5.3 - Platelets Flashcards
Thrombopoesis
- production of platelets
1) myeloid stem cell develop into megakaryocytes
2) megakarocytes fragment into platelets
- thrombopoeitin regulates platelet production
- when platelet levels are low, TPO stimulates bone marrow to produce more platelets
Steps of Hemostasis
Hemostasis - the process of blood clotting
1) Vascular Injury and vasoconstriction
- injured vessel causes vessel to constrict = ↓ blood flow and ↓ blood loss
2) Primary Hemostasis (platelet plug)
1. Plts adhere to blood vessels
2. Plts change shape
3. Plts release substances (promote
agglutination)
4. Plts stick together
3) Secondary Hemostasis (Coagulation Cascade)
- damaged endothelium releases tissue factor
- clotting and tissue factors activate cascade
- fibrinogen converts into fibrin to stabilize the plt plug
4) Clot Contraction
- plts contract edged of the wound together (minimize clot size, reduce area of injury)
5) Fibrinolysis and Healing
- fibrinolysis breaks down fibrin to dissolve the clot
Primary Hemostasis
1) Plt adhesion - Von Willdebrand factor binds collagen to help plts adhere to site of injury
2) Plts change shape (activation)
- ADP and thromboxane are released to activate and aggregate platelets
- serotonin and Ca are releases to vasoconstrict
3) Platelet aggregation
- fibrinogen binds to glycoprotein receptors to create the plug
key Players in Primary Hemostasis
1) Nitric Oxide and Prostacyclin
- inhibit aggregation and vasoconstriction
- to prevent unnecessary clotting
2) von Willdebrand Factor
- facilitates platelet adhesion to exposed collagen
3) Thromboxane
- vasoconstricts
- activates plts
4) ADP
- activates and recruits platelets
5) Fibrinogen
- aggregates platelet’s
Secondary Hemostasis
1) Intrinsic Pathway
- activated by internal damage to blood vessel
- damage activates hagemen factor (factor 12)
- factors 7, 8, 9, 11 are sequentially activated
- Ca helps factor 9 activate factor 10
2) Extrinsic Pathway
- activated by external trauma to blood vessels
- tissue factor (released by damage endothelium) combines with factor 7 to activate factor 7
- activates factor 7 activates factor 10
- Ca helps bind tissue factor to factor 7
3) Common Pathway
- activated factor 10 converts prothrombin into thrombin
- Ca helps convert prothrombin into thrombin
- fibrinogen gets converted into fibrin
- thrombin and other factors cross-link the fibrin strands to stabilize fibrin clot
Regulation of Clot Formation
Antithrombin
- inactivates thrombin and other clotting factors
- produced by liver
Tissue Factor Inhibitor
- inhibits tissue factor 7 complex - prevents excessive activation of extrinsic pathway
Protein C and S
- degrades factor 5 and 8
- down-regulates the clotting cascade
Role of Ca in Coagulation
- Ca is a cofactor for factors 7,9,10
- Ca converts prothrombin to thrombin
Ca is needed in both pathways
Intrinsic - helps factor 9 activate factor 10
Extrinsic - helps factor 7 bind to tissue factor
Role of Vitamin K in Clotting
- Vit K activates factors 2,7,9,10
- helps factors 2,7,9,10 bind to Ca and participate in clotting process
- Low vitamin K inhibits the clotting process = excessive bleeding ad increased risk of hemorrhage
Platelet count
Thrombocytosis - elevated plts
- increases clotting risk: hypercoagulation
Pgradoxial Hyper coagulation - plts count is high but plts are not functional; increased bleeding risk
Thrombocytopenia - low plts count
- increased bleeding risk bc less plts are available for clotting
- can occur in bone marrow suppression
Coagulation Tests
Prothrombin Time (PT)
- test of extrinsic pathway
- how long it takes for blood to clot
- high PT(blood takes longer to clot) = bleeding risk
- low PT = clotting risk
Partial Thromboplastin Time (PTT)
- tests intrinsic path
- high PTT = bleeding risk
- low PTT = clotting risk
Factor V Leiden (hypercoagulability)
Cause
- mutation of F5 gene which encodes for factor 5 (V)
- causes it to be resistant to degradation by APC (activated protein C)
Patho
- NORMALLY, factor 5 helps convert prothrombin into thrombin and then into fibrin (for stable clot)
- protein C inactivates factor 5 to limit clot formation
- mutation in factor 5 is active for longer = excessive thrombin = excessive fibrin = clot formation
Changes
- point mutation where Guanine is replaced with Adenine
- mutation where APC cleaves factor 5 to inactivate it
Significance
- Deep vein Thrombosis
- Pulmonary Embolism - clot travels to lungs
Hypo coagulability Conditions
1) Thrombocytopenia
2) von Willebrand Disease
3) Hemophilia
4) Liver Disease
Inherited Thombocytopenia
Disorders characterized by low plt count
Cause
- mutations in genes involved in plt production
Patho
- defects in megakaryocytes
- plts are structurally abnormal and non-functional
Changes
- impaired plt production = low plt count
- Bernard Syndrome: deficient in glyco proteins which help plts adhere to vessel walls = large, dysfunctional plts
Significance
- Mild: easy bruising, prolonged bleeding
Sever: spontaneous bleeding, joint malformation
Management: plt transfusion
Von Willebrand Disease
Cause
- deficiency in von willebrand factor: essential for plt adhesion
Patho
- defective VWF impaires plt adhesion to vessel wall
- decreases stabilization of factor 8 - it is easier to break down which impairs clot formation
Changes
- mutated binding sites that impair binding of plts
Type 1: reduced VWF
Type 2: abnormal VWF
Type 3: absent vWF
Signifiance
- Mucocutanous bleeding: prolonged bleeding, nosebleeds, heavy menstrual bleeding, easy bruising
Hemophilia
Deficiency in clotting factors
- hemophilia: deficient factor 8
- hemophilia b : deficient factor 9
Cause
- absent or dysfunctional factor 8 and 9 impair intrinsic pathway
- thrombin formation is delayed = impairs conversion of fibrinogen into fibrin = insufficient clot
Significance
- prolonged bleeding
- severe: spontanous bleeding
Treatment: factor 8 and 9 concentrates
