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Impact of Anemia on Cerebral Venous Thrombosis Patients Compared to Arterial Stroke

    Authors

    • Ahmed Jubair Khamees 1
    • Wassem . F Al Tameemi 2
    • Hasan Azeez Al-Hamadani 3

    1 Al-Zahraa Teaching Hospital in Kut, Wasit/ Iraq

    2 Haematology Department, College of Medicine, Al-Nahrain University, Baghdad/ Iraq

    3 Neuromedicine, College of Medicine, Al-Nahrain University, Baghdad/ Iraq

,

Document Type : Research Paper

10.52573/ipmj.2021.176986
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Abstract

BACKGROUND:
Cerebral venous thrombosis (CVT) is a condition where a thrombotic event involves cerebral venous sinuses of varied temporal evolution. It causes stroke with incidence of ≈1.3 per 100000 especially in young female. Many - risk factors had attributed in its etiology assuming, anemia, as one of these factor, - based on case reports and case series.
AIM OF STUDY:  
Toassess the impact of anaemia on cerebral venous thrombosis (CVT) in comparison with arterial stroke 
PATIENTS AND METHODS: 
A case control prospective study performed at   Al-Imamain Al-Kadhimain Medical City throughout      the period from December-2017 to December-2019. It included 42 randomly selected cerebral venous thrombosis (CVT) patients who compared with another 60 patients with arterial stroke as control patient group -Both groups were offered complete blood count (CBC) within 48 hours as part of routine investigation. Those discovered to have anemia were categorized according to severity using WHO definition in both groups as well as their mean corpuscular volume (MCV). Statistical analyses performed to define the relationship between anemia, microcytosis and CVT diagnosis. Kaplan-Meier curve used to assess the survival of patients with CVT during the early outcome period of 14 days.
RESULTS:
Mean patients Hb was 11.05±3.11mg/dl versus 13.62±3.73 mg/dl in control group (p value < 0.001) with lower MCV (74.88±12.85 fl versus86.43±9.02 fl) (p value < 0.001). Severe anemia and severe microcytosis were associated significantly with CVT (OR= 13.5, 95% CI= 2.47-73.71, p= 0.001), (OR=2.87, 95%CI=2.17-3.8, p<0.001) respectively independently but not as such in combination with other confirmed other risk factors like age and gender. It is observed that mean duration of death was 8.5 days in CVT patients with anamia ( p value 0.227 ). All dead cases had severe anemia.
CONCLUSION:
There is inverse association between severity of anemia, microcytosis with CVT incidence, which may be considered as separate risk factors. The presence of anemia in CVT patient may result in - poor outcome and increasing early mortality rate.
 

Keywords

  • Cerebral venous thrombosis
  • anaemia and stroke
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References
1.     Bousser MG Chiras J, Berics J, Castagine P.  Cerebral venous thrombosis – a review of 38 cases.  Stroke 1985; 16: 199 -213.
2.     Nagaraja D, Taly AB, Puerperal venous sinus thrombosis in India. In: Sinha KK  ed.
3.     Coutinho JM, Zuurbier SM, Aramideh M, Stam J.  The incidence of cerebral venous thrombosis: a cross-sectional study.  Stroke. 2012;43:3375-77. doi: 10.1161/STROKEAHA.112.671453.
4.     Bousser MG, Ferro JM. Cerebral venous thrombosis: an update.  Lancet Neurol. 2007;6:162–70. doi: 10.1016/S1474-4422(07)70029-7.
5.     Ferro JM, Canhão P, Bousser MG, Stam J, Barinagarrementeria F; ISCVT Investigators. Cerebral vein and dural sinus thrombosis in elderly patients.  Stroke. 2005;36:1927–32. doi: 10.1161/01. STR.0000177894.05495.54.
6.     Villringer A, Mehraein S, Einhaupl KM. Pathophysiological aspects of cerebral sinus venous thrombosis (SVT). J Neuroradiol. 1994;21:72-80.
7.     Holger Allroggen, Richard J Abbott. Cerebral venous sinus thrombosis. Postgrad Med J 2000;76:12-5.
8.     Bousser MG, Russell RR. Cerebral venous thrombosis. London: W B Saunders, 1997.
9.     Van Gijn J.Cerebral venous thrombosis: pathogenesis, presentation and prognosis. J R Soc Med. 2000;93:230-33.
10.Coutinho JM, Ferro JM, Canhão P, Barinagarrementeria F, Cantú C, Bousser MG, et al. Cerebral venous and sinus thrombosis in women.  Stroke.  2009;40:2356–61.  doi:  10.1161/STROKEAHA. 108.543884.
11.World Health Organization. The Global Prevalence of Anaemia in 2011. Geneva: WHO, 2015.
12.De  Benoist B, McLean E, Ines E, et al.  Worldwide prevalence of anaemia 1993 - 2005. Geneva: WHO, 2008.
13.Who, Chan M. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Geneva, Switz World Heal Organ.  2011;1-6.
14.Wintrobe MM. Anemia, classification and treatment of, on the basis of differences in the average volume and hemoglobin content of the red corpuscles. Arch Int Med 20: 987–988, 1934.
15.Byrnes JR, Wolberg  AS.  Red blood  cells  in thrombosis.  Blood.  2017; 130: 1795-99.
16.Sergueeva A, Miasnikova  G, Shah BN, et  al.  Prospective study of thrombosis and thrombospondin-1 expression in Chuvash polycythemia.  haematologica. 2017;102: e166-e169.
17.Kassebaum NJ, Jasrasaria R, Naghavi M, et al. A systematic analysis of global anemia burden from 1990 to 2010.  Blood  2014;123:615–24.
18.Franchini M, Targher  G, Montagnana  M, et al.  Iron and thrombosis. Ann Hematol. 2008; 87: 167-73.
19.Piety  NZ,  Reinhart  WH,  Pourreau  PH,  et  al.  Shape  matters:  the  effect of  red  blood  cell  shape  on  perfusion  of  an  artificial  microvascular network.  Transfusion. 2016;56: 844-51.
20.Whelihan M, Lim M, Mooberry M, et al.  Thrombin generation and cell-dependent hypercoagulability in sickle cell disease.  Journal of Thrombosis and Haemostasis. 2016;14: 1941-52.
21.Setty BY, Rao AK, Stuart MJ.  Thrombophilia in sickle cell disease:  the red cell connection.  Blood. 2001; 98: 3228-33.
22.Rother RP, Bell L, Hillmen P, et al.  The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin:  a novel mechanism of human disease.  Jama. 2005; 293:1653-62.
23.Santos M, Valles J, Marcus A, et al.  Enhancement of platelet reactivity and modulation of eicosanoid production by intact erythrocytes.  A new approach to platelet activation and recruitment.  The Journal of clinical investigation. 1991;87: 571-80.
24.Lin CL, Tzeng SL, Chung WS. Aplastic anemia and risk  of  deep  vein thrombosis  and  pulmonary  embolism:  A  nationwide  cohort  study. Thromb Res. 2017;149:70-75.
25.Li YD, Ye BQ, Zheng SX, et al.  NF-kappaB transcription factor p50 critically regulates  tissue factor  in deep  vein thrombosis.  J Biol Chem. 2009; 284: 4473-83.
26.Stolz E,  Valdueza JM, Grebe M, Schlachetzki F, Schmitt E, Madlener K, et al.  Anemia as a risk factor for cerebral venous thrombosis?  An old hypothesis revisited. Results of a prospective study.  J Neurol. 2007;254:729–34. doi: 10.1007/s00415-006-0411-9.
27.Coutinho JM, Zuurbier SM, Gaartman AE, Dikstaal AA, Stam J, Middeldorp S, et al. Association between anemia and cerebral venous thrombosis: Case-control study. Stroke. 2015;46:2735–40
28.Lanotte L, Mauer J, Mendez S, et al. Red cells’ dynamic morphologies govern blood shear thinning under microcirculatory flow conditions. Proc Natl Acad Sci USA. 2016;113: 13289-94.
29.Baskurt OK, Meiselman HJ. Iatrogenic hyperviscosity and thrombosis. Semin Thromb Hemost. 2012;38:854-64.
30.Errill EW. Rheology of blood. Physiol Rev. 1969; 49(4):863-888.
31.Lowe GD, Lee AJ, Rumley A, Price JF, Fowkes FG. Blood viscosity and risk of cardiovascular events: the Edinburgh Artery Study. Br J Haematol. 1997;96(1):168-173.
32.Holley L, Woodland N, Hung WT, Cordatos K, Reuben A. Influence of fibrinogen and haematocrit on erythrocyte sedimentation kinetics. Biorheology. 1999;36(4):287-297.
33.Rampling MW. The binding of fibrinogen and fibrinogen degradation products to the erythrocyte membrane and its relationship to haemorheology. Acta Biol Med Ger. 1981;40:373-78.
34.Wandersee NJ, Olson SC, Holzhauer SL, Hoffmann RG, Barker JE, Hillery CA. Increased erythrocyte adhesion in mice and humans with hereditary spherocytosis and hereditary elliptocytosis. Blood. 2004;103:710-16.
35.Colin Y, Le Van Kim C, El Nemer W. Red cell adhesion in human diseases. Curr Opin Hematol. 2014;21:186-92.
36.Turitto VT, Baumgartner HR. Platelet interaction with subendothelium in a perfusion system: physical role of red blood cells. Microvasc Res. 1975;9:335-44.
37.Turitto VT, Weiss HJ. Red blood cells: their dual role in thrombus formation. Science. 1980; 207:541-43.
38.Fogelson AL, Neeves KB. Fluid mechanics of blood clot formation. Annu Rev Fluid Mech. 2015; 47:377-403.
 
 
39.      Walton BL, Lehmann M, Skorczewski T,  et al. Elevated hematocrit enhances platelet accumulation following vascular injury. Blood. 2017;129:2537-46.
40.      Wang W, Diacovo TG, Chen J, Freund JB, King MR. Simulation of platelet, thrombus and erythrocyte hydrodynamic interactions in a 3D arteriole with in vivo comparison. PLoS One. 2013;8:e76949.
41.      Reimers RC, Sutera SP, Joist JH. Potentiation by red blood cells of shear-induced platelet aggregation: relative importance of chemical and physical mechanisms. Blood. 1984;64:1200-6.
42.      Gupta NK, Chhaparwal JK, Kanwaria D, Meena RR, Nayak K. Association of Anemia with Cerebral Venous Thrombosis in Puerperium and its Pattern of Recovery. Int Arch Biomed Clin Res. 2017;3:60–63.
43.      Mooij PN, Thomas CM, Doesburg WH, Eskes TK. The effects of oral contraceptives and multivitamin supplementation on serum ferritin and hematological parameters. Int J Clin Pharmacol Ther Toxicol. 1992;30:57–62.
44.      Grace E, Emans SJ, Drum DE. Hematologic abnormalities in adolescents who take oral contraceptive pills. J Pediatr. 1982;101:771–74.
45.      Ferro JM, Correia M, Pontes C, Baptista MV, Pita F. Cerebral vein and dural sinus thrombosis in Portugal: 1980–1998. Cerebrovasc Dis. 2001; 11:177–18.
 
 
1.     Bousser MG Chiras J, Berics J, Castagine P.  Cerebral venous thrombosis – a review of 38 cases.  Stroke 1985; 16: 199 -213.
2.     Nagaraja D, Taly AB, Puerperal venous sinus thrombosis in India. In: Sinha KK  ed.
3.     Coutinho JM, Zuurbier SM, Aramideh M, Stam J.  The incidence of cerebral venous thrombosis: a cross-sectional study.  Stroke. 2012;43:3375-77. doi: 10.1161/STROKEAHA.112.671453.
4.     Bousser MG, Ferro JM. Cerebral venous thrombosis: an update.  Lancet Neurol. 2007;6:162–70. doi: 10.1016/S1474-4422(07)70029-7.
5.     Ferro JM, Canhão P, Bousser MG, Stam J, Barinagarrementeria F; ISCVT Investigators. Cerebral vein and dural sinus thrombosis in elderly patients.  Stroke. 2005;36:1927–32. doi: 10.1161/01. STR.0000177894.05495.54.
6.     Villringer A, Mehraein S, Einhaupl KM. Pathophysiological aspects of cerebral sinus venous thrombosis (SVT). J Neuroradiol. 1994;21:72-80.
7.     Holger Allroggen, Richard J Abbott. Cerebral venous sinus thrombosis. Postgrad Med J 2000;76:12-5.
8.     Bousser MG, Russell RR. Cerebral venous thrombosis. London: W B Saunders, 1997.
9.     Van Gijn J.Cerebral venous thrombosis: pathogenesis, presentation and prognosis. J R Soc Med. 2000;93:230-33.
10.Coutinho JM, Ferro JM, Canhão P, Barinagarrementeria F, Cantú C, Bousser MG, et al. Cerebral venous and sinus thrombosis in women.  Stroke.  2009;40:2356–61.  doi:  10.1161/STROKEAHA. 108.543884.
11.World Health Organization. The Global Prevalence of Anaemia in 2011. Geneva: WHO, 2015.
12.De  Benoist B, McLean E, Ines E, et al.  Worldwide prevalence of anaemia 1993 - 2005. Geneva: WHO, 2008.
13.Who, Chan M. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Geneva, Switz World Heal Organ.  2011;1-6.
14.Wintrobe MM. Anemia, classification and treatment of, on the basis of differences in the average volume and hemoglobin content of the red corpuscles. Arch Int Med 20: 987–988, 1934.
15.Byrnes JR, Wolberg  AS.  Red blood  cells  in thrombosis.  Blood.  2017; 130: 1795-99.
16.Sergueeva A, Miasnikova  G, Shah BN, et  al.  Prospective study of thrombosis and thrombospondin-1 expression in Chuvash polycythemia.  haematologica. 2017;102: e166-e169.
17.Kassebaum NJ, Jasrasaria R, Naghavi M, et al. A systematic analysis of global anemia burden from 1990 to 2010.  Blood  2014;123:615–24.
18.Franchini M, Targher  G, Montagnana  M, et al.  Iron and thrombosis. Ann Hematol. 2008; 87: 167-73.
19.Piety  NZ,  Reinhart  WH,  Pourreau  PH,  et  al.  Shape  matters:  the  effect of  red  blood  cell  shape  on  perfusion  of  an  artificial  microvascular network.  Transfusion. 2016;56: 844-51.
20.Whelihan M, Lim M, Mooberry M, et al.  Thrombin generation and cell-dependent hypercoagulability in sickle cell disease.  Journal of Thrombosis and Haemostasis. 2016;14: 1941-52.
21.Setty BY, Rao AK, Stuart MJ.  Thrombophilia in sickle cell disease:  the red cell connection.  Blood. 2001; 98: 3228-33.
22.Rother RP, Bell L, Hillmen P, et al.  The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin:  a novel mechanism of human disease.  Jama. 2005; 293:1653-62.
23.Santos M, Valles J, Marcus A, et al.  Enhancement of platelet reactivity and modulation of eicosanoid production by intact erythrocytes.  A new approach to platelet activation and recruitment.  The Journal of clinical investigation. 1991;87: 571-80.
24.Lin CL, Tzeng SL, Chung WS. Aplastic anemia and risk  of  deep  vein thrombosis  and  pulmonary  embolism:  A  nationwide  cohort  study. Thromb Res. 2017;149:70-75.
25.Li YD, Ye BQ, Zheng SX, et al.  NF-kappaB transcription factor p50 critically regulates  tissue factor  in deep  vein thrombosis.  J Biol Chem. 2009; 284: 4473-83.
26.Stolz E,  Valdueza JM, Grebe M, Schlachetzki F, Schmitt E, Madlener K, et al.  Anemia as a risk factor for cerebral venous thrombosis?  An old hypothesis revisited. Results of a prospective study.  J Neurol. 2007;254:729–34. doi: 10.1007/s00415-006-0411-9.
27.Coutinho JM, Zuurbier SM, Gaartman AE, Dikstaal AA, Stam J, Middeldorp S, et al. Association between anemia and cerebral venous thrombosis: Case-control study. Stroke. 2015;46:2735–40
28.Lanotte L, Mauer J, Mendez S, et al. Red cells’ dynamic morphologies govern blood shear thinning under microcirculatory flow conditions. Proc Natl Acad Sci USA. 2016;113: 13289-94.
29.Baskurt OK, Meiselman HJ. Iatrogenic hyperviscosity and thrombosis. Semin Thromb Hemost. 2012;38:854-64.
30.Errill EW. Rheology of blood. Physiol Rev. 1969; 49(4):863-888.
31.Lowe GD, Lee AJ, Rumley A, Price JF, Fowkes FG. Blood viscosity and risk of cardiovascular events: the Edinburgh Artery Study. Br J Haematol. 1997;96(1):168-173.
32.Holley L, Woodland N, Hung WT, Cordatos K, Reuben A. Influence of fibrinogen and haematocrit on erythrocyte sedimentation kinetics. Biorheology. 1999;36(4):287-297.
33.Rampling MW. The binding of fibrinogen and fibrinogen degradation products to the erythrocyte membrane and its relationship to haemorheology. Acta Biol Med Ger. 1981;40:373-78.
34.Wandersee NJ, Olson SC, Holzhauer SL, Hoffmann RG, Barker JE, Hillery CA. Increased erythrocyte adhesion in mice and humans with hereditary spherocytosis and hereditary elliptocytosis. Blood. 2004;103:710-16.
35.Colin Y, Le Van Kim C, El Nemer W. Red cell adhesion in human diseases. Curr Opin Hematol. 2014;21:186-92.
36.Turitto VT, Baumgartner HR. Platelet interaction with subendothelium in a perfusion system: physical role of red blood cells. Microvasc Res. 1975;9:335-44.
37.Turitto VT, Weiss HJ. Red blood cells: their dual role in thrombus formation. Science. 1980; 207:541-43.
38.Fogelson AL, Neeves KB. Fluid mechanics of blood clot formation. Annu Rev Fluid Mech. 2015; 47:377-403.
 
 
39.      Walton BL, Lehmann M, Skorczewski T,  et al. Elevated hematocrit enhances platelet accumulation following vascular injury. Blood. 2017;129:2537-46.
40.      Wang W, Diacovo TG, Chen J, Freund JB, King MR. Simulation of platelet, thrombus and erythrocyte hydrodynamic interactions in a 3D arteriole with in vivo comparison. PLoS One. 2013;8:e76949.
41.      Reimers RC, Sutera SP, Joist JH. Potentiation by red blood cells of shear-induced platelet aggregation: relative importance of chemical and physical mechanisms. Blood. 1984;64:1200-6.
42.      Gupta NK, Chhaparwal JK, Kanwaria D, Meena RR, Nayak K. Association of Anemia with Cerebral Venous Thrombosis in Puerperium and its Pattern of Recovery. Int Arch Biomed Clin Res. 2017;3:60–63.
43.      Mooij PN, Thomas CM, Doesburg WH, Eskes TK. The effects of oral contraceptives and multivitamin supplementation on serum ferritin and hematological parameters. Int J Clin Pharmacol Ther Toxicol. 1992;30:57–62.
44.      Grace E, Emans SJ, Drum DE. Hematologic abnormalities in adolescents who take oral contraceptive pills. J Pediatr. 1982;101:771–74.
45.      Ferro JM, Correia M, Pontes C, Baptista MV, Pita F. Cerebral vein and dural sinus thrombosis in Portugal: 1980–1998. Cerebrovasc Dis. 2001; 11:177–18.
 
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Iraqi Postgraduate Medical Journal
Volume 21, Issue 4
October 2022
Page 404-411
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APA

Khamees, A., Al Tameemi, W. .., & Al-Hamadani, H. (2021). Impact of Anemia on Cerebral Venous Thrombosis Patients Compared to Arterial Stroke. Iraqi Postgraduate Medical Journal, 21(4), 404-411. doi: 10.52573/ipmj.2021.176986

MLA

Ahmed Jubair Khamees; Wassem . F Al Tameemi; Hasan Azeez Al-Hamadani. "Impact of Anemia on Cerebral Venous Thrombosis Patients Compared to Arterial Stroke". Iraqi Postgraduate Medical Journal, 21, 4, 2021, 404-411. doi: 10.52573/ipmj.2021.176986

HARVARD

Khamees, A., Al Tameemi, W. .., Al-Hamadani, H. (2021). 'Impact of Anemia on Cerebral Venous Thrombosis Patients Compared to Arterial Stroke', Iraqi Postgraduate Medical Journal, 21(4), pp. 404-411. doi: 10.52573/ipmj.2021.176986

VANCOUVER

Khamees, A., Al Tameemi, W. .., Al-Hamadani, H. Impact of Anemia on Cerebral Venous Thrombosis Patients Compared to Arterial Stroke. Iraqi Postgraduate Medical Journal, 2021; 21(4): 404-411. doi: 10.52573/ipmj.2021.176986

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