257 - Acquired Coagulopathies

Question 1

Which coagulation/anticoagulation proteins are Vitamin K dependent?

Answer 1

• Pro-coagulant
  
  • II
  • VII
  • IX
  • X
• Anti-coagulant
  
  • Protein C
  • Protein S

Question 2

What two molecules are required for the action of coagulation factors?

Answer 2

Phospholipids

Calcium

Anti-phospholipid antibodies! Can interfere with clotting times, but more associated with clotting than bleeding

Question 3

What is the treatment for DIC?

Answer 3

Treat the underlying cause

(ex: sepsis)

Only give blood products if necessary

• Give:
  
  • platelets if <20k or <50k with active bleeding
  • FFP if bleeding and elevated PT/PTT
  • Fibrinogen if <100 (or <200 in obstetric cases)

Question 4

What is a key difference in the lab values of DIC and TTP?

Answer 4

DIC will have prolonged PT and PTT

TTP (and HUS) will have normal PT and PTT

Question 5

How is a Bethesda assay performed?

Answer 5

Serial dilutions of pt plasma incubated with normal plasma

VIII activity measured at each dilution

1 Bethesda Unit (BU) = amount of antibody that inhibits 50% of FVIII in a normal sample

Low titier inhibitor is ≤ 5 BU

Bethesda Assay = used to test how much FVIII antibody (inhibitor) is present in the sample

Question 6

What is the treatment for vitamin K deficiency?

Answer 6

• If no bleeding
  
  • Oral vitamin K
  • Give subcutaneous only if malabsorption or NPO
• If bleeding
  
  • IV vitamin K
  • Plasmaproducts (FFP or prothrombin complex concentrates)

Question 7

What kind of inhibitors are present in congenital vs. acquired hemophilia?

Answer 7

Congenital hemophilia has alloantibodies

Acquired hemophilia has autoantibodies

Not exactly sure why this is - lmk if you have any ideas!

Question 8

List 2 key differences between antiphospholipid antibody syndrome and F VIII inhibitor (acquired hemophilia A)

(bleed or clot? and what level of FVIII?)

Answer 8

• Anti-phospholipid antibody
  
  • Thrombosis
  • Normal FVIII
• F VIII inhibitor
  
  • Bleeding
  • Low FVIII
• Neither will correct on mixing study;*
• APA will correct when phospholipid is added*

Question 9

What are the criteria for diagnosing anti-phospholipid syndrome?

Answer 9

• 1 clinical outcome
  
  • Thrombosis
  • Adverse pregnancy outcome
• 1 laboratory criteria (phospholipid antibody) on 2 or more occasions, 12 weeks apart
  
  • Lupus anticoagulant
  • Anticardiolipin
  • Beta-2 glycoprotein

Question 10

List 4 ways that liver disease can predispose somebody to bleeding

Answer 10

• Decreased platelets/platelet function (decreased TPO?)
• Decreased synthesis of coagulation factors
• Decreased fibrinogen (produced in the liver)
• Decreased vitamin K absorption
  
  • Due to decreased bile acid production

Question 11

How will these labs change in DIC?

• PT/PTT
• D-Dimer
• Fibrinogen
• Platelets

Answer 11

• PT/PTT - High
• D-Dimer - High
• Fibrinogen - Low
• Platelets - Low

Will also see MAHA; elevated LDH + schistocytes on blood smear

Question 12

List 3 clinical manifestations of anti-phospholipid syndrome

Answer 12

Venous thrombosis

Arterial thrombowiss

Adverse pregnancy outcomes

May also see thrombocytopenia, hemolytic anemia, livedo reticularis, cognitive deficits, cardiac valvular disease…

Question 13

Describe the pathophysiology of DIC

Answer 13

• Trigger (often sepsis)
  
  • Widespread clotting factor activation
  • Consumes platelets and clotting factors
• Deficiency in clotting factors –> bleeding state

Result is bleeding AND microthrombi that cause organ damage

Question 14

Which newborns are at risk of vitamin K deficiency?

Answer 14

All of them!

Usually given vitamin K shot

Question 15

List the causes of DIC (8)

Answer 15

SSTOP Making New Thrombi

• Sepsis
• Snake bite
• Trauma
• Obstetric complication
• Pancreatitis (acute)
• Malignancy
• Nephrotic syndrome
• Transfusion

Question 16

What clot-based assays will be abnormal in a patient with an acquired FVIII inhibitor?

Answer 16

aPTT is prolonged

Mixing study:

• aPTT shortens and then proglongs
  => presence of VIII inhibitor

Question 17

What is the difference in presentation of acute vs. chronic DIC?

Answer 17

• Acute
  
  • Clotting factors depleted rapidly
  • More bleeding -> shock
  • MAHA
• Chronic
  
  • Liver and bone marrow can compensate
  • More clotting
  • More often seen in malignancy

Question 18

What is the treatment for acquired FVIII inhibitors?

Answer 18

• Prevent bleeding
  
  • Low titer: vasopressin + FVIII concentrate
  • High titer: Prothrombin complex concentrate + recombinant FVIIa
• Get rid of the antibody
  
  • Immunosuppressant
  • Rituximab

Question 19

Are hemarthroses more common in congenital or acquired hemophilia?

Answer 19

Congenital

Hemarthroses = blood within a joint

Question 20

How can liver disease can predispose someone to clotting?

Answer 20

Decreased anticoagulants

• Protein C
• Protein S
• Antithrombin

Question 21

Describe the pathophysiology of how anti-phospholipid syndrome leads to clotting

Answer 21

• Antiphospholipid antibody recognizes B2GP1 antigen bound to endothelium
• Binds
• Activates endothelium
  
  • ​Increased adhesion molecules, tissue factor
• Monocyte activation (upregulator of tissue factor and cytokines)
• Platelet activation –> clotting

Question 22

What is the dietary source of vitamin K?

Where is it absorbed?

Answer 22

Leafy green vegetables

Terminal ilium

Vitamin K deficiency can result from severe malnutrition

Question 23

Answer 23

C. prothrombin time

• D dimer is not specific*
• Everything else will be low in liver disease*