Week 3 Flashcards
What is Hemostasis
The arrest of bleeding and the maintenance of vascular patency
Components of Normal hemostatic system
Formation of platelet plug (Primary hemostasis)
Formation of fibrin clot (Secondary hemostasis)
Fibrinolysis
Anticoagulant Defences
What happens when the endothelial wall is damaged
Exposes collagen and releases von Willebrand Factor and other proteins which platelets have receptor -Platelet adhesion at the site of injury
What happens when the platelets adhere to a damaged vessel wall
Secretion of various chemicals from platelets - leads to aggregation of platelets at the site of injury
What is reduced number of plateles called
Thrombocytopenia
Consequences of failure of platelet plug formation
Spontaneous bruising and purpura
Mucosal bleeding
Intracranial hemorrhage
Retinal hemorrhage
What is the screening tests for primary hemostasis
Platelet count
Secondary hemostasis has what pathways
Extrinsic pathway
Intrinsic pathway
Common pathway
2nd hemo - The Extrinsic pathway involves what components
Tissue factor
Clotting factor VII
Clotting factor X
2nd hemo - The Intrinsic pathway involves what components
Clotting factor 8-12
2nd hemo - The Common pathway involves what components
Clotting factor X
Thrombin
Fibrin
Single clotting factor deficiency cause
Usually hereditary
ie Hemophilia
Multiple clotting factor deficiency cause
Usually acquired
ie Disseminated Intravascular Coagulation
How does Fibrinolysis pathway work
Plasminogen –(Tissue Plasminogen Activator, tPA)–>Plasmin
Fibrin–(Plasmin)–>Fibrin Degradation Products
Naturally occuring anticoagulants
Serine Protease Inhibitors (Anti-thrombin III)
Protein C and Protein S
What activates Protein C and Protein S. What do they block
Thrombin activates
Block Intrinsic and common pathway
What is Thrombophilia
Deficiency of naturally occuring anticoagulants, may be hereditary.
Increased tendency to develop enous thrombosis (Deep vein thrombosis/pulmonary embolism)
What is shock
Shock is the clinical syndrome of Tissue hypoperfusion due to Circulatory Failure
How to calculate Mean arterial pressure
(2x Diastolic+ systolic) /3
What is the Virchow’s triad
Stasis of blood flow
Endothelial injury
Hypercoagubility
Three things that lead to thrombis
Inadequate perfusion causes
Systemic acidosis
Microcapillary thrombus
Ischemia of organs
Signs of hypoperfusion
Mottling of skin, clammy
Kidney - Oliguria
Blood test to confirm hypoperfusion
Lactate levels
>2mmol/L diagnostic
>4mmol/L significant mortality
Mean arterial pressure is due to four physiological causes
1.Heart rate
2.Stroke Volume
3. Cardiac output
4. Systemic vascular resistance
1 and 2 makes up 3
Four mechanism can create drop in Mean arterial pressure
Cardiogenic Shock
Obstructive Shock
Hypovolemic Shock
Distributive Shock
What is Cardiogenic shock
Reduced force of cardiac contraction and stroke volume.
Result in Cool, clammy peripheries due to compensatory systemic vasorestriciton
Treatment for Myocardial infarction if it’s within 90 minutes
Percutaneous cardiac intervention (PCI)
What is Obstructive shock
Obstruction to cardiac outflow, not caused by cardiac failure. Evidence of raised JVP and distended neck veins may be seen
Examples of causes of Obstructive shock
Cardiac tamponade
Tension pneumothorax
Pulmonary embolous
What is Hypovolemic shock
Reduced blood volume
Lower venous return
Reduced force of cadiac contraction and CO (Frank-Starling law)
What is Distributive shock
Reduced systemic vascular resistance due to Vasodilation with warm, red peripheries
Compensatory increase in Cardiac output
Explain Intrinsic pathway
Clotting factor VIIIa+IXa activates X into Xa
Explain Extrinsic pathway
Tissue Factor and Clotting factor VIIa together activates Clotting factor X to Xa
Explain the common pathway
Clotting factor Xa and Va together converts Prothrombin into Thrombin.
Thrombin then activates Fibrinogen into Fibrin
What is Henoch-Schonlein Purpura
Small vessel vasculitis where IgA and complement 3 deposits in arterioles, capillaries and venolos. Present with palpable purpura and kidney problems, Affect kids. Similar to IgA nephropathy but it affect young adults.
Causes of peripheral platelet destruction
Coagulopathy (Disseminated intravascular coagulation)
Autoimmune (Immune thrombocytopenic purpura, ITP)
Hypersplenism
von Willenbran Factor deficiency cause
Autosomal dominant
Common
Variable severity, generally mild
Commonest cause of primary hemostatic failure
Thrombocytopenia
Multiple clotting factor deficiency is causes
Liver failure
VitK deficiency/Warfarin therapy
Complex coagulopathy
Lab results in Multiple clotting factor deficiency
Prolonged Prothrombin time (PT) and Activated partial thromboplastin time (APTT)
Vitamin K act on which clotting factors and how
Factors 2, 7, 9 and 10.
VitK carboxylates them
Why does liver failure cause clotting factor deficiency
Because all coagulation factors are synthesized in hepatocytes
How and where is VitK absorbed
Absorbed in upper intestine
Requires bile salts for absorption
Causes of VitK deficiency
Poor diet intake Malabsorption Obstructive jaundice VitK antagonists (Warfarin) Hemorhagic disease of the newborn
Disseminated Intravascular coagulation is what
Innapropriate activation of coagulation cascade, causes microvascular thrombus and organ failure. Due to clotting factor consumption it also leads to bruising, purpura and generalised bleeding
What test is done for the Extrinsic pathway
Prothrombin time
What test is done for the intrinsic pathway
Activated partial thromboplastin time
Causes of Disseminated Intravascular Coagulopathy
Sepsis
Obstetric emergencies
Malignancy
Hypovolemic shock
Treatment of Disseminated Intravascular coagulopathy
Treat underlying cause Replacement therapy (Platelet, Plasma Fibrinogen transfusions and replacement)
Genetics of Hemophilia
X-linked
Types of hemophilia and what it effects, most common
Hemophilia A - Factor 8 deficiency
Hemophilia B - Factor 9 deficiency
Hemophilia A is more common
Features of Hemophilia bleeds
No abnormality of primary hemostasis
Bleeding from medium to large blood vessels
Severity ranges
Clinical features of severe hemophilia
Recurrent Hemarthroses
Bleeding into joints
Recurrent soft tissue bleeds (bruising in toddlers)
Prolonged bleeding after dental extractions, surgery or invasive procedures
Types of Venous thrombotic events
DVT
PE
Features of Arterial thrombosis
High pressure system
Atherosclerosis
Platelet rich thrombus
Features of Venous thrombosis
Low pressure system
Platelets not activated
Activated coagulation cascade - rich in fibrin clot
Treatment for Venous thrombosis
Heparin
Warfarin
New oral anticoagulants
Features of DVT
Limbs feel hot, swollen, tender
Pitting edmea
Categorize of causes of thrombosis
Virchow’s triad
Stasis
Vessel wall (injury)
Hypercoagulability
What is Thrombophilia
Familial or acquired disorders of the hemostatic mechanism which are likely to predispose to thrombosis
Mechanisms of Thrombophilia
Increased coagulation activity
Decreased fibrinolytic activity
Decreased anticoagulant activity
Types of Hereditary thrombophili
Factor V Leiden Prothrombin 20210 mutation Antithrombin deficiency Protein C deficiency Protein S deficiency
When should you consider hereditary thrombophilia screening
Venous thrombosis
Management of Hereditary Thrombophilia
Advice avoiding risk
Short term prophylaxis (prior to known risk event)
Short term anticoagulation (to treat thrombotic events)
Long term anticoagulation (only if recurrent thrombotic events)
Acquired Thrombophilia can occur in
Antiphospholipid antibody syndrome
Features of Antiphospholipid syndrome
Recurrent thromboses (Arterial and Venous)
Recurrent Fetal loss
Mild thrombocytopenia
Treatment of Anti-phospholipid syndrome
Aspirin
Warfarin
Indictions for anticoagulant drugs
Venous thrombosis
Atrial fibillation
What is the target of anticoagulant drugs
secondary hemostasis
What is the action of Heparin
Potentiates antithrombin
What are the two forms of Heparin
Unfractionated
Low Molecular weight (LMWH)
How is Heparin given, how fast does it act
Parentral (IV or SC)
Immediated effect
Types of Heparin has a slightly different affinity to the same two targets, what are they?
Unfractioned - Thrombin
LMWH - Factor Xa
How is heparin monitored
Unfractionated - Activated partial thromboplastin time (APTT)
LMWH - Anti-Xa assay but usually does not need monitoring
Complications of Heparin
Bleeding
Heparin induced thrombocytopenia (w/thrombosis)
Osteoperosis in long term
Heparin used in pregnancy
LMWH
Antidot for heparin
Protamine sulphate
Unfractionated - complete reverse
LMWH - partial reverse
Is antidot for heparin needed
Only in severe bleed
Otherwise short half-life
What are Coumarin
Vit K antagonists
Types of Coumarin anticoagulants
Warfarin
Phenindione
Acenocoumarin
Phenprocoumon
MOA of Coumarin
Inhibits VitK to carboxylase
Factors 2, 7, 9 and 10.
Add a -COOH group
What is VitK
Fat soluble vitamin absorbed in upper intestine
What factors need VitK
Factors 2 (prothrombin) 7,9 and 10. Protein C and protein S
Issues with Warfarin
Narrow therapeutic window
Needs monitoring
Needs regular dose taking at same time every day
How is Warfarin monitored
INR
International Normalized Ratio
How is INR calculated
(Patient’s PT in seconds/Mean normal PT in seconds)^ISI
International sensitivity index
Target between 2-3
What are mild bleeding complications on Warfarin
Skin bruising
Epistaxis
Hematuria
Warfarin reversal and how fast drug acts
Administer VitK (6 hours) If more is needed Administer clotting factors (immediate)
Name a Thrombin inhibitor
Dabigatran
Name a Xa inhibitor
Rivaroxaban
Apixaban
Pro’s and Con’s about new anticoagulants such as Dabigatran, Rivaroxaban, Apixaban
Pro- Oral and no monitoring needed, less drug interactions
Con- No specific antidote for reversal
What type of drug is given in arterial vs venous thrombosis
Arterial - Anti-platelet
Venous - Anticoagulants
What is Atherosclerosis
Damage to endothelium and recruitment of foamy macrophages rich in cholesterol
Forms plaques rich in cholestrol
Features of Stable Atherosclerotic plaques
Hyalinised and calcified
When are stable atherosclerotic plaques seen
Stable angina
intermittent claudication
Prevention of arterial thrombosis
Stop smoking
Treat hypertension and diabetes
Lower cholesterol
Anti-platelet drugs
How does Aspirin act as an antiplatelet
Inhibits Cyclo-oxygenase (COX) which is necessary to produce Thromboxane A2 (a platelet agonist released from granules on activation)
Side effects of Aspirin
Also blocks prostaglandin, this may cause GI ulceration, bronchospasm
MOA of Clopidogrel, prasugrel
ADP receptor antagonist
platelet activation/recruiting agent
MOA of Dipyridamole
Phosphodiesterase inhibitor
Reduces cAMP production which is a second messenger in platelet activation
MOA of Abciximab
GP IIb/IIIa inhibitor
Inhibits aggregation of platelets, molecule needed for platelet to aggregate to each other
How long before elective surgery should anti-platelet drugs be stopped
7 days
What is immune thrombocytopenic purpura
Low platelet with normal bone marrow. Present with purpuric rash and bleeding.
Acute version happens in kids post infection, however this is normally resolved within 2months
Signs of shock
Pale, clammy
Tachycardia
Hypotension
Hypoxia
Symptoms and signs of Pulmonary embolism
Shortness of breath
Pleuretic chest pain
Rub
Hypoxia
What is a blood test to look for in DVT or PE
D-dimer
May also occur in many other conditions
What are D-dimers
Cross linked product of fibrin degradation
Produced whenever fibrin is generated
Produced when coagulation has been activated
Relationship between D-dimer and Venous thromboembolism
Elevated D-dimer is not always VTE
Normal D-dimer is most likely not VTE
DVT prophyaxis and treatment
TED stockins
Physio - Early mobilisation
Heparin – Warfarin
Week 3 lectures done
Yes
