Hemophilia Flashcards
What activity levels for Hemophilia A and B classify the disease as either mild, moderate, or severe?
Mild: > 5% factor activity level, on assay.
Moderate: 1-5% factor activity level, on assay.
Severe: < 1% factor activity level, on assay.
Will Hemophilia A or B patients be more likely to develop inhibitors to factor recombination therapy?
Hemophilia A
20-25% of pts with severe hemophilia A will develop factor inhibitors. < 5% of severe hemophilia B pts will develop inhibitors.
When should you suspect factor inhibitor development? How do you test for it? What levels indicate severity?
Test for inhibitors of recombinant factor formulations when there is a sub-optimal or failure to rise in measure activity levels following infusion treatment.
Test using a Bethesda assay
< 5 Bethesda Units = Low-Titer Inhibitors
> 5 Bethesda Units = High-Titer Inhibitors.
How would you treat Low-Titer Inhibitor (+) Hemophilia Patients? What about High-Titer?
Low-Titer Inhibitor –> Increase the infusion requirement of the recombinant factors.
High-Titer Inhibitor –> Infuse activated Prothrombin Activated Complex Concentrates, either FEIBA (For Factor 8) or Recombinant Activated Factor VII (For Factor 7).
What monoclonal antibody can be used in patients with inhibitors?
Emicizumab
How will the Von Willebrand Disease assays appear in Type 1 (Quantitative) vWF Disease? In Type II (Qualitative)?
Type 1 Quantitative –> vWF activity DECREASED, vWF antigen DECREASED, Ristocetin Assay DECREASED, Multimer Pattern = NORMAL (uniformly less intense)
Type 2 Qualitative –> vWF activity DECREASED, vWF antigen DECREASED, Ristocetin Assay DECREASED, Multimer Pattern = Large and Intermediate Multimers are DECREASED/ABSENT.
What is different about vWF Type 2N?, what other disease does it resemble? How can you tell the difference between the two diseases?
vWF Type 2N will have normal vWF assay results and multimer pattern, ONLY abnormality will be DECREASED Factor VIII level.
Thus, this resembles Hemophilia Type A, you can tell the difference (for the most part) by the presence of affected women in the family pedigree, as Hemophilia A is x-linked recessive and predominately male disease.
What is special about vWF Type 2b assay results? What common lab abnormality is present in these patients?
Typically, Type 2 Qualitative –> Ristocetin Assay (RIPA) DECREASED….however in Type 2b, there is a gain-of-function mutation which leads to RIPA being INCREASED
Thrombocytopenia is commonly seen in these patients, due to a gain-of-function mutation.
How often can DDAVP be administered for treatment? What side-effects are common?
No more than 2 doses within 48 hours
Can cause tachyphylaxis and hyponatremia.
True/False: Pregnant Patients with vWF Disease will require increased treatment during pregnancy? When does this answer change?
False, most pregnant woman will have a physiologic increase in vWF due to the onset and duration of pregnancy (estrogen related?)
Patients may be at increased risk for bleeding 1-2 weeks post-partum due to loss of estrogen leading to decreased vWF levels.
What did the HAVEN 3 trial show? What is a major benefit in this medication administration?
Showed Emicizumab had a 97% reduction in annualized bleeding rates for patients with hemophilia, without any increase in blood clot risk.
This medication is sub-Q, whereas treatment of hemophilia with recombinant factor supplementation is an IV formulation which is needed to be given between 2-4 times per week.
