Platelet proaggregating effect of heparin: possible mechanism for non-immune heparin-associated thrombocytopenia.
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Heparin↗
Biomedical subjects
B H Chong
Publications and source records attributed to B H Chong.
Use of Org 10,172 in the treatment of heparin-induced thrombocytopenia and thrombosis.
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Aged↗
Thrombotic thrombocytopenic purpura unresponsive to plasma infusion and plasma exchange, but responsive to splenectomy.
A 60-yr-old female presented with typical thrombotic thrombocytopenic purpura (TTP). She remained in coma with frequent seizures for 1 wk, with persisting severe thrombocytopenia and microangiopathic haemolytic anaemia, despite treatment with prednisolone, plasma exchange, fresh frozen plasma, sulphinpyrazone and dipyridamole. Splenectomy induced haematological improvement within 1 d, there was cessation of fitting after 2 d, and full neurological recovery ensued over 3 wk. Laboratory studies did not reveal the presence of a platelet-aggregating factor (PAF), stated to be present in some two-thirds of cases. While plasma exchange and plasma infusion are beneficial in many cases, splenectomy appears still to be of value in unresponsive disease.
Blood Transfusion↗
Acquired storage pool in heparin-induced thrombocytopenia.
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Aged↗
Molecular characterization of quinine/quinidine drug-dependent antibody platelet interaction using monoclonal antibodies.
Two murine monoclonal antibodies, FMC 25 and AN 51, directed against distinct epitopes on the glycoprotein Ib complex, have been used to further define the mechanism of quinine/quinidine drug-dependent antibody interaction with platelets. FMC 25, directed against an epitope on glycoprotein IX, had no effect on platelet aggregation induced by collagen or adenosine diphosphate and little, if any, effect on ristocetin-induced platelet agglutination. FMC 25 and its (Fab)2 fragment, however, were potent inhibitors of drug-dependent antibody-induced platelet aggregation and blocked binding of drug-dependent antibody to platelets as assessed by indirect platelet immunofluorescence. In contrast, AN 51, directed against an epitope on the alpha-subunit of glycoprotein Ib, blocked ristocetin-induced, factor VIII/von Willebrand factor (FVIII/vWF)-dependent platelet agglutination but not drug-dependent antibody-induced platelet aggregation or binding of drug-dependent antibody to platelets. Selective proteolytic removal of the majority of the alpha-subunit of glycoprotein Ib (glycocalicin) from platelets by treatment with calcium-dependent protease did not affect binding of drug-dependent antibody. In addition, a quinidine-dependent antiplatelet antibody immunoprecipitated glycoprotein Ib complex from normal platelets and the membrane-associated proteolytic remnant of the glycoprotein Ib complex from calcium-dependent protease-treated platelets. Preincubation of drug-dependent antibody with purified glycoprotein Ib complex inhibited subsequent binding of antibody to platelets, but the separated components, glycoprotein Ib and glycoprotein IX, were both ineffective, suggesting that the normal interaction between glycoprotein Ib and glycoprotein IX in the intact complex was necessary for drug-dependent antibody recognition. The functional response of platelets to drug-dependent antibody was not mediated by way of platelet Fc receptor, since aggregation of washed platelets by acetone-aggregated IgG was not inhibited by FMC 25 (Fab)2. FVIII/vWF was not required for drug-dependent antibody-induced platelet aggregation. The combined evidence is consistent with quinine/quinidine-dependent antibody-platelet interaction occurring by way of a FVIII/vWF-independent, Fc receptor-independent mechanism that probably involves binding of antibody to glycoprotein IX or the beta-subunit of glycoprotein Ib or both.
Antibodies, Monoclonal↗
Qualitative platelet defect in a case of heparin-induced thrombocytopenia.
A qualitative platelet defect was demonstrated in a patient with heparin-induced thrombocytopenia. His platelets showed impaired aggregation to collagen and arachidonate and absent second wave aggregation to adenosine diphosphate and epinephrine but normal response to ristocetin. These aggregation abnormalities were similar to those reported in idiopathic thrombocytopenia and systemic lupus erythematosus. This platelet function defect may contribute to haemorrhagic complications which appear to be common in heparin-induced thrombocytopenia.
Adenosine Diphosphate↗
Quinidine-induced thrombocytopenia and leukopenia: demonstration and characterization of distinct antiplatelet and antileukocyte antibodies.
A patient with the rare syndrome of simultaneous quinidine-induced thrombocytopenia and leukopenia was studied. A quinidine-dependent antiplatelet antibody was detected in her serum by platelet aggregometry and by indirect platelet-suspension immunofluorescence. A drug-dependent antileukocyte antibody was demonstrated by leukoagglutination and by granulocyte immunofluorescence. Both antibodies were found to belong to the IgG class by immunofluorescence using monospecific antisera. There appeared to be two distinct antibodies, since the antibody eluted off sensitized platelets reacted only with platelets and that eluted off sensitized granulocytes reacted only with granulocytes. In addition, the patient's serum and quinidine gave a negative reaction on immunofluorescence with platelets from a patient with Bernard-Soulier syndrome (BSS), which lack glycoprotein lb (GPlb) complex, but gave a positive reaction with BSS granulocytes. The quinidine-dependent antiplatelet antibody immunoprecipitated GPlb and a glycoprotein of molecular weight 22,000 (GPlb complex) from Triton-solubilized, periodate-labeled platelets. Similar attempts to identify the granulocyte surface receptor/antigen were unsuccessful. Factor VIII/von Willebrand factor was not required for binding of the drug-dependent antibody to platelets.
Antibody Specificity↗
Additional glycoprotein defects in Bernard-Soulier's syndrome: confirmation of genetic basis by parental analysis.
The glycoprotein profile of Bernard-Soulier platelets was examined by labeling washed platelets with periodate 3H-sodium borohydride, a procedure that labels greater than 30 glycoproteins on the membrane surface of normal platelets. Three Bernard-Soulier patients were studied; two were siblings and the third was unrelated. The platelet protein and glycoprotein profiles were evaluated under nonreduced and reduced conditions using 5%-15% exponential SDS-polyacrylamide gel electrophoresis. The two siblings completely lacked glycoprotein Ib (GPIb). The unrelated patient had congruent to 7% of the normal level. This was confirmed by two-dimensional nonreduced-reduced SDS-polyacrylamide gel electrophoresis, a procedure that allows clear separation of the disulfide-linked subunits of GPIb, GPIb alpha (mol wt 145,000), and GPIb beta (mol wt 25,000) from other membrane glycoproteins. On one-dimensional analysis, Bernard-Soulier's syndrome (BSS) platelets also lacked the peripheral membrane glycoprotein, GPV (mol wt 82,000) and a low molecular weight glycoprotein, GPIX, (nonreduced or reduced, mol wt congruent to 22,000). The two-dimensional gel system also revealed the absence of a minor glycoprotein with a molecular weight of congruent to 100,000 (GP 100). Quantitation of these proteins solubilized from electrophoretograms showed that the siblings' parents had congruent to 50% levels of GPIb, GPIX, and GP 100. A monoclonal antibody against glycoprotein Ib, FMC 25, was negative by immunofluorescence against Bernard-Soulier platelets and immuneprecipitated both GP Ib and GPIX from Triton X100 solubilized, labeled platelets. The combined results suggest that the apparent genetic absence of multiple proteins in Bernard-Soulier platelets is due, in part, to the presence in normal platelets of a tight membrane complex between glycoprotein Ib and at least one of the other absent glycoproteins.
Adolescent↗
Heparin-induced thrombocytopenia: association of thrombotic complications with heparin-dependent IgG antibody that induces thromboxane synthesis in platelet aggregation.
Eleven patients in whom thrombocytopenia developed during heparin therapy were studied. Six patient (group 1) had severe thrombocytopenia with delayed onset and five of these patients had thromboembolic complications. A serum factor which induced heparin-dependent thromboxane B2 synthesis, 14C-serotonin release, and platelet aggregation was found in all patients in group 1. The serum factor was shown to be IgG. These findings suggest that the mechanism of the severe thrombocytopenia secondary to heparin therapy is immunological and the associated thromboembolic complications may be attributed to in-vivo activation of the platelet prostaglandin pathway and platelet aggregation induced by the heparin-dependent antibody. The five patients in group 2 had mild symptomless thrombocytopenia with early onset. In this group, the heparin-dependent antibody was not found and the mechanism of the thrombocytopenia is probably a direct action of heparin on platelets.
Adult↗
Heparin-induced thrombocytopenia: effect of heparin platelet antibody on platelets.
The plasma of two patients with heparin-induced thrombocytopenia has been shown to cause platelet aggregation in the presence of heparin. The platelet aggregating factor was isolated in the IgG reaction of the patients' sera suggesting that it was an antibody. This heparin anti-platelet antibody (HAP-Ab) induced platelet aggregation and release but did not cause platelet lysis, although it fixed complement. Platelet aggregation was inhibited by EDTA and by inactivation of complement. There was a significant production of malondialdehyde (MDA) and thromboxane B2 (TXB2) implying a role of the prostaglandin synthesis pathway in HAP-Ab induced aggregation. ADP-release also appeared to be involved as apyrase blocked aggregation while hirudin, a thrombin inhibitor, had no effect. The thrombotic complications that have recently been reported in patients with heparin-induced thrombocytopenia may be explained by some effects of HAP-Ab on platelets, namely: the antibody mediated platelet factor 3 release, prostaglandin endoperoxides and thromboxane A2 (TXA2) production and platelet aggregation in vivo. These HAP-Ab mediated effects could be inhibited by anti-platelet drugs such as aspirin, indomethacin and dipyridamole and thus may have therapeutic implications.
Adenosine Diphosphate↗
Anuric renal failure due to encasement of the ureters by lymphoma--ureteric obstruction without dilatation.
A case of anuric renal failure due to encasement of the ureters by tumour is described in a patient with advanced non-Hodgkin's lymphoma. In this patient as well as in two previously reported cases, the IVP showed delayed pyelogram and increasingly dense nephrogram on delayed films with little or no dilatation of the collecting systems. These radiographic features in a patient with extensive intra-abdominal tumour should strongly suggest the possibility of this unusual form of obstructive uropathy. Correct diagnosis in these cases may enable the administration of effective palliative treatment for the renal failure.
Acute Kidney Injury↗
Occlusive cerebrovascular disease in young adults.
13 patients under 40 years of age had cerebral infarction and angiographic evidence of arterial stenosis or occlusion. None of them had cardiac disorders prone to cerebral embolism. Five patients had occlusion at the origin of the internal carotid artery, one had occlusion of the common carotid artery and one each had stenosis at the origin of the internal carotid and common carotid arteries, respectively. Two patients had unilateral occlusion of the supraclinoid portion of the carotid artery with basal collaterals that had some resemblance to the Moyamoya disease. Three patients demonstrated stenosis or occlusion of the middle and/or anterior cerebral arteries. Three patients had hypercholesterolemia, one of whom was hypertensive. None had confirmed diabetes mellitus. One female, who died, had taken oral contraceptives for 3 years. A male, with internal carotid artery occlusion, had serological evidence for syphilis.
Adolescent↗
The Lewis system and secretor status in autoimmune hemolytic anemia complicating infectious mononucleosis.
Two patients with acute infectious mononucleosis and associated immune hemolysis were found to be Le(a-b-). One of them had anti-Leb antibodies during the acute phase of the disease, which disappeared during convalescence. Two other patients with previous infectious mononucleosis and hemolysis were found to be Le(a-b-) and Le(a+b-) respectively. Of the four patients, three were nonsecretors and the fourth likely to be so. The Lewis status of these four patients varies significantly from that of other patients with uncomplicated infectious mononucleosis and from the known distribution of the Lewis type in the Caucasian population. The findings suggest that the Lewis status of the patient is important in the development of hemolysis in infectious mononucleosis.
Adolescent↗