Coagulation the presentation of the intrinsic factor Xase (FIXa–FVIIIa)

Coagulation mechanisms included extrinsic pathway,intrinsic pathway, and common pathway. Healthy endothelial cells express ecto –ADPase on its surface and produces prostacyclin and nitric oxide which togetherinhibit platelet adhesion and prevent clotting formation (Marcus AJ, Broekman MJ, Drosopoulos JH, et al.

The endothelial cellecto-ADPase responsible for inhibition of platelet function is CD39. Journal ofClinical Investigation. 1997;99(6):1351-1360). When a blood vessel is ruptured, the endothelium is damagedand present the membrane-bound tissue factor (TF) that binds with factor VIIa(FVIIa) thus initiate the extrinsic pathway of the coagulation system. The FVII-tissuefactor complex activates factor X (FX). The factor Xa (FXa) generated by the factorVIIa (FVIIa)-tissue factor complex activates a small amount of thrombin, whichactivates factor V (FV) and factor VIII (FVIII), leading to the presentation ofthe intrinsic factor Xase (FIXa–FVIIIa) and prothrombinase complex (FXa–FVa). Factor IXa, factor VIII, calcium and phospholipid (Xasecomplex) amplify the activation of factor X generating a large amount ofthrombin. Thrombin cleaves fibrinogen to form soluble fibrin monomers which arepolymerised to form soluble fibrin polymer.

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Thrombin then activates FXIII whichwith calcium cross links and stabilises the fibrin polymer forming cross-linkedfibrin which is the insoluble fibrin clot (ChristineA. Lee (MD), Erik E. Berntorp (MD), and W.

Keith Hoots (MD).Textbook ofHemophilia. Blackwell Publishing Ltd 2005, pp.1-3).The initial diagnostic tests for haemostaticdisorder should include a prothrombin time (PT), activated partialthromboplastin time (aPTT) and a platelet count (Marshall A. Lichtman (MD), Kenneth Kaushansky (MD), Josef T.

Prchal(MD), et al. William’s Manual of Haematology 9th edition. McGraw-HillEducation 2017, p.679). The prothrombin time (PT) evaluates the overallefficiency of the coagulation factors of the common and extrinsic pathways (factorsV, VII, X, prothrombin and fibrinogen). It measures the clotting time of plasmafollowing the addition of tissue factor (thromboplastin) and calcium to hypocalcemicplasma. The tissue factor activates FX in the presence of FVII, therebyactivating the extrinsic system.

The activated partial thromboplastin time (aPPT)evaluates the efficiency of the common and intrinsic pathway (factors VIII, IX,X, XI, XII, and V, prothrombin, fibrinogen, and the contact factors). Itmeasures the clotting time of plasma following the activation of contactfactors without adding tissue factor (thromboplastin). In this experiment, plasma samples from two patientswere screened by measuring the PT and aPTT clotting time, and correction screeningwas perform for prolongation PT and aPTT clotting time.Results:Table1: Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) ofPatient A and Patient B Plasma.     Prothrombin time (PT) (Normal = 13 – 20 seconds) Activated Partial Thromboplastin Time (aPTT) (Normal = 27 – 40 seconds) Patient A 95 220 Normal Plasma (contains all clotting factors) (0.

05 ml) 166 146 Absorbed Plasma (contains factors I, V, VIII, XI, XII) (0.05 ml)   60   160 Patient B 80 125 Normal Plasma (contains all clotting factors) (0.05 ml) 95 155 Absorbed Plasma (contains factors I, V, VIII, XI, XII) (0.05 ml)   85   130  Table 1 shows plasma clotting times of two differenttests (PT & APTT) of patient A and B. The results indicated prolongedclotting times for both patients as compared to normal range. Hence, further PTand APTT correction tests were performed by adding half of patient’s plasma(0.

05 ml) to half of normal plasma (0.05 ml) and absorbed plasma (0.05 ml)respectively. The PT and APTT clotting times of normal and absorbed plasma witheach patient’s plasma mixtures were recorded in table 1.

The PT and aPTT correction results were prolongedand out of normal range. Since the concentration and properties of thethromboplastin and the type of instrumentation can influence the results. (Christine A. Lee (MD), Erik E. Berntorp(MD), and W.

Keith Hoots (MD).Textbook of Hemophilia. Blackwell Publishing Ltd2005, p.16). Therefore, the results of PT and aPTT clotting times in table1 could be affected by the possible causes that were mentioned.  Since all the results in table 1 were affected,another unaffected PT and aPTT results will be used in table 2 for thediscussion.

      Discussion: Table2: Unaffected Prothrombin Time (PT) and Activated Partial Thromboplastin Time(aPTT) of Patient A and Patient B Plasma.   Prothrombin time (PT) (Normal = 13 – 20 seconds) Activated Partial Thromboplastin Time (aPTT) (Normal = 27 – 40 seconds) Patient A 25 50 Normal Plasma (contains all clotting factors) (0.05 ml) 16 40 Absorbed Plasma (contains factors I, V, VIII, XI, XII) (0.

05 ml)   26   51 Patient B 17 67 Normal Plasma (contains all clotting factors) (0.05 ml) – 41 Absorbed Plasma (contains factors I, V, VIII, XI, XII) (0.05 ml)   –   70  According to table 2 results, prothrombin time (PT)and activated partial thromboplastin time (aPTT) from patient A were prolongedcompared to normal range. Therefore, PT and aPTT corrections were performedwith normal plasma and the results were normal which means the problem iscorrected with normal plasma.

However, since normal plasma contains allclotting factors, the specific missing clotting factor could not be determined. Hence, PT and aPTT corrections wereperformed again with absorbed plasma and the results were prolonged for both PTand aPTT tests. Since PT tests for the efficiency of the extrinsic pathway, andaPTT tests for the efficiency of the intrinsic pathway, which means thatpatient A may developed inhibitors against both extrinsic and intrinsic factors(Marshall A. Lichtman (MD), Kenneth Kaushansky(MD), Josef T. Prchal (MD), et al. William’s Manual of Haematology 9thedition.

McGraw-Hill Education 2017, p.679). This condition may cause byacquired coagulation disorder – anticoagulant drug therapies, blood transfusion,surgical intervention, and antibiotics (FranchiniM, Lippi G. Acquired factor V inhibitors: a systematic review.

J ThrombThrombolysis. 2011;31:449–57.). The prothrombin time (PT) test for patient B shows anormal result which indicated that the patient has efficient extrinsic pathwayfactors. Hence, no further PT corrections needed to be carried out. However,the activated partial thromboplastin time (aPTT) from patient B was prolonged. Therefore,aPTT corrections were performed with normal and absorbed plasma. The results wereprolonged for absorbed plasma, and almost seemed normal with normal plasma (overby just 1 second) which means that patient B may have a deficiency of vitamin K- dependent factors (II, VII, IX, and X) cause by liver disease and mal-absorptionof vitamin K.