Fiser Chaper 2. HEMATOLOGY Flashcards
Intrinisic pathway
-Exposed collagen, prekallikrein, HMW kininogen, factor 7
–> activate 11
–> activate 9, then add 8
-> activate X, then add V
–> contvert prohrombin (2) to thrombin
-> thrombin converts fibrinogen to fibrin
Extrinisic pathway
Injured cells: tissue factor + 7
- > convert prothrombin to thrombin
- > thrombin converts fibrinogen to fibrin
Prothrombin complex
10, 5, calcium, platelet facotr 3, prothrombin
Forms on platelets
Catalyzes the formation of thrombin
What is the convergent point for intrinsic and extrinsic pathways
X
Tissue factor pathway inhibitor does what?
Inhibits factor 10
Factor13 does what?
Helps crosslink fibrin
Fibrin dose what?
Binds GpIIb/IIIa molecule to link platelets together and form platelet plug
Thrombin does what?
Key to coagulation
COnverts fibrinogen to fibrin and fibrin split products
Activates 5 and 13, and platelets
Key to normal AC?
Antithrombin III
What does AT-III do?
Key to anticoagulation
Binds and inhibits Thrombin
Also inhibits 9, 10, 11
How does heparin work?
Activates AT-III (up to 1000x normal activity)
Protein C and S
Both vitamin K dependent
C: decreades 5and 8 and fibrinogen
S: protein Ccofactor
Fibrinolysis needs what?
Tissue plasminogen activator: released from endothelium and converts plasminogen to plasmin
–> Plasmin degrades factors 5, 8, fibrinogen, fibron
–> lose platelet plug
Alpha-2 antiplasmin
Natural inhibitor of plasmin, released from endothelium
Shortest half life factor?
7
Only factor not synthesized in liver?
8 (endothelium)
Vit K dependent factors
2, 7, 9, 10, C and S
How long does vit k take?
6 hours to have effect
How long does FFP take?
Immediate, lasts 6 hours
Half life of RBCs, platelets, PMNs
RBCs: 120 days
Platelets: 7 days
PMNs: 1-2 days
PGI2
prostacyclin
from endothelium
decreases platelet aggregation and promotes vasodilation
antagonist to TXA2
TXA2
Thromboxane
From platelets
Increases platelets aggregation and vasoconstriction
Triggers release of calciumin platelets –> exposes GpIIb/IIIa receptor and causes platelet-to0platelet binding; platelet-to-collagen binding also occurs (Gp1b receptor)
Cryoprecipitate
highest conc of vWF-8; also has fibrinogen
used in vWF disease and hemophilia A
FFP
all coag factors, C, S, AT-III
DDAVP and conjugated estrogens
Cause release of 8 and vWF from endothelium
PT
measures 2, 5, 7, 10, fibrinogen; best for liver synthetic function
PTT
measures most factors except 7 and 13 (so does NOT pick up factor 7 def)
ACT goals
Activated clotting time
150-200 sec for AC
> 460 for cardioplum bypass
MCC surgical bleeding
Incomplete hemostasis
MCC congenital bleeding disorder
vWF disease
Types 1 (MCC) and 2 are AD, 3 (severe) is autosomal recessive
vWF
Links Gp1b receptor on platelets to collagen
vWF disease labs
INR/PT normal
PTT normal or abnormal
Prolonged bleeding time (ristocetin test)
vWF disease types
- MCC, reduced vWF quantity, tx recombinant 8:vWF, DDAVP, cryo
- defect, vWF molecule not working well, tx recombinant 8:vWF, cryo
- absent (rare), tx recombinant 8:vWF, cryo; DDAVP WILL NOT WORK
Hemophilia A
8 deficiency
sex-linked recessive
need levels 100% preop
80-100% for 10-14 days after surgery
prolonged PTT, normal PT
factor 8 crosses placenta so newborns may not bleed at circumcision
Join bleed: DO NOT ASPIRATE: tc ice, ROM exercises, factor 8 concentrate or cryo
Epistatxis or ICH or hematuria: tx recombinant factor 8 or cryo
Hemophilia B
9 deficiency
sex-linked recessive
need level 100% preop
30-40% for 2-3 days after surgery
prolonged PTT, normal PT
Tx recombinant factor 9 or FFP
Factor 7 deficiency
Prolonged PT/INR, normal PTT
Tx: recombinant factor 7 or FFP
Bruising, epistaxis, mucosal bleeding, petechiae, purpura
Platelet disorder (acquired thrombocytopenia, Glanzmann’s thrombocytpoenia, Bernard Soulier thrombocytopenia, Uremia)
Acquired thrombocytopenia causes
H2 blockers
Heparin
Glanzmann’s thrombocytopeniais a deficiency in what?
GIIIb/IIa receptor (so platelets cannot bind to each other)
Fibrin normally links the GpIIb/IIIa receptors together
Tx: platelets
Bernard-soulier thrombocytopenia is a deficiency in what?
Gp1b receptor (platelets cannot bind to collagen)
vWF normally bind Gp1b to collagen
Tx: Platelets
Uremia causes what?
Inhibits platelet function
Tx: HD first, DDAVP, platelets
HIT is due to what?
Antiplatelet antibodies (IgG PF4 ab)
Causing platelet destruction (can also cause aggregation and thrombosis)
White clot
LMWhas a decreased risk of causin HIT
Tx: Stop heparin, start argatroban (DTI)
DIC
Decreased platelets and fibrinogen; high fibrin split products and D-dimer; prolonged PT and PTT
DIC often initiated by waht factor?
Tissue factor
How long before surgery do patients need to stop asa? plavix? warfarin?
7 days
Aspirin MoA
Inhibits COX in platelets and decreases TXA2
Irreversible because platelets lack dNA so cannot resynthesize COX
Clopidegril MoA
ADP receptor antagonist
Tx: platelets
Prostate surgery effects on coag?
Can release urokinase, which activate plasminogen causing thrombolysis
Tx: E-aminocaproic acid (amicar)
Does normal circumcision rule of bleeding disorder?
No
Tooth extraction or tonsillectomy in history good way to tell bleeding risk?
Yes picks up 99% of patients with bleeding disorder
Epistaxis is common in what coag disorder?
vWF and platelet disorders
MCC congenital hypercoag disorder
Factor V LEiden: resistanceto activated proctein C, defect is on factor V
Tx: Heparin and warfarin
Hyperhomocysteinemia tx
B12 and folic acid
Prothrombin gene defect G20210A tx
Heparin and warfarin
Protein C or S def treatment
Heparin and warfarin
AT-III deficiency tx
Heparin does NOT work (heparin activates AT-III)
Can develop after prvious heparin exposure
Tx: Recombinant AT-III concentrate or FFP (highest conc of AT-III), followed by heparin and warfarin
Dysfibrinogenemia, dysplasminogenemia tx
Heparin and warfarin
PV
Defect in platelet function, can get thrombosis
Keep Hct<48, platelets <400 before surgery
Tx: phlebotomy and asa
Anti-phospholipid antibody syndrome
Not all have SLE
Get high PTT but hypercoagulable
Caused by cardiolipin and lupus anticoagulant abs
High PTT but hypercoagulable
Anti-phospholipid ab syndrome
Dx of antiphospholipid ab syndrome
Prolonged PTT, not corrected with FFP
Positive Russell vipor venom time
False-positive RPR test for syphilis
Antiphospholipid ab syndrome tx
Heparin and warfarin
MCC acquired hypercoagulability
Tobacco
Other: malignancy, inflammatory states, IBD, infection, OCP, pregnancy, RA, postop patients, myeloproliferative disorders
Hypercoagulability from cardiopulmonary bypass is due to what?
Hageman factor (Factor 12) activation
Tx: Heparin to prevent
Who is especially susceptible to warfarin induced skin necrosis?
Protein C deficiency
Protein C and S have shortest half life, so these anticoag factors first decrease before the coag factors decrease
Tx: Heparin
Virchow’s triad
Stasis, endothelial injury, hypercoagulability
Key element in development of arterial thrombosis
Endothelial injury
Postop DVT tx for 1st,2md and 3rd postop DVT
1st: 6 months warfarin
2nd: 1 yr warfarin
3rd or significant PE: lifelong warfarin
Who with a DVT gets a Greenfield filter?
Patients with contraindication to AC
Documented PE while on AC
Free-floating DVT in IVF, iliofemoral, or deep femoral
Recent pulmonary embolectomy
Treatment of PE
Heparin (thrombolytics no improvement in survival) or suction catheter-based intervention
If patient in shock despite massive inotropes and pressors, go to OR
Most common source of PE
iliofemoral
Procoagulant agents (anti-fibrinolytics)
E-aminocaproic acid (amicar): inhibits plasmin (which inhibits fibrinolysis), used in DIC, persistent bleeding after cardiopulm bypas, thrombolytic overdose, prostate surgery
Anticoagulation agents
Warfarin
SCDs
Heparin
LMWH
Argatroban
Bivalirudin
Hirudin
Ancrod
Warfarin MoA
Inhibits vit-K dep DECARBOXYLATION of glutamin acid residues on vit-K dep factors
SCD MoA
Improves venous return but also induced fibrinolysis with compression (releast of tPA fromendothelium)
Heparin MoA
Binds and activates AT-III (1000x more activity)
What can you use to reverse heparin?
Protamine (binds heparin)
Cross-reacts with NPH insulin or previous protamine exposure
1% get protamine reaction (hypotension, bradycardia, decreased heart function)
Heparin halft life
60-90 min
How is heparin cleared?
Reticuloendothelial system
Side effects of longterm heparin
Osteoporosis, alopecia
What AC to use in preg?
Heparin (does not cross placental barrier, while warfarin does)
LMWH
Enoxaparin, fondaparinux
Lower risk of HIT
Binds and activates AT-III but increases neutralization of just Xa and thrombin
NOT reversed with protamine
Argatroban MoA
Reversible DTI
Metabolized by liver
Half life 50 min
Used in HIT
Bivalirudin (Angiomax) MoA
Reversible DTI
Metabolized by proteinase enzymes in blood
Half life 25 min
Hirudin (Hirulog; from leeches)
Irreversible DTI
MOST POTENT DIRECT INHIBITOR OF THROMBIN
High risk for bleeding complications
Ancrod
Malayan pit viper venom
StimulatestPA release
Thrombolytics
Streptokinase
Urokinase
tPA
Thrmbolytic MoA
Activate plasminogen
Need to follor fibrinogen levels: <100 associated with increased risk and severity of bleeding
Tx for thrombolytic OD
E-aminocaproic acid (amicar)
CI to thrombolytics (tPA, urokinase, streptokinase)
Absolute: active internal bleeding, recent CVA or neurosurgery <3 mo, intracranial pathology, recent GIB
Major: recent surgery/organ bx/obstetric delivery <10 days ago, left heart thrombus, active peptic ulcer, recent major trauma, uncontrolled HTN, recent eye surgery
Minor: Minor surgery, recept CPR, A fib with mitral valve disease, bacterial endocarditis, hemostatic defects (renal or liver disease), diabetic hemorrhagic retinopathy, pregnancy
