Lecture - Module 2 Flashcards
occurs within the intravascular
compartment lined with endothelium
HEMOSTASIS
A tightly regulated balance between formation and dissolution of hemostatic plugs modulated by a series of enzymes and scaffolding proteins.
PHYSIOLOGIC HEMOSTATIC SYSTEM
Factors involved in Normal
Hemostasis and Thrombosis
Plateletes, Granulocytes & Monocytes
Coagulation Protein Sytem (Clot Forming)
Fibrinolysis Protein System (Clot Lysing)
Anticoagulation Protein System ( Regulating)
serves to form thrombin that initiates the proteolysis of fibrinogen, leading to fibrin clot formation
Coagulation System (Clot Forming)
→ functions to lyse the clot formed by thrombin
Fibrinolytic Sytem (Clot Lysing)
regulates all enzymes of the coagulation and fibrinolytic systems, so that no inappropriate excess of clotting or bleeding occurs.
Anticoagulation System (Regulating)
Vasoconstriction is a short-lived reflex reaction of the smooth muscle in the vessel wall produced by the
sympathetic branches of the autonomic nervous system
increases the adhesiveness of platelets
ADP
Platelet during adhesion will transform from ________ to ______ which produces surface membrane organization
disc shape to a sphere with pseudopods
Internal contraction of the platelet results in release of granular contents of
alpha granules
dense granules
lysosomal granules
Platelets adhere at sites of mechanical vascular injury and then undergo activation and express what functional glycoprotein —- also referred to as?
IIb/IIIa
Alpha 2b Beta 3
Which receptors will mediate the recruitment of local platelets by forming fibrinogen bridges between platelets—a process called platelet cohesion.
glycoprotein IIb/IIIa
A process forming fibrinogen bridges between platelets
platelet cohesion
Glycoprotein ____ is specific for
platelets.
IIb/IIIa
Glycoprotein ______ is the most abundant platelet membrane protein (with approximately _______ receptors per platelet).
IIb/IIIa
50,000
gold standard test to determine platelet function.
Platelet aggregation
Agents capable of producing platelet aggregation in vitro (an energy dependent process):
Collagen
Proteolytic enzymes (thrombin)
Biological amines (epinephrine and serotonin)
results from bridges formed by fibrinogen in the presence of calcium which produces sticky surface on platelets
Aggregation
If these aggregates are reinforced by fibrin, they are referred to as a
thrombus
Aggregation of platelets by at least one pathway can be blocked by substances such as:
PGE (prostaglandin E)
adenosine
- provides basis for platelet consolidation & stabilization.
Fibrinogen
This process involves the precipitation of polymerized fibrin around each platelet
PLATELET PLUG CONSOLIDATION & STABILIZATION
Result of platelet plug consolidation and stabilization
fibrin clot
Fibrin clot will produce
irreversible platelet plug
Quantitative Determination of Platelet
Electronic particle counter
examination of stained blood film
done if the platelet count is normal → assessment of platelet function
Qualitative Assessment of Platelet
Qualitative Assessment of Platelet
a. PBS
b. Platelet Count
c. Template Bleeding Time
d. Petechiometer
e. Platelet Aggregation
f. Platelet lumiaggregation (release)
g. Platelet Antibodies (IgM and IgG)
h. Platelet Membrane Glycoproteins
i. Platelet factor IV
k. Thromboxanes
In vivo measurement of platelet adhesion and aggregation on locally injured vascular subendothelium.
Bleeding Time with and without Aspirin
Provides an estimate of the integrity of the platelet plug and thereby measures the interaction between the capillaries and platelets
Bleeding Time with and without Aspirin
Reflects the number and quality of platelets, fibrinogen concentration, fibrinolytic activity, and packed red cell volume.
Clot Retraction
The degree of clot retraction is __________ to the number of
platelets & __________ to the hematocrit and the level of the blood coagulation factor fibrinogen.
directly proportional
inversely proportional
The principle of the test is that platelet-rich plasma is treated with a known aggregating agent. If aggregated, cloudiness or turbidity can be measured using a spectrophotometer.
Platelet Aggregation
Aggregating agents
ADP Collagen Epinephrine Ristocetin Snake venom Thrombin
Available techniques can include complement fixation methods, lysis of chromium 51 labeled platelets, assays of platelet-bound immunoglobulins, and competitive inhibition assays.
Antiplatelet Antibody Assays
VASCULAR DISORDERS
- Purpura associated with direct endothelial cell damage.
- Purpura associated with an inherited disease of the connective tissue.
- Purpura associated with decreased mechanical strength of the microcirculation.
- Purpura associated with mechanical disruption of small venules.
- Purpura associated with microthrombi (small clots).
- Purpura associated with vascular malignancy.
Demonstrates the smallest platelets seen
Wiskott-Aldrich
syndrome
Characterized by the presence of large platelets and the presence of Döhle-like bodies in the granulocytic leukocytes
May-Hegglin
anomaly
Disorder that exhibits giant platelets and thrombocytopenia
Alport syndrome
Demonstrates the largest platelets. In this disorder, it has been demonstrated that the giant platelets are probably an artifact of the slide
Bernard-Soulier syndrome (giant platelet syndrome)
3 types of thrombocytopenia
Disorder of production
disorder of destruction or utilization
disorder of platelet distribution
Hereditary or familial thrombocytosis associated with ger_x0002_mline mutations of the thrombopoietin (THPO) gene in the THPO receptor (MPL) gene
THROMBOCYTOSIS
associated with myeloproliferative neoplasms and/or myelodysplastic disorders (clonal thrombocytosis associated with somatic mutations of JAK2[V617F], MPL, and additional currently unknown genes)
THROMBOCYTOSIS
reactive disease
secondary thrombocytosis
TYPES OF PLATELET DYSFUNCTION
a) Acquired
b) Drug-Induced
c) Platelet Membrane Receptors
d) Hereditary
Types of acquired platelet dysfunction
Myeloproliferative Uremia Miscellaneous Paraprotein Cardiopulmonary bypass and platelet function
Types of hereditary platelet dysfunction
i. Bernard-Soulier Syndrome
ii. Glanzmann Thrombasthenia and Essential Athrombia
iii. Hereditary Storage Pool Defect
