UREMIC PLASMA, AFTER INFUSION OF DESMOPRESSIN, IMPROVES THE INTERACTION OF NORMAL PLATELETS WITH VESSEL SUBENDOTHELIUM

1987 ◽  
Author(s):  
R Castillo ◽  
G Escolar ◽  
J Monteagudo ◽  
A Cases ◽  
M Garrido ◽  
...  
Keyword(s):  
Bleeding Time ◽  
Surface Coverage ◽  
Glass Beads ◽  
Aggregate Formation ◽  
Perfusion System ◽  
Prolonged Bleeding Time ◽  
Perfusion Studies ◽  
Platelet Aggregate ◽  
Uremic Patients

Desmopressin (DDAVP) shortened the bleeding time and increased the platelet retention on glass beads and the platelet interaction on subendothelium measured by the Baumgartner perfusion system in 11 uremic patients in whom the three tests were abnormal previous to the treatment (1).Patients were chosen at random out of a group of 30 with prolonged bleeding time and decreased platelet retention on glass beads. All tests were performed on blood drawn before and one and six hours after a single dose of DDAVP (0.4 μg/kg body weight). Perfusion experiments were carried out at a shear rate of 800 sec-1.Levels of VIII:C, VIIIR:Ag and RiCof were at the upper limit of normality before DDAVP and significantly increased one hour after treatment. The multimeric structure of vWF in pretreatment plasma was normal ; one hour after DDAVP larger multimers appeared.After injection of DDAVP, the perfusion studies using reconstituted blood with uremic PPP in presence of isolated normal platelets and washed red cells, showed a statistically increased surface coverage and platelet aggregate formation on subendothelium (p < 0.05 respectively when compared to the pretreatment values). In the same perfusion assays, the in vitro addition to pretreatment plasmas of 1 u/ml of purified vWF with normal multimeric structure, or purified VIII:C and vWF (1 u/ml each) did not modify the decreased platelet interaction on subendothelium.These results confirm the shortening of bleeding time by DDAVP in uremic patients and reveal an increase of platelet interaction on vessel subendothelium mediated by a factor present in PPP. Besides, they show that the effect of DDAVP in these patients is not due to the quantitative increase of the plasmatic vWF and FVIII.(1) Blood, 68, 2:337-342, 1986.

ABNORMALITIES OF CYTOPLASMIC [Ca++] IN PLATELETS FROM UREMIC PATIENTS STUDIED WITH AEQU0RIN AND INDO-1

1987 ◽  
Author(s):  
J A Ware ◽  
B A Clark ◽  
M Smith ◽  
E W Salzman
Keyword(s):  
Normal Donor ◽  
Ionophore A23187 ◽  
Platelet Surface ◽  
Surface Receptors ◽  
Prolonged Bleeding ◽  
Prolonged Bleeding Time ◽  
Hemorrhagic Tendency ◽  
Uremic Patients ◽  
Plasma Factors

Uremic patients have a hemorrhagic tendency, often with prolonged bleeding times and abnormalities of platelet function in vitro. Whether these defects result from plasma factors, abnormalities in platelet surface receptors, or intracellular mediators is unknown. Accordingly, blood was obtained from 16 patients with severe uremia (BUN >90), and platelets were washed, loaded with aequorin or indo-1, gel-filtered, and resuspended in either plasma or buffer. Of the 16 patients, 4 had template bleeding times greater than 12 minutes, but platelet aggregation in plasma was not consistently impaired. However, the rise in cytoplasmic [Ca++] in response to the Ca++-ionophore A23187 or ADP in aequorin-loaded platelets from the 4 patients with long bleeding times was much lower than in uremic patients with normal bleejljLng times or in normal volunteers. The reduced [Ca++] response was associated with decreased aggregation of gel-filtered platelets in buffer. Prolonged bleeding time was less consistently correlated with decreased responses to epinephrine or arachidonate. Suspending washed aequorin-loaded uremic platelets in normal plasma for 10-20 min did not reverse the decreased agonist-induced rise in [Ca++]; platelets from a normal donor resuspended in uremic pla^iya responded normally. The agonist-induced rise in [Ca++] shown by indo-1 was not abnormal in patients with prolonged bleeding times; however, uremic patients generally had higher indo-l-indicated basal platelet cytoplasmic [Ca++] than normal. We conclude that the hemorrhagic tendency in some patients with uremia (|s associated with abnormal intracellular platelet [Ca++] regulation marked by elevated resting [Ca++] and a decreased rise in cytoplasmic [Ca++] in response to certain agonists; this latter abnormality appears to be correlated with prolonged bleeding times.

scholarly journals DDAVP enhances platelet adherence and platelet aggregate growth on human artery subendothelium

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 229-236 ◽  
Author(s):  
KS Sakariassen ◽  
M Cattaneo ◽  
A v.d. Berg ◽  
ZM Ruggeri ◽  
PM Mannucci ◽  
...  
Keyword(s):  
Bleeding Time ◽  
Close Association ◽  
Aggregate Formation ◽  
Human Artery ◽  
Primary Hemostasis ◽  
Platelet Adherence ◽  
Normal Individuals ◽  
Before And After ◽  
Platelet Aggregate ◽  
Aggregate Growth

Abstract The effect of intravenous 1-deamino (8-D-arginine)vasopressin (DDAVP) administration on platelet interaction with human artery subendothelium was investigated with flowing blood from five normal individuals and 12 patients with von Willebrand's disease (vWD). Three of the patients were diagnosed as vWD subtype I, four as subtype IIa, and five as subtype IIb. DDAVP administration to normals enhanced platelet adherence, in parallel with increasing plasma levels of factor VIII- related antigen ( FVIIIR :Ag) and ristocetin cofactor activity ( FVIIIR :RCF). Platelet aggregate formation was transiently increased within 90 minutes. Platelet adherence in patient blood before DDAVP infusion was subnormal. In patients with subtype I, administration of DDAVP normalized the bleeding time, enhanced the platelet adherence, and transiently improved the platelet aggregate formation. The platelet adherence was more corrected than would have been expected on the basis of the FVIIIR :Ag and FVIIIR :RCF levels. In patients with subtype IIa, infusion of DDAVP increased the FVIIIR :Ag levels approximately threefold, without affecting the FVIIIR :RCF levels, and in only two of four patients was a transiently enhanced platelet adherence with a corresponding shortening of the bleeding time observed. In patients with subtype IIb, administration of DDAVP increased the FVIIIR :Ag levels about threefold and the FVIIIR :RCF levels five to tenfold, but decreased the platelet adherence significantly. The bleeding time values were not normalized. A close association between the bleeding time values and corresponding platelet adherence values before and after DDAVP infusion was observed. Normalization of the bleeding time was paralleled with normalization of platelet adherence. We conclude that DDAVP improves the primary hemostasis by causing enhanced FVIII- vWF-mediated platelet adherence. DDAVP has little or no effect on the bleeding time in patients with subtype IIa and subtype IIb, because the platelet adherence is not normalized.

scholarly journals Patients with a prolonged bleeding time and normal aggregation tests may have storage pool deficiency: studies on one hundred six patients

Blood ◽  
1987 ◽  
Vol 70 (3) ◽  
pp. 620-623 ◽  
Author(s):  
HK Nieuwenhuis ◽  
JW Akkerman ◽  
JJ Sixma
Keyword(s):  
Platelet Count ◽  
Bleeding Time ◽  
Bleeding Tendency ◽  
Von Willebrand's Disease ◽  
Common Disorder ◽  
Storage Pool ◽  
Prolonged Bleeding ◽  
Prolonged Bleeding Time ◽  
Platelet Serotonin

Abstract One hundred six patients with storage pool deficiency (SPD) were studied with respect to platelet count, bleeding time, total platelet ATP and ADP, platelet serotonin, and in vitro aggregation. The diagnosis of SPD was made on basis of a prolonged bleeding time, a decreased total platelet ADP, and a diminished level of serotonin. Fifty-one patients from 34 unrelated families had congenital SPD, and 55 patients had acquired SPD. Congenital SPD was a common disorder in patients with a lifelong bleeding tendency and a prolonged bleeding time. The frequency in this group of patients was 18%, about one-half the frequency of von Willebrand's disease (vWd). Twenty-three percent of all patients had normal aggregation responses to ADP, epinephrine, and collagen; 33% had aggregation tracings typical for a secretion defect; and 44% had miscellaneous aggregation abnormalities. These findings indicate that SPD is common, heterogeneous, and not necessarily associated with in vitro aggregation abnormalities.

Sustained Bleeding after a leech Bite in the Apparent Absence of Hirudin

1989 ◽  
Vol 61 (03) ◽  
pp. 366-369 ◽  
Author(s):  
R Munro ◽  
F O P Hechtel ◽  
R T Sawyer
Keyword(s):  
Platelet Aggregation ◽  
Bleeding Time ◽  
Medicinal Leech ◽  
Bite Wound ◽  
Apparent Absence ◽  
Coagulation Parameters ◽  
Prolonged Bleeding ◽  
Prolonged Bleeding Time ◽  
Human Volunteers

SummaryThe bite of the medicinal leech bleeds for many hours. For decades it has been assumed that the remarkably prolonged bleeding time of a leech bite wound is due to hirudin, a specific anti-thrombin secreted by the leech during feeding. By measuring haematological parameters of blood oozing from a leech bite wound on 15 different occasions in 7 human volunteers, we demonstrate that the hirudin-sensitive coagulation parameters, including thrombin-induced platelet aggregation, are prolonged for only 15 min, after which they return to normal. This suggests that excess hirudin secreted by the leech is washed out during this period. However, bleeding from the leech bite wound persists for a mean of 10 h. Platelets in smears of exuding blood show no evidence of spontaneous aggregation, but in vitro platelet aggregation can be induced by exogenous collagen at any time. In view of sustained bleeding in the apparent absence of hirudin, attention is focussed onto an unsuspected factor or factors which may better explain the prolonged bleeding phenomenon.

Coagulation Studies after Administration of a Fat Emulsion, Intralipid®

1967 ◽  
Vol 18 (03/04) ◽  
pp. 664-669 ◽  
Author(s):  
S Cronberg ◽  
Inga Marie Nilsson
Keyword(s):  
Parenteral Nutrition ◽  
Whole Blood ◽  
Clinical Relevance ◽  
Bleeding Time ◽  
Fibrinolytic System ◽  
Platelet Adhesiveness ◽  
Single Infusion ◽  
Fat Emulsion ◽  
Prolonged Bleeding Time

SummaryA single infusion of a fat emulsion, Intralipid®, used for parenteral nutrition was given to 11 healthy normals, 3 patients with von Willebrand’s disease and 3 with mild or moderately severe thrombasthenia. The infusion had no effect on coagulation or the fibrinolytic system. Platelet adhesiveness, as determined with Hellem’s whole blood method, was markedly increased but not with his plasma-ADP method or with Salzman’s method. No shortening of the bleeding time was observed in the normals or in the patients with prolonged bleeding time. The change observed in platelet adhesiveness is therefore believed to be an in vitro artefact with no clinical relevance.

scholarly journals Subunit composition of plasma von Willebrand factor in patients with the myeloproliferative syndrome

Blood ◽  
1986 ◽  
Vol 68 (6) ◽  
pp. 1213-1217 ◽  
Author(s):  
U Budde ◽  
JA Dent ◽  
SD Berkowitz ◽  
ZM Ruggeri ◽  
TS Zimmerman
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Time ◽  
Polyacrylamide Gel Electrophoresis ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Prolonged Bleeding Time ◽  
Myeloproliferative Syndrome ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract In order to evaluate the role of proteolysis in acquired von Willebrand's disease (vWD) associated with the myeloproliferative syndrome, we have determined the relative quantity of von Willebrand factor (vWF) fragments as compared with the intact 225 kDa subunit in four patients. The plasma vWF of each individual lacked large multimers; each had a prolonged bleeding time; and both platelet and leukocyte counts were elevated. Plasma was obtained from blood drawn into 1 mmol/L leupeptin, 6 mmol/L N-ethylmaleimide, and 5 mmol/L EDTA to prevent in vitro proteolysis. vWF was isolated from plasma by immunoadsorbent chromatography, reduced, subjected to SDS-5% polyacrylamide gel electrophoresis, and immunoblotted with a mixture of 55 anti-vWF monoclonal antibodies. In three patients with essential thrombocytosis (ET) the 176 and 140 kDa fragments were increased in proportion to the intact 225 kDa subunit indicating increased proteolysis. Treatment of one ET patient with CCNU (Lomustine) decreased the platelet count and, to a lesser extent, the white blood cell count. This was associated with a correction of the bleeding time, a partial correction of the multimeric abnormality, and a lessening of vWF cleavage. In a patient with polycythemia rubra vera (PRV) the proportion of the 176 kDa fragment was increased to the upper limit of normal but there was no definite evidence of increased proteolysis. These studies provide evidence that proteolysis plays a role in the acquired von Willebrand's disease associated with the myeloproliferative syndrome. However, other mechanisms must also be considered.

scholarly journals Relation Between Bleeding Time and Platelet Connective Tissue Reaction After Aspirin

Blood ◽  
1973 ◽  
Vol 41 (3) ◽  
pp. 369-377 ◽  
Author(s):  
J. Hirsh ◽  
D. Street ◽  
J. F. Cade ◽  
H. Amy
Keyword(s):  
Connective Tissue ◽  
Bleeding Time ◽  
Normal Subjects ◽  
Tissue Reaction ◽  
Prolonged Bleeding Time ◽  
Subject Variability ◽  
Analysis Of Results ◽  
Platelet Release

Abstract Aspirin prolongs the bleeding time in normal subjects and inhibits platelet release and aggregation with connective tissue and other biological agents. We have investigated one of the possible mechanisms by which aspirin prolongs the bleeding time by comparing the effects of aspirin and placebo on the bleeding time and platelet aggregation with connective tissue in normal volunteers. Two separate studies were performed. Both showed prolongation of the bleeding time and inhibition of the platelet connective tissue reaction after aspirin, but only the second study showed a significant correlation between these changes. Both studies are reported in detail because the discrepancy between them illustrates some important principles that require consideration when relating the effects of drugs on platelet function in vitro to their effects in vivo. The findings suggest that when particular care is taken to standardize the measurement of the platelet connective tissue reaction in terms of the stimulus used, subject variability, and analysis of results, the prolonged bleeding time after aspirin can be shown to be related to the defect produced in the platelet connective tissue reaction.

scholarly journals Molecular Basis forStaphylococcus aureus–Mediated Platelet Aggregate Formation Under Arterial Shear In Vitro

2008 ◽  
Vol 28 (2) ◽  
pp. 335-340 ◽  
Author(s):  
Steven W. Kerrigan ◽  
Niamh Clarke ◽  
Anthony Loughman ◽  
Gerardene Meade ◽  
Timothy J. Foster ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Aggregate Formation ◽  
Platelet Aggregate

scholarly journals Intercellular calcium communication regulates platelet aggregation and thrombus growth

2003 ◽  
Vol 160 (7) ◽  
pp. 1151-1161 ◽  
Author(s):  
Warwick S. Nesbitt ◽  
Simon Giuliano ◽  
Suhasini Kulkarni ◽  
Sacha M. Dopheide ◽  
Ian S. Harper ◽  
...  
Keyword(s):  
Platelet Adhesion ◽  
Purinergic Receptor ◽  
Cytosolic Calcium ◽  
Calcium Flux ◽  
Aggregate Formation ◽  
Signaling Mechanism ◽  
Activated Platelets ◽  
Platelet Aggregate ◽  
Platelet Aggregates

The ability of platelets to form stable adhesion contacts with other activated platelets (platelet cohesion or aggregation) at sites of vascular injury is essential for hemostasis and thrombosis. In this study, we have examined the mechanisms regulating cytosolic calcium flux during the development of platelet–platelet adhesion contacts under the influence of flow. An examination of platelet calcium flux during platelet aggregate formation in vitro demonstrated a key role for intercellular calcium communication (ICC) in regulating the recruitment of translocating platelets into developing aggregates. We demonstrate that ICC is primarily mediated by a signaling mechanism operating between integrin αIIbβ3 and the recently cloned ADP purinergic receptor P2Y12. Furthermore, we demonstrate that the efficiency by which calcium signals are propagated within platelet aggregates plays an important role in dictating the rate and extent of thrombus growth.

scholarly journals DDAVP enhances platelet adherence and platelet aggregate growth on human artery subendothelium

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 229-236 ◽  
Author(s):  
KS Sakariassen ◽  
M Cattaneo ◽  
A v.d. Berg ◽  
ZM Ruggeri ◽  
PM Mannucci ◽  
...  
Keyword(s):  
Bleeding Time ◽  
Close Association ◽  
Aggregate Formation ◽  
Human Artery ◽  
Primary Hemostasis ◽  
Platelet Adherence ◽  
Normal Individuals ◽  
Before And After ◽  
Platelet Aggregate ◽  
Aggregate Growth

The effect of intravenous 1-deamino (8-D-arginine)vasopressin (DDAVP) administration on platelet interaction with human artery subendothelium was investigated with flowing blood from five normal individuals and 12 patients with von Willebrand's disease (vWD). Three of the patients were diagnosed as vWD subtype I, four as subtype IIa, and five as subtype IIb. DDAVP administration to normals enhanced platelet adherence, in parallel with increasing plasma levels of factor VIII- related antigen ( FVIIIR :Ag) and ristocetin cofactor activity ( FVIIIR :RCF). Platelet aggregate formation was transiently increased within 90 minutes. Platelet adherence in patient blood before DDAVP infusion was subnormal. In patients with subtype I, administration of DDAVP normalized the bleeding time, enhanced the platelet adherence, and transiently improved the platelet aggregate formation. The platelet adherence was more corrected than would have been expected on the basis of the FVIIIR :Ag and FVIIIR :RCF levels. In patients with subtype IIa, infusion of DDAVP increased the FVIIIR :Ag levels approximately threefold, without affecting the FVIIIR :RCF levels, and in only two of four patients was a transiently enhanced platelet adherence with a corresponding shortening of the bleeding time observed. In patients with subtype IIb, administration of DDAVP increased the FVIIIR :Ag levels about threefold and the FVIIIR :RCF levels five to tenfold, but decreased the platelet adherence significantly. The bleeding time values were not normalized. A close association between the bleeding time values and corresponding platelet adherence values before and after DDAVP infusion was observed. Normalization of the bleeding time was paralleled with normalization of platelet adherence. We conclude that DDAVP improves the primary hemostasis by causing enhanced FVIII- vWF-mediated platelet adherence. DDAVP has little or no effect on the bleeding time in patients with subtype IIa and subtype IIb, because the platelet adherence is not normalized.

Sign in / Sign up

Export Citation Format

Share Document