Acquired Storage Pool Deficiency in Platelets during DIC

1975 ◽  
Author(s):  
F. Pareti ◽  
A. Capitanio ◽  
V. Chantarangkul ◽  
P. M. Mannucci
Keyword(s):  
Adenine Nucleotides ◽  
Bleeding Tendency ◽  
Laboratory Findings ◽  
Prolonged Incubation ◽  
Acute Bleeding ◽  
Storage Pool ◽  
Storage Granules ◽  
Metabolic Pool ◽  
Normal Controls

During DIC, circulating platelets are exposed to thrombin and other aggregating agents causing the release reaction. It is conceivable that “stimulated” platelets may have altered functions which contribute, with the decrease in number, to the bleeding tendency of these patients. Platelet aggregation, adenine nucleotides (AN) content and release, serotonin (5 HT) content, uptake and metabolism have been investigated in a patient with an acute bleeding tendency associated to laboratory findings suggesting the occurence of DIC. Secondary aggregation to ADP and adrenaline was absent; collagen aggregation was also defective. Release of AN induced by different collagen concentrations was much lower than in the normal controls. Levels of AN were reduced (mainly ADP) ; ATP/ADP ratio was higher than in control platelets. Since AN of the metabolic pool were normal, the deficiency is due to lack of AN of the storage pool. 5 HT content and the ability to take up the exogenous amine was also reduced in the patient’ platelets. Their prolonged incubation with 14 C 5 HT resulted in a progressive loss of radioactivity in plasma, while normal platelets, in the same conditions, stored the amine throughout the incubation period. This abnormal behaviour has been observed in platelets of patients affected by congenital storage pool deficiency (SPD) and is caused by abnormal platelet metabolism of the amine. The abnormalities observed in this patient with DIC are stikingly similar to those present in congenital SPD and are likely to be produced by in vivo exposure to aggregating agents followed by release of storage granules.

scholarly journals Transfer of adenine nucleotides between the releasable and nonreleasable compartments of rabbit blood platelets.

1975 ◽  
Vol 67 (1) ◽  
pp. 61-71 ◽  
Author(s):  
H J Reimers ◽  
J F Mustard ◽  
M A Packham
Keyword(s):  
Inorganic Phosphate ◽  
Adenine Nucleotides ◽  
Blood Platelets ◽  
Specific Radioactivity ◽  
Releasable Pool ◽  
Rabbit Platelets ◽  
Storage Granules ◽  
Metabolic Pool

The metabolic pool of adenine nucleotides in platelets can be labeled by incubating platelets for 1 h in vitro with [14C]adenosine or [32P]orthophosphate. When these platelets are treated with thrombin, the adenine nucleotides released are not labeled. Because of this, Holmsen's suggestion of a metabolically inert pool of granule nucleotides has been generally accepted. We have found that upon incubation of labeled rabbit platelets for longer times (up to 6 h) in vitro, or upon reinjection and reharvesting at times up to 66 h, the releasable pool of adenine nucleotides becomes labeled. Because the rates of 32p and 14C incorporation into this releasable pool are similar, it seems likely that these labels enter the granules as ATP. Equilibrium between the metabolic and granule pools is complete by 18 h. When rabbit platelets are labeled in vivo by intravenous injection of [32P]orthophosphate, peak labeling occurs between 60 and 70 h; this corresponds to their maturation time. The platelets probably incorporate 32P during their production in the megakaryocytes. The specific radioactivity of the adenine nucleotides in the releasable (granule) pool of these platelets is the same as the specific radioactivity in the nonreleasable (metabolic) pool. Since inorganic phosphate in platelets (and undoubtedly in the megakaryocytes) exchanges with inorganic phosphate in plasma, and since the radioactivity of the latter decreases rapidly, the adenine nucleotides in the two pools must exchange to maintain the same specific radioactivity. Transfer of adenine nucleotides into storage granules may represent a general phenomenon because it has been observed in the chromaffin cells of the adrenal medulla also.

scholarly journals Platelet Alpha-Storage Pool Defect Combined with Non-Classic Delta-Storage Pool Deficiency - with a Severe Bleeding Tendency

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2557-2557
Author(s):  
Frauke Bergmann ◽  
Kathrin Schwierczek ◽  
Stefanie Sollfrank ◽  
Andreas Czwalinna ◽  
Joseph Erkel ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Adenine Nucleotides ◽  
Molecular Genetic ◽  
Surface Expression ◽  
Bleeding Disorder ◽  
Severe Bleeding ◽  
Bleeding Tendency ◽  
Normal Range ◽  
Storage Pool

Abstract Aims :We report about a 35 year old male patient with severe and frequent epistaxis and hematoma since infancy. He presented with mild thrombocytopenia and increased mean platelet volume. Von Willebrand's disease and subhemophilia had been excluded. Previously, he was diagnosed with immune thrombocytopenic purpura. He never underwent elective surgery. His parents were asymptomatic. However, his young daughter also suffers from severe bleeding symptoms and was referred to our coagulation outpatient clinic to investigate the bleeding disorder. Methods:Platelet function was assessed by light transmission-, lumi-aggregometry and flow cytometry. Lysates of gel-filtered platelets were analyzed for total granule P-selectin, CD63 and von Willebrand factor (VWF) content by Western blotting and for serotonin levels by ELISA, respectively. Molecular genetic analysis was performed using whole exome sequencing and pyrosequencing. Results: Platelet aggregation in response to ADP was not inducible. Platelet aggregation in response to epinephrine resulted in monophasic curves. Platelet aggregation in response to TRAP-6 or collagen was inducible but impaired and accompanied by disaggregation. In contrast, arachidonic acid- and U46619-induced platelet aggregation as well as ristocetin-induced platelet agglutination/aggregation was within the normal range. Also platelet surface expression of GPIIb/IIIa, GPIb/V/IX, GPVI and CD29 was normal. Activation of GPIIb/IIIa in response to ADP, convulxin or TRAP-6 was inducible but diminished and in response to epinephrine or arachidonic acid normal. P-selectin (alpha-granule marker) and CD63 (dense body/lysosome marker) surface expression was not inducible by thrombin or convulxin and markedly reduced in response to TRAP-6 and arachidonic acid. Immunoblot analysis of isolated platelets demonstrated pronouncedly decreased content of total P-selectin, VWF and CD63. Fluorescent staining of adenine nucleotides by mepacrine in patient's platelet dense bodies and secretion of ATP induced by arachidonic acid (normal aggregation) were absent. However, patient's platelet serotonin levels were within the normal range. The molecular genetic diagnostic showed an undescribed mutation in the GATA1 gene (c.886A>C hemizygot, p.T296P). The bioinformatic check confirmed a pathogenetic importance of this mutation located in the domain I of the C-terminal zinc finger. Conclusion: We describe the first case of a combined platelet alpha- and partial delta-storage pool disorder where the dense granules lack adenine nucleotides but contain normal levels of serotonin - causing a severe bleeding disorder. Disclosures No relevant conflicts of interest to declare.

scholarly journals Role of P-Selectin Cytoplasmic Domain in Granular Targeting In Vivo and in Early Inflammatory Responses

1998 ◽  
Vol 143 (4) ◽  
pp. 1129-1141 ◽  
Author(s):  
Daqing W. Hartwell ◽  
Tanya N. Mayadas ◽  
Gaëtan Berger ◽  
Paul S. Frenette ◽  
Helen Rayburn ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasma Membrane ◽  
Inflammatory Responses ◽  
Cytoplasmic Domain ◽  
Leukocyte Rolling ◽  
Storage Pool ◽  
Storage Granules

P-selectin is an adhesion receptor for leukocytes expressed on activated platelets and endothelial cells. The cytoplasmic domain of P-selectin was shown in vitro to contain signals required for both the sorting of this protein into storage granules and its internalization from the plasma membrane. To evaluate in vivo the role of the regulated secretion of P-selectin, we have generated a mouse that expresses P-selectin lacking the cytoplasmic domain (ΔCT mice). The deletion did not affect the sorting of P-selectin into α-granules of platelets but severely compromised the storage of P-selectin in endothelial cells. Unstored P-selectin was proteolytically shed from the plasma membrane, resulting in increased levels of soluble P-selectin in the plasma. The ΔCT–P-selectin appeared capable of mediating cell adhesion as it supported leukocyte rolling in the mutant mice. However, a secretagogue failed to upregulate leukocyte rolling in the ΔCT mice, indicating an absence of a releasable storage pool of P-selectin in the endothelium. Furthermore, the neutrophil influx into the inflamed peritoneum was only 30% of the wild-type level 2 h after stimulation. Our results suggest that different sorting mechanisms for P-selectin are used in platelets and endothelial cells and that the storage pool of P-selectin in endothelial cells is functionally important during early stages of inflammation.

scholarly journals Effect of ascorbate on abnormal neutrophil, platelet and lymphocytic function in a patient with the Chediak-Higashi syndrome

Blood ◽  
1981 ◽  
Vol 57 (5) ◽  
pp. 856-865 ◽  
Author(s):  
RS Weening ◽  
EP Schoorel ◽  
D Roos ◽  
ML van Schaik ◽  
AA Voetman ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Bactericidal Activity ◽  
Chemotactic Response ◽  
Bleeding Tendency ◽  
Intracellular Killing ◽  
Storage Pool ◽  
Chediak Higashi Syndrome

A diminished chemotactic response was observed with the neutrophils of a patient with the Chediak-Higashi syndrome, who was not in the accelerated phase of the disease. An abnormally low release of myeloperoxidase from these cells during phagocytosis was also noted; this resulted in a decreased iodination capacity and probably also caused the defect in the intracellular killing of bacteria by the neutrophils. The level of cyclic AMP in these cells was elevated, but decreased after treatment with ascorbate either in vitro or in vivo. During ascorbate therapy, the bactericidal activity of the neutrophils normalized, whereas the chemotactic response remained low. Nevertheless, the patient had significantly less infections during ascorbate therapy. The bleeding tendency, due to a storage-pool disorder of the Chediak-Higashi platelets, was unaffected by treatment with ascorbate. The patient's lymphocytes did not display any activity in antibody-dependent lymphocytotoxicity. This defect was not affected by treatment with ascorbate either.

Effect of ascorbate on abnormal neutrophil, platelet and lymphocytic function in a patient with the Chediak-Higashi syndrome

Blood ◽  
1981 ◽  
Vol 57 (5) ◽  
pp. 856-865 ◽  
Author(s):  
RS Weening ◽  
EP Schoorel ◽  
D Roos ◽  
ML van Schaik ◽  
AA Voetman ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Bactericidal Activity ◽  
Chemotactic Response ◽  
Bleeding Tendency ◽  
Intracellular Killing ◽  
Storage Pool ◽  
Chediak Higashi Syndrome

Abstract A diminished chemotactic response was observed with the neutrophils of a patient with the Chediak-Higashi syndrome, who was not in the accelerated phase of the disease. An abnormally low release of myeloperoxidase from these cells during phagocytosis was also noted; this resulted in a decreased iodination capacity and probably also caused the defect in the intracellular killing of bacteria by the neutrophils. The level of cyclic AMP in these cells was elevated, but decreased after treatment with ascorbate either in vitro or in vivo. During ascorbate therapy, the bactericidal activity of the neutrophils normalized, whereas the chemotactic response remained low. Nevertheless, the patient had significantly less infections during ascorbate therapy. The bleeding tendency, due to a storage-pool disorder of the Chediak-Higashi platelets, was unaffected by treatment with ascorbate. The patient's lymphocytes did not display any activity in antibody-dependent lymphocytotoxicity. This defect was not affected by treatment with ascorbate either.

scholarly journals Evidence for the rapid direct control both in vivo and in vitro of the efficiency of oxidative phosphorylation by 3,5,3′-tri-iodo-l-thyronine in rats

1979 ◽  
Vol 184 (3) ◽  
pp. 527-538 ◽  
Author(s):  
R Palacios-Romero ◽  
J Mowbray
Keyword(s):  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Respiratory Control ◽  
Focused Attention ◽  
Isolated Mitochondria ◽  
Short Times ◽  
Normal Controls

1. Examination of the distribution of L-tri-iodothyronine among rat liver tissue fractions after its intravenous injection into thyroidectomized rats focused attention on mitochondria at very short times after administration. By 15 min this fraction contained 18.5% of the tissue pool; however, the content had decreased sharply by 60 min and even further over the next 3 h. By contrast, the content in all other fractions was constant or increased over 4 h. About 60% of tissue hormone was bound to soluble protein. 2. Mitochondria isolated from thyroidectomized rats showed P/O ratios that were about 50% of those found in normal controls, with both succinate and pyruvate plus malate as substrates. There was no evidence of uncoupling; the respiratory-control ratio was about 6. 3. Mitochondria isolated 15 min after injection of tri-iodothyronine into thyroidectomized rats showed P/O ratios and respiratory-control ratios that were indistinguishable from those obtained in mitochondria from euthyroid animals. The oxidation rate was, however, not restored. 4. Incubation of homogenates of livers taken from thyroidectomized animals injected with L-tri-iodothyronine before isolation of the mitochondria restored the P/O ratio to normal; by contrast, direct addition of hormone to isolated mitochondria had no effect. The role of extramitochondrial factors in rapid tri-iodothyronine action is discussed. 5. Possible mechanisms by which tri-iodothyronine might rapidly alter phosphorylation efficiency are considered: it is concluded that control of adenine nucleotide translocase is unlikely to be involved. 6. The amounts of adenine nucleotides in liver were measured both after thyroidectomy and 15 min after intravenous tri-iodo-thyronine administration to thyroidectomized animals. The concentrations found are consistent with a decreased phosphorylation efficiency in thyroidectomized animals. Tri-iodothyronine injection resulted in very significant changes in the amounts of ATP, ADP and AMP, and in the [ATP]/[ADP] ratio, consonant with those expected from an increased efficiency of ADP phosphorylation. This suggests that the changes seen in isolated mitochondria may indeed reflect a rapid response of liver in vivo to tri-iodo-thyronine.

Von-Willebrand-Syndrom Typ 1 und Schwangerschaft

2011 ◽  
Vol 31 (S 01) ◽  
pp. S11-S13 ◽  
Author(s):  
J. Oppermann ◽  
A. Siegemund ◽  
R. Schobess ◽  
U. Scholz
Keyword(s):  
Clinical Presentation ◽  
Bleeding Disorder ◽  
Bleeding Tendency ◽  
Laboratory Findings ◽  
Mucous Membranes ◽  
Von Willebrand

SummaryThe von Willebrand-Jürgens syndrome (VWJS) type 1 is a common hereditary bleeding disorder with a bleeding tendency located especially in the mucous membranes. Women suffering from VWJS type 1 show menorrhagia and prolonged postoperative bleedings. During pregnancy the clinical presentation varies by the increase of the von Willebrand factors.In this article the laboratory findings and the clinical presentation of patients with VWJS during pregnancy was examined. The necessity of interventions during pregnancy and at the time of delivery was under consideration.

Gastric Fibrinolysis

1975 ◽  
Vol 34 (02) ◽  
pp. 409-418 ◽  
Author(s):  
I. M Nilsson ◽  
S.-E Bergentz ◽  
U Hedner ◽  
K Kullenberg
Keyword(s):  
Gastric Ulcer ◽  
Gastric Juice ◽  
High Activity ◽  
Fibrinolytic Activity ◽  
Duodenal Juice ◽  
Bleeding Tendency ◽  
Local Fibrinolysis ◽  
Heated Plates

SummaryGastric juice from 15 normals, 20 patients with gastric ulcer and 4 patients with erosive haemorrhagic gastroduodenitis was investigated in respect of its activity on unheated and heated fibrin plates and its content of FDP and plasminogen or plasmin with immunochemical methods. Gastric juice from normals showed no activity on unheated and heated fibrin plates, and no FDP or plasminogen could be demonstrated. In the patients with gastric ulcer the gastric juice showed little or no fibrinolytic activity on fibrin plates except in 2, who had regurgitation of duodenal juice and neutral pH of the juice. These patients had equally high activity on heated as on unheated plates and no plasmin could be demonstrated. It was shown that this activity was not due to fibrinolysis, but to non-specific proteolytic activity (probably trypsin). The patients with erosive haemorrhagic gastroduodenitis exhibited quite a different picture. The gastric juice from these patients showed extremely high activity on fibrin plates, the activity was higher on unheated than on heated plates. The activity was inhibited in vitro by addition of EACA and in vivo after administration of AMCA. The occurrence of plasmin could be demonstrated directly immunologically in the gastric juice. By comparison of plasmin and trypsin in various assays it could further be proved that the gastric juice in these cases contained plasminogen activator and plasmin. The patients with erosive haemorrhagic gastroduodenitis showed no increase in fibrinolysis in the blood, but low values for plasminogen and α2M, and the serum contained FDP. These findings in the blood and gastric juice were interpreted as signs of local fibrinolysis in the stomach and duodenum. There is reason to assume that this gastric fibrinolysis contributes substantially to the bleeding tendency. The effect of administration of AMCA on fibrinolytic activity and the haemorrhage lends support to the assumption of such a mechanism.

Studies on the Haemostatic Defect in a Complicated Syndrome

1995 ◽  
Vol 74 (05) ◽  
pp. 1244-1251 ◽  
Author(s):  
H Stormorken ◽  
H Holmsen ◽  
R Sund ◽  
K S Sakariassen ◽  
T Hovig ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Bleeding Tendency ◽  
Clot Retraction ◽  
Abnormal Finding ◽  
Shear Rates ◽  
Perfusion Chamber ◽  
Coagulant Activity ◽  
5 Ht Uptake ◽  
And Storage

SummaryThe Stormorken syndrome is a multifacetted syndrome including a bleeding tendency. No deviations were found in the coagulation- or fibrinolytic systems. Platelet number was low normal, and size abnormal, whereas EM findings were unremarkable. Survival time was half normal. Clot retraction was initially rapid, but clearly decreased, whereas prothrombin consumption was also initially rapid, but complete. Membrane GP’s were normal, so was AA metabolism, PI-cycle, granule storage and secretion, and c-AMP function, whereas 5-HT uptake and storage was decreased. Optical platelet aggregation was low normal with all physiological agonists. The only clearly abnormal finding was that coagulant activity was present on non stimulated platelets at the same level as kaolin-stimulated normal platelets. This indicated a platelet abnormality which should lead to a thrombogenic, not to a haemorrhagic trait. This paradox may have its origin in rheology, because when challenged with in vivo shear rates in an ex vivo perfusion chamber, platelet cohesion was abnormally low. Further studies to better delineate the membrane abnormality are underway.

Determination and Treatment of Disorders of Primary Haemostasis

1999 ◽  
Vol 19 (04) ◽  
pp. 168-175 ◽  
Author(s):  
M. Weippert-Kretschmer ◽  
V. Kretschmer
Keyword(s):  
Platelet Function ◽  
Bleeding Risk ◽  
Bleeding Complications ◽  
Bleeding Tendency ◽  
Platelet Counts ◽  
Platelet Function Disorders ◽  
Perioperative Bleeding ◽  
Before And After ◽  
Low Sensitivity

SummaryPerioperative bleeding complications due to disorders of primary haemostasis are often underestimated. Routine determination of primary haemostasis is still problematic. The in vivo bleeding time (BT) shows low sensitivity and high variability. In this contribution the results and experiences with the IVBT having been obtained in various studies and during 10 years of routine use are reported. Patients and Methods: Blood donors before and after ASA ingestion, patients with thrombocytopenia as well as congenital and acquired platelet function disorders. Monitoring of desmopressin efficacy. IVBT with Thrombostat 4000 (tests with CaCl2 = TST-CaCl2 and ADP = TST-ADP) and PFA-100 (test cartridges with epinephrine = PFA-EPI and ADP = PFA-ADP). Results and Conclusions: IVBT becomes abnormal with platelet counts <100,000/μl. With platelet counts <50,000/μl the results are mostly outside the methodical range. IVBT proved clearly superior to BT in von Willebrand syndrome (vWS). All 16 patients with vWS were detected by PFA-EPI, whereas with BT 7 of 10 patients with moderate and 1 of 6 patients with mild forms of vWS were spotted. The majority of acquired and congenital platelet function disorders with relevant bleeding tendency were detectable by IVBT. Sometimes diagnostic problems arose in case of storage pool defect. Four to 12 h after ingestion of a single dose of 100 mg ASA the TST-CaCl2 became abnormal in all cases, the PFA-EPI only in 80%. However, the ASA sensitivity of TST-CaCl2 proved even too high when looking for perioperative bleeding complications in an urological study. Therefore, the lower ASS sensitivity of the PFA-100 seems to be rather advantageous for the estimation of a real bleeding risk. The good efficacy of desmopressin in the majority of cases with mild thrombocytopenia, congenital and acquired platelet function disorders and even ASS-induced platelet dysfunction could be proven by means of the IVBT. Thus IVBT may help to increase the reliability of the therapy. However, the IVBT with the PFA-100 is not yet fully developed. Nevertheless, routine use can be recommended when special methodical guidelines are followed.

Sign in / Sign up

Export Citation Format

Share Document