Connection between genetically determined blood coagulation factors and haemorheology.

BACKGROUND: The phenotype caracteristic of blood clotting factors are well known, however few data has been documented about effects on haemorheology. The connection among genetic polymorphisms, haemorheological factors and vascular mortality is also studied poorly. PURPOSE: Our aim was: to study six genetic polymorphisms of blood clotting factors, which presents the role of platelet-plasmaprotein-endothel system in thrombotic course in controls and ischaemic stroke cohort. Second, to study the connection of genotypes and haemorheologic factors and both with five years vascular mortality in patients. PATIENTS AND METHODS: It was studied the genetic polymorhisms of GP IIb/IIIa Leu33Pro, prothrombin gene G20210A, ACE I/D, fibrinogen gene-455 G/A, Leiden mutation and MTHFR C677T alleles or genotypes in blood samples of 433 ischaemic stroke patients and 173 controls by PCR. Haematocrit values, plasma fibrinogen (FIB) concentration, whole blood viscosity (WBV) at 90 s(-1) and also the plasma viscosity (PV) were measured. Vascular mortality of patients were followed during five years and studied by curves Kaplan-Meier. RESULTS: A higher plasma FIB concentration in non smoker patients, carrying A alleles of FIB gene could be observed as compared to wild types (p<0.05). Also a moderate WBV increasing in smoker patients with A alleles was found against wild types (p=0.11), at the same time we observed a significant WBV increasing in non smoker patients (p<0.05). The highest quartile of PV showed a connection with Leiden mutation in whole group of patients (p=0.01), in subgroup of young patients (<50 years) (p=0.03) and also in non smoker groups (p<0.05) as compared to patients having wild types. No association could be detected between different genetic polymorphisms and vascular mortality, however it was observed significant mortality increasing in patients having PV above 1.51 mPa s (p=0.03). CONCLUSION: Certain genetic polymorphisms of coagulation system could result unfavorable haemorheological changes, however non of them increases the mortality. The connection between higher mortality and PV focuses the attention for the necessity of PV measuring and correction in stroke patients.

Contribution of the -455G/A polymorphism at beta-fibrinogen gene and of the Leiden mutation to hemorheological parameters in ischemic stroke patients.

UNLABELLED: The concentration of plasma fibrinogen (FIB) is an important factor in the coagulation cascade and also in the determination of blood and plasma viscosity depending on both genetic and acquired factors. The -455G/A polymorphism of the beta-FIB gene is connected to the plasma concentration of FIB but the effect of Leiden mutation on hemorheological parameters is unclear. The two genetic polymorphisms were studied by polymerase chain reaction in healthy subjects and ischemic stroke cohort and the effects on the concentration of plasma FIB, whole blood and plasma viscosity of patients as well. A total of 278 ischemic stroke patients and 173 control subjects were enrolled. Marcro-rheological parameters as plasma FIB concentration, whole blood viscosity (90 sec(-1) shear rate) and plasma viscosity have been measured also in the subgroup of young (age < 50 years) and in a subgroup of non-smoker patients. RESULTS: No significant difference was found in the prevalency of H1/H2 genotype between controls and cases in pooled stroke group OR 0.95 (95% CI: 0.47-1.27), however H2/H2 genotype frequency was increased in young subgroup of patients (OR: 1.66 95% CI: 0.52-5.25). Plasma FIB concentration was increased both in the total cohort (p < 0.05) and in the non-smoker subgroup (p < 0.03) of patients carried H2/H2 as compared to H1/H1 genotype and the prevalence was increased in the group of patients having plasma FIB concentration > 4 g/l (p < 0.05). The whole blood viscosity was elevated in the H2/H2 group as compared to the group carrying wild type (p < 0.03). A tendency of increased plasma viscosity in the group of patients with H2/H2 genotype as compared to wild type was found (p = 0.07). Leiden mutation prevalence showed an increased risk OR: 1.67 (95% CI: 0.75-3.70) in the young patients group as compared to controls. In patients who have had the highest plasma viscosity, higher frequency of Leiden mutation was detected as compared to wild type, in total group (p = 0.01), in young patients (p = 0.03) and in subgroup of non-smoker patients (p = 0.05). CONCLUSIONS: Our findings support the notion that the homozigous variant of beta-FIB gene can raise both plasma FIB concentration and whole blood viscosity. Leiden mutation connected to the elevation of plasma viscosity could demonstrate a new pathway of increased thrombophylic potential in ischemic stroke patients.

Effects of blood hyperviscosity on functional integrity in the brain stem: a brain stem evoked auditory potential study.

Clinical hemorheological and brain stem auditory evoked potential (BAEP) investigations were performed in patients with ischaemic brain stem stroke. Lesions were verified by MRI. 55 healthy persons with negative rheological and BAEP findings were used as controls (group A/1). 33 stroke patients with negative rheological parameters (group A/2) and 34 patients with hyperviscosity (group A/3) were also enrolled. In group A/3 bilateral pathological BAEP patterns were found, that could be explained by microcirculatory disturbances. 36 persons with verified blood hyperviscosity, but without neurological signs were also examined (group A/4). In this group, as in group A/3, either total lack of any waveforms, or a bilateral prolongation of wave III was observed. In 31 cases of group A/4, control BAEP was performed after effective haemodilution therapy, and 6-12 months later (group B/1). Here, normalization of rheological profile had a temporary beneficial effect on BAEP in 14 of 18 cases with former wave III prolongation, but had no effect on BAEP patterns in 13 cases, where lack of waves had been verified by the first investigation. These data suggest that hyperviscosity can result in subclinical pathological symmetric BAEP patterns, both in ischaemic stroke patients and in hyperviscosity patients without neurological symptoms.