The Role of Copper Ions in Blood Coagulation: A Hematology Report

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This hematology report explores the significance of copper ions in the blood clotting process. The research investigates the role of copper ions in hemostasis, the biological process of blood coagulation, and its relation to various blood components. The report details the separation of blood components, quantification of copper ions, and the use of radioactive isotopes to trace their metabolic pathways. It discusses the role of ceruloplasmin and other copper-binding molecules in blood, along with the effects of copper ions on prothrombotic coagulation and platelet activation. The report also examines the use of prothrombin time and partial thromboplastic time to measure the impact of copper ions on blood clotting. The findings highlight the potential therapeutic applications of controlling copper ion levels in managing blood clotting disorders and diseases such as hemophilia and Von Willbrand’s disease. The report also compares the copper ion levels in diseased and normal patients to understand their effects on the clotting mechanism. The study emphasizes the importance of understanding the role of copper ions for various diseases linked to hemostasis and the process of blood clotting. The report concludes with the impact and outcomes of the experiment, emphasizing the role of copper ions in chelation and its importance in various biological processes like blood clotting, which can help in treatment of diseases where the blood clotting system is affected.
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Running head: HEMATOLOGY
Topic: HEMATOLOGY
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Abstract:
Blood coagulation is the biological process of transformation of blood from the liquid to gel
state which is usually followed by hemostasis involved by cessation of blood loss from
damaged vessels. Biological mechanism of coagulation involves the stepwise process of
adhesion, aggregation and activation which involves platelets alongside the maturation and
deposition of fibrin. One of the most important ion which facilitates the process of blood
clotting is calcium ion which acts as a chelating agent which often help in binding to the
calcium in the blood donated. Copper is an important component of blood plasma which
helps and plays an important role in various chronic liver diseases. Ceruloplasmin is the
largest contributor to the copper ions in the plasma and plays an important role in iron
metabolism. Blood contains copper containing molecules mainly proteins which contribute
to the process of copper homeostasis and potential significance regarding health and disease.
This report would revolve around the use of copper ions and their significance in blood
clotting mechanism. Moreover, the various physiological effects of the copper ions on the
process of blood coagulation has been determined. The aims of the research area has been
directed at the pharmacodynamics of the ions in blood and their metabolic pathway tracking
through use of radioactive substances.
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2HEMATOLOGY
Introduction:
The main aims of the research proposal outline here are
1. Separation of the components of blood through ultracentrifugation followed by
quantification of the copper ions through ultrafiltration. This is ultimately followed by
mass spectrometry for finding the molecular mass related details of copper in blood
components.
2. Using radiology to use Cu65 isotopes for understanding their role in copper transport and
their relation to blood binding components through RIA (Radio Immunosolvent Assay) and
ELISA (Enzyme linked Immuno Sorbent Assay) for pharmacodynamics and exploration of
cytoplasm, tissue as well as plasma copper analysis through quantification of Cu ions for
exploration of their metabolic pathway
Copper ions play an important role in essential metabolic functions through its
effective incorporation into various metalloenzymes and proteins. Copper ions have been
found to be linked to high levels of cholesterol as well as high levels of blood pressure. It has
an important role in neuron signaling and its role in neutropenia due to low levels of copper.
Copper deficiency is associated with various low mineral density which ultimately leads to a
high risk of osteoporosis (Sierpinska et al. 2014). According to the findings of Lindin (2016),
copper is an important component for binding with many components of blood.
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Fig 1: The role of copper ions in blood coagulation and its effect through graphical
representation
Cerruplasmin is considered as the largest contributor of copper in the plasma, constituting
40-70 % of the plasma. Thus, cerruplasmin and various copper containing molecules have
been studied extensively and found to be useful in homeostasis. Remainder of copper ions
have been found to be associated with various proteins for comprising the exchangeable
copper pool in the body fluids. For an instance albumin in many mammals have been found
to have a high affinity copper binding site which would be at the N terminus involving a
molecule of histamine.
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Fig 2: The various detailed steps involved in the blood clotting process
Macroglobulin in blood has been found to have a higher affinity for copper than
albumin thus contributing to the process of blood clotting. Macroglobulin acts as inhibitors
for fibrinolysis through inhibition of plasmin as well as kallikrein. Thus it is an inhibitor of
thrombin and there is an indirect role of copper ions in the process of blood clotting through
thrombin. Moreover, these research findings have been supported by the studies of Klinkajon
and Supaphol (2014) which shows that copper (II) ions have caused cross linking in alginate
hydrogels which plays an important role in the coagulation of fibrin. Furthermore, presence
of copper ions has a positive effect on prothrombiotic coagulation as well as platelet
activation. Thus copper ions if incorporated in alginate dressings along with antimicrobial
activity would be effective in minimization of infections in wounds.
Fig 2: The role of copper ions in healing of wounds and the various factors simultaneously
released
Partial thromboplastic time and activated atrial thromboplastic time has been effective
processes in in evaluating the anticoagulant activity of various extracts along with their
therapeutic systems (Felix Silva et al. 2014). Kornblatt, Nicorletti, and Travaglia (2016)
through their research has found affectivity of copper ions in modulating activity of various
proteins which ultimately in healing of wounds. Moreover it has been found that control of
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the process of hemostasis can be used as a potential target for various therapeutic
interventions. Moreover these tests have been used in monitoring therapy along with
anticoagulants as well as screening of deficiencies in extrinsic coagulation systems. Thus
multifactorial assays like PT could be useful in measuring sensitivity of clotting factors in the
coagulation assay. Effect of the copper ions on blood clotting can be measured with the help
of prothrombin time and the partial thromboplastic time (PTT). These tests help in
assessment of the function as well as the amount of the proteins known as coagulation factors
contributing to proper blood clot formation. Thus the PT values can be reflected in healthy
patients in this way (Babilonia and Trulijo et al. 2015).
Fig 4: Stepwise explanation for the process of partial thromboplastic time
This experiment is important for the exploration of copper ions and their roles in the
processes of blood coagulation which if controlled can be a kind of therapeutic treatment for
(Roumenina et al. 2014). Management of various disorders can be done through the proper
utilization of copper ions in the blood clotting mechanism. Moreover a comparison of the
number of copper ions in blood of diseased patients than normal patients would give an
insight into the effects of copper ion in the clotting mechanism. Copper ions are the most
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important ions for hemostasis which if disturbed lead to diseases like platelet disorders,
deficiency of platelets along with vascular hemorrhagic diathesis and thrombotic micro-
angioplasty like hemolytic uremic syndrome (HUS). Copper ions have been simultaneously
found to possess antioxidant as well as pro-oxidant abilities. Thus, the exploration of copper
ions in the blood clotting system would be required for its role in various diseases directly
linked to the hemostasis and the process of blood clotting (Mroczek et al. 2014).
This project will help in finding the relation between chelation and ion binding of the
copper ions in hemostasis and blood clotting and explore the effectiveness of copper ions in
blood clotting mechanisms. In this proposal the separation of various components of blood
would be done through processes like ultracentrifugation. Then the examination of molecular
mass of the ions would be done for quantification through spectrophotometric studies. Thus
the pharmacodynamics of the copper ions would be understood through assays involving
enzyme linked immunosorbent assay and radio immunosorbent assay. The use of radioactive
copper ions is useful for tracing the metabolic pathways of the ions in the blood and its
subsequent role in the clotting process (Duan et al. 2014).
Impact/ Outcomes of the experiment:
Role of various ions in chelation is important for various biological processes like
blood clotting. Exploration of the role of copper ions in the blood components would give an
insight into the process of blood clotting and help in the treatment of diseases where the
blood clotting system is affected like hemophilia and Von Willbrand’s disease (Battle et al.
2016). Moreover it has always been known that calcium ions have an important role to play
in the blood clotting process. Thus this lack in the evidence of the role of copper ions in
clotting or hemostasis have been a major reason for research gap particularly in this research
area. Moreover the role of copper ions and its effect in the human system as well as mice will
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7HEMATOLOGY
give an insight in the difference between the clotting mechanisms and the simultaneous role
of copper in different mammalian systems (Cotruvo et al. 2015).
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8HEMATOLOGY
References
Babilonia, K. and Trujillo, T., 2014. The role of prothrombin complex concentrates in
reversal of target specific anticoagulants. Thrombosis Journal, 12(1), p.8.
Batlle, J., Pérez-Rodríguez, A., Corrales, I., López-Fernández, M.F., Rodriguez-Trillo, A.,
Lourés, E., Cid, A.R., Bonanad, S., Cabrera, N., Moret, A. and Parra, R., 2016. Molecular
and clinical profile of von Willebrand disease in Spain (PCM–EVW–ES): Proposal for a new
diagnostic paradigm. Thrombosis and haemostasis, 115(01), pp.40-50.
Cotruvo Jr, J.A., Aron, A.T., Ramos-Torres, K.M. and Chang, C.J., 2015. Synthetic
fluorescent probes for studying copper in biological systems. Chemical Society
Reviews, 44(13), pp.4400-4414.
Duan, L., Shen, H., Zhao, G., Yang, R., Cai, X., Zhang, L., Jin, C. and Huang, Y., 2014.
Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer
cells. Biochemical and biophysical research communications, 446(4), pp.1010-1016.
Félix-Silva, J., Souza, T., Camara, R.B.B.G., Cabral, B., Silva-Júnior, A.A., Rebecchi,
I.M.M., Zucolotto, S.M., Rocha, H.A.O. and de Freitas Fernandes-Pedrosa, M., 2014. In vitro
anticoagulant and antioxidant activities of Jatropha gossypiifolia L.(Euphorbiaceae) leaves
aiming therapeutical applications. BMC complementary and alternative medicine, 14(1),
p.405.
Klinkajon, W. and Supaphol, P., 2014. Novel copper (II) alginate hydrogels and their
potential for use as anti-bacterial wound dressings. Biomedical Materials, 9(4), p.045008.
Linder, M.C., 2016. Ceruloplasmin and other copper binding components of blood plasma
and their functions: an update. Metallomics, 8(9), pp.887-905.
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Mroczek-Sosnowska, N., Sawosz, E., Vadalasetty, K., Łukasiewicz, M., Niemiec, J.,
Wierzbicki, M., Kutwin, M., Jaworski, S. and Chwalibog, A., 2015. Nanoparticles of copper
stimulate angiogenesis at systemic and molecular level. International journal of molecular
sciences, 16(3), pp.4838-4849.
Roumenina, L.T., Rayes, J., Lacroix-Desmazes, S. and Dimitrov, J.D., 2016. Heme:
modulator of plasma systems in hemolytic diseases. Trends in Molecular Medicine, 22(3),
pp.200-213.
Sierpinska, T., Konstantynowicz, J., Orywal, K., Golebiewska, M. and Szmitkowski, M.,
2014. Copper deficit as a potential pathogenic factor of reduced bone mineral density and
severe tooth wear. Osteoporosis International, 25(2), pp.447-454.
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