Activation Of Blood Coagulation System Research Articles

ГЕМОСТАТИЧЕСКИЕ НАРУШЕНИЯ ПРИ НЕОПУХОЛЕВОЙ МЕХАНИЧЕСКОЙ ЖЕЛТУХЕ И ХОЛАНГИТЕ В ЗАВИСИМОСТИ ОТ ТЯЖЕСТИ И ПОЛИМОРФИЗМА ГЕНА ФИБРИНОГЕНА

Background. Mechanical jaundice (MF) and cholangitis are considered to be of great significance in emergency surgery due to their complex pathogenesis, risk of complications and high mortality. Objective. To establish the severity of hemostatic disorders in association with fibrinogen gene polymorphism (FGB (G(-455)A)) in patients with non-cancerous MF and cholangitis of varying severity. Material and methods. The subjects were 25 patients with benign MF and cholangitis divided into 2 groups: group 1 (n=12) – those with a mild form of the disease; group 2 (n=13) – those with a severe form. The research methods included the assessment of endogenous intoxication, liver function as well as blood coagulation activity. Genetic analysis of the FGB (G(-455) geneA)) was performed using a polymerase chain reaction by Real–time PCR. The severity of the disease was determined using the V.D. Fedorov scale (2000). Results. The early stage of MF and cholangitis is accompanied by endotoxicosis, resulting in the damage of a number of organs and systems, in particular the liver. The latter plays an important role in changing the activity of blood coagulation system. These disorders had a strong correlation with the severity of the disease: in mild cases, the character was less pronounced and reversible, and in severe cases – persistent and severe. Hemostatic disorders recorded in the early period of the disease depend on the severity: in mild cases, hypercoagulation and normofibrinolysis are noted, and in severe cases – hypocoagulation and hypofibrinolysis. Genetic polymorphism of the fibrinogen gene FGB (G(-455)A) had a significant impact on the pathogenetic process of MF and cholangitis. Patients with the mutant genotype (A/A) of the FGB gene were found to show the greatest severity of homeostasis system violation when compared with patients with genotypes G/G and G/A – with minimal imbalance. Conclusions. Hemostatic disorders associated with polymorphism of the fibrinogen gene FGB (G(-455)A) play an important role in the pathogenesis of MF and cholangitis.

RELATIONSHIP BETWEEN PRE- AND POST-THROMBOSIS FACTORS IN PATIENTS WITH STAGE VD CKD TREATED BY LONG-TERM HEMODIALYSIS

The aim: To determine informative value of pre-thrombosis, post-thrombosis and anticoagulation factors as well as their correlations for assessment of hemostasis status in patients with stage VD CKD. Materials and methods: Potential predictors of thrombophilia development as well as their relationships depending on the level of molecular markers of hemostasis were studied in 88 patients with stage VD CKD undergoing long-term hemodialysis with the view to determine their informative value. Results: Accumulation of soluble fibrin (sF) was demonstrated to cause moderate reaction of D-dimer (D-d) being insufficient in the absence of reaction of anticoagulant component of hemostasis. Soluble fibrin levels were found to be associated with D-d concentration (r = 0.39) and functionally inactive prothrombin forms (FIPF) to some extent (r = -0.24). Accumulation of FIPF in individuals with high level of sF implies significant activation of blood coagulation system at the stage prior to thrombin formation. Absence of close relationship between pre- and post-thrombosis indices may be indicative of still preserved potential of anticoagulant component of hemostasis. Conclusions: Accumulation of FIPF is an early marker of activation of blood coagulation and possible thrombosis. Levels of sF correlate with pre-thrombosis (fibrinogen, FIPF) and post-thrombosis (D-d) factors being associated with inhibition of anticoagulation processes. Comprehensive study of basic components of hemostasis in patients with VD stage of chronic kidney disease offer broader opportunities in arranging prophylactic measures to prevent thrombophilia.

TPA as marker of thrombosis development after surgical treatment for pancreatic cancer.

e15679Background: Blood rheology maintenance is associated with activity of blood coagulation system and content of prothrombokinase (tPA-Ag) and active thrombokinase (tPA-act) in particular. The p...

Blood coagulation in falciparum malaria—a review

Falciparum malaria infection influences blood coagulation by various interacting pathobiological mechanisms, the most important being the overwhelming response of the host to sepsis resulting in a cytokine storm. In addition, the parasite infects the red cells leading to changes in the red cell phospholipid composition which supports blood coagulation. Red cells infected with Plasmodium falciparum also adhere to deeper tissue capillary endothelium leading to profound damage to endothelial cells leading to further activation. This results in widespread consumption of platelets and activation of blood coagulation which at times culminates in a clinically and pathologically detectable disseminated intravascular coagulation (DIC). Monocyte-macrophage system also gets activated in this infection compounding the hypercoagulable state. Heavy parasitaemia leading to occlusion of hepatic microcirculation leads to abnormalities in synthesis and secretion of coagulation factors and their inhibitors. Drugs used in the treatment for falciparum malaria can cause thrombocytopaenia, bone marrow suppression and haemolytic anaemia, all of which can interfere indirectly with blood coagulation. Microparticle formation from platelets, red cells and macrophages also causes widespread activation of blood coagulation, and this recently observed mechanism is the focus of intense research in many other inflammatory and neoplastic conditions where there is activation of blood coagulation system. Thus, in severe falciparum malaria, there is activation of blood coagulation system along with thrombocytopaenia, even before widespread DIC and coagulation failure occur.

Degradation of human brain natriuretic peptide (BNP) by contact activation of blood coagulation system

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) were added to venous blood samples from healthy volunteers, and incubated in tubes made of various materials. The residual immunoreactivity was measured with radioimmunoassay for BNP and ANP. In blood samples stored in glass tubes, immunoreactivity of ANP was more stable than that of BNP. In siliconized glass or PET tubes, however, BNP immunoreactivity was more stable than ANP. The activation of blood coagulation factors was evaluated from the kallikrein activity in plasma. Kallikrein activity was increased in plasma stored in glass tube while it was negligible in plasma stored in siliconized glass or PET tubes. In kaolin-activated plasma, more rapid BNP degradation and higher kallikrein activity were observed. Our results indicated that the blood coagulation factors, especially kallikrein, played an important role in digestion of BNP.

PROSTACYCLIN ANALOGUE ENHANCES THE EFFECT OF PROTEASE INHIBITOR AS ANTICOAGULANT FOR LEFT VENTRICULAR ASSIST DEVICE (LVAD)

[Aim] Protease inhibitor (FUT) alone, and the combined administration of FUT and prostacyclin analogue (PG) were studied as anticoagulants for left LVAD instead of heparin. [Materials and Methods] On 36 mongrel dogs, LVAD was performed for 24 hours, and blood coagulative study was made before and during LVAD performance. Dogs were divided into the following 4 groups according to the type of anticoagulation. GroupI: no anticoagulation (n=9), Group II: heparin (0.25 mg/kg/hr) (n=9), Group III: FUT alone (15μ g/kg/min) (n=9), Group IV: FUT (15μ g/kg/min) + PG (1 μ g/kg/min) (n=9) [Results] In all groups, LVAD could be performed without any thrombogenic trouble. Prothrombin time showed marked prolongation in Group II (heparin), but gradual prolongation in other groups. Activated partial thromboplastin time showed gradual prolongation in all groups. Fibrinogen showed a marked decrease and reached 50 % of preoperative value (below 100 mg/dl) in 24 h in Group I (no anticoagulation): whereas, in Group II (heparin) and Group III (FUT). it showed a slight decrease till 3 h after the start, but thereafter came gradually back to the previous level. In Group IV (FUT + PG), it was almost unchanged all the time. α2-plasmin inhibitor was almost unchanged in Group II (heparin), Group III (FUT) and Group IV (FUT + PG); whereas. in Group I (no anticoagulation), it showed severe decrease and reached to 55 % of preoperative value in 24 h. Factor XII showed gradual significant decrease in all groups. [Conclusion] FUT alone can prevent the activation of blood coagulation system to some extent as low dose of heparin. PG combined with FUT can prevent the activation of intrinsic pathway of blood coagulation system to a minimal level through intense inhibition of platelet aggregatin by PG.

Is contact activation of the coagulation system involved in the genesis of the first-use syndrome?

A number of mechanisms have been thought to be involved in the pathogenesis of the first-use syndrome. These include IgE antibody-mediated response to ethylene oxide-related antigens, membrane activation of the alternative complement pathway, activation of tissue mast cells and basophils by materials released from the dialyzer into the circulation, and transfer of bacterial products through high flux dialyzer. However, the possible role of the activation of blood coagulation system and platelets during dialysis has not been considered. The present communication reviews the theoretical basis for a possible connection between dialysis-induced activation of platelets and coagulation system with the first-use syndrome. Although the available data concerning the activation of intrinsic coagulation pathway during dialysis are conflicting, there is no controversy as to the occurrence of platelet activation. It is suggested that biochemical events triggered by activation of these systems may in part contribute to the genesis of first-use syndrome.