Hemostasis Objectives
Hemostasis Overview, Tests
& Disorders
• Describe the activation of all major hemostatic
components following injury.
Linda Sykora
lmsykora@unmc.edu
• Describe the role of the vascular system and
platelets in hemostasis.
• Discuss the activation and function of the:
– Intrinsic, extrinsic and common coagulation pathways,
including the final enzyme thrombin.
– Fibrinolytic system, including the final enzyme plasmin.
• Describe the role of the regulatory system in
maintaining hemostatic balance, e.g. antithrombin.
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• Discuss the screening tests performed to detect
defects of primary and secondary hemostasis.
Hemostasis Objectives
Hemostasis
• Discuss specimen requirements, reference ranges,
and significance of the following tests:
– Platelet count (PLT) and Bleeding time (BT)
– Protime (PT), including the clinical use of the International
Normalized Ratio (INR)
– Partial thromboplastin time (PTT)
• Evaluate selected hereditary & acquired disorders
of hemostasis, including cause, clinical findings and
laboratory results.
• Discuss the mode of action, clinical use and the lab
tests affected and/or used to monitor:
– Therapeutic anticoagulants (heparin and coumarin)
– Thrombolytic agents (TPA)
– Antiplatelet agents (aspirin, Plavix®)
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• Prevention and control of bleeding, achieved by a
balance of bleeding and clotting
– Injury initiates a series of spontaneous reactions that
result in a localized clot to arrest bleeding
• Hemostasis should be active only when and where
it is needed and the response must be controlled
– Injury size determines the degree of response
• Depends upon interaction between vessels,
platelets, and plasma proteins
– Occurs in stages
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Stages
Components of Hemostasis
Vessel injury
Primary Hemostasis
Secondary Hemostasis
Fibrinolysis begins
(Intact)
• Vascular system - vasoconstriction of injured
vessel occurs first…controls rate of blood flow
• Platelet activity – vessels and platelets form a
temporary platelet plug…primary hemostasis
• Coagulation (fibrin forming) system – coagulation
factors convert fibrinogen to fibrin forming a stable
fibrin clot… secondary hemostasis
• Fibrinolytic (fibrin lysing) system – the fibrin clot is
slowly removed during healing…fibrinolysis
Platelet
Plasma
proteins
Fibrinolysis & repair complete
• Regulatory system – protein inhibitors shut-down
clotting and lysing
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CLS500 Application and Interpretation of
Clinical Laboratory Data
Hemostasis & Disorders Powerpoint Handout
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Vascular System
Components of Hemostasis
(Intact)
• Arteries, veins, capillaries
• Inactive in presence of intact vascular tissue
• Endothelium
• Upon injury, each component must respond
– Endothelial cells line vessels
– Thromboresistant lining, non-reactive unless injured
– Formation and dissolution of clots is balanced process
• Imbalance can lead to:
• Subendothelium
– Bleeding, a hypocoagulable state
– Thrombosis, a hypercoagulable
state
– Smooth muscle & connective tissue with collagen fibers
– Collagen is exposed upon injury to endothelium
• Endothelial cells release substances that inhibit or
stimulate platelets, coagulation and fibrinolysis
• Many inherited or acquired disorders
– Effective treatment depends on rapid clinical and
laboratory identification
– Tissue factor (TF), tissue plasminogen activator (tPA),
vonWillebrand’s factor (vWF)
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Platelets/Thrombocytes
Platelets/Thrombocytes
Platelets/Thrombocytes
Platelets/Thrombocytes
• Cytoplasmic fragments shed
from bone marrow precursors
called megakaryocytes
• Platelets effectively halt bleeding in small vessels
Platelet Precursors
Megakaryocytes
– Regulated by thrombopoietin (TPO)
– 80% blood, 20% spleen
– About 10 day lifespan
– Activated platelets secrete substances involved in
coagulation, fibrinolysis, and healing
• Normal platelet function results in a platelet plug
Marrow
• Platelet phospholipid surface
(PL/PF3) has binding sites for
clotting factors
Platelet
Giant Platelet
– Exposed after platelet activation by
collagen
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Blood
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Platelet vs Factor Defects
Deep Bleeding
Vessel/Platelet Defect
Coagulation Factor Defect
• Aspirin & Plavix® impair platelet plug formation
– Aspirin inhibits cyclooxygenase needed for aggregation
– Plavix blocks platelet receptors to inhibit aggregation
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Coagulation System
Platelet defects present a different clinical
picture than coagulation factor defects
Superficial Bleeding
– Platelet adhesion requires vonWillebrand’s factor to stick
to exposed collagen at site of injury
– Platelet aggregation forms a temporary platelet plug that
must be reinforced by fibrin
• Coagulation system effectively halts bleeding in
large vessels…joints, muscles
– Complex process of enzymatic reactions involving
plasma proteins, a phospholipid surface and calcium
– Phospholipid is supplied by platelets or tissues
• Coagulation, fibrinolytic and regulatory proteins
are produced by the liver
• Factors II, VII, IX and X require vitamin K
– Coumarin/Warfarin therapy causes production of nonfunctional vitamin K-dependent factors by liver
– Factor VII is most depressed by absence of vitamin K
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CLS500 Application and Interpretation of
Clinical Laboratory Data
Hemostasis & Disorders Powerpoint Handout
12
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Coagulation ‘Waterfall’
Waterfall’
Coagulation System
• All coagulation factors are plasma proteins except
for tissue factor and calcium
– Fibrinogen (Factor I) is the precursor to fibrin
– Prothrombin is activated to the final enzyme thrombin;
therapeutic heparin (with AT) neutralizes thrombin
– Tissue factor is tissue phospholipid released into the
plasma by damaged cells…placenta, brain, lung,
endothelium, liver, RBC stroma, WBCs
• Clotting factors circulate in an inactive form
– Injury initiates factor activation to enzyme form
– Sequential activation of factors that follow in the
‘waterfall’ results in fibrin formation
– All factors in coagulation sequence must be present or
next reaction is delayed
• Activation of coagulation is divided into two
pathways that are alternate ways of activating
factor X.
– Calcium is required by all coagulation pathways;
removed by sodium citrate
– Vessel injury exposes collagen and causes release of
tissue factor into the plasma from damaged cells
– Factor VIII, the antihemophiliac factor, is carried by
vonWillebrand’s factor; sex-linked inheritance
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Coagulation System
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Coagulation Pathways
• 3 interrelated pathways
– Intrinsic pathway is contact activated by collagen
Dominant
in vivo
– Extrinsic pathway is tissue activated by tissue factor;
only factor VII
EXTRINSIC
PATHWAY
INTRINSIC
PATHWAY
– Common pathway begins with activation of factor X
• Final enzyme of coagulation system is thrombin
– Converts fibrinogen to fibrin on a phospholipid surface
at site of injury
COMMON PATHWAY
• These are in vitro pathways…alternate activation
paths exist which link the pathways in vivo
THROMBIN
– Extrinsic pathway is dominant pathway in vivo
In vitro
Coagulation Pathways
Coagulation Pathways
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Regulatory System
Fibrinolytic System
• Fibrinolysis is a normal response activated
simultaneously with initiation of fibrin formation
• Natural inhibitors that control coagulation and
fibrinolysis…maintain balance
• The final enzyme plasmin slowly degrades fibrin
by lysis
• Antithrombin, most potent coagulation inhibitor
– Thrombin and plasmin are not normally in circulation
– Prevent widespread or inappropriate activation of
clotting or lysing
– Degradation products (FDPs) are released into the
plasma and cleared by liver…not normally detectable
– Increased FDPs are detected by D-Dimer & FDP tests
• Thrombolytic drugs, e.g. TPA, are clot lysing
drugs that convert plasminogen to plasmin
CLS500 Application and Interpretation of
Clinical Laboratory Data
Hemostasis & Disorders Powerpoint Handout
– AT neutralizes multiple enzymes including thrombin
– Action is potentiated by therapeutic heparin
– Heparin is not active in the absence of AT (formerly
known as antithrombin III)
• Antiplasmin, principle fibrinolytic inhibitor
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– AP neutralizes plasmin once clot is degraded
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Activation of Hemostatic Components
Hemostatic Imbalance
Injury triggers the activation of ALL components
• Imbalance may result in mild, moderate or lifethreatening bleeding or clotting, depending on the
component affected
– Deficient clotting or increased clot lysis Æ hemorrhage
– Excessive clot formation Æ thrombosis
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Lab Evaluation of Hemostatic Defects
Identify the cell shown
• Patient history and clinical findings are essential to
interpretation of laboratory data
• Lab evaluation begins with screening tests for
primary and secondary hemostasis:
– PLT count and BT assess vessel & platelet activity
– PT and PTT detect defects in clotting factors
• Testing is performed:
The ‘man in the cell’
cell’
– Identify & control inherited or acquired defects
– Monitor/regulate therapeutic heparin or coumarin
– Pre-surgical screens; done pre & post transfusion
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Bleeding Time (BT)
Tests for Primary Hemostasis
• Platelet count
– Normal 150-450 K/uL; critical <40 K/ul
– EDTA blood; heparinized or clotted blood causes error
Cuff
Template
• Bleeding time (BT)
– Measures in vivo platelet plug formation
• Standardized cut is made in forearm with template and timed for
bleeding to stop
– Normal BT <8 minutes; critical >15 minutes
– Prolonged by abnormal platelet function, PLT count
below 100 K/uL or vessel defects; not factor defects
– Done if a patient’s bleeding history is positive
• Patient is bleeding or has previously bled, family history of
bleeding; on meds & needs surgery
CLS500 Application and Interpretation of
Clinical Laboratory Data
Hemostasis & Disorders Powerpoint Handout
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Tests for Secondary Hemostasis
Tests for Secondary Hemostasis
• The PT and PTT each measure
certain clotting factors
• PT & PTT are in vitro plasma clotting tests
– Endpoint is formation of a fibrin clot
– Prolonged/abnormal results indicate a deficiency of one
or more clotting factors
• Testing requires citrated plasma
– If normal, plasma contains all factors
– Platelets are absent
• Normal factor activity is 50% or more
Citrated Plasma
• Errors that cause redraw:
–
–
–
–
Specimen contamination…heparin
Partially clotted blood sample
Traumatic blood draw…hemolysis
Wrong tube or citrate tube not full
– Factor activity must be less than ~30% to obtain
prolonged screening test results = sensitivity
• Reagent + patient citrated plasma Æ time for clot
Hemolyzed
Plasma
– Normal reference ranges vary with reagents, testing
method, instrumentation
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Tests for Secondary Hemostasis
Screening Tests
Primary – PLT count, BT
Secondary – PT, PTT
• PTT, partial thromboplastin time, aPTT
– Measures factors in intrinsic and common pathways
– Normal 22.0-37.0 seconds; critical >100.0 sec
– Used to monitor therapeutic heparin (standard)
Reagent
Reagent
• PT, protime, prothrombin time
– Measures factors in extrinsic and common pathways
– Normal 11.0-13.4 seconds; critical INR value >4.0
– The PT INR value is used to monitor coumarin therapy
• PT/PTT are not prolonged by platelet defects
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Evaluation of Screening Tests
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DIMER TEST
Evaluation of Screening Tests
• Screening tests help pinpoint defects:
• Screening tests help pinpoint defects:
Intrinsic/20 – deep bleeding
Extrinsic/20 – FVII, deep
Abn Plt function/10 - superficial
↓ Plt#, <100K/10 - superficial
No defect – expect no bleeding
• Followed by more specific testing:
• Followed by more specific testing:
– Fibrinogen level, specific factor assays, Dimer test for
fibrinolysis, AT level, DIC screen, platelet function tests
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CLS500 Application and Interpretation of
Clinical Laboratory Data
Hemostasis & Disorders Powerpoint Handout
– Fibrinogen level, specific factor assays, Dimer test for
fibrinolysis, AT level, DIC screen, platelet function tests
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Example:
Patient Evaluation
Normal child Bleeding not expected
• Patient history
– Age of onset, family history, prior bleeding [or clotting]
episodes
• Physical exam
– Mucosal bleeding only vs deep bleeding/hematomas
– Spontaneous bleeding…severe factor deficiency or PLT
count <20,000/ul
– Post-injury bleeding…mild factor deficiency
– Multiple site bleeding…severe combined defects
Child with severe liver disease Bleeding expected
• Underlying disease
• Medications/drugs
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Bleeding Sites
Superficial Bleeding
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Hemostatic Disorders
Muscular Hematoma
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#/10
Function/10
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10 & 20
Joint Bleeding - Hemophilia A
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Diffuse Hemorrhage - DIC
Vascular Disorders
Quantitative Platelet Disorders
• Causes for vessel abnormalities
• Abnormal #, Thrombocytopenia - PLT <150 K/ul
– Vitamin C deficiency
– Decreased bone marrow production
• Needed for collagen synthesis…gum bleeding
• Injury, drug suppression, replacement, decreased TPO
– Lack of platelet support (↓ # or abnormal function)
– Vessel damage (steroids, organisms, atherosclerosis)
– Increased use (DIC, HUS)
– Destruction by immune mechanisms
• Idiopathic thrombocytopenic purpura (ITP) occurs in kids after
viral infection that alters IR causing platelet autoantibodies
• Heparin-induced antibodies; should monitor platelet count
• Lab results
– BT may be prolonged; normal PT & PTT usual
– Diagnosed by exclusion
– Hypersplenism (liver disease)
• Lab results
• Clinical findings
– Superficial bleeding and petechiae
– BT prolonged if PLT <100 K/uL; normal PT & PTT
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CLS500 Application and Interpretation of
Clinical Laboratory Data
Hemostasis & Disorders Powerpoint Handout
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36
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Quantitative Platelet Disorders
Quantitative Platelet Disorders
• Clinical findings & degree of thrombocytopenia
• Abnormal #, Thrombocytosis - PLT >450 K/ul
– PLT count 50-100 K/ul
• Bleeding tendency not clinically significant unless subjected
to trauma or surgery
– Post-splenectomy…transient increase, 100% of platelets
in blood circulation
– Reactive increase in bone marrow production
– PLT count below 50,000/ul
• Chronic inflammation, acute infection, after acute blood loss
• PLT <1 million/ul, not associated with bleeding problems
• Superficial, mucosal, retinal and GI bleeding, petechiae
• Bleeding severity tends to parallel PLT count
– Malignant increase in bone marrow production
– PLT below 20,000/ul
• PLT >1 million/ul, often with abnormal platelet function
• GI bleeding or thrombosis possible
• Prolonged BT if performed
• Severe and spontaneous bleeding possible including fatal
intracranial bleeds
• PLT count is strictly monitored; patient transfused
– Thrombocytopenia is a common cause of bleeding
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Qualitative Platelet Disorders
Hemostasis Case #1
A 65 year old female with complaints of fatigue is noted to have numerous
petechiae on her calves. Her lab results are:
• Abnormal platelet function, normal PLT count
• VonWillebrand’s disease, many types
– #1 hereditary bleeding disorder, males & females
– Defect of vWF needed for platelet adhesion and carries
factor VIII…impairs primary & secondary hemostasis
• Prolonged BT and PTT usual
A bone marrow revealed predominantly blasts with few normal precursors.
Does this patient have a defect of primary and/or secondary hemostasis?
• Acquired defects of platelet function
– Aspirin & Plavix® cause abnormal platelet aggregation
• Takes ~ 5 days for BT to normalize
Are her symptoms consistent with her defect?
What BT result would you expect? The BT was not done because…..
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Hemostasis Case #1
Hemostasis Case #2
A 65 year old female with complaints of fatigue is noted to have numerous
petechiae on her calves. Her lab results are:
WBC
HGB
PLT
PT
APTT
55.5 K/uL ↑
WBC diff: 2% segs-3% lymphs-95% blasts
8.0 g/dL ↓
30 K/uL ↓
11.1 sec (11.0-13.4) N INR 0.9 Normal
30.0 sec (22.0-37.0) N
A bone marrow revealed predominantly blasts & few normal precursors.
What is her most likely diagnosis? Acute leukemia
Does this patient have a defect of primary and/or secondary hemostasis?
Primary hemostasis due to low platelet number; normal PT/PTT rule
out defect of secondary hemostasis…factors measured, not platelets
Are her symptoms consistent with her defect? Yes, superficial bleeding
What BT result would you expect? The BT was not done because…..
Prolonged BT due to decreased platelets (<100 K/uL); BT should
be avoided when PLT count is below 50 K/uL
CLS500 Application and Interpretation of
Clinical Laboratory Data
Hemostasis & Disorders Powerpoint Handout
55.5 K/uL
WBC diff: 2% segs-3% lymphs-95% blasts
8.0 g/dL
30 K/uL
11.1 sec (11.0-13.4)
INR 0.9
30.0 sec (22.0-37.0)
What is her most likely diagnosis?
– Superficial, mucosal bleeding; deep bleeding unusual
– Renal failure…uremic metabolites inhibit platelets
WBC
HGB
PLT
PT
APTT
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The patient is a 51 year old male with a history of coronary artery disease
and chronic renal failure requiring dialysis due to extremely high BUN
levels. He eats Cheerios for breakfast each morning. On this admission,
cardiac catherization was to be done to evaluate the patient’s angina.
Bruising was observed on the physical exam. Pre-operative testing:
PLT
BT
PT
APTT
240,000/cmm
14 mins (< 8)
11.3 sec (11.0-13.4)
26.0 sec (22.0-37.0)
INR 1.0
Does this patient have a defect of primary and/or secondary hemostasis?
Do the clinical symptoms correlate with the defect?
Name two possible causes for the defect.
Why was the bleeding time performed?
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Hemostasis Case #2
The patient is a 51 year old male with a history of coronary artery disease
and chronic renal failure requiring dialysis due to extremely high BUN
levels. He eats Cheerios for breakfast each morning. On this admission,
cardiac catherization was to be done to evaluate the patient’s angina.
Bruising was observed on the physical exam. Pre-operative testing:
PLT
BT
PT
APTT
240,000/cmm N
14 mins (< 8) ↑
11.3 sec (11.0-13.4) N INR 1.0
26.0 sec (22.0-37.0) N
Does this patient have a defect of primary and/or secondary hemostasis?
Primary hemostasis, prolonged BT with normal PLT count indicates
impaired platelet function, acquired defect; normal factors
Do the clinical symptoms correlate with the defect? Yes, superficial
Name two possible causes for the defect.
Aspirin or Plavix (cardiac patient); uremia (renal disease)
Why was the bleeding time performed?
Potential for bleeding during heart cath; delay ~5 days
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Coagulation & Fibrinolytic Disorders
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Coagulation & Fibrinolytic Disorders
• Acquired disorders usually affect more than one
factor or hemostatic component
• Hereditary disorders are single clotting factor
deficiencies
– May result in hemorrhage and/or thrombosis
– Most often characterized by deep tissue hemorrhage
• Liver disease
• Hemophilia A
– Decreased synthesis of coagulation, fibrinolytic and
regulatory proteins
– #2 hereditary bleeding disorder, males only
– Mild, moderate or severe deficiency (<1%) of factor
VIII…defect of secondary hemostasis
• Prolonged PT first sign of worsening disease
• Platelet problems due to enlarged spleen, low TPO, alcohol
• Impaired liver clearance of activated factors and FDPs
• Prolonged PTT, normal platelets and BT
– Severe, often spontaneous bleeds…abdominal, CNS,
intramuscular hematomas, recurrent joint bleeding
– Require lifelong factor VIII concentrates
• Vitamin K deficiency
– Causes synthesis of inactive factors II, VII, IX, X
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Coagulation & Fibrinolytic Disorders
• Antibiotics, liver disease, newborns; give vitamin K
Triggering Event
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Diffuse intravascular coagulation (DIC)
• Disseminated intravascular coagulation (DIC), a
thrombo-hemorrhagic disorder
– Secondary complication of conditions that trigger
widespread clotting in microvessels
1st
Low PLT count
• Sepsis, OB complications, tissue trauma, malignancy, etc.
– Begins as out of control clotting that leads to bleeding
Thrombin
• Platelets & coagulation factors are consumed in clots
• Clotting activates fibrinolysis to remove fibrin clots Æ ↑ FDPs
– Symptoms that suggest DIC
RBC Fragmentation
• Diffuse bleeding from multiple sites, GI bleeds, petechiae,
organ damage/failure due to vessel occlusion by clots…death
– Treat condition; FFP, PLTs, packed RBCs, AT
CLS500 Application and Interpretation of
Clinical Laboratory Data
Hemostasis & Disorders Powerpoint Handout
1st
Fibrinolysis
FDPs
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Increased Dimer
Bleeding
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Hemostasis Case #3
Hemostasis Case #3
A 3 year old boy was first noticed to bleed easily at the age of 2 years. He
recently bled with hematoma formation. His older brother has had bleeding
episodes involving major joints. Lab findings:
A 3 year old boy was first noticed to bleed easily at the age of 2 years.
He recently bled with hematoma formation. His older brother has had
bleeding episodes involving major joints. Lab findings:
PLT
BT
PLT
BT
200,000/cmm
5 mins (< 8)
PT
APTT
11.0 sec (11.0-13.4)
115.0 sec (22.0-37.0)
INR 1.0
200,000/cmm N
5 mins (< 8) N
PT
11.0 sec (11.0-13.4) N INR 1.0
APTT 115.0 sec (22.0-37.0) ↑
Does this patient have a defect of primary and/or secondary hemostasis?
Does this patient have a defect of primary and/or secondary hemostasis?
Defect of secondary hemostasis (factors); normal PLT count & BT
Are the bleeding symptoms characteristic of this defect?
Are the bleeding symptoms characteristic of this defect?
Yes, deep bleeding suggests factor deficiency
Is this a hereditary or acquired defect? Hereditary, sex-linked (males)
Is this a hereditary or acquired defect?
Which coag pathway appears to be defective? What do you suspect?
Which coag pathway appears to be defective? What do you suspect?
Intrinsic coagulation pathway; Hemophilia A Æ factor VIII deficiency
Why was the bleeding time done?
Why was the bleeding time done?
Patient & family bleeding history is positive; BT prolonged in vWD
Treatment?
Lifelong factor VIII concentrates
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Treatment?
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Hemostasis Case #4
Hemostasis Case #4
A 40 year old male is admitted with frequent episodes of epistaxis and
bleeding from the gums. The family bleeding history is negative. His own
history reveals both a recent and past abuse of alcohol. PE finds an
enlarged liver and spleen, and slight icterus. He has elevated AST, LD,
alkaline phosphatase, GGT and bilirubin values. Other lab results:
A 40 year old male is admitted with frequent episodes of epistaxis and
bleeding from the gums. The family bleeding history is negative. His own
history reveals both a recent and past abuse of alcohol. PE finds an
enlarged liver and spleen, and slight icterus. He has elevated AST, LD,
alkaline phosphatase, GGT and bilirubin values. Other lab results:
PLT
BT
PLT
BT
68,000/cmm
10 mins (< 8)
PT
APTT
20.6 sec (11.0-13.4)
48.6 sec (22.0-37.0)
INR 2.6
Does this patient have a defect of primary and/or secondary hemostasis?
Is this a hereditary or acquired defect?
What do you suspect?
Treatment?
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68,000/cmm ↓
10 mins (< 8) ↑
PT
20.6 sec (11.0-13.4) ↑ INR 2.6
APTT 48.6 sec (22.0-37.0) ↑
Does this patient have a defect of primary and/or secondary hemostasis?
Defect of both primary (platelets) and secondary hemostasis (factors)
Is this a hereditary or acquired defect? Acquired
What do you suspect?
Liver disease (alcoholic), abnormal liver enzymes; impaired synthesis
of hemostatic proteins; low platelet # due to enlarged spleen and/or
decreased production; alcohol impairs platelet function
Treatment? FFP, vitamin K
Note: BT was done because of bleeding symptoms & would definitely
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be indicated before doing a liver biopsy
Hemostasis Case #5
Hemostasis Case #5
A patient was admitted in labor to the obstetrical floor at 1 a.m. At the
time of admission, she was having irregular contractions. In the delivery
room, bleeding became extensive. A stat HGB, HCT, crossmatch for 4
units of blood and coagulation testing was ordered. Lab data:
A patient was admitted in labor to the obstetrical floor at 1 a.m. At the
time of admission, she was having irregular contractions. In the delivery
room, bleeding became extensive. A stat HGB, HCT, crossmatch for 4
units of blood and coagulation testing was ordered. Lab data:
HGB & HCT
PLT
PT
APTT
Fibrinogen
D-Dimer
Antithrombin
HGB & HCT
PLT
PT
APTT
Fibrinogen
D-Dimer
Antithrombin
8.0 g/dl and 25.0%
70,000/cmm
A few schistocytes were noted on smear
19.0 sec (11.0-13.4)
INR 2.2
65.0 sec (22.0-37.0)
90 mg/dL (150-450)
Abnormally increased
Decreased
Does this patient have a defect of primary and/or secondary hemostasis?
What do you suspect?
Treatment?
53
CLS500 Application and Interpretation of
Clinical Laboratory Data
Hemostasis & Disorders Powerpoint Handout
8.0 g/dl and 25.0% ↓, bleeding
70,000/cmm ↓ A few schistocytes were noted on smear
19.0 sec (11.0-13.4) ↑ INR 2.2
65.0 sec (22.0-37.0) ↑ Decreased factors & platelets
90 mg/dL (150-450) ↓ due to increased use
Abnormally increased ↑
Decreased ↓
Does this patient have a defect of primary and/or secondary hemostasis?
Defect of both primary and secondary hemostasis & fibrinolysis
What do you suspect? DIC secondary to placental damage; release of
↑↑TF triggered widespread clotting
Treatment?
Treat underlying condition if possible; replacement therapy
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Thrombotic Disorders
Example:
• Inappropriate clotting… not a response to injury
Patient died in DIC following traumatic delivery of stillborn
MI
– Life-threatening if blood to vital organ cut off
• No good screens to identify persons at risk
PE
Stroke
• Thrombi occur in areas of ↓ blood flow or
result from trauma to vessel interior
– Formation of intravascular clot that blocks a
vessel Æ DVT causes tissue necrosis
• Pain, swelling, redness in leg, thigh, pelvis
Fibrin Strands
– Portions of thrombus break off and travel Æ
PE (embolism) occludes vessels in lungs
DVT
• SOB, hyperventilation, chest pain
RBC
Blood smear with presence of
schistocytes & lack of platelets
RBC fragmentation on fibrin strands
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Thrombotic Disorders
• Therapeutic anticoagulants prevent the initiation
and extension of thrombus formation
– FV Leiden & FII 20210 are genetic mutations of factors V
and II; the two most common hereditary causes
– Antithrombin deficiency…a hereditary lack of this
coagulation inhibitor or low levels occur in liver disease,
during pregnancy or oral contraceptive use
• Therapy requires strict monitoring to avoid serious
bleeding complications (GI/CNS)
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Treatment of Thrombotic Disorders
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Treatment of Thrombotic Disorders
• Coumarin therapy is monitored by PT INR value
• Standard heparin, infusion or injection
– The INR (International Normalized Ratio) standardizes PT
results between labs for better regulation of patient therapy
– Markedly enhances action of antithrombin (AT) to
inactivate multiple factors including thrombin
• Different reagents and instrumentation may yield different PT
results in seconds for the same patient
• INR value ~1.0 is typical for persons with a normal PT in secs
In presence of heparin, AT action is immediate
Heparin is not active if a person is severely AT deficient
Causes prolonged PTT (and PT) at therapeutic doses
Standard heparin therapy is best monitored by PTT
– To minimize hemorrhagic complications, the target INR
therapeutic range recommended for patients on oral
anticoagulants is between 2.0-3.0
• Coumarin/Warfarin, oral
– Vitamin K antagonist that causes the production of
inactive vitamin K-dependent factors II, VII, IX, X
• Vitamin K is given to counteract bleeding
• Takes 2-3 days to clear normal factors; FVII is most depleted
• Causes prolonged PT (and PTT) at therapeutic doses
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CLS500 Application and Interpretation of
Clinical Laboratory Data
Hemostasis & Disorders Powerpoint Handout
– Cause defects in ability to form clots; do not lyse clots
– Heparin & coumarin are regularly used to treat cardiac,
pulmonary, post-surgical or immobilized patients
– Heparin is treatment for acute thrombotic events
– Coumarin is used for long-term therapy
– Baseline tests (PLT count, PT, PTT) are done before
initiating anticoagulant therapy
– Risk factors…post-surgical/immobilized patients,
pulmonary disease, coronary artery disease, cancer,
travel, obesity, homocysteinemia
•
•
•
•
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Treatment of Thrombotic Disorders
• Hereditary states, acquired conditions and risk
factors associated with thrombosis [incomplete list]
– Spontaneous clotting for unexplained reasons
– Negative Dimer test used to exclude PE or DVT
– For patients requiring anticoagulant therapy
• Heparin is monitored with PTT; switch to oral drugs requires
overlap; oral coumarin is then monitored with PT INR value 60
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Treatment of Thrombotic Disorders
• Clot lysing drugs
– Convert plasminogen to plasmin and used to dissolve
formed clots in patients with acute MI, DVT, pulmonary
clots or stroke victims (if within 3 hours)
• Thrombolytic agents are recombinant TPA (Activase®) and
possibly urokinase or streptokinase
• Serious bleeding is a risk; causes increased Dimer test
Hemostasis Case #6
A 62 year old woman went to the UNMC ER due to painful swelling of her
left leg. This doting grandmother had been traveling in a car for 23 hours
after visiting her 8 grandchildren in Seattle. She was well when she left
Seattle. Her initial blood counts and coagulation screening tests were
within normal reference limits.
What do you suspect?
Next step?
• Anti-platelet agents
– Aspirin or Plavix® are most often used to impair platelet
aggregation in patients with cardiac disease
• Not necessary to monitor except prior to a surgical procedure
• Will cause prolonged BT; does not prolong the PT or PTT
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Evaluation:
Hemostasis Case #6
A 62 year old woman went to the UNMC ER due to painful swelling of
her left leg. This doting grandmother had been traveling in a car for 23
hours after visiting her 8 grandchildren in Seattle. She was well when she
left Seattle. Her initial blood counts and coagulation screening tests were
within normal reference limits.
42 yo male with recent MI; monitoring of switch from heparin to oral therapy
What do you suspect? Deep vein thrombosis
(Overlap)
Next step?
Can rule out with D-Dimer test before further testing (most useful
for outpatients)
If Dimer is negative, not a DVT (Dimer has negative predictive value)
If Dimer is positive, it does not confirm a DVT but it is a possibility
Perform Doppler, ultrasound, venogram, lung scan, MRI
Give TPA to lyse clot
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Is the INR value within the recommended target range? Yes, 2.0-3.0
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CLS500 Application and Interpretation of
Clinical Laboratory Data
Hemostasis & Disorders Powerpoint Handout
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