257 - Acquired Coagulopathies Flashcards
Which coagulation/anticoagulation proteins are Vitamin K dependent?
- Pro-coagulant
- II
- VII
- IX
- X
- Anti-coagulant
- Protein C
- Protein S
What two molecules are required for the action of coagulation factors?
Phospholipids
Calcium
Anti-phospholipid antibodies! Can interfere with clotting times, but more associated with clotting than bleeding
What is the treatment for DIC?
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)
What is a key difference in the lab values of DIC and TTP?
DIC will have prolonged PT and PTT
TTP (and HUS) will have normal PT and PTT
How is a Bethesda assay performed?
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
What is the treatment for vitamin K deficiency?
- If no bleeding
- Oral vitamin K
- Give subcutaneous only if malabsorption or NPO
- If bleeding
- IV vitamin K
- Plasmaproducts (FFP or prothrombin complex concentrates)
What kind of inhibitors are present in congenital vs. acquired hemophilia?
Congenital hemophilia has alloantibodies
Acquired hemophilia has autoantibodies
Not exactly sure why this is - lmk if you have any ideas!
List 2 key differences between antiphospholipid antibody syndrome and F VIII inhibitor (acquired hemophilia A)
(bleed or clot? and what level of FVIII?)
- 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*
What are the criteria for diagnosing anti-phospholipid syndrome?
- 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
List 4 ways that liver disease can predispose somebody to bleeding
- 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
How will these labs change in DIC?
- PT/PTT
- D-Dimer
- Fibrinogen
- Platelets
- PT/PTT - High
- D-Dimer - High
- Fibrinogen - Low
- Platelets - Low
Will also see MAHA; elevated LDH + schistocytes on blood smear
List 3 clinical manifestations of anti-phospholipid syndrome
Venous thrombosis
Arterial thrombowiss
Adverse pregnancy outcomes
May also see thrombocytopenia, hemolytic anemia, livedo reticularis, cognitive deficits, cardiac valvular disease…
Describe the pathophysiology of DIC
- 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
Which newborns are at risk of vitamin K deficiency?
All of them!
Usually given vitamin K shot
List the causes of DIC (8)
SSTOP Making New Thrombi
- Sepsis
- Snake bite
- Trauma
- Obstetric complication
- Pancreatitis (acute)
- Malignancy
- Nephrotic syndrome
- Transfusion
What clot-based assays will be abnormal in a patient with an acquired FVIII inhibitor?
aPTT is prolonged
Mixing study:
- aPTT shortens and then proglongs
=> presence of VIII inhibitor
What is the difference in presentation of acute vs. chronic DIC?
-
Acute
- Clotting factors depleted rapidly
- More bleeding -> shock
- MAHA
-
Chronic
- Liver and bone marrow can compensate
- More clotting
- More often seen in malignancy
What is the treatment for acquired FVIII inhibitors?
-
Prevent bleeding
- Low titer: vasopressin + FVIII concentrate
- High titer: Prothrombin complex concentrate + recombinant FVIIa
-
Get rid of the antibody
- Immunosuppressant
- Rituximab
Are hemarthroses more common in congenital or acquired hemophilia?
Congenital
Hemarthroses = blood within a joint
How can liver disease can predispose someone to clotting?
Decreased anticoagulants
- Protein C
- Protein S
- Antithrombin
Describe the pathophysiology of how anti-phospholipid syndrome leads to clotting
- 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
What is the dietary source of vitamin K?
Where is it absorbed?
Leafy green vegetables
Terminal ilium
Vitamin K deficiency can result from severe malnutrition
C. prothrombin time
- D dimer is not specific*
- Everything else will be low in liver disease*
