Platelet reactions

A. Hoffmann and F. MaikwaodL Inhibition of the thrombin platelet reaction by... 

Jobin, F., Tremblay, F., Platelet Reactions and Immune Processes. I. 

Certain physiologic and dietary materials affect the platelet reactions. Catechol amines enhance platelet aggregation and promote thrombus formation. Fatty acids appear to enhance platelet aggregation, with saturated fatty acids being more effective than unsaturated fatty acids. Thrombosis is produced in the dog by single rapid infusion of long-chain saturated fatty acids but chronic slow infusions are nonthrombogenlc. Apparently the dog has sufficient thrombolytic power to handle the latter situation. 

The sequence of fibrinogen/albumin pre-adsorption influences platelet reactions in vivo. 

Hatayama, K. Kambayashi, J. Nakamura, K. Ohshiro, T. Mori, T. Fluorescent calcium indicator quin 2 as an intracellular calcium antagonist in platelet reaction. Thromb. Res. 1985, 38, 505-512. 

Contamination of blood products with lymphocytes can lead to transfusion-induced reactions ranging from a mild fever to severe reactions such as alloimmunization and graft versus host disease (GvHD), in which the transfused lymphocytes (graft) survive the defensive immune reaction of the patient (host) and start a reaction which destroys the cells of the host. The patient also may develop an immune response to the human leukocyte antigen (HLA) type of the graft s cells and reject all platelet transfusions that do not match their own HLA system. The HLA system, found on blood platelets and lymphocytes, is more compHcated than, but similar to, the ABO blood group system of red cells. 

Transfusion-induced autoimmune disease has been a significant complication in the treatment of patients who require multiple platelet transfusions. Platelets and lymphocytes carry their own blood group system, ie, the human leukocyte antigen (HLA) system, and it can be difficult to find an HLA matched donor. A mismatched platelet transfusion does not induce immediate adverse reactions, but may cause the patient to become refractory to the HLA type of the transfused platelets. The next time platelets with an HLA type similar to that of the transfused platelets are transfused, they are rejected by the patient and thus have no clinical efficacy. Exposure to platelets originating from different donors is minimized by the use of apheresis platelets. One transfusable dose (unit) of apheresis platelets contains 3-5 x 10 platelets. An equal dose of platelets from whole blood donation requires platelets from six to eight units of whole blood. Furthermore, platelets can be donated every 10 days, versus 10 weeks for whole blood donations. 

Filtration Filtration (qv) is appHed in blood cell separation to remove leukocytes from ted blood cell (RBC) and platelet concentrates. Centtifugational blood cell separators do not reduce white blood cells (WBC) in red cell and platelet products sufficiently to avoid clinical complications such as GvHD and alloimmunization. A post-apheresis filtration step is needed to further reduce the WBC load. Modem filters are capable of a 3-log reduction in white cell contamination of the blood product, eg, apheresis single-donor platelet units having a typical white cell contamination of 5 x 10 white cells in 4 x 10 platelets can be reduced to a 5 x 10 white cell contamination, a sufficiently low number to avoid severe transfusion reactions. 

Iodine monochloride [7790-99-0] ICl, mol wt 162.38, 78.16% I, is a black crystalline soHd or a reddish brown Hquid. SoHd ICl exists ia two crystalline modifications the a-form, as stable mby-red needles, d = 3.86 g/mL and mp 27.3°C and as metastable brownish red platelets, d = 3.66 g/mL, mp 13.9°C and bp 100°C (dec). Iodine monochloride is used as a halogenation catalyst and as an analytical reagent (Wij s solution) to determine iodine values of fats and oils (see Fats and fatty oils). ICl is prepared by direct reaction of iodine and Hquid chlorine. Aqueous solutions ate obtained by treating a suspension of iodine ia moderately strong hydrochloric acid with chlorine gas or iodic acid (118,119). 

Aluminum iodide [7884-23-8] AIL, is a crystalline soHd with a melting poiat of 191°C. The presence of free iodine ia the anhydrous form causes the platelets to be yellow or brown. The specific gravity of this soHd is 3.98 at 25°C. Aluminum iodide hexahydrate [10090-53-6] AIL -6H20, and aluminum iodide pentadecahydrate [65016-30-0], AIL -15H20, are precipitated from aqueous solution. They may be prepared by the reaction of hydroiodic acid [10034-85-2], HI, with aluminum or aluminum hydroxide. 

Titanium disulfide can also be made by pyrolysis of titanium trisulfide at 550°C. A continuous process based on the reaction between titanium tetrachloride vapor and dry, oxygen-free hydrogen sulfide has been developed at pilot scale (173). The preheated reactants ate fed iato a tubular reactor at approximately 500°C. The product particles comprise orthogonally intersecting hexagonal plates or plate segments and have a relatively high surface area (>4 /g), quite different from the flat platelets produced from the reaction between titanium metal and sulfur vapor. The powder, reported to be stable to... 

Dismption of the endothehal surface of blood vessels expose coUagen fibers and connective tissue. These provide surfaces that promote platelet adherence, platelet release reaction, and subsequent platelet aggregation. Substances Hberated from the platelets stimulate further platelet aggregation, eg, adenosine diphosphate maintain vasoconstriction, eg, serotonin and participate in blood coagulation, eg, platelet Factors III and IV. In addition, the release reaction modifies platelet membranes in a manner that renders phosphoHpid available for coagulation. The thrombin [9002-04-4] elaborated by the coagulation mechanism is a potent agent in the induction of the platelet release reaction. 

Thrombin, the two-chain derivative of the prothrombin molecule, has a molecular weight of approximately 37,000 daltons. Its proteolytic properties induce the conversion of fibrinogen to fibrin to produce the initial visible manifestation of coagulation, the soluble fibrin clot. In addition, thrombin influences the activity of Factors V, VIII, and XIII and plasmin. Thrombin affects platelet function by inducing viscous metamorphosis and the release reaction with subsequent aggregation. 

Itazigrel (137) is an antithrombotic compound because of its inhibition of platelet aggregation induced by collagen. It is synthe.sizcd froin l-bromo-l-(4-methoxy)benzoyl-4-methoxytol-uene (135) by reaction in the usual way with triflucffothioacetamide (136) to give itazigrel 471. 

In a related reaction, (V,iV-dimethylcyclopent[c ]azepin-l-amine (5) is obtained as blood-red platelets by cyclization of 4 with ammonia.68... 

Direct laser-assisted myocardial revascularization (DMR) is an approved technique in the US, Europe, and parts of Asia to create numerous myocardial channels. This results in the induction of a massive inflammatory reaction, which in turn induces angiogenesis. The other FDA-approved pro-angiogenic therapy is the use of recombinant human platelet-derived growth factor (Regranex) for use in the treatment of diabetic neuropathic foot ulcer s. 

Enzymology of proteases in a water-phase is well known, but its alteration in a compartment is poorly understood. There are dramatical changes in reaction rates, in enzyme contractions and in enzyme sensitivity to inhibitors, which are not exactly described. In addition, besides fibrin and platelets there are several cellular and molecular components present in a thrombus compartment, where their influence on the basic fibrinolytic reactions is not known. To study this aspect of fibrinolysis is a task of the near future [4]. 

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