The document discusses interpretation of coagulation tests for coagulation disorders. It provides an overview of the physiology of coagulation, classification of coagulation disorders, description of specific disorders like hemophilia A and B, von Willebrand disease, fibrinogen disorders and disseminated intravascular coagulation. It also discusses interpretation of screening coagulation tests like prothrombin time, activated partial thromboplastin time and thrombin time as well as factor assays and interpretation for specific coagulation factor deficiencies.

1. Interpretation of tests in Coagulation
disorders
Moderator: Dr Deepak DC
Presenter: Dr Rashmi Budha

2. Layout
• Introduction
• Physiology of coagulation
• Classification of coagulation disorders
• Description of coagulation disorders
• Interpretation of tests
• Automation in coagulation tests
• Recent advances
• References

3. Introduction
• Blood clotting (coagulation) is initiated within
seconds after vascular injury and is considered
one of fastest tissue repair system in human
body.
• The main purpose of coagulation is to seal an
injured vessel, which is accomplished by
aggregation of platelets along with activation
of coagulation factors and fibrinolytic system.

4. Physiology of coagulation
• Hemostasis consists of three steps:
– Vasoconstriction
– Platelet plug (primary hemostasis)
– Activation of the coagulation cascade (secondary
hemostasis)
– Activation of fibrinolytic system

5. Components

6. Role of Endothelium in Coagulation
• The balance between the anticoagulant and
procoagulant activities of endothelium often
determines whether clot formation,
propagation, or dissolution occurs.

11. Clotting Factors

12. Coagulation Cascade

17. Coagulation disorders-Hypocoagulable
disorders
• Hereditary
– X-linked recessive trait
• Haemophilia-A
• Haemophilia-B
– Autosomal recessive trait
• Afibrinogenemia
• Factor XIII deficiency
– Autosomal Dominant trait
• Von-Willbrand Disease
• Acquired
– Haemorrhagic disease of
new born
– Biliary obstruction
– Malabsorption of Vitamin K
– Drugs
– Liver disease
– DIC

18. hyper

19. Hemophilia A & B
• Hemophilia A is an X-linked, recessive disorder
caused by deficiency of functional plasma
clotting factor VIII (FVIII), which may be
inherited or arise from spontaneous mutation.
• Hem b
• Hemophilia A- 17.1 per 100,000 males
• Hemophilia B- 3.8 per 100,000 males

20. Clinical Features
– Easy bruising
– Hemarthrosis (most common)
• Fixed joints
– Soft tissue hematomas (e.g., muscle)
• Muscle atrophy
• Shortened tendons
– Other sites of bleeding
• Urinary tract
• CNS, neck (may be life-threatening)
– Prolonged bleeding after surgery or dental extractions
PETECHIAE ARE CHARECTERISTICALLY ABSENT

21. Lab Evaluation
• Laboratory studies for suspected hemophilia
include the following:
– Complete blood cell count
– Screening coagulation studies (prothrombin time
[PT], activated partial thromboplastin time [aPTT])
– FVIII assay (clot based or chromogenic)
– FVIII inhibitor assay (Bethesda assay, Nijmegen
modified Bethesda assay)

22. Expected laboratory values are as follows:
• Hemoglobin/hematocrit: Normal (or low if
associated bleeding)
• Platelet count: Normal
• Prothrombin time (PT): Normal
• APTT: Significantly prolonged in severe
hemophilia, but may be normal or minimally
prolonged in mild or even moderate
hemophilia

23. Prenatal Diagnosis
• Various methods are available for prenatal
diagnosis; the method of choice varies with the
type of mutation anticipated.
• A chorionic villus biopsy can be done at 11 weeks
of gestation and tested with DNA studies such as
restriction enzymes (restriction fragment length
polymorphism [RFLP]) or PCR methods.
• Direct sampling of fetal blood from the umbilical
vein is possible at many institutions, and a factor
assay can be performed on the blood sample.

24. von Willebrand disease (VWD)
• Von Willebrand disease (vWD) is a common,
inherited, genetically and clinically
heterogeneous hemorrhagic disorder caused
by a deficiency or dysfunction of the protein
termed von Willebrand factor (vWF).
• In vWD, defective vWF interaction between
platelets and the vessel wall impairs primary
hemostasis.

25. • vWF, a large, multimeric glycoprotein,
circulates in blood plasma at concentrations of
approximately 10 mg/mL.
• In response to numerous stimuli, vWF is
released from storage granules in platelets
and endothelial cells.
• It performs two major roles in hemostasis.
– First, it mediates the adhesion of platelets to sites
of vascular injury.
– Second, it binds and stabilizes the procoagulant
protein factor VIII (FVIII).

26. EPIDEMIOLOGY
• Clinically significant vWD affects approximately
125 persons per million population, with severe
disease affecting approximately 0.5-5 persons per
million population.
• Reports from screenings of unselected individuals
indicated a higher prevalence of vWD
abnormalities, ie, close to 1% of the population.
• Males and females are affected equally by vWD.
• However, the phenotype may be more
pronounced in females, because of menorrhagia
and the greater visibility of bruises.

28. WORK UP
Screening tests typically include the following:
• Prothrombin time (PT)
• Activated partial thromboplastin time (aPTT)
• Factor VIII (FVIII) coagulant activity
• Ristocetin cofactor (RCoF) activity
• Concentration of vWF antigen (vWF:Ag)

29. Additional testing to confirm the specific
subtype may include the following:
• VWF collagen-binding activity
• Low-dose ristocetin vWF-platelet binding
• FVIII-VWF binding
• VWF multimer analysis
• VWF propeptide antigen

30. • Genetic analysis can aid diagnosis of vWD
type.
• Newer techniques, such as next-generation
sequencing, have the capacity to analyze
several genes simultaneously when necessary
and to identify exon deletions and
duplications, which makes it possible to
identify causative vWF defects in more
patients than previously.

31. FIBRINOGEN DISORDERS
• Fibrinogen disorders can be
– Quantitative (Afibrinogenemia)
– Qualitative (Dysfibrinogenemia)
• They may be
– Congenital
– Acquired.

32. • Afibrinogenemia is defined as a deficiency or
absence of fibrinogen (coagulation factor I) in
the blood.
• Dysfibrinogenemias involve structural defects
in fibrinogen that alter the conversion of
fibrinogen to fibrin.

33. Mechanisms of dysfibrinogenemias include the following:
• Impaired release of fibrinopeptides
• Defective fibrin polymerization
• Abnormal cross-linking by activated factor XIIIa (factor XIIIa)
• Abnormal interactions with platelets
• Defective fibrinolysis
• Defective assembly of the fibrinolytic system
• Abnormal calcium binding

34. The laboratory diagnosis of dysfibrinogenemias is difficult. Considerations
include the following:
• Fibrinogen antigen level is preserved but activity is markedly decreased.
• Prothrombin time (PT) appears to be more sensitive than activated partial
thromboplastin time (aPTT).
• Thrombin time (TT) and reptilase time (RT) are typically prolonged.
• Fibrinogen levels are usually less than 100 mg/dL in the absence of
iatrogenic causes (eg, massive blood loss,antifibrinolytics agents).
• Screening test results (eg, PT, aPTT) may be within reference ranges or
only slightly prolonged.
• Fibrinogen levels are decreased with DIC, primary and secondary
fibrinolysis, and liver disease.

35. Disseminated intravascular
coagulation (DIC)
• Disseminated intravascular coagulation (DIC) is a
condition in which the normal balance of
hemostasis is altered, allowing the uncontrolled
and inappropriate formation and lysis of fibrin
within the blood vessels.
• DIC occurs in approximately 1 in 1000
hospitalized patients.
• It can occur at any age, although it is more often
seen in the very young and the elderly.

36. Etiology

37. Pathophysiology

38. Clinical features

39. Coagulation Factor Deficiencies

40. Factor V deficiency
• An inherited autosomal recessive deficiency of
factor V, also known as proaccelerin (or
accelerator globulin or labile factor) leads to a
rare hemorrhagic tendency known as Owren
disease or parahemophilia.
• The severity of the condition varies from
bruising to lethal hemorrhage.
• Both PT and aPTT may be prolonged.

41. Factor VII deficiency
• Factor VII is a vitamin K–dependent glycoprotein essential to
the extrinsic pathway of coagulation.
• Deficiencies may be inherited as an autosomal recessive
characteristic or acquired in association with vitamin K
deficiency, sepsis, autoantibodies, and inhibitors.
• This defect produces prolonged PT, reduced factor VII activity,
and normal aPTT.

42. Factor X deficiency
• Factor X deficiency is a coagulation disorder usually inherited
as an autosomal recessive trait, though it can be acquired.
• This deficiency is characterized by defective activity in both
the intrinsic and extrinsic pathways, impaired thromboplastin
time, and impaired prothrombin consumption.
• Both PT and aPTT are prolonged.

43. Factor XI deficiency
• Factor XI deficiency is a congenital deficiency of blood
coagulation factor XI (known as plasma thromboplastin
antecedent [PTA] or antihemophilic factor C) resulting in a
systemic blood-clotting defect called hemophilia C or
Rosenthal syndrome, which may resemble classic hemophilia.

44. Factor XII deficiency
• Factor XII deficiency is defined as an absence or
reduced level of blood coagulation factor XII
(Hageman factor).
• Factor XII initiates the intrinsic coagulation
cascade and is linked to the fibrinolytic, kallikrein-
kinin, and complement systems.
• The disorder may be considered in patients with
prolonged aPTT, normal PT, normal bleeding time,
and no clinical history of bleeding.

45. Factor XIII deficiency
• Factor XIII deficiency is a decrease or absence of factor XIII
(fibrin-stabilizing factor [FSF]) that prevents blood-clot
formation and results in a clinical hemorrhagic diathesis.
• Bleeding in a patient with both normal PT and aPTT should
raise the suspicion.
• Congenital factor XIII deficiency is a severe autosomal
recessive bleeding disorder associated with a characteristic
pattern of neonatal hemorrhage and lifelong bleeding
diathesis.

46. • The disorder affects both sexes, and bleeding
may occur during pregnancy.
• Acquired factor XIII deficiency has been
described in HSP, various forms of colitis,
erosive gastritis, and some forms of leukemia.

51. Coagulation Tests
Screening Tests Special Tests
- Clotting time
- PT - Mixing Tests
- aPTT - Factor assays
- TT - Reptilase Time

52. Blood Collection
 Venous blood sample should be obtained
 Excessive stress & vigorous exercise must be avoided
– will increase factor VIII ,VW antigen & fibrinolysis .
 Blood should be collected without a pressure cuff –
venous occlusion causes hemoconcentration ,
increase of fibrinolytic activity ,platelet release &
activation of some clotting factors .
 Contact activation must be minimized .

53. Blood Sample for Coagulation Tests
 Anticoagulant used –3.2% Tri sodium citrate
 Blood : citrate ratio – 9:1
 Platelet poor plasma
 The anticoagulated blood is centrifuged at 2500
rpm for 15 mins.
 For PT test ,Lupus anticoagulant or factor VII
assay , sample must be kept at room temp.
For other assays – kept at 4°C

54. CLOTTING TIME
 Time taken for whole blood , drawn from a vein &
immediately placed in a container to clot
 Measures all stages of intrinsic coagulation
 Care must be taken to avoid contamination with
tissue fluid
 Methods
1) Modified Lee & White method
2) Capillary tube method
3) Slide method
 Normal value – 8-15 mins.

55. Slide 43

56. PROTHROMBIN TIME
 Time required for the clotting of plasma in a glass
tube in the presence of an optimal concentration of
tissue extract (thromboplastin)
 Indicates the overall efficiency of the extrinsic
clotting system .
 Measures activity of prothrombin , Factors V , VII
& X , & fibrinogen concentration of the plasma .
 Normal value – 11-16 s.

57.  Reagents :
a) Plasma samples – platelet poor plasma
from the patient & control
b) Tissue Thromboplastin –
• Extract of rabbit brain or lung
• Recombinant thromboplastin -
manufactured using recombinant
human tissue factor produced in E.coli
& synthetic phospholipids
c) Calcium chloride

58.  Method :
1) Deliver 0.1 ml of plasma in a glass tube
placed in a water bath .
2) Add 0.1 ml of thromboplastin .
3) Allow the mixture for warm for 1-3 mins.
4) Then add 0.1 ml warmed CaCl2 & start the
stopwatch .
5) The tube is lifted up & gently tipped back
& forth
6) The stopwatch is stopped at the moment
the clot is observed .

60. INTERNATIONAL NORMALIZED RATIO (INR)
• Standardized reporting of results
• Needed for patients on oral anticoagulant therapy
• PT ratio further modified by taking into account the
sensitivity of the reagent – International sensitivity
Index (ISI)
• ISI value for the WHO reference reagent is set at 1.0
• INR = (PTR)ISI
• INR value desired – 2.0 – 3.0

61. PARTIAL THROMBOPLASTIN TIME
 The time required for clotting of citrate plasma in a
glass tube after the addition of kaolin ,
phospholipid & calcium
 Activated Partial Thromboplastin Time – PTT is
refined by minimizing the variations of time due to
surface activation by maximally activating the surface
factors .
 Normal range – 26-40 s

62.  Indicates the overall efficiency of the intrinsic
pathway
 Used for - monitoring heparin therapy
- detecting inhibitors of
coagulation
 Sensitive to the level of activity of surface factors
(factor XII & XI) , factors IX , VIII , X , V , II &
fibrinogen .
 To standardize the activation of contact factors the
plasma is preincubated for a set period with a
contact activator

63.  Reagents :
1) Platelet poor plasma – patient & control
2) Surface activator – kaolin /silica /celite
/ellagic acid .
3) Phospholipid – ensures immediate
availability of optimum material for
complex formation without waiting for
release of phospholipid from platelets .
4) Calcium chloride

64.  Method :
a) Mix equal volumes of phospholipid reagents
& kaolin suspension in a glass tube in water
bath at 37°C .
b) Place 0.1 ml of plasma into a new glass tube
& add 0.1 ml of the above solution , mix &
start the stopwatch simultaneously
c) Leave for 10 mins. with occasional shaking
d) Add 0.1 ml of prewarmed CaCl2 & start a
second stopwatch .
e) Record the time taken for the mixture to clot .

66. THROMBIN TIME
 The time taken for clotting to occur after the
addition to thrombin to plasma
 It is affected by the presence of fibrinogen/
fibrin degradation products & heparin .
 The appearance of the clot is equally
informative .
 A commercial bovine thrombin is used .
 Normal range – 15-19 s

68. FIBRINOGEN ASSAY
Various methods to determine fibrinogen
concentration :
 Precipitation /denaturation
 Turbidimetry
 Immunological assay
 UV measurement of fibrin clot
 Clot based Clauss assay
The reference method for quantitative determination
of fibrinogen is the clot based Clauss assay .

69. Clauss Assay
 Principle – Diluted plasma is clotted with a strong
thrombin solution
 Fibrinogen concentration is inversely proportional to
the TT of diluted plasma
 TT is performed on 1:10 dilution of patients platelet
poor plasma & time for clot formation is recorded
 Normal range – 150-350 mg/dl

70. • Thromboelastography (TEG)or
thromboelastometry are found to be the most
accurate measurement of dysfibrinogenemia
or qualitative dysfunctions.
• These assays evaluate clot strength and
firmness, with elastometry showing a better
association with the Clauss method of
measuring fibrinogen levels.

71. Conditions 2nd line investigations
 Disorder of platelet
function
 Mild Von Willebrand
disease
 Factor XIII deficiency
 Vascular disorder of
hemostasis
 Normal hemostasis with
bleeding from a severely
damaged vessel/vessels
 Disorder of fibrinolysis
Specific factor assays for the
suspected factor deficiencies
 Appropriate screening tests
(PFA-100 system , bleeding
time , clot solubility test )
PT , APTT , TT , Fibrinogen , PC – All Normal

72. PT – Prolonged
APTT , TT , Fibrinogen , PC - Normal
Conditions 2nd line Investigations
 factor VII deficiency
 Start of oral
anticoagulant therapy
 Lupus anticoagulant
 Mild deficiency of factor
II , V , X
 Mixing test
 Specific factor assay
 Specific test for lupus
 Biochemical measures
of liver function tests
 History of oral
anticoagulant drugs

73. APTT - Prolonged
PT , TT , Fibrinogen , PC – Normal
Conditions 2nd line investigations
 Congenital deficiencies/
defects of the intrinsic pathway
 Mild deficiency of factor II ,
V , X
 Von Willebrands disease
 Presence of circulating
anticoagulants (inhibitors)
 Heparin
Establish whether patient has
a deficiency or an inhibitor
(50:50 mixture test )

74. PT , APTT – Prolonged
TT , Fibrinogen , PC – Normal
Conditions 2nd line investigations
 Lack of Vitamin K
 Administration of oral
anticoagulant
 Liver disease
 Rarely , congenital/
acquired defects of factor
V , X , prothrombin &
combined V & VIII
 Mixing experiments
using PTT
 If correction obtained –
specific factor assay

75. PT , APTT , TT – Prolonged
Fibrinogen – Normal/ abnormal
PC – Normal
Conditions 2nd line Investigations
o Presence of large
amounts of
unfractioned heparin
o Systemic
hyperfibrinolysis
o Fibrinogen deficiency
/ disorder
o Reptilase / Ancrod
time
o Measure fibrinogen
concentration
o FDPs / D-dimer

76. PC – Low
PT , APTT – Prolonged
TT – Normal
Fibrinogen – Normal /abnormal
Conditions 2nd line Investigations
• After massive
transfusion with stored/
plasma reduced blood
• Some cases of chronic
liver failure
• DIC
• Specific factor assay
• Consider that low PC
has a separate etiology

77. PT , APTT , TT – Prolonged
Fibrinogen , FDP – low
Conditions 2nd line Investigations
 Acute DIC
 Some cases of
acute liver disease
with DIC
 Confirm diagnosis
of DIC

78. MIXING STUDIES
 They are performed to differentiate a factor
deficiency from the presence of a circulating
inhibitor
 The abnormal coagulation test is repeated using
several dilutions of patient plasma & normal plasma
 Approximately 50% of the factor level is sufficient to
produce a normal PT & APTT .
 Therefore , a correction indicates a factor deficiency
.

79. The following agents can be used for mixing tests:
normal plasma
aged serum
adsorbed plasma
FVIII-deficient plasma
FIX-deficient plasma
Aged serum - deficient in factors I ,II ,V and VIII.
Adsorbed plasma - deficient in factors II, VII, IX, and X
(vitamin K-dependent factors).

80. (Equal volumes)
patient plasma + adsorbed normal plasma
Correction No correction
PT prolonged APTT prolonged
Deficiency of factor
II/VII/X/X
Deficiency of Deficiency of
factor factor
I/V VIII/XI/XII

81. (Equal volumes)
patient plasma + aged normal serum
Correction No correction
PT prolonged APTT prolonged
Deficiency of
factor
I/II/VIII/V/XIII
Deficiency of Deficiency of
factor factor
VII/X IX/X/XI/XII

82. (Equal volumes)
patient plasma + adsorbed plasma + aged serum
Corrected only by Corrected only by
adsorbed plasma aged serum
Corrected by both
adsorbed plasma
Factor XII & aged serum Factor IX
deficiency deficiency
Factor XI /X deficiency

83. REPTILASE / ANCROD TIME
 Reptilase – purified enzyme of snake Bothrops atrox
 Ancrod – a similar enzyme from the snake Agkistrodm
rhodostoma
 Used to replace thrombin in TT test
TT RT
Heparin
contamination
Prolonged Normal
Dysfibrinogenemia Prolonged More prolonged
Presence of FDP More prolonged Prolonged

84. Factor Assays
• Normal values for FVIII assays are 50-150%.

85. vWF Activity
• vWF activity (the binding of VWF to platelet
glycoprotein Ib [GPIb]) has traditionally been
assessed by ristocetin cofactor (RCoF) activity.
• In this test, ristocetin is added to a suspension
of washed formalin- or paraformaldehyde-
fixed platelets in the presence of the patient's
plasma (as a source of vWF).

86. • The rate of aggregation is then measured
using an aggregometer, a device specifically
designed to monitor this activity.
• Normal RCoF values are 50-200 IU/dL.
• A level below 30 IU/dL is considered definitive
for vWD, although levels of 30-50 IU/dL may
be found in some patients with type 1 or 2
vWD.

87. vWF:Ag
• This assay is usually performed (with rabbit
antibody to vWF) using either a quantitative
immunoassay or an enzyme-linked
immunosorbent assay.
• A discrepancy between the vWF:Ag value and
RCoF activity suggests a qualitative defect that
should be further investigated by
characterization of the vWF multimeric
distribution.

88. • As with RCoF, a vWF:Ag level below 30 IU/dL is
considered diagnostic of vWD, but levels of
30-50 IU/dL may be found in some patients
with type 1 or 2 vWD.

89. EVALUATION OF THE FIBRINOLYTIC SYSTEM
1) Fibrin Degradation Products
 Its presence indicates increased fibrinolytic
activity
 Conditions associated with increased FDPs :
 DIC
 Liver Disease
 Alcoholic cirrhosis
 Kidney disease
 Cardiac disease ,etc

90.  It is identified through a specific antigen-
antibody reaction
 Latex agglutination method
 A suspension of latex particles sensitized with
specific antibodies to FDP is used .
 Aggregation indicates the presence of FDP ,
 it’s a semi-quantitative assay - by testing different
dilutions of the unknown sample – 1:2 & 1:8

91.  Normal value - < 5 µg/ml
 The standard assay does not distinguish
between fibrin & fibrinogen degradation
products
1:2 Dilution 1:8 Dilution FDP Value
+ + > 20µg/ml
+ _ 5 – 20 µg/ml
_ _ < 5 g/mlµ

92. 2) D-Dimer
 It is a specific marker for plasmin degradation
(lysis) of fibrin .
 It is a fibrin degradation product generated from
factor XIIIa crosslinked fibrin
 Latex particles coated with monoclonal
antibodies for D-dimer is added to undiluted &
1:2 diluted samples

93.  Increased in :
 DIC with secondary fibrinolysis
 Pulmonary embolism
 DVT
 Arterial thromboembolism
 Recent trauma
 Cirrhosis , Renal failure
 Patients with hyperfibrinolysis without
thrombin generation have increased FDPs but
normal D-dimer level

94. Undiluted sample
(Agglutination)
1:2 Diluted sample
(Agglutination)
D-dimer Level
- - < 0.5 µg /ml
+ - 0.5 – 1.0 µg /ml
+ + > 1.0 µg /ml
 Normal value - <0.5 µg/ml
 D-dimer assay is performed on plasma as well as
serum (as fibrin & fibrinogen does not cross react
with D-dimer)

95. 3) Euglobin Clot Lysis
 Measures overall fibrinolysis
 The euglobin fraction of plasma consists of
fibrinogen , plasminogen & the activators of
plasminogen
 This fraction is isolated from plasma & thrombin
is added to clot the euglobulins
 The resulting clot is incubated at 37°C for 2 hrs &
at 30 minute intervals the clot is observed for
lysis
 Normal value - > 2 hrs

96.  Euglobin clot lysis time < 2hrs indicates
increased fibrinolytic activity
 It is seen in :
 DIC
 Liver diseases
 Surgery
 Factor XIII deficiency
 OCP’s & during menstruation

97. Investigation of Hypercoagulable states

98. 1) Antithrombin III
 Measured by –
 Immunologic assay – enzyme immunoassay ,
ELISA , radial immuno- deficiency or microlatex
particle immuno- logic assay
 Functional assays – they assess inhibitor activity
in the presence /absence of heparin & use either
thrombin/factor Xa as targets for inhibition .

99. 2) Protein C :
 Quantitative analyses – EIA/ ELISA .
 Functional assay – uses either thrombin /
thrombomodulin complex to activate protein C
.
 Enzyme activity is then assessed by
chromogenic substrate / clot-based assay .
 Acquired deficiencies of protein C are
associated with
 DIC
 Vitamin k deficiency
 Liver Disease
 Oral anticoagulant therapy

100. 3) Protein S :
 Circulating protein S (PS) exist in free form
(40%) & bound to C4b binding protein (60%)
 Lab evaluation includes –
 Assays of total PS – ELISA assay
 Assays of free PS – immunoassay using a
monoclonal antibody specific for the free form
 Functional assay – based on the ability of PS to
serve as a cofactor for the anticoagulant effect
of activated protein C

101. 4) Plasminogen / Plasminogen activator :
 Plasminogen – measured based on its conversion
to plasmin by an excess of activator .
 Plasminogen activator – quantitated by cleavage
of specific chromogenic substrates
 Plasminogen activator inhibitor is assessed by its
activation-neutralization capacity
.
 Antigenic levels of the above are determined by
ELISA / RID

102. AUTOMATION IN COAGULATION STUDIES
 Leads to increased precision & accuracy &
therefore , improved diagnostic testing &
monitoring of therapy .
1) Electromechanical Instruments :
a. Fibrometer – it detects completion of an
electrical circuit between 2 electrodes when a
clot forms .

103. b. STArt 4 Clot Detection – based on the
increasing viscosity of plasma as clot
formations occurs .
Detects decrease in movement of an iron ball
in an electromagnetic field when a clot forms .
2) Optical Density Instruments :
 It utilizes the change in optical density.
3) Chromogenic /Clot detection Instruments :
 It combines clot-based detection with
chromogenic analysis .