Haemostatic profile of the San (Bushmen} relocated to Schmidtsdrif

Objective. To document the routine haemostatic variables of a group of San relocated from Namibia to South Africa.Design. Cross-sectional study done in two stages.Setting. Schmidtsdrif military camp in late 1990 and early 1991.Subjects. Healthy adult San volunteers: 31 males and 54 females from the Vasakela and Barakwena groups in 1990; 135 males from the Vasakela group in 1991. The subjects were all soldiers or their dependants.Main outcome measures. The following tests were performed: activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen and coagulation factors V, VII, VIII, IX, X, XI and XII. The results were compared with a Western population reference group (N =50).Main results. Almost all the haemostatic variables were statistically significantly lower than those of the reference group. The mean derived fibrinogen concentration in the plasma in the first stage of the study (1990) was significantly higher, but this reverted to normal during the second stage (1991), perhaps reflecting a general improvement in health.Conclusions. Even though the San are one of the best studied groups of indigenous people, this is the first published report on their haemostatic condition. The generally lower levels of haemostatic variables may reflect the lower prevalence of cardiovascular disease in the San. The population needs to be followed up as they westernise

Haematology outreach clinics in the Free State and Northern Cape

Objective. Evaluation of haematology outreach clinics in the Northern Cape and Free State.Design. Retrospective analysis of records from March 1994 to February 1996.Setting. Central South Africa is sparsely populated. Consultants from Bloemfontein held outpatient clinics in hospitals (with laboratories) in Bethlehem, Kimberley and Kroonstad.SUbjects. 117 patients with suspected haematological disease.Main outcome measures. Input measures (population, number of clinics and costs), process measures (patient numbers, patients per clinic, new consultations per clinic, patients' domicile, how they were referred, types of diagnoses and number of patients with nonhaematologicaldisorders) and output measures (attrition, changes in attendance and savings).Main results. The 84 clinics that were held, with 636 consultations, did not cost the State anything. Only 6% of the 117 patients had no haematological problem. Sixtyeight per cent had chronic haematological neoplasms. In Kimberley most of the patients came from Kimberley Hospital, while most of the patients at the other clinics were referred via Bloemfontein. There was only a 10% attrition rate and only one-third of patients were referred to Bloemfontein. We saved paying patients an estimated R21 260 in transport costs, while saving the State R172 992 by seeing patients at secondary, instead of tertiary, hospitals.Conclusions. It is cheaper to send a doctor to an outreach clinic than to refer patients to a central facility, provided there is enough work for a doctor at the clinic. It costs the State much less for patients to be seen at a secondary than a tertiary hospital. Positive spin-offs include academic stimulation of doctors and laboratories in the periphery, with more appropriate referrals to teaching hospitals. Weaknesses include poor availability of expensive drugs at the clinics and lack of standardised records. By commuting to outreach clinics, specialists can greatly reduce health expenditure and spread it from tertiary to lower levels. At the same time more patients have access to their services

Coronary artery in-stent stenosis persists despite inhibition of the von Willebrand factor - collagen interaction in baboons

Revascularization techniques, such as angioplasty and stent implantation, frequently lead to restenosis due to the formation of neointima after platelet activation and the concomittant release of various smooth muscle cell mitogenic and attractant factors. We here investigate whether inhibition of initial platelet adhesion after stent implantation can decrease neointima formation in a clinically relevant baboon model of in-stent stenosis using standard treatment with aspirin, clopidogrel and heparin. Inhibition of platelet adhesion was established by administration of the anti-von Willebrand factor (VWF) monoclonal antibody 82D6A3, which inhibits VWF binding to collagen. Administration of 82D6A3 resulted in a complete inhibition of VWF binding to collagen during the first three days after stent implantation. No thrombocytopenia or prolongation of the bleeding time was observed. Our results show that the formation of neointima was not affected in the group of baboons where primary platelet adhesion was abolished with 82D6A3 when compared to the control group. Vascular injury scores were the same in both groups. Inhibition of platelet adhesion during the first three days after stenting, on top of standard treatment with aspirin, clopidogrel and heparin, had no effect on neo-intima formation in a baboon model of in-stent stenosis. During the last decade, attempts to translate seemingly effective therapies based on smaller animal experimentation to the clinic have consistently failed. This study, using a non-human primate model that more closely resembles the clinical situation, presents a model that may be of further clinical interest for studying the prevention of restenosis.status: publishe

Thrombotic thrombocytopenic purpura directly linked with ADAMTS13 inhibition in the baboon (Papio ursinus)

Thrombotic thrombocytopenic purpura (TTP) is the prototypical microangiopathy characterized by disseminated microthromboses, hemolytic anemia, and ultimately organ dysfunction. A link with deficiency of the von Willebrand factor (VWF) cleaving protease (ADAMTS13) has been demonstrated but additional genetic and/or environmental triggers are believed to be required to incite acute illness. Here we report that four days of ADAMTS13 functional inhibition is sufficient to induce TTP in the baboon (Papio ursinus), in the absence of inciting triggers, since injections with an inhibitory monoclonal antibody (mAb) consistently (n=6) induced severe thrombocytopenia (<12x10(9)/L), microangiopathic hemolytic anemia with schistocytes and a rapid rise in serum lactate dehydrogenase. Immunohistochemical staining revealed the characteristic disseminated platelet-and VWF-rich thrombi in kidney, heart, brain and spleen but not lungs. Prolonged inhibition (14 days, n=1) caused myocardial ischemic damage and asplenia but not death. Control animals (n=5) receiving equal doses of a non-inhibitory anti-ADAMTS13 mAb remained unaffected. Our results provide evidence for a direct link between TTP and ADAMTS13 inhibition and for a mild disease onset. Furthermore, we present a reliable animal model of this disease as an opportunity for the development and validation of novel treatment strategies.status: publishe

Thrombotic thrombocytopenic purpura directly linked with ADAMTS13 inhibition in the baboon (Papio ursinus)

Thrombotic thrombocytopenic purpura (TTP) is the prototypical microangiopathy characterized by disseminated microthromboses, hemolytic anemia, and ultimately organ dysfunction. A link with deficiency of the von Willebrand factor-cleaving protease (ADAMTS13) has been demonstrated, but additional genetic and/or environmental triggers are thought to be required to incite acute illness. Here we report that 4 days of ADAMTS13 functional inhibition is sufficient to induce TTP in the baboon (Papio ursinus), in the absence of inciting triggers because injections with an inhibitory monoclonal antibody (mAb) consistently (n = 6) induced severe thrombocytopenia (< 12 x 10(9)/L), microangiopathic hemolytic anemia, and a rapid rise in serum lactate dehydrogenase. Immunohistochemical staining revealed the characteristic disseminated platelet-and von Willebrand factor-rich thrombi in kidney, heart, brain, and spleen but not lungs. Prolonged inhibition (14 days, n = 1) caused myocardial ischemic damage and asplenia but not death. Control animals (n = 5) receiving equal doses of a noninhibitory anti-ADAMTS13 mAb remained unaffected. Our results provide evidence for a direct link between TTP and ADAMTS13 inhibition and for a mild disease onset. Furthermore, we present a reliable animal model of this disease as an opportunity for the development and validation of novel treatment strategies