Platelet-related fibrinolysis resistance in patients suffering from PV. Impact of clot retraction and isovolemic erythrocytapheresis

Rusak, Tomasz; Piszcz, Jarosław; Misztal, Tomasz; Brańska-Januszewska, Justyna; Tomasiak, Marian

doi:10.1016/j.thromres.2014.04.025

Cited by 21 publications

(17 citation statements)

References 33 publications

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“…Tutwiler et al [ 4 ] presented similar effects of different platelet counts and fibrinogen levels on clot contraction. Increased platelet count results in faster clot retraction depending on contractile forces generated by the platelet cytoskeleton [ 22 ], while fibrin is essential for transmitting those forces between platelets [ 3 ]. Our data suggest that the contraction of the whole blood clot depends also on the size of RBCs trapped within the fibrin network.…”

Section: Discussionmentioning

confidence: 99%

Erythrocyte compression index is impaired in patients with residual vein obstruction

Ząbczyk

Natorska

Undas

2018

J Thromb Thrombolysis

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Defective clot contraction has been postulated to contribute to thrombosis. We aimed to evaluate the association of residual vein obstruction (RVO) with erythrocyte compression within the whole-blood clot. We studied 32 patients with venous thromboembolism (VTE) taking vitamin K antagonists (VKAs) for at least 3 months (median time in therapeutic range 60%), including 12 (37.5%) with RVO, and 32 age- and sex-matched controls. In all study participants we evaluated whole blood clot retraction, expressed as the erythrocyte compression index (ECI), defined as a ratio of mean polyhedrocyte area to mean native erythrocyte area, along with clot area covered by polyhedrocytes, plasma clot permeability (Ks), clot lysis time (CLT), and thrombin generation. In both groups higher ECI, indicating impaired clot contraction, increased with older age, higher body mass index, red blood cell distribution width, and lower platelet count (all p < 0.05), but not with red blood cell count. In VTE patients ECI was 15.8% higher than in controls (median 63.6 vs. 54.9%, p = 0.021). Subjects with RVO had 20% higher ECI and 155% lower clot area covered by polyhedrocytes. RVO patients had also prolonged CLT by 41%, but not Ks, and elevated peak thrombin generation by 33%, as compared to those without RVO (all p < 0.05). This study is the first to show impaired compression of erythrocytes in RVO patients despite VKA anticoagulation. Altered ECI coexisted with hypolysability and increased thrombin generation. ECI might be useful in the diagnostic process of RVO or post-thrombotic syndrome and can help optimize the anticoagulant therapy.Electronic supplementary materialThe online version of this article (10.1007/s11239-018-1650-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Erythrocyte compression index is impaired in patients with residual vein obstruction

Ząbczyk

Natorska

Undas

2018

J Thromb Thrombolysis

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“…78 Similar trends might be expected in polycythemia vera, which is associated with thrombosis, increased hematocrit, and activated platelets. Here, studies on bulk clot contraction have shown increased contractility, 79,80 although more research is needed to elucidate the exact mechanisms. As such, this work suggests that platelet contractile forces may play an important role in the pathophysiology of diseases, but should be studied in the context of the composition and structure of fibrin, and other entrapped cells.…”

Section: Clot Contractile Force Implicated In Diseasementioning

confidence: 99%

Feeling the Force: Measurements of Platelet Contraction and Their Diagnostic Implications

Williams

Oshinowo

Ravindran

et al. 2018

Semin Thromb Hemost

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In addition to the classical biological and biochemical framework, blood clots can also be considered as active biomaterials composed of dynamically contracting platelets, nascent polymeric fibrin that functions as a matrix scaffold, and entrapped blood cells. As platelets sense, rearrange, and apply forces to the surrounding microenvironment, they dramatically change the material properties of the nascent clot, increasing its stiffness by an order of magnitude. Hence, the mechanical properties of blood clots are intricately tied to the forces applied by individual platelets. Research has also shown that the pathophysiological changes in clot mechanical properties are associated with bleeding and clotting disorders, cancer, stroke, ischemic heart disease, and more. By approaching the study of hemostasis and thrombosis from a biophysical and mechanical perspective, important insights have been made into how the mechanics of clotting and the forces applied by platelets are linked to various diseases. This review will familiarize the reader with a mechanics framework that is contextualized with relevant biology. The review also includes a discussion of relevant tools used to study platelet forces either directly or indirectly, and finally, concludes with a summary of potential links between clotting forces and disease.

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“…1 The exact nature of this so-called t-PA resistance is not yet fully understood, but location, size, and composition of the occluding thrombus have been reported to be important factors influencing t-PA outcome. [4][5][6][7][8] Interestingly, various studies have shown that in particular arterial platelet-rich clots are more resistant to thrombolysis with t-PA. 7,[9][10][11] Surprisingly little is known about the precise composition of human stroke clots. Nevertheless, such information is crucial for the design of novel thrombolytic strategies.…”

Section: Introductionmentioning

confidence: 99%

ADAMTS13-mediated thrombolysis of t-PA–resistant occlusions in ischemic stroke in mice

Denorme

Langhauser²,

Desender

et al. 2016

Blood

147

172

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Key Points• ADAMTS13 dissolves t-PAresistant cerebral occlusions in a mouse model of stroke.• The thrombolytic activity of ADAMTS13 could become useful for more efficient and safer thrombolytic treatment of acute ischemic stroke.Rapid vascular recanalization forms the basis for successful treatment of cerebral ischemia. Currently, tissue plasminogen activator (t-PA) is the only approved thrombolytic drug for ischemic stroke. However, t-PA does not always result in efficient thrombus dissolution and subsequent blood vessel recanalization. To better understand thrombus composition, we analyzed thrombi retrieved from ischemic stroke patients and found a distinct presence of von Willebrand factor (VWF) in various samples. Thrombi contained on average 20.3% 6 10.1% VWF, and this was inversely correlated with thrombus red blood cell content. We hypothesized that ADAMTS13 can exert a thrombolytic effect in VWF-containing thrombi in the setting of stroke. To test this, we generated occlusive VWF-rich thrombi in the middle cerebral artery (MCA) of mice. Infusion of t-PA did not dissolve these MCA occlusions. Interestingly, administration of ADAMTS13 5 minutes after occlusion dose-dependently dissolved these t-PA-resistant thrombi resulting in fast restoration of MCA patency and consequently reduced cerebral infarct sizes (P < .005). Delayed ADAMTS13 administration 60 minutes after occlusion was still effective but to a lesser extent (P < .05). These data show for the first time a potent thrombolytic activity of ADAMTS13 in the setting of stroke, which might become useful in treatment of acute ischemic stroke.

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Platelet-related fibrinolysis resistance in patients suffering from PV. Impact of clot retraction and isovolemic erythrocytapheresis

Cited by 21 publications

References 33 publications

Erythrocyte compression index is impaired in patients with residual vein obstruction

Erythrocyte compression index is impaired in patients with residual vein obstruction

Feeling the Force: Measurements of Platelet Contraction and Their Diagnostic Implications

ADAMTS13-mediated thrombolysis of t-PA–resistant occlusions in ischemic stroke in mice

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