Coagulation Disorders

Question 1

MC inherited factor deficiencies

Answer 1

HEMOPHILIAS

X-linked diseases caused by deficiency of factor (F) VIII (hemophilia A) or FIX (hemophilia B)

Question 2

ISOLATED prolonged PT

Answer 2

FVII deficiency

Question 3

PROLONGED aPTT

Answer 3

Intrinsic pathway factor deficiency – hemophilia A or B (FVIII or FIX, respectively) or FXI deficiency

Question 4

Prolongation of both PT and aPTT

Answer 4

deficiency of FV, FX, FII, or fibrinogen abnormalities

Question 5

X-linked recessive hemorrhagic disease due to mutations in the F8 gene (hemophilia A or classic hemophilia) or F9 gene (hemophilia B)

Answer 5

HEMOPHILIA A AND B

Question 6

FVIII

Answer 6

1 IU/kg → ↑ FVIII by 2%

FVIII dose (IU) = (Target – baseline %) × weight (kg) × 0.5

Half-life: 8–12 h → BID dosing

Question 7

FIX

Answer 7

Recovery ≈ 50%

FIX dose (IU) = (Target – baseline %) × weight (kg) × 1

Half-life: ~24 h → once daily

Question 8

~80 IU FVIII per bag

Use ONLY if factor concentrates unavailable

Answer 8

Cryoprecipitate

Still used in developing countries

Question 9

Releases FVIII & VWF (not FIX)

Use in mild–moderate Hemophilia A

Answer 9

DDAVP

Dose: 0.3 μg/kg IV over 20 min

↑ FVIII 2–3×

Question 10

MAJOR COMPLICATION of hemophilia treatment

Answer 10

inhibitor formation – formation of alloantibodies to FVIII or FIX

neutralize coagulation factors – ineffective factor replacement treatment

Question 11

Bispecific antibody: FIXa ↔ FX

FVIII-independent

Effective with or without inhibitors

Answer 11

EMICIZUMAB

Question 12

Rare autosomal bleeding disorder

Incidence: ~1 per 1,000,000

Answer 12

FACTOR IX DEFICIENCY

mucocutaneous bleeding predominates

High prevalence in Jews:
o Ashkenazi & Iraqi Jews
o 6% heterozygotes
o 0.1–0.3% homozygotes

Question 13

An ACQUIRED syndrome of systemic intravascular coagulation with loss of localization –> microvascular thrombosis, consumption of platelets and clotting factors and potentially organ dysfunction and bleeding

Answer 13

Disseminated Intravascular Coagulation (DIC)

• Platelet count ↓
• Fibrinogen ↓
• D-dimer/FDP ↑
• PT prolonged

Question 14

Severe DIC with skin necrosis associated with protein C deficiency

Often post-infection in children

Answer 14

Purpura fulminans

Question 15

Low Responder

Answer 15

< 5 BU

High-dose FVIII (50–100 IU/kg)

Question 16

High Responder

Answer 16

≥5 BU or anamnestic response

Bypass agents
o Activated PCC (aPCC)
o Recombinant FVIIa

Question 17

Central mechanism in the pathophysiology of DIC

Answer 17

UNCONTROLLED THROMBIN generation

Question 18

ISTH Criteria for Overt DIC

Answer 18

Platelets
>100,000 × 109/L 0
>50 – <100 × 109/L 1
<50 × 109/L 2

D Dimer
Normal 0
Moderate increase 2
Severe increase 3

PT prolonged
<3 s 0
3 – <6 s 1
>6 s 2

Fibrinogen
>1 g/L 0
<1 g/L 1

<5 - LOW GRADE DIC
>5 OVERT DIC