21 - Inherited Coagulation Disorders Flashcards
Common Inherited Coagulopathies
▪ Von Willebrand Disease
▪ Hemophilia A
▪ Hemophilia B
▪ Other factor deficiencies
lab abnormalities in congenital coagulopathies
Von Willebrand’s Disease (vWD)
- Von Willebrand Factor (vWF) produced in megakaryocytes and endothelial cells; stored/released from alpha granules of platelets in circulation
- vWF multimers cleaved by ADAMTS13
- vWF function:
- Binds to GIb/IX receptors of activated platelets to form a platelet plug
- Platelet aggregation via GPIIb/IIIa
- Binds to FVIII in plasma
- vWD is a genetic mutation in vWF gene that causes a quantitative or qualitative deficiency in vWF
- Mostly autosomal dominant
- Individuals with type O blood usually have 25-30% less vWF than other blood types
- There are acquired vWD diseases as well (in MPNs, aortic stenosis)
ADAMTS13 Function
coagulation disorder lab value meanings
* vWF:Ag
* vWF:RCo
* fVIII
* LD-RIPA
* PFA-100
* BT
- vWF:Ag – amount of vWF in the plasma, quantity
- vWF:RCo – ristocetin cofactor, ability of vWF to
function in platelet adhesion, activity or quality - fVIII – factor 8 activity
- LD-RIPA – low dose ristocetin-induced platelet
aggregation (2B and platelet-type) - PFA-100 – automated platelet function test
- BT – bleeding time
typical coagulation disorder lab value findings (table)
lab findings in common coagulation disorders (table)
Von Willebrand Disease - subtypes
Type I (75-80%) – Quantitative
* Lower than normal vWF; partial deficiency
* Autosomal dominant
* Mild symptoms
Type II (20%) - Qualitative
* Defect in structure of vWF or its binding to platelets
* Mild-moderate symptoms
* 2A – decreased vWF-platelet adhesion with deficiency of HMW multimers
* 2B – increased affinity for platelet GPIb
* 2N – Decreased binding to FVIII
* 2M – decreased vWF-platelet adhesion without deficiency of HMW multimers
Type III (rare) – Quantitative
* Almost absent or no vWF
* Autosomal recessive
* Severe symptoms including bleeding in muscles/joints
Flowchart for determining type of VWBF deficiency
Von Willebrand’s Disease: diagnosis
Von Willebrand’s Disease - treatment
* Desmopression (DDAVP)
* Causes release of granules containing vWF from platelets and endothelium
* Not useful/contraindicated in type IIB
* Non-specific Factors
* Antifibrinolytics/clot stabilizers
* Amicar (aminocaproic acid) - inhibits plasminogen activators which then interferes
with plasmin’s ability to lyse clots
* Lysteda (tranexamic acid) – synthetic derivative of lysine and binds to lysine binding sites on plasminogen which inhibits plasmin formation, also may directly inhibit plasmin
* Specific factors
* Humate P
* Alphanate
* Wilate
* Contain VIII and vWf in varying degrees
Factor VIII deficiency (Hemophilia A)
- X-linked recessive
- > 2000 different mutations known
- Lab values
- fVIII activity <40%
- Prolonged pTT
* Clinical manifestations depend on fVIII activity level - Early – joint, muscle, intracranial, GU, GI
- Later – hemarthrosis, infections, inhibitors
* Differential: - vWD type 2N
- vWD type 3
- fIX and fXI deficiency
* Treatment: replace with factor
Clinical Presentation - Factor VIII deficiency (Hemophilia A)
Mild 6-30%
– Rare spontaneous bleeds
– Bleeding after surgery
Moderate 1-5%
– bleeding during circumcision
– Infrequent spontaneous bleeds
– Bleeding after surgery
Severe <1%
– Frequent spontaneous bleeds
– Crippling hemarthroses
Hemophilia A Treatment - Drugs
Hemophilia A Treatment - classification and time course
Hemophilia B Treatment - Drugs
Factor Levels Needed to Achieve Hemostasis
