scholarly journals Toward understanding thrombus fracture: Dissipative phenomena of whole blood clots

2020 ◽  
Author(s):  
Gabriella P. Sugerman ◽  
Sapun H. Parekh ◽  
Manuel K. Rausch

When thrombus fractures and breaks off it can occlude vital vessels such as those of the heart, lung, or brain. These thromboembolic conditions are responsible for 1 in 4 deaths world-wide. This problem is also of significant current interest as 1 in 3 COVID-19 intensive care patients exhibit thromboembolic complications. Thrombus resistance to fracture is driven by its intrinsic fracture toughness as well as other, non-surface-creating dissipative mechanisms. In our current work, we identify and quantify these latter mechanisms toward future studies that aim to delineate fracture from other forms of dissipation. To this end, we use an in vitro thrombus mimic system to produce whole blood clots and explore their dissipative mechanics under simple uniaxial extension, cyclic loading, and stress-relaxation. We found that whole blood clots exhibit Mullins effect, hysteresis, permanent set, strain-rate dependence, and nonlinear stress-relaxation. Interestingly, we found that performing these tests under dry or submerged conditions did not change our results. However, performing these tests under room temperature or body temperature conditions yielded differences. Overall, we have demonstrated that whole blood clots show several dissipative phenomena - similarly to hydrogels - that will be critical to our understanding of thrombus fracture.

1971 ◽  
Vol 25 (02) ◽  
pp. 354-378 ◽  
Author(s):  
R Gottlob ◽  
L Stockinger ◽  
U Pötting ◽  
G Schattenmann

SummaryIn vitro whole blood clots of various ages, experimental thrombi produced in the jugular vein of rabbits and human thrombi from arteries and veins were examined in semi-thin sections and by means of electron microscopy.In all types of clots examined a typical course of retraction was found. Retraction starts with a dense excentrical focus which grows into a densification ring. After 24 hours the entire clot becomes almost homogeneously dense; later a secondary swelling sets in.Shortly after coagulation the erythrocytes on the rim of the clot are bi-concave discs. They then assume the shape of crenate spheres, turn into smooth spheres and finally become indented ghosts which have lost the largest part of their contents. In the inner zone, which makes up the bulk of the clot, we observed bi-concave discs prior to retraction. After retraction we see no crenations but irregularly shaped erythrocytes. Once the secondary swelling sets in, the cross-section becomes polygonal and later spherical. After extensive hemolysis we observe the “retiform thrombus” made up of ghosts.Experimental and clinical thrombi present the same morphology but are differentiated from in vitro clots by: earlier hemolysis, immigration of leukocytes, formation of a rim layer consisting of fibrin and thrombocytes, and the symptoms of organization. Such symptoms of organization which definitely will prevent lysis with streptokinase were found relatively late in experimental and clinical thrombi. Capillary buds and capillary loops were never found in clinical thrombi prior to the third month.The morphological findings agree with earlier physical and enzymatic investigations. The observation that phenomena of reorganization occur relatively late and frequently only in the rim areas of large thrombi explains why lytic therapy is possible in some of the chronic obliterations.


Transfusion ◽  
2021 ◽  
Vol 61 (S1) ◽  
Author(s):  
Turid Helen Felli Lunde ◽  
Lindsay Hartson ◽  
Shawn Lawrence Bailey ◽  
Tor Audun Hervig
Keyword(s):  

2017 ◽  
Vol 23 (3) ◽  
pp. 607-617 ◽  
Author(s):  
Albe C. Swanepoel ◽  
Odette Emmerson ◽  
Etheresia Pretorius

AbstractCombined oral contraceptive (COC) use is a risk factor for venous thrombosis (VT) and related to the specific type of progestin used. VT is accompanied by inflammation and pathophysiological clot formation, that includes aberrant erythrocytes and fibrin(ogen) interactions. In this paper, we aim to determine the influence of progesterone and different synthetic progestins found in COCs on the viscoelasticity of whole blood clots, as well as erythrocyte morphology and membrane ultrastructure, in an in vitro laboratory study. Thromboelastography (TEG), light microscopy, and scanning electron microscopy were our chosen methods. Our results point out that progestins influence the rate of whole blood clot formation. Alterations to erythrocyte morphology and membrane ultrastructure suggest the presence of eryptosis. We also note increased rouleaux formation, erythrocyte aggregation, and spontaneous fibrin formation in whole blood which may explain the increased risk of VT associated with COC use. Although not all COC users will experience a thrombotic event, individuals with a thrombotic predisposition, due to inflammatory or hematological illness, should be closely monitored to prevent pathological thrombosis.


2004 ◽  
Vol 92 (11) ◽  
pp. 980-985 ◽  
Author(s):  
Lisa Gherardini ◽  
Christoph Mayer ◽  
Martin Gröschl ◽  
Christoph Kaun ◽  
Ewald Benes ◽  
...  

SummaryUltrasound of 2 MHz frequency and 1.2 W/cm2 acoustic intensity was applied to examine the effect of sonication on recombinant tissue-type plasminogen activator (rt-PA)-induced thrombolysis as well as on the distribution of plasminogen and t-PA within whole blood clots in vitro. Thrombolysis was evaluated quantitatively by measuring clot weight reduction and the level of fibrin degradation product D-dimer (FDP-DD) in the supernatant. Weight reduction in the group of clots treated both with ultrasound and rt-PA was 35.2% ± 6.9% which is significantly higher (p<0.0001) than in the group of clots treated with rt-PA only (19.9% ± 4.3%). FDP-DD level in the supernatants of the group treated with ultrasound and rt-PA increased sevenfold compared to the group treated with rt-PA alone, (14895 ± 2513 ng/ml vs. 2364 ± 725 ng/ml). Localization of fibrinolytic components within the clots was accomplished by using gel-entrapping technique and immunohistochemistry. Spatial distributions of t-PA and plasminogen showed clearly that ultrasound promoted the penetration of rt-PA into thrombi significantly (p<0.0001), and broadened the zone of lysis from 8.9 ± 2.6 µm to 21.2 ± 7.2 µm. We speculate that ultrasound enhances thrombolysis by affecting the distribution of rt-PA within the clot.


2019 ◽  
Vol 57 (4) ◽  
pp. 521-531 ◽  
Author(s):  
Ruggero Dittadi ◽  
Aline S.C. Fabricio ◽  
Giulia Rainato ◽  
Edoardo Peroni ◽  
Fulvio Di Tonno ◽  
...  

Abstract Background [-2]proPSA seems to outperform free/total prostate-specific antigen (PSA) ratio in prostate cancer diagnosis. However, [-2]proPSA stability remains an underestimated issue. We examined [-2]proPSA stability over time in whole blood before separation of serum and plasma and its implications for prostate health index (Phi) determination. Total PSA (tPSA) and free PSA (fPSA) stabilities were also assessed. Methods Blood was drawn from 26 patients and separated in two tubes for plasma (K2EDTA and K2EDTA plus protease inhibitors – P100) and one for serum (clot activator plus gel separator). Tubes were stored at room temperature before centrifugation 1, 3 and 5 h for serum and EDTA plasma or 1 and 5 h for P100 plasma. To investigate the influence of gel separator on markers’ stability, blood was collected from 10 patients in three types of tubes to obtain serum: tubes with clot activator plus gel separator, with silica particles or glass tubes. Biomarkers were assayed with chemiluminescent immunoassays. Results [-2]proPSA and Phi levels significantly and progressively increased over time in serum (+4.81% and +8.2% at 3 h; +12.03% and +14.91% at 5 h, respectively, vs. 1 h; p<0.001). Conversely, [-2]proPSA levels did not change in plasma (EDTA or P100). tPSA levels did not change over time in serum or plasma, whereas fPSA decreased in serum. All markers were higher in plasma than in serum at any time point. This difference did not seem to be attributable to the use of gel for serum preparation. Conclusions EDTA prevented spurious in vitro modifications in PSA-related isoforms, confirming that a stabilized blood sample is a prerequisite for [-2]proPSA measurement and Phi determination.


Transfusion ◽  
2011 ◽  
Vol 51 ◽  
pp. 15S-24S ◽  
Author(s):  
Pieter F. van der Meer ◽  
Jose A. Cancelas ◽  
Rebecca Cardigan ◽  
Dana V. Devine ◽  
Hans Gulliksson ◽  
...  

1985 ◽  
Vol 24 (04) ◽  
pp. 173-179 ◽  
Author(s):  
B. R. R. Persson ◽  
V. Kempi

SummaryClots of 1 ml venous blood formed in glass tubes after 10 min at room temperature were incubated at 37° C with the radiopharmaceutical to be studied. Methods for quality control of the radiopharmaceuticals were compared. Gel chromatography scanning was found to give reliable information. The incorporation into the clot was studie’d at different pH values and after various time intervals. The highest incorporation was found for 125I-fibrinogen and for 99mTc-mac-roaggregates of albumin, followed by 99mTc-sulphur colloid and 99mTc-strep-tokinase at pH less than 2. The titrated initial dose of 99mTc-streptoki-nase was studied at various pH levels. The lysing effect was less in the pH range 1-2.5, where the best labeling yield was obtained. The inactivation of streptokinase by the labeling procedure was also studied with im-munoelectrophoresis and decomposition of casein. In vitro studies of the interaction of radiopharmaceuticals with clots add information for the clinical use of radiopharmaceuticals for thrombus localization.


1966 ◽  
Vol 15 (03/04) ◽  
pp. 570-590 ◽  
Author(s):  
R Gottlob ◽  
G Blümel

Summary1. Blood clots are lysed by SK before the beginning of retraction. Retracted clots are only very little lysed.2. Recalcified citrated blood is easily lysed since the excess of added calcium ions inhibits the retraction.3. The determination of the water content of the clots gives information on their retraction state.4. The determination of water content made it possible to prove that thrombus retraction takes place in vivo. Already one day after thrombosis the water content is clearly lower than in fresh clots. Later the water content increases again slightly.5. Clots formed in vitro and in vivo are lysed by SK after retraction if they come into contact with fibrin or fibrinogen containing plasminogen.6. Heated fibrin plates or heated fibrin tubes both with SK, casein degradation and an immunological method allowed to prove that whole blood clots loose their activable plasminogen during retraction. One assumes that plasminogen is expressed during retraction.7. The possibility of a therapeutical fibrinolysis with SK is due to the fact that SK can penetrate into the clot and the SK containing thrombus continuously comes in contact with circulating blood rich in plasminogen. The importance of these results for thrombolysis with SK is discussed.


1968 ◽  
Vol 19 (01/02) ◽  
pp. 094-098 ◽  
Author(s):  
R Gottlob ◽  
G Blümel

SummaryIn vitro whole blood clots were incubated in SK, washed several times in Ringer-solution and then introduced into plasminogen solution. These clots showed marked signs of lysis surpassing those observed in clots that had only been incubated in SK. There was a correlation between the duration of the SK incubation and the clot lysis in the plasminogen solution. We deduce from these findings that SK enters the clots by diffusion and that this process lasts several hours.If SK-incubated clots are placed into an SK-free environment, the SK slowly diffuses out of the thrombi.Even in contact with very slight plasminogen concentrations, SK-incubated clots undergo distinct degrees of lysis.


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