Wide coagulation assays born from expertise
The prothrombin time is a coagulation screening test. It measures, as a whole, the activity of the coagulation factors II, V, VII, X and I, the extrinsic and common pathway.
The PT is commonly used for monitoring vitamin K antagonist therapy because of its sensitivity to variations in the concentration of the vitamin K dependent factors II, VII and X. Consequently, the comparability of results of his test is essential for finding the therapeutically range. The use of the INR is recommended for the assessment of the vitamin K antagonist therapy in patients.
|*APTT is a general coagulation screening test of the coagulation factors XII, XI, IX, VIII, X, V, II and fibrinogen.|
A prolongation of the APTT is encountered in the following situations: congenital deficiencies or acquired deficiencies related to the disorder coagulation in intrinsic and common pathway.
An increase of the fibrinogen level is found in cases of diabetes, inflammatory syndromes, obesity; a decrease of the fibrinogen level is observed in Disseminated Intravascular Coagulation (DIC), fibrinogenolysis. Furthermore, fibrinogen seems to be involved in the pathogenicity of thrombotic cardiovascular events.
The Thrombin Time is a rapid and simple test designed for the assessment of fibrin formation. The TT remains normal in deficiencies of factor XIII (fibrin stabilizing factor). The TT should be performed before any other specific assays are attempted, when a prolongation of the overall tests (PT, APTT) cannot be explained.
Prolongation of the TT indicates: an abnormality of fibrinogen, or the presence of antithrombins.
|*Heparins (UFH and LMWH) and Direct Anti-Xa Oral Anticoagulants are used for the prevention and treatment of thromboembolic diseases.|
The quantitative determination of anti-Xa activity:
– of the heparin (UFH), is helpful for monitoring treatment efficacy
– of rivaroxaban, apixaban or edoxaban level, in conjunction with clinical examination, is helpful in the assessment of the clinical status in certain situations.
|*Heparin induced thrombocytopenia type II (HIT) is a life-threatening disease associated with exposure to unfractionated or less commonly low-molecular-weight heparin.|
– HIT occurs in up to 5 % of patients on heparin.
– HIT is caused by IgG antibodies that recognize complexes of platelet factor 4 (PF4) and heparin inducing platelet activation and thrombin generation that promote venous and/or arterial thromboembolism.
Hemophilia A is the most common of the serious haemorrhagic diseases. It is caused by a deficiency in factor VIII (anti-haemophilia factor A) and affects around 1 in 5000 male infants at birth.
Haemophilia B is a disease caused by a deficiency in factor IX (anti-haemophilia factor B) that affects around one in 30 000 male infants at birth.
The disease is inherited as an X-linked recessive trait and thus occurs in males and very rarely in homozygous females. Heterozygous females for the disease are known as carriers.
Thrombophilia which may be congenital or acquired, is a clotting disorder associated with hypercoagulability that causes the appearance of deep venous thrombosis (DVT). Herein, we discuss only congenital thrombophilia, in other words anomalies in patients with a familial history of thrombosis. We do not describe situations involving acquired hypercoagulability (e.g. antiphospholipid syndrome, cancer, etc.).
|*Antithrombin (AT) is a glycoprotein of a molecular weight of approximately 58,000 daltons, synthesized in the liver. As an inhibitor of thrombin, the activity of AT is dramatically enhanced by heparin. It also inhibits factor Xa and to a lesser extent the factors IXa, XIa, XIIa as well as plasmin and kallikrein.|
Since the first report (1965) of a hereditary deficiency of AT and its consequences, AT has been considered an important parameter in thromboembolic disorders.
|*Protein C belongs to the group of vitamin K-dependent proteins.|
It is synthesized in the liver. In the activated state protein C regulates the coagulation process by neutralising the procoagulant activities of the factors Va and VIIIa in the presence of protein S, itself also a vitamin K-dependent protein and is a cofactor of activated protein C.
There is a clinical interest in determining the protein C level because of the existence of protein C deficiencies, both acquired and congenital. In order to characterize a protein C deficiency it is recommended that the STA-Staclot Protein C test be complemented with the immunological Asserachrom Protein C assay and with the chromogenic STA-Stachrom Protein C assay.
|*Activated Protein C Resistance (APCR). The factor V Leiden mutation is autosomal dominant and it is frequently found in Caucasians. This anomaly is associated with a higher risk of thromboses, especially when the co-existence of other risk factors is present in the carrier.||*Lupus anticoagulants (LA) are associated with numerous clinical states: systemic lupus erythematosus, recurrent spontaneous abortions, thrombosis, infections. The diagnosis of LA is often difficult because of variable reagent sensitivity and the intrinsic heterogeneity of LA.|
Lupus anticoagulants are antibodies directed against phospholipid/protein complexes. They have the ability to prolong the clotting times of the phospholipid-dependent tests. In practice, factor deficient plasmas are easily identified with APTT, since the addition of normal plasma restores normal in vitro clotting time.
However additional tests are necessary to provide clear-cut differentiation between LA and anti-coagulation factor antibodies and/or heparin.
*Protein S is a vitamin K-dependent protein that does not possess any esterase function.
Physiologically, protein S has an essential anticoagulant function. It acts as the cofactor of activated protein C.
In the presence of calcium, this complex binds strongly to the phospholipid surfaces and thus regulates the coagulation process, inactivates by proteolysis thrombin-activated factors V and VIII.
The biochemistry of protein S appears to be quite complex by the fact that it forms a dynamic equilibrium with the protein that binds the C4b-binding protein (C4b-BP) – the free protein S form which acts as the cofactor of activated protein C and represents about 40 % of total protein S the high molecular weight C4b-BP bound protein S form which exhibits no activity as a cofactor of activated protein C and represents about 60 % of total protein S.
The congenital or acquired deficiency of protein S increases the risk of thrombo-embolism, owing to a decrease of blood anticoagulant potential. It may produce recurrent thrombotic episodes.
Von Willebrand Factor (VWF) is a multimeric plasmatic glycoprotein involved in primary hemostasis and in the coagulation process. It plays an important role in the adhesion of platelets to the vascular subendothelium and in the formation of thrombi via its linkages with the glycoprotein (GP) complexes Ib/IX and IIb/IIIa. In the coagulation process, VWF serves as a carrier for factor VIII (antihemophilic factor A) and protects it from degradation.
Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. Clinically, it is often characterized by muco-cutaneous hemorrhages.
Depending on the generated quantity and environmental conditions, the fibrin monomers may join with fibrinogen and various fibrinogen/fibrin degradation products resulting in the formation of soluble complexes.
These complexes usually called “soluble fibrin” are observed in prethrombotic situations such as Disseminated Intravascular Coagulation (DIC), etc. DIC is an invasion of the circulation by microthromboses which are at the origin of a reactive fibrinolysis.
The consumption of the coagulation factors (factors II, V and X) and of the platelets involves a hemorrhagic risk of variable intensity. High plasma levels of fibrin monomers are usually observed in DIC.
The International Society on Thrombosis and Haemostasis (ISTH) has defined a scoring system to diagnose DIC. An “overt DIC score” may be calculated for each patient and is based on the platelet count, the elevated fibrin-related markers (soluble fibrin monomers or fibrin degradation products), the prolonged Prothrombin Time (PT) and the fibrinogen level.
It is established that a normal D-Dimer level is an important element to rule out the diagnosis of evolutive Deep Venous Thromboses (DVT) or Pulmonary Embolisms (PE). STA-Liatest DDi PLUS in clinically validated to safely exclude DVT & PE.
• Disseminated Intravascular Coagulation (DIC)
In DIC the fibrinolytic system is activated and therefore the D-Dimer level increases. D-Dimer assays can help in the diagnosis of DIC.
• Activation States of Coagulation
The D-Dimer level increases during the activation states of coagulation because such states induce the production of thrombin which is followed by the formation of fibrin and leads to fibrinolysis, the latter being most frequently reactive. The D-Dimer level thus increases following coagulation activation.
Increasing levels of D-Dimer have been reported in the following cases: post-operative period, cancers, hemorrhages, severe infections.
FDP are considered to be useful for the diagnosis of thrombosis, such as Deep Vein Thrombosis (DVT) and Disseminated Intravascular Coagulation (DIC).
FDP may be used as a fibrin formation marker in the calculation of the DIC score defined by the ISTH (International Society on Thrombosis and Haemostasis), the JAAM (Japanese Association for Acute Medicine) and the JMHW (Japanese Ministry of Health and Welfare).