07: Bleeding Disorders Flashcards
1
Q
Hemophilia bleeding symptoms
A
- Hemarthorsis: bleeding of joints
- Cerebral hemorrhage
- Soft tissue hemorrhage
- Hematoma (bruising)
- Hematuria
- GI bleeding
- Surgical bleeding
- Epistaxis (nosebleed)
2
Q
Hemophilia phenotypes
A
- Mild: factor activity >5%, asymptomatic, only bleed when challenged (“on-demand treatment”).
- Moderate: factor activity 1-5%, variable penetrance and often need prophylaxis.
- Severe: factor activity <1%, require prophylactic treatment (i.e., factor replacement).
3
Q
Hemophilia treatment
A
- Prophylactic recombinant factor replacement: standard-of-care for moderate/severe disease
- Factor VIII: 3x weekly
- Factor IX: 2x weekly
- Both given IV
- On-demand factor replacement dosing:
- Based on factor type, weight, type of bleed/operation
4
Q
von Willebrand Disease (vWD)
A
- Autosomal dominant w/ variable penetrance
- Most common inherited hemorrhagic disorder
- Most common in O blood type (shorter t1/2)
- May have normal aPTT
- Clinical manifestations:
- Menorrhagia (abnormally heavy menstrual period)
- Easy bruising
- Dental and surgical bleeding
- Disease subtypes:
- 1: ↓synthesis vWF (common)
- 2: functional impairment (rare)
- 3: absent synthesis vWF (very rare)
- Diagnosis:
- 1: ↓Factor VIII antigen, vWF antigen, vWF:RCo activity; normal vWF multimers
- 2: ↓Factor VIII antigen, vWF antigen; ↓↓vWF:RCo activity
- 3: ↓↓↓ Factor VIII antigen, vWF antigen, vWF:RCo activity; vWF multimers very abnormal
5
Q
vWD Treatment
A
By increasing severity:
- None
- **Aminocaproic acid **(inhibit breakdown of already-formed clots)
- Desmopressin (ddAVP) (cause endothelial cells to release vWF)
- vWF concentrates
- Cryoprecipitates (precipitation of blood clotting factors, given in emergencies)
6
Q
Factor XI Deficiency
A
- Hemophilia C
- Autosomal recessive
- aPTT often (not always) prolonged
- May be discovered during surgery
- Treatment (only when necessary) = FFP
- Ashkenazi populations
7
Q
Vitamin K Deficiency
A
- Vitamin K sources: gut flora, diet
- Malnutrition and antibiotics (kill gut flora which produce Vitamin K) can prolong PT/INR
- Seen in patients taking warfarin, newborn infants
- Not producing clotting factors (II, VII, IX, X) or coagulation inhibitors (**PC **& PS). –> general coagulation defect
8
Q
Idiopathic/Immune Thrombocytopenic Purpura (ITP)
A
- Marked reduction in the number of circulating platelets, abundant megakaryocytes in the bone marrow, and a shortened platelet life span.
- Purpura: red or purple discolorations on the skin that do not blanch on applying pressure.
- Petechiae: pinpoint, round spots that appear on the skin as a result of bleeding under the skin.
- Blood smear: Large, few platelets
- Pathogenesis: Antiplatelet IgG directed against fibrinogen receptor (glycoprotein IIb/IIIa);** **spleen is primarily the site of platelet destruction, may also be a significant source of autoantibody production.
- ITP = diagnosis of exclusion (but may be found with other conditions)
9
Q
ITP treatment
A
- Steroids (prednisone or dexamethasone): first line; prevent macrophage removal of platelets
- IV Ig: overwhelm splenic macrophage Fc receptors so they won’t engulf platelets
- IV anti-D (WinRho): macrophages attack RBCs instead (can simply transfuse new RBCs)
- Splenectomy
- Rituximab (anti-B-cell Ab)
- Thrombopoietin mimetics: stimulate thrombopoietin receptor –> bone marrow production of platelets
- Romiplostim
- Eltrombopag
10
Q
Other common platelet disorders
A
- Uremic platelet dysfunction
- Renal failure –> bleeding
- Platelet dysfunction
- Endothelial dysfunction
- Partially treated w/ dialysis
- Acute tx: desmopressin (ddAVP) –> vWF
- Poisoned platelets
- ASA
- NSAIDs
- Clopidogrel
- Prasugrel
- Alcohol
- Normal platelet numbers, but abnormal function
- Medication-induced thrombocytopenia
- Ab formation (e.g., penicillins)
- Bone marrow suppression (e.g., chemo, anti-rejection Rx, alcohol)
11
Q
Other causes of thrombocytopenia
A
From most common to least common
- Sepsis
- Infx, cancer invading bone marrow
- Splenomegaly
- Leukemias and MDS
- Pelvic radiation
- Aplastic anemia
12
Q
Bernard-Soulier Syndrome
A
Rare inherited platelet disorder
Absence of GpIB receptor (vWF receptor)
13
Q
Glanzmann Thrombasthenia
A
Rare inherited platelet disorder
Absence of GpIIB/IIIA receptor (fibrinogen receptor)
14
Q
May-Hegglin Anomaly
A
Rare inherited platelet disorder
Macrothrombocytopenia 2/2 non-muscle myosin heavy chain mutation.
15
Q
Grey Platelet Syndrome
A
Rare inherited platelet disorder.
Platelet granule packaging defect.
