perfusion and clotting D6 Flashcards
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Describe the protective mechanism
Protective mechanism whereby the formation of a thrombus prevents excessive blood loss from the body
Several clotting factors are _______ and are made in what part of the body
Several clotting factors are proteins made in the liver that are constantly circulating throughout the blood in their inactive form.
What is required by the liver to make the four clotting factors and what produces it?
Vitamin K which is made by bacteria residing in the large intestine, is required for the liver to make four of the clotting factors.
What patients are likely to have coagulation disorders?
Patients with liver disorders often have abnormal coagulation.
Coagulation blood tests include?
Coagulation blood tests include LFTs (liver function tests),
clotting times include what tests?
clotting times including activated partial thromboplastin time (aPTT), and prothrombin time (PT)
What are the three steps that occur in homeostasis (clotting process)
Vasoconstriction
Platelet plug formation
Blood coagulation
What are the steps involved in blood coagulation?
coagulation factors undergo the coagulation cascade which results in thromboplastin converting:
prothrombin → thrombin which results in →
fibrinogen → fibrin creation →
to form cross-linked fibrin clot
What blood cells begins clot and aids in homeostasis?
Platelets (thrombocytes) are the blood cells that begin clots and assist in hemostasis
Describe the structure of a thrombus?
A thrombus (clot) is a collection of aggregated platelets (and trapped RBCs) reinforced by fibrin
To counterbalance coagulation (beginning within 24-48 hours of clot formation) ___________(clot dissolving) process ensures clots do not extend inappropriately
To counterbalance coagulation (beginning within 24-48 hours of clot formation) a fibrinolytic (clot dissolving) process ensures clots do not extend inappropriately
Describe the process of clot dissolving?
tissue plasminogen activator (tPa) activates →
plasminogen → plasmin creation to cause →
fibrino“lysis” → degrade fibrin into small D-dimers (fibrin degradation products) which dissolves the clot (can measure D-dimer level in blood)
What is the lifespan of the platelets and what stimulates its production and where is it synthesized.
Production stimulated by thrombopoietin, synthesized in the liver (stimulated by low level of platelets), platelet lifespan is 7-10 days
What percentage of platelets are stored in the spleen and what happens when we have an enlarged spleen and hyperactive spleen?
1/3 platelets are stored in spleen (an enlarged and hyperactive spleen may sequester up to 80%)
Normally endothelium of blood vessel is smooth and anti-thrombotic
When a vessel is injured, ________substances are released and attract platelets for aggregation
Normally endothelium of blood vessel is smooth and anti-thrombotic
When a vessel is injured, pro-thrombotic substances are released and attract platelets for aggregation
In the injured vessel what further activate platelets and coagulation factors?
In the injured vessel, exposed collagen and von Willebrand factor (vWF) further activate platelets and coagulation factors (fibrin is created)
Platelet adhesion results in activation of what?
Platelet adhesion results in activation of the glycoprotein (GP) IIb/IIIa receptor,
Glycoprotein when activated will bind to ________ that leads to the formation of __________ stabilized by _____
which bind to fibrinogen and leads to →
→ formation of an occlusive platelet thrombus stabilized by fibrin, in addition →
→ Red blood cells will simultaneously be caught up and trapped among the adhesive platelets and fibrin becoming part of the forming thrombus (clot)
A clot attached to a vessel wall is called a ________, when clots are small and floating, they are __________, when clots are attached to the lining of the heart, they are a ________.
A clot attached to a vessel wall is called a thrombus, when clots are small and floating, they are thrombo-emboli, when clots are attached to the lining of the heart, they are a mural thrombus
Antiplatelet drugs interfere with ?
Antiplatelet drugs interfere with platelet activation and adhesion to each other and to fibrin.
Clopidogrel irreversibly binds to ADP receptors causing what?
ADP receptor blockers – clopidogrel – irreversibly binds to ADP receptors blocking chemical signals for aggregation
Glycoprotein IIb/IIIa receptor blockers inhibits?
inhibits receptor necessary for platelets to bind to fibrinogen
If the binding is irreversible what will happen?
If the binding is irreversible – the effect lasts for the 7-10-day life of the platelet
What will happen when platelet aggregation is interfered with?
Interference with platelet aggregation will increase bleeding time and reduce clotting.
What are the four anticoagulants?
unfractionated heparin, LMWH (low molecular weight heparin), warfarin, direct thrombin inhibitors
The coagulation cascade is initiated by two different pathways that converge into the common pathway:
Intrinsic pathway and Extrinsic pathway
When is the intrinsic pathway activated?
From contact with a damaged blood vessel
Function of the intrinsic and common pathway is tested with?
Function of the intrinsic and common pathway is tested with the aPTT coagulation test (activated partial thromboplastin time)
What anti-coagulants interfere mainly with the intrinsic pathway
Unfractionated heparin and LMWH interfere primarily with this pathway
Unfractionated heparin therapy is effective for anticoagulation for when?
Unfractionated heparin therapy is effective for anticoagulation when the aPTT is ↑ above normal into its “therapeutic range
What is the normal range for aPTT, and the therapeutic range varies with what?
(normal aPTT 30-40 sec, therapeutic range varies with purpose).
How is heparin (unfractionated heparin) administered and where can we not administer it?
Unfractionated heparin (commonly known as heparin) is administered by repeated subcutaneous injections or continuous IV infusion (destroyed in GI tract, so no po)
What is used to determine the dose of LWMH and what is the route of administration, are we allowed to massage it?
the dose is calculated using body weight and injected subcutaneously - to prevent bruising, heparin injection areas should never be massaged,
Which of them it more reliable unfractionated heparin or
LWMH and safer for home use.
alf-life is 2-3 times longer than unfractionated heparin, safer for home use.
Does LMWH require aPPT monitoring?
The effect of LMWH is more reliably predicted and does NOT require aPTT monitoring
what will reverse the effect of heparin during overdose or uncontrolled bleeding
Protamine sulfate IV will reverse the effect of heparin during overdose or uncontrolled bleeding
Extrinsic pathway is activated from contact with what?
Extrinsic pathway – from contact with tissue damage (uses Tissue Factor)
Function of the extrinsic and common pathway is tested with the?
Function of the extrinsic and common pathway is tested with the PT/INR coagulation test (prothrombin time/International Normalization Ratio)
Extrinsic pathway is heavily dependant on what vitamin and where is it stored?
This pathway is heavily dependent on Vitamin K which is stored in adipose tissue (K for Koagulation in German), dietary Vitamin K is in many leafy green vegetables
__________interferes with the synthesis of Vitamin K-dependent clotting factor and thereby inhibit coagulation
Warfarin interferes with the synthesis of Vitamin K-dependent clotting factor and thereby inhibit coagulation
How is the effectiveness of warfarin measured?
The effectiveness of warfarin is monitored using the PT/INR coagulation tests
Prothrombin time measures_______blood to clot, INR provides a ___________that can be compared between different labs and is used most often
Prothrombin time measures how long it takes blood to clot, INR provides a standardized PT value that can be compared between different labs and is used most often
normal INR is near _____; therapeutic INR __-__)
(normal INR is near 1.0; therapeutic INR 2.0-3.0)
What is the antidote for warfarin overdose?
Vitamin K (po most often) is the antidote to warfarin overdose/over-effect/high INR
Where does the common pathway begin and what does it include to complete clot stabilization?
Common pathway – begins at Factor X and includes the activation of prothrombin→thrombin and fibrinogen→fibrin to complete clot stabilization.
What anti-coagulant works on the common pathway?
Direct Thrombin Inhibitors – newer class of anticoagulant – work here
What
Bind to both clot-bound and circulating thrombin, preventing the formation of fibrin clots
What can be used to monitor direct thrombin inhibitor effectiveness?
aPTT can be used to monitor effectiveness
What is the MOA of direct thrombin inhibitor ?
Bind to both clot-bound and circulating thrombin, preventing the formation of fibrin clots
Do anticoagulants increase the breakdown of clots?
What naturally activated enzyme will dissolve any existing clots?
What does the anticoagulant do to the existing clots ?
Anticoagulants reduce clot formation but do not increase the breakdown of clots – naturally activated plasmin will dissolve any existing clots while the anticoagulant prevents new clots and existing clots from growing/extending.
What is used to prevent thrombus formation in the veins?
What is used to prevent thrombus formation in the arteries?
Anticoagulants are primarily used to prevent thrombus formation in veins, while antiplatelet drugs are often used to prevent clot formation in arteries.
Figure 32-4 Lewis 699
What could happen when anti -coagulants are overlapped?
the patient is at increased risk for bleeding when overlapping anticoagulants during transition from one to another.
Between Heparin and warfarin which of them has a shorter half life and what is the half life of each?
Heparin has a short half-life (90 min) and coagulation returns to normal in 2-3 hours. Warfarin has a longer half-life of 1-3 days.
When transitioning a patient form IV heparin to order warfarin what must happen?
When transitioning a patient from IV heparin to po warfarin, administration of both must overlap for approximately 5 days until the INR is safely within the therapeutic range (typically an INR 2-3).
What two foods can increase bleeding and may add to anticoagulant effects.
Garlic and ginger both increase bleeding time and may add to anticoagulant effects.
Thrombolytic drugs promote what, and what does it activate?
Thrombolytic drugs – promote fibrinolysis (clot destruction) – tissue plasminogen activator (tPa)
What is the function of thrombolytic drugs on plasminogen?
Convert plasminogen → plasmin → digests clots into fibrin degradation products (D-dimer)
Is it effective on both thrombi and emboli (thrombolytic drugs)
Effective on both thrombi and emboli
When is the thrombotic drug most effective?
Most effective when given close in time to when the clot was formed (preferably within 4 hours)
What are three things that need to be verified as normal before the use of thrombotic drugs?
Hct, Hgb and platelet levels should be verified as normal before use for safety
(thrombotic drugs)
What is the half life of the thrombotic drug (short or long)?
What is it usually given as?
What is the time of onset?In emergency cases what is it used for?
Very short half-life (5 min) – usually an IV bolus is given, followed by a continuous IV infusion for the following hour. Onset 5-10 min. Common life saving treatment related to blocked artery.
Alteplase (Activase) IV (thrombolytic drug) is commonly used for?
MI Myocardial infarction (clot in artery of heart), CVA (clot in brain), and PE Pulmonary Embolism(clot in artery of lung)
thrombolytic drug
You are at high risk for ? particularly where?
Very high risk of serious hemorrhage – particularly in GI tract and brain, or any pre-existing injuries or puncture sites.
When using the thrombolytic drug what do we monitor for?
monitor for ↓ Hgb/Hct, ↓BP/pulse ↑rate and ↓strength, blood in stool (frank red, very black melena, or occult FOBT), vomiting blood (hematemesis), coughing blood (hemoptysis) and most importantly – changes in LOC and cognition suggesting CVA bleeding in brain. Benefit of use must outweigh risk of hemorrhage.
What are some of the contradictions of using the thrombolytic drug?
Contraindications - Recent trauma, surgery, biopsy, GI bleeding, thrombocytopenia, post-partum – any current bleeding or increased risk of serious bleeding (concomitant use of other anticoagulants is at minimum a relative contraindication for the physician to examine)
What is the function of antifibrinolytics?
Antifibrinolytics – shorten bleeding time – to prevent and treat excessive bleeding following surgery
What medication is used to prevent clots from dissolving and they are also called what. What do we have to monitor for when they are being used as a risk factor?
aminocaproic acid (Amicar) - prevents fibrin from dissolving – used for very specific purposes only Also be called “hemostatic agents” May result in unwanted “over-clotting” – continuously assess for adequate perfusion
Antiplatelet Agents
ASA (past prep guide) (po)
ADP receptor blockers
Clopidogrel (Plavix) (po)
Glycoprotein IIb/IIIa receptor blockers
Thrombolytics
alteplase (Activase) tPa (IV)
Thrombocytopenia
Reduction in platelets below normal
Immune Thrombo-cytopenic purpura (ITP)
platelets are mistakenly coated with antibodies, when they reach the spleen they are destroyed by macrophages within 1-3 days.
Thrombotic Thrombo-cytopenic purpura (TTP)
uncommon, usually lack enzyme to break down aggregation factor, excessive small clot formation which uses up/occupies platelets, this may result in bleeding from lack of available platelets.
Heparin-Induced Thrombo-cytopenia /with Thrombosis (HIT or HITT) results in
result is clots and bleeding at the same time - development of a new or larger venous thrombosis is a classic sign, arterial vascular infarcts resulting in bleeding/ischemic events such as purpuric lesions or stroke, MI, renal failure
Describe Heparin-Induced Thrombo-cytopenia /with Thrombosis (HIT or HITT
develop thrombocytopenia 3-5 days after starting heparin therapy, platelets drop by 50% - immune-mediated response to heparin resulting in increased platelet aggregation (platelets and fibrin in emboli) and platelets are marked for early destruction (may see an increase in “baby” megakaryocytes on CBC)
Thrombocytosis (thrombocythemia) is defined as what?
Thrombocytosis (thrombocythemia) – abnormal increase in platelets is possible, less common, often symptomless but increase risk of clotting exists
Phlebitis is defined as?
Phlebitis – inflammation (redness, tenderness, warmth, mild edema) of a superficial vein without the presence of a thrombus – very common with IV therapy
Describe Venous thrombo-embolism (VTE)?
vein inflammation with a resulting thrombus
Superficial Vein thrombosis describe it?
Superficial Vein thrombosis – thrombus in a vein near the skin surface – generally benign
Deep Vein thrombosis (DVT) describe it?
thrombus in a deep vein, most commonly the iliac and femoral veins of the leg – varies in severity
What are some of the signs associated with DVT?
reduces blood return from the limb, increases vessel distention/edema distal to the blockage, thrombo-emboli may break away and travel to the lung causing a Pulmonary Embolism (PE – potentially life threatening
