1
Q
What is a pulmonary Embolism? WHat is it usually secondary to?
A
Pulmonary embolism is blockage in one or more arteries in your lungs. In most cases, pulmonary embolism is caused by blood clots that travel to your lungs from another part of your body — most commonly, your legs. Pulmonary embolism is a complication of deep vein thrombosis (DVT), which is clotting in the veins farthest from the surface of the body.
2
Q
What are the common signs and symptoms of a pulmonary embolism? (3)
A
- Shortness of breath. This symptom typically appears suddenly, and occurs whether you’re active or at rest.
- Chest pain. You may feel like you’re having a heart attack. The pain may become worse when you breathe deeply, cough, eat, bend or stoop. The pain will get worse with exertion but won’t go away when you rest.
- Cough. The cough may produce bloody or blood-streaked sputum.
3
Q
What are the three main symptoms of a pulmonary embolism? (3)
What are the less common symptoms of a pulmonary embolism? (7)
A
3 main:
- Sudden shortness of breath
- Chest Pain
- Cough with bloody sputum
Other:
- Wheezing
- Leg swelling, usually in only one leg
- Clammy or bluish-colored skin
- Excessive sweating
- Rapid or irregular heartbeat
- Weak pulse
- Lightheadedness or fainting
4
Q
What gets stuck in the arteries of the lungs in a pulmonary embolism? (4) How many blockages do there tend to be?
What is PE secondary to DVT known as?
A
Blockages to the lungs in PE:
- Usually a blood clot
- Occasionally fat from within the marrow of a broken bone
- Occasionally part of a tumor
- Occasionally air bubbles
It’s rare to experience a solitary pulmonary embolism. In most cases, multiple clots are involved.
Because pulmonary embolism almost always occurs in conjunction with deep vein thrombosis, most doctors refer to the two conditions together as venous thromboembolism (VTE).
5
Q
What are the risk factors for DVT and Pulmonary Embolism? (14)
A
- Damage to the inside of a blood vessel due to trauma or other conditions
- Changes in normal blood flow, including unusual turbulence, or partial or complete blockage of blood flow
- Hypercoagulability/family history of blood clots
- Prolonged immobility
- Older age
- Dehydration
- Recent surgery
- Heart Disease
- Pregnancy/recent childbirth
- Cancer
- Previous blood clots
- Smoking
- Being overweight
- Oestrogen supplements in the pill/HRT
6
Q
Why does older age predispose to blood clots? (3)
A
Older people are at higher risk of developing clots. Factors include:
- Valve malfunction. Tiny valves in your larger veins keep your blood moving in the right direction. However, these valves tend to degrade with age. When they don’t work properly, blood pools and sometimes forms clots.
- Dehydration. Older people are at higher risk of dehydration, which may thicken the blood and make clots more likely.
- Medical problems. Older people are also more likely to have joint replacement surgery, cancer or heart disease.
7
Q
Why does surgery increse y our risk of blood clots\? What type of surgery is particularly risky?
A
Surgery is one of the leading causes of problem blood clots, especially joint replacements of the hip and knee. During the preparation of the bones for the artificial joints, tissue debris may enter the bloodstream and help cause a clot. Simply being immobile during any type of surgery can lead to the formation of clots. The risk increases with the length of time you are under general anesthesia.
8
Q
Why does pregnancy increase the risk of blood clots?
Why do certein types of cancer increase the risk of blood clots? Which types of cancer and cancer treatment are particularly risky?
A
Pregnancy. The weight of the baby pressing on veins in the pelvis can slow blood return from the legs. Clots are more likely to form when blood slows or pools.
Cancer. Certain cancers — especially pancreatic, ovarian and lung cancers — can increase levels of substances that help blood clot, and chemotherapy further increases the risk. Women with a history of breast cancer who are taking tamoxifen or raloxifene also are at higher risk of blood clots.
9
Q
What tests might you order to help confirm a diagnosis of pulmonary embolism? (7)
A
- CXR - may appear normal in PE, but can rule out other conditions.
- Lung scan (ventilation/perfusion rate)
- Spiral (helical) computerized tomography (CT) scan with contrast agent.
- D-dimer blood test - increased D-dimer, increased risk of clotting
- Ultrasound.
- MRI (reserved for pregnant women and those whose kidneys would be damaged by the dyes in CT)
- Pulmonary angiogram (difficult to perform, used when other tests do not give a definitive answer)
10
Q
Describe a lung scan. In what situation is this test less reliable?
A
Lung scan. This test, called a ventilation-perfusion scan (V/Q scan), uses small amounts of radioactive material to study airflow (ventilation) and blood flow (perfusion) in your lungs. First, you inhale a small amount of radioactive material while a special camera designed to detect radioactive substances records air movement in your lungs. Then a small amount of radioactive material is injected into a vein in your arm. Images taken after the injection show whether you have a normal or diminished flow of blood to your lungs. This test is less reliable if you’re a smoker.
11
Q
What arterial blood gases would you expect to see in Pulmonary Embolism? Is this exclusive to PE?
A
pO2 will be lowererd - hypoxaemia. This also occurs in other conditions which present in a similar way to PE, so it is not exclusive to PE.
Very often seen in combination with hypocapnoea (reduced blood co2) and alkylosis.
12
Q
What is hypocarnoea, and what usually causes it?
A
Hypocapnia or hypocapnea also known as hypocarbia is a state of reduced carbon dioxide in the blood. Hypocapnia usually results from deep or rapid breathing, known as hyperventilation.
13
Q
In Pulmonary embolism (PE), what is the extent of the hypoxaemia (surprisingly) not related to?
A
The severity of the hypoxaemia is not related to the extent of the damage to the vasular bed of the lungs - except when the lungs are very severly compromised with 40% or more of the vascular bed affected by the clot.
14
Q
Which two drugs are commonly used to treat clots? Why is one given before the other? What are the risks of these medication?
What type of clot treating drug is set aside for emergency situations and why?
A
Anticoagulants. The drugs heparin and warfarin (Coumadin) prevent new clots from forming. Heparin works quickly and is usually delivered with a needle. Warfarin (Coumadin) comes in pill form and doesn’t start working until a few days after your first dose. Risks include bleeding and easy bruising.
Clot dissolvers (thrombolytics). While clots usually dissolve on their own, certain medications can dissolve clots quickly. Because these clot-busting drugs can cause sudden and severe bleeding, they usually are reserved for life-threatening situations.
15
Q
Which surgical procedures are sometimes used in the treatment of blood clots? When are they indicated? (3)
A
- Clot removal. If you have a very large clot in your lung and you’re in shock, your doctor may use a catheter to suction out the clot. It can be difficult to remove a clot this way, and this procedure isn’t always successful.
- Vein filter. A catheter can also be used to place a filter in the inferior vena cava. This filter catches and stops blood clots moving toward your lungs. Filter insertion is typically reserved for people who can’t take anticoagulant drugs or when these drugs don’t work well enough.
- Surgery. If you’re in shock and thrombolytic medication isn’t working quickly enough, your doctor might attempt emergency surgery. This happens infrequently, and the goal is to remove as many blood clots as possible, especially if there’s a large clot in your pulmonary artery.
16
Q
- What preventative measures are taken in hospitals to try and avoid the complication of clotting before and after operations?(4)
- Which patients are given a preventative medication as soon as they present in A&E? (4)
A
- Anticoagulant therapy. A heparin injection, is given to anyone at risk of clots before and after an operation — as well as to people admitted to the hospital with a heart attack, stroke, complications of cancer or burns. Oral warfarin can be given for a few days before major elective surgery to reduce your risk of clots.
- Graduated compression stockings steadily squeeze your legs, helping your veins and leg muscles move blood more efficiently. They offer a safe, simple and inexpensive way to keep blood from stagnating after general surgery.
- Use of pneumatic compression. This treatment uses thigh-high or calf-high cuffs that automatically inflate every few minutes to massage and squeeze the veins in your legs.
- Physical activity. Moving as soon as possible after surgery can help prevent pulmonary embolism and speed your overall recovery.
17
Q
Which test would you most likely use to diagnose DVT? Why?
A
Doppler ultrasound: Using high-frequency sound waves, this system can visualize the large, proximal veins and detects a clot if one is present. Painless and without complications, this is the most commonly used method to diagnose deep vein thrombosis. However, sometimes the test can miss a clot, especially in the smaller veins.
18
Q
Which clots may require more aggressive treatment with thrombolytics? How is this treatment administerd and what drugs are used?
A
Blood clots located in the femoral vein near the groin that extend into the iliac vein in the abdomen may require more aggressive treatment with thrombolytic (thrombo=clot + lysis=breakdown) therapy. Clot-busting drugs (alteplase [Activase], streptokinase [Streptase]) may be injected directly into the clot itself.
19
Q
Who would you not prescribe anticoagulants? What alternative treatment for a DVT would you give them?
A
Those who have gastrointestinal bleeding (bleeding from the stomach or bowel), intracranial bleeding (bleeding in the brain), or who have had recent major trauma potentially could bleed to death if anticoagulation medications are prescribed. The alternative for leg DVT treatment in these situations may be an inferior vena cava filter.
20
Q
Other than medication, what can be used after a DVT has occured? What does this help to prevent? How long should this be used for?
A
Compression stockings are useful in preventing a complication of a leg blood clot called postthrombotic syndrome or postphlebitis syndrome, in which the affected leg swells and becomes chronically painful. These stockings may be purchased over-the-counter or can be custom fitted. It is recommended that they be worn for at least a year after the diagnosis of deep venous thrombosis.
21
Q
- What is the other name for warfarin?
- What can affect the levels of warfarin needed? (3)
- What blood test is done to monitor Warfarin dosage? How often?
A
- Warfarin (Coumadin)
- dose needs to be individualized for each person, and blood clotting must monitored routinely since changes in diet, activity, and the administration of other medications may affect the levels of warfarin.
- Blood tests (usually INR, or international normalized ratio) are done routinely to monitor the blood thinning effects. Ideally, the INR should be kept in a range between 2.0 and 3.0. Blood tests are done weekly until the INR stabilizes and then are done every two weeks to every month.
22
Q
- What is the name of the heparin-like drug given as a short term initial treatment for blood clots?
- How is this given, and what is the dosage?
- When might this be used as a long term treatment?
A
- Enoxaparin (Lovenox) is a low molecular weight heparin injected beneath the skin to thin the blood.
- The dose is usually 1milligram per kilogram of weight injected twice daily or 1.5 milligrams per kilogram injected once daily.
- Enoxaparin may be used over the long-term in some patients with cancer.
23
Q
- What is the name of the condition in which nearly all of the venous return from the leg is obstructed by clots in the iliac and femoral veins?
- How is this treated?
A
- Phlegmasia Cerulea Dolens describes a situation in which a blood clot forms in the iliac vein of the pelvis and the femoral vein of the leg, obstructing almost all blood return and compromising blood supply to the leg.
- In this case surgery may be considered to remove the clot, but the patient will also require anti-coagulant medications.
24
Q
Describe platelets: shape, size and main function
A
Platelets are flattened discs that appear round when viewed from above, spindle shaped in section or or in a blood smear. They average about 4um in diamaeter and are roughly 1um thick. Platelets are a major participant in a vascular clotting system that also includes plasma proteins and the cells and tissues of the blood.
25
How long does a platelet last in the bloodstream? How are they removed from the bloodstream? What is the normal platelet concentration? Where are platelets found on mass? Why?
Platelets are continuously replaced. Each platelet circulates for 9-12 days before being removed by phagocytes, mianly in the spleen. Each microliter of circulating blood contains 150000-500000 platelets; 350000/uL is the average concentration. Roughly one third of the platelets in the body at any moment are held in the spleen and other vascular organs rather than in the bloodstream. The reserves are mobilised during a circulatory crisis, such as severe bleeding.
26
What is the medical terms platelet concentration which is too low? What concentration is considered too low? What causes this? What are the signs for this?
What is the medical terms platelet concentration which is too high? What concentration is considered too high? What causes this?
The normal platelet count in adults ranges from 150,000 to 450,000/microL
* Low platelet count: Thrombocytopenia is defined as a platelet count less than 150,000/microL (150 x 109/L). This generally indicates excessive platelet destruction or inadequate platelet production. Signs include bleeding along the digestive tract, within the skin and occasionally inside the CNS.
* High platelet count: Thrombocytosis, platelet counts can exceed 500,000/uL. Results from accelerated platelet formation in response to infection, inflammation or cancer.
27
What are the functions of platelets? (3)
* The release of chemicals important to the clotting process. By releasing enzymens and other important factors at the appropriate times, platelets help initiate and control the clotting process.
* The formation of a temporary patch in the walls of damaged blood vessels. Platelets clump together at an injury site, forming a platelet plug which can slow the rate of blood loss while clotting occurs.
* Active contraction after clot formation has occurred. Platelets contain filaments of actin and myosin. After a blood clot has formed, the contraction of platelet filaments shrinks the clot and reduces the size of the break in the vessel wall.
28
What is the name for platelet production, and where does it occur? What type of cells produce platelets, and how do they do this? How many platelets can one cell produce?
Platelet production or thrombocytopoeisis, occurs in the bone marrow. Normal bone marrow contains a number of megakaryocytes, enormous cells (up to 160um in diameter) with large nuclei. During their development and growth, megakaryocytes manufacture structural proteins, enzymes and membranes. They then begin shedding cytoplasm in small membrane enclosed packets. A mature megakaryocyte gradually loses all its cytoplasm, producing about 4000 platelets before the nucleus in engulfed by phagocytes and broken down for recycling
29
What is the rate of megakaryocyte activity and platelet formation stimulated by? (3)
* Thrombopoietin (TPO) or thrombocyte stimulating factor, a peptide hormone produced in the kidneys (and perhaps other sites) that accelerates platelet formation and stimulates the production of megakaryocytes
* Interleukin 6 (IL6) a hormone that stimulates platelet formation
* Multi- CSF, which stimulates platelet production by promoting the formation and growth of megakaryocytes.
30
What is haemostasis? What are the three stages of haemostasis?
The process of haemostasis, the cessation of bleeding, halts the loss of blood through the walls of damaged vessels. At the same time, it establishes a framework for tissue repair. Haemostasis consists of three phases, the vascular phase, the platelet phase and the coagulation phase.
However the boundaries of these phases are somewhat arbitrary. In reality, haemostasis is a complex cascade in which many things happen at once, and all of them interact to some degree.
31
If a blood vessel wall is damaged, the vascular phase of haemostasis begins. What happens to the blood vessel wall? Why does this happen? How long does this effect last?
Cutting the wall of a blood vessel triggers a contraction in the smooth muscle fibres of the vessel wall. This local contraction of the vessels is a vascular spasm, which decreases the diameter of the vessel at the site of injury. Such a constriction can slow or even stop the loss of blood through the walls of a small vessel. The vascular spasm lasts about 30 minutes, a period called the vascular phase of haemostasis.
32
During the vascular phase, what changes occur at the endothelium of the blood vessel at the injury site? (2) Why?
* The endothelial cells contract and expose the underlying basal lamina to the bloodstream.
* The endothelial plasma membrane becomes sticky with a coating of von Willebrand Factor: A tear in the wall of a small artery or vein may be partially sealed off by the attachment of endothelial cells on either side of the break. In small capillaries, endothelial cells on opposite sides of the vessel may stick together and prevent blood flow along the damaged vessel. The stickiness is also important because it facilitates the attachment of platelets as the platelet phase gets underway.
33
During the vascular phase, why do endothelial cells contract and expose the basal lamina to the bloodstream?
The basal lamina contains collagen, which Von Willebrand Factor can bind to. Platelets then bind to the vWF - causing adhesion and aggregation of platelets at sites of vascular injury.
34
Where is von Willebrand Factor produced (2), and where is it present in the body (3)?
Von Willebrand factor is made in the bone marrow and in endothelial cells. It is released by endothelial cells at injury sites. It is also bound to inactive Factor 8 in the circulation: vWF is released when Factor 8 is activated by Thrombin. VWF is also found in secretory granules in platelets.
35
During the vascular phase of haemostasis, what do the endothelial cells begin to release? (4)
The endothelial cells begin releasing chemical factors and local hormones including ADP, tissue factor and Prostacyclin. Endothelial cells also release Endothelins, peptide hormones that 1) stimulate smooth muscle contraction and promote vascular spasms and 2) stimulate the division of endothelial cells, smooth muscle cells and fibrocytes to accelerate the repair process.
36
What signals the onset of the platelet phase of haemostasis? Why does this happen? How quickly does this occur after the injury?
The attachment of platelets to vWF on exposed collagen fibres of the endothelial surfaces, the basal lamina marks the start of the platelet phase or haemostasis. The attachment of platelets to exposed surfaces is called platelet adhesion. As more and more platelets arrive, they begin sticking to one another as well. This process called platelet aggregation forms a platelet plug that may close the break in the vessel wall if the damage is not severe or the vessel is relatively small. Platelet aggregation begins within 15 seconds of an injury occurring
37
What triggers a platelet to become activated? (4)
Coming into contact with collagen, which is found almost everywhere except in a blood vessel (and therefore found at vessel injury sites) activates platelets. In adddition, thromboxane A2 and ADP (released by other platelets) and thrombin (from the clotting pathways) trigger activation.
38
How do platelets change in shape when they become activated at a blood vessel injury site? What receptors do they begin to display on their surfaces? (3)
As they arrive at the injury site, platelets become activated. The first sign of activation is that they become more spherical and develop cytoplasmic processes that extend towards adjacent platelets.
Upon activation, platelets display receptors for thrombin, fibrinogen and other clotting factors.
39
When platelets become activated, what do they release? (6) What does each chemical secreted do?
* adenosine diphosphate (ADP) is released in 'dense granules', which stimulates platelet aggregation and secretion
* thromboxane A2 and
* serotonin, which stimulate vascular spasms
* clotting factors, proteins that play a role in blood clotting
* platelet derived growth factor (PDGF) a peptide that promotes vessel repair and
* calcium ions which are required for platelet aggregation and in several steps in the clotting process.
40
Why does the platelet phase of haemostasis progress so rapidly?
The platelet phase proceeds rapidly because ADP, thromboxane, and calcium ions are released from each arriving platelet further stimulating aggregation. This positive feedback loop ultimately produces a platelet plug that will be reinforced as clotting occurs
41
How is platelet aggregation controlled and restricted to the site of injury? (5)
Several key factors limit the growth of a platelet plug: 1) Prostacyclin, a prostaglandin that inhibits platelet aggregation and is released by endothelial cells. 2) inhibitory compounds released by white blood cells entering the area. 3) circulating plasma enzymes that break down ADP near the plug 4) compounds that, when abundant, inhibit plug formation (eg serotonin which at high concentrations inhibits the action of ADP) 5) the development of a blood clot, which reinforces the plug but also isolates it from the general circulation.
42
How long after injury to a blood vessel does the coagulation phase of haemostasis begin? What is the end chemical reaction of the coagulation phase? How does the blood clot form?
The coagulation phase does not start until 30 seconds or more after the vessel has been damaged. Coagulation or blood clotting involves a complex series of steps leading to the conversion of circulating fibrinogen into the insoluble protein fibrin. As the fibrin network grows, it covers the surface of the platelet plug. Passing blood cells and additional platelets are trapped in the fibrous tangle, forming a blood clot that effectively seals off the damaged portion of the vessel.
43
What type of chemicals are the clotting factors (procoagulants)? What do they usually become during a clotting cascade?
Important clotting factors include Ca2+ and 11 different proteins. Many of the proteins are pro-enzymes which, when converted to enzymes, direct essential reaction in the clotting response. The activation of one proenzyme commonly creates an enzyme that activates a second proenzyme, and so on, in a chain reaction, or cascade.
44
What are the three clotting pathways? Where do they begin?
There are cascades involved in the extrinsic, intrinsic and common pathways. The extrinsic pathways begin outside the bloodstream, in the vessel wall: the intrinsic pathway beginning in the bloodstream, with the activation of a circulating proenzyme. These two pathways converge at the common pathway.
45
Describe the steps of the extrinsic pathway that lead to the first step of the common pathway. (3ish)
The extrinsic pathway begins with the release of Factor 3, also known as tissue factor (TF), by damaged endothelial cells or peripheral tissues. The greater the damage, the more tissue factor is released and the faster clotting occurs. Tissue factor then combines with Ca2+ and another clotting factor (Factor 7) to form an enzyme complex capable of activating Factor 10, the first step in the common pathway.
* Factor 3 (TF) + Ca2+ + Factor 7 \>\> Factor 7 tissue factor complex \>\> activated Factor 10
46
Describe the steps of the intrinsic pathway that lead to the first step of the common pathway.
The intrinsic pathway begins with the activation of pro-enzymes (Usually Factor 12) exposed to collagen fibres at the injury site (or to a glass surface of a slide or collection tube.) This pathway proceeds with the assistance of a PF-3, a platelet factor released by aggregating platelets. Platelets also release a variety of other factors that accelerate the reaction of the intrinsic pathway. After a series of linked reactions, activated Factors 8 and 9 combine to form an enzyme complex capable of activating Factor 10.
* Pro-enzymes activated at collagen + PF-3 + Ca2+ + Clotting Factors 8 and 9 \>\> activated Factor 10
47
Describe the steps of the common pathway that lead to blood clotting. (5ish)
The common pathway begins when enzymes from either the extrinsic or intrinsic pathway activate Factor 10, forming the enzyme prothrombinase. Prothrombinase converts the proenzyme prothrombin into the enzyme thrombin. Thrombin then completes the clotting process by converting fibrinogen, a soluble plasma protein, to insoluble strands of fibrin.
* Active Factor 10 \>\> prothrombinase \>\> prothrombin converted to thrombin \>\> fibrinogen converted to fibrin.
48
When a blood vessel is damaged, which clotting pathway produces clotting first?
When a blood vessel is damaged both the intrinsic and extrinsic pathways respond. The extrinsic pathway is shorter and faster than the intrinsic pathway, and it is usually the first to initiate clotting. In essence, the extrinsic pathway produces a small amount of thrombin very quickly. This quick patch is reinforced by the intrinsic pathway, which later produces more thrombin.
49
Which pathway creates Thrombin and in what 2 ways does thrombin help to stimulate blood clotting? How does this accelerate the clotting process?
Thrombin generated in the common pathway stimulates blood clotting by 1) stimulating the formation of tissue factor and 2) stimulating the release of PF-3 by platelets. Thus, the activity of the common pathway stimulates both the intrinsic and extrinsic pathways. This positive feedback loop accelerates the clotting process, and speed can be very important in reducing blood loss after a severe injury.
50
Blood clotting is restricted by substances that either deactivate or remove clotting factors and other stimulatory agents from the blood. Give 7 examples of substances that restrict clotting.
* Plasma protein antithrombin-3 inhibits several clotting factors, including thrombin.
* Heparin, a compound released by basophils and mast cells, is a cofactor that accelerates the activation of antithrombin-3. Heparin is used clinically to impede or prevent clotting.
* Thrombomodulin is released by endothelial cells. This protein binds to thrombin and converts it to an enzyme that activates Protein C.
* Protein C is a plasma protein that inactivates several clotting factors and stimulates the formation of plasmin, an enzyme that gradually breaks down fibrin strands.
* Prostacyclin released during the platelet phase inhibits platelet aggregation and opposed the stimulatory action of thrombin, ADP and other factors.
* Plasma protein alpha-2-macroglobulin inhibits thrombin, and
* Plasma protein C1 inactivator inhibits several clotting factors involved in the intrinsic pathway.
51
Which vitamin and which mineral are necessary for the clotting process to work? What is the vitamin used to make?
Calcium ions and vitamin K affect almost every aspect of the clotting process. All three pathways (intrinsic, extrinsic and common) require Ca2+ so any disorder that lowers plasma Ca2+ concentrations will impair blood clotting. Adequate amounts of vitamin K must be present for the liver to be able to synthesis four of the clotting factors, including prothrombin.
52
How are Vitamin K levels in the body maintained? (2) What can cause Vitamin K deficiency? (3) What is the result of a vitamin K deficiency?
Vitmain K is a fat soluble vitamin present in green veg, grain and organ meats and it is absorbed with dietary lipids. Roughly half of the daily requirement is absorbed from the diet, the other half is manufactured by bacteria in the large intestine. A diet inadequate in fats or in vitamin K, or a disorder that affects fat digestion and absorption (such as problems with bile production) or prolonged use of antibiotics that kill normal intestinal bacteria may lead to a vitamin K deficiency. This condition will cause eventual breakdown of the common pathway due to a lack of clotting factors, and, ultimately, deactivation of the entire clotting system.
53
Describe Clot Retraction. How long after the clot formation does this occur? What is the purpose of clot retraction (2)
Once the fibrin meshwork has formed, platelets and red blood cells stick to the fibrin strands. The platelets then contract and the entire clot begins to undergo clot retraction, or syneresis (drawing together). Clot retraction, which occurs over a period of 30-60 minutes 1) pulls the torn edges of the vessel closer together, reducing residual bleeding and stabilising the injury site and 2) reduces the size of the damaged area, making it easier for fibrocytes, smooth muscle cells and endothelial cells to complete repairs.
54
What is the name of clot breakdown? Describe how this occurs.
As the repair process takes place, the clots gradually dissolve. This process called fibrinolysis begins with the activation of the proenzyme plasminogen by two enzymes: thrombin, produced by the common pathway and tissue plasminogen activator (t-PA) released by damamged tissues at the site of injury. The activation of plasminogen produces the enzyme plasmin, which begins digesting the fibrin strands and eroding the foundation of the clot.
* Thrombin and/or t-PA \>\> activation of plasminogen into plasmin \>\> digests fibrin
55
What type of drug is Warfarin? What is it used to treat (8)
Warfarin is an anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors.
* Warfarin is indicated for the prevention (prophylaxis) and/or treatment of venous thrombosis and its extension, pulmonary embolism
* Treatment of atrial fibrillation with embolization.
* Prevention systemic embolism after myocardial infarction.
* Treatment of retinal vascular occlusion
* cardiomyopathy
* cerebral embolism
* transient cerebral ischaemia
* arterial embolism and thrombosis.
56
What is the mechanism of action of Warfarin?
Warfarin inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). The activation of some coagulant proteins is vitamin K-dependet.
The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. This results in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin.
57
How is Warfarin Absorbed?
Rapidly absorbed following oral tablet administration with considerable variations between patients. Can be absorbed percutaneously.
58
What is the route of elimination of warfarin?
The elimination of warfarin is almost entirely by metabolism. Very little warfarin is excreted unchanged in urine. The metabolites are principally excreted into the urine; and to a lesser extent into the bile.
59
Give an example of a low molecular weight heparin drug. How is it administered? What is it used to treat (3)
Enoxaparin is a low molecular weight heparin (anticoagulant) and is given as a subcutaneous injection. Enoxaparin is used to prevent and treat deep vein thrombosis or pulmonary embolism, and also for the prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin.
60
How does a low molecular weight heparin work?
Enoxaparin binds to and accelerates the activity of antithrombin III. By activating antithrombin III, enoxaparin inhibits factors Xa and IIa. Factor Xa catalyzes the conversion of prothrombin to thrombin, so enoxaparin’s inhibition of this process results in decreased thrombin and ultimately the prevention of fibrin clot formation.
61
In what way is a low molecular weight heparin less effective at preventing coagulation than unfractionated heparin?
Low molecular weight heparins are less effective at inactivating factor IIa due to their shorter length compared to unfractionated heparin.
62
Where can low molecular weight heparin (LMWH) be obtained?
Enoxaparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates.
63
What effect does a LWMH have once thrombosis has formed?
Once active thrombosis has developed, larger amounts of enoxaparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Enoxaparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor.
64
For which patients should the use of Low Molecular Weight Heparin be avoided, and unfractionated heparin used?
The use of LMWH should be avoided in patients with a creatinine clearance less than 20mL/min. In these patients, unfractionated heparin should only be used.
65
How can the efficacy of LMWH be monitored?
As for monitoring, active partial thromboplastin time (aPTT) will only increase at high doses of low molecular weight heparins (LMWH). Therefore, monitoring aPTT is not recommended. However, anti-Xa activity can be measured to monitor the efficacy of the LMWH.
66
How is a Low Molecular Weight Heparin eliminated?
Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerisation. Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion of active and non-active fragments 40% of the dose.
67
What is a potential side effect of Low Molecular Weight Heparin?
One side effect is heparin induced thrombocytopenia (HIT syndrome). HIT is caused by an immunological reaction that makes platelets form clots within the blood vessels, thereby using up coagulation factors.
68
How can LMWH be administered?
Liquid: Intravenous, Liquid: Irrigation, Solution: Intraperitoneal, Solution: Intravenous, Solution: Subcutaneous
69
What are the targets of Low molecular weight heparin? What does the heparin do to each of these targets, and what are the consequences?
* LMWH targets Antithrombin-III, which is the most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin as well as factors IXa, Xa and XIa. Its inhibitory activity is greatly enhanced in the presence of heparin
* LMWH inhibits Coagulation Factor 10. Activated Factor 10 is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor 5a, calcium and phospholipid during blood clotting.
70
Describe Vitamin K, its sources and general role in the body.
Phytonadione is often called vitamin K1. It is a fat-soluble vitamin that is stable to air and moisture but decomposes in sunlight. It is found naturally in a wide variety of green plants. Vitamin K is needed for the posttranslational modification of certain proteins, mostly required for blood coagulation.
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When would you prescribe Vitamin K?
For the treatment of haemorrhagic conditions in infants, antidote for coumarin anticoagulants in hypoprothrombinaemia
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Which clotting factors are Vitamin K dependant?
Vitamin K is necessary for the production via the liver of active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX), and Stuart factor (factor X).
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What is the mechanism of action of Vitamin K?
Vitamin K is an essential cofactor for the gamma-carboxylase enzymes which activate the precursors of coagulation factors II (prothrombin), VII, IX and X. The active coagulation factors are then secreted by hepatocytes into the blood.
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What are the symptoms of vitamin K deficiency?(5)
Supplementing with Phytonadione results in a relief of vitamin K deficiency symptoms which include easy bruisability, epistaxis (nosebleed), gastrointestinal bleeding, menorrhagia and hematuria.
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How is vitamin K absorbed? Where in the body does it become concentrated?
Oral phytonadione is adequately absorbed from the gastrointestinal tract only if bile salts are present. After absorption, phytonadione is initially concentrated in the liver, but the concentration declines rapidly. Very little vitamin K accumulates in tissues.
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How is Vitamin K eliminated from the body?
Almost no free unmetabolized vitamin K appears in bile or urine.
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In what form can Vitamin K be given?
Injection, solution: Intramuscular, Injection, solution: Intravenous, Injection, solution: Subcutaneous
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Which drug will vitamin K interact with? How can this be monitored?
Warfarin: Phytonadione (vitamin K) may antagonize the anticoagulant effects of warfarin. Monitor for changes in prothrombin time if phytonadione intake (either via supplements or vitamin K-rich foods) is increased or decreased.
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What are the targets of vitamin K?
* Vitamin K-dependent gamma-carboxylase is a target of Vitamin K. This activates the precursors of coagulation factors II (prothrombin), VII, IX and X.
* Vitamin K is an agonist of Osteocalcin. This constitutes 1-2% of the total bone protein. It binds strongly to apatite and calcium.
