'n Ondersoek na die patogenese en patologie van die hemostatiese versteurings by akute afrikaanse varkpes

Afrikaans: Die patogenese en patologie van die hemostatiese versteuringe is deur middel van hematologiese, histochemiese, lig- en transmissie-elektronmikroskopiese metodes in 2 groepe varke besmet of met virulente heemadsorberende Afrikaanse varkpes virus isolate of 'n virulente nieheemadsorberende virus isolaat bestudeer. 'n Poging is ook aangewend om die hemostatiese versteurings, bloedings en vaskulere veranderinge by die 2 groepe te probeer vergelyk en moontlike verskille te probeer bepaal. 'n Beraamde trombositopenie en trombosietdisfunksie is gedurende die laaste 2-3 dae voor dood by beide groepe varke waargeneem. Alhoewel trombositopenie en trombosietdisfunksie by 'n groter getal varke besmet met die heemadsorberende virus isolate voorgekom het as by die varke gespuit met die nie-heemadsorberende isolaat, het hierdie veranderinge ook meer dikwels voorgekom by die varke besmet met die nie-heemadsorberende isolaat wat binne 9 dae (gemiddelde oorlewingsperiode van groep) dood is. Die graad van trombositopenie en trombosietdisfunksie is dus blykbaar eerder deur die verloop en strafheid van die siekte as die heemadsorberende eienskap van die bepaalde virus isolaat bepaal. 'n Besmetting van 'n klein persentasie van die trombosiete met die virus kon in hierdie studie waargeneem word. Die besmetting van slegs 'n klein persentasie van megakariosiete in die beenmurg kon elektronmikroskopies waargeneem word. Hieruit is afgelei dat die vermeende trombositopenie by hierdie varke meer waarskynlik die gevolg van periferele trombosietvernietiging as defektiewe trombositopoeiese was. Betekenisvolle verlengings van die geaktiveerde gedeeltelike tromboplastientyd, trombientyd, verhoogde fibrien- en fibrinogeendegradasieprodukvlakke sowel as geringe stygings van die protrombientyd het by die varke besmet met die heemadsorberende virus isolate voorgekom. By varke wat die nie-heemadsorberende virus ontvang het, was slegs die trombientyd en fibrinogeendegradasieproduk vlakke verhoog. Die verlenging van die stollingstye is vertolk as merkbare tekorte van die plasma-stollingsfaktore, die teenwoordigheid van fibrien- en fibrinogeendegradasie produkte of 'n kombinasie hiervan. Verminderde stolselsametrekking en varierende grade van oplossing en disintegrasie van stolsels na inkubasie by 37 grade Celsius is beskou as verdere aanduidings van gedissemineerde intravaskulere stolling of 'n hiperfibrinolitiese toestand. Wydverspreide nekrose (en sitolise) van makrofages is in die limfoiede weefsel waargeneem en aanvaar as die moontlike oorsaak van plasminogeenaktiveerder vrystelling deur makrofages met gevolglike hiperfibrinolise. Hialiene, globulere en granulere trombi en intravaskulere neerslae, wat swak tot sterk positief vir fibrien gekleur het en ooreengestem het met 'n toestand van gedissemineerde-intravaskulerestolling, was by alle varke sigbaar. Fibrinoiede veranderinge van bloedvate kon in verskeie organe maar hoofsaaklik in die limfknope, milt, vel en niere waargeneem word. Endoteelselbesmetting met die virus kon nie aangetoon word nie. Repliserende Afrikaanse varkpes viruspartikels kon wel in die sitoplasma van makrofages wat intiem geassosieer was met kapillere endoteelselle gedemonstreer word. Die fibrinoiede veranderinge ontstaan vermoedelik onder die invloed van chemiese mediators wat vrygestel word deur besmette makrofages en bloedplaatjies of teenwoordig is in plasma eerder as deur 'n direkte besmetting van endoteelselle deur die virus. In beide groepe was bloedings mees uitgesproke in die limfoiede weefsels en was hoofsaaklik gelokaliseer om sinusoidale, kapillere en klein venulere bloedvate waar die wande nekrotiese veranderinge vertoon het. Hierdie waarneming is vertolk as 'n aanduiding dat die disintegrasie van kleiner bloedvate 'n belangriker oorsaak van bloeding by die akute siekte as trombositopenie en onstabiele fibrienstolselvorming verteenwoordig. Hierdie studie verteenwoordig ook die eerste beskrywing van die bloedings en vaskulere patologiese veranderinge by varke besmet met 'n virulente nie-heemadsorberende Afrikaanse varkpes virus isolaat.

English: The pathogenesis and pathology of the haemostatic defects in 2 groups of pigs infected either with haemadsorbing isolates or a non-haemadsorbing isolate of virulent African swine fever virus were studied by haematological, histochemical and light and transmission electron microscopic methods. A comparison was also made of the differences in the haemostatic defects, haemorrhages and vascular changes in the 2 groups of pigs. An estimated thrombocytopenia and thrombocyte dysfunction were observed during the last 2-3 days of life in pigs from both groups. Although these were present in a greater number of pigs infected with the haemadsorbing virus isolates they, also occurred more frequently in those infected with the non-haemadsorbing virus which lived for less than 9 days (mean survival period for group). The estimated degree of these changes was therefore apparently determined more by the acuteness, duration and severity of the disease than by the haemadsorbing property of the virus, or lack of it. A small percentage of thrombocytes were found to be infected with the virus. Only a small percentage of megakaryocytes were found to be infected; this suggests a peripheral destruction of thrombocytes rather than an impaired thrombocytopoiesis. A significant increase of the activated partial thromboplastin time, thrombin time, and fibrin and fibrinogen degradation product levels as well as a slight prolongation of the prothrombin time occurred in the pigs infected with the haemadsorbing virus isolates. In pigs which received the non-haemadsorbing virus only the thrombin time and fibrinogen-degradation-product levels were increased. The causes of these changes were considered to be due to coagulation factor deficiencies, disseminated intravascular coagulation and/or fibrinolysis. This supposition was supported by the reduced clot retraction and clot dissolution and lysis which occurred after blood was incubated at 37°C. Widespread necrosis of macrophages was observed in lymphoid tissue and it is postulated that this is responsible for plasminogen activator liberation by macrophages with consequent fibrinolysis. Hyaline, globular and granular thrombi and intravascular deposits which stained positively for fibrin were convincing indications of intravascular coagulation in all pigs. Fibrinoid changes of blood vessel walls were observed in most organs, especially lymph nodes, spleen, skin and kidneys. Infection of endothelial cells with virus could not be demonstrated. Replicating intracytoplasmic African swine fever virus particles, however, were present in macrophages associated with endothelial cells in the lungs and renal glomeruli. The fibrinoid changes are possibly the result of the action of chemical mediators derived from activated macrophages, blood platelets and plasma rather than the direct effect of the virus on endothelial cells themselves. In both groups of pigs haemorrhages were more pronounced in lymphoid tissues and were mainly around small vessels whose walls appeared necrotic. This indicates that vascular injury is a more important cause of haemorrhage in the acute disease than is thrombocytopenia and defective fibrin clot formation. This study represents the first description of the haemorrhagic and vascular pathological changes induced in pigs by a virulent non-haemadsorbing African swine fever virus isolate.