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What are the interacting factors in hemostasis after an injury with very brief description
- Blood vessels: reduce blood flow
- Platelets: adhere to form aggregates, contribute to coagulation process
- Blood coagulation factors: form fibrin clot
- Fibrinolysis: break down cloth when healing complete
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Describe the 4 types of bleeding patterns
- Petechiae: very small blood spots (<1cm)
- Ecchymosis: small blood spots (>1cm)
- Purpura: red/purple discoloration that doesn't go away with pressure (a bruise)
- Joint bleeding: appears as edema, common in hemophiliacs
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What is the difference between an artery and a vein?
- Artery: carries blood away from the heart
- Vein: carries blood toward the heart
- Capillary: connects them
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Describe the anatomy of an artery (in depth)
- Tunica Interna: endothelium, basement membrane, internal elastic membrane
- Tunica Media: mostly smooth muscle, external elastic membrane
- Tunica Externa: Connective tissue (contains collagen)
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Describe the anatomy of a vein (in depth)
- Tunica Interna: endothelium, basement membrane
- Tunica Media: smooth muscle
- Tunica Externa: connective tissue (contains collagen)
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Describe the anatomy of a capillary (in depth)
Endothelium, basement membrane
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Describe the functions of Blood Vessels (contribution to clotting)
- Vasoconstriction
- Diverts blood flow
- Initiation of contact-activation of platelets to adhere with subsequent aggregation
- Contact-activation of extrinsic and intrinsic blood coagulation pathways leading to the formation of fibrin
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Describe the laboratory evaluation of vascular function
- Difficult to do
- Old test was tourniquet test (capillary fragility/Rumpel-Leedes test)
- take blood pressure
- increase pressure to 100 mmHg and leave for 5 minutes
- may form petechiae
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Describe the acquired vascular defects of blood vessels
- autoimmune purpura: immunoglobins attacking vascular walls
- Purpura associated with infections: immunoglobins attacking vascular walls
- Scurvy due to Vitamin C deficiency:
- Senile purpura: Old people hands
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Describe the congenital vascular defects of blood vessels
- Hereditary hemorrhagic telangiectasia: autosomal dominant
- lack of intervening capillaries between A and V causes pressure building and vein breakage
- Much bleeding (nose, mouth, etc)
- Nodular lesions on mucous membranes of skin and mouth
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Describe the development and kinetics of platelets
- Develop from myeloid stem cell in marrow (Stimulated by thrombopoietin produced in the liver and kidney)
- Development takes 4-5 days in bone marrow (doesn't occur in blood)
- Megakaryoblast:
- Promegakaryocyte: undergoes endomitosis (division of nucleus without splitting)
- Megakaryocyte: 2000-4000 platelets
- Metamegakaryocyte: naked nucleus (very little cytoplasm)
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What is the normal range for platelets in blood? Turnover per day? Approximate location found in the body? Life Span?
- Normal: 130-400x10^3/uL
- Turnover: ~35x10^3/ul per day
- Location: 2/3 in blood, 1/3 in spleen
- Life span: 7-10 days (death - RE system in spleen, clots)
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Describe the anatomy of a platelet in very basic detail
- Hyalomere: the outside
- consists of peripheral zone and sol-gel (cytoskeletal) zone
- Granulomere: the inside
- consists of the organelle zone
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Describe the peripheral zone of a platelet in detail
- Glycocalyx: ABO antigens, human leukocyte antigen, glycoproteins Ib, IIb, IIIa
- Open Canalicular system:
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Describe the cytoskeleton zone in detail
- Microfilaments:
- Microtubules:
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Describe the Organelle Zone in detail
- Mitochondria:
- Glycogen: energy source
- Alpha granules (20-200): beta-thromboglobulin, platelet factor 4, platelet-derived growth factor, thrombospondin
- Dense bodies (2-10): ADP, ATP, calcium, seratonin
- *seratonin increases vasoconstriction at site of damage
- Lysosomes: bacteriocidal enzymes, neutral proteases, acid hydrolases
- Dense Tubular system:
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Describe the functions of platelets
- Platelet plug formation
- Contributions to coagulation (platelet factors)
- Transport of substances such as serotonin (vasoconstrictor)
- Phagocytosis (highly limited by size)
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List the platelet factors
- PF 1: coagulation factor V
- PF 2: thromboplastin-like material
- PF 3: platelet thromboplastin
- PF 4: antiheparin factor
- PF 5: fibrinogen coagulant factor
- PF 6: antifibrolytic factor
- PF 7: platelet cothromboplastin
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Describe the events of clotting following a vascular injury (including timeframe for each step)
- Vascular injury
- Vasoconstriction
- Adherence of platelets (1-2s): caused by collagen exposure from vessels
- Aggregation of platelets (10-20s): after granule release
- Plug formation (1-3m): after granule release
- Consolidation (3-5m): after addition of fibrin (formed after collagen exposure)
- Fibrin stabilization (5-10m): after addition of fibrin stabilizing factor (FSF)
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Describe the substances on the platelet surface necessary for adherence (w/ info?)
- von Willebrand's factor: produced by endothelial cells and megakaryocytes
- carrier for Factor VIII in plasma
- Glycoprotein Ib (in glycocalyx)
- Platelet surface glycoproteins: IIb and IIIa in glycocalyx
- ADP and Ca++ in granules
- Fibrinogen
- Thromboxane A2
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Describe the laboratory evaluation of platelet number and/or function
- Quantitative platelet count (number):
- Bleeding time (number and function): Ivy bleeding time is 2.5-9.5 minutes (increased in thrombocytopenia, inherited platelet dysfunction, aspirin administration)
- Platelet aggregation test (function):
- primary wave - platelets adhere in the presence of ADP, epinephrine, ristocetin
- secondary wave - platelets have been stimulated to secrete the substances in their organelles
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Describe the quantitative platelet defects
- Thrombocytopenia: decreased production of thrombocytes
- ineffective thrombopoiesis
- abnormal distribution of platelets (not 1/3, 2/3)
- increased destruction (drug-induced, idiopathic thrombocytopenia purpura, thrombotic thromocytopenia purpura)
- Thrombocytosis: overproduction of platelets
- essential thrombocytosis- myeloproliferative disorder
- platelet counts up to 1 million/uL
- high tendency to clot
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Describe the qualitative platelet defects
- Aquired defects: renal disease, liver disease, drug therapy (aspirin) causing inhibition of thromboxane A2
- Congenital defects: von Willebrand's disease (decrease in vWF, affects platelet adhesion)
- Bernard-Soulier syndrome- decrease in glycoprotein Ib
- Glanzmann's thrombasthenia- decrease in glycoproteins IIb and IIIa
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