Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2017  |  Volume : 13  |  Issue : 2  |  Page : 193-197

Thrombocytosis in gynecological cancers

Department of Radiation Oncology, VMMC and Safdarjung Hospital, New Delhi, India

Date of Web Publication23-Jun-2017

Correspondence Address:
Deepti Sharma
VMMC and Safdarjung Hospital, Room No 264, Second Floor, New OPD Block, New Delhi - 110 029
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.189234

Rights and Permissions
 > Abstract 

Thrombocytosis has been suggested to be a poor prognostic indicator in malignancies. Studies have shown that thrombocytosis is associated with a poor prognosis in various gynecological malignancies such as carcinoma ovary, cervical cancer, and endometrial cancer. The aim of this study is to analyze the impact of thrombocytosis on the prognosis of gynecological cancer. All the relevant data were retrieved by PubMed, MEDLINE, and Web of Science, and then studies were chosen in this analysis of association between thrombocytosis and gynecological malignancy. Thrombocytosis is common in advanced disease in patients with ovarian cancer, endometrial cancer, and cervical cancer. Therefore, it may be a marker of tumor burden or biologically more aggressive disease. Thrombocytosis is bad prognostic factor and associated with poorer outcomes.

Keywords: Gynecological malignancy, platelets, poor prognosis, thrombocytosis

How to cite this article:
Sharma D, Singh G. Thrombocytosis in gynecological cancers. J Can Res Ther 2017;13:193-7

How to cite this URL:
Sharma D, Singh G. Thrombocytosis in gynecological cancers. J Can Res Ther [serial online] 2017 [cited 2022 Nov 26];13:193-7. Available from: https://www.cancerjournal.net/text.asp?2017/13/2/193/189234

 > Introduction Top

The association of thrombocytosis with malignancies has been known for more than 100 years.[1] Thrombocytosis was reported in patients with lung [2] colon [2] renal cell carcinomas,[3] cervical cancer,[4],[5] ovarian cancer,[6] and vulvar cancers.[7] We conducted MEDLINE and PubMed search of literature on the prognostic impact of thrombocytosis in gynecological cancer. References of all publication were also searched. The aim of this study is to analyze the impact of thrombocytosis on the prognosis of gynecological cancer.

 > Etiopathology of Thrombocytosis Top

Thrombocytosis is defined as an elevated platelet counts above 4.5 × 109/L. Platelets are small, irregularly shaped anuclear cell fragments which are derived from fragmentation of precursor megakaryocytes.[8] Their production is regulated by thrombopoietin (TPO), a hormone usually produced by the liver and kidneys.[9] Old platelets are destroyed by phagocytosis in the spleen and by Kupffer cells in the liver.

 > Interaction of Tumor Cells and Platelets Top

Platelets participate in tumor progression by contributing to the metastatic cascade, protecting tumor cells from immune surveillance, regulating tumor cell invasion, and angiogenesis.[10],[11] Thrombin is being generated either by direct contact with platelets or indirectly by stimulating tissue factor-mediated activation of the coagulation system.[12] The ovarian cancer-induced platelet activation is mediated by adenosine 59-diphosphate released from tumor cells and can be blocked by adenosine 59-diphosphate receptor (P2Y12 and P2Y1) antagonists.[13] Certain studies have also shown that tumor cells could lead to secretion of dense granules containing adenine nucleotides via the platelet Fcg receptor IIa.[14] Platelet activation by tumors throughout all phases of the metastatic cascade leads to the release of platelet-derived factors stored in their granules leading to inflammatory, proliferative, and proangiogenic activities of platelets to promote tumor growth, tissue invasion, and metastasis.[15] The platelets secrete thrombospondin-1 which facilitates the adhesion of tumor cells to the endothelium and promotes extravasations in the metastatic cascade.[16] The thrombospondin levels have found to be elevated in women with gynecologic malignancies. Once the tumor cells have exited circulation, factors derived from activated platelets are able to induce neoangiogenesis, thereby enabling growth at the metastatic site.[17]

Reactive or secondary thrombocytosis associated with malignancies has been established since the early 1870s, with an incidence of 10–57%.[16] Possible mechanisms include an overproduction of cytokines/growth factors stimulating megakaryocytes and their precursors. Serum interleukin (IL-6) is increased in most patients with reactive thrombocytosis, and elevation of this cytokine has been detected in a significant number of patients with cancer. Bone marrow endothelial cells, kidney, and spleen are capable of TPO production. TPO is produced and released into the circulation at a constant rate by the liver.[18] Normal physiology of platelet production involves the clearance of TPO by high-affinity TPO receptors on platelets and formation of a steady TPO concentration, thereby providing a basal stimulation of bone marrow megakaryocytes and normal rate of platelet production. However, in secondary thrombocytosis that can occur with malignancies, there can be upregulation of TPO production by the liver causing enhanced thrombopoiesis. Plasma TPO levels have also been shown to correlate with IL-6.[19] Platelets have capabilities to enhance sequestration, adherence, and penetration of malignant cells through the endothelial wall.[16] They may also prevent the immune system from clearing tumor cells from the circulatory system. Tumor growth depends on the formation of new blood vessels from preexisting capillaries (i.e., angiogenesis).[20] Tumor angiogenesis depends not only on endothelial cells and cancer cells but also on platelet-endothelium interactions. Platelets adhere to the tumor-related endothelium and release high concentrations of vascular endothelial growth factor (VEGF), which is a potent stimulator of angiogenesis.

Platelet granules contain a variety of factors such as VEGF, basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor beta (TGF-β), IL-6, thrombin, and fibrinogen.[21] These modulators are secreted immediately after platelet activation, and many have been implicated in various steps of tumor progression and the development of metastasis. TGF-β has an active role in platelet aggregation, regulation of megakaryocyte activity, and activity of the VEGF system [Table 1].[22]
Table 1: Summary of studies on thrombocytosis in gynecological cancers

Click here to view

 > Thrombocytosis in Carcinoma Ovary Top

Thrombocytosis is more common in carcinoma ovary as compared to benign tumors.[44] In different studies, the prevalence of thrombocytosis ranges from 7% to 43%.[6],[23],[32] Crasta et al. revealed that patients with preoperative thrombocytosis were found to have lower hemoglobin (P < 0.0002), advanced stage (P < 0.05), and higher grade tumors (P < 0.02).[23] Zeimet et al. investigated 130 women with epithelial ovarian tumors and found that thrombocytosis was associated with advanced stage disease, higher serum levels of CA 125, ascites, and greater chance of suboptimal cytoreduction.[6]

Menczer et al. carried out a similar retrospective study in a cohort of seventy patients with invasive epithelial ovarian carcinoma and reported a higher incidence of thrombocytosis in women with advanced stage disease and significantly shorter periods of survival.[24] Other studies also found that thrombocytosis was significantly correlated with advanced stage and higher grade epithelial ovarian tumors, lymph node metastases, greater volume of ascites, and less optimal tumor cytoreduction with significantly shorter disease-free and overall survival.[25],[26]

 > Thrombocytosis in Endometrium Carcinoma Top

Preoperative thrombocytosis is an independent prognostic factor in Stage III and IV endometrial cancer was studied by Scholz et al. They reported that 5 years disease-free survival and overall survival were influenced significantly by FIGO stage, thrombocytosis, and cervical involvement.[33]

Gorelick et al. evaluated the role of preoperative thrombocytosis and its association with survival in a predominantly African-American and Caribbean-American urban population. Fourteen (18.2%) of 77 patients exhibited thrombocytosis. The median overall survival in patients without thrombocytosis was 24.0 ± 4.5 months (n = 21) and in patients with thrombocytosis was 7.0 ± 3.8 months (n = 8, P= 0.015). Data indicated that preoperative thrombocytosis among high-risk inner-city patients with Stages III to IV endometrial cancer is an independent prognostic indicator.[34] In a recent study, Gu et al. showed that the prevalence of thrombocytosis increases with stage. Furthermore, patients with thrombocytosis died at a younger age as compared to those with normal platelet count (64.3 years and 74.5 years, respectively).[37]

 > Thrombocytosis in Cervical Cancer Top

Thrombocytosis has been suggested to be a poor prognostic indicator in patients with cervical cancer. In a retrospective study by De Jonge et al., cumulative survival rate for the 93 patients with normal platelet counts was 65% whereas it was 25% for the twenty with thrombocytosis.[38]

Lopes et al. reviewed pretreatment platelet counts of 643 women treated for cervical cancer between 1983 and 1992 and correlated to each patient's age, stage of disease, histologic type, node status (when available), and outcome. The 5-year survival rate for patients with thrombocytosis was 57.1%, which was significantly worse than the 76.5% for those with normal platelet counts (P < 0.01). Thrombocytosis was not found to be an independent prognostic factor in patients with carcinoma of the cervix in this study.[39]

Kawano et al. showed that thrombocytosis is associated with younger age (P = 0.0003), an advanced clinical stage (P < 0.0001), larger tumor (P = 0.0025), lower hemoglobin levels (P < 0.0001), and more frequent treatment failure (P = 0.0015).[40]

 > Thrombocytosis in Vulvar Carcinoma Top

Ofer et al. reviewed pretreatment platelet counts of 201 women treated for vulvar cancer and correlated to the patient's age, stage of disease, node status, histologic type, and outcome. Thrombocytosis was presented in 14.92% of patients with vulvar malignancies and in 15.46% of patients with squamous cell carcinoma of the vulva. No correlation was found between thrombocytosis and tumor size, incidence of lymph node metastases, or stage of the disease. The 5-year survival rate for patients with thrombocytosis was 89.29%, which was not significantly different from the 76.47% 5-year survival of patients with normal platelet counts (P = 0.586). When adjusted for age, histological differentiation, number of tumors, staging, incidence of nodal metastases, platelet count, hemoglobin, and white blood count, only the staging, number of tumors, and histological differentiation were associated with an unfavorable prognosis (P = 0.0001, P= 0.003, P= 0.03, respectively). Thrombocytosis was not found to be a prognostic factor in patients with carcinoma of the vulva in this series of 201 patients.[42]

A study by Hefler et al. in 62 patients, also demonstrated that pretreatment tumor anemia (hemoglobin < 12 g/dL) and elevated platelet count (>300,000/ÌL) were significantly associated with a poor overall survival.[7]

 > Results Top

The association of thrombocytosis with malignancies has been known for more than 100 years. Various studies have shown that thrombocytosis is associated with a poor prognosis in various gynecological. Carcinoma ovary with thrombocytosis is associated with suboptimal tumor resection, raised CA125 level. Thrombocytosis is common in advanced disease in patients with ovarian cancer, endometrial cancer, and cervical cancer. Therefore, it may be a marker of tumor burden or biologically more aggressive disease.

 > Conclusion Top

The prevalence of thrombocytosis associated with various cancers portrays a worse survival, independent of other clinical or biochemical factors. With further studies, this single independent prognostic factor may provide a simple approach to improved risk stratification of patients in future clinical trial protocols.


We acknowledge the help of our families, especially our little angels (Avishi and Saranya) for providing time and support.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 > References Top

Reiss L. Zur Pathologischen Anaatomie des Blutes. Arch Anat Physiol Wiss Med 1872;39:237-49.  Back to cited text no. 1
Costantini V, Zacharski LR, Moritz TE, Edwards RL. The platelet count in carcinoma of the lung and colon. Thromb Haemost 1990;64:501-5.  Back to cited text no. 2
Symbas NP, Townsend MF, El-Galley R, Keane TE, Graham SD, Petros JA. Poor prognosis associated with thrombocytosis in patients with renal cell carcinoma. BJU Int 2000;86:203-7.  Back to cited text no. 3
Rodriguez GC, Clarke-Pearson DL, Soper JT, Berchuck A, Synan I, Dodge RK. The negative prognostic implications of thrombocytosis in women with stage IB cervical cancer. Obstet Gynecol 1994;83:445-8.  Back to cited text no. 4
Hernandez E, Donohue KA, Anderson LL, Heller PB, Stehman FB. The significance of thrombocytosis in patients with locally advanced cervical carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 2000;78:137-42.  Back to cited text no. 5
Zeimet AG, Marth C, Müller-Holzner E, Daxenbichler G, Dapunt O. Significance of thrombocytosis in patients with epithelial ovarian cancer. Am J Obstet Gynecol 1994;170:549-54.  Back to cited text no. 6
Hefler L, Mayerhofer K, Leibman B, Obermair A, Reinthaller A, Kainz C, et al. Tumor anemia and thrombocytosis in patients with vulvar cancer. Tumour Biol 2000;21:309-14.  Back to cited text no. 7
Burstein SA, Harker LA. Control of platelet production. Clin Haematol 1983;12:3-22.  Back to cited text no. 8
Qian S, Fu F, Li W, Chen Q, de Sauvage FJ. Primary role of the liver in thrombopoietin production shown by tissue-specific knockout. Blood 1998;92:2189-91.  Back to cited text no. 9
Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, et al. Platelets and fibrin (ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood 2005;105:178-85.  Back to cited text no. 10
Battinelli EM, Markens BA, Kulenthirarajan RA, Machlus KR, Flaumenhaft R, Italiano JE Jr. Anticoagulation inhibits tumor cell-mediated release of platelet angiogenic proteins and diminishes platelet angiogenic response. Blood 2014;123:101-12.  Back to cited text no. 11
Bambace NM, Holmes CE. The platelet contribution to cancer progression. J Thromb Haemost 2011;9:237-49.  Back to cited text no. 12
Egan K, Crowley D, Smyth P, O'Toole S, Spillane C, Martin C, et al. Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells. PLoS One 2011;6:e26125.  Back to cited text no. 13
Mitrugno A, Williams D, Kerrigan SW, Moran N. A novel and essential role for FcγRIIa in cancer cell-induced platelet activation. Blood 2014;123:249-60.  Back to cited text no. 14
Sharma D, Brummel-Ziedins KE, Bouchard BA, Holmes CE. Platelets in tumor progression: A host factor that offers multiple potential targets in the treatment of cancer. J Cell Physiol 2014;229:1005-15.  Back to cited text no. 15
Levin J, Conley CL. Thrombocytosis associated with malignant disease. Arch Intern Med 1964;114:497-500.  Back to cited text no. 16
Tuszynski GP, Gasic TB, Rothman VL, Knudsen KA, Gasic GJ. Thrombospondin, a potentiator of tumor cell metastasis. Cancer Res 1987;47:4130-3.  Back to cited text no. 17
Kopp HG, Placke T, Salih HR. Platelet-derived transforming growth factor-beta down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res 2009;69:7775-83.  Back to cited text no. 18
Hollen CW, Henthorn J, Koziol JA, Burstein SA. Elevated serum interleukin-6 levels in patients with reactive thrombocytosis. Br J Haematol 1991;79:286-90.  Back to cited text no. 19
Suppiah R, Shaheen PE, Elson P, Misbah SA, Wood L, Motzer RJ, et al. Thrombocytosis as a prognostic factor for survival in patients with metastatic renal cell carcinoma. Cancer 2006;107:1793-800.  Back to cited text no. 20
Möhle R, Green D, Moore MA, Nachman RL, Rafii S. Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc Natl Acad Sci U S A 1997;94:663-8.  Back to cited text no. 21
Viñals F, Pouysségur J. Transforming growth factor beta1 (TGF-beta1) promotes endothelial cell survival during in vitro angiogenesis via an autocrine mechanism implicating TGF-alpha signaling. Mol Cell Biol 2001;21:7218-30.  Back to cited text no. 22
Crasta JA, Premlatha TS, Krishnan SM, Vallikad E, Rameshkumar K. Significance of preoperative thrombocytosis in epithelial ovarian cancer. Indian J Pathol Microbiol 2010;53:54-6.  Back to cited text no. 23
[PUBMED]  [Full text]  
Menczer J, Schejter E, Geva D, Ginath S, Zakut H. Ovarian carcinoma associated thrombocytosis. Correlation with prognostic factors and with survival. Eur J Gynaecol Oncol 1998;19:82-4.  Back to cited text no. 24
Li AJ, Madden AC, Cass I, Leuchter RS, Lagasse LD, Karlan BY. The prognostic significance of thrombocytosis in epithelial ovarian carcinoma. Gynecol Oncol 2004;92:211-4.  Back to cited text no. 25
Gungor T, Kanat-Pektas M, Sucak A, Mollamahmutoglu L. The role of thrombocytosis in prognostic evaluation of epithelial ovarian tumors. Arch Gynecol Obstet 2009;279:53-6.  Back to cited text no. 26
Allensworth SK, Langstraat CL, Martin JR, Lemens MA, McGree ME, Weaver AL, et al. Evaluating the prognostic significance of preoperative thrombocytosis in epithelial ovarian cancer. Gynecol Oncol 2013;130:499-504.  Back to cited text no. 27
Stone RL, Nick AM, McNeish IA, Balkwill F, Han HD, Bottsford-Miller J, et al. Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med 2012;366:610-8.  Back to cited text no. 28
Qiu J, Yu Y, Fu Y, Ye F, Xie X, Lu W. Preoperative plasma fibrinogen, platelet count and prognosis in epithelial ovarian cancer. J Obstet Gynaecol Res 2012;38:651-7.  Back to cited text no. 29
Digklia A, Voutsadakis IA. Thrombocytosis as a prognostic marker in stage III and IV serous ovarian cancer. Obstet Gynecol Sci 2014;57:457-63.  Back to cited text no. 30
Lee M, Kim SW, Nam EJ, Yim GW, Kim S, Kim YT. The impact of pretreatment thrombocytosis and persistent thrombocytosis after adjuvant chemotherapy in patients with advanced epithelial ovarian cancer. Gynecol Oncol 2011;122:238-41.  Back to cited text no. 31
Cohen JG, Tran AQ, Rimel BJ, Cass I, Walsh CS, Karlan BY, et al. Thrombocytosis at secondary cytoreduction for recurrent ovarian cancer predicts suboptimal resection and poor survival. Gynecol Oncol 2014;132:556-9.  Back to cited text no. 32
Scholz HS, Petru E, Gücer F, Haas J, Tamussino K, Winter R. Preoperative thrombocytosis is an independent prognostic factor in stage III and IV endometrial cancer. Anticancer Res 2000;20:3983-5.  Back to cited text no. 33
Gorelick C, Andikyan V, Mack M, Lee YC, Abulafia O. Prognostic significance of preoperative thrombocytosis in patients with endometrial carcinoma in an inner-city population. Int J Gynecol Cancer 2009;19:1384-9.  Back to cited text no. 34
Heng S, Benjapibal M. Preoperative thrombocytosis and poor prognostic factors in endometrial cancer. Asian Pac J Cancer Prev 2014;15:10231-6.  Back to cited text no. 35
Menczer J, Geva D, Schejter E, Zakut H. Elevated platelet count in patients with endometrial carcinoma: Correlation with selected prognostic factors and with survival. Int J Gynecol Cancer 1996;6:463-6.  Back to cited text no. 36
Gu D, Guo T, Szallasi A. Prognostic significance of preoperative thrombocytosis in patients with endometrial carcinoma: Our experience and review of the literature. Gynecol Oncol Trends 2015;1:1.  Back to cited text no. 37
De Jonge ET, Viljoen E, Lindeque BG, Amant F, Nesland JM, Holm R. The prognostic significance of p53, mdm2, c-erbB-2, cathepsin D, and thrombocytosis in stage IB cervical cancer treated by primary radical hysterectomy. Int J Gynecol Cancer 1999;9:198-205.  Back to cited text no. 38
Lopes A, Daras V, Cross PA, Robertson G, Beynon G, Monaghan JM. Thrombocytosis as a prognostic factor in women with cervical cancer. Cancer 1994;74:90-2.  Back to cited text no. 39
Kawano M, Mabuchi S, Matsumoto Y, Sasano T, Takahashi R, Kuroda H, et al. Prognostic significance of pretreatment thrombocytosis in cervical cancer patients treated with definitive radiotherapy. Int J Gynecol Cancer 2015;25:1656-62.  Back to cited text no. 40
Hernandez E, Heller PB, Whitney C, Diana K, Delgado G. Thrombocytosis in surgically treated stage IB squamous cell cervical carcinoma (A Gynecologic Oncology Group study). Gynecol Oncol 1994;55 (3 Pt 1):328-32.  Back to cited text no. 41
Ofer L, Giuseppe C, Vasillas D, Brendan SB, Alberto L, John M. Thrombocytosis in women with vulvar carcinoma. Gynecol Oncol 1999;72:82-6.  Back to cited text no. 42
Yu M, Liu L, Zhang BL, Chen Q, Ma XL, Wu YK, et al. Pretreatment thrombocytosis as a prognostic factor in women with gynecologic malignancies: A meta-analysis. Asian Pac J Cancer Prev 2012;13:6077-81.  Back to cited text no. 43
Hakverdi AU, Yayla M, Göcmen A, Gül T, Erden AC, Demiroglu S. The clinical significance of preoperative serum CA-125 levels and thrombocytosis in patients with pelvic mases. Jinekoloji Obstetrik Dergisi 1995;9:205-9.  Back to cited text no. 44


  [Table 1]

This article has been cited by
1 Haemostatic alterations in patients with cirrhosis and hepatocellular carcinoma: laboratory evidence and clinical implications
Alberto Zanetto, Elena Campello, Filippo Pelizzaro, Fabio Farinati, Patrizia Burra, Paolo Simioni, Marco Senzolo
Liver International. 2022;
[Pubmed] | [DOI]
2 Significance of platelet parameters in squamous cell carcinoma of oral cavity – A case-control study
Ankit Anand, Kalyani Raju, SM Azeem Mohiyuddin
Journal of Cancer Research and Therapeutics. 2022; 0(0): 0
[Pubmed] | [DOI]
3 Disi Köpeklerde Vajinal Hiperplazi ve Vajinal Tümörler ile Iliskili Hematolojik Parametrelerde Degisiklikler
Dicle Üniversitesi Veteriner Fakültesi Dergisi. 2021;
[Pubmed] | [DOI]
4 Prognostic significance of pretreatment thrombocytosis in endometrial cancer: an Israeli Gynecologic Oncology Group study
Ori Tal, Ram Eitan, Ofer Gemer, Limor Helpman, Zvi Vaknin, Sofia Leytes, Ofer Lavie, Alon Ben-Arie, Amnon Amit, Ahmet Namazov, Inbar Ben Shahar, Ilan Atlas, Ilan Bruchim, Tally Levy
International Journal of Gynecologic Cancer. 2021; 31(11): 1437
[Pubmed] | [DOI]
5 Dihydroartemisinin and its anticancer activity against endometrial carcinoma and cervical cancer: involvement of apoptosis, autophagy and transferrin receptor
T Tang, QJ Xia, MR Xi
Singapore Medical Journal. 2021; 62(2): 96
[Pubmed] | [DOI]
6 Laboratory parameters as predictors of prognosis in uterine cervical neoplasia
Patrícia Santos Vaz de Lima, Priscila Thais Silva Mantoani, Eddie Fernando Candido Murta, Rosekeila Simões Nomelini
European Journal of Obstetrics & Gynecology and Reproductive Biology. 2021; 256: 391
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Etiopathology of...>Interaction of T...>Thrombocytosis i...>Thrombocytosis i...>Thrombocytosis i...>Thrombocytosis i...>Results>Conclusion>Article Tables
  In this article

 Article Access Statistics
    PDF Downloaded311    
    Comments [Add]    
    Cited by others 6    

Recommend this journal