Hemostasis Defects

Question 1

List major congenital or acquired disease states causing bleeding and/or clotting.

Answer 1

Q

1. Hemophilia A (VII def)
2. Hemophilia B (Christmas/IX def)
3. Factor XI Deficiency (Christmas disease/Hemophilia C)
4. Factor VII Deficiency
5. Von Willebrand Disease

Question 2

Hemophilia A
What is it?
Genetic disorder type?
PTT result?

Answer 2

(VII def)
Most common cause of severe bleeding tendency
X-linked, results in prolonged PTT only.

(1 in 5000 male births with 30% new mutations)

Question 3

Hemophilia B
What is it?
Genetic disorder type?
PTT result?

Answer 3

(Christmas/IX def)
10x less common than A
X-linked, results in prolonged PTT only.

Question 4

Factor XI Deficiency
What is it?
Genetic disorder type?
PTT?

Answer 4

(Hemophilia C)

○ AR so presented in both genders.
○ Classic presentation is post-operative hemorrhage

PPT will be prolonged

Question 5

Activated partial thromboplastin time (aPTT) involve what factors?

Answer 5

Helpful note: the test with the longer name (APTT) is associated with the factors that have the higher numbers: VIII, IX, XI, XII (vs the VII for PT)

Question 6

Prothrombin PT/INR measures which factors?

Answer 6

VII, X, V, II and fibrinogen
(extrinsic pathway and lower part of the coagulation cascade)

Normal INR = 1

Question 7

Pt has liver disease, and ends up with Vit K deficiency. What would the PT show?

Answer 7

PT will be prolonged, meaning time to clot takes longer

PT tests for Vit K dependent factors VII, X, V, II
without these factors you cant clot as well!

Question 8

What can cause prolonged Protime to be more prolonged than PTT?

Answer 8

Liver disease
Vit K def
Warfarin/rat poison

Question 9

What can cause PTT to be more prolonged than protime?

Answer 9

DIC

Question 10

What causes a prolonged PTT?

Answer 10

Heparin 
Hemophilia A and B (VIII and IX def) 
Factor XI def 
Factor XII def 
Von willebrand dis 
Lupus anticoagulant

Question 11

thrombin time

Answer 11

○ thrombin time measure procoagulant activity of fibrinogen; sensitive to heparin and fibrin split products.
○ Normal 12-18 sec

Question 12

PFA-100

Answer 12

○ Platelet Function Analyzer that can perform an invitro bleeding time.
§ Can determine platelet response to agonists.

Question 13

role of liver disease in coagulopathy.

Answer 13

• Decreased synthesis of most factors
• Decreased vitamin k dependent carboxylation of II, VII, IX and X
• Decreased fibrinogen production and increased fibrinolysis
○ Prolonged PT, PTT, and TT
• Increased consumption of platelets → ↓ platelet counts b/c portal hypertension causes spleen to consume platelets.
• Causes deficiencies in protein C and S and antithrombin (which will cause abnormalities of the fibrinolytic system)

Question 14

disseminated intravascular coagulation (DIC)

Answer 14

Q

coag cascade is activated→fibrin and platelet microthrombi form and plug capillaries →causes tissue infarction.

At the same time:
factors and platelets are consumed so that the patient develops multiple coagulation factor deficiencies and hemorrhage can result.

But wait! There’s more:
Fibrinolytic system is activated in order to try and remove the fibrin-platelet microthrombi. Fibrin cleavage products releases as fibrin split products which can also inhibit PTT assay and thrombin time prolonging it.

Question 15

Abnormalities in DIC

Answer 15

Q 
prolonged PT 
greatly prolonged PTT 
Low platelet count 
low fibrinogen level 
increased fibrin split products 
increased D-dimer

Question 16

lupus anticoagulant:
What is it?
how it affects coagulation?
Q

Answer 16

Q
lupus anticoagulant is an IgG antibody that reacts against the phospholipid in the platelet membrane and endothelial cells. (prothrombotic agent)
• Common acquired abnormality → Results in hypercoaguable state.
• Causes Antiphospholipid Antibody Syndrome (APS) → in vivo thrombotic disorders)

Question 17

lupus anticoagulant:

How to test for it?

Answer 17

Q
• Detect by:
- greatly prolonged PTT,
- no bleeding tendency,
- can have thrombotic syndromes (DVT, PE, thrombotic strokes, or recurrent miscarriages).
(more likely to clot, but slower to clot)

Question 18

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

Answer 18

• A 1:1 mixing study of normal plasma with patients plasma can indicate if disease is due to a clotting factor deficiency or from an inhibitor of coagulation.
○ If PTT is not corrected after two hours of incubation–> disease is due to inhibitor.
○ If PTT corrects, clotting factor deficiency.