Coagulation and Hemophilia Flashcards
Hemophilia C is the deficiency in which Factor
Factor XI
Go through Intrinsic coagulation cascade
Contact activators (Prekallikrein and HMWK), then XII, XI, IX, and X (using VIIIa as a cofactor)
Why can patients with Factor XII and factor XI deficiencies have no bleeding phenotype?
Thrombin has a positive feedback (“thrombin burst”) that increases activation of XI and VIII
How does the DRVVT test work? If it’s positive, what does that suggest?
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.
What is the use of the reptilase time? (two things it is useful for)
Low fibrinogen
Dysfunctional fibrinogen
What factor deficiencies (3) are clinically silent but will prolong PTT?
HMWK and prekallikrien
Factor XII
What are the factor cutoffs for mild, moderate, and severe Hemophilia?
Mild: 5-40%
Moderate: 1-5%
Severe: <1%
1 u/kg of Factor VIII raises blood levels by how much?
2%
1 u/kg of Factor IX raises blood levels by how much?
0.75-1%
Goal factor levels for hemophilia patient with CNS bleed
80-100%
Goal factor levels for hemophilia patient with major surgery
80-100%
Goal factor levels for hemophilia patient with RP, epiglottis, floor of mouth bleed
80%
Goal factor levels for hemophilia patient with joint, muscle, GI tract, epistaxis, or hematuria
50%
How does DDAVP work to help bleeding in hemophilia?
It releases endogenous Factor VIII:vWF complexes from endothelia
What is the mechanism of action of Emicizumab
Binds to FIXa and FX to simulate the activity of Factor VIII
What medication can you NOT give Emicizumab with and why?
FEIBA because it causes a TMA
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?
Pathognomonic for a factor inhibitor - but the re-prolongation isn’t always present
Three prongs to treating acquired hemophilia A due to an inhibitor?
- Increase Factor VIII levels with recombinant porcine FVIII (Obizur)
- Use bypassing agents like recombinant FVIIa or aPCC
- Eradicate the inhibitor with Rituximab or prednisone +/- cyclophosphamide
What group of disorders is most closely associated with Factor V deficiency?
MPNs
You see a bleeding patient with a history of essential thrombocythemia with prolonged PTT, prolonged INR, normal thrombin time, normal reptilase time. Diagnosis?
Factor V deficiency
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?
Factor V deficiency
FFP to keep Factor V above 20%
(could also give platelets since FV is in platelet granules)
Goal Factor V levels in a bleeding patient with FV deficiency?
20%
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)?
Factor X deficiency
Replace FX with recombinant X or PCC
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)
Factor VII deficiency
Recombinant FVII and antifibrinolytics
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?
Factor XI deficiency (Hemophilia C)
FFP to increase FXI levels, also antifibrinolytics
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?
Factor XIII deficiency
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?
Factor XIII deficiency
If a patient with Factor XIII deficiency is pregnant, how do you manage it?
Give recombinant FXIII by five weeks gestational age to maintain levels above 10%
At what level of Factor XIII do you give prophylactic recombinant FXIII?
Less than 10%
Prolonged reptilase time is indicative of what disorders?
Dysfibrinogenemia or hypofibrinogenemia
In HHT, what is the inheritance pattern and what genes are commonly seen mutated?
AD, TGF-B pathway
Diagnostic criteria for HHT (4)
Telangectasias on mucocutaneous sites, face, ears, fingertips
Recurrent epistaxis
Visceral AVMs
Family history of HHT
Treatment of mild bleeding in HHT?
Antifibrinolytics
Treatment of severe bleeding in HHT? Aside from local procedures
Antiangiogenics (Bevacizumab)
