Hemorrhagic Disorders Flashcards
What are the two distinct functions of VWF in hemostasis?
- It acts as the fuzzy part of velcro, helping platelets stick down to the injured subendothelium.
- Ferries FVIII around the circulation—protecting it from degradation
How are Factor VIII and VWF related in plasma?
Noteworthy that VWF is generated from megakaryocytes, which also generate platelets.
What is the most common inherited bleeding disorder?
Von Willebrand Disease
What is the inheritance pattern of VWF?
Autosomal co-dominant
80% of patients with VWD have Type ___. Explain.
Type 1
This is a quantitative disorder (levels of VWF are about 30% of normal)
What are the clinical manifestations of VWD?
Mucocutaneous bleeding (esp. heavy menstrual bleeding)
Excessive bleeding after surgery (especially on mucosal surfaces)
NOT joint and muscle bleeding.
____ is found in 75-95% of women with VWD
Menorrhagia
Fibroids may “unmask” VWD
FHx may “mask” severity of problem if all girls are affected
What are the lab findings associated with Type 1 VWD? (include PT, aPTT, TCT, PFA-100, Factor VIII level, VWF antigen, and VWF activity)
Why is it difficult to test for VWD?
•VWD levels may vary within a single individual
- Increase with stress, anxiety, exercise
- Change with time of menstrual cycle
- VWD levels can be increased by estrogen in OCPs and HRT
- VWD levels are increased in pregnancy
- VWF activity assays are difficult to perform and are affected by specimen collection and processing
- VWD levels can vary with ABO type
- Type O makes VWF low
- Uncertain clinical significance.
What 3 criteria have to be assessed to diagnose VWD?
Personal history of abnormal bleeding
Family history of abnormal bleeding
Low levels of VWF (<30%)
How is VWD treated?
•Hormonal manipulations – esp. for menorrhagia
•Desmopressin (DDAVP)
- Releases FVIII and VWF from preformed stores in the endothelial cells
- Tachyphylaxis with repeat doses (stores have to fill back up)
- Hyponatremia with prolonged use
•Antifibrinolytics – stabilize clot on mucosal surfaces
- Tranexamic acid and epsilon aminocaproic acid are used
•Blood products and clotting factors
- Plasma-derived factor concentrates that contain FVIII and vWF.
•A new recombinant VWF product has just been introduced (given intravenously)
Hemophilia A is caused by a deficiency in _____
Factor VIII
Hemophilia B is caused by a deficiency in ____
Factor IX
Compare/contrast lab findings for Hemophilia A and Type 1 VWD. (Include PT, aPTT, TCT, PFA-100, Factor VIII level, VWF antigen, VWF activity)
How does symptom severity/disease manifestation of Hemophilia vary with Factor VIII or IX level?
Alex Atsalotofblood has hemophilia A and an aPTT of 50 sec. Billy Bleedsalot has hemophilia B and an aPTT of 50 sec. Normal is 25-35. We mix Alex’s and Billy’s plasma together. What is the resultant aPTT?
About 30 seconds
Hemophilia A is deficient in Factor VIII
Hemophilia B is deficient in Factor IX
A patients will have normal IX, B patients will have normal VIII, so mixed together, they can supply all the normal factors needed for a normal PTT test. Can correct for each other in this test.
Hemophilia A is a disorder of ____ hemostasis. VWD is a disorder of ____ hemostasis.
Hemophilia A is a disorder of secondary hemostasis.
VWD is a disorder of primary hemostasis.
Where to people with hemophilia typically bleed?
- Hemarthrosis (70-80% of all bleeding episodes) - bleeding into joints
- Bleeding into muscles
- CNS bleeding
- Retroperitoneal bleeding
- GU bleeding (Can be hard to control - a lot of fibrinolytic activity in urinary collection system. We can’t use anti-fibrinolytic agents because if we clot off the ureters, urine can’t exit kidney and kidney develops hydronephrosis which is BAD)
- Oro- and nasopharynx
Orthopedic complications of hemophilia:
- Recurrent joint bleeds
- Synovitis
- Cartilage damage
- Accelerated arthritis
- Muscle wasting, flexion contractures
- Need for joint replacement
How is Hemophilia treated?
•DDAVP - Used for mild hemophilia A (not B) before invasive procedures or to treat bleeding. Usually can only increase FVIII by 3 fold or so. [This releases FVIII (and WVF) from preformed stores in the endothelial cells - can’t use regularly b/c of tachyphylaxis and hyponatremia]
•Replace deficient factor
- Source of plasma
- Plasma-derived
- Recombinant
•Timing of delivery
- •Prophylactic (prevent bleeding)
- •On-demand (treat bleeding)
Hemophilia and Infections:
- In the 1980′s, approximately 90% of people with severe hemophilia were infected with the HIV virus
- Almost all patients with hemophilia who used factor products before 1988 were infected with Hepatitis C (HCV).
- In 2009, a UK patient with hemophilia was diagnosed at death with variant CJD (Creutzfeld Jakob disease) —felt to have infected the patient via infusion of clotting factor
Hemophilia and Inhibitors:
- Some proportion of patients with hemophilia will develop neutralizing antibodies to clotting factor concentrates. These are inhibitors.
- 3-fold more common hemophilia A than Hemophilia B
- More common with certain mutations
- More common in non-Caucasians
- Increases cost, decreases QOL
A woman presents with abnormal bleeding. An aPTT is prolonged and corrects with mixing study. Factor VIII level is 10%. Could she have VWD, Hemophilia A, or both?
Both
(although less common, women can have hemophilia - could have Turner’s Syndrome (one X) with hemophilia, could have a homozygous recessive mutation, or could be a carrier with selective X inactivation/lyonization (most common).
A woman presents with abnormal bleeding. An aPTT is prolonged and corrects with mixing study. Factor VIII level is 10%. The PFA-100 is normal. Could she have Hemophilia A, VWD, or both?
Hemophilia A
(PFA-100 would be prolonged in VWD, because this is a disease of primary hemostasis)
