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Biomedical subjects

M Blombäck

Publications and source records attributed to M Blombäck.

At least 19 recordsLinked to original sources
PubMed1992

Fibrin gel network characteristics and coronary heart disease: relations to plasma fibrinogen concentration, acute phase protein, serum lipoproteins and coronary atherosclerosis.

The native fibrin gel structure formed in vitro from plasma samples was examined by liquid permeation of the hydrated fibrin gel networks in 18 men who had suffered a myocardial infarction before the age of 45 years and in 20 control subjects. Patients with an elevated plasma fibrinogen concentration had a considerably lower fibrin gel porosity (permeability coefficient, Ks) compared with patients with a normal plasma fibrinogen level and with controls. The calculated fiber mass-length ratio of the fibrin gel networks was decreased in both patient groups. Gel porosity differed markedly between individuals at a given plasma fibrinogen concentration. Fairly strong inverse correlations were found between plasma orosomucoid level on the one hand and Ks (r = -0.617, p less than 0.01) or fiber mass-length ratio (r = -0.499, p less than 0.05) on the other. The low density lipoprotein (LDL) cholesterol concentration also correlated inversely with Ks (r = -0.471, p less than 0.05) and fiber mass-length ratio (r = -0.522, p less than 0.05). Significant inverse relations, which were independent of plasma fibrinogen and lipoprotein concentrations, were detected between Ks (r = -0.519, p less than 0.05) and calculated fiber mass-length ratio (r = -0.723, p less than 0.001) and number and severity of coronary artery stenoses determined by angiography. A proneness to formation of tight, rigid and space-filling fibrin network structures with small pores thus appears to be associated with premature coronary artery disease.

Acute-Phase Proteins↗
PubMed1992

von Willebrand factor in plasma and urine of men with premature coronary artery disease.

Plasma and urine samples from 17 men who had suffered a myocardial infarction before the age of 45 years were quantitatively and qualitatively analyzed for von Willebrand factor antigen (vWF), and compared with samples obtained from controls. The levels of vWF in plasma and its characteristic multimeric composition in the patient samples were not different from those of the controls. However, when analyzed for lower molecular weight components, plasma samples from some patients contained more degraded material than those of the controls as indicated by the presence of an extra protein band of vWF related material having a molecular weight of about 200 kDa. The levels in urine of vWF and the molecular weight of the fragments excreted did not differ between patients and controls. A relative increase in excretion of lower molecular fragments was, however, observed in the patient group. In a second group of 97 consecutive post-infarction patients under the age of 45 years the extra 200 kDa vWF band was found in 46% of the patients, whereas it was not detected in control plasmas. Taken together these findings suggest that degraded forms of vWF occur in normal plasma and that a more extensive degradation may occur in patients with coronary atherosclerosis, which could account for the relative increase in the excretion of lower molecular weight fragments observed in these patients.

Adult↗
PubMed1992

On the intraindividual and gender variability of haemostatic components.

The intraindividual variability in terms of coagulation analyses was explored in 10-16 samples collected from each of 15 women during one menstrual cycle. For comparison, six men were sampled six times during a period of 30 days. The following variables were analysed: FVII, FVIII, FX, vWF:Ag, vWF:ristocetin cofactor, fibrinogen, antithrombin, plasminogen and anti-plasmin. The results demonstrated mean coefficients of variation ranging between 4.5 (plasminogen) and 20.7 (vWF:Ag). In certain individuals, the intraindividual variability amounted to nearly 40%, in particular in the assays of FVIII and vWF:Ag. No direct relation between these two factors and oestradiol, progesterone or testosterone levels could be observed in our individuals. The implications of these variations are discussed in terms of disease prediction and diagnosis of coagulation disorders.

Adult↗
PubMed1992

On laboratory problems in diagnosing mild von Willebrand's disease.

By providing some examples of variations in the levels of von Willebrand factor antigen (vWF:Ag), ristocetin cofactor, and Factor VIII during one month, the authors wish to emphasize the difficulty of diagnosing mild forms of von Willebrand's disease (vWD), especially type I. In three of 15 normal female volunteers the vWF:Ag levels, on some sampling occasions, were so low (0.25-0.30 IU/mL, normal greater than 0.50 IU/mL) that the diagnosis of vWD type I might be made while on other occasions normal levels were obtained. The coefficients of variation (CV) for vWF:Ag in these three women were 12%, 25%, and 43%. However, CVs of similar magnitude were also observed for "non-diseased" males and females. The ratio F VIII/vWF:Ag also varied greatly. In the three women with suspected vWD it was 36%, 15%, and 34%. A representative level for the entire cycle of vWF:Ag and ristocetin cofactor seems to have been obtained in the follicular phase and therefore it is suggested that in order to make the diagnosis of vWD type I, at least in females, blood samples should be taken in this phase.

Adult↗
PubMed1992

Genetic and blood coagulation characterization of "Swedish" families with von Willebrand's disease types I and III: new aspects of heredity.

Twenty-five patients with von Willebrand's disease (vWD) type III were analysed with regard to blood coagulation variables and possible deletions. Nine of the probands and their families were further investigated with DNA linkage analyses. Different patterns of heredity can be suggested in our families with vWD type III, on the basis of blood coagulation analyses. The findings suggest homozygosity in five families and the possibility of compound heterozygosity or a new mutation in the proband in three families. The linkage analyses confirm the results of the coagulation analyses. The segregation of the von Willebrand factor (vWF) gene can be followed in the families, and carrier diagnosis can be made in several of the probands' relatives. The possibility of large deletions in the vWF gene of the probands and their parents was investigated with probes representing the whole vWF cDNA. No deletions were found.

Blood Coagulation↗
PubMed1992

Bleeding complications and coagulopathy in acute leukaemia.

Factors and inhibitors of coagulation and fibrinolysis were investigated on admission in 57 patients with acute leukaemia and they were correlated to the occurrence of haemorrhage. Coagulation disturbances were found in 98%. Seventeen of the patients with haemorrhagic symptoms had major bleeding. Severe thrombocytopenia (< 20 x 10(9)/l) was found in 16%. Patients with major bleedings had significantly lower concentrations of prothrombin complex, fibrinogen, protein C and platelets. Low levels of antiplasmin and fibrinogen were characteristic of 'bleeders' with promyelocytic and lymphoblastic leukaemia. We found a positive correlation between vWF:Ag and leukaemic cell count especially in lymphoblastic leukaemia (ks = 0.72). Reduced levels of antithrombin indicated a poorer prognosis.

Acute Disease↗
PubMed1992

Injection of xenogeneic endocrine pancreatic tissue into the portal vein--effects on coagulation, liver function, and hepatic hemodynamics. A study in the pig-to-dog model.

The safety of injecting discordant xenogeneic fetal endocrine pancreatic tissue into the portal vein was studied in a pig-to-dog system. It was found that minced fetal porcine pancreas and fetal porcine isletlike cell clusters prepared by collagenase digestion and culture could be injected with only minor or no hepatic hemodynamic disturbances. Coagulation studies revealed a small increase in plasma fibrinopeptide A, but this increase could be prevented by heparinization of the recipient. There was no consumption of fibrinogen or platelets. In contrast, injection of minced adult porcine pancreas caused pronounced hepatic hemodynamic changes and marked coagulation abnormalities, indicating consumption coagulopathy. The present finding that fetal porcine pancreas can be injected intraportally without deleterious effects in dogs provides a foundation for the eventual clinical use of such material as treatment for insulin-dependent diabetes mellitus.

Animals↗
PubMed1992

Proteolytic activity during storage of platelets in plasma.

Proteolytic activity was studied in platelet concentrates (PC) stored in plasma at 22 degrees C. In experiment 1, two PC with a higher (A) and a lower (B) white cell concentration were prepared from each of nine donors by centrifugation. Aliquots of the cell-free plasma, PPP, were stored as a control. Samples for the assay of fibrinopeptide A (FPA), elastase, spontaneous proteolytic activity (SPA), kallikrein-inhibiting activity, thrombin-antithrombin complexes (TAT) and D-dimers were collected initially and on days 1, 3, 5 and 7 of storage. Consumption of glucose, pH and concentrations of lactate dehydrogenase (LDH) and ATP were determined to investigate the metabolic status of the PC. The decrease in pH correlated to the leucocyte count, r = -0.74, P < 0.001 and to the increase in LDH, r = -0.74, P < 0.01. The levels of elastase and the SPA were consistently low in the PPP bags. In the PC elastase had increased by day 5 and the SPA by day 3; the levels in PC A were significantly higher than in PC B, P < 0.01. The leucocyte count correlated with the elastase activity, r = 0.71, P < 0.01, and with the SPA, r = 0.65, P < 0.01. A minor increase in FPA was demonstrated while no TAT and D-dimers could be detected. The cause of the formation of FPA was studied in experiment 2; three bags of PC and four of PPP were prepared from each of 16 donors. To the PC and three of the PPP bags either hirudin, aprotinin or no enzyme inhibitor (control) was added.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗
PubMed1992

Effect of antithrombin concentrate on haemostatic variables in critically ill patients.

In a controlled pilot study of 32 critically ill patients, we have attempted prospectively to identify laboratory variables which can be used to select and monitor patients on antithrombin (AT) therapy. Patients with plasma AT levels less than 70% of normal were randomized to receive (AT group) or not to receive AT concentrate (non-AT group). The groups did not differ in median age, sex, median APACHE II and TISS scores, number of days spent in the Intensive Care Unit or mortality rate. At the time of inclusion all patients had activated coagulation and fibrinolysis demonstrated as high levels of soluble fibrin, thrombin-antithrombin complexes and fibrin-D-dimers (twice, four and ten times the upper reference range, respectively). In the AT group these levels decreased faster and the prothrombin complex concentration increased more rapidly to normal (i.e. the prothrombin time decreased). The level of C-reactive protein which was high in both groups on inclusion (139 and 98 mg/l, respectively) decreased by 40% in the AT group but did not change in the control group. Our study indicates that laboratory variables normalize faster in seriously ill patients who have activated coagulation and fibrinolysis when they receive AT concentrate and that the variables mentioned above seem to be useful for monitoring the treatment.

Aged↗
PubMed1992

von Willebrand's disease in Scandinavia and on difficulties in diagnosing von Willebrand's disease type I.

The research on von Willebrand's disease performed in Sweden and Finland since the late 1920s is reviewed. The difficulties in diagnosing mild von Willebrand's disease, due to intra-individual variability, is discussed in relation to making correct pedigrees for genetic studies. As shown by some examples, new techniques for genetic studies will eliminate such difficulties and lead to better understanding of the pathogenesis.

History, 20th Century↗
PubMed1992

Blood component processing technique and plasma quality.

To maintain a closed system during the preparation of blood components, including the removal of buffy coat, many centers use a quadruple blood bag additive solution system which in this study has been reduced to a cheaper triple bag system. The buffy coat and plasma were after centrifugation transferred to the first satellite bag and, after a second spin, the plasma separated from the buffy coat was transferred to the second satellite bag and stored for a fortnight at 4 degrees C. This resulted in a statistically significant increase in platelet factor 4 and elastase activity levels. No significant changes were found in the levels of C1-esterase inhibitor and kallikrein inhibiting activity, thrombin-antithrombin complexes, soluble fibrin, fibrinopeptide A and spontaneous proteolytic activity. The changes observed must be regarded as clinically insignificant. The platelet count is low enough to meet the requirements for platelet poor plasma. Using this blood component separation technique, one can reduce the CPD/additive solution 4-pack blood bag system to a less expensive 3-pack blood bag system.

Blood Banks↗
PubMed1992

Freezing technique and quality of fresh-frozen plasma.

Cell-poor plasma was prepared by apheresis from 10 donors. From each donor, an amount of 200 ml was frozen rapidly to -40 degrees C in standard blood bags, and a further 200 ml was frozen slowly to -20 degrees C. Before freezing and after thawing, plasma samples were collected and frozen to -70 degrees C pending analysis. Coagulation factor VIII activity was reduced to 90% by rapid freezing and to 80% by slow freezing. Factor V was not influenced by rapid freezing, but slow freezing reduced the levels to 92% of the pre-freezing levels. In some of the plasma bags a slight increase in fibrinopeptide A occurred. However, soluble fibrin, thrombin-antithrombin complexes and spontaneous proteolytic activity were not altered by freezing. The beta-thromboglobulin increased slightly with slow freezing. Moreover, in a separate experiment, evaluating the possible effects of refreezing plasma samples, an increase in beta-thromboglobulin was also recorded, while the levels of factors VIII and V and von Willebrand factor were not affected. The changes in some variables, which were recorded in the cell-poor plasma, frozen soon after the blood donation at a slow freezing rate, must be regarded as insignificant in most clinical situations.

Antithrombin III↗
PubMed1992

Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I.

von Willebrand disease (vWD) is the most common inherited bleeding disorder in humans. The disease is caused by qualitative and quantitative abnormalities of the von Willebrand factor (vWF). Genomic DNA from 25 patients with vWD type III, the most severe form of the disease, was studied using PCR followed by restriction-enzyme analysis and direct sequencing of the products. Nonsense mutations (CGA----TGA) were detected in exons 28, 32, and 45 by screening of all the 11 CGA arginine codons of the vWF gene. Two patients were found to be homozygous and five heterozygous for the mutation. Both parents and some of the relatives of the homozygous patients carry the mutation. These are the first reported examples of homozygous point mutations associated with the severe form of vWD. In the three heterozygous probands, one of the parents carried the mutation and had vWD type I. Family studies including parents and family members with or without vWD type I indicated that these three heterozygous patients are likely to be compound heterozygous. Twenty-one individuals from these seven families with vWD type I were found to be heterozygous for the mutation.

Adolescent↗
PubMed1992

Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium.

Blood coagulation and fibrinolytic inhibitors and the balance between and within the two systems were investigated in 26 normal pregnant women during pregnancy and the puerperium. The concentration of the coagulation inhibitors antithrombin and protein C remained within normal levels, whereas the mean level of free protein S showed a significant decrease from 0.26 U/mL in early pregnancy to 0.14 U/mL in week 35. At the same time, soluble fibrin levels increased from 9.2 to 13.4 nmol/L and thrombin-antithrombin complexes increased from 3.1 to 7.1 micrograms/L; both are indicators of thrombin activity. A concurrent increase in the levels of the fibrinolytic inhibitors plasminogen activator inhibitor-1 and -2 from 7.4 to 37.8 AU/mL and 31 to 160 micrograms/L, respectively, suggests a decrease in fibrinolytic activity. However, the levels of fibrin D-dimer, ie, fibrin split products, also increased in parallel from 91 to 198 micrograms/L, suggesting that fibrinolysis is present. Thus, a balance normally exists, which is probably why thrombotic events are rare during pregnancy.

Adult↗