Coagulation and Hemophilia

Question 1

Hemophilia C is the deficiency in which Factor

Answer 1

Factor XI

Question 2

Go through Intrinsic coagulation cascade

Answer 2

Contact activators (Prekallikrein and HMWK), then XII, XI, IX, and X (using VIIIa as a cofactor)

Question 3

Why can patients with Factor XII and factor XI deficiencies have no bleeding phenotype?

Answer 3

Thrombin has a positive feedback (“thrombin burst”) that increases activation of XI and VIII

Question 4

How does the DRVVT test work? If it’s positive, what does that suggest?

Answer 4

Directly activates X to Xa, then goes through the rest of the common pathway. If time is prolonged, then test is repeated with and without phospholipid. If the ratio (PL/no PL) is prolonged, it’s indicative of antiphospholipid antibody.

Question 5

What is the use of the reptilase time? (two things it is useful for)

Answer 5

Low fibrinogen
Dysfunctional fibrinogen

Question 6

What factor deficiencies (3) are clinically silent but will prolong PTT?

Answer 6

HMWK and prekallikrien
Factor XII

Question 7

What are the factor cutoffs for mild, moderate, and severe Hemophilia?

Answer 7

Mild: 5-40%
Moderate: 1-5%
Severe: <1%

Question 8

1 u/kg of Factor VIII raises blood levels by how much?

Answer 8

2%

Question 9

1 u/kg of Factor IX raises blood levels by how much?

Answer 9

0.75-1%

Question 10

Goal factor levels for hemophilia patient with CNS bleed

Answer 10

80-100%

Question 11

Goal factor levels for hemophilia patient with major surgery

Answer 11

80-100%

Question 12

Goal factor levels for hemophilia patient with RP, epiglottis, floor of mouth bleed

Answer 12

80%

Question 13

Goal factor levels for hemophilia patient with joint, muscle, GI tract, epistaxis, or hematuria

Answer 13

50%

Question 14

How does DDAVP work to help bleeding in hemophilia?

Answer 14

It releases endogenous Factor VIII:vWF complexes from endothelia

Question 15

What is the mechanism of action of Emicizumab

Answer 15

Binds to FIXa and FX to simulate the activity of Factor VIII

Question 16

What medication can you NOT give Emicizumab with and why?

Answer 16

FEIBA because it causes a TMA

Question 17

You see a isolated prolonged PTT that fails to fully correct at a mixing study, and re-prolongs after incubation at 1-2 hours. What does this indicate?

Answer 17

Pathognomonic for a factor inhibitor - but the re-prolongation isn’t always present

Question 18

Three prongs to treating acquired hemophilia A due to an inhibitor?

Answer 18

1. Increase Factor VIII levels with recombinant porcine FVIII (Obizur)
2. Use bypassing agents like recombinant FVIIa or aPCC
3. Eradicate the inhibitor with Rituximab or prednisone +/- cyclophosphamide

Question 19

What group of disorders is most closely associated with Factor V deficiency?

Answer 19

MPNs

Question 20

You see a bleeding patient with a history of essential thrombocythemia with prolonged PTT, prolonged INR, normal thrombin time, normal reptilase time. Diagnosis?

Answer 20

Factor V deficiency

Question 21

You see a bleeding patient with a history of essential thrombocythemia with prolonged PTT, prolonged INR, normal thrombin time, normal reptilase time. Diagnosis and Treatment?

Answer 21

Factor V deficiency
FFP to keep Factor V above 20%
(could also give platelets since FV is in platelet granules)

Question 22

Goal Factor V levels in a bleeding patient with FV deficiency?

Answer 22

20%

Question 23

You see a bleeding patient with a history of AL amyloidosis who has a prolonged PTT, prolonged INR, normal thrombin time, normal reptilase time. The PTT and INR corrects with mixing study. Diagnosis and treatment (two options)?

Answer 23

Factor X deficiency
Replace FX with recombinant X or PCC

Question 24

Patient seen with post-surgical bleeding and also incidentally noted LLE below knee DVT. Coags show prolonged INR, normal PTT, normal thrombin time, normal reptilase time. What is most likely diagnosis? Treatment (two options)

Answer 24

Factor VII deficiency
Recombinant FVII and antifibrinolytics

Question 25

Older patient presents with post-surgical bleeding. Coags show prolonged PTT and normal PT/INR. Factor VIII and IX levels are normal. What is most likely diagnosis? Treatment?

Answer 25

Factor XI deficiency (Hemophilia C)
FFP to increase FXI levels, also antifibrinolytics

Question 26

Patient presents with surgical site bleeding on POD 4. Coags show normal PT and PTT. Normal platelet studies. Clot stability assay shows clot that readily dissolves in urea. What’s most likely diagnosis?

Answer 26

Factor XIII deficiency

Question 27

In a clot stability assay, the lab adds Ca to plasma to cause a clot, then incubates and placed in 5M urea. If the clot dissolves, what disorder is that indicative of?

Answer 27

Factor XIII deficiency

Question 28

If a patient with Factor XIII deficiency is pregnant, how do you manage it?

Answer 28

Give recombinant FXIII by five weeks gestational age to maintain levels above 10%

Question 29

At what level of Factor XIII do you give prophylactic recombinant FXIII?

Answer 29

Less than 10%

Question 30

Prolonged reptilase time is indicative of what disorders?

Answer 30

Dysfibrinogenemia or hypofibrinogenemia

Question 31

In HHT, what is the inheritance pattern and what genes are commonly seen mutated?

Answer 31

AD, TGF-B pathway

Question 32

Diagnostic criteria for HHT (4)

Answer 32

Telangectasias on mucocutaneous sites, face, ears, fingertips
Recurrent epistaxis
Visceral AVMs
Family history of HHT

Question 33

Treatment of mild bleeding in HHT?

Answer 33

Antifibrinolytics

Question 34

Treatment of severe bleeding in HHT? Aside from local procedures

Answer 34

Antiangiogenics (Bevacizumab)