Altered plasma fibrin clot properties in essential thrombocythemia

Abstract

Patients with increased thromboembolic risk tend to form denser fibrin clots which are relatively resistant to lysis. We sought to investigate whether essential thrombocythemia (ET) is associated with altered fibrin clot properties in plasma. Ex vivo plasma fibrin clot permeability coefficient (Ks), turbidimetry and clot lysis time (CLT) were measured in 43 consecutive patients with ET (platelet count from 245 to 991 × 10(3)/µL) and 50 control subjects matched for age, sex and comorbidities. Fibrinolysis proteins and inhibitors together with platelet activation markers were determined. Reduced Ks (-38%, p < 0.0001) and prolonged CLT (+34%, p < 0.0001) were observed in ET. The differences remained significant after adjustment for fibrinogen and platelet count. ET was associated with a slightly shorter lag phase (-5%, p = 0.01) and higher maximum absorbency of the turbidimetric curve (+6%, p < 0.001). The ET patients had higher plasma P-selectin by 193% (p < 0.00001) and platelet factor 4 (PF4) by 173% (p < 0.00001), with higher P-selectin observed in 19 (44%) patients with JAK-2 gene V617F mutation. Higher t-PA (+20%, p < 0.001), 23% higher plasminogen activator inhibitor-1, PAI-1 (+23%, p < 0.01) and unaltered thrombin-activatable fibrinolysis inhibitor, plasminogen and α2-antiplasmin activity were found in the ET group. Ks inversely correlated with fibrinogen, PF4 and C-reactive protein. CLT positively correlated only with PAI-1. Patients with ET display prothrombotic plasma fibrin clot phenotype including impaired fibrinolysis, which represents a new prothrombotic mechanism in this disease.

Prothrombotic fibrin clot properties associated with increased endogenous thrombin potential and soluble P‐selectin predict occult cancer after unprovoked venous thromboembolism

“…Soluble P‐selectin promotes NET formation . Moreover, the associations between sP‐selectin and both K s and CLT support growing evidence for the impact of platelet‐derived proteins on clot properties reported previously …”

“…40 Moreover, the associations between sP-selectin and both K s and CLT support growing evidence for the impact of platelet-derived proteins on clot properties reported previously. 41 We confirmed that older age 42 and higher platelet count 7 can predict cancer diagnosis following unprovoked VTE. We did not find male sex to be a risk factor, as opposed to the studies by Jara-Palomares et al 7 and Rieu et al, 43 although evidence for this issue is inconsistent.…”

How to Assess Fibrinogen Levels and Fibrin Clot Properties in Clinical Practice?

“…Several studies indicate that K s measurement might be a suitable tool for clinical use; however, differences in the results, given the use of various concentrations of reagents and techniques in laboratories, limit its current applicability and require further efforts to standardize this technique, which has huge potential clinical implications. Prospective studies are Atherosclerotic vascular diseases Stable coronary artery disease, 48 peripheral arterial disease 49 Thromboembolic arterial events Acute coronary syndromes, 28 no-reflow phenomenon after acute MI, 50 instent thrombosis, 51 previous ischemic stroke, 29 acute ischemic stroke 52 Other cardiovascular diseases Chronic heart failure with sinus rhythm, 53 atrial fibrillation (paroxysmal, persistent, and permanent), 37,54 arterial hypertension 55 Venous thrombosis Idiopathic venous thromboembolism, 56 cerebral venous sinus thrombosis 57 Chronic renal disease End-stage renal disease on peritoneal dialysis 58 and long-term hemodialysis 59 Malignancy Digestive tract cancer, 60 multiple myeloma, 61 essential thrombocythemia 62 Autoimmune or chronic inflammatory diseases Inflammatory bowel disease, 63 antiphospholipid syndrome, 64,65 rheumatoid arthritis 66 Other Factor XIII Val34Leu polymorphism, 67 elevated plasma lipoprotein(a), 68 familial history of premature coronary artery disease 27 or venous thromboembolism 69 Increased K s…”

Fibrin Formation, Structure and Properties

“…The structure of fibrin networks is often affected by physical factors, such as hydrodynamic flow or a strong magnetic field that result in formation of oriented anisotropic fibrin fibers (Gersh et al 2010; Campbell et al 2010). Fibrin structure and properties are greatly influenced by the presence of blood cells, namely activated platelets and erythrocytes (Aleman et al 2014; Malecki et al 2015) that form a natural and very active environment for clot formation. In addition to whole cells, the effects of circulating cell-derived microparticles on the fibrin clot structure and properties have been recently demonstrated (Zubairova et al 2015).…”