Prothrombin fragment F1 + 2: correlations with cardiovascular risk factors.

Plasma prothrombin fragment F 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT), fibrinogen and factor VII were related to variables associated with increased cardiovascular risk in 86 plasma donors (49 male and 37 female). F1 + 2 had a log-normal distribution and increased significantly with age and body mass index (BMI). Significantly, higher F1 + 2 levels were found in smoking compared with non-smoking males and in indolent males compared with males taking regular exercise. Higher levels were found in subjects with a parental history of ischaemic heart disease than in those lacking such a history. F1 + 2 correlated strongly with increasing cholesterol in males. Fibrinogen was significantly higher in male smokers than male non-smokers but did not vary with age or BMI. Factor VII correlated strongly with cholesterol and to a lesser extent with fibrinogen, F1 + 2 and BMI, but not with smoking. F1 + 2 correlated more closely with risk factors for cardiovascular disease than fibrinogen and factor VII, and consistently reflected the difference in cardiovascular risk when correlated with risk factors which have markedly different effects between the sexes. It promises to be a useful predictive marker of ischaemic heart disease.

First use of G-CSF in chlorpromazine-induced agranulocytosis: a report of two cases.

Chlorpromazine-induced agranulocytosis is an uncommon disorder associated with a high frequency of fatality. We describe two patients with chlorpromazine-induced granulocytosis in whom granulocyte colony stimulating factor (G-CSF) administration enhanced the speed of neutrophil recovery. No toxicity was noted with G-CSF and both patients made a successful recovery. We propose there is a role for such cytokine therapy in patients with life-threatening agranulocytosis in order to speed the recovery of neutrophils.

Some problems with anticoagulants in dental surgery.

Anticoagulants have been used to reduce the risk of embolic and thrombotic complications in patients at risk since the discovery of the coumarin drug warfarin sodium in 1941. Since then, both the spectrum of disease for which anticoagulation is recommended and the range of anticoagulants has widened. In addition to treatment with conventional anticoagulant drugs, many patients nowadays have an additional bleeding defect due to the therapeutic use of daily low-dose aspirin therapy, either alone or in combination with other drugs. The aim of this report is to highlight some of the important aspects of anticoagulant therapy and its relevance to dental treatment.

The role of venom haemorrhagin in spontaneous bleeding in Bothrops jararaca envenoming. Butantan Institute Antivenom Study Group.

Thirty-eight patients bitten by Bothrops jararaca were investigated. Twenty-six had signs of local or systemic haemorrhage. Twenty-two of these had incoagulable blood, and these patients were found to have low fibrinogen levels (mean 0.17 +/- 0.03 g/l), thrombocytopenia, very high thrombin-antithrombin III complex (850 +/- 184 micrograms/l) and D-dimer (170 +/- 44 micrograms/ml) antigen levels. Serum venom haemorrhagin levels were significantly higher in patients with clinical signs of haemorrhage (36.4 +/- 6.4 ng/ml) than those without (11.7 +/- 3.7 ng/ml; p less than 0.002). Twelve out of 13 patients with thrombocytopenia were bleeding. High levels of thrombomodulin (22.3 +/- 1.5 ng/ml) and haemorrhagin (35.7 +/- 7.7 ng/ml) were detected in these 12 patients, suggesting vascular endothelial damage. Haemorrhagin levels also correlated inversely with platelet count in these patients. It was concluded that thrombocytopenia is one of the main causes of bleeding in B. jararaca victims, possibly as a result of venom haemorrhagin activity.

Anticardiolipin antibodies in leptospirosis.

The clinical course and serology of 16 cases of leptospirosis in an area with an unusually high endemic infection rate were studied to gain further insight into the pathology of the secondary immune phase that is typical of the disease. IgG anticardiolipin antibody concentrations were measured by immunoassay and found to be increased in eight serologically confirmed cases with severe complicated disease, compared with eight patients with relatively uncomplicated leptospirosis who had IgG anticardiolipin concentrations within the control reference range. This previously unreported association suggests that leptospira may induce vascular endothelial injury in severe cases and expose crypt antigens or induce conformational change of cell surface phospholipids. Leptospirosis may provide a model for an infective origin of some cases of the antiphospholipid syndrome.

Effects of recombinant human granulocyte colony-stimulating factor on neutrophil function in vitro and in vivo following chemotherapy and autologous bone marrow transplantation.

Recombinant granulocyte colony-stimulating factor (rG-CSF) primed the ability of human neutrophils to generate increased levels of reactive oxidants in response to fMet-Leu-Phe, and also resulted in an increased rate of protein biosynthesis which was similar to that induced by granulocyte-macrophage colony-stimulating factor. However, rG-CSF reduced the chemotactic activity of neutrophils in response to endotoxin and did not result in an enhanced rate of killing of Staphylococcus aureus. rG-CSF was administered to patients after high dose chemotherapy and autologous bone marrow transplantation for the treatment of either Hodgkin's disease or multiple myeloma. This cytokine decreased the period of neutropenia following such treatment. Neutrophil function in two patients, measured seven days after the final administration of rG-CSF, was severely impaired as indicated by a greatly decreased ability to generate reactive oxidants. However, seven days later (i.e. 14 days post-therapy), the functional activity of the neutrophils from these patients had returned to normal. These data indicate that assays of neutrophil function together with morphological assessment of neutrophil numbers and maturity should be performed in order to evaluate the immune status of patients undergoing such therapy.

Coagulopathy and haemorrhage in human victims of Bothrops jararaca envenoming in Brazil.

Thirty-four patients envenomed by Bothrops jararaca in Brazil were studied. Of these, 20 (59%) had incoagulable blood associated with local and/or systemic bleeding and 10 of the 20 were thrombocytopenic. Among 14 patients with coagulable blood, 6 (43%) had bleeding symptoms and 3 (21%) were thrombocytopenic. High levels of von Willebrand factor (vWF), plasminogen activator inhibitor type 1 (PAI-1) and tissue type plasminogen activator (t-PA) antigens were also recorded in some patients with systemic bleeding with or without incoagulable blood. These substances may have been released from endothelial cells. Admission serum venom antigen levels were similar in both groups. The study indicated that systemic haemorrhage may occur in patients with coagulable blood and thrombocytopenia and that coagulopathy is not therefore the primary cause of haemorrhage.

Aplastic anaemia associated with organochlorine pesticide: case reports and review of evidence.

Three patients with aplastic anaemia had a history of substantial previous exposure to organochlorine pesticides. The temporal association between chemical exposure and the onset of first symptoms of anaemia was strongly supportive. Organochlorines have the property of lipid affinity and accumulation in adipose tissue. Objective evidence of clinically important concentrations of tissue pesticide residues may be a useful confirmation of previous exposure. In the patients studied the presence of Lindane (gamma hexachlorocyclohexane) was shown using gas chromatography/mass spectrometry with selective ion monitoring of fragments obtained from one heavily exposed patient, with concentrations about five times greater than a matched control. The presence of clinically important tissue concentrations of pentachlorophenol was also confirmed in a second patient exposed to this agent. The long term safety of organochlorine pesticides remains doubtful as they were introduced before adequate toxicological screening tests had been developed. The central registration of possible haematological adverse reactions, however, forms an important epidemiological method in the study of environmental chemical hazards and should be complied with whenever possible.