Acquired storage pool disease in platelets during disseminated intravascular coagulation

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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Acquired storage pool disease in platelets during disseminated intravascular coagulation

Blood ◽

10.1182/blood.v48.4.511.511 ◽

1976 ◽

Vol 48 (4) ◽

pp. 511-515 ◽

Cited By ~ 49

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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Thromboembolic and cardiac emergencies

10.1093/med/9780199689842.003.0034 ◽

2018 ◽

Author(s):

Jim Cassidy ◽

Donald Bissett ◽

Roy A. J. Spence OBE ◽

Miranda Payne ◽

Gareth Morris-Stiff

Keyword(s):

Deep Vein Thrombosis ◽

Disseminated Intravascular Coagulation ◽

Medical Emergency ◽

Bleeding Diathesis ◽

Cardiac Events ◽

Intravascular Coagulation ◽

Vein Thrombosis ◽

Pericardial Effusions ◽

Cardiac Emergencies ◽

Deep Vein

Describes the incidence and aetiology of excessive clotting and / or bleeding diathesis in cancer. This includes descriptions of disseminated intravascular coagulation, deep vein thrombosis. Outlines investigations and immediate therapy options.Also discusses cardiac events including pericardial effusions. Describes aetiology, pathophysiology, investiagation and therapy of this medical emergency.

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Secretory mechanisms. Behaviour of adenine nucleotides during the platelet release reaction induced by adenosine diphosphate and adrenaline

Biochemical Journal ◽

10.1042/bj1290067 ◽

1972 ◽

Vol 129 (1) ◽

pp. 67-82 ◽

Cited By ~ 57

Author(s):

Holm Holmsen ◽

H. James Day ◽

Carol A. Setkowsky

Keyword(s):

Adenine Nucleotides ◽

Specific Radioactivity ◽

Adenosine Diphosphate ◽

Second Phase ◽

Release Reaction ◽

Concentration Time ◽

Aggregation Pattern ◽

Induced Aggregation ◽

Phasic Release

1. Platelets containing adenine nucleotides labelled with3H and14C in vitro were aggregated biphasically with ADP and adrenaline. Amounts of ATP and ADP as well as the radioactivity of ATP, ADP, AMP, IMP, hypoxanthine and adenine were determined in platelets and plasma at different stages of aggregation. 2. ATP and ADP were released during the second aggregation phase and had a low specific radioactivity compared with the ATP and ADP retained by the cells. The specific radioactivity of intracellular nucleotides increased during release. The parameters observed with ADP and adrenaline as release inducers were the same as for collagen and thrombin. 3. Release induced by all four inducers was accompanied by conversion of cellular [3H]ATP into extracellular [3H]-hypoxanthine. By variation of temperature, inducer concentration, time after blood withdrawal and use of acetylsalicylic acid, the aggregation pattern caused by adrenaline and ADP could be made mono- or bi-phasic. Release or second-phase aggregation was intimately connected with the ATP–hypoxanthine conversion, whereas first phase aggregation was not. 4. The [3H]ATP–hypoxanthine conversion started immediately after ADP addition. With adrenaline it usually started with the appearance of the second aggregation phase. The conversion was present during first phase of ADP-induced aggregation only if a second phase were to follow. 5. When secondary aggregation took place while radioactive adenine was being taken up by the platelets, increased formation of labelled hypoxanthine still occurred, but there was either no change or an increase in the concentration of labelled ATP. 6. Biphasically aggregated platelets converted [3H]adenine more rapidly into [3H]-ATP and -hypoxanthine than non-aggregated platelets. Addition of [3H]adenine at different stages of biphasic aggregation showed that more [3H]hypoxanthine was formed during than after the release step. 7. We conclude that ADP and adrenaline, like thrombin and collagen, cause extrusion of non-metabolic granula-located platelet adenine nucleotides. During release metabolic ATP breaks down to hypoxanthine, and this process might reflect an ATP-requiring part of the release reaction.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647736 ◽

1974 ◽

Vol 32 (02/03) ◽

pp. 670-677 ◽

Cited By ~ 14

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.

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A New Computerized Impedance Plethysmograph: Accuracy in the Detection of Proximal Deep-Vein Thrombosis in Symptomatic Outpatients

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647489 ◽

1991 ◽

Vol 65 (03) ◽

pp. 229-232 ◽

Cited By ~ 10

Author(s):

Paolo Prandoni ◽

Anthonie W A Lensing ◽

Menno V Huisman ◽

Jan J C Jonker ◽

Mario Vigo ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Sensitivity And Specificity ◽

Impedance Plethysmography ◽

Invasive Technique ◽

Second Phase ◽

Test Results ◽

Anticoagulant Treatment ◽

Vein Thrombosis ◽

Impedance Plethysmograph ◽

Deep Vein

SummaryBecause of the lack of specificity of the clinical diagnosis it is appropriate in patients with clinically suspected deep-vein thrombosis to apply an objective test before starting anticoagulant treatment. Impedance plethysmography is a highly accurate technique for the detection of proximal-vein thrombosis with a reported sensitivity and specificity of 93 and 97%, respectively. In all previous reported evaluations of impedance plethysmography an apparatus which was developed in 1971 was used.A new computerized impedance plethysmograph, using a novel device to measure impedance, was blindly compared against venography in 443 consecutive outpatients with clinically suspected deep-vein thrombosis. In the first phase of the study the computerized impedance plethysmography test results of 242 symptomatic patients were used to develop a discriminant line. Subsequently, this discriminant line was validated in the second phase of the study in another 201 symptomatic patients. The combined sensitivity and specificity of these two phases for proximal-vein thrombosis was 91% [95% confidence interval (Cl), 86 to 94%] and 94% (95% CI, 90 to 96%), respectively, which compares favourably with impedance plethysmography.It is concluded that computerized impedance plethysmography is a simple, portable, non-invasive technique with a high accuracy for the detection of proximal vein thrombosis. However, before computerized impedance plethysmography can be used as the only test in the diagnosis of deep-vein thrombosis, the safety of withholding anticoagulant treatment to patients with repeated normal computerized test results should be assessed during longterm follow-up studies.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647919 ◽

1976 ◽

Vol 35 (01) ◽

pp. 124-138 ◽

Cited By ~ 185

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.

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

10.1055/s-0039-1680407 ◽

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.

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Storage Pool Disease Associated With Von Willebrand?

10.1055/s-0038-1653272 ◽

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

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Storage Pool Disease: Evidence for Clinical and Biochemical Heterogeneity

10.1055/s-0039-1680336 ◽

1977 ◽

Cited By ~ 1

Author(s):

H. J. Weiss ◽

B. A. Lages ◽

L. D. Witte ◽

K. L. Kaplan ◽

DeW S. Goodman ◽

...

Keyword(s):

Dense Granule ◽

Second Phase ◽

Platelet Factor ◽

Cultured Fibroblasts ◽

Dense Granules ◽

Storage Pool ◽

Platelet Storage ◽

Absolute Requirement ◽

Adp Release ◽

Storage Pool Disease

Patients with platelet storage pool disease have decreased numbers and contents (ATP, ADP, serotonin, calcium) of the dense granules. Our studies on 14 patients with this disorder suggest considerable clinical and biochemical heterogeneity. The most pronounced dense granule defect (lowest levels of ATP and ADP, undetectable serotonin) was found in the 5 albinos with the Hermansky-Pudlak syndrome. One non-albino patient is unique in showing a decreased content of β thromboglobulin (βTG), platelet factor 4 (PF4), and the platelet growth factor (PtGF) that stimulated the proliferation of cultured fibroblasts and arterial smooth muscle cells. Her platelets also contained a decreased number of α granules in addition to decreased dense granules, suggesting that βTG, PF4, and PtGF are localized in specific α granules which are morphogenetically related to dense granules. Another patient was unique in that ADP, epinephrine, and arachidonic acid evoked completely normal aggregation responses, associated with normal production of platelet malondialdehyde. Since his platelets were markedly deficient in ADP, these findings provide further evidence that ADP release is not an absolute requirement for ‘second phase’ aggregation and that PGG2 or thromboxane A2 may directly aggregate platelets independent of ADP release. Variable defects in malondialdehyde production in other patients suggest further heterogeneity of the release defect in storage pool disease.

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A Randomised, Double-Blind, Placebo-Controlled Trial of Dermatan Sulphate for Prevention of Deep Vein Thrombosis in Hip Fracture

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648413 ◽

1992 ◽

Vol 67 (02) ◽

pp. 203-208 ◽

Cited By ~ 66

Author(s):

Giancarlo Agnelli ◽

Benilde Cosmi ◽

Paolo Di Filippo ◽

Valeria Ranucci ◽

Franca Veschi ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Hip Fracture ◽

Controlled Trial ◽

Second Phase ◽

Dermatan Sulphate ◽

Heparin Cofactor Ii ◽

Double Blind ◽

Double Blind Placebo ◽

Vein Thrombosis ◽

Deep Vein

SummaryDermatan sulphate (MF 701) is a natural glycosaminoglycan that catalyses thrombin inhibition by heparin cofactor II. The aim of the study was to evaluate the efficacy and safety of MF 701 for prevention of deep vein thrombosis (DVT) in patients with hip fracture. A randomised, double-blind, placebo-controlled design was used to assess two dose regimens of MF 701 in two consecutive study phases. Treatment was started within 48 h from the trauma and continued for 14 days for non-operated patients or until the 10th postoperative day. Bilateral mandatory venography was used to assess the end-point. Eighty patients were included in the first phase (40 MF 701, 40 placebo). MF 701, 100 mg IM b. i. d., did not reduce incidence of DVT from that on placebo and did not induce any bleeding. In the second phase 126 patients were included, with a randomisation ratio of 2:1 (84 MF 701, 300 mg IM b.i.d., 42 placebo). Bilateral venography was obtained for 110 patients. The incidence of DVT was 64% (23/36) in the placebo group and 38% (28/74) in the MF 701 group (p = 0.01; odds ratio [OR] = 0.34, 95% confidence limits [CL] = 0.15-0.80); proximal DVTs were 42% (15/36) and 20% (15/74), respectively (p = 0.02; OR = 0.36, CL = 0.15-0.89). No significant differences were found in haemorrhagic complications (2.4% in each group), blood loss from drains, blood transfusions, haemoglobin and haematocrit values. This study is the first demonstration that dermatan sulphate is a clinically effective antithrombotic agent without bleeding effects. It also provides evidence of the biological role of heparin cofactor II.

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