Global assays of hemostasis

Abstract

Purpose of review There exists an imbalance between our understanding of the physiology of the blood coagulation process and the translation of this understanding into useful assays for clinical application. As technology advances, the capabilities for merging the two areas have become more attainable. Global assays have advanced our understanding of the dynamics of the blood coagulation process beyond end point assays and are at the forefront of implementation in the clinic. Recent findings We will review recent advances in the main global assays with a focus on thrombin generation that have potential for clinical utility. These assays include direct (thrombogram, whole blood, purified systems) and indirect empirical measures of thrombin generation (thromboelastography) and mechanism-based computational models that use plasma composition data from individuals to generate thrombin generation profiles. Summary Empirical thrombin generation assays (direct and indirect) and computational modeling of thrombin generation have greatly advanced our understanding of the hemostatic balance. Implementation of these types of assays and visualization approaches in the clinic potentially will provide a basis for the development of individualized patient care. Advances in both empirical and computational global assays have made the goal of predicting pre-crisis changes in an individual’s hemostatic state one step closer.

Integrated laboratory coagulation tests in hypercoagulation diagnosis and thrombosis risk assessment. Part II. The sensitivity of integral tests to hypercoagulable states

“…Возможным решением являются интегральные или глобальные тесты гемостаза [1][2][3], которые ими-тируют патофизиологические процессы с большей точностью, позволяя оценить потенциал системы ге-мостаза в целом. В этих тестах обычно используются низкие концентрации активаторов (тест генерации тромбина, тромбоэластография) или активаторы, ло-кализованные на поверхности (тромбодинамика, про-точные камеры).…”

“…Важной модификацией метода АЧТВ является так называемый анализ формы сигнала сгустка (clot waveform analysis), в котором анализируется вся кривая изменения оптической плотности, а не только время свертывания. Такую модификацию, в отличие от обычного теста АЧТВ, однозначно относят к гло-бальным тестам [1][2][3]. В частности, появление двух-фазной кривой в этом методе оказалось чувствитель-ным и специфичным ранним признаком развития ДВС (85 % и 92 % соответственно) [12].…”

“…2), но стандартные ошибки в подавляющем большинстве случаев пересекаются, что затрудняет перенос таких результатов в клиниче-ские рекомендации. Недостаток стандартизации так-же ограничивает применение теста, хотя в этом на-правлении достигнуты существенные успехи [1].…”

In silico thrombin generation: Plasma composition imbalance and mortality in human immunodeficiency virus

“…Studies in the healthy population have shown that thrombin generation dynamics differ largely between individuals, but are relatively stable over time in a given individual, supporting the concept that they may have utility as a phenotypic marker 25, 26, 27. The mechanism‐based bridge between thrombin generation assays and individualized risk prediction is plasma composition–based computational modeling 28, 29. Recently, computational models that kinetically describe the tissue‐factor initiated coagulation process (extrinsic pathway) have been utilized to define an individual's thrombin phenotype based upon their individual plasma composition of pro‐ and anticoagulant factors 30…”

Coagulopathy in liver disease: Lack of an assessment tool

“…One is to quantify the activation peptide released from prothrombin upon activation by factor Xa (F1+2 fragment) and the thrombin antithrombin complex. The other is to quantify the amount of thrombin that can be generated ex vivo by the addition of a small amount of trigger (usually tissue factor) to a plasma sample: the endogenous thrombin potential [26] . The analysis of thrombin generation is usually done with platelet-poor plasma, although the method can be modified to test plateletrich plasma.…”