HEALTH – COAGULATION SCREEN EXPLAINED.
Mrs Kayon Lee
Haemophilia is a group of inherited blood disorders in which the blood does not clot properly. This is due to the fact that the coagulations factors are missing therefore bleeding will continues. The blood coagulation mechanism is a process which transforms the blood from a liquid into a solid, and involves several different clotting factors. The mechanism generates fibrin when it is activated, which together with the platelet plug, stops the bleeding. The process of blood clotting involves a series of complex mechanisms involving 13 different proteins, classically termed factors I through XIII and written with Roman numerals. If the lining of the blood vessels becomes damaged, platelets are recruited to the injured area to form an initial plug. These activated platelets release chemicals that start the clotting cascade, activating the series of 13 proteins known as clotting factors. Ultimately, fibrin is formed, the protein that crosslinks with itself to form a mesh that makes up the final blood clot. The protein involved with haemophilia A is factor VIII (factor 8) and with haemophilia B is factor IX
In the laboratory, routine clotting tests comprises of the prothrombin time (PT), fibrinogen, activated partial thromboplastin time (APTT), thrombin time and D-Dimer. These tests are pre-operatively used to assess bleeding risk and also to monitor bleeding conditions and some therapies. Most of these cases without a family history arise due to a spontaneous mutation in the affected gene. Other cases may be due to the affected gene being passed through a long line of female carriers. If there is no known family history of haemophilia, a series of blood tests can identify which part or protein factor of the blood clotting mechanism is defective if an individual has abnormal bleeding episodes. The platelet (a blood particle essential for the clotting process) count and bleeding time test should be measured as well as two indices of blood clotting, the prothrombin time (PT) and activated partial thromboplastin time (APTT). A normal platelet count, normal PT, and a prolonged (APTT are characteristic of haemophilia A and haemophilia B. Specific tests for the blood clotting factors can then be performed to measure factor VII or factor IX levels and confirm the diagnosis.
Prothrombin Time (PT) The PT measures the vitamin K dependant clotting pathways (extrinsic pathway) and is therefore of particular use in measuring the effect of warfarin therapy (warfarin is a vitamin K antagonist).
Activated Partial Thromboplastin Time (APTT) Measures the intrinsic clotting pathway and is particularly useful in monitoring heparin therapy. The APTT ratio provides the ratio of APPT and Normal Clotting time and is the primary calculation used to monitor heparin therapy. The APTT is also useful in detecting clotting factor deficiencies of the intrinsic pathway and can be raised in the presence of factor deficiencies and lupus anticoagulants.
Thrombin Time Is primarily requested by the Liver Disease Units and measures the time it takes for fibrinogen to form fibrin. Fibrin is an insoluble protein involved in blood clotting. Fibrin is deposited around the wound in a form of mesh to strengthen the platelet plug. The whole thing dries and hardens (coagulates) so that the bleeding stops and the wound then heals. Fibrin is developed in the blood from a soluble protein, fibrinogen. It is also requested by the laboratories to confirm the presence of heparin contamination of a sample in the event of an unexplained raised APTT.
Fibrinogen During the formation of a stable clot, amino acids are excised by various enzyme cascade reactions. The D-Dimer peptide is excised from the D portion of fibrin as the clot hardens. It is therefore a useful predictor of recent clot formation. It is not specific however and can be affected by many other conditions such as rheumatoid arthritis. It should only be used as a negative predictor for VTE (venous thromboembolism) i.e. a raised D-Dimer is not diagnostic of a clot formation, but a normal D-Dimer can be a used as a negative predictor of venous thrombosis.
When platelets come into contact with damaged tissue thrombin is formed as a result of a series of chemical processes (coagulation cascade) that culminate in the formation of fibrin from fibrinogen.
The final step of the cascade of chemical reactions is to convert fibrinogen – Factor I – into fibrin, forming a mesh which clumps platelets and blood cells into a solid clot, plugging the hole and stopping the bleeding. Patients with Hemophilia A have deficient levels of Factor VIII, while patients with Hemophilia B have deficient levels of Factor IX.