|Dr Prahlad Ho presenting at ASH15 |
meeting. Image: @marrow
It has long been a conundrum for clinicians and researchers pondering cardiovascular disease; a 90-year-old overweight man who has been smoking heavily all his life is admitted to hospital with an unrelated condition and is found to have a healthy heart while a fit 25-year-old athlete elsewhere inexplicably dies of a massive heart attack.
Now, scientists from the Australian Centre for Blood Diseases, Monash University, Northern Health and the University of Melbourne are collaboratively evaluating a new blood test that could add to the surrogate measures currently used clinically as an assessment of cardiovascular risk. Currently no such blood test exists, they say.
The researchers outlined the first stage of their work into developing a global assay for stroke risk in a letter published in the June edition of ‘Thrombosis Research’.
The study tested 96 “normal” people – those who did not have any history of relevant adverse conditions such as thrombotic or heart disease – aged from 20 to 79 years. It used two global coagulation assays – TEG® (thromboelastography) and CAT (Calibrated automated thrombogram) – to evaluate specifically the impact of age, gender and race. TEG tests whole blood including platelets while CAT measures thrombin, the enzyme in blood plasma which is one of the final products of the coagulation (clotting) system.
The study showed differences in gender, age and race.
Overall, the female population had a bigger prothrombotic profile though this finding contradicted clinical epidemiological data that consistently shows that women are at lower thrombotic and cardiovascular risk compared to their male counterparts. Further studies to evaluate the rationale behind this contradiction were needed, the study said.
The whole blood assay (TEG) for the older age group (over 50 years) was more prothrombotic although the impact on age on CAT parameters were minimal. This suggests that platelets may play a more important role in age-related thrombosis.
East Asian people, defined as ethnic Chinese in this cohort, were found to have less/lower prothrombotic CAT parameters than both Caucasian and “Other Asian” cohorts, suggesting that non-platelet coagulation factors played an important factor in race differences. This also explains the higher risk of venous thromboembolism (VTE or clots that start in veins) seen in the Caucasian population compared to Chinese population.
Further research was needed to explain the various differences but the study nonetheless
highlighted the significant age, gender and race differences within the normal population, and the ability of global coagulation assays to differentiate them, the authors concluded.
“Having established what normal controls look like, we’re now conducting clinical tests on diseased populations – such as those with cardiovascular disease – so we can establish whether the test is something that’s predictive of risk,” first author Dr Prahlad Ho said.
“If this is proven to be the case it will need to be studied in a larger, longitudinal study,” he said.
A global coagulation test that was predictive would allow clinicians to more aggressively treat and manage those at risk. It would be inexpensive and easy to administer, Dr Ho said.
“But it’s very early stage now. We’ve established the normal, control first – the big fish is really looking the diseased population,” he said.
While age and gender differences were already known, the study’s findings on race were significant.
“The differences in thrombosis risk, not reflected in routine coagulation laboratory testing, are very important, particularly for multi-cultural Australia,” Dr Ho said. “We need to start thinking a bit more broadly and maybe in our clinical practice too, that it’s not just one homogenous population of patients.”
Dr Ho, a senior medical staff member at The Alfred Hospital, honorary at the Australian Centre for Blood Diseases (ACBD) and Director of Haematology at Northern Health, is supported by a NHMRC/Heart Foundation scholarship. Senior author is Professor Harshal Nandurkar, Head of the ACBD, Central Clinical School.
Ho P, Ng C, Rigano J, Tacey M, Smith C, Donnan G, Nandurkar H. Significant age, race and gender differences in global coagulation assays parameters in the normal population. Thromb Res. 2017 Jun;154:80-83. doi: 10.1016/j.thromres.2017.04.009. Epub 2017 Apr 12.