Section 4: Vascular Disorders Flashcards
List hereditary vascular disorders
- Hereditary Hemorrhagic Telangiectasia
- Ehlers-Danlos Syndrome
List acquired vascular disorders
- allergic and drug-induced purpuras
- Henoch-Schonlein Purpura
- scurvy
- senile purpura
List disorders of platelet adhesion
- Bernard-Soulier Syndrome
- von Willebrand Disease (Types I, II, III, and Platelet Type)
- Autoimmune disorders (IgG anti-plt Ab)
- Myeloproliferative disorders
- MM and Waldenstrom’s
- Chronic liver disease (alcohol)
- Drugs
List disorders of platelet aggregation
- Glanzmann’s Thrombasthenia
- Hereditary afibrinogenemia
- Uremia
- Aspirin therapy
List disorders of release reaction
- Aspirin therapy
- Storage pool diseases (Delta SPD, Hermansky-Pudlak Syndrome, Gray Platelet Syndrome, Wiskott Aldrich Syndrome, Chediak Higashi…etc)
List disorders of decreased platelet production
- Congenital hypoplasia
- Fanconi hypoplasia
- Wiskott-Aldrich
- May Hegglin
- Neonatal hypoplasia
- Acquire hypoplasia (irradiation, drugs, ethanol, infections, pernicious anemia/folate deficiency…etc)
- Immune mechanisms
Hereditary hemorrhagic telangiectasia
- Vessel walls reduced to single EC layer -> inadequate support -> fragile vessels
- Bleeding: epistaxis, GIT, UG tract, possible in any organ
- Mouth, tongue, face dilated superficial vessels that blanche with pressure (telangiectasia)
Ehlers-Danlos Syndrome
- Indian rubber man with hypermobile joints and stretchy skin
- Collagen disorder
Allergic and drug-induced purpuras
- Autoimmune vascular injury or
- Drug causes Ab to form against vessel walls
Henoch-Schonlein Purpura
- Usually kid following upper resp infection
- IgA deposits in vessels
- Concerned about meningitis-associated rash (diff diagnosis)
- Rash, abdominal/joint pain, proteinuria/hematuria
- Small % advance to renal disease
Scurvy
- Vit C deficiency
- Reduced collagen synthesis leads to weakened capillary walls
- Bruising on back of legs
Senile purpura
- Elderly
- Usually forearms and back of hands
- Loss of collagen and subcut. fat/elastic fibers to support small blood vessels
Bernard-Soulier Syndrome
- Platelet function issue
- Lack of GpIb on platelet
Bernard-Soulier Syndrome lab findings
- Increased bleeding time or PFA
- Decreased platelets
- Large platelets
- Plt aggregation normal with all agents except ristocetin bc ristocetin causes agglutination via GpIb
von Willebrand disease Type I
- Platelet adhesion issue
- most common
- decreased amount of all multimers
- possibly due to abnormal release
- structure is normal
Where is vWF made and stored?
- Made in ECs and megakaryocytes
- Stored in alpha granules, present in plasma
vWF associated with ___
Factor VIII
Which coag function test depends on Factor VIII?
APTT
not PT
vWF Type I FVIII:C level
Low or normal
vWF Type I APTT
Prolonged or normal
bc no FVIII
vWF Type I PT
Normal
PT (prothrombin time)
PT testing measures how long it takes for blood to clot. It’s used to assess the function of certain clotting factors in the blood, specifically factors I, II, V, VII, and X. PT is often used to monitor patients on anticoagulant therapy (like warfarin) and to diagnose bleeding disorders
APTT (Activated Partial Thromboplastin Time)
measures the time it takes for blood to clot through the intrinsic and common pathways of the coagulation cascade. It primarily evaluates factors VIII, IX, XI, XII, and other components involved in clot formation. APTT is useful in diagnosing and monitoring patients with hemophilia and other clotting factor deficiencies
PFA (platelet function assay)
PFA testing assesses the function of platelets, which are crucial for blood clotting. It measures how well platelets stick together and form clots in response to certain chemicals or conditions. PFA tests are used to diagnose platelet function disorders and to assess the effectiveness of antiplatelet medications (like aspirin) in inhibiting platelet function (measures in time it takes for clot to form)
FVIII:C
measures the functional activity of Factor VIII in the blood. This test assesses how well Factor VIII is functioning in facilitating blood clotting, rather than simply measuring its presence. It is a crucial diagnostic test for conditions like hemophilia A, where there is a deficiency or dysfunction in Factor VIII coagulant activity.
“C” stands for coag activity
vWF disease Type II
- Decrease in high MW multimers only possibly due to instability
vWF disease Type III
- Most severe
- All multimers absent possibly due to reduced synthesis or rapid breakdown at site of synthesis
vWF disease platelet type
- GpIb has increased affinity for vWF
- Platelets agglutinate and are removed
List assays that quantitate plasma vWF or separate multimers on basis of molecular size
Quantitate
- ELISA
- Chemiluminescence immunoassay
- Automated method - latex particles
Separate
- Agarose gel electrophoresis
- Crossed immunoelectrophoresis
List assays that measure vWF activity
- Ristocetin induced plt agglut (RIPA)
- Ristocetin cofactor (vWF:Rco)
T/F
RIPA uses pt plasma and donor platelets
False
RIPA uses PRP-pt own plts and plasma
vWF:Rco uses pt plasma and donor plt
List other platelet adhesion disorders
- autoimmune disorders (IgG anti-platelet Ab)
- Myeloproliferative disorders
- MM and Waldenstrom’s
- Chronic liver disease (alcohol)
- Drugs
Glanzmann’s thrombasthenia
Platelets lack GpIIb/IIIa receptor for fibrinogen-mediated aggregation (platelet issue)
Glanzmann’s thrombasthenia lab findings
- Increased PFA
- PT normal
- APTT normal
- Plt count normal
- Plt aggregation only normal with ristocetin bc agglutination is fine (GpIb present)
Hereditary afibrinogenemia
No plt aggregation bc no fibrinogen
Uremia
- Toxins interfere with platelet function
- No adhesion or aggregation
Aspirin therapy
- Inhibits cyclooxygenase needed for TXA2 production - so no aggregation
- Could also be called Disorder of Release Reaction