Platelets lysis

Lysis of formed blood elements other than erythrocytes may produce elevations in serum or plasma constituents. Platelet breakdown during blood collection can introduce enzymes into the plasma (Z3). Aldolase activity is very high in platelets (Dl), and elevations of acid phosphatase in myeloproliferative disease are probably the result of platelet lysis (B6). 

This test requires platelet-rich plasma from a patient recovering from a drug-induced platelet lysis. Various concentrations of the suspected drug have to be used and the mixture incubated in the presence of the patient s serum. Platelet agglutination is best determined on a siliconized slide, using a phase contrast microscope. An indirect method using platelets from a normal donor can also be adapted. It is, however, less sensitive and reliable (Dausset et al. 1964). 

Shulman (1963), also working with quinidine, proposed an alternative explanation to explain the mechanism. He relegates the platelets to a passive role and considers them to be specialized cells capable of adsorbing onto their surface a drug-antibody complex. This hypothesis was a deduction based on the study of a steric and kinetic model for the immunoreactants involved in platelet lysis (Shulman 1958). By varying the concentrations of the reactants in the model, Shulman was able to show that there was only stoichiometric combination between the four reactants, antibody, antigen, platelets, and complement, and that the interactions were most likely bimolecular and sequential. The most probable sequence appeared to be first an initial combination of quinidine with either antibody of platelets, followed by the formation of the complete antibody-quinidine-platelet... 

The immune reaction to platelets is associated with three major alterations of platelet. There is an increased tendency to agglutination, the rate of platelets lysis is accelerated, and the susceptibility of platelets to phagocytosis is increased. Platelet precursors are also altered in thrombocytopenia. The megakaryocytes of the marrow are rare and immature. 

Haemostasis is the mechanism activated after damage to the blood vessel wall that ensures that blood loss is restricted. Blood platelets are are activated and adhere to elements on the damaged lumenal surface of the vessel, eventually forming a platelet plug that stops the leakage of blood. Fibrinolytic mechanisms later produce lysis of the platelet mass when repair of the vessel has occurred. 

C3b immune adherence to platelets with release of factor 3 C5b attaches to platelets to cause lysis with release of... 

Little intravascular coagulation of blood occurs in normal physiological conditions. Hemostasis involves the interplay of three procoagulant phases vascular, platelet, and coagulation) that promote blood clotting to prevent blood loss (Fig. 22.1). The fibrinolytic system prevents propagation of clotting beyond the site of vascular injury and is involved in clot dissolution, or lysis (Fig. 22.2). 

Lecithins and related phospholipids usually contain a saturated fatty acid in the C-l position but an unsaturated acid, which may contain from one to four double bonds, at C-2. Arachidonic acid is often present here. Hydrolysis of the ester linkage at C-2 yields a l-acyl-3-phosphoglycerol, better known as a Iysophosphatidylcholine. The name comes from the powerful detergent action of these substances which leads to lysis of cells. Some snake venoms contain phospholipases that form Iysophosphatidylcholine. Lysophosphatidic acid (l-acyl-glycerol-3-phosphate) is both an intermediate in phospholipid biosynthesis (Chapter 21) and also a signaling molecule released into the bloodstream by activated platelets.15... 

The increased platelet adhesion onto HCP surfaces is mainly due to the high surfacial concentration of fibrinogen associated with immobilized heparin. Therefore one of the solutions to the problem could have been provided by simultaneous immobilization of heparin and proteolytic enzymes which could hydrolyze the adsorbed fibrinogen. The immobilized enzyme could also provide the lysis of the fibrin clot, in case it was formed, for instance in stagnation regions of the complicated devices. 

Van Giezen JJJ, Nerme V, Abrahamsson T (1998) PAI-1 inhibition enhances the lysis of the platelet-rich part of arterial-like thrombi formed in vitro. A comparative study using thrombi prepared from rat and human blood. Blood Co-agul Fibrinol 9 11-18... 

Jang IK, Gold HK, Ziskind A A et al. (1989) Differential sensitivity of erythrocyte-rich and platelet-rich arterial thrombi to lysis with recombinant tissue-type plasminogen activator. Circulation 79 920-928... 

Thrombosthenin from Pig Platelets. The method described by Grette (1962) for the extraction of the contractile protein from pig platelets uses butanol for the lysis of platelets, and the precipitation is effected at an ionic strength of 0.2 y in the presence of Mg++ ions. 

Peerscfake EIB. Glycoprotein lib and nia retention on fibrinogen-coated surfaces after lysis of adherent platelets. Blood 1995 82 3358-3363. 

Stored complement factors that are released upon platelet activation (Table 9.3) are C5-C9 (Houle et al, 1989), the regulatory protein for the formation of C5b-9, Vitronectin (Suzuki et al, 1987), Clusterin, a complement lysis inhibitor, present in the a-granules (Tschopp et al, 1993), also present in Ae o-granules is Cl-INH (Schmaier et al, 1985), FactorD (Kenney and Davis, 1981) and Factor H (Devine and Rosse, 1987). 

Jack Levin, who had an interest in the effects of endotoxin on platelets and human blood coagulation, joined Bang at Woods Hole, MA, for several summers to do research on endotoxin-initiated Limulus blood coagulation. This collaboration produced several publications that explained a simple mechanism of enzyme-mediated interaction of LAL with endotoxin. " " Levin discovered a way to harvest the intracellular fluid by osmotic lysis of stabilized amebocytes. Modern-day preparation of LAL reagent still follows Levin s basic methods. 

Platelet-activating factor (PAE) is a glyceride-derived substance that is released by mast cells, alveolar macrophages, neutrophils, platelets, and other cells but not by basophils. It has potent bron-choconstrictor effects and also causes platelet aggregation and lysis. It attracts neutrophils and causes their activation. Also, PAE enhances vascular permeability and can cause pain, pruritus, and erythema. 

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