Platelets and platelet alloantigens: Lessons from human patients and animal models of fetal and neonatal alloimmune thrombocytopenia

Vadasz, Brian; Chen, Pingguo; Yougbaré, Issaka; Zdravic, Darko; Li, June; Li, Conglei; Carrim, Naadiya; Ni, Heyu

doi:10.1016/j.gendis.2015.02.003

Cited by 25 publications

(15 citation statements)

References 192 publications

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“…Platelets, via their contributions to the "protein wave" and to the classical first and second waves of hemostasis, play key roles in the arrest of bleeding [ 31 ] . Thrombocytopenias caused by either genetic deficiencies [ 86 ] or autoimmune [ 87 - 89 ] and alloimmune responses lead to bleeding disorders [ 21 , 32 , 33 , 90 - 96 ] . However, the same platelet accumulation and coagulation may lead to thrombosis.…”

Section: Discussionmentioning

confidence: 99%

Platelets in hemostasis and thrombosis: Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectinmediated protein wave of hemostasis

Hou¹,

Carrim²,

Wang³

et al. 2015

J Biomed Res

121

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Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet generation, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 decades. In blood circulation, platelets can quickly adhere and aggregate at sites of vascular injury, forming the platelet plug (i.e. the first wave of hemostasis). Activated platelets can also provide negatively charged phosphatidylserine-rich membrane surface that enhances cell-based thrombin generation, which facilitates blood coagulation (i.e. the second wave of hemostasis). Platelets therefore play central roles in hemostasis. However, the same process of hemostasis may also cause thrombosis and vessel occlusion, which are the most common mechanisms leading to heart attack and stroke following ruptured atherosclerotic lesions. In this review, we will introduce the classical mechanisms and newly discovered pathways of platelets in hemostasis and thrombosis, including fibrinogen-independent platelet aggregation and thrombosis, and the plasma fibronectin-mediated “protein wave” of hemostasis that precedes the classical first wave of hemostasis. Furthermore, we briefly discuss the roles of platelets in inflammation and atherosclerosis and the potential strategies to control atherothrombosis.

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Section: Discussionmentioning

confidence: 99%

Platelets in hemostasis and thrombosis: Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectinmediated protein wave of hemostasis

Hou¹,

Carrim²,

Wang³

et al. 2015

J Biomed Res

121

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“…The present study was performed in order to investigate the thrombosis of tumor-bearing mice using LDPI in combination with blood cell analysis. Platelets are essential mediators of the process of pathologic thrombosis (10). Previous experimental evidence has demonstrated that platelets support tumor metastasis (11).…”

Section: Introductionmentioning

confidence: 99%

Low local blood perfusion, high white blood cell and high platelet count are associated with primary tumor growth and lung metastasis in a 4T1 mouse breast cancer metastasis model

et al. 2015

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Abstract. It was originally thought that no single routine blood test result would be able to indicate whether or not a patient had cancer; however, several novel studies have indicated that the median survival and prognosis of cancer patients were markedly associated with the systemic circulation features of cancer patients. In addition, certain parameters, such as white blood cell (WBC) count, were largely altered in malignant tumors. In the present study, routine blood tests were performed in order to observe the change of blood cells in tumor-bearing mice following the implantation of 4T1 breast cancer cells into the mammary fat pad; in addition, blood flow in breast tumor sites was measured indirectly using laser Doppler perfusion imaging (LDPI), in an attempt to explain the relevance between the blood circulation features and the growth or metastasis of breast cancer in mice model. The LDPI and blood test results indicated that the implantation of 4T1 breast cancer cells into BALB/c mice led to thrombosis as well as high WBC count, high platelet count, high plateletcrit and low blood perfusion. Following implantation of the 4T1 cells for four weeks, the lung metastatic number was determined and the Pearson correlation coefficient revealed that the number of visceral lung metastatic sites had a marked negative association with the ratio of basophils (BASO%; r=-0.512; P<0.01) and the mean corpuscular hemoglobin was significantly correlated with primary tumor weight (r=0.425; P<0.05). In conclusion, the results of the present study demonstrated that tumor growth led to thrombosis and acute anemia in mice; in addition, when blood BASO% was low, an increased number of lung metastases were observed in tumor-bearing mice. IntroductionOver the past several decades, developments in clinical and surgical treatments for cancer patients has led to increased overall survival rates (1). However, the growth of primary tumors and subsequent cancer metastases continue to cause mortality and prevent effective treatment (2). Vascular dissemination is a major mechanism by which breast cancer cells migrate into the systemic circulation, leading to distant metastasis and mortality (3). Clinical observations have indicated a potential association between the bloodstream and cancer metastasis (4-5). However, few studies have investigated the systemic circulation characterization in mouse breast cancer metastasis models, which therefore limits the development of experimental oncology research.Cancer patients have frequently been reported to present with symptoms of thrombosis, which are more severe if the disease has progressed to a metastatic stage (6,7). In order for metastases to form, cancer cells must be able to survive in the harsh circulatory environment and extravasate into distant sites. Thrombosis may improve the anchoring of 'seed' (tumor cells that have escaped surgical removal or that may have already disseminated) to 'soil' (target organ) (8). Therefore,

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“…PLTs are the primary mediators of pathological thrombosis [23]. Previous empirical evidence has shown that PLTs support tumor malignancy [24].…”

Section: Discussionmentioning

confidence: 99%

The Beneficial Use of Melanin in Inhibiting and Treating HCC Through Preventing CBC, Liver Enzymes, Oxidative Stress, and Lipid Peroxidation Alterations

Abdelhalim

AL-Mohy

Al-Ayed

2020

Preprint

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Abstract Hepatocellular carcinoma (HCC) accounts for more than 90% of primary liver cancers and is a major global health problem. The present application relates to normalizing abnormal levels of hematological blood parameters, oxidative stress indicators, and liver enzyme levels in the rats using melanin, and particularly, to treating their abnormal levels, in addition to evaluate the role of melanin during and after the progression of HCC, which will be supplemented histologically. Hematological blood parameters such as white blood cells (WBCs), red blood cells (RBCs), hemoglobin (HGB), hematocrit (HCT), and platelets (PLTs); liver enzymes such as alanine transaminase (ALT) and aspartate transaminase (AST); oxidative stress such as glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD); LP malondialdehyde (MDA) were evaluated in all groups of rats. Injection of Diethylnitrosamine (DEN) and 2-Acetyaminofluorine (2-AFF) induced HCC in the rats accompanied with a significant reduction in WBCs, RBCs, HGB, HCT, and PLTs, GSH-PX, and SOD; while a significant elevation was observed in ALT and AST, and MDA compared to the control. Melanin normalized all the above mentioned parameters during and after the progression of cancer towards their control values. These results demonstrate the beneficial use of melanin as a powerful antioxidant tool in inhibiting and treating HCC in the rats.

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Platelets and platelet alloantigens: Lessons from human patients and animal models of fetal and neonatal alloimmune thrombocytopenia

Cited by 25 publications

References 192 publications

Platelets in hemostasis and thrombosis: Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectinmediated protein wave of hemostasis

Platelets in hemostasis and thrombosis: Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectinmediated protein wave of hemostasis

Low local blood perfusion, high white blood cell and high platelet count are associated with primary tumor growth and lung metastasis in a 4T1 mouse breast cancer metastasis model

The Beneficial Use of Melanin in Inhibiting and Treating HCC Through Preventing CBC, Liver Enzymes, Oxidative Stress, and Lipid Peroxidation Alterations

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