Coagulation

Question 1

Which interaction leads to adhesion? Which leads to aggregation?

Answer 1

Adhesion between GPIba:vWF

Aggregation between GPIIb/IIIa:Fibrinogen

Question 2

What are some molecules that bind receptors on passing platelets for recruitment/activation?

Answer 2

5-HT and ADP

Question 3

What are the vitamin K dependent cofactors?

Answer 3

II, VII, IX and X

Protein C & Protein S

Question 4

What screening tests should be done for mucosal bleeding (nosebleeds, menorrhagia)?

Answer 4

Platelet defect and vWF

Question 5

What screening tests should be done for deep bleeding (joints, muscles, intracranial)?

Answer 5

Factor deficiency tests

Question 6

Thrombocytopenia due to decreased production

Answer 6

Vit B12 deficiency, marrow failure or disease

Question 7

Thrombocytopenia non-immune mediated

Answer 7

blood film often abnormal (DIC)

Question 8

Thrombocytopenia immune mediated–Fab mediated

Answer 8

Blood film usually normal (ITP)

Question 9

Thrombocytopenia immune mediated–Non-fab mediated

Answer 9

Heparin induced thrombocytopenia (Fc mediated)
Immune complex disease (HIV)
TTP (autoantibody to ADAMTS13–>deficiency)

Question 10

Transient autoimmune disease about 10 days after heparin therapy

Answer 10

Heparin-induced Thrombocytopenia

Auto-antibodies to PF4:Heparin

Question 11

Congenital absence of GPIb

Answer 11

Bernard Soulier Syndrome

Failure of adhesion

Question 12

Congenital absence of GPIIb/IIIa

Answer 12

Glanzman’s Thrombasthenia

Failure of platelets to aggregate

Question 13

Autoimmune production of IgG against platelet antigens (eg GPIIb/IIIa) –> consumed by splenic macrophages

Answer 13

Immune Thrombocytopenic Purpura

Question 14

What are some differences between the acute and chronic form of ITP?

Answer 14

Acute: usually in children, weeks after viral infection/immunization; self-limiting
Chronic: usually adults (women of child-bearing age), less likely to recover –> txt: corticosteroids, IVIG, Rituximab, last resort splenectomy

Question 15

Platelets consumed in formation of microthrombi –> RBCs are sheared as they cross microthrombi (hemolytic anemia with schistocytes)

Answer 15

Microangiopathic hemolytic anemia

TTP
HUS

Question 16

What is the PFA-100 lab test?

Answer 16

Screens for platelet and vWF function
Membrane is coated with collagen, blood is drawn through membrane, vWF sticks to collagen, platelets stick to vWF and eventually clog the hole –> measure the time to occlusion

Question 17

What causes TTP?

Answer 17

An acquired auto-antibody or congenital mutation to ADAMTS13 that results in large uncleaved multimers that lead to abnormal platelet adhesion –> develop microthrombi

Question 18

What form of E. coli will put you at risk for HUS?

Answer 18

O157:H7

Question 19

What is added to a prothrombin time?

Answer 19

Tissue factor, phospholipid and calcium to citrated plasma

Question 20

What is added in a PTT?

Answer 20

Surface activator, phospholipid and calcium to citrated plasma

Question 21

What does it mean if the clotting time corrects with a 1:1 mix test?

Answer 21

A factor deficiency is likely

If it does not correct than it is likely an inhibitor

Question 22

How is hemophilia inherited?

Answer 22

X linked recessive

Question 23

What are some things that may cause vitamin K deficiency?

Answer 23

Drugs (warfarin, antibiotics that decrease bowel flora)
Malabsorption or dietary deficiency
Liver disease
Newborns

Question 24

What will the labs look like in someone who has vWF deficiency?

Answer 24

Increased bleeding time
Increased PTT
Normal PT

Question 25

What is the pathophysiology behind vWF deficiency?

Answer 25

vWF normally stabilizes factor VIII -- deficiency ruins this and decreased the half life of factor VIII

Question 26

What is a treatment for vWF deficiency?

Answer 26

Desmopressin (Increases vWF release from Weibel Palade bodies)

Question 27

Treatment for heparin induced thrombocytopenia

Answer 27

Stop heparin | Start direct thrombin inhibitor

Question 28

Which factors does antithrombin inactivate?

Answer 28

IIa and Xa

Question 29

Which factors does Protein C inactivate?

Answer 29

Va and VIIIa

Question 30

Widespread microthrombi result in ischemia and infarction --> consumption of platelets and factors results in bleeding (IV and mucosal sites)

Answer 30

DIC

Question 31

Mutated form of factor V that lacks the cleavage site for deactivation by protein C

Answer 31

Factor V Leiden -- VENOUS thrombotic risk factor | Arg 506 replaced with Gln

Question 32

what increases the risk of warfarin skin necrosis?

Answer 32

Protein C deficiency

Question 33

Antibodies against phospholipids that damage cells leading to the formation of clots in arteries and veins

Answer 33

Antiphospholipid Antibody Syndrome

Question 34

What are some antiphospholipid antibodies to test for?

Answer 34

Anti-cardiolipin | Lupus anticoagulant

Question 35

Some syndromes associated with DIC?

Answer 35

``` Malignancy Amniotic fluid Fat embolism Acute hemolytic process Heparin assoc thrombocytopenia Sepsis ```

Question 36

what might Purpura Fulminans be a presenting symptom for?

Answer 36

Meningococcal sepsis | Severe protein C deficiency in a newborn

Question 37

What is hemophilia C?

Answer 37

Deficiency in factor XI affecting men and women equally

Question 38

What is the clinical pentad of TTP?

Answer 38

``` Thrombocytopenia Microangiopathic hemolytic anemia (schistocytes/RBC fragments) Renal insufficiency Neurological symptoms Fever ```