2 - Hematology Flashcards
Initial events for thrombus formation
Plt adhesion
Shape change
Granule release -> recruitment
Hemostatic plug at area of subendothelial collagen exposure
Three initial responses to vascular injury
Vascular vasoconstriction
Platelet adhesion
Thrombin generation
Activates factor XI
Exposed collagen + prekallikrein + HMW kininogen + factor XII
Activates factor IX
Activated XI
Activates factor X
Activated IX, add VIII
Convert prothrombin (factor II) to thrombin
Activate X, then add V
What does thrombin do?
Converts fibrinogen to fibrin
First step of extrinsic pathway
Tissue factor (injured cells) + factor VII
Second step of extrinsic pathway
Activate X, add V
Prothrombin complex
X, V, Ca, Platelet factor 3, prothrombin
Forms on platelets
Catalyzes thrombin formation
Tissue factor pathway inhibitor
Inhibits factor X
Fibrin activity
Links platelets together
Binds GpIIb/IIIa to form platelet plug -> hemostasis
Thrombin activity
Key to coagulation
Converts fibrinogen to fibrin and fibrin split products
Activates factors V and VIII
Activates platelets
Antithrombin III
Key to anticoagulation
Binds and inhibits thrombin
Inhibits factors IX, X, XI
Function of heparin
Activates AT-III (up to 1000x normal activity)
Protein C
Vitamin K-dependent
Degrades factors V and VIII
Degrades fibrinogen
Protein S
Vitamin K-dependent
Protein C cofactor
Fibrinolysis 1st step
Tissue plasminogen activator - released from endothelium and converts plasminogen to plasmin
Plasmin function
Degrades factors V and VIII, fibrinogen, and fibrin -> loss of platelet plug
Alpha-2 antiplasmin function
Natural plasmin inhibitor
Released from endothelium
Shortest factor half life
VII
Factors V and VIII - labile factors - stored activity?
Activity lost in stored blood
Activity not lost in FFP
Synthesis of factor VIII
Only factor not in liver
Synthesized in endothelium along with vWF
Vitamin K-dependent factors
II, VII, IX, X; protein C, S
Effect time of IV vitamin K
12 hours
Effect time of FFP
Immediate
Blood cell half-life
RBC: 120 days
Platelets: 7 days
PMNs: 1-2 days
Prostacyclin (PGI2) source/function
From endothelium
Decreases platelet aggregation, promotes vasodilation (antagonizes TXA2)
Increases cAMP in platelets
Thromboxane A2 source/function
From platelets
Increases platelet aggregation and promotes vasoconstriction
Triggers Ca release in plts -> exposes GpIIB/IIIa receptor, causes platelet-platelet binding, platelet-to-collagen binding
Cryoprecipitate
Highest concentration of vWF-VIII
Used in von Willebrand’s disease and hemophilia A
High levels of fibrinogen
FFP
High levels of all coagulation factors, protein C, protein S, AT-III
DDAVP/conjugated estrogens
Cause release of VIII and vWF from endothelium
Prothrombin time (PT)
Measures II, V, VII, X, fibrinogen
Best for liver synthetic function
Partial thromboplastin time (PTT)
Measures most factors except VII and XIII (does not pick up factor VII deficiency)
Also measures fibrinogen
Goal PTT for routine anticoagulation
60-90seconds
ACT goal time
150-200 sec for routine anticoagulation
>480 sec for cardiopulmonary bypass
INR level relative contraindication to surgery
> 1.5
INR >1.3
Relative contraindication to:
CVL placement
Perc needle biopsies
Eye surgery
MCC surgical bleeding
Incomplete hemostasis
MC congenital bleeding disorder
von Willebrand’s disease
MC Sx vWD
Epistaxis
Genetics of vWD
Types 1, 2 autosomal dominant
Type 3 autosomal recessive
Function of von Willebrand factor
Links GpIb receptor on plts to collagen
vWD Type I
Most common (70%), often only mild
Reduced quantity of vWF
Tx: recombinant VIII:vWF, DDAVP, cryo
vWD type II
Defect on vWF molecule itself, doesn’t work well
Tx: recombinant VIII:vWF, cryoprecipitate, DDAVP
vWD Type III
Complete vWF deficiency (rare)
Tx: recombinant VIII:vWF, cryoprecipitate
DDAVP WILL NOT WORK
Hemophilia A
VIII deficiency, sex-linked recessive
Prolonged PTT, normal PT (follow PTT q8h p surgery)
Tx with recombinant factor VIII or cryo
Goal levels in hemophilia A
Need 100% pre-op
80-100% for 10-14 days p surgery
Hemophilia B
IX deficiency, sex-linked recessive
Prolonged PTT and normal PT
Tx: recombinant factor IX or FFP
Goal levels in hemophilia B
Need 100% pre-op
Keep at 20-30% 2-3 days p surgery
Factor VII deficiency
Prolonged PT and normal PTT
Bleeding tendency
Tx: recombinant factor VII concentrate, FFP
Platelet disorder sx
Bruising, epistaxis, petechiae, purpura
Acquired thrombocytopenia
Can be caused by H2 blockers, heparin
Glanzmann’s thrombocytopenia
GpIIb/IIIa receptor deficiency on platelets
(fibrin normally links GpIIb/IIIa together)
Tx: platelets
Bernard Soulier
GpIb receptor deficiency on platelets (can’t bind collagen)
(vWF normally links GpIb to collagen)
Tx: platelets
Uremia (platelet disorder)
BUN>60-80
Inhibits plt function by inhibiting release of vWF
Tx: hemodialysis, DDAVP for acute reversal, cryo for moderate/severe bleeding
HIT
Thrombocytopenia d/t anti-heparin Ab -> plt destruction
Can also cause plt aggregation and thrombosis
Dx: plts <100, drop in plts > 50% admission levels, thrombosis on heparin
ELISA for heparin Abs, serotonin release assay
Tx: STOP heparin, start argatroban, avoid giving plts (risk of thrombosis)
DIC
Decreased plts, low fibrinogen, high fibrin split products (high D-dimer)
Prolonged PT and PTT
Often initiated by tissue factor
Treat underlying cause
ASA
Stop 7 days before surgery - prolonged bleeding time
Inhibits cyclooxygenase in plts and decreases TXA2
Plts lack DNA, cannot resynthesize COX
Clopidogrel
Stop 7 days before surgery, ADP receptor antagonist
Tx for bleeding: platelets
Coronary stent and need to stop Plavix for elective surgery
Tx: bridge with Integrin (eptifibatide [GpIIb/IIIa inhibitor])
Coumadin
Stop 7 days a surgery, consider starting heparin while Coumadin wears off
Tx for bleeding: Vit K and FFP
Plts goal for surgery
Want >50k before surgery
>20k p surgery
Prostate surgery and coagulation
Can release urokinase, activates plasminogen -> thrombolysis
Tx: aminocaproic acid (Amicar, inhibits fibrinolysis
Best way to predict bleeding risk
H&P
