Hemostasis (Ch. 22)-- Definition First Flashcards
Exam 2
Actin & Myosin contract → Fibrin strands pulled toward platelet plug → Clot retraction → Plasma (liquid) squeezed out of clot → Clot shrinks
Fourth Step of Hemostasis
-
Autosomal dominant coagulation disorder
- Deficiency or defect in vWf
- Mild-moderate bleeding
Treatment– DDAVP (Desmopressin Acetate) an analog of ADH/Vasopressin
von Willebrand Disease
- Platelet count out of range
- Abnormal platelet function
- Coagulation factor dysfunction
- Loss of blood vessel integrity
Causes of Blood Disorders
Activation, adhesion & aggregation of platelets → Platelet plug
Damaged vessel → Activation of platelets
Endothelial cells → vWf → Binds platelet receptors (GPIIb/IIa) to vessel wall → Adhesion
Platelets release mediators (ADP & TXA2) → Aggregation
Second Step of Hemostasis
-
X-linked recessive coagulation disorder
-
Factor VIII deficiency
- Works w/ vWf to promote adhesion
-
Factor VIII deficiency
- S/S
- Mild
- Bleeding w/ trauma/injury
- Severe
- Spontaneous, uncontrolled bleeding
- Mild
Treatment– Factor VIII replacement therapy
Hemophilia A
- 3 Stages
-
Vascular constriction
- Vessel spasm → ⇣ Blood flow
-
Platelet Plug (unstable)
- Platelets play a major role
-
Blood coagulation (stable)
- Clotting factors (CF) play a major role
-
Vascular constriction
- End result
-
Fibrin (CF Ia)
- Rope-like substance wraps around platelet plugs
- Structural basis of clot
- Blood becomes gel-like
- Traps RBCs in clot
- Clot & fibrous tissue grow together
- Seal hole in vessel wall
-
Fibrin (CF Ia)
Mechanisms of Hemostasis
- Factor I to XII
- Synthesized in liver (mostly)
-
Factor X
- Beginning of final common pathway
-
Factor VIII
- Not present in hemophilia
- Factor I (Fibrinogen)
- Factor Ia (Fibrin)
- Factor II (Prothrombin)
- Factor IIa (Thrombin)
- Factor IV (Calcium)
-
Vitamin K
- Required to make CF II, VII, IX, & X
Plasma Clotting Factors
Thrombocytopenia (platelets < 150,000/uL) → Bleeding disorder
d/t– Drug-induced, Malignancies, Immune response, Pooling of platelets in the spleen (sequestration)
Manifestation– Petechiae (platelet count < 20,000/uL in small vessels)
Low Platelet Count
Requires Ca2+
-
Intrinsic pathway
-
Inside vessel wall
- Ex: Atherosclerosis
- Slow
- 1-6 min.
- Begins in circulation
- Factor XII activated
-
Inside vessel wall
-
Extrinsic Pathway
-
Outside wall of the vessel
- Ex: Gunshot wound
- Faster
- 15 sec.
- Factor III activated
-
Outside wall of the vessel
-
Final Common Pathway
- Both pathways converge @ Factor X
- Factor II → IIa (Prothrombin → Thrombin)
- Factor I to Ia (Fibrinogen → Fibrin)
- Both pathways converge @ Factor X
Clotting Cascade
Impaired platelet function → Bleeding disorder
d/t– ASA/NSAID use (ASA irreversibly ⇣ TXA2 activity), Adhesion disorder (von Willebrand disease)
Thrombocytopathia
Clotting Cascade:
Factor XII activated → Intrinsic pathway (slow, begins in circulation)
Factor III activated → Extrinsic pathway (fast, exposed tissue)
Factor X activated → Final common pathway → Fibrinogen (H2O soluble) → Fibrin (H2O insoluble)
Third Step of Hemostasis
Endothelial cells → tPA → Plasminogen → Plasmin (active) → Digestion of fibrin strands → Clot dissolution (Fibrinolysis)
Fifth Step of Hemostasis
Clotting/Stoppage of Blood Flow
Red blood cells trapped in fibrin meshwork (semisolid clot)
Clot=Thrombus
-
Normal
- Blood vessel seals to stop bleeding
-
Abnormal
-
Thrombosis
- Inappropriate formation of blood clots
-
Hemorrhage
- Failure to form a blood clot in the presence of bleeding
-
Thrombosis
Hemostasis
- Bleeding
- Petechiae
- Oozing from puncture sites
- Severe hemorrhage
-
Hypoxia & organ damage
-
Microemboli obstruct blood vessels
- Renal, circulatory, or respiratory failure
- Convulsions
- Coma
- Renal, circulatory, or respiratory failure
-
Microemboli obstruct blood vessels
Treatment– Manage primary disease, Replace clotting components (Factor VIII, FFP (fresh-frozen plasma), platelets, cryoprecipitate), Heparin
Clinical Manifestations of Disseminated Intravascular Coagulation (DIC)
Major role in platelet adhesion & blood clotting
- von Willebrand Factor (vWf) Synthesis
- Required for blood clotting
- Cell wall integrity disrupted → vWf → Aggregation
-
Promote blood flow
- Block platelet adhesion
- Inhibit coagulation
- Clot lysis
Endothelial Cells
-
PT/INR
- Prothrombin time
- Time (sec.) it takes for blood to clot
- Extrinsic pathway
- Prothrombin time
-
PTT
- Partial prothrombin time
- Time (sec.) it takes for blood to clot
- Intrinsic pathway
- Partial prothrombin time
-
⇡ PT/PTT/INR
- Clotting too slow
- ⇡ Risk of hemorrhage
-
⇣ PT/PTT/INR
- Clotting too fast
- ⇡ Risk of clotting
Blood Coagulation Clinical Assessment (“Coags”)
- Anuclear fragment of megakaryocyte
- Originate from myeloid stem cells
- Life span: 8-12 days
- Normal levels: 150,000-400,000 cells/uL
-
Thrombopoietin
- Hormone that stimulates thrombocyte proliferation
- Released from liver & kidneys
- Hormone that stimulates thrombocyte proliferation
- Function
- Aggregate → Blood coagulation & Vessel repair
- Components
- Glycoprotein Ilb/Ila (GPIIb/IIa)
- ADP
- Serotonin
- Thromboxane (TXA2)
- Actin/Myosin II
-
Alpha & Delta Granules
- Secrete mediators
Platelets (Thrombocytes)
INJURY → Vasoconstriction/Vessel Spasm → ⇣ Blood flow from rupture
Nerve reflexes & Humoral factors → Short vessel spasm
Platelets → TXA2 → ⇡ Aggregation & Vasoconstriction
First Step of Hemostasis
Widespread coagulation and bleeding due to underlying disorder
d/t– Obstetric complication, Malignant neoplasms, Systemic infections (Sepsis), Severe trauma, Surgery, Burns (extrinsic pathway), Endothelial or tissue injury (intrinsic pathway)…
- MASSIVE activation of clotting pathway
-
Excessive thrombin generation
- Fibrinogen converted to fibrin via thrombin
- Fibrin deposited in capillaries
- Systemic microvascular clots
-
Excessive thrombin generation
-
Vicious cycle (steps 3-5 repeat)
- Clotting, dissolution (bleeding), clotting, dissolution (bleeding)…
-
Uncontrolled, excessive bleeding
- All clotting factors have been used up
Disseminated Intravascular Coagulation (DIC)
