Haemostasis and Thrombosis
Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple in Basic Urological Sciences, 2021
AggregationThe activation of platelets causes GPIIbIIIa to change into an active configuration which binds fibrinogen.Fibrinogen binding to IIbIIIa results in platelet aggregation and signalling, which further reinforces activation.Other adhesion molecules — including VWF and fibronectin — also bind to IIbIIIa and contribute to aggregation.Platelets change configuration to mediate clot retraction which strengthens the clot.
Clinical Toxicology of Snakebite In Africa and The Middle East / Arabian Peninsula
Jürg Meier, Julian White in Handbook of: Clinical Toxicology of Animal Venoms and Poisons, 2017
Among 17 cases of proven bites in northern Nigeria, 14 occurred at night. Eleven patients were bitten inside their homes, 10 while they were asleep. All patients complained of feeling pain at the site of the bite immediately. Five began to vomit within six hours of the bite. Signs of local envenoming developed in all cases with swelling of the entire bitten limb or beyond in more than half, local blistering in 60% and local tissue necrosis in 70% (Figure 24). Tissue necrosis usually involves the skin and subcutaneous connective tissues only (Figure 25). The commonest signs of systemic envenoming were leucocytosis, fever and absence of clot retraction in vitro. Classical signs of elapid neurotoxicity were not seen. Evidence of complement activation, principally by the alternative pathway, was found in the majority of patients, and a minority showed biochemical abnormalities suggestive of a transient hepatocellular abnormality. Spontaneous bleeding and failure of clot retraction sugggested a haemostatic defect in some patients. Subspecies of N. nigricollis in other parts of Africa (for example, by the “zebra snake" (N. n. nigricincta) of northern Namibia and southwestern Angola) can cause just as severe local effects as N. nigricollis in West and East Africa. Chronic ulcers at the site of these injuries may eventually show malignant change (Figure 26).
Physiology and Basic Investigation of Blood Coagulation
Hau C. Kwaan, Meyer M. Samama in Clinical Thrombosis, 2019
Whole blood clot retraction is directly linked to a vital platelet function, but, in addition, is influenced by hematocrit and fibrinogen concentration. A significant anemia or fibrinogenopenia increases clot retraction. On the other hand, hyperfibrinogenemia and increased hematocrit over 50% reduces or impedes clot retraction.13 The role of clot retraction in hemostasis is still being debated. Decrease of the clot volume reduces the obstruction at the site of vascular injury and tends to restore the normal uninterrupted vascular lumen. Clot retraction is studied in the laboratory either on whole blood or on plasma and may also be evaluated with the thromboelastograph.
Mind the gap: connexins and pannexins in platelet function
Published in Platelets, 2021
Kirk a Taylor, Gemma Little, Jonathan M. Gibbins
Of the 16 connexins screened from blood cells and megakaryocytes, notable levels of Cx37, Cx40 and Cx62 mRNA were detected from cultured megakaryocytes [18]. Expression of Cx37 and Cx40 has been confirmed by Western blotting, immunocytochemistry and flow cytometry [5,6,18]. More recently, Cx62 was identified in human platelets, where it was shown to reside intracellularly before translocating to the plasma membrane upon stimulation by the thromboxane A2 mimetic U46619 [7]. People carrying a single nucleotide polymorphism P319S in the Cx37 gene display modestly enhanced platelet activation, suggesting a role for Cx37 in regulating platelet activation [5]. To date, platelet connexins have been shown to function both as hemichannels and gap junctions [5–7,18]. Of the platelet connexins, evidence suggests that whilst Cx37 and Cx40 cannot form heteromeric structures, they are able to assemble in a heterotypic manner between apposite cells [23]. Clot retraction is a coordinated process whereby microtubules contract to facilitate wound healing [24]. Interestingly, selective peptide inhibitors of either Cx37, Cx40 or Cx62 inhibit clot retraction, suggesting that there may be a role for gap junctions in the coordination of this process [6,7,18]. Connexin intermixing has not been studied in platelets but this could serve to regulate platelet interactions within a thrombus or with other cell types.
Marginal band microtubules are acetylated by αTAT1
Published in Platelets, 2021
Anne-Sophie Ribba, Morgane Batzenschlager, Clotilde Rabat, Thierry Buchou, Sylvie Moog, Saadi Khochbin, Ekaterina Bourova-Flin, Laurence Lafanechère, François Lanza, Karin Sadoul
We have previously reported that the higher acetylation level of HDAC6−/− platelets correlates with faster activation/spreading kinetics. Accordingly, we wondered whether αTAT1−/− platelets would show a retardation of their spreading capacity. We decided to use again a spreading assay to compare the speed of activation and spreading between the different genotypes. HDAC6 deficient platelets spread faster than WT platelets confirming our previously published observations, while αTAT1 deficient platelets behave similar to WT platelets under these conditions (Figure 1C). We also used a clot retraction assay to compare the functional efficiency of the three different platelet populations. Clot retraction reflects the capacity of platelets to activate and to perform a “three-dimensional spreading” within the fibrin network as well as their ability to subsequently reorganize their cytoskeleton to contract the fibrin network. While HDAC6 deficient platelets behave similar to WT platelets, we observe a slight retardation of clot retraction by αTAT1KO platelets (Figure 1D, see also supplementary Figure 1B for a typical example of clot retraction kinetics).
The platelets’ perspective to pathogen reduction technologies
Published in Platelets, 2018
Abdimajid Osman, Walter E. Hitzler, Patrick Provost
Having a circulation lifespan of 8–10 days [6, 7], blood platelets play a critical role in the maintenance of hemostasis and vascular integrity. Circulating platelets also stimulate the growth of endothelial cells, mediate vessel wall remodeling, support the endothelium ultrastructure, and release factors that enhance the barrier function of the endothelium [8]. Thus, patients with thrombocytopenia (i.e. with low platelet count) not only are at risk of reduced hemostatic efficacy but may also be afflicted by a compromised, more leaky and permeable, vasculature. Platelets are also increasingly recognized to play an active role in the immune system. They express Toll-like receptors (TLRs) that play a key role in the innate immune system, and interact with bacteria via surface receptors, and release factors that activate other cells of the immune system when they interact with bacteria [9]. In addition to these functions, platelets are acknowledged for their vital role in clot retraction and wound healing [10]. Thus, despite being tiny and anucleate, platelets play key roles in diverse and important physiological processes.
Related Knowledge Centers
- Thrombus
- Blood Vessel
- Coagulation
- Platelet
- Fibrin
- Thrombocytopenia
- Glanzmann'S Thrombasthenia
- Thrombosis Prevention