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SYNOPSIS Plasma fibrinogen concentration and whole-blood viscosity, the latter measured at two shear rates (23 and 230 sec-1), were estimated during eight episodes of sickle-cell crisis and compared with values in 26 sickle-cell anaemia patients who were not in crisis. Painful crisis was associated with a significant increase in both plasma fibrinogen and whole-blood viscosity. Increased fibrinogen-erythrocyte interaction in vivo may be a significant contributory factor to raising blood viscosity and precipitating vaso-occlusive crisis in sickle-cell disease.The viscosity of whole blood is largely determined by the number of red cells (haematocrit) and by the deformability of individual red cells. Viscosity is also influenced by fibrinogen and other proteins which induce red-cell aggregation by protein-cell membrane interaction (Chien et al, 1967;Replogle et al, 1967;Rosenblum, 1969), and this is particularly important at low flow rates as in large veins, venules, and the microcirculation.The role of hyperfibrinogenaemia in vivo in increasing viscosity and leading to vaso-occlusive crisis in sickle-cell disease is not well defined although it has been suggested that the rise in fibrinogen during pregnancy and in acute infection may play a major role in precipitating crisis (Harris and Murphy, 1973). A study has therefore been made of plasma fibrinogen and whole-blood viscosity in children with sickle-cell disease to determine the changes which occur in vaso-occlusive crisis. Patients and methodsBlood was taken from 26 asymptomatic children (aged 3-16 years) attending a haematology outpatient clinic, of whom 18 had homozygous sicklecell anaemia (SS) and eight had sickle-cell/flthalassaemia. Blood specimens were also obtained from eight children (seven with SS) during admission for painful crisis. Routine bacteriological studies included blood, throat, and mid-stream urine cultures and the cytocentrifuge-NBT score Blood for viscosity studies was collected with minimal venous stasis into solid EDTA (1-8 mg/ml), with thorough mixing to avoid microclot formation, and measured within four hours of collection. Viscosity was measured using a Wells-Brookfield cone-plate microviscometer incorporating a 1-565°c one. Measurements were made at 37°C and at two shear rates corresponding to estimated physiological shear rates in veins and vessels of capillary diameter (23 sec-1) and large arteries (230 sec-1). Before viscosity measurements were made the blood was bubble oxygenated for 5 minutes and then mixed for 10 minutes on a roller-type blood mixer. When the temperature of the microviscometer sample-cup had reached 37°C, 0-8 ml of blood was introduced into the cup and the specimen was sheared at 23 sec-1 for 3 minutes to allow stabilization before a reading was taken. The sample was then sheared at the same rate for a further 2 minutes to give a second reading. The instrument was cleaned, a second 0-8 ml aliquot of the same blood sample was introduced, and a further two readings were taken at 23 sec-1. The value obtained f...

SYNOPSIS A study of fibrinolytic activity in sickle-cell patients during asymptomatic periods has shown a normal fibrinolytic response to exercise and local heat to the arm. During vasoocclusive crises there was no significant decrease in fibrinolytic activity. These results contrast with earlier reports of decreased fibrinolysis during crisis and a suggestion that fibrinolytic activators might be of value in preventing vasoocclusive episodes.Patients in painful crisis showed a significant rise in fibrinogen concentration and fall in platelet count. The former may contribute to localized vascular sludging by increasing whole-blood viscosity, while the latter probably results from local trapping of platelets in areas of sickling or from subsequent splenic sequestration of damaged platelets. There was no evidence of disseminated, as opposed to localized, intravascular coagulation during crisis.

SYNOPSIS An increase in low molecular weight fibrin-fibrinogen degradation products (FDP) was demonstrated in cerebrospinal fluid (CSF) from 17 of 18 patients with bacterial or viral meningitis compared with 29 patients without meningitis. The CSF also showed an increase in coagulation proteins of molecular weight less than 90 000 (factors VII, IX, and plasminogen) but did not contain fibrinogen (MW 340 000) or plasminogen activator. It is concluded that low molecular weight FDP in the CSF in infective meningitis result from leakage through a damaged blood-CSF barrier rather than from local digestion of fibrin deposited on the meninges.Fibrin-fibrinogen degradation products (FDP) are not found in normal cerebrospinal fluid (CSF) but have been demonstrated following subarachnoid haemorrhage (Tovi, 1972), meningococcal meningitis (Brueton et al, 1974), and in patients with raised CSF protein (Hunter et al, 1974). The source of origin of the FDP is not clear although this is an important point in view of the potential diagnostic value of raised FDP and also in relation to the treatment of subarachnoid haemorrhage by fibrinolytic blockade (Mullan and Dawley, 1968;Gibbs and Corkill, 1971;Tovi, 1972).Normal CSF does not contain plasminogen activator (Tovi, 1972) although the meninges and choroid plexus are rich in this fibrinolytic activator. The release of an increased amount of activator from these tissues could therefore result in the local digestion of fibrin-fibrinogen to give rise to FDP in the CSF. Alternatively, FDP could leak into the CSF via a damaged blood-CSF barrier. The latter would be analogous to the appearance of low molecular weight FDP in the urine when glomerular basement membrane damage results in highly selective proteinuria (Hall et al, 1975).A study has therefore been made of coagulationfibrinolytic proteins of differing molecular weight in the CSF and blood from 47 patients undergoing diagnostic lumbar puncture in order to determine the source of origin of FDP in the CSF in meningitis. Patients and MethodsFifty-eight specimens of CSF were obtained from 47 patients undergoing diagnostic lumbar puncture. Received for publication 30 September 1975The 47 patients (42 were children) included 13 patients with bacterial and five with viral meningitis (meningitis group). The remaining 29 patients (nonmenigitis group) comprised 10 with acute lymphoblastic leukaemia (three with meningeal involvement), five with febrile convulsions, and eight with infections such as pneumonia which did not involve the CNS but were associated with meningism; the remaining six patients had a variety of conditions affecting their level of consciousness but without evidence of CNS infection. Patients with bacterial meningitis were initially treated for two weeks with either parenteral chloramphenicol, penicillin, and sulphadimidine, or intravenous ampicillin.Lumbar CSF (1-0 ml) was taken directly into a plastic tube containing 01 ml of 3-8 % sodium citrate for estimation of plasminogen, fibrinogen, and factors VII and IX, an...

The NBT test is a non-specific test of neutrophil membrane stimulation which has application to the study of neutrophil function, particularly in the septicaemic patient. An improved cytochemical test which eliminates potential sources of laboratory error has been developed. Venous or capillary blood samples may be studied and the technique can be applied to the neutropenic patient since available neutrophils are concentrated by cytocentrifugation. Clinical evaluation in 443 patients is described.