Coagulation

Question 1

What level of the vessel has the tissue factor?

Answer 1

It is in the adventitia (connective tissue)

If the adventitia is exposed, something bad has happened

Question 2

Which vessels are more likely to have damage?

Which vessels clot better?

Answer 2

arteries have more damage d/t fast flow

veins clot better d/t slow flow

Question 3

What does Von Willebrand factor do?

Answer 3

• Nothing until it comes in contact with collagen
• Then it acts like a bridge between the collagen and the glycoprotein Ib platelet receptor
  
  • this receptor sticks the platelet to the von willebrand factor
• Once bound to von Willebrand factor the platelets will expose their GpIIb-IIIa receptors which will bind to fibrinogen and bind platelets together

Question 4

What is D-dimer indicative of?

Answer 4

clot breakdown

Question 5

What is Hemophilia A?

Answer 5

• Factor 8 deficiency
• X-linked
• Factor 8 must be <1% of normal to have severe bleeding
• Prolonged PTT
  
  • PT is normal
• These patients will still have extrinsic pathway, but without Factor 8a or 9a (deficient in hemophilia B), they cannot have “explosive” activation of 10a
  
  • external cuts on skin are no problem b/c they have extrinsic pathway
  • internal bleeding, like in joints are problematic
    
    • cause arthritis

Question 6

How is Hemophilia B different from Hemophilia A?

Answer 6

• Hemophilia B is Factor 9 deficient

Question 7

Factor XI deficienty

genetics:

who has it?

diagnosed it what lab?

Answer 7

• Autosomal recessive
• affects about 5% of Ashkenazi Jews
• Prolonged PTT
• generally mild

Question 8

What does Factor XIII deficiency cause?

How is it diagnosed?

Answer 8

• Factor 13 deficiency prevents the crossbridges of fibrinogen from being built. This makes the clots weak
• PT and PTT both measure the clotting cascade from 12 down to 1, but 13 is the last step and problems with it are not picked up on these labs
  
  • very difficult to diagnose

Question 9

Von Willebrand disease

gentetics

types

Answer 9

• Autosomal dominant or autosomal recessive
• Can either be no vWF, which is the most life threatening form but is very rare
• Or they can have vWF, but it doesnt work as well
  
  • form clots, just slower than normal

Question 10

What are Acquired factor 8 or 9 inhibitors?

Answer 10

• acquired disease that looks like Hemophilia 8 or 9, but instead of not having the factors, they are getting destroyed
• Cannot treat by giving them ffp or factors because the transfused factors will just be ruined as well

Question 11

What are some congenital disorders that result in low platelets?

Answer 11

• Congenital hypoplastic thrombocytopenia with absent radii
  
  • autosomal recessive, missing radius
• Fanconi anemia
  
  • autosomal recessive
  • congenital aplastic anemia with severe pancytopenia
  • often progresses to acute leukemia
• May-Hegglin anomoly
  
  • ineffective platelet production
  • thrombocytopenia with giant platelets
• Wiskott-Aldrich syndrome
  
  • X-linked
  • presents with eczema, immunodeficiency, and throbocytopenia

Question 12

What are acquired issues that result in defective platelet production?

Answer 12

• bone marrow damage
  
  • aplastic anemia, myelofibrosis, or leukemia with pancytopenia
• Vitamin B12 or folate deficiency
  
  • DNA synthesis needed for megakaryocyte production

Question 13

What characterizes Thrombotic thrombocytopenic purpura (TTP)?

What causes it?

What are the 5 signs?

Answer 13

• Characterized by formation of platelet-rich thrombi in the arterial and capillary microvasculature
• Deficiency of ADAMTS13 protease
  
  • usually this protease cuts ultra large vWF ultimers into smaller pieces
  • without it, they become too big, making throbus and using up all the platelets
• Five signs of TTP:
  
  • fever
  • renal failure
  • thrombocytopenia
  • microangiopathic hemolytic anemia
  • neurologic abnormalities
• TTP is an emergency!

Question 14

What is hemolytic uremic syndrome (HUS)?

Answer 14

• Typically seen in children with bloody diarrhea due to infection with a particular strain of E.coli that produces a shiga-like toxin
• Toxin causes coagulation to occur, traps RBCs
  
  • RBCs then get chopped up and chunks get caught in the basement membrane of the kidney
  • this causes renal failure

Question 15

What is HELLP syndrome?

Answer 15

• Combination of RBC hemolysis (H), elevated liver enzyme levels (EL), and low platelet count (LP)
• Thrombocytopenia is a frequent complication of pregnancy

Question 16

What is DIC?

Answer 16

• Some kind of trauma causes LOTS of tissue factor to be released
  
  • clotting starts hapening everywhere, leading to ischemia
• Plasmin is activated to break down the clots
  
  • this leeds to bleeding
• simultaneously bleeding and clotting (microvascular thrombus) makes it VERY difficult to treat

Question 17

Heparin induced thrombocytopenia

types

When does it occur?

stats

Answer 17

• Types:
  
  • type 1: nonimmune HIT
  • type 2: immune-mediated HIT
• Antibodies form the heparin-platelet factor 4 complex
  
  • occurs btw days 5 and 10 of heparin use
• Occurs with bovine heparine more than porcine
• <10% with antibody will have thrombotic event

Question 18

Thrombocytopenia is a common manifestation of _________

Answer 18

autoimmune disease

Question 19

What is Virchow’s triad?

Answer 19

• Endothelium integrity is the most important factor
  
  • injury can alter blood flow and affect coagulability
• Abnormal blood flows (stasis or turbulance) can cause endothelial injury

Question 20

What are the inheritable causes of hypercoagulability?

Answer 20

• Thrombophilia due to decreased Anti-thrombotic proteins
  
  • Hereditary antithrombin deficiency- 20x more likely to develop venous thromboembolism
  • Hereditary Protein C and S deficiency- same VTE risk as above
    
    • synthesis of protein C and S require Vit K
• Thrombophilia due to increased Pro-thrombotic proteins
  
  • Factor V leiden- coag factors are resistant to de-activation; end up with more circulating
  • Prothrombin Gene mutation- increased levels of prothrombin

Question 21

What are the acquired causes of hypercoagulability?

Answer 21

• Myeloproliferative disorders- polycythemia vera, thrombocytosis, paroxysmal nocturnal hgb
• Malignancies
  
  • adenocarcinoma of pancreas, colon, stomach, ovaries
  • present with DVT
  • tumor releases pro-coagulant factors that can directly activate factor X
• Pregnancy and oral contraceptive use
  
  • increase risk of thrombosis
• Nephrotic syndrome
• Antiphospholipid antibodies- SLE
• Heart disease- afib, venous stasis