Advertisement

Clinical disorders responsible for plasma hyperviscosity and skin complications

Published:April 05, 2017DOI:https://doi.org/10.1016/j.ejim.2017.04.001

      Highlights

      • Primary plasma hyperviscosity is associated with several clinical conditions.
      • Skin ulcers may be often observed in subjects with plasma hyperviscosity.
      • Medical therapy or plasma exchange may improve this hemorheological parameter.

      Abstract

      In this brief review, we have examined some clinical disorders which are associated to an altered hemorheological profile and at times accompanied by skin ulcers. This skin condition may be, in fact, observed in patients with primary plasma hyperviscosity such as multiple myeloma, Waldenstrom macroglobulinemia, cryoglobulinemia, cryofibrinogenemia, dysfibrinogenemia and connective tissue diseases. It must be underlined that the altered hemorheological pattern is not the only responsible for this skin complication but, as it worsens the microcirculatory flow, it contributes to determine the occurrence of the skin ulcers.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Castillo J.J.
        Plasma cell disorders.
        Prim Care. Dec 2016; 43: 677-691
        • Kwaan H.C.
        Hyperviscosity in plasma cell dyscrasias.
        Clin Hemorheol Microcirc. 2013; 55: 75-83
        • Dumas G.
        • Merceron S.
        • Zafrani L.
        • Canet E.
        • Lemiale V.
        • Kouatchet A.
        • et al.
        Hyperviscosity syndrome.
        Rev Med Interne. Sep 2015; 36: 588-595
        • Uggla B.
        • Nilsson T.K.
        Whole blood viscosity in plasma cell dyscrasias.
        Clin Biochem. Feb 2015; 48: 122-124
        • Jurczyszyn A.
        • Czepiel J.
        • Gdula-Argasińska J.
        • Paśko P.
        • Czapkiewicz A.
        • Librowski T.
        • et al.
        Plasma fatty acid profile in multiple myeloma patients.
        Leuk Res. Apr 2015; 39: 400-405
        • Wang W.Q.
        • Zhao X.Y.
        • Wang H.Y.
        • Liang Y.
        Increased fatty acid synthase as a potential therapeutic target in multiple myeloma.
        J Zhejiang Univ Sci B. Jun 2008; 9: 441-447
        • Chatziantoniou V.
        • Alexia S.
        • Konstantopoulos K.
        • Repousis P.
        • Megalakaki A.
        • Kotsopoulou M.
        • et al.
        Significance of the detection of paroxysmal nocturnal hemoglobinuria clones in patients with multiple myeloma undergoing autologous stem cell transplantation.
        Hematol Oncol Stem Cell Ther. 2015; 8: 150-159
        • Meletis J.
        • Terpos E.
        • Samarkos M.
        • Meletis C.
        • Apostolidou E.
        • Komninaka V.
        • et al.
        Detection of CD55- and/or CD59-deficient red cell populations in patients with plasma cell dyscrasias.
        Int J Hematol. 2002; 75: 40-44
        • Terpos E.
        • Samarkos M.
        • Meletis C.
        • Apostolidou E.
        • Tsironi M.
        • Korovesis K.
        • et al.
        Unusual association between increased bone resorption and presence of paroxysmal nocturnal hemoglobinuria phenotype in multiple myeloma.
        Int J Hematol. 2003; 78 (94): 344-348
        • Varma S.
        • Varma N.
        • Reddy V.V.
        • Naseem S.
        • Bose P.
        • Malhotra P.
        Detection of paroxysmal nocturnal hemoglobinuria-phenotype in patients with chronic lymphocytic leukemia and multiple myeloma.
        Indian J Pathol Microbiol. 2012; 55: 206-210
        • Daoud M.S.
        • Lust J.A.
        • Kyle R.A.
        • Pittelkow M.R.
        Monoclonal gammopathies and associated skin disorders.
        J Am Acad Dermatol. Apr 1999; 40: 507-535
        • Satta R.
        • Casu G.
        • Dore F.
        • Longinotti M.
        • Cottoni F.
        Follicular spicules and multiple ulcers: cutaneous manifestations of multiple myeloma.
        J Am Acad Dermatol. 2003; 49: 736-740
        • Phatak D.R.
        Serum hyperviscosity in Waldenstrom's macroglobulinemia.
        Transfusion. Aug 2003; 43: 989
        • Menke M.N.
        • Feke G.T.
        • McMeel J.W.
        • Treon S.P.
        Effect of plasmapheresis on hyperviscosity-related retinopathy and retinal hemodynamics in patients with Waldenstrom's macroglobulinemia.
        Invest Ophthalmol Vis Sci. Mar 2008; 49: 1157-1160
        • Stone M.J.
        Waldenström's macroglobulinemia: hyperviscosity syndrome and cryoglobulinemia.
        Clin Lymphoma Myeloma. Mar 2009; 9: 97-99
        • Stone M.J.
        • Bogen S.A.
        Evidence-based focused review of management of hyperviscosity syndrome.
        Blood. Mar 8 2012; 119: 2205-2208
        • Sigle J.P.
        • Buser A.
        Hyperviscosity syndrome.
        Blood. Feb 3 2011; 117: 1446
        • Zgouras D.
        • Engels K.
        • Lindhoff-Last E.
        Lymphoplasmacytic lymphoma with Waldenstrom's macroglobulinemia as a reason for peripheral arterial perfusion disorders.
        Vasa. May 2009; 38: 193-196
        • Nishijima S.
        • Hosokawa H.
        • Yanase K.
        • Asada Y.
        • Fujinami S.
        Primary macroglobulinemia presenting as multiple ulcers of the legs.
        Acta Derm Venereol. 1983; 63: 173-175
        • Wagner D.R.
        • Eckert F.
        • Gresser U.
        • Landthaler M.
        • Middeke M.
        • Zöllner N.
        Deposits of paraprotein in small vessels as a cause of skin ulcers in Waldenström's macroglobulinemia.
        Clin Investig. Dec 1993; 72: 46-49
        • Ramakrishnan S.
        • Degenhardt R.
        • Vietzke K.
        Erythrocyte deformability in Waldenström's macroglobulinemia.
        Clin Hemorheol Microcirc. 2000; 22: 17-20
        • Cicco S.
        • Ditonno P.
        • Reale A.
        • Savino S.
        • Castrovilli A.
        • Catacchio I.
        • et al.
        Could multiple myeloma VEGF modify the sistemic microcirculation?.
        Adv Exp Med Biol. 2012; 737: 155-160
        • Lowe G.D.O.
        Rheology of paraproteinemias and leukemias.
        in: Lowe Gordon D.O. Clinical Blood Rheology. vol. I. CRC Press, Inc., 1988: 67-87
        • Alt S.
        • Banyai S.
        • Banyai M.
        • Koppensteiner R.
        Blood rheology in deep venous thrombosis—relation to persistent an transient risk factors.
        Thromb Res. 2002; 107: 101-107
        • Coppola A.
        • Tufano A.
        • Di Capua M.
        • Franchin M.
        Bleeding and thrombosis in multiple myeloma and related plasma cell disorders.
        Semin Thromb Hemost. 2011; 37: 929-945
        • Vaya A.
        • Suescun M.
        Hemorheological parameters as independent predictors of venous thromboembolism.
        Clin Hemorheol Microcirc. 2013; 53: 131-141
        • Fukumoto J.S.
        • Gotlib J.
        A patient with paroxysmal nocturnal hemoglobnuria, T cell large granular lymphocyte clonal expansion, and monoclonal gammopathy of undetermined significance.
        Am J Hematol. 2006; 81: 870-874
        • Meletis J.
        • Terpos E.
        • Samarkos M.
        • Meletis C.
        • Konstantopoulos K.
        • Komninaka V.
        • et al.
        Detection of CD55 and/or CD59 deficient red cell population in patients with aplastic anaemia, myelodisplastic syndromes and myeloproliferative disorders.
        Haematologia. 2001; 31: 7-16
        • Meletis J1.
        • Terpos E.
        • Samarkos M.
        • Meletis C.
        • Apostolidou E.
        • Komninaka V.
        • et al.
        Detection of CD55 and/or CD59-deficient red cell population in patients with lymphoproliferative syndromes.
        Hematol J. 2001; 2: 33-37
        • Meletis J.
        • Terpos E.
        • Samarkos M.
        • Meletis C.
        • Apostolidou E.
        • Komninaka V.
        • et al.
        Red cells with paroxysmal nocturnal hemoglobinuria-phenotype with acute leukemia.
        Hematology. 2002; 7: 69-74
        • Ramos-Casals M.
        • Stone J.H.
        • Cid M.C.
        • Bosch X.
        The cryoglobulinaemias.
        Lancet. 2012; 379: 348-360
        • Cacoub P.
        • Sène D.
        • Saadoun D.
        Cryoglobulinemia.
        Rev Med Interne. Mar 2008; 29: 200-208
        • Ferri C.
        • Mannini L.
        • Bartoli V.
        • Gremignai G.
        • Genovesi-Ebert F.
        • Cristofani R.
        • et al.
        Blood viscosity and filtration abnormalities in mixed cryoglobulinemia patients.
        Clin Exp Rheumatol. 1990; 8: 271-281
        • Ferri C.
        • Sebastiani M.
        • Giuggioli D.
        • Cazzato M.
        • Longombardo G.
        • Antonelli A.
        • et al.
        Mixed cryoglobulinemia: demographic, clinical, and serologic features and survival in 231 patients.
        Semin Arthritis Rheum. 2004; 33: 355-374
        • Ferri C.
        Mixed cryoglobulinemia.
        Orphanet J Rare Dis. 2008; 3: 25
        • Giuggioli D.
        • Manfredi A.
        • Lumetti F.
        • Sebastiani M.
        • Ferri C.
        Cryoglobulinemic vasculitis and skin ulcers. Our therapeutic strategy and review of the literature.
        Semin Arthritis Rheum. 2015; 44: 518-526
        • Auzerie V.
        • Chiali A.
        • Bussel A.
        • Brouet J.C.
        • Fermand J.P.
        • Dubertret L.
        • et al.
        Leg ulcers associated with cryoglobulinemia: clinical study of 15 patients and response to treatment.
        Arch Dermatol. 2003; 139: 391-393
        • Rieu V.
        • Cohen P.
        • André M.H.
        • Mouthon L.
        • Godmer P.
        • Jarrousse B.
        • et al.
        Characteristics and outcome of 49 patients with symptomatic cryoglobulinaemia.
        Rheumatology (Oxford). 2002; 41: 290-300
        • Yamazaki T.
        • Akimoto T.
        • Okuda K.
        • Sugase T.
        • Takeshima E.
        • Numata A.
        • et al.
        Purpura with ulcerative skin lesions and mixed cryoglobulinemia in a quiescent hepatitis B virus carrier.
        Intern Med. 2014; 53: 115-119
        • Michaud M.
        • Pourrat J.
        Cryofibrinogenemia.
        J Clin Rheumatol. 2013; 19: 142-148
        • Saadoun D.
        • Elalamy I.
        • Ghillani-Dalbin P.
        • Sene D.
        • Delluc A.
        • Cacoub P.
        Cryofibrinogenemia: new insights into clinical and pathogenic features.
        Am J Med. 2009; 122: 1128-1135
        • Kolopp-Sardaa M.N.
        • Chapuis-Celliera C.
        • Dimeta I.
        • Lombard C.
        Protéines cryoprécipitantes en pathologie: cryoglobuline et cryofibrinogène.
        Rev. Fr. Lab. 2012; 444: 53-62
        • Daumas A.
        • Boucraut J.
        • Bernard F.
        • Boufi M.
        • Rossi P.
        • Aissi K.
        • et al.
        Unusual cause of peripheral arterial thromboses.
        Rev Med Interne. Feb 2012; 33: 107-108
        • Amdo T.D.
        • Welker J.A.
        An approach to the diagnosis and treatment of cryofibrinogenemia.
        Am J Med. 2004; 116: 332-337
        • Begin P.
        • Leclerc G.
        Images in clinical medicine. Familial primary cryofibrinogenemia.
        N Engl J Med. 2013; 369: e10
        • Beightler E.
        • Diven D.G.
        • Sanchez R.L.
        • Solomon A.R.
        Thrombotic vasculopathy associated with cryofibrinogenemia.
        J Am Acad Dermatol. 1991; 24: 342-345
        • Blain H.
        • Cacoub P.
        • Musset L.
        • Costedoat-Chalumeau N.
        • Silberstein C.
        • Chosidow O.
        • et al.
        Cryofibrinogenaemia: a study of 49 patients.
        Clin Exp Immunol. 2000; 120: 253-260
        • Kwaan H.C.
        • Levin M.
        • Sakurai S.
        • Kucuk O.
        • Rooney M.W.
        • Lis L.J.
        • et al.
        Digital ischemia and gangrene due to red blood cell aggregation induced by acquired dysfibrinogenemia.
        J Vasc Surg. 1997; 26: 1061-1068
        • Rubegni P.
        • Flori M.L.
        • Fimiani M.
        • Andreassi L.
        A case of cryofibrinogenaemia responsive to stanozolol.
        Br J Haematol. 1996; 93: 217-219
        • Sakieda K.
        • Sumikawa Y.
        • Imaoka K.
        • Murata S.
        • Nakamura C.
        • Mizumoto K.
        • et al.
        Successful treatment of leg ulcer caused by cryofibrinogenemia by using a systemic corticosteroid and warfarin.
        Int J Dermatol. 2011; 50: 1538-1541
        • Sandouk Z.
        • Alirhayim Z.
        • Hassan S.
        • Qureshi W.
        Cryofibrinogenaemia: not just skin deep.
        BMJ Case Rep. 2013; 2013
        • Winkens T.
        • Pfeil A.
        • Theis B.
        • Jung C.
        Cryofibrinogenemia associated with cryoglobulinemia—a severe case with amputation of four extremities.
        Jpn J Clin Oncol. 2014; 44: 1013-1014
        • Grada A.
        • Falanga V.
        Cryofibrinogenemia-induced cutaneous ulcers: a review and diagnostic criteria.
        Am J Clin Dermatol. Feb 2017; 18: 97-104
        • Viot C.
        • Bouldouyre M.A.
        • Chauvineau A.
        • Boussadia A.
        • Bakir R.
        Cryofibrinogenemia revealed by digital ischemia with stroke.
        Presse Med. May 2013; 42: 913-915
        • Belizna C.
        • Loufrani L.
        • Subra J.F.
        • Godin M.
        • Jolly P.
        • Vitecocq O.
        • et al.
        A 5-year prospective follow-up study in essential cryofibrinogenemia patients.
        Autoimmun Rev. Jul 2011; 10: 559-562
        • Morsdorf S.
        Haemostatical and rheological aspects of dysfibrinogenemia.
        Clin Hemorheol Microcirc. 1997; 17: 13-19
        • Nguyen F.
        • Drouet L.
        • Boisseau M.
        • Léger P.
        • Juchet H.
        • Bierme R.
        • et al.
        Erythrocyte hyperaggregation and thrombogenic dysfibrinogenemia.
        Clin Hemorheol Microcirc. Jul 1998; 18: 235-243
        • Acharya S.S.
        • Dimichele D.M.
        Rare inherited disorders of fibrinogen.
        Haemophilia. 2008; 14: 1151-1158
        • Hayes T.
        Dysfibrinogenemia and thrombosis.
        Arch Pathol Lab Med. 2002; 126: 1387-1390
        • Hill M.
        • Dolan G.
        Diagnosis, clinical features and molecular assessment of the dysfibrinogenaemias.
        Haemophilia. 2008; 14: 889-897
        • Roberts H.R.
        • Stinchcombe T.E.
        • Gabriel D.A.
        The dysfibrinogenaemias.
        Br J Haematol. 2001; 114: 249-257
        • Undas A.
        Acquired dysfibrinogenemia in atherosclerotic vascular disease.
        Pol Arch Med Wewn. 2011; 121: 310-319
        • Martinez J.
        • Palascak J.E.
        • Kwasniak D.
        Abnormal sialic acid content of the dysfibrinogenemia associated with liver disease.
        J Clin Invest. Feb 1978; 61: 535-538
        • Martinez J.
        • MacDonald K.A.
        • Palascak J.E.
        The role of sialic acid in the dysfibrinogenemia associated with liver disease: distribution of sialic acid on the constituent chains.
        Blood. Jun 1983; 61: 1196-1202
        • Narvaiza M.J.
        • Fernández J.
        • Cuesta B.
        • Páramo J.A.
        • Rocha E.
        Role of sialic acid in acquired dysfibrinogenemia associated with liver cirrhosis.
        Ric Clin Lab. Oct–Dec 1986; 16: 563-568
        • Kotlín R.
        • Sobotková A.
        • Riedel T.
        • Salaj P.
        • Suttnar J.
        • Reicheltová Z.
        • et al.
        Acquired dysfibrinogenemia secondary to multiple myeloma.
        Acta Haematol. 2008; 120: 75-81
        • Post G.R.
        • James L.
        • Alapat D.
        • Guillory V.
        • Cottler-Fox M.
        • Nakagawa M.
        A case of acquired dysfibrinogenemia in multiple myeloma treated with therapeutic plasma exchange.
        Transfus Apher Sci. Feb 2013; 48: 35-38
        • Ashby M.A.
        • Lazarchick J.
        Acquired dysfibrinogenemia secondary to mithramycin toxicity.
        Am J Med Sci. Jul 1986; 292: 53-55
        • Casini A.
        • Blondon M.
        • Lebreton A.
        • Koegel J.
        • Tintillier V.
        • de Maistre E.
        • et al.
        Natural history of patients with congenital dysfibrinogenemia.
        Blood. 2015; 125: 553-561
        • Shapiro S.E.
        • Phillips E.
        • Manning R.A.
        • Morse C.V.
        • Murden S.L.
        • Laffan M.A.
        • et al.
        Clinical phenotype, laboratory features and genotype of 35 patients with heritable dysfibrinogenaemia.
        Br J Haematol. 2013; 160: 220-227
        • Hafner J.
        • Schneider E.
        • Burg G.
        • Cassina P.C.
        Management of leg ulcers in patients with rheumatoid arthritis or systemic sclerosis: the importance of concomitant arterial and venous disease.
        J Vasc Surg. Aug 2000; 32: 322-329
        • Oien R.F.
        • Håkansson A.
        • Hansen B.U.
        Leg ulcers in patients with rheumatoid arthritis—a prospective study of aetiology, wound healing and pain reduction after pinch grafting.
        Rheumatology (Oxford). Jul 2001; 40: 816-820
        • Reddy V.
        • Dziadzio M.
        • Hamdulay S.
        • Boyce S.
        • Prasad N.
        • Keat A.
        Lupus and leg ulcers—a diagnostic quandary.
        Clin Rheumatol. Jul 2007; 26: 1173-1175
        • Clarke J.T.
        • Werth V.P.
        Rheumatic manifestations of skin disease.
        Curr Opin Rheumatol. Jan 2010; 22: 78-84
        • Chapnick S.L.
        • Merkel P.A.
        Skin ulcers in a patient with Sjögren's syndrome.
        Arthritis Care Res. Jul 2010; 62: 1040-1046
        • Kerr G.S.
        • Aggarwal A.
        • McDonald-Pinkett S.
        A woman with rheumatoid arthritis, Sjögren's syndrome, leg ulcer, and significant weight loss.
        Arthritis Care Res. May 2012; 64: 785-792
        • Dabiri G.
        • Falanga V.
        Connective tissue ulcers.
        J Tissue Viability. Nov 2013; 22: 92-102
        • Chia H.Y.
        • Tang M.B.
        Chronic leg ulcers in adult patients with rheumatological diseases — a 7-year retrospective review.
        Int Wound J. 2014; 11: 601-604
        • Doveri M.
        • Della Rossa A.
        • Salvadori S.
        • D'Ascanio A.
        • Tavoni A.
        • Bazzichi L.
        • et al.
        Systemic sclerosis: outcome and long term follow-up of 429 patients from a single italian centre.
        Ann Rheum Dis. 2011; 70: 660
        • Hachulla E.
        • Clerson P.
        • Launay D.
        • Lambert M.
        • Morell-Dubois S.
        • Queyrel V.
        • et al.
        Natural history of ischemic digital ulcers in systemic sclerosis: single-center retrospective longitudinal study.
        J Rheumatol. 2007; 34: 2423-2430
        • Nitsche A.
        Raynaud, digital ulcers and calcinosis in scleroderma.
        Reumatol. Clin. 2012; 8: 270-277
        • Seitz C.S.
        • Berens N.
        • Bröcker E.B.
        • Trautmann A.
        Leg ulceration in rheumatoid arthritis—an underreported multicausal complication with considerable morbidity: analysis of thirty-six patients and review of the literature.
        Dermatology. 2010; 220: 268-273
        • Shanmugam V.K.
        • Steen V.D.
        • Cupps T.R.
        Lower extremity ulcers in connective tissue disease.
        Isr Med Assoc J. 2008; 10: 534-536
        • Taniguchi T.
        • Asano Y.
        • Hatano M.
        • Tamaki Z.
        • Tomita M.
        • Kawashima T.
        • et al.
        Effects of bosentan on nondigital ulcers in patients with systemic sclerosis.
        Br J Dermatol. 2012; 166: 417-421
        • Wahezi D.M.
        • Ilowite N.T.
        • Kenney-Riley K.M.
        • Belamarich P.F.
        Chronic leg ulceration as the presenting feature of diffuse systemic sclerosis in childhood.
        J Pediatr. 2011; 159: 698
        • Ernst E.
        • Hein A.
        • Meurer M.
        • Ruzicka T.
        Blood rheology in lupus erythematosus.
        Ann Rheum Dis. Oct 1991; 50: 710-712
        • Simón J.A.
        • Lazo-Langner A.
        • Duarte-Rojo A.
        • Velázquez-González A.
        • Sánchez-Guerrero S.A.
        • Sánchez-Guerrero J.
        Serum hyperviscosity syndrome responding to therapeutic plasmapheresis in a patient with primary Sjögren's syndrome.
        J Clin Apher. 2002; 17: 44-46
        • Spengler M.I.
        • Svetaz M.J.
        • Leroux M.B.
        • Bertoluzzo S.M.
        • Carrara P.
        • Van Isseldyk F.
        • et al.
        Erythrocyte aggregation in patients with systemic lupus erythematosus.
        Clin Hemorheol Microcirc. 2011; 47: 279-285
        • Lo Presti R.
        • Milio G.
        • Montana M.
        • Lucido D.
        • Raimondi F.
        • Caimi G.
        Effetti emoreologici del trattamento con iloprost in pazienti con fenomeno di Raynaud secondario a sclerodermia.
        Minerva Cardioangiol. 2006; 54: 221-222
        • Luquita A.
        • Urli L.
        • Dominighini A.
        • Svetaz M.J.
        • Gennaro A.M.
        • Volpintesta R.
        • et al.
        Haemorheological variables as a rheumatoid arthritis activity indicator.
        Clin Hemorheol Microcirc. 2004; 30: 9-16
        • Luquita A.
        • Urli L.
        • Svetaz M.J.
        • Gennaro A.M.
        • Volpintesta R.
        • Palatnik S.
        • et al.
        Erythrocyte aggregation in rheumatoid arthritis: cell and plasma factor's role.
        Clin Hemorheol Microcirc. 2009; 41: 49-56
        • Rosenson R.S.
        • Shott S.
        • Katz R.
        Elevated blood viscosity in systemic lupus erythematosus.
        Semin Arthritis Rheum. 2001; 31: 52-57
        • Vayá A.
        • Suescun M.
        • Micó L.
        • Todolí J.
        • Ricart J.M.
        Hemorheological profile in primary Sjögren's syndrome: a case-control study.
        Clin Hemorheol Microcirc. 2011; 47: 287-293
        • Tsai A.G.
        • Acero C.
        • Nance P.R.
        • Cabrales P.
        • Frangos J.A.
        • Buerk D.G.
        • et al.
        Elevated plasma viscosity in extreme hemodilution increases perivascular nitric oxide concentration and microvascular perfusion.
        Am J Physiol Heart Circ Physiol. 2005; 288: H1730-H1739
        • Cabrales P.
        • Tsai A.G.
        Plasma viscosity regulates systemic and microvascular perfusion during acute extreme anemic conditions.
        Am J Physiol Heart Circ Physiol. 2006; 291: H2445-H2452
        • Tsai A.G.
        • Friesenecker B.
        • McCarthy M.
        • Sakai H.
        • Intaglietta M.
        Plasma viscosity regulates capillary perfusion during extreme hemodilution in hamster skinfold model.
        Am J Physiol. 1998; 275: H2170-H2180