFD, but the genes responsible for the pathology are not yet known. The diagnosis of these pathologies is complex and poorly standardized. It is based on orientation tests performed by light transmission aggregometry or flow cytometry, which are supplemented by complementary tests based on the quantification of platelet dense-granules by electron microscopy using the whole platelet mount technique and the direct determination of granule contents (ADP/ATP and serotonin). The objective of this review is to present the state of our knowledge concerning platelet dense-granules and the tools available for the diagnosis of different forms of δ-SPD.

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