|Year : 2016 | Volume
| Issue : 2 | Page : 87-90
Cancer-associated thrombosis in some African populations: A growing concern
Hannah E Omunakwe1, Theresa U Nwagha2
1 Department of Pathology, Hematology Unit, Braithwaite Memorial Specialist Hospital, Port Harcourt, Rivers State, Nigeria
2 Department of Hematology and Immunology, Thrombosis and Bleeding Unit, University of Nigeria Teaching Hospital, Enugu State, Nigeria
|Date of Web Publication||12-Oct-2016|
Hannah E Omunakwe
Department of Pathology, Hematology Unit, Braithwaite Memorial Specialist Hospital, Port Harcourt, Rivers State
Source of Support: None, Conflict of Interest: None
The burden of cancer is gradually increasing in developing countries in Africa. This has accounted for significant rates of morbidity and mortality. The development of thrombosis in cancer patients impacts significantly on the outcome of care. Cancer-associated thrombosis may occur due to the stage of cancer, its organ site, treatment modality among other reasons. Some reports of studies of the management of patients with deep venous thrombosis (DVT) from African centers have identified malignancy as a significant risk factor for DVT. However, there are no reported studies in cancer patient groups to evaluate the prevalence, risk factors, and efficacy of prophylactic measures in Africa. This review focuses on the epidemiology, pathophysiology, risk indicators, and reports of thrombosis affecting cancer patients in Africa. The aim is to increase awareness and draw the attention of clinicians and oncologist in cancer management in Africa to the need for a robust multicenter research, establishing evidence-based interventions, and guidelines for improved patient outcome.
Keywords: Africa, cancer-associated thrombosis, deep venous thrombosis, risk assessment
|How to cite this article:|
Omunakwe HE, Nwagha TU. Cancer-associated thrombosis in some African populations: A growing concern. Int J Non-Commun Dis 2016;1:87-90
|How to cite this URL:|
Omunakwe HE, Nwagha TU. Cancer-associated thrombosis in some African populations: A growing concern. Int J Non-Commun Dis [serial online] 2016 [cited 2019 Oct 15];1:87-90. Available from: http://www.ijncd.org/text.asp?2016/1/2/87/192017
| Introduction|| |
The connection between cancer and thrombosis had been established over 140 years ago by Trousseau.  Since then, there have been many studies to provide significant evidence to attest to this patient with cancer are at increased risk of deep venous thrombosis (DVT). This could be as a result of aggressive antitumor therapy, surgery, use of central venous catheters or other access lines, or the etiology of cancer.  Cancer-associated thrombosis is underdiagnosed in patients with malignancies in Africa thus; morbidity and mortality due to venous thromboembolism (VTE) may be high. There is a growing pool of data and research in this area of medicine in many parts of the developed world. However, from Africa, there appears to be a paucity of research and data in this area. Some oncologists do not appreciate the link between cancer, its treatment, the risk of thrombosis and the need for thromboprophylaxis in patients at-risk.  According to the Frontline survey, 50% of surgical cancer and 95% of medical cancer patients did not receive appropriate thromboprophylaxis.  This paper reviews reports of venous thrombosis as it affects cancer patients, with a bid to shed light on the severity of cancer-associated thrombosis in Africa.
| Epidemiology of Cancer-associated Thrombosis|| |
The incidence of venous thrombosis differs according to race, in studies from America, it has been shown that African-Americans have over 5-fold greater incidence than Asian-ancestry populations, and an intermediate risk for European and Hispanic populations.  The overall incidence of VTE is 30-60% higher in blacks than in whites.  This holds true across age groups and for both men and women.  This however is thought to be influenced by some genetic factors and environmental factors. In developed countries, there is research, improved diagnostic equipment and apparently more awareness compared to developing countries. Although cancer is one of the strongest risk factors,  the rate of VTE in black and white hospitalized patients with cancer has been reported to be similar. 
The cancer patient is at a greater risk of VTE compared to the general population; they are thought to be in an acquired thrombophilic state.  They make up to 15-20% of patients diagnosed with VTE  and VTE is the second leading cause of mortality in cancer patients.  Overall, the incidence of clinically important thrombosis ranges from 5% to 60% in various malignancies.  Autopsy data find evidence of VTE in as many as 50% of cancer patients, but this does not define clinically significant events. ],[],[
Sometimes, VTE in cancer patients may be without clinical signs and symptoms,  the detection of asymptomatic VTE is becoming more frequent with computerized tomography scans performed for cancer staging  and they have a negative clinical impact on prognosis of cancer patients, which is similar to symptomatic VTE. 
For those who survive an episode of VTE, postthrombotic complications may have a significant impact on the quality of life.  The incidence of VTE in cancer patients in Africa may increase over time from contributing effects of improved awareness, heightened index of clinical suspicion among clinicians and oncologists, improved diagnostic capabilities for VTE as well as the use of novel anticancer therapeutic agents that promote VTE.
| Pathophysiology and Risk Indicators|| |
The bidirectional association between cancer and venous thrombosis has been known for almost two centuries, and this association has been widely studied; VTE is the clinically overt sign of up-regulation of the coagulation cascade in cancer. There is evidence that the activation of hemostasis in malignant disease contributes to tumor growth and progression by stimulation of intracellular signaling pathways.  Cancer cells utilize hemostatic constituents for their growth progression, and this involves multiple pathways. Cancer cells have a growth advantage with reduced sensitivity to programmed cell death-apoptosis. They also develop functions of increased motility and cellular adhesion. It has been well established that the essential factors of hemostasis (e.g. coagulation, fibrinolytic proteins, and platelets), apart from their pro-coagulant effects, directly play a role in these processes. However, fibrin formation itself is essential as a supportive scaffold for angiogenesis that ensures the tumor's oxygen supply. 
The risk factors for VTE in cancer patients have been grouped into patient-related (older age, female sex, race, comorbidities, lower performance status), cancer-related (site, advanced stage, histology, period after diagnosis), treatment-related factors (major surgery, hospitalization, hormonal therapy, chemotherapy, transfusions, etc.),  and candidate biomarkers of the risk of thrombosis have been identified  and validated.
| Venous Thrombosis in Cancer Patients from African Reports|| |
There have been reports of venous thrombosis from some centers in Africa as case reports, clinical experience of radiological diagnosis and treatment, postmortem findings of hospital deaths and risk groupings of hospitalized patients.
Early retrospective reports from Ibadan, Nigeria by Awotedu et al. in 1992, of pulmonary embolism in postmortem reports, showed a prevalence of 3.2% and cancer was one of the major predisposing factors.  Another retrospective report of 989 autopsies 10 years after Awotedu et al.'s report, from the same center, recorded 2.9% as the prevalence of venous thrombosis in postmortem cases, and malignancy was the most common predisposing factor in 37.9% of the cases. 
Apart from postmortem reports, some clinicians have reported their findings of predisposing factors and treatment of patients with thromboembolic diseases. Retrospective reports of management of sixty patients seen between 1986 and 1990 at the University College Hospital Ibadan did not include malignancy as a predisposing factor.  However, a revisit to the subject in the same facility, 17 years later (2007-2012) reported an increase to 178 cases of DVT treated in the hematology department, and cancer patients made up to 12.2% of cases treated; prostate cancer patients were most affected.  A report of the clinical and sonographic features of VTE as diagnosed in Cameroun by Kingue et al. showed neoplasia as one of the important risk factors in 22.2% of the patients evaluated. 
Muleledhu et al. in Uganda carried out a prospective study of DVT following major abdominal surgery for 82 patients. They found that 5% had DVT postsurgery and cancer was the commonest risk factor.  Fall et al. also did a 3 year cross-sectional case-control study of patients admitted to emergency wards on account of DVT or PE, in various hospitals in Dakar, Senegal.  Their results showed that cancer was a risk for VTE in 3.81% of the 105 patients evaluated during the study. The patients in this study were drawn largely from medical units and not surgical units. Another retrospective review of 865 Doppler ultrasound scan of patients suspected to have DVT in a South African public hospital showed that of 685 of them were confirmed to have DVT, 4.1% of them were patients who had a concomitant diagnosis of cancer. 
From the reports from different countries in Africa [Table 1], there is evidence to confirm that thromboembolic disease is significant comorbidity in cancer patients, and it is associated with substantial mortality. It will be expedient for clinicians in oncology care in Africa to have more awareness of this condition and risk assess their cancer patients for this condition. A risk stratification model developed by Khorana utilizes the site of tumor and laboratory indices that can be evaluated in most hospitals in Africa-leukocyte counts, platelet count, hemoglobin level, D-dimer and others biomarkers like soluble P-selectin and tissue factor levels , (which may not be routinely done in most of our hospitals). This model has been validated in many populations and has been used to predict cancer patients at high risk of VTE and thromboprophylaxis has been shown to be effective in reducing mortality.
| Conclusion|| |
The venous thromboembolic disease impacts significantly on the overall management of cancer patient. , We reiterate the need for more robust multicenter studies to test risk stratification models and their applicability in our setting. In most African communities where patients do out of pocket expenses for their treatment because of nonexisting cancer policies, subsidies on anticancer medications, health insurance schemes, thromboprophylaxis for at-risk cancer patients as well as early detection and treatment of cancer-related thrombosis could be a cost-effective strategy to reduce morbidity as well as improve the quality of life of these patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Trousseau A. Phlegmasia alba dolens. Clinique Medicale de l′Hotel-Dieu de Paris. Vol. 3. Paris: Baillière; 1865.
Bick RL. Cancer-associated thrombosis. N Engl J Med 2003;349:109-11.
Noble S, Pasi J. Epidemiology and pathophysiology of cancer-associated thrombosis. Br J Cancer 2010;102 Suppl 1:S2-9.
Kakkar AK, Levine M, Pinedo HM, Wolff R, Wong J. Venous thrombosis in cancer patients: Insights from the FRONTLINE survey. Oncologist 2003;8:381-8.
Zakai NA, McClure LA. Racial differences in venous thromboembolism. J Thromb Haemost 2011;9:1877-82.
Zakai N, Lutsey P, Folsom A, Cushman M. Black-white differences in venous thrombosis risk: The Longitudinal Investigation of Thromboembolism Etiology (LITE). Blood ASH Annu Meet Abstr 2010;116:478.
White RH, Zhou H, Romano PS. Incidence of idiopathic deep venous thrombosis and secondary thromboembolism among ethnic groups in California. Ann Intern Med 1998;128:737-40.
White RH, Keenan CR. Effects of race and ethnicity on the incidence of venous thromboembolism. Thromb Res 2009;123 Suppl 4:S11-7.
Stein PD, Beemath A, Meyers FA, Skaf E, Sanchez J, Olson RE. Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med 2006;119:60-8.
Walker AJ, Card TR, West J, Crooks C, Grainge MJ. Incidence of venous thromboembolism in patients with cancer - A cohort study using linked United Kingdom databases. Eur J Cancer 2013;49:1404-13.
Lee AY. Management of thrombosis in cancer: Primary prevention and secondary prophylaxis. Br J Haematol 2005;128:291-302.
Haddad TC, Greeno EW. Chemotherapy-induced thrombosis. Thromb Res 2006;118:555-68.
Sutherland DE, Weitz IC, Liebman HA. Thromboembolic complications of cancer: Epidemiology, pathogenesis, diagnosis, and treatment. Am J Hematol 2003;72:43-52.
Lyman GH, Khorana AA, Falanga A, Clarke-Pearson D, Flowers C, Jahanzeb M, et al.
American Society of Clinical Oncology guideline: Recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 2007;25:5490-505.
Rickles FR, Levine MN, Dvorak HB. Abnormalities of hemostasis in malignancy. In: Colman RW, Hirsh J, Marder VJ, Clowes A, George JN, editors. Hemostasis and Thrombosis. Ch. 69. Philadelphia: Lippincott, Williams and Wilkins; 2001. p. 1132-52.
Rickles FR, Levine MN. Epidemiology of thrombosis in cancer. Acta Haematol 2001;106:6-12.
Gary T, Belaj K, Steidl K, Pichler M, Eisner F, Stöger H, et al.
Asymptomatic deep vein thrombosis and superficial vein thrombosis in ambulatory cancer patients: Impact on short-term survival. Br J Cancer 2012;107:1244-8.
Cronin CG, Lohan DG, Keane M, Roche C, Murphy JM. Prevalence and significance of asymptomatic venous thromboembolic disease found on oncologic staging CT. AJR Am J Roentgenol 2007;189:162-70.
Dentali F, Ageno W, Giorgi Pierfranceschi M, Imberti D, Malato A, Nitti C, et al.
Prognostic relevance of an asymptomatic venous thromboembolism in patients with cancer. J Thromb Haemost 2011;9:1081-3.
Winter PC. The pathogenesis of venous thromboembolism in cancer: Emerging links with tumour biology. Hematol Oncol 2006;24:126-33.
Rickles FR, Patierno S, Fernandez PM. Tissue factor, thrombin, and cancer. Chest 2003;124 3 Suppl: 58S-68S.
Connolly GC, Francis CW. Cancer-associated thrombosis. Hematology Am Soc Hematol Educ Program 2013;2013:684-91.
Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008;111:4902-7.
Awotedu AA, Igbokwe EO, Akang EE, Aghadiuno PO. Pulmonary embolism in Ibadan, Nigeria: Five years autopsy report. Cent Afr J Med 1992;38:432-5.
Sotunmbi PT, Idowu AT, Akang EE, Aken′Ova YA. Prevalence of venous thromboembolism at post-mortem in an African population: A cause for concern. Afr J Med Med Sci 2006;35:345-8.
Okunade MA, Kotila TR, Shokunbi WA, Akenova YA. Venous thrombosis in Ibadan: A five year experience (1986 to 1990). Nig Q J Hosp Med 1998;8:80-2.
Kotila TR, Fasola FA, Busari EO. A revisit of venous thromboembolism. Afr J Med Med Sci 2013;42:177-81.
Kingue S, Tagny-Zukam D, Binam F, Nouedoui C, Teyang A, Muna WF. Venous thromboembolism in Cameroon (report of 18 cases). Med Trop (Mars) 2002;62:47-50.
Muleledhu AL, Galukande M, Makobore P, Mwambu T, Ameda F, Kiguli-Malwadde E. Deep venous thrombosis after major abdominal surgery in a Ugandan hospital: A prospective study. Int J Emerg Med 2013;6:43.
Fall AO, Proulle V, Sall A, Mbaye A, Ba PS, Diao M, et al.
Risk factors for thrombosis in an African population. Clin Med Insights Blood Disord 2014;7:1-6.
Alsheri MF. Risk Factors for Deep Vein Thrombosis in a South African Public Hospital. Dissertation for Masters of Emergency Medicine, Faculty of Health Sciences, University of Cape Town. South Africa. Available from: http://www.uctscholar.uct.ac.za/PDF/99882_Alshehri_MH.pdf
. [Last accessed on 2016 Mar 16].
Gomes M, Khorana AA. Risk assessment for thrombosis in cancer. Semin Thromb Hemost 2014;40:319-24.
Falanga A, Zacharski L. Deep vein thrombosis in cancer: The scale of the problem and approaches to management. Ann Oncol 2005;16:696-701.
Prandoni P, Trujillo-Santos J, Surico T, Dalla Valle F, Piccioli A, Monreal M; RIETE Investigators. Recurrent thromboembolism and major bleeding during oral anticoagulant therapy in patients with solid cancer: Findings from the RIETE registry. Haematologica 2008;93:1432-4.