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Coagulation Corner

Thursday, July 8, 2010


The 2010 FIFA World Cup is the 19th FIFA World Cup, the premier international association football tournament, which is being held in South Africa. It is the first time the finals of the tournament have been staged in an African host nation.  Held every four years since 1930, the previous tournament was held in Germany, while the 2014 finals will be hosted by Brazil. The finals tournament sees 736 players representing 32 teams compete for the World Cup trophy in games held in ten stadiums across South Africa. The qualifying teams were selected through a qualification process that began in August 2007. With a pool of entrants comprising 204 of the 208 FIFA national teams, the 2010 World Cup shares with the 2008 Summer Olympics the record for most competing nations in a sporting event.

So this got me thinking, how is coagulation performed throughout the world?  We only know what we are used to and what we know.  Different healthcare systems as well as disease prevalence can drive how and what testing is performed.  Different countries have limited  resources and their diagnostic and treatment testing may be restrictive.

The Coagulation Testing Market: US, Europe, Japan

The growing cost-containment pressures in major industrialized nations, coupled with continued technological advances in chromogenic substrates, monoclonal antibodies, immunoassays, molecular diagnostics, computers and laboratory automation will radically change the coagulation testing practice during the next ten years. New specific and sensitive markers of hemostasis will be increasingly used on automated instrumentation. Coagulation testing will also become more standardized, offering opportunities for quality control products and services.

The following processes may turn out to be the major impacts on global coagulation testing:

-     The status of POC and decentralization in lab medicine
-     Miniaturization and molecularization of devices
-     Geo-economic and demographic influences on markets
-     Non-invasive sampling
-     Greatly expanded market data on PGx and SNP testing
-     More information about more immunoassays
-     World blood banking developments

Coagulation Laboratories in the United States:

US laboratories were questioned to determine which test out of 29 coagulation tests, what were the most frequent tests performed. The 5 most commonly performed coagulation laboratory tests were PT, 100%; with an estimated annual test volume of 65.9 million, and that the second most commonly performed coagulation laboratory test was APTT, with an estimated annual test volume of 45.6 million.  Those tests are followed by the bleeding time, 90.0%; fibrinogen, 69.2%; and D-dimer 56.5%. A significantly (P < .05) greater proportion of the large hospitals performed each of the 29 surveyed tests in house compared with the small hospitals.

in Europe, coagulation monitoring is moving towards point-of-care (POC) testing, which ensures quick generation of results.  This may provide better patient care.  POC coagulation tests have made life simpler, as they enable patients to be well informed about the disease state. The number of patients undergoing anticoagulant therapy have increased. It is very important to closely monitor the PT and the INR.  POC instruments are showing up in emergency units, outpatient wards as well as patient homes to enable self-testing. This reduces the burden on hospitals as well as physician offices and prevents the drastic effects of anticoagulants and other bleeding disorders.
Clearly, the growth of POC is generated by quick turn-around-times and easy-to-use technology. At the same time, laboratory tests continue to be preferred in some European countries since they are cost effective and well reimbursed when compared to POC tests. Presently, laboratory tests generate delayed results and do not support fast treatment processes. Hence, there is a need to produce timely results that will result in improved patient care. With an increasing number of tests moving towards POC, the volume of tests in laboratories is adversely affected. To overcome this challenge, laboratories are slowly adopting high-volume analyzers to perform special coagulation tests, which have not yet reached the POC market.

An accurate detection of Lupus Anticoagulant is of utmost importance in patients suspected of an antiphospholipid syndrome.  Even though guidelines have been established by ISTH, testing practices are varied. Based on a European proficient test (ECAT)). Fifty nine laboratories participating in this trial were asked to test for the presence of a LA in the 3 samples submitted. The most frequently used screening tests were the aPTT and the dRVVT. Additional testing included the dilute prothrombin time (dPT), the dilute Russell Viper Venom time (dRVVT) and the Kaolin Clotting time. The present study also shows that many laboratories still rely on poorly responsive screening assays for their LA tests. Other laboratories rely on sensitive and more specific integrated test systems based on a sensitive screening assay with a low phospholipid content and a confirmatory test employing high phospholipid concentrations. The most used integrated system was dRVVT based. However, also here the LA responsiveness was largely reagent dependent. In conclusion, many laboratories still rely on poorly responsive screening assays by which weakly positive LA samples are misdiagnosed.Bottom of Form

Coagulation testing in India:

In the year 2000 an external quality assessment scheme (EQAS) was implemented in India to 25 laboratories.  Their participation is critical for ensuring acceptable laboratory performance. Participation in such programs is uncommon for laboratories performing tests of hemostasis in developing countries. There are several reasons, including lack of awareness of its significance, absence of locally administered and easily accessible programs, and costs associated with some of the international schemes. This was converted to a national program in 2003, in association with the Indian Society of Haematology and Transfusion Medicine. Local manufacture of survey samples began in 2004, along with analysis of results. Currently, more than 100 laboratories are registered in the program. They receive samples three times a year for the following tests: prothrombin time, activated partial thromboplastin time, and factor assays. Some surveys also include samples for fibrinogen and von Willebrand factor assays. In recent surveys, 60 to 95% of laboratories had their clotting times and 57 to 77% of laboratories had their factor assays within consensus.


A problem that occurs in India are snake bites.  This has a major impact on the coagulation system.  Not to mention the impact on the nervous system!! Experts in Indian snakebites developed a protocol specifically designed for snakebite treatment in India. A training program was implemented in Midnapore Medical College in West Bengal, India, under the direction of the Health Minister to train care providers in the new protocol. After training, data were collected for 839 snakebite victims over a 12-month period and included epidemiological data, ASV volumes administered, and mortality. The results were collated and compared with results calculated from 780 snakebite victims treated during the 12-month period before implementation of the protocol. Treatment prior to protocol implementation was based on knowledge gained by the care providers from western and forensic medicine textbooks.

About 80% of the venomous snakebites in India come from the saw scaled viper Echis carinatus, cobra, krait and Russel’s viper.  Recognize these names?  Look at your coagulation reagents- snake venom are used in many of the testing.  On admission, and at relevant intervals afterwards, doctors will probably check on how well the blood is clotting.  The most common tests are simple- the bleeding time, and whole blood clotting time. Sometimes tests like PT and aPTT, kidney function (urine output, blood urea, creatinine and electrolyte levels), and of course the vital signs – pulse, breathing, temperature, blood pressure and the amount of oxygen in the blood (pO2). They may also keep tabs on the patient’s haemoglobin, blood cell counts, and perhaps the blood gases. A minimal amount of testing is conducted.

What happens in Malaria?

Different parameters of fibrinolytic systems like t-PA, PAI, D-dimer, and inhibitors of blood coagulation, i.e., protein C (PC), protein S(PS), and antithrombin III (AT-III), have been studied in cases of acute malaria due to Plasmodium falciparum and plasmodium vivax infection, and these patients were followed up. It was observed that the plasma PAI-1 was very high in cases of P. falciparum malaria infection as compared to normal controls and P. vivax infection. The changes in complicated cases of P. falciparum were remarkable as compared to uncomplicated ones. The PC, PS, and AT-III levels were also low in P. falciparum, particularly so in complicated cases, and were normal in P. vivax infection. The factor VIII R:Ag levels were invariably high in acute malaria. On follow-up of some of these cases the values came back to normal after the antiparasite treatment. The monocyte procoagulant activity was found to be significantly higher in P. falciparum infection as compared to that of P. vivax infection. All these findings therefore contribute towards the production of a hypercoagulable state in P. falciparum infection and partly explain the complications of P. falciparum infection like cerebral malaria. 

What about Dengue Fever?

The pathophysiological basis of hemorrhage in dengue infections remains poorly understood.  In a large prospective study of 167 Vietnamese children demonstrated only a minor prolongation of the PT and APTT, with severe depression of plasma fibrinogen as well as Protein C, S and AT. While increases were seen in thrombomodulin, tissue factor, and plasminogen activator inhibitor (PAI-!).  Increased thrombomodulin suggests endothelial activation correlated with increased shock severity, PAI-1 levels correlated bleeding severity.  Dengue can directly activate plasminogen resulting in activating fibrinolysis, degrading fibrinogen directly and prompting secondary activation of procoagulant mechanisms. 

I have always said, coagulation is a puzzle, and you diagnosis and treat by putting the pieces together.  Expect the unexpected!  Understand how different components are affected by different disease states and how testing is impacted by what hospital have available to them.  More importantly understand, while things may be different globally, good patient care is something everyone strives for!  

Donna Castellone

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About the Author

Donna Castellone,  MS, MT(ASCP)SH

Donna Castellone,

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