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Haemostasis and Thrombosis
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Platelet plug formation (primary haemostasis)Platelets:There are 150-400 billion platelets per litre of blood.Produced by megakaryocytes in the bone marrow.Life span of 8-12 days.Recognises the disruption of EC and the exposed underlying extracellular matrix (primarily collagen).
Fetal alloimmune thrombocytopenia
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
In typical cases of AIT, the mother is healthy (without thrombocytopenia) and her pregnancy, labor, and delivery are uncomplicated. The neonates who are otherwise normal present with symptomatic thrombocytopenia within several hours of birth. Affected infants often develop a generalized distribution of petechiae, as well as ecchymoses over the presenting fetal part. Visceral bleeding and bleeding during circumcision or venipuncture may be present. Of greatest consequence is the risk of ICH, occurring in up to 30% of cases (3) and responsible for the 6.5% mortality rate (12) and the significant long-term neurologic sequelae, including hydrocephaly and porencephaly. Laboratory data are remarkable for an isolated and often severe thrombocytopenia, with normal or increased numbers of megakaryocytes found on bone marrow aspirate. The hematocrit may be decreased if significant bleeding has occurred. A definitive diagnosis can be made by phenotyping parental platelets and demonstrating antiplatelet antibodies in the maternal serum, which are specific for the antigen incompatibility identified.
Congenital Amegakaryocytic Thrombocytopenia
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
During thrombopoiesis, a pluripotent hematopoietic stem cell divides and forms myeloid stem cell which makes early commitment to megakaryoblast. After undergoing further division, megakaryoblast becomes immature megakaryocyte which completes its terminal differentiation into mature megakaryocytes and finally platelet that possesses many polyploid nuclei, extensive intracellular organelles (for platelet function), and membrane structures (for platelet shedding) [2,3].
Pro106Leu MPL mutation is associated with thrombocytosis and a low risk of thrombosis, splenomegaly and marrow fibrosis
Published in Platelets, 2022
Musa Alzahrani, Saeed Al Turki, Waleed Al Rajban, Fatimah Alshalati, Fahad Almodaihsh, Khadega A. Abuelgasim, Bader Alahmari, Thamer Al Bogami, Osama Ali, Talal Al Harbi, Mohammed A. AlBalwi, Maram Alotaibi, Aamer Aleem, Ahmed Al Asker, Areej Al Mugairi
Out of the 115 patients, 33 (29%) had an evaluable BM. BM cellularity ranged from 20–100%, 12/33 (36%) were hypocellular, 17/33 (52%) normocellular, and 4/33 (12%) hypercellular. See Table I. Figure 1 shows examples of BM cellularity and megakaryocyte morphology. Megakaryocyte morphology revealed dysplastic changes in 20 (60%) (hypolobated or with separated lobes); only 7 (21%) of cases had cloud-like megakaryocytes, and none had staghorn or giant shape, as described in ET. BM megakaryocytes were increased in 29 (87%). Small size megakaryocytes were observed in 15/33 (45%). Some patients showed both loose and dense clusters, but overall clustering of megakaryocytes was seen in the majority of the cases 30/33 (90%), of which 29 (87%) had loose and 20 (60%) dense clusters.
Potential inflammatory biomarkers for tinnitus in platelets and leukocytes: a critical scoping review and meta-analysis
Published in International Journal of Audiology, 2022
Raheel Ahmed, Alice Shadis, Rumana Ahmed
Leukocytes include macrophages, neutrophils and lymphocytes which all play a role in the immune response and its associated cytokine interactions. Platelets are produced by megakaryocytes. Interleukin 6 (IL-6) activated megakaryocytes have greater ploidy and produce platelets with greater MPV, younger platelets also have a greater volume (Burstein et al. 1992). Platelets with a greater volume also activate faster to promote thrombosis or inflammation (Franco, Corken, and Ware 2015; Korniluk et al. 2019). Activated platelets can also promote IL-6 and TNFα release in macrophages (Scull, Hays, and Fischer 2010). Single nucleotide polymorphisms affecting IL-6 and tumour necrosis factor alpha TNFα are associated with tinnitus. TNFα − 308 G > A and IL6 − 174 G > C allele frequency are significantly associated with tinnitus in the elderly with a history of occupational noise exposure (Doi et al. 2015; Marchiori et al. 2018).
Mutated JAK2 signal transduction in human induced pluripotent stem cell (iPSC)-derived megakaryocytes
Published in Platelets, 2022
Jaturawat Pawinwongchai, Panchalee Jangprasert, Nungruthai Nilsri, Nipan Israsena, Ponlapat Rojnuckarin
The activating mutation of JAK2 gene (JAK2p.V617F) is critical for MPN pathogenesis as it is found in over 90% of PV and 60% of ET and MF patients [4–7]. Janus kinase 2 (JAK2) is a tyrosine kinase protein which plays roles in the signal transduction of both erythropoietin (EPO) and thrombopoietin (TPO) receptors [8]. The underlying reasons why the same JAK2 gene mutation can cause either erythrocytosis (PV) or thrombocytosis (ET) are unclear. Subsequently, JAK2 exon 12 mutations were described in patients with pure erythrocytosis and no thrombocytosis [9,10]. Identifying the signal differences between these two JAK2 mutants may give use deeper insights in the molecular mechanisms of pathological erythroid vs. megakaryocytic proliferation. Upon EPO or TPO engagement with their receptors, JAK2 can activate signal transducer and activator of transcription (STAT) proteins, especially STAT3 and STAT5 [11–14], the mitogen activated protein kinase (MAPK) [15,16] and phosphatidylinositol 3-kinase (PI3K) [17,18] signaling pathways. These molecules synergistically promote cellular proliferation, differentiation, and survival. We proposed that their aberrations should be found in MPN.