RSS-Feed abonnieren
DOI: 10.1055/s-2003-44641
Impact of Rheological Variables in Cancer
Publikationsverlauf
Publikationsdatum:
21. November 2003 (online)
![](https://www.thieme-connect.de/media/sth/200305/lookinside/thumbnails/10.1055-s-2003-44641-1.jpg)
ABSTRACT
Rheological alterations are commonly found in malignant disease and are most pronounced in advanced-stage cancer. Although most of these changes are caused by cancer-unspecific mechanisms, it has been shown that the extent of these changes in some cancer types is related with the stage of cancer, prognosis of disease, and the patient's risk for thrombosis. Monitoring of rheological variables during follow-up of patients has been useful in gynecologic cancer; a significant increase in the main determinants of blood viscosity was found when metastasis became clinically apparent. The most frequent constellation in newly diagnosed cancer is an increase in plasma viscosity (PV) and red blood cell (RBC) aggregation that produces hyperviscosity and is compensated for by anemia. Unconditional elevation of the hematocrit in cancer can deteriorate microcirculatory flow properties and may plunge the patient into an undesirable hemorheological condition that limits effectiveness of cytoreductive treatment and favors dissemination of cancer cells and the development of thrombosis. Modification of hyperviscosity, most likely at the plasma level, may represent a concept for cancer treatment and prevention of thrombosis. Anticoagulants and anti-inflammatory substances seem most suitable at this point, because high fibrinogen turnover is an important determinant of hyperviscosity in malignancy.
KEYWORDS
Hyperviscosity - cancer prognosis - anemia - thrombosis - plasma viscosity
REFERENCES
- 1 Rickles F R, Levine M, Edwards R L, Moritz T E, Zacharski L R. Abnormalities of blood coagulation in patients with cancer. In: Serneri GGN, Gensini GF, Abbate R, Prisco D, eds. Thrombosis An Update Scientific Press 1992 : 241-260
- 2 von Tempelhoff G-F, Heilmann L. Thrombosis and hemorheology in patients with breast cancer and adjuvant chemotherapy. Clin Hemorheol . 1995; 15 311-323
- 3 Riley V. Erythrocyte sedimentation rate in breast cancer. Science . 1976; 191 86-88
- 4 Miller B, Heilmann L. Hemorheologic variables in breast cancer patients at the time of diagnosis and during treatment. Cancer . 1988; 62 350-354
- 5 Laffargue F, Brun J F, Boulet P, Elbouhmadi A, Orsetti A. Blood rheology in ovarian cancer (Abst). Clin Hemorheol . 1995; 15 550
- 6 El Bouhmadi A, Laffargue F, Brun J F. Aggregability and disaggregability of erythrocytes in women suffering from ovarian cancer: evidence for an increased disaggregation threshold. Clin Hemorheol Microcirc . 2000; 22 91-97
- 7 von Tempelhoff G-F, Heilmann L, Hommel G. et al . Hyperviscosity syndrome in ovarian malignancy. Cancer . 1998; 82 1104-1111
- 8 Miller B, Heilmann L. Hemorheological parameters in patients with gynecologic malignancies. Gynecol Oncol . 1989; 33 177-181
- 9 Chen H, Yunpeng W, Shaoxi C, Mian L A. Research on rheological properties of erythrocyte of lung cancer patients. Clin Hemorheol . 1996; 16 135-141
- 10 Khan M M, Puniyani R R, Huilgol N G, Hussain M A, Ranade G G. Hemorheological profiles in cancer patients. Clin Hemorheol . 1995; 15 37-44
- 11 Ranade G G, Puniyana R R, Huilgol N G, Khan M M. Application of PV to assess the status of cancer patients. Clin Hemorheol . 1995; 15 755-761
- 12 Beshara S, Letocha H, Linde T. et al . Anemia associated with advanced prostatic adenocarcinoma: effects of recombinant human erythropoietin. Prostate . 1997; 31 153-160
- 13 Dintenfass L. Elevation of PV and of aggregation of red cells in melanoma metastasis. Biorheology . 1978; 15 99-110
- 14 Dintenfass L. Hemorheology of cancer metastases: an example of malignant melanoma. Survival times and abnormality of blood viscosity factors. Clin Hemorheol . 1982; 2 259-271
- 15 Humphreys W V, Walker A, Charlesworth D. Altered viscosity and yield stress in patients with abdominal malignancy: relationship to deep venous thrombosis. Br J Surg . 1976; 63 559-561
- 16 Tietjen G W, Chien S, Scholz P, Gump F E, Kinney J M. Changes in blood viscosity and plasma proteins in carcinoma. J Surg Oncol . 1977; 9 53-59
- 17 Lowe G DO. Rheological influences on thrombosis. Baillieres Clin Haematol . 1994; 7 573-589
- 18 Lip G Y, Chin B S, Blann A D. Cancer and the prothrombotic state. Lancet Oncol . 2002; 3 27-34
- 19 Dintenfass L. Hemorheology of cancer metastasis-an example of malignant melanoma, survival times and abnormality of blood viscosity factors. Clin Hemorheol . 1982; 2 259-271
- 20 von Tempelhoff G-F, Schönmann N, Pollow K, Hommel G, Heilmann L. Prognostic role of PV in breast cancer. Clin Hemorheol Microcirc Blood Flow Vessels . 2002; 26 55-61
- 21 Weiss L. The hemodynamic destruction of circulating cancer cells. Biorheology . 1987; 24 105-115
- 22 Dong C, Slattery M J, Rank B M, You J. In vitro characterization and micromechanics of tumor cell chemotatic protrusion, locomotion, and extravasation. Ann Biomed Eng . 2002; 30 344-355
- 23 Singh A, Eckardt K U, Zimmermann A. et al . Increased PV as a reason for inappropriate erythropoietin formation. J Clin Invest . 1993; 91 251-256
- 24 Baish J W, Gazit Y, Berk D A. et al . Role of tumor vascular architecture in nutrient and drug delivery: an invasion percolation-based network model. Microvasc Res . 1996; 51 327-346
- 25 Chahwala S B, Hickmann J A. Effect of the antitumor drug adriamycin on human blood cell discocyte-echinocyte transitions. Cancer Res . 1985; 45 4986-4989
- 26 Vasigara-Singh W, Subramaniam S, Shyama S, JagadeEsan M, Sshyamala-Devi C S. Changes in erythrocyte membrane lipids in breast cancer patients after radiotherapy and chemotherapy. Chemotherapy . 1996; 42 65-70
- 27 Levine M N. Prevention of thrombotic disorders in cancer patients undergoing chemotherapy. Thromb Haemost . 1999; 78 133-136
- 28 Denko N C, Giaccia A J. Tumor hypoxia, the physiological link between Trousseaus's syndrome (carcinoma induced coagulopathy) and metastasis. Cancer Res . 2001; 61 795-798
- 29 Keller D K, Nauth C, Thews O, Krueger W, Vaupel P. Localized hypothermia: impact on oxygenation, microregional perfusion, metabolic and bioenergetic status of subcutaneous rat tumours. Br J Cancer . 1998; 78 56-61
- 30 Baron J A, Cole B F, Sandler R S. et al . Randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med . 2003; 348 891-899
- 31 Zacharski L R. Anticoagulants in cancer treatment: malignancy as a solid phase coagulopathy. Cancer Lett . 2002; 186 1-9
- 32 Konerding M A, van Ackern A C, Fait E, Steinberg F, Streffer C. Morphologic aspects of tumor angiogenesis and microcirculation. In: Molls M, Vaupel P, eds. Blood Perfusion and Microenvironment of Human Tumors Berlin: Springer-Verlag 1998: 5-18
- 33 Less J R, Posner M C, Boucher Y. et al . Interstitial hypertension in human tumors. Cancer Res . 1992; 52 6371
- 34 Milosevic M F, Fyles A W, Hill R P. The relationship between elevated interstitial fluid pressure and blood flow in tumors: a bioengineering analysis. Int J Radiat Oncol Biol Phys . 1999; 43 1111-1112
- 35 Jain R K. Determinants of tumor blood flow: a review. Cancer Res . 1988; 48 2641-2658
- 36 Sevick E M, Jain R K. Blood flow and venous pH of tissue-isolated Walker 256 carcinoma during hyperglycemia. Cancer Res . 1988; 48 1201-1207
- 37 Lowe G DO. Blood rheology, haemostasis and vascular disease. In: Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD, eds. Haemostasis and Thrombosis London: Churchill Livingstone 1994: 1169-1188
- 38 Butler T P, Grantham F H, Gullino P M. Bulk transfer of fluid in the interstitial compartment of mammary tumors. Cancer Res . 1975; 35 512-516
- 39 Funakoshi N, Onizuka M, Yanagi K. et al . A new model of lung metastasis for intravital studies. Microvasc Res . 2000; 59 361-367
- 40 Lane D W, L'Anson S. Viscosimetric effect of fibrinogen. J Clin Pathol . 1994; 47 1004-1005
- 41 Dintenfass L, Kammer S. PV in 615 subjects. Effect of fibrinogen, globulin, and cholesterol in normals, peripheral vascular disease retinopathy, and melanoma. Biorheology . 1977; 14 247-251
- 42 Dintenfass L. Criteria and values in diagnosis and treatment, and prevention of metastasis in neoplastic disease. In: Dintenfass L, ed. Rheology of Blood in Diagnostic and Preventive Medicine London: Butterworths 1976: 137-162
- 43 von Tempelhoff G-F, Nieman F, Hommel G, Heilmann L. Association between blood rheology, thrombosis, and cancer survival in patients with gynecologic malignancy. Clin Hemorheol Microcirc Blood Flow Vessels . 2000; 22 107-130
- 44 Thompson D K, Haddow J E, Smithe D E, Ritchi R F. Elevated serum acute phase protein levels as predictors of disseminated breast cancer. Cancer . 1983; 51 2100-2104
- 45 Jung F, Kieseweter H, Roggenkamp H G, Nüttgens H P, Ringelstein E B. Bestimmung der Referenzbereiche rheologischer Parameter: Studie an 653 zufällig ausgewählten Probanden im Kreis Aachen. Klin Wochenschr . 1986; 64 375-381
- 46 von Tempelhoff G-F, Heilmann L. Coagulation disorders in gynecologic malignancy. In: Rath W, Heilmann L, eds. Coagulation Disorders in Obstetrics and Gynecology New York: Thieme 1999: 66-88
- 47 Zacharski L R, Memoli V A, Ornstein D L. et al . Tumor cell procoagulant and urokinase expression in carcinoma of the ovary. J Natl Cancer Inst . 1993; 85 1225-1230
- 48 Moradi M M, Carson L F, Weinberg B. et al . Serum and ascitic fluid levels of interleukin-1, interleukin-6, and tumor necrosis factor alpha in patients with ovarian epithelial cancer. Cancer . 1993; 72 2433-2440
- 49 Semeraro N, Montemurro P, Conese M. et al . Procoagulant activity of mononuclear phagocytes from different anatomical sites in patients with gynecological malignancies. Int J Cancer . 1990; 45 251-254
- 50 Zacharski L R, Howell A L, Memoli V A. The coagulation biology of cancer. Fibrinolysis . 1992; 6(suppl) 39-42
- 51 Sorensen H T, Mellemkjaer L, Olsen J, Baron J A. Prognosis of cancers associated with venous thromboembolism. N Engl J Med . 2000; 343 1846-1850
- 52 Schulman S, Lindmarker P. Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. Duration of anticoagulation trial. N Engl J Med . 2000; 342 1953-1958
- 53 von Tempelhoff G-F, Heilmann L, Hommel G. Thrombosis-a clue of poor prognosis in primary non-metastatic breast cancer. Breast Cancer Res Treatment . 2002; 73 275-277
- 54 Zacharski L R, Henderson W G, Rickles F R. et al . Effect of sodium warfarin on survival in small carcinoma of the lung. JAMA . 1981; 245 831-835
- 55 Hettiarachchi R JK, Smorenburg S M, Ginsberg J. et al . Do heparins do more than just treat thrombosis?. <~>The influence of heparins on cancer spread. Thromb Haemost . 1999; 82 947-952
- 56 Goldhaber S Z. Epidemiology of pulmonary embolism and deep vein thrombosis. In: Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD, eds. Haemostasis and Thrombosis London: Churchill Livingstone 1994: 1327-1333
- 57 Balendra R, Rumley A, Orr M. et al . Blood lipids, coagulation, fibrinolysis and rheology in spontaneous proven deep vein thrombosis (Abst). Br J Haematol . 1991; 77 (suppl 1) 83-(Abst)
- 58 Chabanel A, Horellou M H, Conrad J, Samama M M. Red blood cell aggregability in patients with a history of leg vein thrombosis: influence of postthrombotic treatment. Br J Haematol . 1994; 88 174-179
- 59 Mercke C E. Anemia in patients with solid tumours and the role of erythrocyte deformability. Br J Cancer . 1981; 44 425-432
- 60 Thomas D P. Pathogenesis of venous thrombosis. In: Colman RW, Hirsh J, Marder VJ, Salzman EW, eds. Hemostasis and Thrombosis Philadelphia: JB Lippincott 1982: 820-830
- 61 Patterson W P, Caldwell C W, Doll D C. Hyperviscosity syndromes and coagulopathies. Semin Oncol . 1990; 17 210-216
- 62 von Tempelhoff G-F, Pollow K, Schneider D M, Heilmann L. State of the art: Chemotherapy and thrombosis in gynaecological malignancy. Clin Appl Thromb Hemost . 1999; 5 92-104
- 63 Subramaniam S, Subramaniam S, Aagadeesan M, Devi S SC. Alterations in erythrocyte membrane structure of breast cancer patients treated with CMF-a lipid profile. Chemotherapy . 1994; 40 427-430
- 64 Vasigara-Singh W, Subramaniam S, Shyama S, Jagade Esan M, Shyamala-Devi C S. Changes in erythrocyte membrane lipids in breast cancer patients after radiotherapy and chemotherapy. Chemotherapy . 1996; 42 65-70
- 65 Baerlocher G M, Beer J H, Owen G R, Meiselman H J, Reinhart W H. The anti-neoplastic drug 5-fluorouracil produces echinocytosis and affects blood rheology. Br J Haematol . 1997; 99 426-432
- 66 Chahwala S B, Hickmann J A. Effect of the antitumor drug adriamycin on human blood cell discocyte-echinocyte transitions. Cancer Res . 1985; 45 4986-4989
- 67 Mark M, Walter R, Meredith D O, Reinhart W H. Commercial taxane formulations induce stomatocytosis and increase blood viscosity. Br J Pharmacol . 2001; 134 1207-1214
- 68 von Tempelhoff G-F, Heilmann L. Thrombosis and hemorheology in patients with breast cancer and adjuvant chemotherapy. Clin Hemorheol . 1995; 15 311-323
- 69 Cwikiel M, Persson S U, Larsson H, Albertsson M, Eskilsson J. Changes of blood viscosity in patients treated with 5-fluorouracil-a link to cardiotoxicity?. Acta Oncol . 1995; 34 83-85
- 70 von Tempelhoff G-F, Niemann F, Schneider D. et al . Blood rheology during chemotherapy in patients with ovarian cancer. Thromb Res . 1998; 90 73-82
- 71 Rapp S. Hemorheology in Cervical and Endometrial Cancer Patients. Mainz, Germany: Johannes Gutenberg Universität Mainz; 2001. Inaugural dissertation
- 72 Höckel M, Schlenger K, Aral B. et al . Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res . 1996; 56 4509-4515
- 73 Vaupel P, Schlenger K, Knoop C, Höckel M. Oxygenation of human tumors: elevation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements. Cancer Res . 1991; 51 3316-3322
- 74 Vaupel P, Briest S, Hockel M. Hypoxia in breast cancer: pathogenesis, characterization and biological/therapeutic implications. Wien Med Wochenschr . 2002; 152 334-342
- 75 von Tempelhoff G-F, Hommel G, Heilmann L Tumor hypoxia, the physiological link between Trousseau's syndrome (carcinoma induced coagulopathy) and metastasis. Cancer Res . 2001; 61 7697-7698
- 76 Akhtar N, Thompson J, Durrant S T. et al . The clinical relevance of plasma viscosity in Hodgkin's disease. Clin Lab Haematol . 1991; 13 1-8
- 77 Koenig W, Sund M, Lowel H, Doring A, Ernst E. Association between PV and all-cause mortality results from the MONICA-Augsburg Cohort Study 1984-92. Br J Haematol . 2000; 109 453-458
- 78 Grau C, Overgaard J. Significance of hemoglobin concentration for treatment outcome. In: Molls M, Vaupel P, eds. Blood Perfusion and Microenvironment of Human Tumors Berlin: Springer-Verlag 1998: 101-112
- 79 Obermair A, Handisurya A, Kaider A. et al . The relation of pretreatment serum hemoglobin level to the survival of epithelial ovarian carcinoma patients. Cancer . 1998; 83 726-731
- 80 Siragusa S, Cosmi B, Piovella F, Hirsh J, Ginsburg J S. Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis. Am J Med . 1996; 100 269-277
- 81 Vaupel P, Menke H. Blood flow, vascular resistance and oxygen availability in malignant tumors upon intravenous flunaritine. Adv Exp Med Biol . 1987; 215 393-398