Module 2.7 Hemostasis Flashcards
Heparin reversal agent
Protamine Sulfate
Where does heparin act in the coagulation path
Inhibits Factor X to produce fibrin formation.
Which pathway does PTT measure?
Intrinsic (Play Table Tennis Inside)
Used to measure heparin effect
Which pathway does PT measure
Extrinsic (Play tennis outside)
Used to measure Warfarin effect.
How is platelet function measured
Bleeding time test.
3 phases of restoring hemostasis
- Vessel Spasm
- Formation of platelet plug.
- Blood Coagulation or development of an insoluble fibrin clot.
(Spazz, plug, clot)
Vessel spasm in hemostatic restoration
Spasm is transient (minutes-hours)
Mechanically slows blood flow to the area.
What initiates vessel spasm
cytokines
Prostaglandins (Thromboxane A2, Prostacyclin)
Thromboxane A2
causes constriction
Prostacyclin
Causes dilation, inhibits platelet aggregation in normal uninjured vessels
Half life of platelets
8-12 days
What produces platelets
megakaryocytes
Listen at 7:30
Listen at 7:30
Vitamin K is soluble in
fat only
Requirements for clotting
Platelets
Von Willebrand Factor
Clotting Factors
Where is Von Willebrand factor generated
by the vessel endothelium
Where are clotting factors synthesized
in the Liver using Vitamin K
Antithrombin III
Contains naturally occurring heparin
Protects against uncontrolled thrombus formation
Protein C
Plasma protein
Acts as anticoagulant by inactivating factors V and VIII
Intrinsic Pathway
Slow
Extrinsic Pathway
Fast
Trauma response
Where do the intrinsic and extrinsic pathways become the same
Activation of Factor X
Describe the activation of the coagulation pathway after factor X
Xa activates prothrombin to thrombin
Thrombin activates fibrinogen to fibrin
Listen to 13:50 Mark)
Listen to 13:50 Mark)
Listen to khan academy vid on clotting
Listen to Khan Academy vid on clotting
Protein S
Accelerates the action of protein C
Negative feedback systems in clotting cascade
Proteins S and C
Plasminogen > Plasmin breaks down fibrin mesh into fibrin degradation products
Thrombin stimulates anti-thrombin production
Anti-thrombin action
inhibits conversion of prothrombin to thrombin
By inhibiting activation of factor X (which is the common pathway!!)
Warfarin MoA
Affects vitamin K and therefore dependent factors
NOT IMMEDIATELY REVERSABLE
Heparin MOA
Affects factor X without other clotting factors
IMMEDIATELY REVERSIBLE
Heparin is measured with
PTT
Warfarin (Coumadin) is measured with
PT
What may also decrease vitamin K levels other than Coumadin
Antibiotics (kills bacteria needed for absorption)
Clofibrate
Conditions that cause increased platelet function
Atherosclerosis Diabetes Smoking HLD and high cholesterol Pregnancy (estrogen increases coagulation) Protein S and C deficiency
Leiden mutation
Factor V mutation
Decreased Protein C effect
Hypercoagulability
Virchow’s Triad
Vessel Injury
Stasis
Hypercoagulable state
Antiphospholipid syndrome
IgG antibodies directed against phospholipids
Recurrent venous and ARTERIAL thrombi
DVT’s, arterial thrombosis in coronary, renal and peripheral arteries
Recurrent pregnancy loss
TIA’s
Risk factors for hypercoagulability states
Pregnancy and puerperium Oral contraceptives (estrogen) Post-surgical state Virchow's Triad/immobility Congestive Heart Failure Malignant diseases
Thrombocytosis
> 1,000,000 platelets/uL
Due to increased thrombopoietin production
Primary thrombocytosis
bone marrow disorders - increased platelet production.
Often dysfunctional platelets.
Secondary Thrombocytosis
Disease states causing more platelet production
Post-op Infection cancer CHRONIC INFLAMMATORY CONDITIONS Myeloproliferative disorders.
Arterial thrombi are associated with
turbulent blood flow.
Venous thrombi are associated with
stasis
Thrombocytopenia
<150,000 platelets/uL
clinical issues really start at <100k though.
Causes of thrombocytopenia
Decreased platelet production secondary to decreased thrombopoietin.
Increased sequestration of platelets in spleen.
Decreased Platelet survival
Impaired platelets function
Types of thrombocytopenia
Drug induced
Immune thrombocytopenia purpura (ITP)
Thrombotic hrombocytopenia purpura
Immune thrombocytopenia purpura (ITP)
autoimmune
increased platelet antibody formation
usually follows viral infections in children
DOESN’T INVOLVE CLOTTING FACTORS
Manifestations of thrombocytopenia
Bleeding (nose, mouth, GI
Petechiae - pinpoint purple-red spots
Purpura - PURPLE areas
Splenic enlargement in ITP due to sequestration. Possible Splenectomy.
Vitamin K deficiencies
Antibiotics - kill bacteria needed for absorption
Impaired fat absorption (bile salts!)
Hemophilia A
Factor VIII deficiency (30% of new cases are new mutations!!!)
X-linked recessive
ayyyy 8
Hemophilia B
Factor IX deficiency
X-Linked Recessive
Von Willibrand Disease
Autosomal Dominant (type 1 and 2)
Autosomal recessive for type 3 (rare)
Normal platelet count
Increased bleeding time
Hemorrhagic Telangiectasia
Autosomal Dominant
thin walled vessels, dilated capillaries and arterioles
Cushing Diseases
protein wasting and loss of vessel tissue support due to increased cortisol
Vit. C Deficiency
Scurvy
Poor collagen synthesis and failure of endothelial cells to cement together
Senile Purpura
old person bruising
Disseminated Intrvascular Coagulation (DIC)
Consumptive process. System wide clotting cascades via INTRINSIC system.
All components of cascade wiped out. Severe Hemorrhage occurs.
Caused by some other disease or injury.
Causes of DIC
Gram negative sepsis Obstetric complications Any trauma Hypoxia Shock Hypotension
