thrombus 

• mass of platelets, RBCs, WBCs, fibrin
• occurs only within a blood vessel
• is attached to blood vessel wall

blood components are highly organized - 

starts where platelets adhere to blood vessel wall àlayer of platelets, then intrinsic pathway is initiated à layer of fibrin, then more platelets stick to fibrin à another layer of

      platelets   and so on

In arterial thrombi there is more organization and smaller size.   Lines of Zahn – more distinct layers seen in thrombus in arteries – swift blood flow  then prevents further buildup of thrombus .

Venous thrombi are larger and less organized. They consist of a mixed region – less distinct layers are seen –  slower blood flow then allows further buildup of thrombus; and also a red cap forms – this is accumulated coagulated blood on top of mixed region in veins or atria, builds up and lengthens in downstream direction

antemortum  - thrombus formed predeath if attached to blood vessel wall, and layers are present  

b. postmortem – clot (not thrombus) formed after death, no attachment, no layers – large, red (or paler if no RBCs), gelatinous, occlusive

a) Endothelial damage  which leads to platelet adhesion to endothelial cells which line blood vessels and activation of the platelets

b) flow abnormalities such as reduction of flow or turbulent blood flow which lead to increased platelet

contact with endothelial cells

c) blood hypercoagulation which happens in pregnancy, elderly, or due to unknown causes

a) arteries – hypertension adding to normal hemodynamic stress, trauma, surgery, radiation, high plasma cholesterol,

tobacco smoke chemicals   

b) veins – irritants from inflammation (as in appendicitis) or tumors, iatrogenic (as with IV infusions), trauma, surgery, radiation, high plasma cholesterol, tobacco, smoke chemicals

Why do reduced blood flow rates through blood vessels increase the risk of thrombosis and what are usual causes of flow rate reduction in arteries vs veins?

With reduced flow rates, platelets usually in central column of formed elements moving through lumen are more likely to be closer to endothelial cells lining blood vessels – thus, platelets are more likely to stick to endothelial cells and begin to form a thrombus.     

Causes in arteries vs veins    

1) causes in arteries  – heart damage with weaker pumping action, increased blood  viscosity due to leukemia, dehydration, blood loss                  

2) causes in veins – same as in arteries, but also physical

inactivity,  also varicose veins à weak spots in walls of veins bulge out, bulging slows blood flow and prevents valves  from closing à these effects lead to pooling of blood in legs

Why does turbulent blood flow in the heart or arteries increase the risk of thrombosis and what are the usual causes of turbulence in heart vs arteries?

Turbulent blood flow causes increased platelet contact with endothelial linings of heart or arteries -  thus, platelets are more likely to stick to endothelial cells and begin to form a thrombus.           

Causes in heart vs arteries

1)causes in heart – turbulence is usually caused  by damaged heart valves or congenital heart defects, this turbulence can  lead to mural thrombus (which is thrombus within cardiac chamber attached to wall of chamber )             

2) causes in arteries – turbulence can be caused by compression by tumor or inflamed organ, aneurysm – can lead to formation of thrombus

a.     resolution – thrombi are broken down by normal body mechanisms; exercise and cardiopulmonary fitness increases probability of this good outcome

b.     organization – after 2 or 3 days, phagocytic digestion of thrombus à  becomes granulation tissue àreplaced with fibrous connective tissue à endothelial cells grow over this tissueà becomes part of blood vessel wall

c.      recanalization – channels form in thrombus during organization (described above), allowing

blood to flow through the thrombus or new fibrous tissue

d.     propagation – occurs mostly in veins – red cap builds up and extends within lumen

e.      Infarction – thrombus blocks blood flow to a certain portion of tissue, this tissue dies and becomes necrotic

a. infarction is the process by which an infarct is formed, infarction is most common and serious in arteries    

b.  infarct – region of necrosis caused by ischemia, most

often caused by thrombus that blocks a blood vessel.  Other possible causes are tumor compressing a blood vessel and atherosclerosis in which there is blockage of a blood vessel.

In ischemia there is a block of blood flow to the affected tissue so that NO oxygen or glucose (energy source) are delivered to the tissue.

Hypoxia is when a decreased amount of oxygen is delivered to the affected tissues, but tissues still receive glucose.  

Glucose can still be broken down anaerobically (without oxygen) to produce some ATP (molecule providing energy to cell), although with less oxygen the process of oxidative phosphorylation cannot take place in mitochondria of cells, so that much less ATP is produced.

MI occurs when a block in a coronary artery leads to death of myocardium supplied by that artery à coagulation necrosis à acute inflammation à healing by fibrosis à healed area consists of fibrous scar tissue

This is due to  block in a brain artery à liquefactive necrosis àfluid filled cavity à no fibrous scar tissue, but cavity may be partly filled by gliosis

Infarction due to venous obstruction is unlikely. 

First of all, veins do not usually bring oxygen and nutrients to a tissue area.  Also, there are usually collateral veins serving the same tissue area - if one is obstructed, blood can low through another vein. 

However, reduced venous drainage can occur à leakage of fluid from veins à swelling, pain,  ulceration of overlying skin in leg –  this is called thrombophlebitis

a. high tissue vulnerability to hypoxia

–   example – brain tissue has great need for oxygen, and cannot survive for long without it

b. low degree of anastamosis (collateral blood vessels) in affected tissue   

c.  low capacity of  blood to deliver oxygen –as in anemia, heart failure, etc.  

d.  greater risk with sudden occlusion than with gradual occlusion                                                   

a. embolism – sudden occlusion of a blood vessel by embolus         

b. embolus – any abnormal mass moving through bloodstream, usually broken off from  thrombus         

c. thromboembolus – most common type of embolus – can become detached from thrombus due to blood pressure changes, as with walking after bed rest, postural changes, exercise.  

Problems arise when embolus lodges in blood vessel and occludes the flow

Arterial thromboemboli usually break off from a cardiac mural thrombus, a cardiac valve thrombus, a thrombus in an aneurysm, or a thrombus at a site of atherosclerosis 

These thromboemboli can easily cause infarcts, since in arteries, blood is traveling away from heart to smaller and smaller blood vessels.   

The  embolus easily lodges in small blood vessel à can cause infarct.

Since veins increase in size on way to heart –thromboemboli originating in veins these seldom lodge in veins on the way to the heart.

Instead they travel all the way to the heart, from heart are pumped through pulmonary arteries à become stuck in small arteries of lung.

There are 4 reasons for this:  

a) clot retraction – normal retraction of fibrin to make denser (thus smaller) clot

b)double blood supply of lung – receives pulmonary arteries and systemic arteries from aorta this tends to minimize damage since if small pulmonary artery is blocked, tissue can still receive oxygen and nutrients from systemic artery.            

c) fibrinolytic system is more active in lung

d) many thromboemboli are very small - occlude only very small blood vessels  à minimal effects

Venous thromboemboli that may arise in the portal veins travel to the liver. Damage is usually not significant since the liver has a double blood supply – from the portal veins and also the systemic arteries. 

If a portal vein in the liver is blocked, the affected tissue can usually still be supplied by a systemic artery

If venous thromboemboli are very large or numerous, there can be blockage of large pulmonary orteries or many small

pulmonary arteries. This can result in significant loss of lung function, death.  

Most large venous thromboemboli  arise in deep veins of leg.  This is called deep vein thrombosis (DVT) – the

thromboemboli can be long, cordlike masses.     These travel to lungs à can become trapped at pulmonary valve of heart or in large pulmonary arteries.    This is called pulmonary embolism (PE), and can cause  hemorrhage in pulmonary tissue. 

Also, the high blood pressure in lungs due to occlusion by the embolus can lead to right ventricular failure

Anticoagulant drugs include:

1. Heparin (given by IV or SC injection )
2. Low molecular weight heparins (LMWH) such as enoxaparin (Lovenox) (given by SC injection)
3. Warfarin (Coumadin) (given PO).               

• heparin  and LMWH get rid or prevent thrombi and emboli by activating antithrombin III, a normal body enzyme that breaks down clotting factors.  These drugs do not break down thrombus or embolus themselves, but prevent growth of thrombus or embolus so that normal body mechanisms can break down thrombus or embolus   

• warfarin – prevents thrombi and emboli by inhibition of vitamin K which is necessary to make clotting factors

These include

• t-PA (Alteplase)
• rt-PA (Retavase)
• streptokinase
• urokinase
• others

These drugs are used to treat existing thrombi and emboli, they work by converting plasminogen to plasmin, which breaks down fibrin, which breaks up thrombus or embolus.  These actually break down clots

The drugs include

• aspirin
• clopidogrel (Plavix)
• ticlopidine (Ticlid)    

Aspirin inhibits COX 1, which decreases formation of TXA2, which inhibits platelet activation and aggregation, which prevents thrombi and emboli   

Clopidogrel (Plavix) or ticlopidine (Ticlid) – block platelet ADP receptors which prevents platelet aggregation, which prevents thrombi and emboli.

• Fat
• air
• amniotic fluid
• foreign body emboli

Fat emboli consist of fatty yellow bone marrow  

They occur especially with fracture of femur  or tibia, within 12 to 48 hours  

Consequences    

1) can lodge in small arterioles or capillaries – if in lung à dyspnea, possibly respiratory failure           

2) sometimes can pass through pulmonary circulation to systemic arteries à can lodge in   blood vessels of skin à petechiae

3) sometimes can lodge in blood vessels of the brain à numerous petechiae, numerous small infarcts of brain tissue à possible coma, death

Air emboli – occur when veins are open to air, as in trauma;  or with sudden drop in  atmospheric pressure à nitrogen gas from tissues boils into bloodstream (the “bends”)   

No problem with a few small bubbles

Big problems if > 100 ml  - can obstruct small capillaries, including in brain; 

If > 300 ml – heart problems – air in ventricle cannot be pumped out – 

• can reduce cardiac output (CO) àtissues do not receive adequate blood  
• damage to platelets à  causes increased risk of thrombosis due to blood that does escape into arteries

With sudden drop in atmospheric pressure à nitrogen gas from tissues boils into bloodstream. 

This can occur when deep sea divers come to surface too quickly, and is reason that airplane interiors are pressurized.

Possible consequences of “the bends” include  joint pain and possible brain damage

Amniotic fluid embolus consists of amniotic fluid with infant’s cells – this reaches bloodstream

This occurs during delivery or C-section – entry of amniotic fluid with infant’s cells into uterine or cervical veins    

Possible consequences   

1)  less severe – embolus is carried to lungs and becomes trapped in small vessels  à pulmonary function

decline      

2) more severe -  injury to lung capillaries can occur, causing  severe pulmonary edema      

3) most severe -  disseminated intravascular coagulation (DIC) – caused by substances in amniotic fluid that cause increased blood coagulation à obstruction of blood flow in lungs à circulatory collapse à tissue hypoxia, including brain à coma, seizures à 80% mortality rate