Coagulation Flashcards
Coagulation part II Bleeding
Coagulation part II Bleeding
What are the defects and genetic inheritance in the following illnesses…
von Willebrands disease?
Hemophilia A
Hemophillia B
Hemophillia C
von Willebrands disease >> vWF; auto dom or auto Rec
Hemophilia A >> VIII; X-linked
Hemophillia B >> IX: X-linked
Hemophillia C >> XI: auto recessive
What are the causes to the following acquired disorders…
Blood loss?
Excess anticoagulation?
Disseminated Intravascular Clotting?
Inhibitors?
Blood loss >> platelet and clotting factor depletion
Excess anticoagulation >> inhibition of clotting factors
Disseminated Intravascular Clotting >> platlet or clotting factor consumption; excess fibrinolysis
Inhibitors >> antibodies to clotting factor usu. VIII
What is glycoprotein 1b?
is a component of the GPIb-V-IX complex on platelets.
The GPIb-V-IX complex binds von Willebrand factor, allowing platelet adhesion and platelet plug formation at sites of vascular injury.
It is deficient in the Bernard-Soulier syndrome. A gain-of-function mutation causes platelet-type von Willebrand’s disease.
What is von Willibrand Disease?
Dec/ Absent or abnormal VW multimers
S/S epistaxis (nose bleed), bruising, menorrhagia, GI, gingival bleeding
Classified into 3 types
Dx: BT bleeding time, FVIII, VWAg, RIPA
Rx: DDAVP
VWF binds to VIII
DDAVP: (desmopressin acetate) are a synthetic analogue of the natural pituitary hormone 8-arginine vasopressin (ADH), an antidiuretic hormone affecting renal water conservation.
What is Bernard Soulier Syndrome?
Deficiency of GP IB, Auto Recessive
Early childhood bruising, mucosal bleeding
Dx: Increased bleeding time, giant platelets, thrombocytopenia, Aggregation studies
Rx : platelets, DDAVP
What is Glanzmann’s Thrombasthenia?
See slide 50
Auto Recessive
Deficiency of glycoprotein IIb/IIIa
symptoms: early childhood bruising and bleeding
DX: bleeding time BT, platelet aggregation studies
What is glycoprotein IIb/IIIa?
In medicine, glycoprotein IIb/IIIa is an integrin complex found on platelets. It is a receptor for fibrin[1] and aids in platelet activation.
What is Virchow’s triad?
Endothelial injury
Abnormal blood flow
Hypercoagulability
What are the examples of endothelial injury?
Heart: endothelial injury adjacent MI, valvulitis
Atherosclerotic ulcerated plaques, vasculitis
Endothelial injury due to bacterial endotoxins, radiation, cigarette smoke products
End product: exposure of sub-endothelial collagen, platelet activation, adherence…..
What are examples in normal blood flow?
- Turbulance; arterial and cardiac thrombosis
- Stasis ; venous thrombosis
- Mechanisn:
- Disrupt laminar flow
- Prevent dilution of activated factors by fresh flowing blood
- Retard clotting factors inhibitors
- Promote endothelial cell activation
- Ulcerated atherosclerotic plaques, aneurysms-local stasis, MI, Mitral valve stenosis.
What is activated protein C resistance?
Activated Protein C cannot inactivate V, and V stays in circulation longer.
See below for details
AA replacement at one of three APC cleavage sites in the factor Va molecule
Factor V Leiden inactivated ~ ten times slower than normal factor V
Persists longer in the circulation results in increased thrombin generation and a mild hypercoagulable state
Individuals heterozygous for the factor V Leiden mutation have a slightly increased risk for venous thrombosis; homozygous individuals have a much greater thrombotic risk
What happens with a 20210 mutation?
causes increased prothrombin
increases risk for thrombosis