1,720,995 research outputs found
In vitro and in vivo effects of desmopressin on platelet function
No full textBACKGROUND AND OBJECTIVE: Desmopressin (DDAVP) may shorten bleeding time in patients with disorders of platelet function, but its mechanism of action in these conditions is still a matter of debate. In particular, contrasting results have been obtained concerning the ability of DDAVP to interact with platelets and to activate them directly. To gain further information on the DDAVP-platelet interaction, we studied the in vitro and ex vivo effects of DDAVP on platelet function.
DESIGN AND METHODS: Platelet responses to DDAVP both as a single agent and in conjunction with agonists of platelet activation were investigated. For in vitro experiments platelets were obtained from healthy adult volunteers, while the ex vivo effects of DDAVP were studied in 12 patients with a bleeding disorder receiving a test dose of this drug.
RESULTS: DDAVP in vitro did not induce either platelet aggregation or surface expression of the activation-dependent antigens; it did, however, greatly inhibit platelet aggregation response to vasopressin (AVP) and increased the maximal extent of platelet aggregation induced by collagen and ADP. DDAVP infusion did not promote the expression of activation antigens, but significantly enhanced ex vivo platelet aggregation stimulated by ADP and collagen. This priming effect was observed in patients with von Willebrand's disease, hemophilia A, May-Hegglin anomaly, gray platelet syndrome and Ehlers-Danlos syndrome. In all these patients bleeding time was shortened by DDAVP infusion. In contrast, neither platelet aggregation nor bleeding time was modified in two subjects with Glanzmann's thrombasthenia.
INTERPRETATION AND CONCLUSIONS: Our in vitro experiments indicate that DDAVP interacts directly with platelets and facilitates their activation via other agonists. In vivo results suggest that this effect occurs and is clinically relevant in patients with platelet dysfunction responding to DDAVP with a shortening of bleeding time
A new variant of Bernard-Soulier syndrome characterized by dysfunctional glycoprotein (GP) IB and severely reduced amounts of GPIX and GPV.
No full textWe describe a new variant of Bernard-Soulier syndrome characterized by almost normal amounts of GPIb and severely reduced GPIX and GPV. Despite surface expression, GPIbalpha failed to support ristocetin-induced platelet agglutination and to bind two conformation-dependent monoclonal antibodies, suggesting a qualitative defect. Sequence analysis of the gene coding for GPIX revealed a T-to-C substitution at base 1811, leading to a Leu40Pro conversion, whereas no defects were found in the coding region of the GPIbalpha gene. Allele-specific restriction enzyme analysis showed that the propositus and one of his sisters. both with severe bleeding diathesis. were homozygous for the GPIX mutation: the members of the family with mild bleeding diathesis and/or giant platelets in the peripheral blood were heterozygous, whereas the healthy ones were homozygous for the normal allele. Infusion of 1-desamino-8-D-arginine vasopressin normalized bleeding time in the two severely affected patients, although it did not modify ristocetin-induced platelet agglutination or membrane expression of GPIbalpha, GPIX, GPIIb-IIIa and GMP-140. Moreover, in one patient, normalization of bleeding time and rise of von Willebrand factor plasma concentration did not seem to be directly related
Ristocetin-induced platelet agglutination stimulates GPIIb-IIIa-dependent calcium influx.
No full textWe found that intracellular Ca2+ concentration ([Ca2+]i) increased during ristocetin-induced agglutination of aequorin loaded platelets resuspended in plasma. Chelation of extracellular Ca2+ had no effect on platelet clumping, but delayed and greatly reduced Ca2+ increase, indicating that it derived for the most part from Ca2+ influx. Nine monoclonal antibodies (MA) against glycoprotein (GP) Ib largely prevented ristocetin-induced platelet clumping and [Ca2+]i increase, while three anti-GPIb MA with no effect on platelet clumping did not interfere with Ca2+ movement. In unstirred samples platelet agglutination was greatly reduced and [Ca2+]i increase was abolished, suggesting that close platelet-to-platelet contact, in addition to von Willebrand factor (vWF) binding to GPIb, is necessary for Ca2+ transient. Nine MA against GPIIb/IIIa, the gly-arg-gly-asp-ser (GRGDS) peptide and GPIIb/IIIa complex dissociation had no effect on platelet agglutination, but significantly reduced Ca2+ increase. Our results suggest that platelet clumping induced by vWF binding to GPIb is responsible for GPIIb-IIIa dependent Ca2+ influx
Thrombocytopenia, giant platelets, and leukocyte inclusion bodies (May-Hegglin anomaly). Clinical and laboratory findings.
No full textPURPOSE: May-Hegglin anomaly is a rare hereditary condition characterized by the triad of thrombocytopenia, giant platelets, and inclusion bodies in leukocytes. Clinical features and the pathogenesis of bleeding in this disease are poorly defined.
PATIENTS AND METHODS: From 1988 to 1996 we studied 15 new May-Hegglin anomaly patients from 7 unrelated Italian families. In addition to clinical examination and routine laboratory testing, we measured bleeding time, platelet aggregation and release reaction, and platelet staining for tubulin, and performed ultrastructural study of polymorphonuclear leukocytes.
RESULTS: Although the mean age of our patients was 33 years, May-Hegglin anomaly had not been previously recognized in any of them. Bleeding diatheses ranged from severe to absent, and platelet count from 26 to 178 x 10(9)/L. No correlation was found between bleeding tendency and platelet count. Previous therapy with corticosteroids, high-dose immunoglobulins, and splenectomy had no effect on platelet count or bleeding diathesis. Desmopressin infusion greatly shortened the bleeding time in the most severely affected patient. The in vitro function of platelets was normal except for the absence of shape change in all subjects and defective response to epinephrine in 8 of 15 patients. Platelet tubulin was distributed unevenly instead of being organized in a circumferential band at the cell periphery.
CONCLUSION: The diagnosis of May-Hegglin is easily missed, and its frequency is probably underestimated. A qualitative defect of platelets may be responsible for mild bleeding diathesis even in the absence of thrombocytopenia, while severe bleeding results from both qualitative and quantitative platelet defects. May-Hegglin anomaly should be suspected whenever a patient has a low platelet count or a bleeding diathesis of unknown origin
EFFECT OF APROTININ ON PLATELET COMPOSITION AND FUNCTION IN PATIENTS UNDERGOING CARDIAC REINTERVENTION UNDER EXTRACORPOREAL-CIRCULATION (ECC)
No full text
An unusual association of paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome, and diffuse large B-cell non-Hodgkin lymphoma in a Caucasian man
No full textWe here report an unusual association of myelodysplastic syndrome, paroxysmal nocturnal hemoglobinuria (PNH), and diffuse large B-cell non-Hodgkin lymphoma (NHL) in a 62- year-old male.PNH is a stem cell disorder caused by a PIG-A gene mutation. As a consequence, blood cells completely or partially lack surface proteins that are tethered to the membrane through the glycosylphosphatidylinositol (GPI) anchor. The resulting absence of CD55 and CD59 molecules on red cells renders them sensitive to complement-mediated intravascular hemolysis and associated hemoglobinuria. In conclusion, in this patient, eculizumab was highly effective in controlling PNH activity and decreasing intravascular
hemolysis; it greatly improved the quality of life, reduced the risk for thrombosis, and eliminated the need for blood transfusions, despite the presence of a concomitant MDS with an abnormal karyotype. Death was related due an aggressive form of high grade nH
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
- …
