Anticoagulation, Hemostasis and Venous clotting(Patho) Flashcards
These are the componenets of the Coagulation of system
- Platelets
- Endothelial Cells
- Tissue-Factor Bearing Cells
- Coagulation factors
- Antithrombotic factors
Platelets
- Fragments of megakaryocytes
- Creation is stimulated by cytokines and thrombopoietin
- Important source of phospholipids which are required for the function of the coagulation system proteins
- Intracellularly contain dense granules and alpha granules
Endothelial Cells
Cells that line blood vessels
Tissue-Factor Bearing Cells
Principle initiator of blood coagulation
Coagulation Factors
Plasma proteins that are enzymes(serine proteases)
Activated forms of factors have an “a” at the end
Most are created by the liver
Factors II,VII,IX,X are dependent on gammacarboxylase which is dependent on Vitamin K
Antithrombotic factors
- Protein C and S (natural anticoagulants that are also vitamin K dependent)
- Antithrombin(inactivates serine proteases IIa,IXa,XIa and XIIa)
Primary Hemostasis
Vasoconstriction
- Adhesion
- Activation
- Aggregation
Secondary Hemostasis
Formation of fibrin
- Initiation
- Amplification
- Propagation
Fribrinolysis
Natural negative feedback loop
Breaks down fibrin clots
PrimaryHemostasis (Adhere)
- Adhere to collagen in the vascular subendothelium
- Exposed collagen releases von willebrand factor
Primary Hemostasis(Activation)
- Granules release ADP, calcium and thromboxane A2 to activate further platelets
- GP IIb/IIa receptors are exposed on the platelet
Primary Hemostasis(Aggregate)
- Changes shape from discord–> spherical with extensions and then a flat shape to cover the injury
- Forms a “platelet plug”
Secondary Hemostasis(Initiation)
- Begins with release of tissue factor (TF) by the injured cells
- TF directly activates factor VII which activates factor IX and X
- Activation of IX and X catalyzes conversion of pro-thromnin to thrombin
- Thrombin cleaves fribrinogen to fibrin(stable clot)
The amount of fibrin generated during initiation is insufficient to stabilize the platelet plug
Secondary Hemostasis(Amplification)
- Thrombin generated in intiation activates platelets and coagulation factors V,VIII and XI(found on plate[let surface)
- Factor VIII is activated by releasing it from von willebrand factor
- Factor XIa catalyzes activation of IX to IXa
Fibrinolysis
- Process of breaking down fibrin into degradation products
- Thrombin catalyzes formation of plasmin from its inactive precursor plasminogen
Plasmin is a serum protease that cleaves fibrin–>breakdown of clot and creation of fibrin degradation products
Secondary Hemostasis(Propagation)
Two major complexes are formed:
1.Tenase–> Factors VIIIa and IXa with phopholipids and calcium (this activates factor X on the platelet surface)
2.Prothrombinase–>Factors Xa and Va with phospholipids and calcium(catalyzes prothrombin => thrombin)
3.Activated thrombin stabilizes the platelet plug
4.Thrombin activates factor XIIIa which stabilizes the fibrin polymer
Virchow’s Triad
Hypercoagulable state <–> Vascular injury<—>Circulatory Stasis
Risk factors Hypercoagulable state
- Malignancy
- Pregnancy
- Inflammatory state
- Factor V Leiden
- Protein C/S deficiency
- Oral contraceptives
Risk factors of Circulatory stasis
- Hospitilization
- Surgery
- Obesity
- Long distance travel
Risk factors of Vascular injury
- Orthopedic surgery
- Trauma
- Venous catheters
- Smoking
Risk factors of Multiple Components
- History of VTE
- Age(older=increased risk)
Other risk factors of the Virchow’s triad
- Metabolic syndrome
- Inflammatory disorders: Crohn’s diseas, ulcerative colitis, RA, infections
What is Venous Thromboembolism(VTE)?
Clot occuring in the VENOUS circulation
Types of VTE
- Deep vein thrombosis(DVT)
- Pulmonary Embolism(PE)
Deep Vein Thrombosis (DVT)
- Usually occurs in the lower extremity
- Due to blockage (thrombosis—>clot in diseased vessel)
- Rarely fatal
Pulmonary Embolism(PE)
- Occurs in the lung
- Usually due to a dislodged blockage (embolism= mobile clot)
- Can be fatal
Types of Clots
- Arterial clot (Platelet rich)
- Venous clot (Fibirn rich)
Signs and symptoms of DVT
- Unilateral leg pain, redness,swelling, and/or warmth
- Positive Homan’s sign
- Elevated D-dimer(by product of thrombin generation)
Proximal DVT
70-80% of DVTs are proximal, ,ost commonly the popliteal and superficial femoral vein
Distal DVT
20-30% of DVTs are isolated in veins of the calf: the anterior, tibial, peroneal, and posterior
Testing for DVT
Usually diagnosed through a duplex ultrasound with doppler flow
Pulmonary Embolism
Large thrombi or an accumulation of smaller ones can cause substantial impairment or cardiac and respiratory function/death
Signs and symptoms of PE
- Cough
- Tachypnea
- Tachycardia
- Often identify signs/symptoms of DVT in the leg
- Elevated D-dimer
Testing for PE
- Ventilation/perfusion scan
- CT pulmonary angiography
PE severity classification
- Low risk(PE not meeting other criteria)
- Intermediate risk(Right ventricular strain-> ECHO,->(+) troponin, ->(+) BNP)
- High risk (systolic BP<90mmHG of decrease of 40 mmHG from baseline,requiring vasopressors, pulseless)
Provoked vs Unprovokes VTE
- Provoked(caused by a known event)
1. Long-distance travel
2. Surgery
3. Hospitilization
4. other elements in VIrchow’s Triad - Unprovoked(no identifiable factor cause VTE)
