Study of some pathophysiological factors in children with acquired aplastic anaemia

Aplastic anaemia [AA] is a heterogenous disease including different pathophysiological conditions, characterized by severely diminished numbers of bone marrow [B.M] haematopiotic cells resulting in failure of the marrow to produce mature blood elements, this study aimed to determine the role of apoptosis, tumour necrosis factor alpha [TNFalpha.] and granulocytes-macrophage colony stimulating factor [GM-CSF] in the pathogensis of AA. Thirty five cases diagnosed as acquired A.A, Twenty cases newly diagnosed, 8 cases in partial remission and 7 cases in complete remission were studied. Twenty age and sex matched children were taken as control group.Mononuclear cell apoptosis was estimated using flowcytometry by TUNEL method.Serum level of TNFa. and GM-CSF were estimated using ELISA technique. The result of this study revealed significant increase of mononuclear cell apoptosis and TNFalpha in newly diagnosed cases of AA and in cases with partial remission more than in control group. Also there was an insignificant increase of apoptosis in the cases in complete remission than in control group. Serum GM-CSF was significantly reduced in all cases of aplastic anaemia except cases in complete remission when compared with control group.There was inverse correlation between mononuclear cell apoptosis,TNFalpha, and GM-CSF [r - 0.52, - 0.55 respectively, p <0.001] In conclusion increase the rate of mononuclear cell apoptosis,TNF-alpha and decreased level of GM-CSF play a role in pathophysiology of B.M failure and their follow up may be one of the important parameters to assure complete recovery

Lupus anticoagulant an additional risk factor in the pathogenesis of diabetic retinopathy

During the past decade there has been growing concern for the role of lupus anticoagulant [LA] as a link between the immunological and haemostatic systems in the mechanism ofendothelial alteration in type one diabetic microangiopathy. This work aimed at studying the possible relation between lupus anticoagulant positivity and diabetic retinopathy [DR] as an evidence of clinically manifest diabetic microangiopathy in type one diabetes mellitus [type 1 DM] patients, regarding its incidence, severity and response to laser therapy. The study was conducted on 60 subjects who were classified into two main groups. Patients group: fifty type 1 DM patients, mean age +/- SD [3 8 +/- 8.7] years, mean duration of diabetes +/- SD [12.4 +/- 1.9] years. Patients with poor glycemic control [HbA> 7%], border line hypertension [> 140/90mm Hg], hypercholesterolemia [> 5.6 mmol/L], hyper trigluyceridaemia [> 1.9 mmol/L] or any others systemic diseases were excluded. According to laboratory investigations [coagulation screen including prothrombin time [PT], partial thromboplastin time [PTT], Fibrinogen, activated protein C [Apc], prothrombin degradaton products [F[1]+2] lupus anticoagulant titre [LA titre]. Patients were classified into LA +ve patients [18] LA -ve patients [32]. Dilated fundus examination was done for all patients DR was classified into non proliferative diabetic retinopathy [NPDR] and proliferative diabetic retinopathy [PDR] and according to response to laser therapy PDR patients were classified into active proliferative diabetic retinopathy laser [active PDRL] and quiescent PDRL. Control group: Ten apparently healthy individuals, age and sex matched with patients' group. A significant decrease in Apc concentration and increase in F[1]+2 plasma level were noticed in LA + ve group compared with LA -ve and control groups [P<0.001 and P<0.001 respectively]. The incidence of DR was significantly higher in LA +ve group [77.78%] than LA -ve one [31.25%] [P < 0.001]. In particular a significantly higher percentage of PDR patients was observed in LA +ve [71.43%] compared to LA -ve ones [40% p<0.001]. There was a significantly higher LA titter in patients with PDR than those with NPDR [p < 0.05]. With application of laser therapy to patients with PDR, 70% of LA +ve showed minimal or no improvement [PDRL active] while only 25% of LA -ve did so during the follow up period of 8-12 weeks. In conclusion this study can suggests that lupus anticoagulant positivity might be an additional risk factor in the pathogenesis of DR affecting not only its incidence but also its severity, and even response to laser therapy. If this concept is true it would offer more weapons [antithrombotic, profibrinolytics, and cytoprotective] to the antidiabetic retinopathy campaign that might have a favourable outcome on prevention and /or retardation of progression of that relatively common complication with markedly puzzling aetiopathogenesis and before the need for laser treatments which always destroy the retinal anatomy