Assessing the periprocedural magnitude of platelet count change in response to lusutrombopag

SummaryThe structural and functional properties of plasma and platelet vWF were studied in 8 patients (5 unrelated families) with vWD demonstrating a mutation at position 611 (R611C or R611H). Following reduction, electrophoresis and immunoblotting with a polyclonal anti-reduced vWF antibody, abnormal proteolysis of vWF was demonstrated in plasma and to a lesser extent in platelets from all patients, leading to the formation of a unique 209 kDa fragment undetectable in control as well as in type 2A, 2B or 2N vWF. Immunoblotting with MoAbs to reduced vWF showed that the C-terminal end of the 209 kDa fragment was located beyond residue 1744 of the subunit and that its N-terminus was between residues 523 and 1114. Multimeric analysis of patients vWF showed an abnormal pattern in both plasma and platelets, with a moderate decrease of the HMW multimers together with a significant increase of the lowest MW forms. The specific sensitivity of vWF R611C and vWF R611H to proteolysis was further evidenced using V-8 protease. In all patient’s samples the enzyme produced a unique monomeric 80 kDa fragment, absent in V-8 digested normal vWF, which overlapped the N-terminal part of the subunit. The functional analysis of vWF showed a markedly decreased affinity of mutated plasma vWF for platelet GPIb in the presence of ristocetin. Infusion of DDAVP in two of these patients did not lead to significant platelet count change. It induced a limited increase of the HMW multimers in plasma together with a poor correction of the vWF binding to platelet GPIb. In conclusion, our data demonstrate that in addition to a normal proteolysis, vWF mutated at position 611 undergoes a specific cleavage in plasma and platelets. In contrast to the increased proteolysis observed in type 2A and 2B patients’ plasma, this additional cleavage produced a unique 209 kDa species but maintained a HMW multimer-like structure of vWF R611C and R611H.

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Predictive role of perioperative platelet count on posthepatectomy liver failure and mortality: a systematic review and meta-analysis

Zeitschrift für Gastroenterologie ◽

10.1055/s-0037-1612829 ◽

2018 ◽

Vol 56 (01) ◽

pp. E2-E89

Author(s):

M Golriz ◽

O Ghamarnejad ◽

E Khajeh ◽

K Hoffmann ◽

A Mehrabi

Keyword(s):

Systematic Review ◽

Platelet Count ◽

Liver Failure ◽

Meta Analysis ◽

Posthepatectomy Liver Failure ◽

Predictive Role

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Do Extra-Platelet Sources Contribute to the Plasma Level of Thrombospondin?

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642769 ◽

1988 ◽

Vol 59 (02) ◽

pp. 273-276 ◽

Cited By ~ 8

Author(s):

J Dawes ◽

D A Pratt ◽

M S Dewar ◽

F E Preston

Keyword(s):

Platelet Count ◽

Background Concentration ◽

Serum Concentrations ◽

Bone Marrow Depression ◽

Serial Sampling ◽

Control Serum ◽

Platelet Release ◽

Highly Correlated ◽

The Relationship

SummaryThrombospondin, a trimeric glycoprotein contained in the platelet α-granules, has been proposed as a marker of in vivo platelet activation. However, it is also synthesised by a range of other cells. The extraplatelet contribution to plasma levels of thrombospondin was therefore estimated by investigating the relationship between plasma thrombospondin levels and platelet count in samples from profoundly thrombocytopenic patients with marrow hypoplasia, using the platelet-specific α-granule protein β-thromboglobulin as control. Serum concentrations of both proteins were highly correlated with platelet count, but while plasma β-thromboglobulin levels and platelet count also correlated, there was no relationship between the number of platelets and thrombospondin concentrations in plasma. Serial sampling of patients recovering from bone marrow depression indicated that the plasma thrombospondin contributed by platelets is superimposed on a background concentration of at least 50 ng/ml probably derived from a non-platelet source, and plasma thrombospondin levels do not simply reflect platelet release.

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1-Desamino-8-D-Arginine Vasopressin (DDAVP) Infusion in Type IIB von Willebrand’s Disease: Shortening of Bleeding Time and Induction of a Variable Pseudothrombocytopenia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647265 ◽

1990 ◽

Vol 64 (01) ◽

pp. 117-120 ◽

Cited By ~ 22

Author(s):

Alessandra Casonato ◽

M Teresa Sartori ◽

Luigi de Marco ◽

Antonio Girolami

Keyword(s):

Monoclonal Antibody ◽

Platelet Count ◽

Arginine Vasopressin ◽

Calcium Concentration ◽

Sodium Citrate ◽

Bleeding Time ◽

Blood Collection ◽

Von Willebrand's Disease ◽

Blood Samples ◽

Von Willebrand’S Disease

SummaryWe have investigated the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) infusion on platelet count and bleeding time in 4 patients with type IIB von Willebrand’s disease (vWd). Three of four patients showed a normalization of the bleeding time within 1 h after the infusion, while bleeding time was not modified in the fourth. In accordance with the literature, thrombocytopenia was observed after DDAVP infusion, but this thrombocytopenia was due to the anticoagulants used for blood collection. In two patients (F. I., G. F.) no thrombocytopenia was observed when platelets were counted by fingerstick method but there was a 20% platelet decrease in blood samples collected in sodium citrate and a 50% decrease in samples collected in EDTA. Dramatic falls in platelet counts (70–95%) were observed in the additional two patients (C. A., D.Z.) after DDAVP infusion, when both sodium citrate or EDTA were used as anticoagulants. In the latter two patients there was also a 50% decrease in platelet count when the fingerstick method was used. The decrease in the patient’s platelet count in EDTA samples after DDAVP infusion could be prevented, in part, by the previous additions of an anti GPIb monoclonal antibody and an anti GPIIb-IIIa monoclonal antibody.Thus, the thrombocytopenia observed in the four IIB vWd patients studied after DDAVP infusion seems to be, at least partially, a pseudothrombocytopenia depending on the calcium concentration in the blood samples and the availability of GPIb and GPIIb-IIIa receptors. These findings and the normalization of the bleeding time observed in three of the four patients has led us to reconsider the possible use of DDAVP in the treatment of our IIB vWd patients.

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Enhancement of ADP-induced Platelet Aggregation by Adrenaline in Vivo and Its Prevention

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647788 ◽

1973 ◽

Vol 29 (02) ◽

pp. 490-498 ◽

Cited By ~ 6

Author(s):

Hiroh Yamazaki ◽

Itsuro Kobayashi ◽

Tadahiro Sano ◽

Takio Shimamoto

Keyword(s):

Platelet Count ◽

Platelet Aggregation ◽

Platelet Rich Plasma ◽

The Other ◽

Endothelial Surface ◽

Important Interaction ◽

Blood Coagulability ◽

The Difference

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P<0.01-0.05). The above change was not observed in each group of rabbits injected with saline, 1 µg per Kg of 1-noradrenaline or 0.1 and 10 µg per Kg of adrenaline. Also, it was prevented by oral administration of 10 mg per Kg of phenoxybenzamine or propranolol or aspirin or pyridinolcarbamate 3 hours before the challenge. On the other hand, the enhancement of ADP-induced platelet aggregation was not observed in vitro, when 10-5 or 3 × 10-6 molar and 129.4 ± 12.8% of the value before 10∼6 molar ADP was added to citrated platelet rich plasma (CPRP) of rabbit after incubation at 37°C for 30 second with 0.01, 0.1, 1, 10 or 100 µg per ml of adrenaline or noradrenaline. These results suggest an important interaction between endothelial surface and platelets in connection with the enhancement of ADP-induced platelet aggregation by adrenaline in vivo.

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Platelet Aggregation in Rats in Relation to Hyperuricaemia Induced by Dietary Single-Cell Protein and to Protein Deficiency

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646695 ◽

1978 ◽

Vol 39 (02) ◽

pp. 346-359 ◽

Cited By ~ 3

Author(s):

P D Winocour ◽

M R Turner ◽

T G Taylor ◽

K A Munday

Keyword(s):

Uric Acid ◽

Platelet Count ◽

Platelet Aggregation ◽

Time Lag ◽

Blood Platelet ◽

Single Cell Protein ◽

Cell Protein ◽

Low Protein ◽

Blood Platelet Count ◽

Rat Platelets

SummaryA major limitation to single-cell protein (SCP) as a human food is its high nucleic acid content, the purine moiety of which is metabolised to uric acid. Rats given a Fusarium mould as a source of SCP in diets containing oxonate, a uricase inhibitor, showed elevated plasma and kidney uric acid concentrations after 21 d, which were related to the level of dietary mould. ADP-induced and thrombin-induced platelet aggregation was greater in the hyperuricaemic rats than in controls and a progressive increase in aggregation with increasing levels of dietary mould was observed. Furthermore a time-lag, exceeding the life-span of rat platelets, was observed between the development of hyperuricaemia and the increase in aggregation. A similar time-lag was observed between the lowering of the hyperuricaemia and the reduction of platelet aggregation when oxonate was removed from the diet.If human platelets react to uric acid in the same manner as rat platelets this might explain the link that has been suggested between hyperuricaemia and ischaemic heart disease. In that event diets high in nucleic acids might be contra-indicated in people at risk from ischaemic heart disease.In rats given a low protein diet (50 g casein/kg) for 21 d ADP-induced and thrombin-induced platelet aggregation and whole blood platelet count were reduced compared with control animals receiving 200 g casein/kg diet but not in rats given 90 or 130 g casein/kg diet. A study of the time course on this effect indicated that the reduction both in aggregation tendency and in whole blood platelet count occurred after 4 d of feeding the low protein diet. These values were further reduced with time.

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Involvement of 5-Hydroxytryptamine in Platelet Aggregation In Vivo in Rats and Guinea Pigs

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646615 ◽

1989 ◽

Vol 61 (03) ◽

pp. 463-467 ◽

Cited By ~ 3

Author(s):

G M Smith

Keyword(s):

Platelet Count ◽

Guinea Pigs ◽

Platelet Adhesion ◽

Adenosine Diphosphate ◽

Rate Of Return ◽

Low Doses ◽

Dose Dependent ◽

Higher Doses ◽

Rat Platelets

SummaryIn this study, 5-hydroxytryptamine (5-HT) caused a dose- dependent fall in the circulating platelet count suggesting that 5-HT receptors are activated in rat platelets to cause platelet adhesion and aggregation. When low doses of adenosine diphosphate (ADP) were simultaneously injected with 5-HT, there was a significant potentiation of the responses to ADR Ketanserin significantly reduced the potentiated responses. When higher doses of ADP were infused with bolus injections of 5-HT there was no potentiation and ketanserin did not reduce these responses. Ketanserin did not inhibit the collagen-induced fall in circulating platelet count, but did significantly increase the rate of return to the basal platelet count compared with control. 5-HT did not cause a fall in platelet count in guinea-pigs

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Platelet Adhesiveness and Fibrinolysis after Recent Cerebro-Vascular Accidents and their Relationship with Subsequent Deep Venous Thrombosis of the Legs

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648016 ◽

1976 ◽

Vol 36 (01) ◽

pp. 127-132 ◽

Cited By ~ 11

Author(s):

C. P Warlow ◽

J. A. N Rennie ◽

D Ogston ◽

A. S Douglas

Keyword(s):

Platelet Count ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Plasminogen Activator ◽

Fibrinogen Level ◽

Plasma Fibrinogen ◽

Platelet Adhesiveness ◽

Plasma Fibrinogen Level ◽

Vascular Accidents ◽

Subsequent Rise

SummaryIn fifteen patients with a cerebro-vascular accident resulting in an acute hemiplegia there was a subsequent rise in the platelet count and plasma fibrinogen level. There were no significant alterations in platelet adhesiveness, plasminogen activator, plasminogen, FR-antigen and haematocrit. Patients diagnosed as developing deep venous thrombosis with the 125I-fibrinogen technique had a significantly lower platelet adhesiveness and plasminogen level than those who were not.

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