1/18. DDAVP normalized the bleeding time in patients with congenital platelet TxA2 receptor abnormality.BACKGROUND: An Arg60-to-Leu mutation was found in the first cytoplasmic loop of the PLT TxA2 receptor as a new congenital PLT disorder characterized by impaired responsiveness to TxA2. However, it has not been clarified whether DDAVP is effective in correcting the bleeding time (BT) in this PLT disorder. STUDY DESIGN AND methods: DDAVP (0.4 microg/kg) was intravenously administered over 20 minutes in five patients with this PLT disorder, and template BT, PLT retention to glass beads, PLT aggregation, and a coagulation study were performed before and after the infusion of DDAVP. PLT TxA2 synthesis defects (cyclo-oxygenase deficiency, volunteers taking aspirin), thrombasthenia, and bernard-soulier syndrome were also included in this study. RESULTS: The normalization of BT was found in all patients with this PLT disorder, and one of the patients successfully underwent oral surgical procedures with DDAVP as the only hemostatic agent. DDAVP was also efficacious in the TxA2 synthesis defect but not in other disorders. FVIII coagulation activity, vWF antigen, and ristocetin cofactor significantly increased in all patients after DDAVP, but no changes were seen in the PLT retention rate and PLT aggregation study after DDAVP infusion. CONCLUSION: DDAVP was effective in correcting BT in patients with impaired responsiveness to TxA2 as well as impaired production of TxA2.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/18. Severe deficiency of glycoprotein VI in a patient with gray platelet syndrome.We report a novel case of gray platelet syndrome (GPS) where a severe deficiency of the platelet collagen receptor, glycoprotein (GP) VI, accompanies classical symptoms of a low platelet count and platelets lacking alpha-granules. Dense granules were normally present. platelet aggregation with collagen was severely decreased, as was the response to convulxin (Cvx), a GPVI agonist. Quantitative analysis of GPVI using fluorescein isothiocyanate (FITC)-Cvx in flow cytometry showed its virtual absence on the patient's platelets. The GPVI deficiency was confirmed using monoclonal antibodies in Western blotting and in immunogold labeling on frozen thin sections where internal pools of GPVI were confirmed for normal platelets. The Fc receptor gamma-chain, constitutively associated with GPVI in normal platelets, was present in subnormal amounts, and the phospholipase c gamma 2-dependent activation pathway appeared to function normally. No autoantibodies to GPVI were found in the patient's serum using monoclonal antibody immobilization of platelet antigen (MAIPA). Sequencing of coding regions of the GPVI gene failed to show abnormalities, and mRNA for GPVI was present in the patient's platelets, pointing to a probable acquired defect in GPVI expression. Our results may provide a molecular explanation for the subgroup of patients with severely deficient collagen-induced platelet aggregation as previously described for GPS in the literature.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
3/18. Management of bleeding in a multi-transfused patient with positive HLA class I alloantibodies and thrombocytopenia associated with platelet dysfunction refractory to transfusion of cross-matched platelets.thrombocytopenia is a common condition in the critical care setting. Repetitive platelet transfusion might lead to formation of alloantibodies. HLA class I and human platelet antigen antibodies can lead to transfusion-refractory thrombocytopenia. Transfusion of cross-matched platelets often is effective in these patients. We report on the successful use of recombinant activated factor VII in an acute bleeding situation in a multi-transfused patient presenting with positive HLA class I alloantibody status and thrombocytopenia associated with platelet dysfunction refractory to even transfusion of cross-matched platelets. The 41-year-old female patient developed HLA class I antibodies during former episodes of massive transfusion. Her former medical history was empty concerning hemorrhagic events. During this specific bleeding episode the patient suffered from intractable profuse bleeding from the nasopharynx and oral cavity. Global coagulation tests were within the normal range. Platelet dysfunction was confirmed by PFA100. Initially the patient responded well to Desmopressin infusion, but after 36 h she became thrombocytopenic and refractory to even transfusion of cross-matched platelets. Recombinant activated factor VII was chosen as the last resort. Two identical boli of 160 microg/kg NovoSeven each were injected via a central line within an interval of 3 h. After the first injection bleeding was significantly reduced and vasopressor support discontinued. After the second bolus bleeding completely ceased and did not reoccur. We did not observe any side effects. The pluripotent hemostatic agent recombinant activated factor VII might be a new option in the treatment of hemorrhagic episodes in patients presenting with this rare disorder, especially when the patient is refractory to cross-matched platelets or matched platelets are not available.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
4/18. Lack of platelet response to collagen associated with an autoantibody against glycoprotein Ia: a novel cause of acquired qualitative platelet dysfunction.Platelets from a patient with an acquired hemorrhagic disorder had a severely impaired response to collagen, whereas platelet aggregation to other agonists and coagulations tests were normal. No abnormalities of the patient's platelet membrane glycoproteins (GP) were seen. Treatment of the patient with immunosuppressive agents temporarily improved both the bleeding tendency and the collagen responsiveness of the platelets. An IgG was found to be present in the plasma, directed against a protein comigrating with GPIa, and coadsorbing with GPIa to insoluble collagen fibers in a Mg2 (-)dependent manner. Furthermore, GPIa was recognized by the patient's antibody when affinity-purified GPIa-IIa was used as antigen. Finally, the GPIa-IIa complex was immunoprecipitated from a platelet lysate by patient's plasma. In addition, purified platelet specific IgG's from the patient inhibited aggregation of normal platelets induced by collagen or by wheat germ agglutinin. We conclude that the lack of response to collagen of the patient's platelets may well be due to the presence of an autoantibody against GPIa.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
5/18. Glanzmann's thrombasthenia associated with a transient deficiency of factor xiii.A three-year-old girl suffering from ecchymoses developed severe epistaxis. The diagnosis of thrombasthenia was made on the basis of platelet aggregation studies, flow cytometric analysis with monoclonal antibodies and gel electrophoretic analysis. In addition, coagulation studies at the time of epistaxis repeatedly showed a transient deficiency of factor xiii activity and antigen.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
6/18. A new congenital platelet abnormality characterized by spontaneous platelet aggregation, enhanced von willebrand factor platelet interaction, and the presence of all von willebrand factor multimers in plasma.A case is reported of a 49-year-old woman with a mild bleeding tendency. Her bleeding time, platelet count and size, plasma ristocetin cofactor activity, von Willebrand factor (vWF) antigen, and vWF multimeric pattern are all within normal limits. Spontaneous platelet aggregation is observed when citrated platelet-rich plasma (PRP) is stirred in an aggregometer cuvette. This aggregation is completely is only slightly diminished by an antiglycoprotein (GP) IIb/IIIa or by an anti GPIb monoclonal antibody. The patient's PRP shows increased sensitivity to ristocetin. The distinct feature of this patient, also present in two family members studied, is that platelet aggregation is initiated by purified vWF in the absence of any other agonist. The vWF-induced platelet aggregation is abolished by anti-GPIb and anti-GPIIb/IIIa monoclonal antibodies and by EDTA (5 mmol/L). apyrase inhibits the second wave of aggregation. Patient's platelets in PRP are four to six times more reactive to asialo vWF-induced platelet aggregation than normal platelets. The amount of radiolabeled vWF bound to platelets in the presence of either low concentration of ristocetin or asialo vWF was increased 30% compared with normal. The patient's platelet GPIb was analyzed by SDS page and immunoblotting and by binding studies with anti-GPIb monoclonal antibodies showed one band with slightly increased migration pattern and a normal number of GPIb molecules. Unlike the previously reported patients with pseudo or platelet-type von Willebrand disease, this patient has normal vWF parameters.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
7/18. Acquired bernard-soulier syndrome. Evidence for the role of a 210,000-molecular weight protein in the interaction of platelets with von willebrand factor.A patient with a lymphoproliferative disorder developed bleeding associated with a prolonged bleeding time and a selective defect of platelet aggregation in response to ristocetin. The patient's purified IgG was shown to inhibit aggregation of washed normal platelets by ristocetin and von willebrand factor (F VIII:vWF). By Western blotting, it was shown that antibody bound specifically to an antigen of Mr 210,000 present on normal platelets but missing on platelets from patients with congenital bernard-soulier syndrome (BSS). Binding was effected by the F(ab)2 portion of the IgG, indicating the presence of an autoantibody rather than an immune complex. These results suggest that the 210,000-Mr protein is involved in the interaction of F VIII:vWF with platelets. Furthermore, we have demonstrated the apparent absence of an additional protein on congenital BSS platelets. Heat-aggregated IgG was also shown to bind to the 210,000-Mr protein, suggesting that this protein may function as an Fc receptor on platelets. The relationship of the 210,000-Mr protein to glycoprotein Ib and the precise role of this protein in the interaction of platelets with F VIII:vWF need to be characterized.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
8/18. The management of dental extractions in cases of thrombasthenia complicated by the development of isoantibodies to donor platelets.Two cases of thrombasthenia, a rare hereditary disorder of platelet function, are presented. The oral surgical and dental management of these cases is discussed in the light of the development of isoantibodies to transfused platelets in one of the cases and in another case encountered. The problems of obtaining donor platelets matched for platelet and HL-A antigens are discussed. Emphasis is placed on the use of local hemostatic measures and antifibrinolytic agents in the management of hemorrhage in this disorder and the avoidance of platelet transfusions as far as possible. Conservative dentistry and early preventive dental advice are considered desirable in order to avoid extractions.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
9/18. Shortening of bleeding time by 1-deamino-8-arginine vasopressin (DDAVP) in the absence of platelet von willebrand factor in gray platelet syndrome.The gray platelet syndrome is a rare disorder characterised by the absence of platelet alpha-granules and their contents. We describe a new patient and the effects of infusions of 1-deamino-8-arginine vasopressin (DDAVP). The patient had a prolonged skin bleeding time and his platelets had reduced numbers of alpha-granules, increased vacuolation and reduced retention on glass beads. Platelet von willebrand factor antigen (vWf:Ag) was undetectable and levels of platelet fibrinogen, beta-thromboglobulin, platelet factor 4 and thrombospondin were reduced. All tests of plasma coagulation factors were normal, including factor viii (F.VIII:C), vWf:Ag, ristocetin cofactor (R:CoF) and botrocetin cofactor. Platelet ATP, ADP, platelet albumin, surface membrane glycoproteins and 14C-serotonin uptake were also normal. Infusions of DDAVP increased plasma F.VIII:C, vWf:Ag and R:CoF and shortened the bleeding time on two occasions. This suggests that DDAVP shortens the bleeding time by releasing vWf:Ag and/or other proteins from cellular storage sites other than the platelet.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
10/18. A novel platelet aggregating factor found in a patient with defective collagen-induced platelet aggregation and autoimmune thrombocytopenia.We found a novel platelet aggregating factor in a patient with steroid-responsive immune thrombocytopenic purpura that is associated with defective collagen-induced platelet functions. The aggregating factor and platelet functions were analyzed. The patient, a 58-year-old female, had purpura and prolonged bleeding time despite adequate platelet counts (greater than 140,000/microL) after steroid therapy. The patient's platelets responded normally to all agonists except collagen. Platelet adhesion to collagen fibrils was decreased. The patient's plasma induced irreversible aggregation and ATP release in normal platelet-rich plasma (PRP). This platelet aggregating factor was found in F(ab')2 fragments of the patient's IgG, which caused thromboxane b2 synthesis, elevation of cytoplasmic Ca2 levels, and phosphorylation of 40 kDa protein in normal platelets. platelet aggregation by the patient's IgG was inhibited by prostacyclin, dibutyryl cAMP, diltiazem, disodium ethylenediaminetetraacetate, and antimycin a plus iodoacetate, but ADP scavengers, cyclo-oxygenase inhibitors, and heparin had little or no effect. The aggregating activity of the patient's IgG absorbed to and eluted from normal platelets. The patient's Fab fragments did not induce platelet aggregation in eight of ten normal PRP but specifically inhibited aggregation induced by collagen and by the patient's IgG. The major component of an immunoprecipitate made with the patient's IgG from radiolabeled membrane proteins of normal platelet extract had a 62 kDa mol wt, while no such precipitate appeared in extracts of the patient's platelets. These results indicated that platelet aggregation by the patient's IgG was induced by the reaction of an antibody with a specific antigen on the normal platelet membrane through stimulus-response coupling. This antigen may be a collagen receptor on the platelet, most likely a polypeptide of 62 kDa under reducing condition. The defect of collagen-induced aggregation of the patient's platelets seemed to be due to alteration of the membrane protein related to this putative collagen receptor.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
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