Module 4: Disorders of Hemostasis (from review- Coagulation disorders) Flashcards
coagulation disorders are due to (4)
Failure of synthesis
Production of abnormal molecules
Excessive destruction or consumption of factors
Inactivation of factor by circulating anticoagulants
Screening tests
PT
PTT
PT test is for which factors
Extrinsic
Factors II, V, VII, X, I
Silly Sluts Love Pillow Fights
PTT test is for which factors
Intrinsic
All factors except III, VII, XIII
Horney Prostitutes Have Coitus And Spread Legs For Precious Pennies
Inherited disorders
all factors can be deficient
3 common inherited disorders
Hemophilia A (factor VIIIc) Hemophilia B (factor IX), christmas disease Von Willebrands Disease
Severity of bleeds %
For factors IX, VIII, X, V, II, I
Severe
What factors cause a marked prolonged PTT but no clinical bleeding (3)
XII, HMWK, PK
What factors cause a disproportionate mild bleed (2)
XI, VII
What factors cause a disproportionate severe bleed (1)
XIII
Normal male and normal female
children all normal unless there is a mutation
Normal male and carrier female (undiagnosed)
most common combination which perpetuates the disease
produces XhX, XX, XhY, XY
50% normal (male and female)
25% carriers (female)
25% hemophiliacs (male)
What is the most common bleeding disorder
von willebrands disease
what is the most common hemophilia
Hemophilia A
Hemophilia A
Factor deficient: VIIIc
Gene affected: Xq28
Therapy: factor VIII infusion
Complication: development of immune VIII antibodies
Hemophilia B
Factor deficient: IX
Gene affected:Xq27
Therapy: Prothrombin group concentrate or IX concentrate
Which hemophilia therapy lasts longer and why
IX because of its longer half-life
Therapy is given less often which reduced the chance of developing antibodies against the therapy
What type of disorder is Von Willebrands disease
platelet adhesion
von Willebrands Disease
What chromosome is affected: 12
Treatment: VIII concentrate
Tests for workup: Plt agglutination with ristocetin, plt aggregation with ristocetin (reduced)
3 types of von Willebrands Disease
Type 1 (most common)
Type 2
Type 3
Lab findings for Hemophilia A
Plt count: normal
Bleeding time: normal
PT: normal
PTT: prolonged
Lab findings for Hemophilia B
Plt count: normal
Bleeding time: normal
PT: normal
PTT: prolonged
Lab findings for von Willebrands Disease, Type 1
Plt count: normal
Bleeding time: usually prolonged
PT: normal
PTT: usually normal but may be prolonged
Acquired coagulation deficiencies (5 types)
Much more common than inherited Circulating abnormal anticoagulants and antifactors Vitamin K deficiency Liver Disease DIC Disorders of Fibrinolysis
Circulating abnormal anticoagulants and antifactors
A) specific factor antibodies
B) non-specific inhibitors “antiphospholipid antibody”
-Lupus anticoagulant
-Anticardiolipin antibody
Test used to differentiate deficiency from circulating anticoagulants or antifactors: mixing study
Vitamin K deficiency
factors are not caboxylated and cannot bind calcium
Factors involved: Prothrombin group (II, VII, IX, X) and Protein C and S
PIVKA stands for: Proteins induced by vitamin K absence = non carboxylated, inactive abnormal prothrombin factor molecules
Oral anticoagulant: Warfarin (Coumadin)
Liver Disease
reduced production in diseased hepatic cells
Factors involved: II, VII, IX, X, V, I
2 liver disorders that affect coagulation
Obstructive jaundice :cannot absorb Vitamin K
Severe hepatitis: Damaged cells produce less factor
3 things destruction of liver cells may result in
DIC: coagulation factors are not removed
Released increased amounts of tPA from hepatic cell triggering fibrinolysis
Spenomegaly, increasing splenic sequestering of platelets
DIC results in
widespread intravascular coagulation and secondary fibrinolysis
Results in: consumption and destruction of coag factors until they are deficient; thrombocytopenia; abnormal bleeding
causes of DIC
any situation which causes exposure of a lot of foreign surfaces to the blood, or the widespread release of coagulation activators (FIII) or activators of fibrinolysis
DIC laboratory findings should confirm (4)
activation of coagulation
activation of fibrinolysis
inhibitor consumption
end organ damage or failure
Main lab results for DIC
Factor deficiencies (cause prolonged PT/PTT) Thrombocytopenia Increased fdp, FDP Increased D-dimer Schistocytes (broken up RBC)
Disorders of fibrinolysis
Primary: activation of fibrinolysis in the absence of coagulation
Secondary: whenever fibrin is deposited as normal (but if abnormal DIC)
Therapeutic: injection of direct plasminogen activators
Impaired Fibrinolysis: due to decreased production, increased destruction or increased inhibition of plasminogen, plasminogen activators or plasmin
Differentiate primary from secondary fibrinolysis
Fibrinogen degradation product test:
Primary = pos
Secondary = pos
D dimer test: Fibrin degradation products:
Primary = NEG
secondary = pos
Thrombosis is
abnormal formation in circulation of solid, localized masses of fibrin and/or platelets that cause partial or complete blockage of vessels
Thromboembolism
thrombi break away and block smaller vessels
pulmonary embolism is
obstruction of pulmonary artery or branch of
Usually from DVT (deep vein thrombosis)
3 factors involved in forming a thrombus are
slowed blood flow
hypercoagulability
vessel wall damage
thrombi
multiple blood clots
thrombus
single blood clot
Inherited disorders
Factor V leiden gene mutation (protein C resistance) Antithrombin III Protein C or S deficiency Homocysteinuria Dysfibrinogenemia Abnormal plasminogen Prothrombin G20210A Variant
What immune condition is an acquired coagulation deficiency and also an acquired disorder that promotes thrombosis
lupus anticoagulant
Factor V Leiden gene mutation (protein C resistance)
most common cause of increased risk of venous thrombosis
Produce an abnormal factor V molecule that resists the action of activated protein C, thus the factor is inappropriately maintained in an active form and therefore continues to promote coagulation
Antithrombin III
normally works with heparin to inhibit factors
Inadequate inhibition of thrombin, Xa and IXa
Protein C or S deficiency
inadequate inhibition of V and VIII
impaired activation of fibrinolysis because activated protein C inhibits antiplasmin
Homocysteinuria
damaged endothelium by deposits of amino acid causes activation of coagulation and atherosclerosis
Dysfibrinogenemia
abnormal fibrinogen makes abnormal fibrin that will not neutralize thrombin
Abnormal plasminogen
impaired formation of plasmin
Prothrombin G20210A variant
abnormal allele of II = increased II levels = increased thrombosis
