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Imperial Journal of Interdisciplinary Research (IJIR) Vol-2, Issue-6, 2016 ISSN: 2454-1362, http://www.onlinejournal.in

Blood Coagulation Parameters and Platelet Count in Pregnant Women Treated With Lactoferrin

Salwa Samir Anter, MD. Obstetric Gynecology Cairo University.

Abstract : Bovine lactoferrin has important role in oxidation ,treatment of preeclampsia in regulating homeostasis,anti-inflammatory combination with antihypertensive drug effect as well as therapeutic treatment of preterm labor as regarded its coagulation effect it acts as Keyword: Lactoferrin, blood coagulation, two faces as prothrombotic and antithrombotic in pregnancy different circumstances and no study w as done on the effect of lactoferrin on 1. Introduction coagulationduringpregnancy. in this study we compared between coagulation profile and platelet Bovine lactoferrin has important role in regulator count in pregnant women in the last trimester of iron and inflammatory homeostasis and in treated with lactoferrin with non lactoferrin therapeutic preterm labor treatmentas. and either treated pregnant women and also compared with thrombosis or hemorrhage during pregnancy is the normal reference of pregnancy in the third major maternal and fetal complication there is no trimester and whatever the results either study on coagulation action of lactoferrin during prothrombotic or antithrombotic or no effect on pregnancy to grade against its coagulation coagulation profile aiming of this study to grade complication if found and be useful of its against coagulation complication of lactoferrin and coagulation benefit. Lacroferrin (LF), a natural to be useful of its coagulation benefit .90 pregnant iron-binding in , LF is a single-chain women in the last trimester divided into group (A) with a molecular mass of ∼80 kea that 45 cases treated with lactoferrin, group (B) 45 belongs to the family of transferrin1, is widely cases without lactoferrin treated . Blood samples distributed in several secretion especially milk and were taken and the level of coagulative parameters also, in neutrophilic granules 2. lactoferrin has been as bleeding time, clotting time, prothrombin assigned with multiple biological function time,active thromboplastin time, and platelet count including considering the first-line defense protein were measured and compared between the two involved in protection against a multitude of groups and between the normal reference of microbial infections3,anti-viral4,anti- pregnancy in the third trimester also, evaluated parasitic5,6,anti- maternal and fetal complication as regarded fungal7,immunomodulationactivity, cell grow coagulation complication as bleeding or regulation function anti- and thromboembolism or the coagulation benefit . the antinociception,8.9. LF and anticancer resulted in lactoferrin treated group Prothrombin activities.Lactoferrin to the time 12.5 ± 0.96 seconds and APTT 31.16 ± 2.83 potential Use of lactoferrin in cancer therapy. second ,bleeding time 3.09 +0.87,clotting Lactoferrin cytotoxicity Against several cancers is time6.08 ±0.47,Platelet 221.57 ± 62.64 × 109 is reported to occur in distinct ways Under different prolonged than non lactoferrin groups conditions, namely by disruption, ,Prothrombin time 12.4 ± 0.86seconds and APTT Apoptosis induction, cell cycle arrest, and cell ,29.2±2.35.second , bleeding time 2.94 ±0.36, immunoreactions10. LF receptors are found in clotting time ,6.08 ±0.47 , Platelet220.00±30.35 lymphocytes, platelets, , dopaminergic with . also compared the results with normal neurons, megakaryocytic, and endothelial cells. reference of pregnancy in last trimester are within Some of these receptors are involved in LF uptake. upper normal range, with no coagulation In the cerebral endothelial cells, LF is transported complication as thrombosis or bleeding . This through -mediated processes without any research paper concludes that in lactoferrin intra endothelial degradation11 ant oxidative treated pregnant in third trimester coagulation mechanisms 12,Sequestration of iron by lactoferrin parameters and platelet count were within upper reduces insult-induced oxidative normal range of pregnancy in the third trimester stress13Lactoferrin is exerting changes on without coagulation complication as bleeding or leukocytes of the innate , through thromboembolismin ,but other benefit obtained increasing natural killer (NK) cell activity,14 during treatment as correction of anemia and treated of preterm labor,immunodulation ,ant

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Imperial Journal of Interdisciplinary Research (IJIR) Vol-2, Issue-6, 2016 ISSN: 2454-1362, http://www.onlinejournal.in

In pregnancy there is activation of blood 1- Lactoferrin and platelet function.The possibility coagulation as increase in the majority of clotting that lactoferrin may influence platelet function is factors, and decrease in the quantity of natural supported by observation such as. (a) The presence anticoagulant , and a reduction in fibrinolytic of lactoferrin receptors on platelet membranes,22 activity,15.The platelet count decreases in normal (b)the inhibition of ADP-treated lactoferrin pregnancy possibly due to increased destruction platelet aggregation,23and (C) inhibition of and hemodilution,with a maximal decrease in the fibrinogen binding to ADP-treated platelets, and ( third trimester16,17 .As most coagulation factors d) the inhibits thrombin inhibition of platelets increase in normal pregnancy, the prothrombin aggregation , thromboxane generation, serotonin time(PT) and the activated partial thromboplastin release and a membrane expression,24. time (APTT) may be shortened ,The PT and its derived measure the international normalized ratio .2- Lactoferrin and (INR) test for factors such as coagulation factors Thrombomodullin.Thrombomodullin is an anionic 11, V, V11, X,and fibrinogen. The APTT is anticoagulant proleoglycan which binds thrombin considered a good screening test for deficiencies of and then activates the anticoagulant protease, active coagulation factor V111, IX, X1 and .in.in study of Wu H.F thrombomodullin X11.Laboratory-based screening is used routinely cofactor activity is enhanced byLactoferrin H- to assess coagulation status in obstetric patient. The terminal .Lactoferrin and the specific test consists of platelet count, PT,APTT, D- binding to moiety of Dimer.and plasma fibrinogen level, 18.Platelet thrombomodullin. 25. count provides a measure of platelet concentration, but not function PT measures the extrinsic and 3- Lactoferrin and Thrombophilia .Paeson R in his common coagulation factor II, V, VII, and study in used bovina lactoferrin in treated anemia X,whereasAPTTassessescoagulation via the in hereditary thrombophilia conclusion that bovina intrinsic and common pathways and its sensitive to lactoferrin safe and effective in curing anemia all coagulation factors except FVII and FXIII. 19 associated with a consistent decrease of interleukin-6.the absence of miscarriage in bovina Reference intervals of routine coagulation assays lactoferrin treated women provided an unexpected during the pregnancy benefit. 26

Study of Jiao-Meigon et al to reference intervals of 4 -Immunity and thrombosis. a-Lactoferrin, routine coagulation assays during the pregnancy interleukin 6, interleukin 8 and and puerperium period in late –pregnancy period thrombosis.Interleukin-6, can produced a were the reference ranges for PT, 9.48-12.58, prothrombotic state by increasing expression of APTT, 20 fibrinogen, tissue factor VIII,factor and von willebrand factor and increasing platelet Referance table for clinicians ObstetricGynecology production. In study of Elena Y et al ,Interleukin by Abbassi-Ghanavatietal.Normal value of 6 potent thrombotic mediates the platelet prothrombin time during pregnancy prothrombin abnormalities and thromobogenesis associated with time, 21 No pregnant adult 12.7-15.4 second experimental colitis.27 as regarded lactoferrin and First Trimester 9.5-12.9second.Second Trimester interleukin 6 lactoferrin decrease interleukin 6 as 9.5-13.4second.Third Trimester 9.6- in study of VesceFet al, resulated that vaginal 12.9second.Normal value Active thromboplastin lactoferrin administration before genetic time during pregnancy.21No pregnant adult 26.3- amniocentesis decrease amniotic interleukin -6 39.4 second.First Trimester 24.3- level.28.other study of Masttsby-Baltzer A, 38.9second.Second Trimester 24.2- resulated that lactoferrin or fragment there of 38.1second.Third Trimester 24 .7- inhibits the end toxin-induced interleukin-6 35.0second.Normal value of platelet count during response in monocytic cells,29 Interleukin8 pregnancy.21No pregnant adult 165- 415 X and thrombosis in study of Franz-Josef ,by study of 103/mm3.First Trimester 165- 415 X 103/mm3 flow cytometry demonstrated that interleukin-6 and Second Trimester 155- 409 X 103/mm3. Third interleukin-8 induced an increase in tissues factor Trimester146- 429 X 103/mm3 expression on monocytes, 30 and also, study of Van Aken BE ,elevated plasma levels of Lactoferrin and coagulation Lactoferrin act as two Interleukin8 associated with recurrent thrombosis faces in regulation of coagulation as prothrombotic 31 opposite to study of Peter K .H , interleukin 8 and antithrombotic in different administration administration enhances venous thrombosis resolution in a rat model 32 . the .Evidence of antithrombotic action of lactoferrin Study of Elisabeth E; lactoferrin inhabits the lipopolysaccharide-induced expression and

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Imperial Journal of Interdisciplinary Research (IJIR) Vol-2, Issue-6, 2016 ISSN: 2454-1362, http://www.onlinejournal.in -binding ability of interleukin-8 in In a patient with lactoferrin deficiency and bleeding human endothelial cells, 33 tendency. Parker RIet al study young male with lactoferrin deficiency and bleeding tendency b- Lactoferrin, complement and thrombosis study absence of the largest platelet- by Umea a et al of molecular intercommunication vonwillebrandmultimers 43 between complement and coagulation, 34 and study of Samulsen O ant complement effect of Aim of this study lactoferrin-derived peptides, 35 compared the coagulation profile and platelet count c- Mast cells bleeding or thrombosis and lactoferrin in lactoferrin treated pregnant women with non Valent P, study the role of mast cells in preventing lactoferrin treated pregnant women in third thrombosis it act as profibrinolytic and trimester and compared result with normal antithrombotic cell36 lactoferrin inhabited mast reference of pregnancy in third trimester as to cell activation lactoferrin uptake by mast cell and grade against coagulation complication if found interaction tryptasecathepsin G chymas 37 and be useful of its coagulation benefit play role in thrombosis and tryptase potent 2. Methods

5-Lactoferrin and oxidative stress and thrombosis This study conducted in department of Obstetrics Daniela S suggests that oxidant stress play a major and Gynecology at Damietta hospital (outpatient). role in sever aspects of septic shock and After taking Written informed consent from disseminated intravascular coagulation 38 pregnant women prior commencing .A total of 90 lactoferrin act as ant oxidation Sequestration of pregnant women in the last trimester were enrolled iron by lactoferrin reduces insult-induced oxidative and randomly assigned into two study groups. stress.13 Group A cases group (lactoferrin treated group) Included 45 pregnant received lactoferrin 100mg 3 B)-Evidences of prothrombotic action of lactoferrin times daily. Group B control group (non lactoferrin treated group) Included 45pregnant. All case I) Lactoferrin and inflammation .Lactoferrin histories were taken included personal obstetric and derived from is an important family history. Examination were done: general physiological mediator in the down-regulation of and obstetric examination were taken, fetal blood anticoagulation, as in study of Adeyemi EO wellbeing by ultrasound and Doppler after two et al, found that augmented release of human month of treatment investigate the effect of leukocyte lactoferrin (and elastase) during treatment coagulation profile on bleeding time coagulation. 39 (BT), clotting time, (CT) the prothrombin time (PT) activated partial thromboplastin time (APTT) 2 -Lactoferrin and disseminated intravascular and platelet (PLC) compared the results between coagulation .The significant elevation of lactoferrin two groups and between normal reference of in blood, or at site of inflammation can contribute pregnancy in third trimester also, reported any significantly to the development of prothrombotic homeostasis complication as bleeding or sequelae, as seen in the disseminated intravascular thromboemolism and benefit of treatment as coagulation (DIC) associated with Bacterial correction of anemia preterm labor, hypertensive infection. 40 with pregnancy

3- Lactoferrin and in study of Wu HF et al 3. Statistical Analysis suggest that prothrombotic squeal of some inflammatory processes may be partly due to Statistical analysis were performed by using various agonists that release lactoferrin, statistical software SPSS version "17" categorical which can neutralize glycosaminoglycan-dependent variations were compared using Mean standard -thrombin inhibition Reactions 41 other study deviation (SD), student t-test. Statistical of Haifeng Wu that arginine 25 and arginine 28 is Significance was defined as P value < 0.05. Critical for effective heparin neutralization in blood

4-the structural determinate(s) of lactoferrin involved in heparin binding is located within a specific sequence (residues 25-31) of terminus. 42

5 _Lactoferrin and von will brand multimers

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Imperial Journal of Interdisciplinary Research (IJIR) Vol-2, Issue-6, 2016 ISSN: 2454-1362, http://www.onlinejournal.in

4. Results

Mean bleeding time, standard deviation value of control and cases

N Mean S.D p-value case 45 3.96 0.87 < 0.05. control 45 2.94 0.36 Table 2 Mean platelet count, standard deviationvalue of control and case group

N Mean S.D p-value case 45 2 21.57 62.64 < 0.05. control 45 2.20 .00 30.35 Table 3 Mean clotting time , standard deviation value of control and cases groups

N Mean S.D p-value case 45 7.31 1.42 < 0.05. control 45 6.08 0.47 Table 4 Mean prothrombin time,standard deviation value of control and case groups

N Mean S.D p-value case 45 12.5 0.96 < 0.05. control 45 12.4 0.86 Table 5 MeanActive partial thromboplastintime,standarddeviationof value of control and cases groups

N Mean S.D p-value case 45 31.16 2.83 < 0.05. control 45 29.2 2.35 Table 6 Coagulation complications of lactoferrin to pregnant women of control and cases group

N Thrombosis hemorrhage case 45 0 4 control 45 2 3 Table 7 show advantages of lactoferrign

number hemoglobin hypertensiont Preterm labor cases 45 10. 4±. 0 9 3 2 contro 45 10± 0.2 5 7

Out of 90 patients, 45 patients were taken as Table 2 Mean platelet count, standard deviation control not treated with lactoferrin during value of control and cases pregnancy and another 45 were included in Study group treated with lactoferrin during pregnancy in Mean platelet count, in our study in lactoferrin last trimester the determined of haemostatic group 2 21.57±62.64 within normal range of parameters in both Abbassi-Ghanavati et al reference in Third Trimester146- 429 103/mm3more than non Table 1 Mean bleeding time, standard deviation lactoferrin group mean 220.00±30.35 with no value of control and cases group Meanbleeding significant difference Thrombocytopenia was time, in our study in lactoferrin group 3.96 ±0.87 defined as platelet count less than 150,000/ mm within upper limited of normal range of reference 1-4 minutes more than non lactoferrin group mean Table 3 Mean clotting time,standard deviation 2.94 ±0.36 no significant difference bleeding time value of control and cases Mean clotting time, in was considered abnormal if it was more than 7.1 our study in lactoferrin group 7.31±1.42 within minutes (430 seconds) normal range of reference 4-11 minutes more than non lactoferrin group mean 6.08 ±0.47 no significant difference

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Imperial Journal of Interdisciplinary Research (IJIR) Vol-2, Issue-6, 2016 ISSN: 2454-1362, http://www.onlinejournal.in

Table 4.Mean prothrombintime standard deviation thromboplastin time (APTT)assesses coagulation value of control and cases via the intrinsic and common pathways and its sensitive to all coagulation factors except FVII and in our study in lactoferrin group PT 12.5 ±0.96 FXIII., 19 upper limited of normal range in comparison to normal reference in third trimester of Jiao-Meigon Reference intervals of routine coagulation assays et al reference according to PT, 9.48-12.58 and during the pregnancy,study of Jiao-Meigon et al to Abbassi-Ghanavati et al reference in Third reference intervals of routine coagulation assays Trimester 9.6- 12.9second more than non during the pregnancy and puerperium period in late lactofehrrin group12.4 ± 0.86 non significant –pregnancy period were the reference ranges for differencedifferenceprothrombin time was PT, 9.48-12.58 , APTT,28,61-40.80,20.Referance considered abnormal if it was more than 13minutes table for clinicians ObstetGynecol By Abbassi- Ghanavati et al.Normal value of prothrombin time Table 5 MeanActive partial during pregnancy prothrombin time21. thromboplastintime,standard deviationof value of Nonpregnantadult 12.7-15.4 second.First control and cases Trimester 9.5-12.9second. Second Trimester 9.5- 13.4second. Third Trimester 9.6- APTT,in our study in lactoferrin group 31.16±2.83 12.9second.Normal value of Active thromboplastin upper normal range in comparison to normal time during pregnancy prothrombin reference in third trimester of Jiao-Meigon et al time21.Nonpregnant adult 26.3-39.4 second . First reference according to , APTT,28,61-40.80 and Trimester 24.3-38.9second.Second Trimester 24.2- upper limited of normal range of Abbassi- 38.1second. Third Trimester 24 .7- Ghanavati et al reference in third trimester 24 .7- 35.0second.Normal value of platelet count during 35.0second more than non lactoferrin group pregnancy20Nonpregnant adult 165- 415 X 29.2±2.35. No significant difference Active partial 103/mm3. First Trimester 165- 415 X 103/mm3 thromboplastin time was considered abnormal if it Second Trimester 155- 409 X 103/mm3. Third was more than 35 minutes Trimester146- 429 X 103/mm3 .platelet count provides a measure of platelet concentration, but Table 6 show complications of lactoferrin to not function Mean platelet count in our study in pregnant women of control and cases group as lactoferrin group 221.57± within normal range of regarded thrombosis no case reported as thrombotic Abbassi-Ghanavati et al reference in Third complication of lactoferrin only 2 cases of deep trimester146- 429 X 103/mm3more than non venous thrombosis in control group cases as lactoferrin group mean 220.00±30.3 with no regraded bleeding 4 case of intrapartum significant difference betweenbothgroupsand the hemorrhage with lactoferrin group but in control value within normal range in contrast to study 3 caes 1 antepartum and 2 postpartum hemorrhage reported by Boehlen F et al platelet count decrease in normal pregnancy possibly due to increase Table 7 show advantage of lactoferrin correction destruction and haemodilution with maximal in of anemia haemoglobin in cases group 10.4±0.09 third trimester,44and not agree with Margareta more than control group 10±0.02.Number of Hellgrenthat in normal pregnancy,the platelet count cases of preterm labour in case group 2 cases less within normal range except during the third than in 7 casea in control group.Number of cases of trimester when benign gestational hypertension with pregnancy in case group 3 cases thrombocytopenia,80 to 150× 109/L,can observed. less than in 5 case a in control lactoferrin platelet turnover is usually normal,Activation 5. Discussion ofplatelet and release of beta-thromboglobullin and were reported,45. Bovine lactoferrin has important role in regulator The possibility that lactoferrin may influence of iron and inflammatory homeostasis and in platelet function is supported by observation such therapeutic ptretem labor treatment .no study was as .(a) The presence of lactoferrin receptors on done on its coagulation action during pregnancy to platelet membranes,22(b)the inhibition of ADP- gurade against its complicationt if found and be treated lactoferrin platelet aggregation,23 and (C) useful of its benefit .Either thrombosis or inhibition of fibrinogen binding to ADP-treated hemorrhage during pregnancy both is major platelets,and ( d) the inhibition of platelets maternal and fatal complication.platelet count aggregation,thromboxanegeneration,serotonin provides a measure of platelet concentration, but release and a granule membrane expression 24. No not function . Prothrombin time (PT ) measures thrombocytopenia was recoded in any case of the extrinsic and common coagulation factor II, V, lactoferrin groups VII, and X,wherease active partial

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Imperial Journal of Interdisciplinary Research (IJIR) Vol-2, Issue-6, 2016 ISSN: 2454-1362, http://www.onlinejournal.in

Bleeding time increase in lactoferrin treated group other 2 case need bilateral uterine ligation and B compared to non lactoferrin treated group and lyunch technique after that in next cases we within upper normal rangeof reference( 1-4 decrease dose in last week before delivery my minutes ) agree with Margareta Hellgren study that recommendation is decrees dose in last week of bleeding time is unchanged during normal pregnany of deliver in control group 1cases with pregnancy 45 abruptio placenta 2 cases postpartum with no case with intrapartum hemorrhage . the benefits of Bleeding time was considered abnormal if it was antithrombtic must taken in consideration as in more than 7.1 minutes (430 seconds) study of .Paeson R in his study in used bovina lactoferrin in treated anemia in hereditary Mean clotting time, in our study in lactoferrin thrombophilia conclusion that bovina lactoferrin group 7.31±1.42 within normal range of reference safe and effective in curing anemia associated with 4-11more than non lactoferrin group mean 6.08 a consistent decrease of serum interleukin-6.the ±0.47 , clotting time was considered abnormal if it absence of miscarriage in bovina lactoferrin treated was more than 10 minutes (600 seconds) women provided an unexpected benefit 26 complications of lactoferrin in case group no lactoferrin and thrombosis in pregnant women no thrombosis as a complication of lactoferrin only 2 evidence of thrombosis in pregnant women treated cases of deep venous thrombosis in control group with lactoferrin evidence by no reported case of advantage of lactoferrin in correction of anemia thrombosis in lactoferrin treated group and by mean haemoglobin in cases group 10.4±8.09 prolonged coagulation prolife .in our study PT more than control group 10±0.02 as in study of ,APTT, prolonged in both group but in cases group Paeson R 26 its value reach upper normal value in third trimester prothrombin time was prolonged in both Number of cases of preterm labour in case group 3 groups in contrast to our results Lioyd R et al cases less than in 5 case in control group Number showed that prothrombin time was decreased in of cases of hypertension with pregnancy in case pregnancy and it was a significant increase in the group 2 cases less than in 7 casea in control activity of factors VII, VIII, IX, and X and in the lactoferrin and methydopa in previous study of SS concentrations of fibrinogen, -1-, and -1- Anter tight controlled of blood pressure in antitrypsin . ,46 other study different from our pregnancy in combination with methydopa and study Hui et al reported that decreased of both PT improved outcome,outcome,50SS Anter ,APTT in pregnancy ,47.study of Orlikwski CE increased most of coagulation factors in normal 6. Conclusion pregnancy but, APTT may be shortened ,48.other hand study of Szecsi P B et al ,proposed that This study concluded that lactoferrin treated prothrombin time remains unchanged in pregnancy normal pregnant women has no thrombotic as well as the level of coagulation factors II, V, X, complication but the prolongation in haemostatic XI, XII and , protein C largely parameters are within upper normal range without remained unchanged ,49 . Agree with Hellgren M hemorrhagic complication add to its benefit as study that proposed that in pregnancy there were correction of anemia ,ant oxidation increase endogenous thromboin generation, immunemodulatry,andtreatent preterm labor and acquired active protein C resistance and increase hypertension prothrombin time ,45.also,agree with study of Cerneca F et al shown that the parameters showing 7. References the greatest variation during pregnancy were PT, Prothrombin fragments F1+2, The existence of a hypercoagulable state in pregnancy was suggested by the increased levels of F1+2 ,49.Thrombosis 1. T. Tsuchiya, T. Takeuchi, K.-I.Hayashida, H. occur only under special circumstances as Shimizu, K. Ando, and E.Harada, “Milk-derived septicemia and in inflammatory conditions also in lactoferrin may block tolerance to morphine dissemination intravascular coagulopathy,40 analgesia,” Brain Research, vol. 1068, no. 1, pp. 102–108, 2006 lactoferrin and hemorrhage in spite of previous studies of antithrombotic action of lactoferrin and 2. Clare DA, Catignani GL, Swaisgood HE. added to our results of prolonged all coagulation Biodefense properties of milk: the role of parameters no hemorrhagic complication in cases antimicrobial and peptides. Curr Pharm group except early in our study 4 cases complicated Des. 2003;9:1239–55. by intrapartum hemorrhage due to e to atony of uterus2 cases controlled by medical measure and

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Imperial Journal of Interdisciplinary Research (IJIR) Vol-2, Issue-6, 2016 ISSN: 2454-1362, http://www.onlinejournal.in

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13. Kruzel ML, Bacsi A, Choudhury B, Sur S, and 25- H. F. Wu ; F. C. Church Thrombomodulin Boldogh I. Lactoferrin decrease spollen antigen - cofactor activity is enhanced by lactoferrin H- induced allergic airway inflammation in a murine terminal peptides Pathology and Laboratory model of asthma. Immunology.2006; 119:159–66. Medicine 1996

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26-Rosalba PaesanoEnricaPacificiSamanta New aspects in thrombosis research: possible role Benedetti Francesca Berlutti Safety and efficacy of of mast cells as profibrinolytic and antithrombotic lactoferrin versus ferrous sulphatein curing iron cells. deficiency and anaemiain hereditary thrombophilia pregnant women:an 37Shaoheng HeAlan R McEuenSally A interventional study Biometals, 2014 BlewettPingLiMark G BuckleyPaulLeufkensAndrew F Wallse ,The 27 -Elena Y. SenchenkovaElena Y. Senchenkova inhibition of mast cell activation by neutrophil Interleukin-6 Interleukin-6 Mediates the Platelet lactoferrin: uptake by mast cells and interaction Abnormalities and Thrombogenesis Associated with tryptase, chymase and cathepsin with Experimental Colitis ,The American Journal .Biochemical.pharmacolgy,2003,vol 65 (6) of Pathology,Volume 183, Issue 1, July 2013, 38-Daniela 28 _VesceF.a • GiuglianoE.a • BignardiS.a • Salvemini,SalvatoreCuzzocrea,oxidative stress in CagnazzoE.a • ColamussiC.a • Marci R.a • Valente septic shock and disseminated intra vascular N.b • SeraceniS.b • MaritatiM.b • ContiniC.b- coagulation VFree Radical Biology and medicine .Vaginal Lactoferrin Administration before Genetic volume 33, Issue 9, 1 November 2002, Pages Amniocentesis Decreases Amniotic Interleukin-6 1173–118 LevelPediatric Research (1996) 40, 257–262; .39-Adeyemi EO1, Hodgson HJ.Augmented release 29- Mattsby-Baltzer1, FortunatoVesceA of human leucocyte lactoferrin (and elastase) Lactoferrin or a Fragment Thereof Inhibits the during coagulation.Journal of Clinical & Endotoxin-Induced Interleukin-6 Response in Laboratory Immunology [1988, 27(1):1-4] Human MonocyticCell.GynecolObstet Invest 2014;77:245-249 40.High Lactoferrin Levels in Disseminated Intravascular Coagulation and Its Possible Negative 30-Franz-Josef Neumann, IlkaOtt,Nikolaus Marx, Role in Coagulation Özsan, Pehlı̇van, Demı̇rkan, Thomas Luther, SilkeKenngott et al,Effect of Ündar, Sayan, Çehrelı̇Thrombosis Research Human Recombinant Interleukin-6 and Interleukin- 98(1):111–114 • April 2000 8 on Monocyte Procoagulant Activity .ArteriosclerThrombVasc Biol. 1997 41-Wu HF1, Lundblad RL, Church Dec;17(12):3399-405. FC.,Neutralization of Heparin Activity by Neutrophil Lactoferrin 1995 Jan 15;85(2):421-8. 31- van Aken BE1, Reitsma PH, RosendaalFR,Interleukin 8 and venous thrombosis: 42_Haifeng M Wua, , , Frank C Churchb,-Arginine evidence for a role of inflammation in 25 and Arginine 28 of lactoferrin are critical for thrombosis.Br J Haematol. 2002 Jan;116(1):173-7. effective heparin neutralization in blood Arch BiochemBiophys. 2003 Apr 1;412(1):121-5. 32-Peter K. HenkeThomas W. Wakefield, Amy M. Kadell, B.S.a, Marisa J. Linna, et alinterleukin-8 43-Parker RI1, McKeown LP, Gallin JI, Absence Administration Enhances Venous Thrombosis of the largest platelet-von Willebrandmultimers in Resolution in a Rat Model a patient with lactoferrin deficiency and a bleeding tendency.ThrombHaemost. 1992 Mar 2;67(3):320- 33-Elisabeth ElassLactoferrin.inhabits the Limpopo 4. my saccharine_induc d Expression and proteoglycan _Binding Ability of interleukin _8 in 44.Boehlen F et al that platelet count decreases in Human Endothelial cells normal pregnancy possibly due to increased destruction and haemodilution with a maximal 34 - decrease in the third trimester AUmmeAMaramara,MichaelA,Flierlt,DanielRittirs ch,etal.Molecular intercommunication between the 45.Hellgren M. Homeostasis during normal complement and coagulation systems pregnancy and puerperium. SeminThrombHemost. 2003 Apr; 29 (2); 125-30 35_ASamuelsen ,HauklandHH,UlavatneH,Vorland LH , Anti-complement effects of lactoferrin - 46.Lloyd R Whitfield, Amol S Lele, Gerhard Levy derived peptides immunology1982 Oct;47(2):263- Amherst et al, Effect of Pregnancy on the 70 relationship between concentration and anticoagulant action of heparin. Clinical .36.Valent P1, Baghestanian M, Bankl HC, Sillaber Pharmacology and Therapeutics (1983) 34, 23-28; C, Sperr WR, Wojta J, Binder BR, Lechner K9- 1983.

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Imperial Journal of Interdisciplinary Research (IJIR) Vol-2, Issue-6, 2016 ISSN: 2454-1362, http://www.onlinejournal.in

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