Coagulation

 The average person circulates about 5 L of blood, of which is 3 L plasma and 2 L cells
 Plasma fluid derives from the intestines and lymphatic systems and provides a vehicle for cell movement
 The cells are produced primarily by bone marrow and account for blood “solids”
 The prime function of the coagulation mechanism is to protect the integrity of the blood vessels while
maintain the fluid state of blood
 Serious medical problems or even death may occur with the inability to stem the loss of blood or with the
inability for a normal clot to form

When are coagulation tests ordered?

 Patients with bleeding disorders

 Vascular injury or trauma
 Coagulopathies

Hypercoagulability States

Two general forms:

 Hyperreactivity of the platelet system

o Results in arterial thrombosis
 Accelerated activity of the clotting system
o Results in venous thrombosis

Hypercoagulability refers to an unnatural tendency toward thrombosis. The thrombus is the actual
insoluble mass (fibrin or platelets) present in bloodstream or chambers of the heart.

 Platelet abnormalities
 Clotting system abnormalities
 Venous thrombosis

Bleeding Time

Measures the primary phase of hemostasis, the interaction of the platelet with the blood vessel wall and the
formation of the hemostatic plug. This is the best single screening test for platelet function disorders and is one of the
primary screening tests for coagulation disorders. Of value in detecting vascular abnormalities and platelet
abnormalities or deficiencies. Critical value is >15 minutes.

Platelet Count

Thrombocytes are the smallest formed elements in the blood. Platelet activity is necessary for blood clotting,
vascular integrity and vasoconstriction, and the adhesion and aggregation activity that occurs during the formation
of platelets plugs that occlude breaks in small vessels.

 Thrombocyte development takes place primarily in the bone marrow

  The life span of a platelet is about 7.5 days
 Normally, 2/3 of all body platelets are found in the circulating blood
 Normally, 1/3 in the spleen
 Of value for assessing bleeding disorders that occur with thrombocytopenia, uremia, liver disease, or
malignancies
 Aides in monitoring the course of disease associated with bone marrow failure

Thrombin Time (TT) (7.0-12.0 seconds)

Stage III fibrinogen defects can be detected by the TT test. It can detect DIC and hypofibrinogenemia and
may also be used for monitoring streptokinase therapy. Measures the time needed for plasma to clot when thrombin
is added.

Prolonged TT

 Hypofibrinogenemia
 Therapy with Heparin
 DIC
 Multiple myeloma
 Severe liver disease

Shortened TT

 Hyperfibrinogenemia
 Elevated Hct

Partial Thromboplastin Time (PTT)

Activated Partial Thromboplastin Time (aPTT) (21.0-35.0 seconds)

The PTT, a one-stage clotting test, screens for clotting disorders. Specifically, it can detect deficiencies in the
intrinsic thromboplastin system and also reveal defects in the extrinsic coagulation mechanism pathway.

The aPTT is used to detect deficiencies in the intrinsic coagulation system, to detect incubating
anticoagulants, and to monitor heparin therapy. >70 seconds signifies spontaneous bleeding.

Prolonged aPTT

 All congenital deficiencies of the intrinsic system coagulation factors

 Heparin therapy
 Liver disease
 DIC
 Vitamin K deficiency

Shortened aPTT

 Extensive cancer, except when the liver is involved

 Immediately after acute hemorrhage
 Activated Clotting Time (ACT) (70-120 seconds)

The ACT test evaluates coagulation status. The ACT responds linearly to heparin level changes and
responds to wider ranges of heparin concentration than does the aPTT. The ACT, however, assays overall
coagulation activity. Therefore, prolonged values may not be exclusively the result of heparin.

 Dialysis
 Coronary artery bypass procedures
 Arteriograms
 Percutaneous transluminal coronary arteriography

Prothrombin Time (PT) (11.0-13.0 seconds)

Prothrombin is a protein produced by the liver for clotting of blood. Prothrombin production depends on
adequate vitamin K intake and absorption. During the clotting process, prothrombin is converted to thrombin. The
prothrombin content of the blood is reduced in patients with liver disease.

 One of the most important screening tests used in diagnostic coagulation studies
 Directly measures a potential defect in the extrinsic coagulation system through analysis of the clotting
ability of five plasma coagulation factors
o Prothrombin
o Fibrinogen
o Factor V
o Factor VII
o Factor X

Increased PT

 Deficiency in factors II, V, VII, or X

 Vitamin K deficiency
 Liver disease
 Current anticoagulation therapy with Coumadin (Warfarin)
 Biliary obstruction
 Circulating anticoagulants, lupus anticoagulant

Conditions that do not affect PT

 Polycythemia vera
 Christmas disease (factor IX deficiency)
 Hemophilia A (factor VIII deficiency)
 von Willebrand’s disease
 Platelet disorders

Interfering factors

 Diet: ingestion of excessive green, leafy vegetables increases vitamin K, which promotes blood clotting
 Alcoholism or excessive ingestion prolongs PT levels
 Diarrhea and vomiting decrease PT due to dehydration
 Many medications
 International Normalized Ratio (0.8-1.2)

The INR is a comparative rating of PT ratios. Used to monitor anticoagulation therapy.

 Primary and secondary prevention of deep vein thrombosis

o 2.0-3.0
 Prevention of systemic embolism in patients with atrial fibrillation
o 2.0-3.0
 Prevention of arterial thrombosis in patients with mechanical heart valves
o 2.5-3.5

Coagulant Factors

Assay of specific factors of coagulation is done in the investigation of inherited and acquired bleeding
disorders.

Inherited deficiencies

 Any of the specific factors – I, II, V, VII, VIII, IX, X, XI, XII, and XIII – may be deficient on a familial basis
 Factor VII is decreased in hypoproconvertinemia (autosomal recessive)
 Factor VIII is decreased in classic hemophilia A and von Willebrand’s disease (inherited autosomally)
 Factor IX is decreased in Christmas disease or hemophilia B (sex-linked recessive)
 Factor XI is decreased in hemophilia C (autosomal dominant, occurring predominantly in Jewish)

Acquired disorders

 Factor II is decreased in
o Liver disease
o Vitamin K deficiency
o Oral anticoagulants (last factor to decrease after starting Coumadin)
o Normal newborns
o Circulating inhibitors or lupus-like anticoagulants
 Factor V is decreased in
o Liver disease
o Factor V inhibitors
o Myeloproliferative disorders
o DIC and fibrinolysis
o Normal newborns
 Factor VII is decreased in
o Liver disease
o Treatment with Coumadin-like drugs (first factor to decrease)
o Normal newborns
o Kwashiorkor
 Factor VIII is increased in
o Thromboembolic conditions
o Liver disease
 Factor VIII is decreased in
o Presence of Factor VIII inhibitors (associated with hemophilia A)
o von Willebrand’s disease
o Myeloproliferative disorders
 Factor IX is decreased in
o Uncompensated cirrhosis, liver disease
 o Nephrotic syndrome
o Vitamin K deficiency
 Factor X is decreased in
o Liver disease
o Vitamin K deficiency
o Oral anticoagulants
o Amyloidosis
 Factor XI is decreased in
o Liver disease
o Intestinal malabsorption (vitamin K)
 Factor XII is decreased in
o Liver disease
o Nephrotic syndrome
o Chronic granulocytic leukemia
 Factor XIII is decreased in
o Liver disease
o Acute myelogenous leukemia

Plasminogen

Plasminogen is a glycoprotein, synthesized in the liver, present in the plasma. Under normal circumstances,
plasminogen is a part of any clot because of the tendency of fibrin to absorb plasminogen from the plasma.

D-Dimer (0-0.6 mg/L)

D-Dimers are produced as a degradation product of fibrin clots resulting from the action of three enzymes:
thrombin, activated Factor XIII, and plasmin. The presence of D-Dimer confirms that both thrombin generation and
plasmin generation have occurred.

 Used in the diagnosis of DIC, venous thromboembolism, and excluding the diagnosis of a pulmonary
embolism

Fibrinogen (200-400 mg/dL)

Fibrinogen is a complex protein (polypeptide) that, with enzyme action, is converted to fibrin. The fibrin,
along with platelets, forms the network for the common blood clot. Although it is of primary importance as a
coagulation protein, fibrinogen is also an acute-phase protein reactant. It is increased in diseases involving damage
or inflammation.

 This test is done to investigate abnormal PT, aPTT, and TT and to screen for DIC and fibrin-fibrinogenolysis
 It is part of a coagulation panel

Protein C

Protein C, a vitamin K-dependent protein that prevents thrombosis, is produced in the liver and circulates
in the plasma. It functions as an anticoagulant by inactivating factors V and VIII.
  This test is used for evaluation of patients suspected of having congenital protein C deficiency
 Resistance to protein C is caused by an inherited defect in the factor V gene (factor V Leiden) and causes
significant risk for thrombosis
 It is the underlying defect in up to 60% of patients with unexplained thrombosis and is the most common
cause of pathologic thrombosis
 If functional protein C is abnormal, a protein C resistance test should be performed

Protein S

Protein S also is dependent on vitamin K for production and function. Protein S serves as a cofactor to
enhance the anticoagulant effects of activated protein C.

Antithrombin III

AT-III inhibits the activity of activated factors XII, XI, IX, and X as well as factor II. The main physiologic
inhibitor of activator factor X. A significant number of patients with mesenteric venous thrombosis have AT-III
deficiency.

Lupus Anticoagulant

An antibody that is responsible for inhibition of the PT, PTT, Russell viper venom time, and kaolin clotting time.

Conditions associated with the presence of the lupus anticoagulant

 SLE (1/5 of patients)

 Multiple myeloma
 Other autoimmune diseases
 Spontaneous abortions
 Lupus anticoagulant is more often associated with thromboembolism that with bleeding problems