scholarly journals "Impotent" Platelets in Albinos With Prolonged Bleeding Times

Blood ◽  
1972 ◽  
Vol 39 (4) ◽  
pp. 490-499 ◽  
Author(s):  
Harold M. Maurer ◽  
James A. Wolff ◽  
Sue Buckingham ◽  
Arthur R. Spielvogel
Keyword(s):  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Bleeding Tendency ◽  
Prolonged Bleeding ◽  
Prolonged Bleeding Time ◽  
Normal Platelet ◽  
Tryptophan Metabolites ◽  
History Of

Abstract Functional, biochemical, and morphologic platelet abnormalities are reported in four children with the syndrome of albinism, mild bleeding tendency, prolonged bleeding time, and normal platelet count. In these children, primary platelet aggregation with adenosine diphosphate occurred normally, but secondary aggregation was impaired. Collagen and norepinephrine produced almost no platelet aggregation. Platelet content of serotonin (5-HT) was markedly reduced, and uptake and retention of 5-HT by the platelets in vivo and in vitro was poor. In one child who was given a tryptophan load, urinary tryptophan metabolites were normal, suggesting that there was no evidence of a block in the 5-HT synthetic pathway in the gastrointestinal tract. Electron microscopy revealed an absence of densely osmophilic granules in 5-HT poor platelets. Platelets from other albinos with no history of bleeding contained normal amounts of 5-HT and densely osmophilic granules.

scholarly journals Guanidinosuccinic Acid on Human Platelet Effects of Exogenous Urea, Creatinine, and Aggregation In Vitro

Blood ◽  
1972 ◽  
Vol 39 (3) ◽  
pp. 388-397 ◽  
Author(s):  
James W. Davis ◽  
James R. McField ◽  
Phyllis E. Phillips ◽  
Barbara A. Graham
Keyword(s):  
Platelet Aggregation ◽  
Optical Density ◽  
Bleeding Time ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Bleeding Tendency ◽  
Blood Concentrations ◽  
Prolonged Bleeding Time ◽  
Guanidinosuccinic Acid

Abstract Patients with severe uremia may have a bleeding tendency associated with a prolonged bleeding time and an adequate platelet count. We have tested the effects on platelet aggregation of three compounds that are found in increased concentration in the blood of patients with renal failure. The addition of urea was followed by an immediate, but transient, increase in optical density of platelet-rich plasma. This precluded the use of turbidimetric techniques for the measurement of platelet aggregation after addition of urea, until the optical density became stable. Adenosine diphosphate-, collagen-, and norepinephrine-induced platelet aggregation were shown to be inhibited 1 hr after urea was added to platelet-rich plasma to produce urea nitrogen increments of 100-300 mg/ 100 ml. Increasing concentrations of creatinine by 10 or 20 mg/100 ml did not inhibit platelet aggregation. Guanidinosuccinic acid, in a concentration in the range found in uremic plasma, also had no effect on platelet aggregation. Through inhibition of platelet aggregation, elevated blood concentrations of urea may be one of the causes of the bleeding tendency of uremic platients.

Essential Athrombia

1975 ◽  
Vol 33 (02) ◽  
pp. 278-285 ◽  
Author(s):  
Şeref Inceman ◽  
Yücel Tangün
Keyword(s):  
Platelet Aggregation ◽  
Bleeding Time ◽  
Bleeding Tendency ◽  
Clot Retraction ◽  
Platelet Factor ◽  
Prolonged Bleeding Time ◽  
Normal Platelet ◽  
Aggregation Response ◽  
Platelet Disorder ◽  
Fibrinogen Content

SummaryA constitutional platelet function disorder in a twelve-year-old girl characterized by a lifelong bleeding tendency, prolonged bleeding time, normal platelet count, normal clot retraction, normal platelet factor 3 activity and impaired platelet aggregation was reported.Platelet aggregation, studied turbidimetrically, was absent in the presence of usual doses of ADP (1–4 μM), although a small wave of primary aggregation was obtained by very large ADP concentrations (25–50 μM). The platelets were also unresponsive to epinephrine, thrombin and diluted collagen suspensions. But an almost normal aggregation response occurred with strong collagen suspensions. The platelets responded to Ristocetin. Pelease of platelet ADP was found to be normal by collagen and thrombin, but impaired by kaolin. Platelet fibrinogen content was normal.The present case, investigated with recent methods, confirms the existence of a type of primary functional platelet disorder characterized solely by an aggregation defect, described in 1955 and 1962 under the name of “essential athrombia.”

scholarly journals Improved Antithrombotic Activity and Diminished Bleeding Side Effect of a PEGylated αIIbβ3 Antagonist, Disintegrin

Toxins ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 426
Author(s):  
Yu-Ju Kuo ◽  
Yao Tsung Chang ◽  
Ching-Hu Chung ◽  
Woei-Jer Chuang ◽  
Tur-Fu Huang
Keyword(s):  
Platelet Aggregation ◽  
Side Effect ◽  
Half Life ◽  
Platelet Rich Plasma ◽  
Drug Stability ◽  
Severe Thrombocytopenia ◽  
Bleeding Tendency ◽  
Dependent Manner

Polymer polyethylene glycol (PEG), or PEGylation of polypeptides improves protein drug stability by decreasing degradation and reducing renal clearance. To produce a pharmaceutical disintegrin derivative, the N-terminal PEGylation technique was used to modify the disintegrin derivative [KGDRR]trimucrin for favorable safety, pharmacokinetic profiles, and antithrombotic efficacy. We compared intact [KGDRR]trimucrin (RR) and PEGylated KGDRR (PEG-RR) by in vitro and in vivo systems for their antithrombotic activities. The activity of platelet aggregation inhibition and the bleeding tendency side effect were also investigated. PEG-RR exhibited optimal potency in inhibiting platelet aggregation of human/mouse platelet-rich plasma activated by collagen or ADP with a lower IC50 than the intact derivative RR. In the illumination-induced mesenteric venous thrombosis model, RR and PEG-RR efficaciously prevented occlusive thrombosis in a dose-dependent manner. In rotational thromboelastometry assay, PEG-RR did not induce hypocoagulation in human whole blood even given at a higher concentration (30 μg/mL), while RR slightly prolonged clotting time. However, RR and PEG-RR were not associated with severe thrombocytopenia or bleeding in FcγRIIa-transgenic mice at equally efficacious antithrombotic dosages. We also found the in vivo half-life of PEGylation was longer than RR (RR: 15.65 h vs. PEG-RR: 20.45 h). In conclusion, injectable PEG-RR with prolonged half-life and decreased bleeding risk is a safer anti-thrombotic agent for long-acting treatment of thrombus diseases.

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.

The microtubule modulator RanBP10 plays a critical role in regulation of platelet discoid shape and degranulation

Blood ◽  
2009 ◽  
Vol 114 (27) ◽  
pp. 5532-5540 ◽  
Author(s):  
Stefan Kunert ◽  
Imke Meyer ◽  
Silke Fleischhauer ◽  
Martin Wannack ◽  
Janine Fiedler ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Critical Role ◽  
Mutant Mice ◽  
Axis Ratio ◽  
Prolonged Bleeding Time ◽  
Normal Platelet ◽  
And Function ◽  
Granule Release

Abstract Terminally mature megakaryocytes undergo dramatic cellular reorganization to produce hundreds of virtually identical platelets. A hallmark feature of this process is the generation of an elaborate system of branched protrusions called proplatelets. We recently identified RanBP10 as a tubulin-binding protein that is concentrated along polymerized microtubules in mature megakaryocytes. RanBP10 depletion in vitro caused the disturbance of polymerized filaments. Here we study the function of RanBP10 in vivo by generating deficient mice using a gene-trap approach. Mutant mice show normal platelet counts, and fetal liver-derived megakaryocytes reveal only slightly reduced proplatelet formation. However, ultrastructural analysis unveiled a significantly increased geometric axis ratio for resting platelets, and many platelets exhibited disorders in microtubule filament numbers and localization. Mutant mice showed a markedly prolonged bleeding time. Granule release, a process that depends on internal contraction of the microtubule marginal coil, also was reduced. Flow cytometry analysis revealed reduced expression of CD62P and CD63 after PAR4-peptide stimulation. These data suggest that RanBP10 plays an essential role in hemostasis and in maintaining microtubule dynamics with respect to both platelet shape and function.

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.

Prostaglandins and Platelet Aggregation in Vivo

1970 ◽  
Vol 23 (02) ◽  
pp. 286-292 ◽  
Author(s):  
J Kloeze
Keyword(s):  
Platelet Aggregation ◽  
Intravenous Injection ◽  
Adenosine Diphosphate ◽  
Causative Factor ◽  
Respiratory Arrest ◽  
Platelet Thrombi ◽  
Eventual Death ◽  
The Brain

SummaryProstaglandins E1 and ω-homo-E1 which were shown previously to inhibit adenosine diphosphate (ADP)-induced platelet aggregation in vitro have now been found to inhibit this process also in vivo. Both prostaglandins inhibit transient thrombocytopenia induced by intravenous injection of ADP; PGE1 increases also the LD 50 of ADP when injected in high amounts into young rats. In both cases platelet aggregation in vivo is the primary cause of the phenomena observed.The symptoms observed on overdosing ADP by intravenous injection are unconsciousness within 10-20 sec after completion of the injection immediately followed by respiratory arrest and eventual death of the animal, generally within 10 min. It seems that blocking of the supply of blood to the brain by platelet thrombi, which on histological examination were found to occlude blood vessels in different organs, is the most important causative factor of the symptoms observed.

Platelet Unresponsiveness to Collagen: Involvement of Glycoprotein Ia-IIa (α2β1 Integrin) Deficiency Associated with a Myeloproliferative Disorder

1995 ◽  
Vol 73 (03) ◽  
pp. 521-528 ◽  
Author(s):  
Makoto Handa ◽  
Yohko Kawai ◽  
Tetuji Kamata ◽  
Takushi Koyama ◽  
Hirofumi Nagai ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Past History ◽  
Surface Membrane ◽  
Surface Expression ◽  
Myeloproliferative Disorder ◽  
Prolonged Bleeding Time ◽  
Normal Platelet ◽  
Activated T Lymphocytes ◽  
History Of ◽  
Α2β1 Integrin

SummaryWe studied a 66-year-old man with a myeloproliferative disorder who presented with a prolonged bleeding time and marked thrombocytosis (platelet count, 3,890 × 109/1). There was no past history of a bleeding disorder. The patient had normal coagulation data. His platelets completely lacked collagen-induced platelet aggregation and adhesion, but showed normal responses to other agonists. All family members tested showed normal platelet aggregation with collagen.Analysis of 125I surface-labeled platelets by two-dimensional SDS gel electrophoresis disclosed absence of the spot corresponding to platelet membrane GPIa (α2) but no other significant deficiencies of major platelet glycoproteins i.e., GPIb, IIb-IIIa, and IV. Immunoisolation studies of the patient’s platelets indicated that neither anti-GPIa nor anti-GPIIa (β1) monoclonal antibody (mAb) isolated any surface membrane proteins corresponding to GPIa. GPVI, a putative collagen receptor, was immunoisolated from the platelets. Indirect immunofluorescence study using flow cytometry confirmed that the patient’s platelets were totally deficient in surface expression of the GPIa-IIa complex (α2β1, integrin). In contrast, phytohemoagglutinin-activated T-lymphocytes from the patient expressed normal concentrations of this complex.The data suggest that our patient had an acquired deficiency of the platelet GPIa-IIa complex, due to a myeloproliferative disorder, which might account for the absence of responsiveness of his platelet to collagen.

scholarly journals Effect of propranolol on platelet function

Blood ◽  
1977 ◽  
Vol 49 (2) ◽  
pp. 185-196 ◽  
Author(s):  
BB Weksler ◽  
M Gillick ◽  
J Pink
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Direct Action ◽  
Blood Platelets ◽  
Adenosine Diphosphate ◽  
Ionophore A23187 ◽  
Atherosclerotic Vascular Disease ◽  
Clot Retraction

Abstract Excessive reactivity of blood platelets may contribute to atherosclerotic vascular disease. Hence drugs which alter platelet function may be protective. Prompted by findings that propranolol therapy normalized hyperactive platelet aggregation in patients with coronary artery disease, we studied propranolol in vitro to assess its action on platelets. At concentrations similar to those achieved in vivo (0.1–1 muM), propranolol raised the thresholds for aggregation of some normal paltelets by adenosine diphosphate (ADP). At higher concentrations (10-50 muM), propranolol abolished the second wave of platelet aggregation induced by ADP and epinephrine, and inhibited aggregation induced by collagen, thrombin, and the ionophore A23187. Propanolol blocked the release of 14C-serotonin from platelets, inhibited platelet adhesion to collagen, and interfered with clot retraction. Propranolol blocked ionophore-induced uptake of 45Ca by platelets. Inhibition appeared unrelated to beta-adrenergic blockage, as d(+) propranolol (which lacks beta-blocking activity) was equipotent with 1(-) propranolol. Moreover, practolol, a beta-blockading drug which is nonlipophilic, did not inhibit platelet function. These studies suggested that propranolol, like local anesthetics, decreased platelet responsiveness by a direct action on the platelet membrane, possibly by interfering with calcium availability. Modulation of platelet function by propranolol may occur at concentrations achieved at usual clinical doses of the drug.

SEVERE VON WILLEBRAND'S DISEASE WITH ABNORMAL PLATELET AGGREGATION

1987 ◽  
Author(s):  
A Ihara ◽  
Y Kobayashi ◽  
Y Aramitsu ◽  
Y Hara ◽  
K Fujimura ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Bleeding Tendency ◽  
Clot Retraction ◽  
Plasma Clot ◽  
Laboratory Findings ◽  
Prolonged Bleeding Time ◽  
History Of ◽  
Platelet Aggregation Defect ◽  
Minor Injuries ◽  
Storage Pool Disease

A 17-year-old boy with a life long history of easy bruising, epistaxis, subcutaneous hematoma and prolonged bleeding time from minor injuries, was initially diagnosed as having von Willebrand's disese, when he presented epistaxis at 2 years of age. Since his initial diagnosis, he has been treated with cryoprecipitate on many occasions to correct his bleeding tendency. The laboratory findings in the patient and his family are summarized in the table. The patient's mother, father and one brother have not complained any bleeding tendency.Multimeric analysis of vWF using SDS agarose gels showed absence of large multimer in the patient's plasma, decreased large multimer in mother's and brother's plasma. When the patient's PRP was tested for aggregation and release of ATP by ADP, epinephrine and collagen, using lumi aggregometer, platelet aggregation was abnormal as shown by disaggregation and almost no ATP activity was detectable in the supernatant. ATP contents of patient's and father's platelet was about 50% of normal platelets. Washed platelets of the patient in normal plasma did not aggregate normally, but washed normal platelets in the patient's plasma aggregate normally. No inhibitor of vWF could be demonstrated in the patient's plasma. Clot retraction was normal. These findings suggest that our patient has inherited vWD from materal side and the platelet aggregation defect, probably a kind of storage pool disease, from the paternal side of the family.

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