Scanning electron microscopy of fibrin networks in rheumatoid arthritis: a qualitative analysis

Abstract

Rheumatoid arthritis is a chronic inflammatory condition that affects mainly synovial joints and has an impact on approximately 1% of the Western population. The coagulation process is altered in this condition, and this is frequently complicated by thrombocytosis. Changes in fibrin morphology have been linked with inflammation, and this, in turn, plays an important role in thrombosis. Changes in the fibrin fiber formation cause the alterations observed in thrombus morphology. In the current study, the ultrastructure of platelets and fibrin networks was investigated to determine whether any morphological changes are present in these structures in patients suffering from rheumatoid arthritis. Six patients diagnosed with rheumatoid arthritis took part in this study, and their clot morphology was compared to that of control subjects. Citrated blood with and without the addition of thrombin was used. Results indicated that the fibrin networks in the arthritis patients formed thick, matted layers. This matted appearance is due to a changed ultrastructure of the minor, thin fibers. Also, in these patients, spontaneous networks were created without the addition of thrombin, which indicates an abnormal hemostatic protein functioning, and the latter is expressed as visible changes in ultrastructure.

Carbon monoxide: Anticoagulant or procoagulant?

“…A similar increase in clot matrix density and fine fiber formation was observed in PPP obtained from smokers as determined by scanning electron microscopy (SEM) [83]. Using PRP, Pretorius and colleagues demonstrated by SEM the formation of not just finer fibers, but also sheet-like matting of thrombus ultrastructure in the settings of smoking [84], type II diabetes mellitus [85] and rheumatoid arthritis [86]. Representative SEM figures of normal PRP and the preceding three conditions are represented (Fig.…”

“…Investigations of platelet poor plasma (PPP) or platelet rich plasma (PRP) obtained from samples exposed to CORM-2 [50], obtained from smokers [83,84], obtained from patients with type II diabetes mellitus [85], and rheumatoid arthritis [86] all display similar Nielsen et al 16 16 features that may be secondary to CO exposure compared to normal subject plasma.…”

“…Representative SEM figures of normal PRP and the preceding three conditions are represented (Fig. 4), with methods used to generate these images as previously cited [84][85][86]. Considered together, these investigations involved conditions or disease states wherein increased CO would be expected to be present, resulting in thrombus ultrastructure (e.g., finer or matted fibers) consistent with enhanced clot strength demonstrated in vitro [48,[51][52][53][54][55][56][57]67,68,[70][71][72][73][74][75][76] or in vivo [68,69] following CO exposure.…”

Iron and carbon monoxide enhance coagulation and attenuate fibrinolysis by different mechanisms

“…HO-1 activity is also increased systemically in inflammatory disorders associated with thrombophilia, such as diabetes mellitus [21] and rheumatoid arthritis [22]. Critically, SEM-based investigations demonstrated that the fibrin matrix formed from blood obtained from individuals with diabetes mellitus [23] or rheumatoid arthritis [24] was very similar to that observed when normal blood was exposed to ferric chloride [2][3][4][5][6][7]. In a complementary fashion, using a viscoelastic methodology validated to detect carbon monoxide-mediated hypercoagulability in the setting of tobacco smoking [25], it was determined that a patient with a clotted ventricular assist device and hemolysis had carbon monoxide-mediated hypercoagulability, and upregulation of HO-1 was documented by increased carboxyhemoglobin concentrations [26].…”

An ultrastructural analysis of platelets, erythrocytes, white blood cells, and fibrin network in systemic lupus erythematosus

“…As was shown in our previous study on rheumatoid arthritis, the same microenvironment is responsible for the transformation of the fibrin network from a regular net of fibrils in healthy subjects to an amorphous fibrin deposit [17]. It is possible that inflammatory cellular elements, caught by the transformed network of fibrin fibres, trigger the firm clot formation resistant to anti-thrombotic agents.…”