kaolinite and Thrombosis

In order to examine the physiological role of thrombin-activatable fibrinolysis inhibitor (TAFI), we generated homozygous TAFI deficient mice by targeted gene disruption. Intercrossing of heterozygous TAFI mice showed that TAFI mice were born in the expected Mendelian ratio, indicating that transmission of the mutant TAFI allele did not lead to embryonic lethality. TAFI deficient mice developed normally and reached adulthood. No physical abnormalities were observed. They were fertile and pregnancies were carried to full term. Hematological analysis of TAFI deficient mice did not show any major differences compared with their wild type littermates, including plasma fibrinogen level, PT and aPTT. Prolongation of lysis time upon activation of TAFI was observed only with plasma from wild type and heterozygous mice in an in vitro clot lysis assay. TAFI deficiency did not lead to increased bleeding as determined by blood loss following tail transection. In vivo, TAFI deficiency did not influence occlusion time in either an arterial or a venous thrombosis model. The effects of TAFI deficiency were also investigated in thrombin-induced pulmonary thromboembolism, Factor X coagulant protein-induced thrombosis and endotoxin-induced disseminated intravascular coagulation models. In these models, TAFI deficiency did not improve the morbidity or mortality. Based on the kaolin-induced writhing test, TAFI did not play a major role in bradykinin degradation under normal conditions. These studies demonstrate that TAFI deficiency is compatible with murine life

Topics: Animals; Bradykinin; Carboxypeptidase B2; Carboxypeptidases; Fertility; Fibrinolysis; Humans; Kaolin; Mice; Mice, Knockout; Models, Biological; Thrombosis

Topics: Adrenal Cortex Hormones; Autoantibodies; Azathioprine; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; DNA; Factor VIII; Female; Fetal Death; Humans; Immunoglobulin G; Immunoglobulin M; Kaolin; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Partial Thromboplastin Time; Phospholipids; Pregnancy; Pregnancy Complications, Hematologic; Prothrombin Time; Thrombosis; von Willebrand Factor

Activation of coagulation cascades, especially FX and prothrombin, prevents blood loss and reduces mortality from hemorrhagic shock. Inorganic salts are efficient but cannot stop bleeding completely in hemorrhagic events, and rebleeding carries a significant mortality risk. The coagulation mechanism of biominerals has been oversimplified in the past two decades, limiting the creation of novel hemostats. Herein, at the interface, the affinity of proteins, the protease activity, fibrinolysis, hydration shell, and dynamic microenvironment are monitored at the protein level. Proteomic analysis reveals that fibrinogen and antithrombin III's affinity for kaolin's interface causes a weak thrombus and rebleeding during hemostasis. Inspiringly, amorphous bioactive glass (BG) with a transient-dynamic ion microenvironment breaches the hydration layer barrier and selectively and slightly captures procoagulant components of kiniogen-1, plasma kallikrein, FXII, and FXI proteins on its interface, concurrently generating a continuous biocatalytic interface to rapidly activate both intrinsic and extrinsic coagulation pathways. Thus, prothrombin complexes are successfully hydrolyzed to thrombin without platelet membrane involvement, speeding production of high-strength clots. This study investigates how the interface of inorganic salts assists in coagulation cascades from a more comprehensive micro-perspective that may help elucidate the clinical application issues of kaolin-gauze and pave the way to new materials for managing hemorrhage.

Topics: Blood Coagulation; Hemorrhage; Humans; Kaolin; Proteomics; Prothrombin; Salts; Thrombosis

Age, race, and gender differences in coagulation status of healthy volunteers have been reported in previous case series; however, rigorous multivariate analysis adjusting for these factors is lacking. We aimed to investigate the effects of age, race, and gender on baseline coagulation status in healthy volunteers.. Thirty healthy volunteer controls with no history of bleeding or thrombotic events and no previous anticoagulant or antiplatelet use were recruited. Citrated and heparinized blood samples were drawn, and kaolin and platelet-mapping thromboelastography (TEG) assays performed.. Thirty participants had a mean age of 37, mean body mass index of 29 kg/m. Women at baseline have relatively hypercoagulable fibrin deposition kinetics, platelet contributions to clot formation, and overall clot strength compared to men, even when adjusted for age and race. Additional research is needed to specifically detail the key patient-level factors, clinical implications, and opportunities for tailored therapy related to gender-associated hypercoagulability.

Topics: Adult; Anticoagulants; Female; Fibrin; Humans; Kaolin; Male; Thrombelastography; Thrombophilia; Thrombosis

Spontaneous abortion (SA) is a common complication of pregnancy. Presence of lupus anticoagulant (LA), one of the antiphospholipid antibodies, has been associated with SA in many studies, especially in Caucasians. This study was carried out to determine the prevalence of LA in women with SA in ABUTH, Zaria.. A cohort of 100 consecutive women presenting with SA with no history of thrombotic episodes were enrolled into the study. Prothrombin time (PT), kaolin clotting time (KCT), and activated partial thromboplastin time (APTT) were conducted on samples of all the participants. Eight patients had prolonged APTT, and after a 50:50 mixture of their plasma with pooled control plasma, four (50%) had uncorrected APTT. Staclot® (a hexagonal-phase phospholipid) test and calculated Rosner index for prolonged KCT were used for the confirmation of LA in samples with uncorrected APTT after mixing studies.. We analyzed 100 women with one or more SA with a mean age of 31.0 ± 3.8 years. Nearly 4% and 3% of the participants were LA positive with Staclot® and KCT tests, respectively. Patients with LA were more likely to have had a past history of preeclampsia/eclampsia, small for gestational age deliveries, and previous SA (prevalence odds ratio [95% confidence interval]) of 1.9 (0.2, 20.1), 3.2 (0.3, 34.3), and 1.4 (0.1-13.6), respectively. The PT, APTT, and KCT were significantly prolonged in patients with LA (P ≤ 0.001 for each, respectively).. LA may be one of the causes of SA and other adverse pregnancy outcomes such as preeclampsia/eclampsia and small for date deliveries. It is recommended that patients with prolonged APTT, uncorrected with 50:50 mixing study with pooled control plasma, should be evaluated further for LA.

Topics: Abortion, Spontaneous; Adult; Female; Humans; Kaolin; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Nigeria; Partial Thromboplastin Time; Pregnancy; Prevalence; Prothrombin Time; Thrombosis

Inflammation is implicated in the progression of coronary artery disease and the molecular processes of inflammation and thrombosis are closely intertwined. Elevated levels of C-reactive protein (CRP) have been associated with an elevated risk of adverse ischaemic events after coronary stenting and hypercoagulability. Heightened whole blood clot strength measured by thrombelastography (TEG) has been associated with adverse ischaemic events after stenting. We intended to examine the relationship of CRP to plasma fibrin clot strength in patients after coronary stenting. Plasma fibrin clot strength was measured by TEG in 54 patients 16-24 h after undergoing elective percutaneous coronary intervention (PCI). Coagulation was induced in citrated plasma by addition of kaolin and CaCl2. Plasma levels of CRP and fibrinogen were measured by enzyme-linked immunoassay. Increasing quartiles of CRP were associated with increasing levels of maximal plasma fibrin clot strength measured by TEG (P < 0.001) and increasing BMI (P = 0.04). Patients in the highest quartile of CRP had significantly higher maximal fibrin clot strength (G) than the patients in the lowest quartile (G: 3438 ± 623 vs. 2184 ± 576 dyn/cm, P < 0.0001). Fibrinogen concentration was not significantly different across quartiles of CRP (P = 0.97). Patients with established coronary artery disease undergoing coronary stenting who have elevated CRP after PCI exhibit heightened maximal plasma fibrin clot strength as compared with those with low CRP. Thrombotic risk associated with elevated CRP may be linked to procoagulant changes and high tensile fibrin clot strength independent of fibrinogen concentration.

Topics: Aged; Angioplasty, Balloon, Coronary; Blood Coagulation; C-Reactive Protein; Calcium Chloride; Coronary Artery Disease; Female; Fibrin; Fibrinogen; Humans; Inflammation; Kaolin; Male; Middle Aged; Risk Factors; Stents; Thrombelastography; Thrombophilia; Thrombosis

In people, studies have shown that resistance to fibrinolysis could be a contributing factor to thrombosis. Tissue-plasminogen-activated (t-PA) thromboelastography (TEG) has been used to evaluate endogenous fibrinolytic potential. In dogs, TEG has been used for the diagnosis of various hemostatic disorders, but studies evaluating fibrinolysis are limited. Investigations into the potential of t-PA-modified TEG to monitor endogenous fibrinolytic potential are lacking in both healthy dogs and dogs with diseases predisposing to development of thrombosis.. The aim of this study was to compare 3 t-PA-modified TEG assays and compare the endogenous fibrinolytic potential in dogs suffering from diseases associated with thrombosis with a group of healthy dogs.. Three different TEG assays, such as native, tissue factor-activated, and kaolin-activated, were modified with t-PA and used to compare whole blood samples from 16 healthy control dogs and 20 diseased dogs.. Thromboelastography lysis variables were significantly affected by addition of t-PA in all 3 assays. Lysis results in diseased dogs were comparable to those in healthy dogs prior to addition of t-PA. After addition of t-PA, lysis results were significantly decreased in the diseased group compared with healthy dogs. The lowest median lysis levels were found in dogs with systemic inflammation and protein-losing disorders.. Addition of t-PA activates fibrinolysis in TEG of blood from both healthy dogs and dogs with diseases predisposing to thrombosis. The significantly decreased fibrinolysis in diseased dogs suggests that this may be a potential prothrombotic risk factor in dogs.

Topics: Animals; Dog Diseases; Dogs; Female; Fibrinolysis; Fibrinolytic Agents; Kaolin; Male; Pilot Projects; Prospective Studies; Thrombelastography; Thrombosis; Tissue Plasminogen Activator

It is uncertain whether reactive thrombocytosis is associated with an increased risk of thrombosis. This prospective case-control study assessed the in vitro thrombotic tendency of patients with reactive thrombocytosis. Forty-eight patients with reactive thrombocytosis, defined by platelet count >500x10(9)/l and 55 similar, randomly selected critically ill patients who did not have reactive thrombocytosis were considered. In vitro thrombotic tendency in both groups of patients was assessed using maximal amplitude (normal range 54 to 72 mm) and alpha angle (normal range 47 to 74°) on the thromboelastograph. The associations between reactive thrombocytosis and C-reactive protein, the coagulation profile and Sequential Organ Failure Assessment score were also evaluated. Patients with reactive thrombocytosis had an associated increased in vitro thrombotic tendency (maximal amplitude 77 vs 69 mm, mean difference 8 mm, 95% confidence interval 4.9 to 10.9, P=0.001), a higher fibrinogen concentration (7.2 vs 5.8 g/l, P=0.003), and a higher incidence of infection requiring antibiotics (50 vs 27%, P=0.025) compared to patients without thrombocytosis. Platelet count had a relatively linear relationship with the maximal amplitude and the alpha angle of the thromboelastograph tracing (Pearson correlation coefficient: 0.53, P=0.001). In the multivariate analysis, only reactive thrombocytosis (odds ratio 5.9, 95% confidence interval 1.3-27.8, P=0.025) and activated partial thromboplastin time (odds ratio 0.93 per second increment, 95% confidence interval 0.87 to 0.99, P=0.016) were significantly associated with a strong in vitro thrombotic tendency. In summary, reactive thrombocytosis was associated with infection requiring antibiotics and evidence of increased in vitro thrombotic tendency in critically ill patients.

Topics: Adult; Aged; Case-Control Studies; Cohort Studies; Critical Illness; Data Collection; Female; Heparin Lyase; Humans; Kaolin; Male; Middle Aged; Odds Ratio; Platelet Count; Prospective Studies; Thrombelastography; Thrombocytosis; Thrombosis; Young Adult

In vivo data for the kaolin-based ACT test from the Sonoclot Analyzer (SkACT, Sienco Inc, Arvada, CO) are lacking. The aim of this study was to compare SkACT with an established kaolin-based ACT from Hemochron (HkACT) and anti-Xa activity in patients undergoing cardiopulmonary bypass (CPB).. Prospective observational study.. Community hospital.. Fifty patients scheduled for elective cardiac surgery.. Blood samples were taken before CPB at baseline (T0) and after heparinization (T1 and T2), on CPB after administration of aprotinin (5, 15, 30, 60 minutes; T3-T6), and at the end after protamine infusion (T7).. A total of 375 blood samples were analyzed. ACT measurements were comparable for SkACT and HkACT at each measurement time point. Overall bias +/- standard deviation between SkACT and HkACT was -19 +/- 75 seconds (-2.4% +/- 11.7%). Mean bias between SkACT and HkACT at each time point ranged from -35 to 3 seconds (-4.5% to 2.6%) and showed no statistical significance over time. Heparin sensitivity of SkACT and HkACT, defined as (ACT(Tx)-ACT(T0))/(anti-Xa(Tx)-anti-Xa(T0)), significantly increased for measurements during CPB (p < 0.001) but without significant difference between the 2 methods. Test variability was comparable for both ACT measurement techniques. Overall test variability was 7.5% +/- 7.4% for SkACT and 7.8% +/- 11% for HkACT.. Accuracy and performance of SkACT and HkACT were comparable for heparin monitoring in patients undergoing CPB for elective cardiac surgery. However, both tests were affected significantly after initiating CPB and aprotinin infusion.

Topics: Aged; Antidiarrheals; Aprotinin; Blood Coagulation; Cardiopulmonary Bypass; Elective Surgical Procedures; Factor Xa; Factor Xa Inhibitors; Female; Hemostatics; Heparin Antagonists; Humans; Infusions, Intravenous; Intraoperative Complications; Kaolin; Male; Myocardial Ischemia; Postoperative Complications; Prospective Studies; Protamines; Thrombosis; Treatment Outcome; Whole Blood Coagulation Time

A new low molecular weight heparin (LMWH) and a conventional unfractionated heparin (H) were tested in rats for venous antithrombotic activity and bleeding tendency after intravenous administration. Both drugs showed antithrombotic activity, but LMWH at the low dosages tested (0.1 and 0.25 mg/kg) demonstrated significantly higher activity than H. In a rat bleeding time test (transection model) both heparins produced a prolonged bleeding time, but LMWH possessed significantly less potency than H at all the dosages tested. Ex vivo coagulation parameters (activated partial thromboplastin time and antiXa activity) were also evaluated: LMWH presented very low activity on the APTT test and a sustained antiXa activity, comparable to that of H.

Topics: Animals; Factor X; Factor Xa; Hemorrhage; Heparin; In Vitro Techniques; Kaolin; Male; Partial Thromboplastin Time; Rats; Rats, Inbred Strains; Thrombosis

Topics: Heparin; Humans; Kaolin; Monitoring, Physiologic; Partial Thromboplastin Time; Thrombosis

Topics: Animals; Arginine; Bradykinin; Dexamethasone; Dimercaprol; Endotoxins; Esterases; Factor XII; Female; Hepatic Veins; Hyperlipidemias; Kallikreins; Kaolin; Male; Pregnancy; Prekallikrein; Rats; Shwartzman Phenomenon; Sulfinpyrazone; Thrombosis

Topics: Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Cardiovascular Diseases; Humans; Kaolin; Male; Platelet Adhesiveness; Prothrombin Time; Purpura; Radiation Injuries; Risk; Thromboplastin; Thrombosis; Thyroid Diseases

Topics: Animals; Blood Coagulation; Blood Coagulation Factors; Coronary Disease; Fibrinolysin; Fibrinolysis; Heparin Antagonists; Injections, Intravenous; Kaolin; Mercury; Rabbits; Streptokinase; Thrombin; Thromboembolism; Thrombophlebitis; Thrombosis

Topics: Animals; Blood Coagulation Tests; Blood Platelets; Cholesterol; Clot Retraction; Dogs; Fatty Acids; Fatty Acids, Essential; Fatty Acids, Nonesterified; In Vitro Techniques; Injections, Intravenous; Kaolin; Lipids; Male; Oleic Acids; Palmitic Acids; Phospholipids; Prothrombin Time; Silicon; Stearic Acids; Thrombosis; Triglycerides

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Collagen; Elastin; Factor XII; Hemophilia B; Humans; Kaolin; Rabbits; Thrombosis

Topics: Animals; Chiroptera; Fatty Acids; Kaolin; Palmitic Acid; Research; Stearic Acids; Thrombosis; Vasomotor System; Wings, Animal