scholarly journals Factor XII-Deficient Chicken Plasma as a Useful Target for Screening of Pro- and Anticoagulant Animal Venom Toxins

Toxins ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 79
Author(s):  
Benedito C. Prezoto ◽  
Nancy Oguiura
Keyword(s):  
High Sensitivity ◽  
Factor Xii ◽  
Dependent Manner ◽  
Clotting Time ◽  
Natural Factor ◽  
Rotational Thromboelastometry ◽  
Factor Xii Deficiency ◽  
Dose Dependent ◽  
Recalcification Time ◽  
Coagulation Pathway

The sensitivity of vertebrate citrated plasma to pro- and anticoagulant venom or toxins occurs on a microscale level (micrograms). Although it improves responses to agonists, recalcification triggers a relatively fast thrombin formation process in mammalian plasma. As it has a natural factor XII deficiency, the recalcification time (RT) of chicken plasma (CP) is comparatively long [≥ 1800 seconds (s)]. Our objective was to compare the ability of bee venom phospholipase A2 (bvPLA2) to neutralize clot formation induced by an activator of coagulation (the aPTT clot) in recalcified human and chicken plasmas, through rotational thromboelastometry. The strategy used in this study was to find doses of bvPLA2 that were sufficient enough to prolong the clotting time (CT) of these activated plasmas to values within their normal RT range. The CT of CP was prolonged in a dose-dependent manner by bvPLA2, with 17 ± 2.8 ng (n = 6) being sufficient to displace the CT values of the activated samples to ≥ 1800 s. Only amounts up to 380 ± 41 ng (n = 6) of bvPLA2 induced the same effect in activated human plasma samples. In conclusion, the high sensitivity of CP to agonists and rotational thromboelastometry could be useful. For example, during screening procedures for assaying the effects of toxins in several stages of the coagulation pathway, such as clot initiation, formation, stability, strength, or dissolution.

scholarly journals The Effects of Atorvastatin on Arterial Stiffness in Male Patients with Type 2 Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Colin Davenport ◽  
David T. Ashley ◽  
Eoin P. O’Sullivan ◽  
Claire M. McHenry ◽  
Amar Agha ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Arterial Stiffness ◽  
Statin Therapy ◽  
Vascular Inflammation ◽  
High Sensitivity ◽  
Serum Markers ◽  
Dependent Manner ◽  
Male Patients ◽  
Dose Dependent

Statin therapy improves lipid profiles and reduces vascular inflammation, but its effects on central arterial stiffness in type 2 diabetes are unclear. The aim of this study was to determine whether statin therapy reduces central arterial stiffness, in a dose-dependent manner, in male patients with type 2 diabetes. Fifty-one patients ceased statin therapy for 6 weeks, followed by randomisation to either 10 or 80 mg of atorvastatin. At randomization, 3 and 12 months, central arterial stiffness was measured via carotid-femoral pulse wave velocity (PWV), along with serum markers of vascular inflammation including high-sensitivity c-reactive protein (hsCRP) and osteoprotegerin (OPG). PWV decreased from 10.37 ± 1.30 to 9.68 ± 1.19 m/sec (p<0.01from baseline) at 3 months and 9.10 ± 1.17 m/sec (p<0.001from baseline) at 12 months. hsCRP and OPG decreased significantly at 3 and 12 months. Reductions in PWV did not differ significantly between the groups. Baseline PWV and OPG values correlated strongly (r=0.48,p<0.01), as did their response to atorvastatin over 12 months (r=0.36delta-OPG and delta-PWV,p<0.01). Atorvastatin therapy appeared to reduce central arterial stiffness in male type 2 diabetes, with no dose-dependent effect observed. The correlation observed between reductions in PWV and OPG suggests that atorvastatin reduces PWV via direct anti-inflammatory effects on the vasculature.

scholarly journals Third-Generation Hydroxyethyl Starch Causes Dose-Dependent Coagulopathy in Patients Undergoing Off-Pump Coronary Artery Bypass with Continuation of Preoperative Aspirin

2021 ◽  
Vol 24 (5) ◽  
pp. E949-E854
Author(s):  
GO KUSUMOTO ◽  
Midoriko Higashi ◽  
Kenji Shigematsu ◽  
Ken Yamaura
Keyword(s):  
Coronary Artery ◽  
Blood Loss ◽  
Artery Bypass ◽  
Dependent Manner ◽  
Third Generation ◽  
Off Pump ◽  
Pump Coronary Artery Bypass ◽  
Crystalloid Administration ◽  
Dose Dependent ◽  
Coagulation Pathway

Background: We aimed to evaluate the effect of third-generation hydroxyethyl starch (6% HES 130/0.4) on hemostasis and perioperative blood loss in patients undergoing off-pump coronary artery bypass (OPCAB) with continuation of preoperative aspirin. Methods: Forty-nine consecutive patients, who underwent OPCAB at a single institution between November 1, 2014 and March 31, 2016, were included. Coagulation tests, including thromboelastometry and clinical data of all patients, retrospectively were collected from anesthesia and medical records. Results: The total amount of intraoperative crystalloid and HES was 2057.5 ± 771.6 mL (N = 32) and 1090.6 ± 645.0 mL (N = 32), respectively. In the coagulation pathway, the change ratio of fibrinogen concentration, prothrombin time, and fibrinogen thromboelastometry-maximum clot firmness (FIBTEM-MCF) significantly correlated with HES (P < 0.001, P = 0.00131, and P < 0.001, respectively), but not with crystalloid. In the coagulation pathway concerning interaction with platelets, the change ratio of platelet count, extrinsic thromboelastometry-clotting formation time (EXTEM-CFT), and EXTEM-MCF significantly were correlated with HES (P < 0.001, P < 0.001, and P < 0.001, respectively), but not with crystalloid. At chest closure, the hematocrit decreased in a dose-dependent manner with HES (P < 0.001), but not with crystalloid administration. There was an association between the change ratio of hematocrit and EXTEM-MCF (P = 0.00122). However, intra-postoperative blood loss was not correlated with HES 130/0.4 or crystalloid administration. Conclusion: We found that 6% HES 130/0.4 prolonged coagulation testing in a dose-dependent manner due to hemodilution but did not increase blood loss in patients undergoing OPCAB with continuation of preoperative aspirin.

INCREASED PLATELET AGGREGABILITY IN NATIVE WHOLE BLOOD IN THE ADULT RESPIRATORY DISTRESS SYNDROME (ARDS)

1987 ◽  
Author(s):  
I J Mackie ◽  
D Bihari ◽  
S J Machin
Keyword(s):  
Whole Blood ◽  
Electrical Impedance ◽  
Distress Syndrome ◽  
Dependent Manner ◽  
Clotting Time ◽  
Serum Thromboxane ◽  
Low Levels ◽  
The Difference ◽  
Induced Aggregation ◽  
Dose Dependent

The measurement of aggregation in whole blood allows the study of platelets in their natural milieu, but may still have anticoagulant induced artifacts; citrate decreases extracellular (Ca++) and heparin activates platelets. A technique for measuring aggregation in unanticoagulated (native) whole blood (NWB) was developed; blood is diluted in prewarmed saline with and without platelet agonists and aggregation is monitored by electrical impedance. Spontaneous and collagen induced aggregation were measured and the effect of prostacyclin analogue ZK 36,374 studied. The time until response (lag), aggregation rate, and clotting time were measured. Normal blood gave a cv of <7% for the NWB parameters; collagen gave a shorter lag and higher rate than in citrated whole blood (CWB). The lag and rate were inhibited in a dose dependent manner by ZK 36,374. 6 patients were studied on admission with ARDS and followed for several days. All had increased aggregation to collagen, which was more pronounced in NWB than CWB. A shortened lag was seen in some patients, but none showed spontaneous aggregation. ARDS patients showed no inhibition to ZK 36,374, and the heightened aggregation was not influenced by 2mM ASA, or normal plasma, while 2.5mM EDTA abolished all responses. Serum thromboxane B2 was normal, and increased flux through the cyclo-oxygenase pathway therefore unlikely. A parallel study has shown very low levels of antithrombin III (ATIII) in these patients, which may mean an increased thrombin generation rate with more thrombin available for platelet activation. This partly explains the difference in degree of hyperaggregability seen with NWB and CWB. During recovery from ARDS, collagen aggregation and the response to ZK 36,374 normalises at the same time as AT-III increases.

scholarly journals Global cerebral infarction after aortic arch replacement surgery in a patient with postoperatively revealed factor XII deficiency: a case report

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Keisuke Yoshida ◽  
Shiori Tanaka ◽  
Yuki Sato ◽  
Kazuhiro Watanabe ◽  
Kenichi Muramatsu ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Cerebral Infarction ◽  
Acute Type ◽  
Factor Xii ◽  
Clotting Time ◽  
Type A Aortic Dissection ◽  
Factor Xii Deficiency ◽  
Replacement Surgery ◽  
Activated Clotting Time ◽  
Heparin Administration

Abstract Background This case report presents a case of a patient with global cerebral infarction of uncertain etiology following an emergency surgery for acute type A aortic dissection. As a result, factor XII deficiency was revealed postoperatively. To date, there have been several reports of cardiovascular surgery in patients with factor XII deficiency. However, all previous reports were of patients whose factor XII deficiency had been detected preoperatively; therefore, before this, there had been no reports of complications associated with factor XII deficiency following cardiovascular surgery. Case presentation We report a case of emergency aortic arch replacement surgery for acute type A aortic dissection in a 57-year-old Japanese man. A blood test prior to the surgery showed coagulopathy, a platelet count of 117 × 109/L, a prothrombin time–international normalized ratio of 1.78, an activated partial thromboplastin time of 69.7 seconds, and fibrinogen < 50 mg/dl. A smaller-than-usual dose of heparin (8000 IU) was administered because the patient’s activated clotting time was extremely prolonged (> 999 seconds). After the heparin administration, the activated clotting time, measured every 30–60 minutes, remained unchanged (> 999 seconds); therefore, additional heparin was not administered during the surgery, and there was no clinical problem during cardiopulmonary bypass. However, a diagnosis of global cerebral infarction was made on the first postoperative day. An additional blood coagulation test performed on postoperative day 9 revealed factor XII deficiency (8.0%). Regarding the reason that global cerebral infarction occurred in the present case, two reasons were considered: One was factor XII deficiency itself, and the other was low-dose heparin administration during the cardiopulmonary bypass due to excessively prolonged activated clotting time caused by factor XII deficiency. Conclusions Factor XII deficiency should be considered in patients with prolonged activated clotting time and spontaneous thrombosis in vascular surgeries. Moreover, the present case emphasizes that management of heparin during cardiopulmonary bypass should not be performed on the basis of activated clotting time monitoring alone, especially in a case with prolonged activated clotting time.

scholarly journals Endogenous Betaglycan Is Essential for High-Potency Inhibin Antagonism in Gonadotropes

2009 ◽  
Vol 23 (7) ◽  
pp. 1033-1042 ◽  
Author(s):  
Ezra Wiater ◽  
Kathy A. Lewis ◽  
Cynthia Donaldson ◽  
Joan Vaughan ◽  
Louise Bilezikjian ◽  
...  
Keyword(s):  
Rna Interference ◽  
Anterior Pituitary ◽  
Feedback Loop ◽  
High Sensitivity ◽  
Negative Feedback Loop ◽  
Dependent Manner ◽  
High Potency ◽  
Inhibin A ◽  
Endocrine Hormones ◽  
Dose Dependent

Abstract Inhibins are endocrine hormones that regulate gametogenesis and reproduction through a negative feedback loop with FSH. Inhibin action involves antagonism of signaling by activin or other TGFβ family ligands. In transfection assays, antagonism by inhibin can be potentiated by betaglycan, a coreceptor for selected TGFβ family ligands. We tested whether betaglycan is an obligate inhibin coreceptor through disruption of betaglycan function by RNA interference-mediated knockdown and immunoneutralization. Betaglycan knockdown and anti-betaglycan IgG each independently prevented inhibin-A binding to betaglycan and reversed functional effects of transfected betaglycan. Neither betaglycan immunoneutralization nor knockdown affected activin responsiveness in cell lines or in rat anterior pituitary cultures. Betaglycan knockdown decreased the potency of inhibin antagonism of activin-induced FSH secretion in primary gonadotropes. Similarly, anti-betaglycan IgG decreased the potency of inhibin antagonism in primary gonadotropes in a dose-dependent manner, with a reduction in the sensitivity to inhibin-A of greater than 1000-fold. These data establish that betaglycan is an endogenous inhibin coreceptor required for high-sensitivity inhibin antagonism of activin signaling in rat anterior pituitary gonadotropes.

Activation of Hageman Factor in Rat Anaphylaxis

1975 ◽  
Author(s):  
L. Fésüs ◽  
L. Muszbek
Keyword(s):  
Blood Clotting ◽  
Plasminogen Activators ◽  
Factor Xii ◽  
Clotting Time ◽  
Hageman Factor ◽  
Kaolin Clotting Time ◽  
Aggregation Of Platelets ◽  
Recalcification Time

At various intervals after antigen injection assays concerning haemostatic parameters were carried out in anaphylactic shock of rats pretreated with Bordetella Pertussis Vaccine. These were as follows: measurement of whole blood clotting time, recalcification time, partial thromboplastin time, kaolin clotting time in siliconised tubes, determination of the level of factor XII, measurement of plasminogen activator level, in vitro aggregation of platelets. The different clotting times shortened and the aggregation of platelets was inhibited within the first three-four minutes. The clotting times lengthened, the level of plasminogen activators increased, the level of factor XII decreased during the further minutes. These results and their comparison with that of produced by ellagic acid injection suggest that during anaphylaxis of rats the activation of Hageman factor takes place, which is followed by its partial consumption.

Cardiopulmonary bypass in a child with severe Factor XII deficiency

Perfusion ◽  
2021 ◽  
pp. 026765912199930
Author(s):  
Nicole Shrimpton ◽  
Aditya Patukale ◽  
Mark Rane ◽  
Pasquale Barbaro ◽  
Nelson Alphonso ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Fresh Frozen Plasma ◽  
Factor Xii ◽  
Clotting Time ◽  
Factor Xii Deficiency ◽  
Activated Clotting Time ◽  
Heparin Anticoagulation ◽  
Fresh Frozen ◽  
Clinically Significant ◽  
Frozen Plasma

Factor XII (FXII) deficiency presents as a prolonged activated partial thromboplastin time (aPTT) but is not associated with clinically significant bleeding. Activated clotting time (ACT) is used routinely to monitor anticoagulation with unfractionated heparin in patients undergoing cardiopulmonary bypass (CPB). The coagulation activator reagents in most ACT tests are dependent on adequate FXII concentrations to initiate contact factor coagulation pathways. We report the case of a 14.7 kg girl undergoing CPB with a pre-admission FXII concentration of <1% and aPTT >200 seconds. The child was transfused with fresh-frozen plasma to replenish FXII, allowing safe ACT monitoring of heparin anticoagulation throughout CPB.

Effects of Low Molecular Weight Heparin and Unfragmented Heparin on Induction of Osteoporosis in Rats

1990 ◽  
Vol 63 (03) ◽  
pp. 505-509 ◽  
Author(s):  
Thomas Mätzsch ◽  
David Bergqvist ◽  
Ulla Hedner ◽  
Bo Nilsson ◽  
Per Østergaar
Keyword(s):  
Molecular Weight ◽  
Bone Mineral ◽  
Low Molecular Weight Heparin ◽  
Zinc Content ◽  
Low Molecular Weight ◽  
Dependent Manner ◽  
Bone Mineral Mass ◽  
Bone Ash ◽  
Dose Dependent ◽  
Mineral Mass

SummaryA comparison between the effect of low molecular weight heparin (LMWH) and unfragmented heparin (UH) on induction of osteoporosis was made in 60 rats treated with either UH (2 IU/ g b w), LMWH in 2 doses (2 Xal U/g or 0.4 Xal U/g) or placebo (saline) for 34 days. Studied variables were: bone mineral mass in femora; fragility of humera; zinc and calcium levels in serum and bone ash and albumin in plasma. A significant reduction in bone mineral mass was found in all heparin-treated rats. There was no difference between UH and LMWH in this respect. The effect was dose-dependent in LMWH-treated animals. The zinc contents in bone ash were decreased in all heparin-treated rats as compared with controls. No recognizable pattern was seen in alterations of zinc or calcium in serum. The fragility of the humera, tested as breaking strength did not differ between treatment groups and controls. In conclusion, if dosed according to similar factor Xa inhibitory activities, LMWH induces osteoporosis to the same extent as UH and in a dose-dependent manner. The zinc content in bone ash was decreased after heparin treatment, irrespective of type of heparin given.

Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto
Keyword(s):  
Blood Flow ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Red Cell ◽  
Cell Velocity ◽  
Red Cell Velocity ◽  
The Mean ◽  
Wall Shear ◽  
Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

Sign in / Sign up

Export Citation Format

Share Document