This document provides an overview of coagulation and tests used to evaluate coagulation function. It discusses how coagulation maintains hemostasis and the mechanisms involved. Factors that can cause bleeding disorders are described, including vessel defects, platelet disorders, and factor deficiencies. Key tests for evaluation of coagulation are outlined, including platelet count, bleeding time, clotting time, prothrombin time, and activated partial thromboplastin time. Specific coagulation factor deficiencies like hemophilia A, hemophilia B, and von Willebrand disease are explained. Causes of acquired bleeding disorders like anticoagulant therapy and liver disease are also summarized.
2. WHAT IS COAGULATION?
●Coagulation is a complex process by which blood forms clots.
Blood must be remain fluid with in the vasculature and yet clot
quickly when expose to non endothelial surface at a site of
vascular injury.
●It is an important part of haemostasis (the cessation of blood
loss from a damaged vessel), where in a damaged blood vessel
wall is covered by a platelet and fibrin-containing clot to stop
bleeding and begin repair of the damaged vessel.
●Disorders of coagulation can lead to an increased risk of
bleeding (hemorrhage) or clotting (thrombosis).
3. Hemostasis is maintained in the body via three
mechanisms:
●Vascular spasm - Damaged blood vessels.
constrict
●Platelet plug formation - Platelats adhere to
damaged endothelium to form platelet plug
(primary hemostasis) and then degranulate.
●Blood Coagulation - Clots form upon the
conversion of fibrinogen to Fibrin, and its
addition to the platelet plug (secondary
hemostasis).
4. Factor I Fibrinogen Factor VIII
Factor II Prothrombin Factor IX
Factor III Thromboplastin Factor X
Factor IV Calcium Factor XI
Factor V Factor XII
Antihemophilic
globulin
Partial
thromboplastin
component
Stuart-Prower
factor
Plasma
thromboplastin
antecedent
Hageman factor
Factor VII
Labile or
proaccelerin
Stable factor or
proconvertin
Factor XIII Fibrin-
stabilizing factor
11. THROMBOCYTOPATHY
) ADEQUATE NUMBER BUT ABNORMAL FUNCTION )
causes
UREMIA
INHERITED DISORDERS
MYELOPROLIFERATIVE DISORDERS
DRUG INDUCED(ASPIRIN, NSAIDS)
12. FACTOR DEFICIENCIES
● Inherited:
1. Hemophilia A
HEMHHHHOPHILIA A
2. HEMOPHILIA B
3. VON WILLEBRAND’S
DISEASE
● Acquired:
1. Anticoagulant therapy
2. Liver diseases
3. DIC
19. Clotting Time - Slide Method
• The surface of the glass tube
This test
initiates the clotting process.
is sensitive to the
•
factors involved in the intrinsic
pathway
The expected range for clotting
time is 4-10 min.
21. PT
●The prothrombin time: is therefore the time required for the plasma
to clot after an excess of thromboplastin and an optimal concentration
of calcium have been added.
●Measures the function of the Extrinsic Pathway.
●Sensitive to Factors I, II, V, VII, X.
●The PT evaluates patients suspected of having an inherited or
acquired deficiency in these pathways.
23. When is it ordered?
●Used to monitor oral anticoagulant therapy (Warfarin /
Coumadin).
●When a patient who is not taking anti-coagulant drugs
has signs or symptoms of a bleeding disorder.
●When a patient is to undergo an invasive medical
procedure, such as surgery, to ensure normal clotting
ability.
24. An elevated prothrombin time
may indicate the presence of:
Vitamin K deficiency
(Vitamin K is needed to make prothrombin and other clotting factors)
➢
➢
➢
DIC
liver disease
a deficiency in one or more of the following factors:
I, II, V, VII, X.
Anticoagulant (warfarin)
25. INR
●A PT test may also be called an INR test.
●INR (international normalized ratio) stands for a way of
standardizing the results of prothrombin time tests, no
matter the testing method.
●So your doctor can understand results in the same way
even when they come from different labs and different
test methods.
●Using the INR system, treatment with (anticoagulant
therapy) will be the same. In some labs, only the INR is
reported and the PT is not reported
26. ●An INR of 1.0 means that the patient PT is normal.
●An INR greater than 1.0 means the clotting time is
elevated.
●INR of greater than 5 or 5.5 = unacceptable high risk of
bleeding,whereas if the INR=0.5 then there is a high
chance of having a clot.
●Normal range for a healthy person is 0.9–1.3, and for
people on warfarin therapy, 2.0–3.0, although the target
INR may be higher in particular situations, such as for
those with a mechanical heart valve.
28. PTT
●The partial thromboplastin time (PTT) or activated partial
thromboplastin time (aPTT or APTT( is a performance
indicator measuring the efficacy of both the "intrinsic" and
the common coagulation pathways.
●It is also used to monitor the treatment effects with
heparin a major anticoagulant.
●Kaolin cephalin clotting time (KccT) is a historic name for
the activated partial thromboplastin time
30. ●Normal PTT times require the presence of the
following coagulation factors:
I, II, III, IV, V, VI, VIII, IX, X, XI, & XII
31. When is it ordered?
●When a patient presents with unexplained bleeding or
bruising,
●It may be ordered as part of a pre-surgical evaluation for
bleeding tendencies,
●When a patient is on intravenous (IV) or injection heparin
therapy, the APTT is ordered at regular intervals to
monitor the degree of anticoagulation.
32. Prolonged APTT may indicate:
●Use of heparin.
●antiphospholipid antibody:especially lupus anticoagulant,
which paradoxically increases propensity to thrombosis
●coagulation factor deficiency ,
e.g hemophilia
●DIC
●Liver disease
33.
34. FACTOR DEFICIENCIES
❖ Inherited:
1. HEMOPHILIA A
2. HEMOPHILIA B
3. VON
WILLEBRAND’S
DISEASE
❖ Acquired:
1. Anticoagulant
therapy
2. Liver diseases
3. DIC
35. HEMOPHILIA A (Classic Hemophilia)
● 80-85% of all Hemophiliacs
● Deficiency of Factor VIII
● Lab Results - Prolonged PTT
36. ●HEMOPHILIA B (Christmas Disease)
● 10-15% of all Hemophiliacs
● Deficiency of Factor IX
● Lab Test - Prolonged PTT
37. ●VON WILLEBRAND’S DISEASE
● Deficiency of VWF & amount of Factor VIII
● Factor VIII is bound to vWF while inactive in circulation;
Factor VIII degrades rapidly when not bound to vWF
● Lab Results - Prolonged BT, PTT
38. ANTICOAGULANTS
● An anticoagulant is a substance that prevents
coagulation; that is, it stops blood from clotting
● This prevents deep vein thrombosis,
pulmonary embolism, myocardial infarction
and stroke.
ANTICOAGULANTS
1. Coumadins (Vitamin K antagonists)
2. Heparin
39. Coumadin's
●These oral anticoagulants that antagonize the effects of
vitamin K.
●Examples include warfarin. It takes at least 48 to 72 hours
for the anticoagulant effect to develop. Where an
immediate effect is required, heparin must be given
concomitantly.
●Monitored by PT times
●These anticoagulants are used to treat patients with deep-
vein thrombosis (DVT), pulmonary embolism (PE), atrial
fibrillation (AF), and mechanical prosthetic heart valves.
40. Heparin
●Heparin is a biological substance.
●It works by activating antithrombin III, which blocks
thrombin from clotting blood.
●Heparin Therapy is Monitored by PTT times
●Low molecular weight heparin is a more highly processed
product that is useful as it does not require monitoring of
the APTT coagulation parameter (it has more predictable
plasma levels) and has fewer side effects.
42. DIC
●Disseminated intravascular coagulation (DIC is a
pathological activation of coagulation) blood clotting)
mechanisms that happens in response to a variety of
diseases
●DIC leads to the formation of small blood clots inside the
blood vessels throughout the body
●The small clots also disrupt normal blood flow to organs
(such as the kidneys), which may malfunction as a result
43. ●As the small clots consume coagulation proteins and
platelets, normal coagulation is disrupted and abnormal
bleeding occurs from the skin the gastrointestinal tract,
the respiratory tract and surgical wounds.
●The PT and APTT are usually very prolonged and the
fibrinogen level markedly reduced
●High levels of fibrin degradation products, including D-
dimer, are found owing to the intense fibrinolytic activity
stimulated by the presence of fibrin in the circulation.
44. Definitive diagnosis depends on the result of DIC:
● Thrombocytopenia (prolonged bleeding time)
●Prolongation of prothrombin time and activated partial
thromboplastin time
● A low fibrinogen concentration
● Increased levels of fibrin degradation products
45. Pre-analytic errors
● Problems with blue-top tube
● Partial fill tubes
● Vacuum leak and citrate evaporation
● Problems with phlebotomy
● Heparin contamination
● Wrong label
● Slow fill
● Underfill
● Vigorous shaking
■
Biological effects
•
•
Hct ≥55 or ≤15
Lipemia, hyperbilirubinemia,
hemolysis
■
Laboratory errors
•
•
•
Delay in testing
Prolonged incubation at 37°C
Freeze/thaw deterioration