2. Coagulation Special Assays ANTICOAGULANT LINE HEMOPHILI0 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 […]
| 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 characterise 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, inactivating 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.
