Hemostasis Defects (complete)

Question 1

What are the major congenital disease states causing bleeding and/or clotting?

Answer 1

1) Hemophilia A (F8)
2) Hemophilia B (F9)
3) Hemophilia C (F11)
4) von Willebrand Disease
5) Factor VII deficiency

Question 2

What are the major acquired disease states causing bleeding and/or clotting?

Answer 2

1) Liver disease
2) Vit K deficiency/Warfarin administration
3) Disseminated Intravascular Coagulation (DIC)

Question 3

What is PT/INR? What is it testing?

Answer 3

• Prothrombin time (PT), international normalized ratio (INR)
• Measures extrinsic and common pathway
• Sensitive to Warfarin

PT: Time to clot in seconds (nl: 9-12)

INR: 1 is normal, 2 is twice normal (this is a standardized measurement b/c each test manufacturer is different)

Question 4

What is APTT? What is it testing?

Answer 4

• Measures intrinsic and common pathways
• Sensitive to inhibition by heparin and fibrin split products
• Nl: 25-32 seconds

Question 5

What is TT? What is it testing?

Answer 5

• Measures procoagulant activity of fibrinogen
• Sensitive to inhibition by heparin and fibrin split products
• Nl: 12-18 seconds

Question 6

What is bleeding time? What is it testing?

Answer 6

• Measures platelet and vessel interaction
• Standardized cut + simplate bleeding time device on forearm => time to clot is measured
• Nl: 2-9 minutes

Question 7

What is PFA? What is it testing?

Answer 7

• New device => perform in vitro bleeding time

- Can also determine platelet response to agonists

Question 8

What is a differential diagnosis for an abnormal PT/INR?

Answer 8

Prolong PT:

• Vit K deficiency
• Warfarin therapy
• Liver Disease
• Factor 2, 7, 5, 10 deficiencies
• Fibrinogen deficiency

Question 9

What is a differential diagnosis for an abnormal APTT?

Answer 9

Prolonged APTT:

- Hemophilia

Question 10

What is a differential diagnosis for an abnormal TT?

Answer 10

Prolonged TT:

• Heparin contamination
• Fibrinogen deficiency
• Abnormal fibrinogen

Question 11

What is a differential diagnosis for an abnormal bleeding time?

Answer 11

Prolonged BT:

• Thrombocytopenia
• von Willebrand disease
• abnormalities in platelet function

Question 12

What are some other tests used to evaluate patients w/ thrombotic or bleeding disorders?

Answer 12

PFA-100: determines platelet response to agonists

Question 13

Describe the clinical features for hemophilia A&B

Answer 13

• Unexplained hematomas, bruises, post-surgical or traumatic bleeding
• Joint bleeding => joint fusion/destructive arthritis
• CNS bleeds (COD usually)
• Retroperitoneal/psoas bleeds

Question 14

Describe the molecular basis for hemophilia A&B

Answer 14

• X-linked deficiency of Factor 8 (A) or Factor 9 (B)

- Affects males, females = carriers

Question 15

Describe the clinical features for factor 7 deficiency

Answer 15

• Severe bleeding disorder similar to hemophilia (joints, muscles, soft tissue, retroperitoneal space, CNS)
• Prolonged PT
• Normal PTT

Question 16

Describe the molecular basis for factor 7 deficiency

Answer 16

• AR genetics
• Severe = homozygous
• underproduction of Factor 7

Question 17

Describe the clinical features for von Willebrand disease

Answer 17

Primary hemostasis problems: bleeding in mucosa, under skin

• Prolonged BT
• Prolonged PTT

Question 18

Describe the molecular basis for von Willebrand disease

Answer 18

• Platelets can’t adhere to exposed collagen/subendo
• Also deficiency in Factor 8 (vWF normally carries this guy)
• AD genetics

Question 19

Describe the role of liver disease in coagulopathy

Answer 19

Liver produces almost all coag factors

Liver disease => deficiencies in those factors

Prolonged PT, PTT, TT

Question 20

Describe disseminated intravascular coagulation (DIC)

Answer 20

• Systemic activation of coagulation => intravascular fibrin deposition & depletion of platelets and coag factors
• Fibrin dep => thrombosis and organ failure
• Depletion => bleeding

Question 21

Explain diagnostic testing for DIC

Answer 21

• Low fibrinogen level
• Low platelet count
• Increased D-dimers
• Prolonged PTT
• Prolonged TT

Overall: TREAT THE UNDERLYING CONDITION

Question 22

What is a lupus anticoagulant?

Answer 22

• IgG Ab => reacts against phospholipid in platelet membrane or endo cell
• causes Antiphospholipid Antibody Syndrome (APS)

Question 23

How does a lupus anticoagulant affect coagulation?

Answer 23

• Although there is a prolonged PTT, there is no bleeding problem
• Actually causes thrombosis!!

Question 24

How can one test for a lupus anticoagulant?

Answer 24

• dilute Russell’s Viper Venom Test (dRVVT) => directly activates factor 10
• Reveals a prolonged clotting time w/ dRVVT

Question 25

Explain how a 1:1 mixing study can distinguish a clotting factor deficiency from an inhibitor of coagulation

Answer 25

- Patient's plasma and normal plasma mixed together - clotting factor deficiency => will return to normal PTT - coag inhibitor (like an Ab against a factor) => unchanged

Question 26

Why does the PTT change to normal during a 1:1 mixing study for clotting factor deficiency?

Answer 26

- The pt's plasma now has the clotting factor present from donor plasma - Will normalize PTT

Question 27

Why does the PTT remain unchanged during a 1:1 mixing study for a coagulation inhibitor?

Answer 27

- The Ab continues to targets the specific factor - Donor plasma just gives more factor for Ab to target - No change to PTT