Blood 2 Flashcards
Function of platelets
To seal breaks in blood vessels
Other name for platelets
Thrombocytes
What are platelets derived from?
Cell fragments shed from megakaryocytes
Structure of platelets
Lack nuclei
Have organelles and cytosolic enzymes for generating energy and synthesizing secretory products
High concentrations of actin and myosin
Lifespan of platelets
Remain functional for an average of 10 days
How are platelets removed from circulation?
by tissue macrophages
Do platelets leave blood like WBCs?
No
About 1⁄3 are stored in blood-filled spaces in spleen
Released when needed by sympathetically induced splenic contraction
How is platelet production regulated?
Self-regulating process
Regulation factors (Thrombopoietin (TPO), Interleukin-3 (IL-3), IL-6, IL-11)
How is TPO produced and what is its effect?
Hormone produced by liver
increases number of megakaryocytes and therefore increases platelet production
How do intact endothelial cells prevent platelets from aggregating
Release prostacyclin and nitric oxide
Steps for formation of hemostatic plug
1) Vessel injury exposes underlying collagen fibers
2) Platelets adhere. A large plasma protein called the von Willebrand factor stabilizes the platelets by forming bridge with collagen fibres
3) Platelets swell, form spiked processes and become sticky.
4) Prostaglandin synthesis in platelets occurs, and thromboxane A2 (TXA2) is produced. Serotonin is also released. These messengers enhance vasoconstriction and platelet aggregation
5) ADP release causes platelets to well and aggregate
Primary hemostatic plug is formed
Stability of primary hemostatic plug
Unstable
Temporary control of bleeding
Becomes stabilized by fibrin network
Function of hemostasis
Prevents blood loss from a broken blood vessel
essential to life
Three major steps of hemostasis
Vascular spasm (constriction of vessel)
Formation of platelet plug
Blood coagulation (clotting)
Reason for vascular spasm in hemostasis
Reduces blood flow through damaged vessel
General outcome of blood clotting
Transformation of blood from liquid into a solid gel
What is the purpose of clot formation?
Reinforce platelet plug
Converts blood in the vicinity to non flowing gel
When are clotting factors present in blood plasma?
Clotting factors are always present in blood plasma in inactive precursor form
Vessel damage that exposes collagen initiates cascade of reactions that involve successive activation of clotting factors
Fibrinogen
Precursor of fibrin
Insoluble protein - creates protein meshwork of clot
Thrombin
Converts fibrinogen to fibrin at site of injury
Factor XIII
Fibrin stabilizing factor
xlink fibrin molecules
Factor X
Last component of clotting cascade that activates thrombin from prothrombin
Platelet factor 3
Stimulator of clotting cascade secreted by platelets
What is the clotting cascade?
series of steps
involves 12 plasma clotting factors
Leads to conversion of fibrinogen into a fibrin mesh
How is the clotting cascade triggered?
Intrinsic pathway
Extrinsic pathway
See figure
Number of steps in intrinsic pathway of clotting cascade
Seven separate steps
When does intrinsic pathway start?
When factor XII (Hageman factor) is activated by coming into contact with exposed collagen in injured vessel or foreign substance such as test tube
What are all the clotting factors in the intrinsic pathways
Either cofactors or enzymes
All enzymes except factor XIII are serine protease
Scale of amplification in intrinsic pathway
1 mol of activated factor XI -> IX -> X -> prothrombin -> 2x108 mol of fibrin
Number of steps in extrinsic pathway
Four
When does extrinsic pathway start?
Requires contact with tissue factors external to the blood
Tissue thromboplastin released from traumatized tissue directly activates factor X
Why is the clotting cascade so extensive?
Ensure coagulation occur only when needed
Otherwise, serious consequences
e.g. atherosclerosis -> thrombus -> emboli -> heart attack or stroke
Amplification at each step (reduces loss of blood)
Why is ASA (aspirin) used to prevent heart attack/ stroke?
ASA blocks platelet aggregation -> prevents clot formation
Clot dissolution
Tissue heals (new tissue formed) -> plasminogen converted to plasmin by action of factor XII (Hageman factor) -> plasmin slowly dissolves clot
Fibrin also produced by healthy vessels -> dissolved by tissue plasminogen activator (tPA)
Anticoagulant drugs
Heparin
Hirudin (lepirudin)
Warfarin
Fibrinolytic drugs
Streptokinase
Urokinase
Anistreplase
Tissue plasminogen activator (t-PA)
Antiplatelet drugs
Aspirin
Ticlopidine
Thrombus
Abnormal intravascular clot attached to a vessel wall
Emboli
Freely floating clots
Factors that cause thromboembolism
Roughened vessel surfaces associated with atherosclerosis
Imbalances in the clotting-anticlotting systems
Slow-moving blood
Occasionally triggered by release of tissue thromboplastin into blood from large amounts of traumatized tissue
Septicemic shock
Widespread clotting that is caused by toxins released by infectious bacteria
Hemophilia (cause and treatment)
Excessive bleeding caused by deficiency of one of the factors in the clotting cascade (80% defect in making Factor VIII)
Treatment by infusion of factor VIII and IX
Thrombocytopenia purpura
Condition in which individual develops many small purple blotches
Arise from small ruptures in capillaries and vessels
Lack platelets to seal sites (reduced or no formation of platelet plugs)
Blood leaks -> excessive bleeding at these sites
Vitamin K deficiency
Vitamin K is required for prothrombin synthesis in liver
How does thrombocytopenia purpura arise?
Rare autoimmune disorder
break down of platelets in the blood by autoantibodies (detected in 60-70% patients)
low platelet count
thought to be triggered viral infection, after which young children develop large bruises and petechiae (small purple dots under the skin).
Exact mechanism unclear
Von Willebrand disease
Genetic mutation in chromosome 12
3 types categorized depending on vWF levels
Lab findings: increased bleeding time, normal PT, activated partial thromboplastin time decreases, decrease in Factor VIII, decrease in vWF
Symptoms of deep vein thrombosis
swelling, pain, or unusual redness or warmth in one of the legs
How to prevent deep vein thrombosis
annual checkups
take medication as prescribed
avoid being sedentary (lifestyle & flight)
stretching
weight
quit smoking
watch for symptoms
Diagnosis of deep vein thrombosis
d-Dimer test
ultrasound scan of the legs
blood samples to check for clotting problems (such as inherited biochemical conditions)
venogram
Treatment of deep vein thrombosis
LMW Heparin (iv or sc), warfarin
Prevent larger clot, pulmonary embolism, new clot formation, post-thrombotic syndrome (PTS)
Who does hemophilia A affect?
Males
X-linked disorder
What happens in hemophilia A?
Reduced synthesis of factor VIII
<1% - frequent spontaneous bleeding
1-5% severe bleeding following injury
> 5% bleeding after injury or surgery
What occurs in disseminated intravascular coagulation?
Widespread generation of fibrin within blood vessels
What can severe disseminated intravascular coagulation cause?
Organ dysfunction
Myeloproliferative neoplasms
Incluces many diseases
Abnormal megakaryocytic proliferation
Common mutation: Janus Kinase 2 (JAK2), V617F
RCT ongoing: TPO receptor agonists, JAK2 inhibitors
