BL hemostasis defects

Question 1

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

Answer 1

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

Question 2

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

Answer 2

(VIII 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

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

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

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?

Answer 16

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

• 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.