week 2- hemostasis Flashcards
(76 cards)
• What is hemostasis?
o Rapid, localized process; balance bw bleeding and clotting
o Body stops bleeding after injury, maintains blood in fluid state in vascular compartment
o Controlled activation of plts and soluble clotting factors, form stable fibrin clots
• What are the major constituents of the hemostatic pathway?
o Coagulation proteins, plts, endothelium
o Each interacts and influences all others
• What are the 3 simultaneous pathways that cause stable hemostatic plug after BV injury?
o Neural → BV constriction → reduced blood flow
o TF → coagulation activation → thrombin, fibrin
o Plt activation → primary hemostatic plug → plt fusion
• What are the 2 stages of hemostasis?
o Primary: response to BV injury, form plt plug adhere to endothelium, immediately limit bleeding
o Secondary: stable clot formation, enzymatic activation of coagulation proteins, produce fibrin, reinforce plt plug, gradual fibrinolysis dissolves plug
• What is the main purpose/advantage of the endothelium vascular system?
o Smooth endothelium helps blood flow
o Intact endothelial cells inhibit plt adherence and coagulation
o Endothelial injury promotes local clot formation
• What role does vasoconstriction play in hemostasis?
o Narrows lumen to reduce blood loss
o Brings plts and proteins closer to vessel wall
o Enhance contact activation of plts (VWF, collagen, plt membrane glycoprotein Ib)
o Activated plts enhance activation of coagulation proteins
• How quickly does coagulation occur after BV injury?
o Normally, coagulation initiated within 20 seconds of injury
• What are plts?
o Small, anucleated, cytoplasmic fragments of megakaryocytes
o Normal: 150-400 x 10E9 /L
o Live 9-12 days
o old cells removed by spleen and liver
o ~2/3 circulate in peripheral blood
o ~1/3 sequestered in spleen (2 pools constantly exchanging, equilibrium)
o Spontaneous hemorrhage <10 x 10E9 /L
• Where do plts come from?
o released from BM by megakaryocytes
o Megakaryocyte proliferation stimulated by thrombopoietin (TPO)
o TPO: humoral factor; produced by liver, kidney, spleen, BM; made at constant rate
• How does plt adhesion happen?
o Damaged endothelium exposes blood to subendothelial (SE) tissue matrix w adhesive molecules
o Plt receptor GPIb binds SE collagen fibers via VWF
o Plt adherence stops initial bleeding
• What is VWF?
o Multimeric glycoprotein
o Parts made in endothelial cells and megakaryocytes
o Stored in endothelial cells (Weibel-Palade Bodies) and Plt alpha-granules
o Circulate in plasma, 7-10 mg/mL
o Ligand for Plt receptor Ib/IX
• What happens to plts after aggregation?
o Undergo a shape change
o Oval → dendrites → more dendrites → fried egg
• What things are necessary for plt-plt interaction in aggregation?
o Dense granule release from adhering plts
o Requires Ca2+ and ATP; fibrinogen; fibrinogen recptors GPIIB and IIIA
• What plt-plt interaction happens in aggregation?
o Begins 10-20 sec after injury and adhesion
o ADP released from plt cytoplasm → expose GIIb and GIII, fibrinogen binds
o EC Ca2+-dependent fibrinogen bridges form bw plts, promote agg
o = primary/reversible aggregation
o 2nd/irreversible: begins w release of dense granules
• What is the purpose of secretion of dense granules?
o Begin 2nd agg
o Have lots of ADP, binds plt membrane triggering synthesis and release of TXA2
o Amplifies initial plt agg into big plt mass
o = primary hemostatic plug
• What is the primary plt plug?
o Dt plt interaction with vessel wall, each other
o Plug: fragile, can easily be dislodged from vessel wall
• What are some inherited plt defects?
o Bernard soulier dz: def GPIb o Von Willebrand dz: def VWF o Glanzmann’s Thrombasthenia: GPIIb, GPIIIA o Storage pool dz: dense body o Gray plt syndrome: alpha granule o Defective procoagulant activity o COX deficiency: dense tubular system
• What is von Willebrand dz?
o Most frequent inherited bleeding disorder, ~1/100
o many clinical manifestations
o Clinically significant vWD : 125/1 million
o Severe dz in 0.5-5/ 1 million
o Autosomal inheritance pattern
o M=F
• Who discovered vWD? What did he find? Future findings?
o 1931-Erik von Willebrand o Hereditary pseudohemophilia o Prolonged BT, normal plt ct o Mucosal bleeding o M=F o 1950s: prolonged BT assoc w def fx VIII o 1970s: discover VWF o 1980s: VWF gene cloned
• What is the classification of vWD?
o Type I: partial quant def; 70%; mild-mod dz
o Type II: qual def; 25%; mild-mod dz
o Type III: near/total def; 5%; severe dz
o Additional subclass: acquired vWD
• What is bleeding time? Recommended criteria prior to testing?
o Test adequacy of primary hemostasis or plt fxn
o 1. Plt ct: >75,000/mm3
o 2. Only I BT/24 hrs, unless excuse
o 3. stop heparin 6 hrs prior
• How is bleeding time done?
o BP cuff on arm (@40 mm Hg)
o 2 incisions made on inner forearm
o Blot w filter paper every 30 sec
o Record time for clotting to occur (bleeding stops)
• What are sources of error giving false + results in BT?
o BP cuff too high (>40) or too low o lo fibrinogen (<100 mg/dl) or plt ct (100,000 /mm3). o Drugs that affect plt fxn (aspirin) o Incision too shallow/deep o disturb clot w filter paper
• what are the ref ranges for BT?
o 1-3 mins (duke method)
o 2-7 mins (template Ivy method)
