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AGPC 4 > Bleeding Disorders > Flashcards

Bleeding Disorders Flashcards

1
Q

What are the phases of homeostasis in clot formation?

A

(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

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2
Q

What is the intrinsic pathway in the coagulation cascade?

A

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

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3
Q

What is the extrinsic pathway in the coagulation cascade?

A

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

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4
Q

What is the role of clotting factors in clot formation?

A

stabilize the platelet plug

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5
Q

What are clotting factors?

A

proteins produced in the liver with the help of Vitamin K

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6
Q

What is fibrin?

A

insoluble fibers that help to reinforce the platelet plug

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7
Q

Which therapies that reduce clot formation act on platelets?

A

aspirin and clopidogrel (Plavix)

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8
Q

How does aspirin prevent clot formation?

A

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

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9
Q

How does clopidogrel (Plavix) prevent clot formation?

A

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

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10
Q

How does Vitamin K deficiency contribute to bleeding?

A

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)

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11
Q

How does coumadin (Warfarin) prevent clotting?

A

acts as an indirect anticoagulant => reduces Vitamin K

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12
Q

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

A

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

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13
Q

How does dabigatran (Pradaxa) prevent clotting?

A

directly inhibits thrombin production

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14
Q

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

A

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

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15
Q

What does the presence of D-Dimer indicate?

A

recency of a clot - reflects active/fresh coagulation

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16
Q

What is the International Normalized Ratio (INR)?

A

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

17
Q

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

A

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

18
Q

What is the best indicator of Warfarin level?

A

prothrombin time (PT)

19
Q

What is the best indicator of Heparin level?

A

partial thromboplastin time (PTT)

20
Q

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

A

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

21
Q

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

A

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

22
Q

What is the Rule of 10 for remembering coagulation tests?

A

drug name and lab acronym add up to 10 letters:

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

23
Q

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

A

(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)

24
Q

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

A

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)

25
Q

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

A

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

26
Q

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

A

Inherited: von Willebrant Disease

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

27
Q

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

A

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

28
Q

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

A

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

29
Q

What is idiopathic thrombocytopenic purpura (ITP)?

A

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)

30
Q

What are the signs and symptoms of ITP?

A

mostly asymptomatic or platelet-type/superficial bleeding

31
Q

What is the treatment for ITP?

A

severe thrombocytopenia (< 50,000) => prednisone (prevents macrophages from grabbing antibodies on platelets)

repeated episodes => splenectomy (prevents destruction of platelets)

32
Q

What is von Willebrant Disease (VWD)?

A

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

33
Q

How is VWD diagnosed?

A

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

34
Q

What is the treatment for VWD?

A

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)

35
Q

What is hemophilia?

A

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

36
Q

What are the signs and symptoms of hemophilia?

A

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

37
Q

How is hemophilia diagnosed?

A

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

38
Q

What is the treatment for hemophilia?

A

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
39
Q

What distinguishes the clinical presentation of VWD and hemophilia?

A

VWD - both male and female patients, bleeding is superficial

hemophilia - affects only male patients, bleeding is deep

AGPC 4 (22 decks)

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