Introduction: of FVII, thereby activating the extrinsic system. The

Introduction:

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 together
inhibit platelet adhesion and prevent clotting formation (Marcus AJ, Broekman MJ, Drosopoulos JH, et al. The endothelial cell
ecto-ADPase responsible for inhibition of platelet function is CD39. Journal of
Clinical Investigation. 1997;99(6):1351-1360).

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When a blood vessel is ruptured, the endothelium is damaged
and present the membrane-bound tissue factor (TF) that binds with factor VIIa
(FVIIa) thus initiate the extrinsic pathway of the coagulation system. The FVII
binds with tissue factor activates factor X (FX). The factor Xa (FXa) generated
by the factor VIIa (FVIIa)-tissue factor complex activates a small amount of thrombin,
which activates factor V (FV) and factor VIII (FVIII), leading to the
presentation of the intrinsic factor Xase (FIXa–FVIIIa) and prothrombinase
complex (FXa–FVa).

Factor IXa, factor VIII, calcium and phospholipid (Xase
complex) amplify the activation of factor X generating a large amount of
thrombin. Thrombin cleaves fibrinogen to form soluble fibrin monomers which are
polymerised to form soluble fibrin polymer. Thrombin then activates FXIII which
with calcium cross links and stabilises the fibrin polymer forming cross-linked
fibrin which is the insoluble fibrin clot (Christine
A. Lee (MD), Erik E. Berntorp (MD), and W. Keith Hoots (MD).Textbook of
Hemophilia. Blackwell Publishing Ltd 2005, pp.1-3).

The initial diagnostic tests for haemostatic
disorder should include a prothrombin time (PT), activated partial
thromboplastin 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-Hill
Education 2017, p.679).

The prothrombin time (PT) evaluates the overall
efficiency of the coagulation factors of the common and extrinsic pathways (factors
V, VII, X, prothrombin and fibrinogen). It measures the clotting time of plasma
following the addition of tissue factor (thromboplastin) and calcium to hypocalcemic
plasma. The tissue factor activates FX in the presence of FVII, thereby
activating 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). It
measures the clotting time of plasma following the activation of contact
factors without adding tissue factor (thromboplastin).

In this experiment, plasma samples from two patients
were screened by measuring the PT and aPTT clotting time, and correction screening
was perform for prolongation PT and aPTT clotting time.

   

 

 

 

 

Results:

Table
1: 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

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 different
tests (PT & APTT) of patient A and B. The results indicated prolonged
clotting times for both patients as compared to normal range. Hence, further PT
and 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 with
each patient’s plasma mixtures were recorded in table 1.

The PT and aPTT correction results were prolonged
and out of normal range. Since the concentration and properties of the
thromboplastin 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 Ltd
2005, p.16). Therefore, the results of PT and aPTT clotting times in table
1 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 the
discussion.

 

 

 

 

 

 

Discussion:

Table
2: 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 prolonged
compared to normal range. Therefore, PT and aPTT corrections were performed
with normal plasma and the results were normal which means the problem is
corrected with normal plasma. However, since normal plasma contains all
clotting factors, the specific missing clotting factor could not be determined.
 Hence, PT and aPTT corrections were
performed again with absorbed plasma and the results were prolonged for both PT
and aPTT tests. Since PT tests for the efficiency of the extrinsic pathway, and
aPTT tests for the efficiency of the intrinsic pathway, which means that
patient 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 9th
edition. McGraw-Hill Education 2017, p.679). This condition may cause by
acquired coagulation disorder – anticoagulant drug therapies, blood transfusion,
surgical intervention, and antibiotics (Franchini
M, Lippi G. Acquired factor V inhibitors: a systematic review. J Thromb
Thrombolysis. 2011;31:449–57.).

The prothrombin time (PT)
test for patient B shows a normal result which indicated that the patient has
efficient extrinsic pathway factors. 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 were prolonged for absorbed plasma, and almost
seemed normal with normal plasma (over by 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-absorption of vitamin K.