Testing of coagulation Numerous tests are used to assess the function of the coagulation system:
- Common:
aPTT,
PT (also used to determine
INR),
fibrinogen testing (often by the
Clauss method),
latelet
count, platelet function testing (often by
FA-100).
- Other:
TCT,
bleeding time,
mixing test (whether an abnormality corrects if the patient's plasma is
mixed with normal plasma), coagulation factor assays,
antiphosholipid antibodies,
-dimer,
genetic tests (eg.
factor V Leiden,
prothrombin mutation G20210A),
dilute Russell's viper venom time (dRVVT), miscellanous platelet
function tests,
thromboelastography (TEG or ROTEM),
euglobulin lysis time (ELT), .
The contact factor pathway is initiated by activation of the "contact
factors" of plasma, and can be measured by the
activated partial thromboplastin time (aPTT) test.
The tissue factor pathway is initiated by release of
tissue factor (a specific cellular lipoprotein), and can be measured by the
prothrombin time (PT) test. PT results are often reported as ratio (NR
value) to monitor dosing of oral anticoagulants such as
arfarin.
The quantitative and qualitative screening of fibrinogen is measured by the
thrombin clotting time (TCT). Measurement of the exact amount of fibrinogen
present in the blood is generally done using the
Clauss method for fibrinogen testing. Many analysers are capable of
measuring a "derived fibrinogen" level from the graph of the Prothrombin time
clot.
If a coagulation factor is part of the contact or tissue factor pathway, a
deficiency of that factor will affect only one of the tests: thus
hemophilia A, a deficiency of factor VIII, which is part of the contact
factor pathway, results in an abnormally prolonged aPTT test but a normal PT
test. The exceptions are prothrombin, fibrinogen and some variants of FX which
can only be detected by either aPTT or PT. If an abnormal PT or aPTT is present
additional testing will occur to determine which (if any) factor is present as
aberrant concentrations.
Deficiencies of fibrinogen (quantitative or qualitative) will affect all
screening tests.
Role in disease Problems with coagulation may dispose to hemorrhage, thrombosis, and
occasionally both, depending on the nature of the pathology.
Platelet disorders
Platelet conditions may be inborn or acquired. Some inborn platelet
pathologies are
Glanzmann's thrombasthenia,
Bernard-Soulier syndrome (abnormal glycoprotein Ib-IX-V complex),
gray platelet syndrome (deficient
alpha granules) and
delta storage pool deficiency (deficient
dense granules). Most are rare conditions. Most inborn platelet pathologies
predispose to hemorrhage.
von Willebrand disease is due to deficiency or abnormal function of
von Willebrand factor, and leads to a similar bleeding pattern; its milder
forms are relatively common.
Decreased platelet numbers may be due to various causes, including
insufficient production (e.g. in
myelodysplastic syndrome or other bone marrow disorders), destruction by the
immune system (mmune
thrombocytopenic purpura/ITP), and consumption due to various causes (hrombotic
thrombocytopenic purpura/TTP,
hemolytic-uremic syndrome/HUS,
paroxysmal nocturnal hemoglobinuria/PNH,
disseminated intravascular coagulation/DIC,
heparin-induced thrombocytopenia/HIT). Most consumptive conditions lead to
platelet activation, and some are associated with thrombosis.
Disease and clinical significance of thrombosis
The best-known coagulation factor disorders are the
hemophilias. The three main forms are
hemophilia A (factor VIII deficiency),
hemophilia B (factor IX deficiency or "Christmas disease") and
hemophilia C (factor XI deficiency, mild bleeding tendency). Hemophilia A
and B are X-linked recessive disorders whereas Hemophilia C is much more rare
autosomal dominant disorder most commonly seen in Ashkenazi Jews.
von Willebrand disease (which behaves more like a platelet disorder except
in severe cases), is the most common hereditary bleeding disorder and is
characterized as being inherited autosomal recessive or dominant. In this
disease there is a defect in von Willebrand factor (vWF) which mediates the
binding of glycoprotein Ib (GPIb) to collagen. This binding helps mediate the
activation of platelets and formation of primary hemostasis.
Bernard-Soulier syndrome there is a defect or deficiency in GPIb. GPIb, the
receptor for vWF, can be defective and lead to lack of primary clot formation
(primary hemostasis) and increased bleeding tendency. This is an autosomal
recessive inherited disorder.
Thrombasthenia of Glanzman and Naegeli (lanzmann
thrombasthenia) is extremely rare. It is characterized by a defect in GPIIb/IIIa
fibrinogen receptor complex. When GPIIb/IIIa receptor is dysfunctional
fibrinogen cannot cross-link platelets which inhibits primary hemostasis. This
is an autosomal recessive inherited disorder. In
iver
failure (acute and chronic forms) there is insufficient production of
coagulation factors by the liver; this may increase bleeding risk.
Deficiency of Vitamin K may also contribute to bleeding disorders because
clotting factor maturation depends on Vitamin K.
Thrombosis is the pathological development of blood clots. These clots may
break free and become mobile forming an
embolus or grow to such a size that occludes the vessel in which it
developed. An
embolism is said to occur when the
hrombus
(blood clot) becomes a mobile embolus and migrates to another part of the body,
interfering with blood circulation and hence impairing organ function downstream
of the occlusion. This causes
schemia
and often leasds to ischemic
ecrosis of
tissue. Most cases of thrombosis are due to acquired extrinsic problems (urgery,
ancer,
immobility,
obesity,
economy class syndrome), but a small proportion of people harbor
predisposing conditions known collectively as thrombophilia (e.g.
antiphospholipid syndrome,
factor V Leiden and various other rarer genetic disorders).
Mutations in
actor XII
have been associated with an asymptomatic prolongation in the clotting time and
possibly a tendency towards
thrombophlebitis. Other mutations have been linked with a rare form of
ereditary
angioedema (type III).
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