Bleeding Disorders

Question 1

What are the phases of homeostasis in clot formation?

Answer 1

(1) vasocontriction - endothelin release at the site of injury causes reflex vasoconstriction; (2) platelet adhesion - von Willebrant Factor (protein layer that acts like glue when endothelium is breeched) causes platelets to adhere and release cytokines; (3) platelet aggregation - activation of cytokines (ADP and TXA2) cause platelets to aggregate and form a platelet plug at the site of injury; (4) release of t-PA (fibrinolysis) and thrombomodulin (blocks coagulation cascade) prevent the clot from growing too large

Question 2

What is the intrinsic pathway in the coagulation cascade?

Answer 2

includes Factors XII, XI, IX, and VIII to Factor X (more stable because it produces more fibrin) => affects the Partial Thromboplastin Time (PTT)

Question 3

What is the extrinsic pathway in the coagulation cascade?

Answer 3

includes tissue factor and Factor VII (unstable because tissue factor is short-lived) => affects Prothrombin Time (PT)

Question 4

What is the role of clotting factors in clot formation?

Answer 4

stabilize the platelet plug

Question 5

What are clotting factors?

Answer 5

proteins produced in the liver with the help of Vitamin K

Question 6

What is fibrin?

Answer 6

insoluble fibers that help to reinforce the platelet plug

Question 7

Which therapies that reduce clot formation act on platelets?

Answer 7

aspirin and clopidogrel (Plavix)

Question 8

How does aspirin prevent clot formation?

Answer 8

blocks TXA2 - prevents platelets from aggregating => platelet plug cannot form

Question 9

How does clopidogrel (Plavix) prevent clot formation?

Answer 9

blocks ADP - prevents platelets from aggregating => platelet plug cannot form

Question 10

How does Vitamin K deficiency contribute to bleeding?

Answer 10

Vitamin K deficiency causes a decrease in Factor VIII which, in turn, stops the intrinsic clotting cascade (liver will not produce clotting factors without Vitamin K)

Question 11

How does coumadin (Warfarin) prevent clotting?

Answer 11

acts as an indirect anticoagulant => reduces Vitamin K

Question 12

How do rivaroxaban (Xarelto) and apixaban (Eliquis) prevent clotting?

Answer 12

act as direct anticoagulant => directly inhibit Factor X (think rivaroXaban and apiXaban = X for Factor X)

Question 13

How does dabigatran (Pradaxa) prevent clotting?

Answer 13

directly inhibits thrombin production

Question 14

What is the mechanism of tissue plasminogen factor (t-PA) in preventing clots?

Answer 14

breaks up only fresh clots (acts only on newly released fibrin) - has to be given within 3.5 hours of a thrombotic stroke

Question 15

What does the presence of D-Dimer indicate?

Answer 15

recency of a clot - reflects active/fresh coagulation

Question 16

What is the International Normalized Ratio (INR)?

Answer 16

a standardized tissue factor that is added to a test tube of blood to test time to formation of fibrin clot

Question 17

How is prothrombin time (PT) used in Warfarin management?

Answer 17

Warfarin has strongest effects on Factor VII (has the shortest half-life of all Factors) - affects the extrinsic pathway of the clotting cascade

Question 18

What is the best indicator of Warfarin level?

Answer 18

prothrombin time (PT)

Question 19

What is the best indicator of Heparin level?

Answer 19

partial thromboplastin time (PTT)

Question 20

How is partial thromboplastin time (PTT) used in Heparin management?

Answer 20

Heparin has strongest effects on Factors IX and XI - affects the intrinsic pathway of the clotting cascade

Question 21

What is the role of Xarelto/Eliquis in management of clotting disorders?

Answer 21

used for non-valvular A-fib, DVTs and PE - affect both PT and PTT, but extent of effect is unreliable => no good correlation between drug level and anticoagulant effect - give standard doses and hope for no negative effects

Question 22

What is the Rule of 10 for remembering coagulation tests?

Answer 22

drug name and lab acronym add up to 10 letters:

(1) Heparin + PTT = 10 letters
(2) Coumadin + PT = 10 letters

Question 23

What are the tests for tracking primary hemostasis (disorders involving platelets)?

Answer 23

(1) CBC (platelets) - normal = 150,000 to 450,000 (# of platelets can be normal but platelet function can be abnormal)
(2) bleeding time (controlled, superficial cut) - normal = < 10 minutes (provides indication of platelet function but not used in practice)

Question 24

What are the tests for tracking secondary hemostasis (disorders involving clotting factors)?

Answer 24

measure the time it takes for fibrin clot to form
(1) PT/INR - extrinsic pathway - normal = 11-14 seconds (dependent on tissue factor’s effect on Factor VII - tissue factor is extrinsic/does not exist in the blood and has to be added to the test tube)

(2) PTT - intrinsic pathway - normal = 25-35 seconds (depends on Factors XII, XI, IX, and VII - intrinsic/already exist in the blood)

Question 25

What are the characteristics of bleeding due to primary hemostasis disorders (i.e., disorders of platelets)?

Answer 25

superficial (mucosal) bleeding (epistaxis, gingival, vaginal); skin bleeding - petechia (< 0.5 cm, purpura 0.5-1. cm) => non-blanchable (out of the blood vessels)

Question 26

What are the causes of bleeding due to primary hemostasis disorders (i.e., disorders of platelets)?

Answer 26

Inherited: von Willebrant Disease Acquired: idiopathic thrombocytopenic purpura (ITP - autoimmune disorder against platelets), drug-induced (aspirin, NSAIDs, clopidogrel), splenomegaly, viral infections (HIV, HCV), uremia

Question 27

What are the characteristics of bleeding due to secondary hemostasis disorders (i.e., disorders of clotting factors)?

Answer 27

deep bleeding in joints (hemarthrosis), bleeding/bruises in muscles and retroperitoneal cavity

Question 28

What are the causes of bleeding due to secondary hemostasis disorders (i.e., disorders of clotting factors)?

Answer 28

hemophilia, Vitamin K deficiency (malnutrition), drug-induced (Warfarin/Heparin), cirrhosis (dysfunctional liver cannot produce enough clotting factors)

Question 29

What is idiopathic thrombocytopenic purpura (ITP)?

Answer 29

an autoimmune disease, sometimes preceded by a viral illness - body develops antibodies to one's own platelets (antibodies cover platelets, macrophages then carry platelets to spleen for destruction) => dysfunction in the number of platelets, but platelet function is normal (normal RBCs, WBCs, and clotting factors)

Question 30

What are the signs and symptoms of ITP?

Answer 30

mostly asymptomatic or platelet-type/superficial bleeding

Question 31

What is the treatment for ITP?

Answer 31

severe thrombocytopenia (< 50,000) => prednisone (prevents macrophages from grabbing antibodies on platelets) repeated episodes => splenectomy (prevents destruction of platelets)

Question 32

What is von Willebrant Disease (VWD)?

Answer 32

most common inherited bleeding disorder (autosomal dominant inheritance - not on sex chromosome, only need 1 defective gene to cause disease - 50% likelihood with each pregnancy/male or female) - deficiency in von Willebrant factor => abnormality in platelet function, but platelet number is normal - leads to prolonged PTT

Question 33

How is VWD diagnosed?

Answer 33

normal platelet number, prolonged bleeding time (> 10 minutes), PTT may be prolonged, PT normal, VWF level is decreased

Question 34

What is the treatment for VWD?

Answer 34

desmopressin (deamino-d-arginine vasopressin - DDAVP) - a synthetic ADH (given IV or intra-nasally) => induces endothelial cells to release VWF from stores (those affected by VWD do not completely lack VWF, it is just not released)

Question 35

What is hemophilia?

Answer 35

x-linked recessive disorder (carried on sex chromosome - need 2 defective genes to cause disease and only 1 to be carrier) - 2 types: (1) A - deficiency of Factor VIII (2) B - deficiency of Factor IX - less common

Question 36

What are the signs and symptoms of hemophilia?

Answer 36

only affects males, hemarthrosis (most commonly the knee), progressive joint destruction, retroperitoneal bleed, intracranial bleed => bleeding time is normal (affects Factors, not platelets)

Question 37

How is hemophilia diagnosed?

Answer 37

platelet count is normal, bleeding time is normal, PTT increased (prolonged), PT is normal, Factor VIII or IX is decreased

Question 38

What is the treatment for hemophilia?

Answer 38

clotting factor replacement (recombinant FVIII or FIX): - given 3X per week (for life) - prophylactically - give additional Factors when injury occurs - heavy bleeding - need to give plasma - acute hemarthrosis - analgesia and immobilization

Question 39

What distinguishes the clinical presentation of VWD and hemophilia?

Answer 39

VWD - both male and female patients, bleeding is superficial hemophilia - affects only male patients, bleeding is deep