THE EFFECT OF EARLY BLOOD TRANSFUSION ON THE OUTCOME OF GASTROINTESTINAL HAEMORRHAGE

1987 ◽  
Author(s):  
S D Blair ◽  
S B Javanvrin ◽  
C N McCollum ◽  
R M Greenhalgh

It has been suggested that mortality due to upper gastrointestinal haemorrhage may be reduced by restricting blood transfusion [1], We have assessed whether this is due to an anticoagulant effect in a prospective randomised trial.One hundred patients with severe, acute gastrointestinal haemorrhage were randomised to receive either at least 2 units of blood during the first 24 hours of admission, or no blood unless their haemaglobin was lessthan 8g/dl or they were shocked. Minor bleeds and varices were excluded As hypercoagulation cannot be measured using conventional coagulation tests, fresh whole blood coagulation was measured by the Biobridge Impedance Clotting Time (ICT). Coagulation was assessed at 24 hour intervals and compared to age matched controls with the results expressed as mean ± sem.The ICT on admission for the transfusion group (n=50) was 3.2±0.2 mins compared to 10±0.2 mins in controls. This hyper-coagulable state was partially reversed to 6.4±0.3 mins at 24 hours (p<0.001). The 50 allocated to receive no blood had a similar ICT on admission of 4.4±0.4 mins but the hypercoagulable state was maintained with ICT at 24 hours of 4.320.4 mins. Only 2 patients not transfused rebled compared to 15 in the early transfusion group (p<0.001). Five patients died, and they were all in the early transfusion group.These findings show there is a hypercoagulable response to haemorrhage which is partially reversed by blood transfusion leading to rebleeding

Toxins ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 583 ◽  
Author(s):  
Supun Wedasingha ◽  
Geoffrey Isbister ◽  
Anjana Silva

Venom-induced consumption coagulopathy is the most important systemic effect of snake envenoming. Coagulation tests are helpful to accurately and promptly diagnose venom-induced consumption coagulopathy and administer antivenom, which is the only specific treatment available. However, bedside clotting tests play a major role in diagnosing coagulopathy in low-income settings, where the majority of snakebites occur. We conducted a literature search in MEDLINE® from 1946 to 30 November 2019, looking for research articles describing clinical studies on bedside coagulation tests in snakebite patients. Out of 442 articles identified, 147 articles describing bedside clotting assays were included in the review. Three main bedside clotting tests were identified, namely the Lee–White clotting test, 20-min whole blood clotting time and venous clotting time. Although the original Lee–White clotting test has never been validated for snake envenoming, a recently validated version has been used in some South American countries. The 20-min whole blood clotting time test is the most commonly used test in a wide range of settings and for taxonomically diverse snake species. Venous clotting time is almost exclusively used in Thailand. Many validation studies have methodological limitations, including small sample size, lack of case-authentication, the inclusion of a heterogeneous mix of snakebites and inappropriate uses of gold standard tests. The observation times for bedside clotting tests were arbitrary, without proper scientific justification. Future research needs to focus on improving the existing 20-min whole blood clotting test, and also on looking for alternative bedside coagulation tests which are cheap, reliable and quicker.


1987 ◽  
Author(s):  
S D Blair ◽  
K K Tan ◽  
C N McCollum ◽  
R M Greenhalgh

Blood is hypercoagulable following GI haemorrhage [1], and vascular thrombosis has been reported to be the main cause of death [2]. To study the relationship between coagulation and clinical outcome, Impedance Clotting Time (ICT) wac measured daily using the Biobridge [1] and clinical outcome prospectively recorded in 125 patients with acute severe GI haemorrhage.Mean (±se mean) ICT on admission was markedly shortened at 4.8±0.2 mins (normal range 8-12 mins) (p<0.001, t-Cest). Sixty patients received blood transfusion within 24 hours resulting in significantly prolonged ICT of 6.2±0.4 mins compared to 4.0±0.3 mins in the 56 not transfused (p<0.01). In 23 patients who rebled, the ICT at 24 hours of 6.7±0.4 mins demonstrated reduced hypercoagulability. Twenty of these 23 patients had bee:: transfused prior to rebleeding, a significantly greater proportion than in those who did not rebleed (p<0.00l). Six patients died, 3 of myocardial infarction, 1 of stroke, and 2 of continued haemorrhage. Mean ICT in the 4 patients dying from thrombotic vascular disease was 2.3±0.1 mins although 2 had also rebled.Clinical outcome in GI haemorrhage is strongly related to coagulation changes. The main cause of death was thrombotic vascular disease.1. Blair SD, Janvrin SB, McCollum CN, Greenhalgh RM. The effect of early blood transfusion on gastrointectinal haemorrhage. Br J Surg 1986; 73: 792-4.2. Allan R, Dykes P. A study of the factors influencing mortality rates fron gastrointestinal haenorrhage. Quart JMed 1976; 180: 533-50.


2017 ◽  
Vol 43 (07) ◽  
pp. 772-805 ◽  
Author(s):  
Julie Larsen ◽  
Anne-Mette Hvas

AbstractExcessive perioperative bleeding is associated with increased morbidity and mortality as well as increased economic costs. A range of whole blood laboratory tests for hemostatic monitoring has emerged, but their ability to predict perioperative bleeding is still debated. We conducted a systematic review of the existing literature assessing the ability of whole blood coagulation (thromboelastography [TEG]/thromboelastometry [ROTEM]/Sonoclot), platelet function tests, and standard plasma-based coagulation tests to predict bleeding in the perioperative setting. We searched PubMed and Embase, covering the period from 1966 to November 2016. In total, 99 original studies were included. The included studies assessed TEG/ROTEM/Sonoclot (n = 29), platelet function tests (n = 27), both test types (n = 8), and standard coagulation tests only (n = 18), and some (n = 17) investigated the predictive value of testing in patients receiving antithrombotic medication. In general, studies reported low positive predictive values for perioperative testing, whereas negative predictive values were high. The studies yielded moderate areas under receiver operator characteristics (ROC) curve (for the majority, 0.60–0.80). In conclusion, while useful in the diagnosis and management of patients with overt bleeding, whole blood coagulation and platelet function tests as well as standard coagulation tests demonstrated limited ability to predict perioperative bleeding in unselected patients. Therefore, we recommend that both whole blood and plasma-based coagulation tests are primarily used in case of bleeding and not for screening in unselected patients prior to surgery.


1977 ◽  
Author(s):  
R.D. Hamstra ◽  
G.E. Ens ◽  
S. Simons

A new coagulation instrument (Sonoclot) has been evaluated in the laboratory, at the bedside, and in surgery. It was compared to the prothrombin time, activated partial thromboplastin time, activated clotting time, Lee-White clotting time, fibrinogen and thrombelastograph. Most coagulation tests are reported as time to a clot end point while the Sonoclot records a continuous thrombokinetic pattern by measuring the energy required to maintain axial vibration of a hollow plastic probe in 0.4 ml of whole blood while it clots. Disposable plastic probes and non-siliconized glass cuvettes are rapidly changed after testing. Results are a line pattern which has been analysed for Clot Onset (C0) and Clot Formation Rate (CFR). Native whole blood from normal adults (54 studied) has a C0 of 2-4.5 minutes and CFR of 4-8 chart units/minute. The only similar clotting instrument is the thrombelastograph (TEG). Sonoclot and TEG patterns correlate, the Sonoclot sensing change before the TEG. Whole blood clotting measured with the Sonoclot is a new method which distinguishes hypercoagulation, various levels of heparin, and severe bleeding problems from normal. The device is durable, stable, easy to operate, and portable, providing a permanent record in a few minutes.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2256-2256
Author(s):  
Zhu Chen ◽  
Weizhen Wu ◽  
Yiming Xu ◽  
Martin L Ogletree ◽  
Andrew S Plump ◽  
...  

Abstract Abstract 2256 Blood coagulation is marked by sequential proteolytic activation of the coagulation factors and complex feedback modulation which is central to haemostasis. The fine balance between the coagulation cascade and the fibrinolytic system is also an integral component in haemostasis. Multiple coagulation factors, including FIIa (thrombin), FXa, FXIa, and FXIIa, are attractive targets for treating thrombosis, and novel inhibitors for several targets are already in late stage development or on the market. However, the responsiveness of these inhibitors to intrinsic vs. extrinsic cues warrants further study because in different disease settings the relative signaling intensities from the two pathways could be different in vivo. It is also poorly understood how these inhibitors might differentially modulate fibrinolytic activity, and a dysregulated fibrinolytic cascade is a potential contributing factor to both thrombosis and bleeding. We therefore sought to gain insight by comparing effects of four agents (dabigatran, apixaban, FXIa inhibitory antibody (FXIa Ab), and FXIIa inhibitory antibody (FXIIa Ab)) in whole blood coagulation and fibrinolysis in vitro using thromboelastography (TEG). We first established optimal clot-triggering conditions for TEG by using either a low concentration of kaolin (approximately 100-fold less kaolin than in standard aPTT assay), or a low concentration of tissue factor (TF) (1:8000 dilution of Recombiplastin in blood), along with recalcification. We then performed titration of tissue plasminogen-activator (tPA) with these clotting conditions and identified a tPA concentration of 125 ng/ml as optimal in inducing a fibrinolytic phase without significantly altering the clotting phase. Compound profiling was then pursued by dose titration with the individual agent in normal human donor's blood and tested TEG responses to kaolin+/− tPA and TF+/−tPA. Key TEG parameters that were assessed include R (clotting time), reflecting anticoagulant effect, MA (maximal amplitude), representing clot strength, and Ly30 (percent lysis at 30 minutes after MA), reflecting fibrinolytic activity. For clotting time, dabigatran and apixaban both delayed R in response to both kaolin and TF. FXIa Ab and FXIIa Ab delayed R only in response to kaolin and not to TF. This is consistent with the understanding that thrombin and FXa are in the common pathway, and FXIa and FXIIa are in the intrinsic pathway. For agents that affected the response to kaolin, stack-ranking of the magnitude of effect was FXIa Ab > dabigatran > apixaban > FXIIa Ab. For agents that affected the response to TF, dabigatran was slightly more effective than apixaban. Regarding clot strength, none of the agents appreciably altered MA in the absence of tPA; in the presence of tPA, dabigatran, apixaban, and FXIa Ab reduced MA to a greater extent than FXIIa Ab. Regarding fibrinolytic activity, none of the agents modulated Ly30 in the absence of tPA, consistent with the notion that these inhibitors alone are not fibrinolytic agents. However, in the presence of tPA, dabigatran, apixaban, FXIa Ab, but not FXIIa Ab, enhanced Ly30, suggesting that inhibition of thrombin, FXa, or FXIa may potentiate tPA-induced fibrinolysis. In summary, each inhibitory agent examined with this whole blood spike-in paradigm exhibited a distinct profile of effects on clotting time, clot strength and fibrinolysis with intrinsic and extrinsic cues in the presence and absence of tPA. Because the thrombotic cues in different patient segments are highly complex, and the endogenous fibrinolytic activities in different tissues may vary considerably, our results provide a benchmarking dataset for these inhibitory agents and their respective targets and represent a step forward in differentiating specific agents and targets in our effort to optimize safety and efficacy with novel anticoagulant therapies. Disclosures: Chen: Merck Research Laboratories: Employment. Wu:Merck Research Laboratories: Employment. Xu:Merck Research Laboratories: Employment. Ogletree:Merck Research Laboratories: Employment. Plump:Merck Research Laboratories: Employment. Graziano:Merck Research Laboratories: Employment. Wang:Merck Research Laboratories: Employment.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4770-4770
Author(s):  
Jawed Fareed ◽  
Debra Hoppensteadt ◽  
Omer Iqbal ◽  
Schuharazad Abro ◽  
Martin Emanuele

Background Poloxamer 188 (P188; Mast Therapeutics, Inc.) is a surface-active, non-ionic block copolymer which binds to hydrophobic surfaces on damaged cells improving membrane hydration and lowering adhesion and viscosity.  It is known to improve microvascular function in various pathologic states.  Currently, this agent is under investigation in a phase 3 clinical trial for treatment of sickle cell disease patients experiencing acute vaso-occlusive crisis.  The effect of P188 on blood coagulation and platelet function has been evaluated in several clinical trials where no clinically significant effect has been observed.   In these trials, coagulation studies were based on standard clot based methods (e.g., PT and aPTT) and did not include viscoelastic measurements such as thromboelastography (TEG).   Given P188 alters viscosity, we compared the effect of this agent using various clotbased, chromogenic and viscoelastic measurements of blood coagulation. Materials and Methods Whole blood activated clotting time studies were carried out in groups of healthy individuals (n=10) at a concentration range of 1.872-15.0mg/mL. TEG analysis on native and citratedwhole blood was carried out on TEG 5000 (Haemoscope Corp, Niles, IL) at concentrations of 0-0.45 mg/mL. The effect of P188 on normal plasma clotting parameters, such as PT and aPTT, was measured at a concentration range of 0-10 mg/mL. The effect of P188 on thrombin-induced clot formation was investigated using a fibrinokinetic method. The effect of P188 on thrombin generation was measured using the fluormetric method (Technoclone, Vienna, Austria). The anti-protease effects of P188 were studied using chromogenic substrate methods using isolated biochemical systems. Results At concentrations up to 10 mg/mL, P188 did not produce any modification of Celiteactivated clotting time (Celite-ACT).  At all concentrations the Celite-ACT values remained comparable to saline (138-140 sec for P188 vs. 140 sec for saline).  In the TEG analysis, P188 produced a concentrationdependent hypocoagulant effect in both native and citratedblood as evidenced by increased angle and shortening of maximum amplitude (MA).   In standard PT and aPTT tests, P188 did not produce any effect on the clotting profile at concentrations up to 20 mg/mL.  In fibrinokinetic studies, P188 produced an increase in the fibrin clot density and rate of fibrin polymerization. Discussion These studies demonstrate that even at very high concentrations, P188 does not produce an effect on whole blood clotting as measured by the Celite-ACT assay;   this result was confirmed in other standard assays.  Fibrinokinetic studies revealed an increase in the rate of fibrin formation and clot density.   However, at relatively low concentrations, P188 exhibited a hypocoagulant profile in TEG analysis.  The marked discordance between TEG and other coagulation tests suggest that P188’s effect on viscosity and adhesive interactions result in an artifact in TEG analysis and an incorrect indication of a hypocoagulant effect.  This effect may be due to the viscoelastic endpoint in the TEG assay. Further studies are needed to confirm this hypothesis. Disclosures: Fareed: Mast Therapeutics: Research Funding. Emanuele:Mast Therapeutics: Employment.


1957 ◽  
Vol 189 (3) ◽  
pp. 470-474 ◽  
Author(s):  
W. L. Milne ◽  
S. H. Cohn

Effects of serotonin (5HTA) were studied a) in whole blood ( in vitro) from both normal and x-irradiated animal, and b) in isolated clotting systems of plasma and purified fibrinogen. 5HTA was found to play an active role in blood coagulation in addition to its previously demonstrated role as a vasoconstrictor. In whole blood from normal and irradiated animals, and in platelet-deficient plasma, 5HTA acts in a manner similar to platelet factor 2 in accelerating the conversion of fibrinogen to fibrin. In a purified fibrinogen solution, 5HTA inhibits the fibrinogen-fibrin reaction, and thus differs from platelet factor 2. This may be due to the absence of an antithrombin in the purified fibrinogen solution. Serotonin appears to have a therapeutic effect on the postirradiation coagulation defect in that it decreases the prolonged heparin clotting time. This increased sensitivity to heparin during the postirradiation thrombocytopenia may be due to a deficiency of serotonin, which acts as an antagonist to heparin (an antithrombin). The action of 5HTA is postulated as an antagonist of an antithrombin which blocks the fibrinogen to fibrin reaction.


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