Transcript Coagulation Disorders: Primary

MLAB 1227- COAGULATION
KERI BROPHY-MARTINEZ
Coagulation Disorders: Primary Hemostasis
CLINICAL MANIFESTATIONS OF BLEEDING
DISORDERS

Type of bleeding indicates which component of the hemostatic
system is

Defects in primary hemostasis
 Easy bruising, petechiae (small dots), purpura (bleeding into the
skin), ecchymoses (large superficial hemorrhaging), and
spontaneous bleeding, especially from mucosal surfaces
 Defects in secondary hemostasis
 Prolonged deep bleeding into joints/muscles or hematomas: With
these disorders can see spontaneous bleeding (severe factor
deficiency) or post-injury (mild factor deficiency)
 Combination
 Multiple site bleeding occurs in severe combined defects (DIC).
Platelet activity and coag proteins are related so disorders of one
can affect the other since platelets provide phospholipid binding
sites for clotting factor interaction.
A: Petechiae
B: Ecchymosis
C: Hematoma
EVALUATION OF POTENTIAL BLEEDING
DISORDER



Obtain Medical history
 Age of onset
 Symptoms
 Family history
 Drug history
 Exposure to toxins
Physical exam
 Type and sites of bleeding
 Spontaneous/ result of trauma
Order and interpret lab screening tests
 Platelet count
 PT
 PTT
 BT or PFA
VASCULAR SYSTEM DISORDERS
Defects may be due to abnormalities in the
endothelial cell lining of the blood
vessel(acquired) or the connective tissue
supporting the vessels(hereditary)
 Symptoms

Superficial bleeding
 Hemostatic testing is normal

VASCULAR DISORDERS

Inherited
Rare
 Bleeding and easy bruising are common symptoms
 Conditions

Marfan syndrome
 Ehlers-Danlos syndrome

VASCULAR DISORDERS: ACQUIRED
Patient exhibits bruising and petechiae
 In all acquired disorders, the patient exhibits
purpura.


Defects in vasculature is caused by:
Conditions that decrease the supportive connective
tissue in the blood vessel walls
 Presence of abnormal proteins in the vascular tissues
 Infections or allergic conditions
 Mechanical stress

VASCULAR DISORDERS: ACQUIRED

Classification
 Purpura due to decreased connective tissue
 Collagen and elastin fibers, which form the
support for blood vessels, are lost, causing
fragility
 Senile purpura( elderly people)
 Scurvy ( deficiency of vitamin C)
 Purpura associated with paraprotein disorders
 Purpura due to vasculitis
 Inflammation of small blood vessels due to
complement activation on subendothelium
 drugs and infectious agents
PLATELET DISORDERS
 Platelet
disorders are the most common
cause of abnormal bleeding.
 Qualitative: abnormalities of platelet
function
 Quantitative: platelet count is below or
above reference range
 Hallmarks
Petechiae
Excess bleeding from superficial sites
Mucous membranes, skin
PLATELET ABNORMALITIES
Giant platelet
Agranular
platelet
QUANTITATIVE DISORDERS- ITS ALL
ABOUT THE NUMBERS..

Thrombocytopenia





Decrease in the number of circulating plateletsbelow 100,000/µL
Most common cause of clinical important bleeding
Symptom of underlying disease
Bleeding time is prolonged
PT, PTT not affected
QUANTITATIVE DISORDERS:
THROMBOCYTOPENIA
1.
Increased destruction : bone marrow function is normal
 Immune Mediated Destruction
 Immune Thrombocytopenic Purpura (ITP):
Caused by antibodies that cover the platelets
 Acute and chronic forms
 Resulting from an unknown cause (Idiopathic)
 Often follows a viral infection
 Believed to be antibody mediated, may produce a
specific platelet autoantibody, specifically IgG.
 Spontaneous remission occurs in approximately
80% of the cases

Alloimmune Thrombocytopenia
 Alloantibodies stimulated by foreign antigens cause
destruction
ACUTE VS. CHRONIC ITP
Acute ITP
Chronic ITP
Predominantly in children,
following viral illness
Adults aged 20-50 years
Idiopathic
Sudden onset
Lasts les than 6 months
Insidious onset
Lasts more than 6 months
Platelet counts <20,000/µL
Platelet counts 30,000/µL80,000/µL
Petechiae, ecchymoses,
mucosal bleeding
Mucosal bleeding, easy
bruising, petechiae
Affects both sexes equally
Prevalence in females
QUANTITATIVE DISORDERS:
THROMBOCYTOPENIA (CON’T)


Drugs
 HIT: Heparin Induced Thrombocytopenia
 Heparin causes platelets to activate which
eventually causes antibodies to target the
heparin/PF4 complex
 Results in thrombocytopenia
Other Diseases
 Collagen disorders
 LE, RA
 Infections
 Infectious Mononucleosis
 HIV
QUANTITATIVE DISORDERS:
THROMBOCYTOPENIA

Nonimmune: excessive consumption
 Platelets are activated without the cascade
activating
 TTP: Thrombotic Thrombocytopenic Purpura
 DIC: Disseminated intravascular coagulation
 HUS: Hemolytic uremic syndrome
 Mechanical destruction by artificial heart
valves
QUANTITATIVE DISORDERS:
THROMBOCYTOPENIA
Decreased production : bone marrow is abnormal
 bone marrow impairment, radiation, malignancy,
drugs, congenital conditions
3. Abnormal distribution
 sequestering by the spleen or liver
3. Excessive dilution
 transfusions of stored blood or plasma expanders
3. Conditions with multiple mechanisms of
2.
thrombocytopenia
Example: Alcoholism: Patients that have cirrhosis
present, can have problems with the coagulation proteins as
well as their platelets. Alcohol reduces platelet numbers and
causes defects of aggregation, release and procoagulant
activity. Platelet production is suppressed by the toxic effect
of alcohol on the bone marrow.
QUANTITATIVE DISORDERS

Thrombocytosis
Temporary rise in the number of circulating platelets
 Plateletshave normal function.
 Counts > 1000 x 103/mL



Primary thrombocytosis: uncontrolled production of
megakaryocytes
 CML
 Polycythemia vera
 Essential thrombocythemia
Secondary or reactive thrombocytosis: due to another
disease or condition
 Surgery, particularly splenectomy ( since spleen normally
contains 20-30% of the platelets
 Inflammation
 Acute blood loss
 Exercise
ESSENTIAL THROMBOCYTHEMIA

Clonal disorder
Results in very high platelet counts (> 1 million)
 Results in variable-sized platelets

Seen in middle-aged population, both men and
women
 Clinical signs

Hemorrhage
 Platelet dysfunction
 Thrombosis

QUALITATIVE DISORDERS: FUNCTIONAL

Manifestations include:
Petechiae
 Easy and spontaneous bleeding from mucous
membranes
 Prolonged bleeding from trauma


Lab Diagnosis
Platelet count is normal to slightly decreased
 Prolonged bleeding time
 PT, PTT, Fibrinolysis tests are normal
 Platelet aggregation studies variable

INHERITED DISORDERS OF PLATELET
FUNCTION

Disorders of adhesion


Defects in platelet-vessel wall interaction
Disorders of aggregation

Defects in platelet-platelet interaction
Disorders of platelet secretion and abnormalities
of granules
 Disorders of platelet secretion and signal
transduction
 Disorders of platelet coagulant-protein
interaction

QUALITATIVE (FUNCTIONAL) DISORDERS:
INHERITED

Disorders of Platelet Adhesion: platelet to vessel
wall interaction

Bernard-Soulier syndrome
Deficiency of a membrane glycoprotein (GPIb/IX)
 Giant platelets with coarse granulation and vacules may
be seen.
 Platelet adhesion, aggregation and bleeding time/ PFA-100
are abnormal
 No treatment available, only supportive measures


Von Willebrand’s disease
Deficiency of the von Willebrand factor(vWF) OR production
of a dysfunctional protein
 Abnormal platelet adhesion and bleeding time/PFA-100 as
well as abnormal PTT ( due to VIII defect)

Bernard-Soulier syndrome
@2007 Rector and Visitors of the University of Virginia
Charles E. Hess, M.D and Lindsey Krstic, B.A.
QUALITATIVE (FUNCTIONAL) DISORDERS:
INHERITED

Disorders of Platelet Aggregation: platelet to
platelet interaction

Glanzmann’s thrombasthenia
Deficiency of thrombasthenin
 Lack the GPIIb/IIIa complex, which is where fibrinogen
attaches to platelet surface
 Abnormal platelet aggregation, clot retraction and bleeding
time


Absence of Fibrinogen
QUALITATIVE (FUNCTIONAL) DISORDERS:
INHERITED

Disorders of Platelet Secretion, Abnormalities of granules
and Signal transduction
 Deficiencies of Dense Granules
 Storage pool disease
 Platelets appear normal on peripheral smear, but
there is a decrease or absence of dense granules
 Platelet aggregation abnormal
 Deficiencies of Alpha Granules
 Gray Platelet Syndrome
 Agranular platelets
 Defective Thromboxane A2 Synthesis
 Platelet secretion and aggregation affected
 Defects in Signal transduction
 Affects platelet to agonist interactions
QUALITATIVE (FUNCTIONAL) DISORDERS:
INHERITED

Disorders of Platelet Procoagulant Activity
Scott syndrome
 Activated platelets secrete and aggregate normally
but fail to bind coagulation factors

INHERITED PLATELET DISORDERS
Disorder
Defective
Platelet
Component
Platelet
Count
BT/PFA-100
Other
Bernard- Soulier
Syndrome
Glycoprotein
Ib/IX
Normal or
decreased
Increased
Giant platelets
Glanzman
thrombasthenia
Glycoprotein
IIb/IIIa
Normal
Increased
Storage pool
disease
Dense granule
deficiency
Normal
Increased
Gray Platelet
syndrome
Alpha granule
deficiency
Decreased
Variable
Defective
thromboxane A2
synthesis
Deficiency of
cyclooxygenase,
or TXA2
synthase
Normal
Increased
Agranular
platelets
QUALITATIVE DISORDERS:
ACQUIRED

Uremia


Liver Disease/Alcohol


Reduction in clotting proteins, platelets
Hematologic Disorders


Presence of toxin or waste products affects action of
platelets
Myeloproliferative Disorders, Acute leukemias,
myelodysplasia, multiple myeloma and macroglobulinemia
Drugs
Aspirin: prevents the release of thromboxane A2, thus
decreasing platelet secretion. Those platelets affected by
aspirin still circulate but are nonfunctional
 Antibiotics: penicillins & cephalosporins. Drug coats the
platelet membrane blocking ADP and epinephrine
receptors, so platelet can not respond to agonist.

SCREENING TESTS OF PRIMARY
HEMOSTASIS
Platelet
Count
PT
aPTT
Template
BT
Vascular
Disorders
Normal
Normal
Normal
Normal or
abnormal
Thrombocytopenia
Decreased
Normal
Normal
Abnormal
Platelet
Dysfunction
Usually
normal
Normal
Normal
Normal or
abnormal
VASCULAR DAMAGE
Platelet Adhesion
Bleeding Time
Von Willebrand Disease
PFA-100
Bernard-Soulier
Platelet Activation/Release
Aggregometry
Storage-pool disease
PFA-100
Aspirin/ Certain other drugs
Platelet Aggregation/Thrombin Generation
TEG
Glanzmann’s thrombasthenia
REFERENCES
@2007 Rector and Visitors of the University of
Virginia Charles E. Hess, M.D and Lindsey
Krstic, B.A
 Castellone, D. D. (2010, October). Complexities of
Immune Platelet Disorders. Advance for
Administrators of the Laboratory, 19(10), 27-30.
 http://image.bloodline.net/stories/storyReader$61
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