by Donna Castellone, MS, MT (ASCP) SH •
August 11, 2020
The interpretations below are provided by Donna Castellone, MS, MT (ASCP) SH for Aniara Diagnostica.
Last month we covered bleeding disorders in relation to race and ethnicities, this coagulation corner will look at clotting disorders among groups.
Both deep vein thrombosis (DVT) and pulmonary embolism (PE) make up venous thrombosis which occurs with an incidence of 1/1000 annually in adult populations with rates being slightly higher in men versus women. Most episodes (2/3) manifest as DVT while the remaining (1/3) result in PE. The rate of mortality is about 6% in DVT and 10% in PE, however it has been estimated that it can be as high as 30%. Mortality is highest when thrombosis occurs in the setting of cancer. Risks also occur in advancing age with a lower rate (1/10,000) prior to the fourth decade of life and rising rapidly and approaching 5-6/1000 by the age of 80 with also increasing morbidity. Reasons for increasing risk with age are not well understood but may relate to comorbidities in this population.(1)
It is important to understand the risk factors associated with clotting, which include obesity, genetic factors compounded with triggering factors such as surgery, advancing age, cancer, trauma, immobility or pregnancy. A study looked at 21,680 people for the occurrence of venous thromboembolism (VTE) for 7.6 years and showed that one-half of all VTE events were secondary to triggering factors and in up to 65% had multiple triggering factors. Most common triggers were due to hospitalization (52%), cancer (48%) and surgery (42%).(2) Studies have found that some ethnic groups have a higher incidence of deep vein thrombosis (DVT) compared to other groups. DVT can lead to a pulmonary embolism (PE) which is the most common cause of death in hospitalized patients secondary to the condition in which they were admitted(3). Up to 25% of all VTE findings could be prevented if thromboprophylaxis were administered optimally in patients at risk for VTE.(4)
Studies have also shown differences in the incidence of VTE in ethic groups. Lower rates were found in Asiana, Pacific Islanders and Hispanics than in whites.(5) While the risk for African-Americans could be up to 25% higher. A warning was issued in 2009 from the Office of Minority Health that they were at a much higher risk for DVT and PE than other ethnic backgrounds. In a study form the University of California, Davis, found that the incidence was particularly high following surgery or serious illness. DVT is less frequent in Hispanics, Asians and Pacific Islanders.(6)
It has been suggested in various publications that Asians when compared to Whites have a lower rate of VTE. Two reports suggest that the rates of hospital trigged DVT is similar in Asian and in Western countries, but the population rate of DVT in China is only 0.17/1000 annually. This may be attributed to lower prevalence in disorders of factor V leiden or the prothrombin 20210A mutation in non-Caucasians. All of this suggests that there may be unidentified gene variants that play a role in thrombosis risks. It has been demonstrated that people of African descent have a higher levels of von Willebrand factor, FVIII and D-dimer which are markers of hemostatic risks.(1)
In a study of 61,459 persons, ethnicity was classified as 53% white, 28.4% black, 11.6% ASAM (Asian American), and 6.8% Other. Of ASAM, 44.7% were Chinese, 32.8% Filipinos, 12.9% Japanese, 4.5% South Asians (SA) and 5.0% Other Asian. There were 4674 VTE subjects. Chinese, Japanese, Filipinos and other Asian participants had lower VTE risks than both White and SA participants whose risks were similar. Reduced ASAM risks were similar in men and women. However increasing age and body mass were related to increased risk.(7)
Lower VTE risks in these populations suggest the presence of acquired or genetic protective traits in these ethnic groups. Factor V Leiden is rare in this population and there may also be lower levels of fibrinogen, and Factor VIII in this population. However the study was unable to control for lifestyle factors such as diet and exercise and may limit generalization to other populations. The SA cohort is known to not be genetically homogeneous and genetic studies have revealed that many northern Indians have gene pools closer to Middle Easterners, Central Asians and Europeans which may make them genetically closer to whites which concurs with the study findings.(7)
Three perspective studies: the Atherosclerosis Risk in Communities study (ARIC), the Cardiovascular Health Study (CHS), and the Reasons for Geographic and Racial Differences in Stroke study (REGARDS) looked at regional differences in VTE. In over 438,090 person years, 916 VTE incidents occurred in which 51, 149 individuals, 17,318 which were black. Black participants had a higher incidence of VTE than whites participants, and it was also seen in the REGARDS study that there was a significant regional presentation. Black participants in the southeast had a higher rate of VTE than those in the rest of the US. This same correlation was not seen in whites. Further studies are needed to determine if environmental and genetic risk factors contribute to the regional differences that were found.(8) There is little information on the epidemiology of thrombosis in Africa.
When looking at the incidence of heart attacks, African Americans have not only a greater chance of heart attacks but also their survival rates are 2.5 times lower than whites. Researchers at Thomas Jefferson University found that African Americans have a more potent PAR4 clotting ability than whites. They tested 70 black subjects and 84 white subjects. PAR4 binds more thrombin faster. Also a gene – PCTP, which mediates platelet activation of PAR4 was another difference found in the clot formation between black people and white people and was expressed higher in this population. Many blood thinners target the PAR gene family however there are no blood thinners that work by targeting PAR4. Having individualized treatment could be very helpful in this population.(9)
Evidence of rates of increased hospitalizations and deaths have pointed to disparity that non-Hispanic black people, Hispanics, Latinos, American Indians/Alaska Natives are at an increase risk of getting COVID 19, or experiencing severe illness regardless of age. The age adjusted hospitalization rates are highest among non-Hispanic American Indian or Alaska Native and non-Hispanic black persons.(10)
Non-Hispanic American Indian or Alaska Native persons have a rate approximately 5 times that of non-Hispanic white persons,
Non-Hispanic black persons have a rate approximately 5 times that of non-Hispanic white persons,
Hispanic or Latino persons have a rate approximately 4 times that of non-Hispanic white persons.(10)
History shows that severe illness and death rates tend to be increased for racial and ethnic minority populations during public health emergencies than for other populations.
Understanding not only risk factors for VTE but also how ethnicity plays a role in VTE can help lead to the diagnosis and treatment in patients. Knowing that possibly certain groups of people may have more cancers or orthopedic surgeries can also play a role in anticoagulation. In populations where VTE is very low, administering anticoagulation may place the patient at a higher risk of bleeding. Non-O blood type is also the most common genetic risk factor for VTE, but may not be the predominant blood type in certain ethnic groups. BMI, dietary restrictions and the use of herbal medicine all needs to be evaluated when looking at groups to determine risk for VTE.
Cushman M. (2007). Epidemiology and risk factors for venous thrombosis. Seminars in hematology, 44(2), 62–69.
Cushman M, Tsai AW, White RH, Heckbert SR, Rosamond WD, Enright P, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the Longitudinal Investigation of Thromboembolism Etiology. Am J Med. 2004;117:19–25.
Pini M, Spyropoulos AC. Prevention of venous thromboembolism. Semin Thromb Hemost. 2006;32:755–766
Stein PD, Kayali F, Olson RE, Milford CE. Pulmonary thromboembolism in Asians/Pacific Islanders in the United States: analysis of data from the National Hospital Discharge Survey and the United States Bureau of the Census. Am J Med. 2004;116:435–442.
Tran, N., Klatsky, AL., Lower risk of venous thromboembolism in multiple Asian ethnic groups, Prev Med Rep., March 2019.,268-269
Zakai, A., McClure, A, Judd, Se., Safford, MM., Folson, AR., Lutsety., PL., Cushman, M. Racial and Regional Differences in Venous Thromboembolism in the United States in Three Cohorts, Circulation, 2014.
Leonard C Edelstein, Lukas M Simon, Raúl Teruel Montoya, Michael Holinstat, Edward S Chen, Angela Bergeron, Xianguo Kong, Srikanth Nagalla, Narla Mohandas, David E Cohen, Jing-fei Dong, Chad Shaw, Paul F Bray. Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c. Nature Medicine, 2013.