patho sheet # 4 of Dr.Faisal - Reham Kelano

Pathology
Thrombosis
Many types of endothelial injuries promote thrombosis as well as changes in the laminar blood flow like turbulence and heavy current and most importantly in the lower limb where stagnation of blood occur due to immobilization .
Other factors that may lead to thrombosis :
• Hypercoagulation
This maybe due to:
1-certain conditions ,most of them might be inherited and genetically determined such as in the case of the Factor V Leiden which causes hypercoagulability disorder.
2-Also elderly are more susceptible to hyper coagulability which may lead to thrombosis this is due to many factors such that the coagulation factors(produced by the liver) are promoted more than in the younger people and other factors like stasis ,immobilization and recumbent (lying down).
• Cigarette smoking
which may lead to endothelial injury and direct toxic activity to many structures like in the case of platelets where they are brought together and adhere to one another and to the underlying connective tissue due to this toxic effect
• Heart failure: incases of trauma ,endothelial injury …etc
• Oral contraceptives (OC): might promote thrombosis to a certain extent, although many researchers go to the extremes by denoting it as non thrombotic or severly thrombotic. Also pregnancy may play a role in thrombosis due to recumbent ,immbolization and increase secretion of coagulation substances …etc
These two conditions ( OC and pregnancy promote thrombosis but only to a limited degree)
• Rheumatic heart : is a condition in the mitral valves where it does not open(stenosis) or close fully, a condition termed incompetence this allows regurgitation of some of the blood to the atrium and sometimes to the venous circulation, this will eventually lead to thrombosis *there is an area behind this valve which is known as maccallum patch which may promote maccallum thrombus*

• Incases of cancers there are many types of coagulation factors being secreted specially in certain condition ,statistically speaking, in adenocarcinoma.

Note : the term Thrombophlebitis and venous thrombosis are used simultaneously ,Thrombophlebitis have the ability to be fragmented to a 2nd ,3rd and a 4th place causing what’s known as tyrso syndrome, finding these thrombi in many locations can indicate an underlying adenocarcinoma
• HIT : Heparin inducing thrombosis, heparin is known to be anti-coagulant factor but sometimes it might stimulate auto antibodies which could be directed to certain substances on the platelets or the endothelium so that they have some sort of conflict and at the end formation of a thrombus.
• antibodies against the phospholipids of membranes
the last two factors cause thrombosis very rarely !!

Morphology of the thrombus:
In the arterial side the thrombus most probably occurs due to endothelial injury and/or changes in the laminar flow (turbulence)
In the venous side the thrombus is mainly due to stasis and stagnation of blood.
Some notes :
 There is a tendency for the thrombus to be attached to the underlying cardiac wall or the vessel wall whereas in the postmortem clot there is no such attachment which makes its removal much easier.
 If untreated, the thrombus may spread to both sides distal and proximal(propagation), this is an irregular spreading and the thrombus may have a tail which is not attached, this tail moves back and forth with the blood flow direction and because it is rather solid, it may fragment and detach forming an embolus which circulates with the blood.
 Lines of zahn: are characteristics of thrombi, They have visible and microscopic laminations produced by alternating pale layers of platelets-and little or very few RBCs-and darker layer containing red blood cells mixed with fibrin. These lines appear more intense in the arterial side where the flow is speedy and quicker, unlike the venous side where the flow is slower so they appear less prominently. And of course you wouldn’t find such lines in the postmortem clot.
 Mural thrombus: which means that the thrombi tends to be non obstructive/occlusive like in the chambers of the heart where the thrombi attaches to the walls and does not completely obstruct the vessels nor the chamber.
 In the large arteries the thrombi are rather mural whereas in the small arteries it’s obstructive like in the coronary artery.
 In the veins, the thrombi are always obstructive whether it’s a large or small vein( especially in the lower limb)!! This is also due to stasis and stagnation.
Examples about the mural thrombus are:
- In the heart :MI and arrhythmia ,they promote mural thrombosis
-In Aorta: atherosclerosis (AS): which is actually a thickening of the intimal layer of the vessel wall especially in the brain, kindy, spleen and the L.L .aneurysm(or aneurism):which is a localized blood-filled bulge of a blood vessel which occurs especially in the lower abdominal aorta. in this aneurysm there is an irregular current which will eventually lead to thrombosis.
- In the valves due to Endocarditis which can be either infected endocarditis or it could be due to some other agents like (SLE ”lse”, Systemic lupus erythematosus ), this SLE can promote valve thrombosis without being infected !!
~ In the Arteries the thrombi can be either mural or obstructive according to the artery’s size as was pointed out before.
~ Once again, lines of zahn are more prominent in the arterial circulation than the venous one.
Differences between thrombus and postmortem clots:
1-consistency: the thrombus is solid whereas the postmortem clot is gelatinous (rubbery)
2-color: there is no lamination (lines of zahn) in the postmortem clot while you can find this lamination in both the arteries and the veins with different intensities .
The postmortem clot is separated into a deep red(bluish red) layer called “ the current jelly” and an upper supernatant “chicken fat” fluid layer !!
3- also we said before that there is no vascular attachment and no fibrin.
Outcome of a thrombus:
If left untreated, it most probably will propagate and may fragment giving rise to emboli
~ lysis of the thrombus occurs if it is a small one and there is a highly active plasminogen activating factors and an active fibrinolytic system .
Sometimes exogenous materials are used to lyse the thrombus like plasminogen activating substances ( reteplase,rectaplase…etc) and also streptokinase is used to lyse the thrombus especially if it was recent and small. Thus it’s of no surprise that these substances can be life saving !!
BUT, these fibrinolytics are not always indicated, there are certain indications as well as contraindications, in some cases they might actually promote death, increasing the mortality rate!!!
~ Thrombus leads eventually to the formation of granulation tissue with its endothelial collagen, recanalization and so on.
 of most importance is the thrombus of the deep veins of the lower limb which is abbreviated as DVT, these thrombi are highly susceptible to fragmentation and is the most important factor in pulmonary embolism.
 years ago, it was thought that this DVT affects the calf muscle only, but now it is well established that it affects this muscle as well as the popliteal fossa and its structures . there is what is called the HOMAN’S SIGN:it’s a sign of DVT, A positive sign is present when there is pain in the calf or popliteal region with examiner's abrupt dorsiflexion of the patient's foot at the ankle while the knee is flexed to 90 degrees. This sign is falling into disfavor due to poor reliability –in only 50% of the patients-.
A more reliable method is the DOPPLER ULTRASOUND which is a test uses reflected sound waves to evaluate blood as it flows through a blood vessel. It helps doctors evaluate blood flow through the major arteries and veins of the arms, legs, and neck. It can show blocked or reduced blood flow through narrowing in the major arteries of the neck that could cause a stroke. It also can reveal blood clots in leg veins (deep vein thrombosis, or DVT) that could break loose and block blood flow to the lungs (pulmonary embolism).
Varicose veins on the other hand, which affects the superficial veins does not lead to embolism, rather it leads to some localized subacute conditions (eczema, dermatitis, localized thrombosis and so on )

 in certain diseases of body like in major surgeries, there is a stimulation of the coagulation factors and therefore something called DIC ( disseminated intravascular coagulation) may occur, this DIC after a while will be followed by bleeding everywhere due to consuming of all the body’s platelets “consumption hemorrhage “ or “ hemorrhagic coagulopathy” which means hemorrhage after coagulation !!

Embolism:
• An intravascular moving mass which could be gas, liquid, semi-liquid or solid
• Arises from a certain origin and ending up another remote place.
• The vast majority of its sources are the thrombi (98%)
That’s all for today, Good luck 
Reham Kilano
Lecture 27 “ 4th for Dr. Faisal kamal”
Sunday 28/11/10