scholarly journals Constitutional Thrombocytopathia with Abnormal Aggregation Different from Storage-Pool Disease and Aspirin-Like Syndrome

1977 ◽  
Author(s):  
J. Conard ◽  
M. Samama ◽  
B. Vargaftig ◽  
C. Lecrubier ◽  
J. Breton-Gorius ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Bleeding Time ◽  
Tolerance Test ◽  
Clot Retraction ◽  
Storage Pool ◽  
Dense Bodies ◽  
Arachidonic Acid Production ◽  
Storage Pool Disease ◽  
Induced Aggregation

A thrombocytopathi a associated with a lifelong hemorragic diathesis has been observed in a 18 years old woman. The bleeding time is prolonged. Platelet count and size, and clot retraction are normal. Adrenalin-induced aggregation is abolished and response to ADP and arachidonic acid are impaired. A storage-pool disease is unlikely since platelet ultrastructural aspects appear normal and the number of dense bodies is overnormal, that is confirmed by examination of platelets charged with mepacrine. The uptake of 14(c) serotonin is not increased and it is in correlation with abnormal fluorescence of meracrine-stained dense bodies. Contrasting with aspirin-like syndrome, the first phase aggregation is decreased and in vitro aspirin tolerance test abnormal. Finally, although platelets do not aggregate normally to arachidonic acid, production of Tromboxane A2 and transferable platelet aggregating activity are present. Hence, the thrombocytorathia reported here could not be classified, but a congenital defect is suspected.

DN.9693 COMPARED WITH PROSTACYCLIN AND PROSTAGLANDIN E1 IN SEVEN PLATELET TESTS

1987 ◽  
Author(s):  
J R O'Brien ◽  
M D Etherington ◽  
G P Salmon
Keyword(s):  
Bleeding Time ◽  
Prostaglandin E ◽  
Minor Effect ◽  
Membrane Glycoproteins ◽  
Clot Retraction ◽  
Platelet Factor ◽  
Active Concentration ◽  
A Minor ◽  
Induced Aggregation

A new drug, DN.9693, has low Km phosphodiesterase inhibitory properties. Its effect on seven broad spectrum platelet "function" tests has been compared with the effects of prostacyclin E1 (PGI1) and prostaglandin E (PGE ). The tests were (1) platelet aggregation induced by ADP, collagen, adrenaline, thrombin, arachidonic acid and ristocetin; (2) a new test in which platelets aggregate after adding distilled water to cause osmotic stress; (3) the loss of platelets washed in buffered saline; (4) clot retraction; (5) the glass bead column platelet retention test; (6) the in vitro filter "bleeding time" (see two other submitted abstracts); (7) the amount of platelet factor 4 (PF4) which "leaks" from platelets at room temperature.PGI2 inhibited all seven tests, 50% inhibition of the various tests required from 0.1 to 44ng/ml of PGI2. PGE1 also inhibited in all tests but on average required 18 times higher concentrations. Thus an increase in cAMP may be relevant to all these tests, but an understanding of the mechanisms involved is incomplete. DN.9693 inhibited only the first four tests; the equi-active concentration was about 600 times that of PGI2. DN.9693, 2.5μg/ml, caused 50% inhibition of ristocetin induced aggregation and at 4μg/ml had a minor effect on the filter bleeding time. Thus DN.9693 may affect the platelet membrane glycoproteins. In conclusion it is confirmed that PGE1 is less active than PGI^ but has similar activities. DN.9693 whenstudied in these tests has many, but notall, of the prostaglandin-like properties.

Platelet Adhesion, Release and Aggregation in Flowing Blood: Effects of Surface Properties and Platelet Function.

1976 ◽  
Vol 35 (01) ◽  
pp. 124-138 ◽  
Author(s):  
Hans R Baumgartner ◽  
Reto Muggli ◽  
Thomas B Tschopp ◽  
Vincent T Turitto
Keyword(s):  
Platelet Adhesion ◽  
Fibrillar Collagen ◽  
Flow Conditions ◽  
Initial Attachment ◽  
Shear Rates ◽  
Storage Pool ◽  
High Concentrations ◽  
Storage Pool Disease ◽  
Induced Aggregation

SummaryPlatelet adhesion to natural and artificial surfaces and adhesion-induced aggregation were investigated in vitro using an annular perfusion chamber. The surfaces were exposed to anticoagulated blood under identical flow conditions (~ arterial shear rates). The initial attachment of platelets (contact) appeared less surface specific than spreading and release. Fibrillar collagen was the most powerful inducer of platelet degranulation whereas elastin, microfibrils and epon were virtually inactive. Fibrillar collagen caused release also in the absence of spreading. Surface coverage with platelets did not exceed 25 % unless spreading occurred. Perfusion with platelet-free plasma or platelet-poor blood did not remove adhering platelets. However, platelets were translocated from mural thrombi to the surface by such perfusion. In addition, platelets which detached from mural thrombi adhered more readily to elastin or microfibrils than platelets from the circulating blood. The initial attachment of platelets to subendothelium was inhibited in von Willebrand’s disease, the Bernard-Soulier syndrome and at high concentrations of dipyridamole; spreading was inhibited in storage pool disease of rats, at low temperature (20° C), with EDTA (3 mM) and Prostaglandin E1 (1 μM); and adhesion-induced aggregation was inhibited in thrombasthenia, storage pool disease and after ingestion of sulfinpyrazone or Aspirin.It is concluded that the initial attachment (contact) of platelets, spreading and surface-induced release of platelet constituents are at least partially independent phenomena, the latter two being highly surface specific. At flow conditions which cause the disappearance of platelet thrombi, platelet adhesion appears as an irreversible process.

Storage Pool Disease Associated With Von Willebrand?

1981 ◽  
Author(s):  
S Meschengieser ◽  
M Schattner ◽  
G Elgue ◽  
M A Lazzari
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Minor Bleeding ◽  
Bleeding Tendency ◽  
Storage Pool ◽  
Prolonged Bleeding Time ◽  
Aggregation Pattern ◽  
Storage Pool Disease ◽  
Induced Aggregation ◽  
Ristocetin Cofactor

We evaluated a group of 11 patients (10 female, 1 male) complaining of minor bleeding symptoms that showed the pattern of storage pool disease (SPD) and besides, presented a lack of aggregation induced by ristocetin, which corrected with the addition of normal plasma (pool of 15 donors). Only two patients had familiar history of bleeding tendency. Bleeding time (Ivy) was prolonged in 63% of the patients and platelet retention (Pellem II) was decreased in 72% of them.Three of the patients showed, apart from the SPD, a clear pattern of VW disease (low factor VIII: C and VIII: Ag). In four patients the levels of factor VIII: C and f, VIII:Ag were normal, but one of them presented a Ristocetin Cofactor (McFarlane) below normal, associated with a prolonged bleeding time and low adhesiveness. Three patients had low levels of VIII: C with normal levels of VIII:Ag. The last patient with border line levels of VIII: C and VIII:Ag, presented a low Ristocetin Cofactor. Thus, 5 of the 11 patients have undoubtful elements of VW. In the others this diagnosis could not be accomplished clearly.As a conclusion, the presence of a characteristic aggregation pattern of SPD with absence of ristocetin induced aggregation, could suggest a variant of SPD or perhaps an association of both diseases

The d-Enantiomer Form of Indobufen Totally Accounts for the Anti-Cyclooxygenase and Antiplatelet Activity Ex Vivo and for the Increase in Bleeding Time by Indobufen in Man

1992 ◽  
Vol 67 (02) ◽  
pp. 258-263 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
An Yan ◽  
Walter Bernini ◽  
Daniela Giannessi ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Plasma Levels ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Random Sequence ◽  
Antiplatelet Agent ◽  
Antiplatelet Drug ◽  
Double Blind

SummaryIndobufen is an antiplatelet drug able to inhibit thromboxane production and cyclooxygenase-dependent platelet aggregation by a reversible inhibition of cyclooxygenase. Indobufen exists in two enantiomeric forms, of which only d-indobufen is active in vitro in inhibiting cyclooxygenase. In order to verify that also inhibition of platelet function is totally accounted for by d-indobufen, ten patients with proven coronary artery disease (8 male, 2 female, age, mean ± S.D., 58.7 ± 7.5 years) were given, in random sequence, both 100 mg d-indobufen and 200 mg dl-indobufen as single administrations in a double-blind crossover design study with a washout period between treatments of 72 h. In all patients thromboxane (TX) B2 generation after spontaneous clotting (at 0, 1, 2, 4, 6, 8, 12, 24 h), drug plasma levels (at the same times), platelet aggregation in response to ADP, adrenaline, arachidonic acid, collagen, PAF, and bleeding time (at 0, 2, 12 h) were evaluated after each treatment. Both treatments determined peak inhibition of TXB2 production at 2 h from administration, with no statistical difference between the two treatments (97 ±3% for both treatments). At 12 h inhibition was 87 ± 6% for d-indobufen and 88 ± 6% for dl-indobufen (p = NS). Inhibition of TXB2 production correlated significantly with plasma levels of the drugs. Maximum inhibitory effect on aggregation was seen in response to collagen 1.5 pg/ml (63 ± 44% for d-indobufen and 81 ± 22% for dl-indobufen) and arachidonic acid 0.5-2 mM (78 ± 34% for d-indobufen and 88 ± 24% for dl-indobufen) at 2 h after each administration. An effect of both treatments on platelet aggregation after 12 h was present only for adrenaline 2 μM (55 ± 41% for d-indobufen and 37 ± 54% for dl-indobufen), collagen 1.5 pg/ml (69 ± 30% for d-indobufen and 51 ± 61% for dl-indobufen), arachidonic acid 0.5-2 mM (56 ± 48% for d-indobufen and 35 ± 49% for dl-indobufen). The extent of inhibition of TX production and the extent of residual platelet aggregation were never significantly different between treatments. Bleeding time prolongation was similar in the two treatment groups without showing a pronounced and long lasting effect (from 7.0 ± 2.0 min to 10.0 ± 3.0 min at 2 h and 8.0 ± 2.0 min at 12 h for d-indobufen; from 6.0 ±1.0 min to 8.5 ± 2.0 min at 2 h and 8.0 ± 1.0 min at 12 h for dl-indobufen). These results demonstrate that the biological activity of dl-indobufen as an antiplatelet agent in vivo is totally accounted for by d-indobufen.

Decreased Platelet Vitamin C in Diabetes Mellitus; Possible Role in Peraggregatoon

1979 ◽  
Author(s):  
K.E. Sarji ◽  
J. Gonzalez ◽  
H. Hempling ◽  
J.A. Colwell
Keyword(s):  
Ascorbic Acid ◽  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Vitamin C ◽  
Platelet Rich Plasma ◽  
Solution Ph ◽  
Dose Dependent Fashion ◽  
Insulin Dependent Diabetic ◽  
Induced Aggregation

To determine whether Vitamin C might relate to the increased platelet sensitivity in the diabetic, we have measured levels of platelet Vitamin C and studied the effects of Vitamin C on platelet aggregation. Ascorbic acid levels in washed platelets from diabetics were significantly lower than from normals (4s.2±3 μg/1010 platelets vs. 2s.s±2 μg/1010 platelets, p<.001). The effects of ascorbic acid on platelet aggregation in vitro were studied by adding ascorbic acid in buffered solution (pH 7.35) prior to-aggregating agents. Ascorbic acid in platelet-rich plasma consistently inhibited platelet aggregation with threshold concentrations of ADP, epinephrine, and collagen. With washed platelets, ascorbic acid inhibited arachidonic, acid-induced aggregation. When platelets were incubated at 37°C for 10 minutes with varying concentrations of ascorbic acid, rewashed, and aggregation with arachidonic acid tested, aggregation was inhibited in a linear dose-dependent fashion. Oral ingestion of ascorbic acid (2 gm/day) for seven days by normal non-smoking males produced a marked inhibition of aggregation. In a similar study, platelets from an insulin-dependent diabetic showed no change in aggregation. These results suggest that platelet levels of ascorbic acid may relate to the hyperaggregat ion of platelets from diabetics.

Effects of Ethanol on Pathways of Platelet Aggregation In Vitro

1988 ◽  
Vol 59 (03) ◽  
pp. 383-387 ◽  
Author(s):  
Margaret L Rand ◽  
Marian A Packham ◽  
Raelene L Kinlough-Rathbone ◽  
J Fraser Mustard
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Secondary Phase ◽  
Primary Phase ◽  
Rabbit Platelet ◽  
Membrane Phospholipids ◽  
Rabbit Platelets ◽  
Induced Aggregation

SummaryEthanol, at physiologically tolerable concentrations, did not affect the primary phase of ADP-induced aggregation of human or rabbit platelets, which is not associated with the secretion of granule contents. Potentiation by epinephrine of the primary phase of ADP-induced aggregation of rabbit platelets was also not inhibited by ethanol. However, ethanol did inhibit the secondary phase of ADP-induced aggregation which occurs with human platelets in citrated platelet-rich plasma and is dependent on the formation of thromboxane A2. Inhibition by ethanol of thromboxane production by stimulated platelets is likely due to inhibition of the mobilization of arachidonic acid from membrane phospholipids, as ethanol had little or no effect on aggregation and secretion induced by arachidonic acid or the thromboxane mimetic U46619. Rabbit platelet aggregation and secretion in response to low concentrations of collagen, thrombin, or PAF were inhibited by ethanol. Inhibition of the effects of thrombin and PAF was also observed with aspirin-treated platelets. Thus, in addition to inhibiting the mobilization of arachidonate for thromboxane formation that occurs with most agonists, ethanol can also inhibit aggregation and secretion through other effects on platelet responses.

scholarly journals Acquired storage pool disease in platelets during disseminated intravascular coagulation

Blood ◽  
1976 ◽  
Vol 48 (4) ◽  
pp. 511-515
Author(s):  
FI Pareti ◽  
A Capitanio ◽  
PM Mannucci
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Adenine Nucleotides ◽  
Second Phase ◽  
Intravascular Coagulation ◽  
Vein Thrombosis ◽  
Storage Pool ◽  
Storage Pool Disease ◽  
Deep Vein ◽  
Induced Aggregation ◽  
Uptake And Metabolism

A patient with clinical and laboratory evidence of disseminated intravascular coagulation associated with deep-vein thrombosis and pulmonary embolism developed a qualitative platelet abnormality characterized by a defective release reaction. Second-phase aggregation induced by ADP and adrenaline was impaired, and reduced collagen- induced aggregation was accompanied by defective release of ADP and ATP. The decrease in total platelet ATP and ADP, the high ATP:ADP ratio in the presence of normal amounts of metabolic adenine nucleotides, and the low content of serotonin associated with abnormal uptake and metabolism of the exogenous amine suggested that the defective platelet function was due to lack of the platelet organelles in which serotonin and nonmetabolic adenine nucleotides are normally stored. Acquired storage pool disease is likely to be related to exposure of circulating platelets to aggregating agents, with their degranulation occurring during disseminated intravascular coagulation.

Sex-Associated Differences On The Effect Of Asa Or Flurbiprofen On Platelet Function Ex Vivo

1981 ◽  
Author(s):  
E E Nishizawa ◽  
B A Molony ◽  
M M Meinzinger ◽  
D J Williams
Keyword(s):  
Arachidonic Acid ◽  
Platelet Function ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Normal Male ◽  
Normal Response ◽  
Beneficial Effects ◽  
Acid Pathway ◽  
Induced Aggregation ◽  
Arachidonic Acid Pathway

It has been reported that although ASA may have some beneficial effects in males, no differences from placebo was detected in females in clinical trials on venous thrombosis, TIA and stroke. Since ASA inhibits platelet function and because the end-points measured in the above clinical studies may be related to platelet function, we measured bleeding time and platelet aggregation induced by collagen or arachidonic acid following oral administration of ASA (650 mg) or flurbiprofen (100 mg) in normal male and female volunteers (10 per group, total of 40 subjects) between the age of 50 and 70.No sex-associated differences in response with either drug were observed in bleeding time or platelet function. Thus, we were unable to confirm that the observation of beneficial effect of ASA in males was due to its effect on platelets. However, more interestingly there was a statistically shorter bleeding time in males (p = 0.026) before administration of drug. It was also found that despite the normal response to collagen, PRP prepared from pre-drug blood samples from 6 individuals (15%) did not aggregate when stimulated with arachidonic acid at concentrations as high as 1 mM. These results suggest that, at least in some individuals, collagen-induced aggregation may proceed by a pathway independent of the arachidonic acid pathway.

scholarly journals Acquired storage pool disease in platelets during disseminated intravascular coagulation

Blood ◽  
1976 ◽  
Vol 48 (4) ◽  
pp. 511-515 ◽  
Author(s):  
FI Pareti ◽  
A Capitanio ◽  
PM Mannucci
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Adenine Nucleotides ◽  
Second Phase ◽  
Intravascular Coagulation ◽  
Vein Thrombosis ◽  
Storage Pool ◽  
Storage Pool Disease ◽  
Deep Vein ◽  
Induced Aggregation ◽  
Uptake And Metabolism

Abstract A patient with clinical and laboratory evidence of disseminated intravascular coagulation associated with deep-vein thrombosis and pulmonary embolism developed a qualitative platelet abnormality characterized by a defective release reaction. Second-phase aggregation induced by ADP and adrenaline was impaired, and reduced collagen- induced aggregation was accompanied by defective release of ADP and ATP. The decrease in total platelet ATP and ADP, the high ATP:ADP ratio in the presence of normal amounts of metabolic adenine nucleotides, and the low content of serotonin associated with abnormal uptake and metabolism of the exogenous amine suggested that the defective platelet function was due to lack of the platelet organelles in which serotonin and nonmetabolic adenine nucleotides are normally stored. Acquired storage pool disease is likely to be related to exposure of circulating platelets to aggregating agents, with their degranulation occurring during disseminated intravascular coagulation.

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