Analysis Of Haemostatic Defects

2B30 Workshop #2: Analysis of haemostatic defects
Patient 1: Factor V Leiden (fV Leiden)
The patient does not have any abnormal blood results that are apparent from the blood tests conducted. The fV Leiden mutation is a common missense mutation in the factor V coagulation factor which causes an increase in the tendency for blood to clot. Factor V’s activity is usually regulated by activated protein C (aP) and the mutation causes fV to become resistant to the anticoagulant effect of the aPC pathway by preventing efficient inactivation of fV. This facilitates the overproduction of thrombin leading to the generation of excess fibrin and therefore excess clotting. Standard clotting tests (e.g. aPTT) are not influenced by this anticoagulant pathway therefore abnormalities are not apparent in clotting assays. Other tests such as an aPC test, (to test if blood is resistant to aPC – an anticlotting protein) and a genetic test (to determine whether there is factor V gene mutation by inheriting two copies of the mutated gene) can be carried out (Bertina et al, 1994.)
Patient 2: Dysfibrinogenaemia
Abnormal blood results for patient 2 are shown below (patient value/control value.)
- Increased PT (sec):16.5(11.4-14.2)
- Increased aPTT (sec): 44.3(25-40)
- Increased Thrombin Time: 29.4 (10-15)
- Increased Reptilase time (sec): 35.3(14-19)
- Decreased Fibrinogen (mg/dL): 60(146-390)
- Increased Bleeding time (min):10(2-9)
Dysfibrinogenemia is a condition where there is a defect in fibrin clotting. Thrombin turns fibrinogen into fibrin (a mechanical meshwork supporting platelet adhesion/aggregation forming a blood clot) by proteolytically removing a short peptide from the A and B chains of fibrinogen FpA/FpB residues. This allows the polymerisation of fibrinogen which in turn helps the formation of blood clots. Mutations in fibrinogen will affect blood coagulation as the conversion of fibrinogen to fibrin in disturbed and therefore blood clot will not form effectively. An increased bleeding time is therefore apparent and the thrombin time test measures the time it takes for a clot to form in the plasma of a blood and this is therefore increased. Reptilase time measures the conversion of fibrinogen to fibrin clot and is also increased as there is an inhibition of the polymerisation of fibrin monomers and also explains why there is a decrease in fibrinogen levels.

Patient 3: Heparin treatment
Abnormal blood results for patient 5 are shown below (patient value/control value.)
- Increased PT (sec): 16.5 (11.4-14.2)
- Increased aPTT (sec): 75.5(25-40)
- Increased Thrombin Time: 34.6 (10-15)
Heparin is an anticoagulant that is used to stop blood clots forming. It does this by binding to antithrombin (AT) causing a conformational change inducing faster inhibition of thrombin and therefore slower clotting. There is also inhibition of coagulation factors Xa, IXa, XIa and XIIa (intrinsic pathway) which would be indicative of the increased aPTT(activated partial thromboplastin time.) This test is used to monitor heparin anticoagulant therapy as measures the intrinsic pathway explaining why Heparin has more profound effects of the factors of the intrinsic arm than those in the extrinsic arm. This also explains why there is an increase in both PT and aPTT, with the aPTT having a much more significant increase than the control values. The prolonged thrombin time suggests that a thrombin inhibitor is present, (fibrin production can be excluded as the reasoning for this as fibrinogen-from which fibrin is generated- has normal values.)
Patient 4: Haemophilia A

Abnormal blood results for patient 5 are shown below (patient value/control value.)
- Increased aPTT (sec): 62.3(25-40)
- Decreased factor VIII (%): 15 (50-250)
Haemophilias are blood disorders that impair the body's ability to control blood clotting or coagulation. Haemophilia A is an X-linked disorder and represents 80% of haemophilia cases.It is

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