Blood products and related biologicals

Thromboplastin reagents

For the most part cardiovascular disorders are linked to circulatory diseases, such as heart attack and stroke, which account for at least 15 million deaths every year. Many millions more are disabled by them. The costs of caring for patients with circulatory diseases account for about 10% of direct health care costs in developed countries.

Prevention and treatment of cardiovascular diseases are improved as a result of new recommendations adopted by the WHO Expert Committee on Biological Standardization in 1997. The guidelines pave the way for a more effective treatment of millions of patients suffering from thrombotic disorders.

The Committee hammered out a new set of guidelines for oral anticoagulants - a class of drugs inhibiting blood clotting. These drugs cannot be prescribed at a fixed dose. For each patient the dose must be adjusted according to the result of a vitally important blood clotting test to be conducted every four weeks. If the dose is low the patient is at risk of developing thrombosis. If the dose is high the patient is at risk of spontaneous bleeding.

This test requires the use of laboratory reagents called thromboplastins which are commercial products producing different clotting times for a particular blood sample. In the past, all too often, patients going to different hospitals were given different prescriptions depending on the type of thromboplastins used by the hospital.

WHO International Standards improve the management of patients treated with oral anticoagulants, making health care more cost-effective.

International Standards (IS)

Thromboplastin reagents are used to monitor oral anticoagulant therapy with vitamin K antagonists for patients with thromboembolic disorders. The calibration of secondary standards for the standardization of thromboplastin reagents by manufacturers and reference laboratories requires the assignment of an International Sensitivity Index (ISI) for each International Standard (IS). Currently, three ISs for thromboplastin are available:

  • a recombinant human thromboplastin;
  • a native IS of rabbit and
  • a native IS of bovine origin.

The ISI for each new IS is established from a multicentre study in which all current ISs (i.e., human, rabbit and bovine) are included using the manual (tilt tube) technique for clotting time determination.
The ISI is defined in terms of the first IS of thromboplastin (preparation 67/40, which is no longer available). Each time when an IS is replaced by the next, the uncertainty in the ISI of the new IS is slightly greater than that of the redecessor. Increase in ISI uncertainty can be limited by including a large number (e.g., 20) of laboratories in the collaborative study. In this respect, it is worthwhile to include the bovine IS in each multicentre study for replacement of the rabbit and human IS, because the bovine IS is the only IS which had been compared directly to the first IS (preparation 67/40). The bovine IS thus serves as an "internal" standard, as long as it will be available.

Reference preparations are established for:

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OTHER WHO INTERNATIONAL REFERENCE MATERIALS

The characteristics of all reference preparations as well as the information regarding establishment can be found in the WHO Reference Material section.

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