scholarly journals A Web of Coagulotoxicity: Failure of Antivenom to Neutralize the Destructive (Non-Clotting) Fibrinogenolytic Activity of Loxosceles and Sicarius Spider Venoms

Toxins ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 91 ◽  
Author(s):  
Dwin Grashof ◽  
Christina N. Zdenek ◽  
James S. Dobson ◽  
Nicholas J. Youngman ◽  
Francisco Coimbra ◽  
...  

Envenomations are complex medical emergencies that can have a range of symptoms and sequelae. The only specific, scientifically-validated treatment for envenomation is antivenom administration, which is designed to alleviate venom effects. A paucity of efficacy testing exists for numerous antivenoms worldwide, and understanding venom effects and venom potency can help identify antivenom improvement options. Some spider venoms can produce debilitating injuries or even death, yet have been largely neglected in venom and antivenom studies because of the low venom yields. Coagulation disturbances have been particularly under studied due to difficulties in working with blood and the coagulation cascade. These circumstances have resulted in suboptimal spider bite treatment for medically significant spider genera such as Loxosceles and Sicarius. This study identifies and quantifies the anticoagulant effects produced by venoms of three Loxoscles species (L. reclusa, L. boneti, and L. laeta) and that of Sicarius terrosus. We showed that the venoms of all studied species are able to cleave the fibrinogen Aα-chain with varying degrees of potency, with L. reclusa and S. terrosus venom cleaving the Aα-chain most rapidly. Thromboelastography analysis revealed that only L. reclusa venom is able to reduce clot strength, thereby presumably causing anticoagulant effects in the patient. Using the same thromboelastography assays, antivenom efficacy tests revealed that the commonly used Loxoscles-specific SMase D recombinant based antivenom failed to neutralize the anticoagulant effects produced by Loxosceles venom. This study demonstrates the fibrinogenolytic activity of Loxosceles and Sicarius venom and the neutralization failure of Loxosceles antivenom, thus providing impetus for antivenom improvement.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1225-1225
Author(s):  
Michael L Schmitz ◽  
Edgar D St. Amour ◽  
Kimo Stine ◽  
Mark A Austen ◽  
Chanhee Jo ◽  
...  

Abstract Introduction: Thromboelastography (TEG) is a point-of-care whole blood coagulation test used commonly with cardiac and liver operations, surgeries for which intraoperative and postoperative bleeding and coagulopathies occur and transfusion is likely. Angiotensinconverting enzyme inhibitors (ACEI) have been found to decrease plasminogen activator inhibitor I (PAI-1), increase tissue plasminogen activator (tPA), decrease tissue factor (TF) production by monocytes, and decrease platelet aggregation. Methods: With IRB approval, kaolin-activated heparinase TEG data were collected on 634 infants and children under 18 yr presenting for elective cardiac surgery between January 2004 and December 2007 for retrospective review utilizing the Haemoscope Thromboelastograph® Coagulation Analyzer (Haemoscope Corp., Niles, IL). Six TEG parameters are analyzed: R (reaction time to reach clot initiation), K (time to reach 20 mm amplitude after R), alpha (clot kinetics), MA (maximum amplitude), LY30 (amount of lysis 30 min after MA), and CI (coagulation index). Infants and children are analyzed based on preoperative therapy with an ACEI. Results: In those receiving ACEI, the time to initial fibrin formation is faster (R, p=0.0007), although subsequent clot formation is slower (K, p=0.0201; alpha, p=0.0092) than without ACEI drugs. Moreover, there is markedly less fibrinolysis (LY30, p=0.0019) in those receiving an ACEI. Clot strength and overall clot dynamics (MA and CI, p=NS) were similar in both groups (Table 1). Subjects with baseline oxygen saturation of 88% differ in that they do not have a significant change in K or alpha but do have a higher CI. Table 1. Ranges for Kaolin-activated Heparinase Thromboelastography Parameters Group R (min) K (min) alpha (degrees) MA LY30% CI Control 7.27±2.20 1.83±0.68 65.0±8.4 64.2±6.4 2.28±2.87 −0.68±2.81 ACEI 6.54±1.88 1.99±0.81 62.7±10.2 63.3±5.8 1.12±2.05 −0.39±2.87 p value 0.0007 0.0201 0.0092 NS 0.0019 NS Discussion: A number of investigators have found antithrombotic effects of ACEI drugs in adults but children have not been studied. The TEG provides an ex vivo means of assessing whole blood clotting dynamics. This preliminary analysis of infants and children reveals a delay in the time required to initiate clot via the intrinsic coagulation cascade as activated by kaolin (R) and slowed clot formation (K and alpha). Final clot strength shows no difference and LY30 shows less fibrinolysis. A shift in plasma hemostasis towards fibrinolysis would potentially delay R, prolong K, decrease alpha, and increase LY30. Paradoxically, we see a decrease in R and LY30. Reduced platelet aggregation is consistent with slowed kinetics of clot formation (K and alpha) but would be expected to cause a reduction in MA that is not seen. Further analysis of this data will separate the subjects into age groups as TEG parameters vary with age in infants and children. Also, since there is evidence that enalapril may not have the antiplatelet effects of captopril and may increase tPA in women but not men, further analysis of gender and type of ACEI given will be completed.


Author(s):  
F. Jacob Seagull ◽  
Danny Ho ◽  
James Radcliffe ◽  
Yan Xiao ◽  
Peter Hu ◽  
...  

2010 ◽  
Vol 30 (04) ◽  
pp. 212-216 ◽  
Author(s):  
R. Jovic ◽  
M. Hollenstein ◽  
P. Degiacomi ◽  
M. Gautschi ◽  
A. Ferrández ◽  
...  

SummaryThe activated partial thromboplastin time test (aPTT) represents one of the most commonly used diagnostic tools in order to monitor patients undergoing heparin therapy. Expression of aPTT coagulation time in seconds represents common practice in order to evaluate the integrity of the coagulation cascade. The prolongation of the aPTT thus can indicate whether or not the heparin level is likely to be within therapeutic range. Unfortunately aPTT results are highly variable depending on patient properties, manufacturer, different reagents and instruments among others but most importantly aPTT’s dose response curve to heparin often lacks linearity. Furthermore, aPTT assays are insensitive to drugs such as, for example, low molecular weight heparin (LMWH) and direct factor Xa (FXa) inhibitors among others. On the other hand, the protrombinase-induced clotting time assay (PiCT®) has been show to be a reliable functional assay sensitive to all heparinoids as well as direct thrombin inhibitors (DTIs). So far, the commercially available PiCT assay (Pefakit®-PiCT®, DSM Nutritional Products Ltd. Branch Pentapharm, Basel, Switzerland) is designed to express results in terms of units with the help of specific calibrators, while aPTT results are most commonly expressed as coagulation time in seconds. In this report, we describe the results of a pilot study indicating that the Pefakit PiCT UC assay is superior to the aPTT for the efficient monitoring of patients undergoing UFH therapy; it is also suitable to determine and quantitate the effect of LMWH therapy. This indicates a distinct benefit when using this new approach over the use of aPPT for heparin monitoring.


1968 ◽  
Vol 19 (03/04) ◽  
pp. 526-532 ◽  
Author(s):  
L. B Nanninga ◽  
M. M Guest

SummaryThe purified anticoagulant split product of fibrinogen has antifibrinolytic and anti-fibrinogenolytic activity. This was investigated by lysis times of fibrin and by the rate of disappearance of fibrinogen in plasma and in a purified system. A new method was used to measure fibrinogenolytic activity. In the experimental system which we have used no indication of additional breakdown of the anticoagulant split product in the presence of fibrinolysin was obtained.


Author(s):  
Krittika Singh

The Internet of things is the internetworking of physical devices, vehicles, buildings, and other items—embedded with electronics, software, sensors, actuators, and network connectivity that enable these objects to collect and exchange data. The IoT allows objects to be sensed and/or controlled remotely across existing network infrastructure, creating opportunities for more direct integration of the physical world into computer-based systems, and resulting in improved efficiency, accuracy and economic benefit in addition to reduced human intervention. In this research an expert system based upon the IOT is developed in which the next event in the flight schedules due to any kind of medical emergencies is to be predicted. For this the medical data of all the patients are to be collected through WBAN.


2020 ◽  
Vol 4 (1) ◽  
pp. 63
Author(s):  
Elfan Winoto

<p>Abortion is the fifth highest cause of maternal mortality. Legal abortions are called <em>abortus provocatus medicinalis</em> and those that are illegal are called <em>abortus provocatus criminalis</em>. Indonesian law prohibits abortion except indications of medical emergencies and the consequences of rape. This study aims to determine the legal consequences of someone who failed an abortion and the legal protection of the doctor who treated her.</p><p>This legal research uses a juridical normative with a conceptual and legislative approach.</p><p>The results of the perpetrators and those who helped the abortion that caused medical emergencies to be threatened with Criminal Code Article 53. They cannot be convicted if in accordance with professional standards and standard operating procedures.</p><p>The conclusion and suggestion are the doctor cannot be convicted as a criminal offender or as an assistant to an abortion crime if it can be proven that an abortion is carried out in emergency condition to save mother or fetus and prevent disability. The government needs to make laws that regulate who will carry out safe, qualitative and responsible abortions.</p><p> </p><p>Abortion is the fifth highest cause of maternal mortality. Legal abortions are called <em>abortus provocatus medicinalis</em> and those that are illegal are called <em>abortus provocatus criminalis</em>. Indonesian law prohibits abortion except indications of medical emergencies and the consequences of rape. This study aims to determine the legal consequences of someone who failed an abortion and the legal protection of the doctor who treated her.</p><p>This legal research uses a juridical normative with a conceptual and legislative approach.</p><p>The results of the perpetrators and those who helped the abortion that caused medical emergencies to be threatened with Criminal Code Article 53. They cannot be convicted if in accordance with professional standards and standard operating procedures.</p><p>The conclusion and suggestion are the doctor cannot be convicted as a criminal offender or as an assistant to an abortion crime if it can be proven that an abortion is carried out in emergency condition to save mother or fetus and prevent disability. The government needs to make laws that regulate who will carry out safe, qualitative and responsible abortions.</p>


Sign in / Sign up

Export Citation Format

Share Document