Congenital Bleeding Disorders (Ma. Ysabel Lesaca-Medina, MD) Flashcards
Phases of hemostasis
Vascular phases Platelet phase Coagulation phase Clot retraction Clot destruction
Automatic response of vessel to contain bleeding to site of injury
Transient vasoconstriction (reflex neurogenic and endothelin secretion)
Three As of the platelet phase
Adhesion
Activation
Aggregation
Platelet activators
ADP
Epinephrine
Serves as bridge in the aggregation of platelets
Fibrinogen
Goal of coagulation phase of hemostasis
Fibrin thombus formation (for stability)
Factors that play a role in clot destruction
Thrombin Factor XII (Hageman)
How is the intrinsic pathway activated?
Release of kininogens/kallikrein from injured surface
Pathway measured by PTT
Intrinsic pathway
Brad P(I)TT has a P(E)T!
What does automated PTT measure?
Factor XII
Trace the intrinsic pathway
XII -> XI -> IX + VIIIa -> X -> Common Pathway
Durations of intrinsic and extrinsic pathways
Intrinsic pathway: 20 – 30 seconds
Extrinsic pathway: 10 – 12 seconds
How is the extrinsic pathway activated?
Trauma
Trace the extrinsic pathway
Factor VII + Tissue Factor -> X -> Common pathway
Pathway measured by PT
Extrinsic pathway
Brad P(I)TT has a P(E)T!
Describe: Prothrombin Time
Time for III and CaCl to form a clot
Trace the common pathway
X -> Prothrombin to Thrombin -> Fibrinogen to Fibrin + Factor XIIIa -> Fibrin clot
Pathway measured by TT
Common pathway
How does deficiency in Factor XIII manifest
Normal hemostasis but persistent bleeding
Used to measure Factor XIII
Urea Clot Lysis Assay
Vitamin K-dependent factors
IX, X, VII and II (1972)
T/F: Factor VI has the shortest half-life at 8 hours
False
Factor VII. Factor VI does not exist.
First factor to get depleted
Factor VII
T/F: In acute Vit. K deficiency, only Factor VII decreases
True
T/F: Mucosal bleeding points to a coagulation problem.
False
It points to a platelet problem.
T/F: Deep tissue bleeding points to a coagulation problem.
True
When is there delayed onset bleeding?
Factor XIII deficiency
Liver disease affects the production of all clotting factors except these.
Factor VIII
vWF
T/F: A person with liver disease is more prone to thrombosis and exhibits a longer PT.
True
Given to the patient if vitamin K does not correct the PT.
Fresh frozen plasma
Examples of antiplatelet drugs
Aspirin
NSAIDs
Examples of anticoagulants
Heparin
Coumadin
Warfarin (combats vit. K)
Examples of antibiotics that can disrupt vit. K synthesis
Penicillin
Cephalosporin
Amphotericin
Useful in ruling in congenital bleeding disorders
Consanguinity
Criteria for menorrhagia
> 3 pads/day
Flooding
Hb < 10g/L
Common manifestation of hemophilia
Hemarthrosis
Indicative of a coagulation problem
Hemarthrosis
Intramuscular bleeds
Differentiate petechiae, purpura and ecchymoses on the basis of size
Petechiae - < 2 mm
Purpura - 2 mm to 1 cm
Ecchymoses - > 1 cm
Used to check the status of fibrinogen
Thrombin time
Blood is passed into a machine and the time it takes to measure hole closure corresponds to “bleeding time”
Platelet Function Analyzer (PFA)
Used to determine whether a patient has factor deficiency or antibodies against clotting factors
Mixing studies
T/F: If mixing patient blood with normal blood solves the problem, patient has antibody inhibitors in the blood.
False
Patient has factor deficiency.
Finding if clot lyses quickly in urea clot lysis assay
Factor XIII deficiency
Differentials if PT is elevated while PTT and platelet levels are normal
Early liver disease
Early Vit. K deficiency
Factor VII deficiency
Differentials if PTT is elevated while PT and platelet levels are normal
Factor VIII deficiency (hemophilia or vWD)
Factor IX, XI or XII deficiency
Inhibitors
Differentials if both PTT and PT are elevated and platelet levels are normal
Late liver disease
Late Vit. K deficiency
Massive transfusion
Differentials if PTT and TT are elevated and platelet and PT levels are normal
Heparin
Differentials if PTT, TT, PT and platelet levels are all normal
vWD Platelet function disorder Mild factor deficiency (VIII, IX, XI or XIII) Collagen disorder Vit. C deficiency
Differentials if platelet levels are decreased
CAMT, TAR, BSS, WAS, GPOS or ITP
Infection
Most common inherited bleeding disorder
Von Willebrand’s disease
Rare bleeding disorder where there is no megakaryocyte in the bone marrow
Congenital Amegakaryocytic Thrombocytopenia (CAMT)
Rare bleeding disorder where alpha-granules are lacking and patient is prone to infection
Gray Platelet Syndrome (GPS)
Rare bleeding disorder involving multiple congenital anomalies and thrombocytopenia
Thrombocytopenia with Absent Radius (TAR)
Rare bleeding disorder where platelets are small
Wiskott Aldrich Syndrome (WAS)
Most common severe congenital bleeding disorder
Hemophilia
Severity classifications for hemophilia
Severe - <1% activity
Moderate - 1 - 5% activity
Mild - 5 - 50% activity
Types of hemophilia
Hemophilia A - FVIII
Hemophilia B - FIX
Characteristics of hemophilia carriers
Factor VIII usually below normal levels
Mild bruising
Heavy menstrual periods
Complications of hemophilia
Hemarthroses
Intracranial hemorrhage
Intramuscular hematomas
Common sites of intramuscular hematomas
Anterior forearm
Anterior tibial compartments
General aim of hemophilia management
Correct FVIII to normal limits
Synthetic vasopressin analog that causes transient rise in FVIII and vWF and used for mild cases of hemophilia
Desmopressin or DDAVP
Used to treat moderate to severe hemophilia B
Fresh frozen plasma or cryosupernate (if available)
Used to treat moderate to severe hemophilia A in the absence of FVIII
Cryoprecipitate
Not used in treatment of hemophilic patients < 6 months old due to increased risk of inhibitor development
Preventive Factor VIII infusions
Quantifies inhibitor formation
Bethesda units (BU)
Define: 1 Bethesda unit (1 BU)
Amount of antibodyt hat neutralizes 50% of FVIII or IX present after 2 hours incubation at 37 degrees Celsius
Treatment for inhibitor patients with BU < 5
Increase dose of FVIII
Treatment for inhibitor patients with BU > 5
Bypass agents
Prothrombin complex concentrates
Immune tolerance induction
Immunosuppressive agents (rituximab)
Methods of immune tolerance induction (ITI)
Malmo Regimen
Van Cremeld Regimen
Bonn Regimen
Infectious diseases hemophilic patients are still at risk for during treatment
Hepatitis A
Creutzfeld-Jakob Disease
Parvovirus B19
Complication of gene transfer treatment of hemophilia
Hepatitis with concomitant destruction of transferred gene
Types of Von Willebrand’s Disease (vWD)
Type 1 - Classic partial quantitative deficiency
Type 2 - Qualitative deficiency
Type 3 - Near complete deficiency
Mode of inheritance of Von Willebrand’s Disease (vWD)
Autosomal dominant (mostly), but can be autosomal recessive
Most common cause of acquired vWD
Presence of antibody to vWF
T/F: Theoretically, there should be equal cases of vWD in both sexes
True
T/F: Sometimes, PTT is elevated in Type 2 vWD
False
Type 3 vWD
T/F: Platelet count may be decreased in vWD Types 2 and 3.
True
T/F: Blood type O has lower levels of vWF
True
Used for definitive testing of vWD
vWF assay
Treatment of vWD
Desmopressin (types 1 & 2)
Mode of inheritance of rare congenital coagulation factor deficiencies
Autosomal recessive
Congenital coagulation factor deficiency that causes the most bleeding
Factor X deficiency
Factor XIII deficiency
SSx of rare coagulation disorders
Umbilical stump bleeding Delayed cord separation Intracranial or intestinal hemorrhage Muscle hematomas Easy bruising Prolonged bleeding following prick
Disorder characterized by absence of GPIb/IX receptor
Bernard-Soulier Syndrome (BSS)
Mode of inheritance of Wiskott-Aldrich Syndrome
X-linked
Mode of inheritance of Gray Platelet Syndrome
Autosomal dominant or recessive
Mode of inheritance of Bernard-Soulier Syndrome
Autosomal recessive
Disorder characterized by defective GP IIb/IIIa interaction
Glanzmann Thrombasthenia (GT)
How much Factor VIII should be infused in non-life threatening bleeds?
25 - 40 U/kg
How much Factor VIII should be infused in life-threatening bleeds?
50 U/kg
T/F: vW antigen levels are normal in Type II vWD
True
Characteristics of Factor VII responsible for isolated prolonged PT in early liver disease or Vitamin K deficiency
Short half-life
