Thrombotic Disorders Flashcards
what are thrombi?
clots that form within vessels and stay where they are
what are emboli?
little chunks of clot that break off and float downstream to other places
what are thrombotic disorders?
diseases that predispose a patient to forming abnormal clots (thrombi)
usually hereditary, and they usually involve an abnormality in the coagulation cascade
what are the three general causes of thrombic disorders?
- making too much of a coagulation factor
- making a coagulation factor that can’t be turned off
- making too little of a coagulation cascade inhibitor
what’s usually the cause of thrombi?
risk factors like obesity, smoking and oral contraceptives
don’t start by looking for rare thrombotic disorders
what is Virchow’s Triad
the causes of thrombosis and embolism
- endothelial damage
- abnormal blood flow
- hypercoagulability
what is endothelial damage?
Anything that rips up the endothelium increases the chances of clot formation.
atherosclerosis falls into this category, due to the damage that atherosclerotic plaques do to the endothelium
what are the two types of abnormal blood flow?
stasis
turbulence
what is abnormal blood flow?
normally, blood should flow in a nice, laminar, smooth fashion
this keeps the clotting factors away from each other and from platelets
what is stasis?
abnormal blood flow
the velocity of flow drops to a point where coagulation factors can attach to each other and platelets, initiating the coagulation cascade
what is turbulence?
abnormal blood flow
flow is chaotic, and little eddies form
blood is more static in these areas, allowing the factors and platelets to come into contact with each other
what are examples of stasis?
- varicose veins
- atrial fibrillation = blood collects in the heart because it’s not pumping uniformly
- prolonged immobilization (like in a plane ride, or after surgery)
when does turbulent blood flow happen?
can occur when there’s a congenital heart defect
what risk factors can cause hypercoagulablity?
- smoking
- oral contraceptive use
- adenocarcinoma (because the mucin in the tumor cells is a pro-coagulant)
- thrombotic disorders
they all stimulate the coagulation cascade in some way!!
what are the risk factors for thrombosis?
1 risk factor is usually fine but if you start getting more than one you’re in trouble
- atherosclerosis
- trauma
- obesity
- prolonged immobilization
- varicose veins
- pregnancy
- oral contraceptive use
- atrial fibrillation
- carcinoma (especially adenocarcinoma)
- smoking
what should raise suspicion that someone has a thrombotic disorder?
- the thrombosis in an abnormal place (“normal” places are leg veins and lungs)
- a history of recurrent thromboses
- there family members have had thrombotic episodes
- he patient is young (<50).
- the patient has had one or more miscarriages
what are the hereditary thrombotic disorders?
- factor V leiden
- antithrombin deficiency
- protein C and S deficiencies
- factor II gene mutation
what are the acquired thrombotic disorders?
antiphospholipid antibody syndrome
what is factor V leiden?
most common of all the thrombotic disorders
caused by a point mutation in the factor V gene which makes the resulting factor V resistant to inactivation
so factor V Leiden participates in the coagulation cascade just fine – but it can’t be turned off, and the cascade continues to make fibrin when it shouldn’t
what is antithrombin deficiency?
super rare genetic defect
patients make too little antithrombin
AT is a super-important inhibitor of the coagulation cascade
what are protein C and S deficiencies?
super rare genetic defects
they are inhibitors of the coagulation cascade so if they’re missing, it’s going to be pretty hard to turn the cascade off, and the result is too much fibrin formation
what is factor II gene mutation?
rare genetic defect
patients make too much prothrombin
too much prothrombin leads to too much thrombin = lots of clotting
what is antiphospholipid antibody syndrome?
the main acquired thrombotic disorder
patients for one reason or another make antibodies to phospholipids
these antiphospholipi antibodies wreak havoc on the endothelium and on platelets in complex ways, leading to a syndrome involving abnormal and excessive clotting
