Chapter 2 - Hematology Flashcards
What are the three initial responses to vascular injury
Vasoconstriction, platelet adhesion, thrombin generation
Intrinsic Pathway starts with?
exposed collagen, prekallikrein, HMW kininogen, factor XII
Intrinsic pathway steps?
collagen, prekallikrein, hmw kininogen, factor XII—> activate XI —-> IX, then add VIII—> activate X then add V —> convert prothrombin (factor II) to thrombin—> thrombin converts fibrinogen to fibrin
Extrinsic pathway starts with?
Tissue factor from incured cells + factor VII
Steps of extrinsic?
tissue factor + factor VII —> activate X then add V—> confert prothrombin to thrombin —>thrombin then converts fibrinogen to fibrin
What is the prothrombin complex and what does it do?
X, V, Ca, PF-3, Prothrombin. It forms on platelets and catalyzes the formation of thrombin
What is the convergence point for both intrinsic and extrinsic paths?
Factor X
What dies the Tissue factor pathwa inhibitor do?
Inhibits factor X
What does Fibrin do?
combines with platelets to form the platelet plug to create hemostasis
What does factor XIII do?
helps crosslink Fibrin
Why is thrombin the key to coagulation? What does it activate?
Converts Fibrinogen to Fibrin and Fibrin split products. It activates factors V and VIII. It activates platelets
What is Protein C, what does it do?
Vitamin K-dependen, degrades factors V and VIII, Degrades fibrinogen
What is protein S, what does it do?
Vitamin K dependent, cofactor of Protein C
TPA is released from where and does what?
Released from endothelium, converts plasminogen to plasmin
Plasmin does what?
degrades factor V and VIII, fibrinogen, and fibrin. Causes destruction of platelet plug.
What is Alpha-2 antiplasmin?
natural inhibitor of plasmin released from endothelium
What factor has the shortest half life?
VII
What factors’ activity is lost in stored blood but not FFP?
V and VIII
What factor is not synthesized in the liver? where is it synthesized?
VIII- synthesized in the endothelium
What are the vitamin K dependent factors?
II, VII, IX, C and S
How long does it take for Vitamin K to take effect?
6 hours
How long does it take FFP to work and how long does it last?
immediately. Lasts 6 hours
What is factor II?
Prothrombin
What is the normal half life of RBC’s? Platelets? PMN’s?
RBC: 120 days, platelets 7 days, PMN’s 1-2 days
Where is Prostacyclin released from and what does it do?
Endothelium. Decreases platelet aggregation and causes vasodilitation (antagonistic to TXA2)
Thromboxane (TXA2)- where is it released from, what does it do?
Platelets. Increases aggregation and promotes vasoconstriction. Triggers the release of Ca2+ in platelets. It exposes GpIIb/IIIa recepter and causes platelet-platelet and platelet to collagen binding. activates PIP system to further release calcium.
What is in high concentration in cryoprecipitate and what is it used for?
high concentrations of vWf VIII, use in von Willebrands disease and hemophilia A. Contains fibrinogen.
What is in FFP?
High levels of all factors including V and VIII, C, S, AT-III
Why are DDAVP and conjugated estrogens used in the setting of coagulopathy?
Cause release of VIII and vWF from endothelium
What factors does PT measure?
II, V, VII, X, fibrinogen- best for liver synthetic function
What does PTT measure?
All but VII and VIII- Does not pick up VII deficiency.
What is an ACT?
Activated clotting time. 150-200 for routine anticoagulation, 460 for Cardiopulmonary bypass
What level INR is a contraindication for surgical procedures?
> 1.5
What level INR is a contraindication for central line, PCT biopsies, and eye surgery?
> 1.3
What is the most common cause of surgical bleeding?
Incomplete hemostasis
What is the most common congenital bleeding disorder?
von willebrands
what is the inheritance of von willebrand’s disease?
I and II are AD. III is AR.
what does vWf do?
links GpIb receptor on platelets to collagen
In von willebrand’s, what is the PT and PTT? Bleeding time?
PT normal; PTT normal or abnormal; bleeding time long (ristocetin test)
In these types of von willebrand’s disease there is a problem in vWf quantity
I- reduced, III- non. Treat with recombinant VIII:vWf. DDAVP, cryoprecipitate, conjugated estrogens.
This type of Von willebrand’s disease has a problem in the quality of vWf
Type II. recombinant factors, cryoprecipitate
What is Hemophilia A and what is its inheritance?
Factor VIII deficiency. Sex linked recessive.
Does factor VIII cross the placenta?
Yes. Circumcision may not cause bleeding in hemophila A pts.
What is the treatment for Hemophiliac joint?
no aspiration, ice, range of motion, factor VIII concentrate or cryoprecipitate.
What is Hemophilia B and what is its inheritance?
Factor IX deficiency- Christmas disease. Sex linked recessive.
What can cause an acquired thrombocytopenia?
H2 blockers, heparin
What is Glanzmann’s thrombocytopenia?
GpIIb/IIIa receptor deficiency- cannot bind to each other. Fibrin normally links them together at this site. Tx with platelets
What is Bernard Soulier?
GpIb receptor deficiency on platelets. Can’t bind to collagen. Tx with platelets.
What does Uremia do to platelets and what is the treatment?
Inhibits platelet function. Tx with hemodialysis first, then DDAVP, Platelets.
What does Ticlopidine do to platelets?
decreases ADP in platelets, prevens exposure of GpIIb/IIIa. Tx with platelets
What does Dipyridamole do to platelets?
inhibits cAMP phosphodiesterase, increases cAMP, decreases ADP induced platelet aggregation. Tx with platelets
What does Pentoxifyllene do to platelets?
inhibits platelet aggregation. Tx with platelets
What does Clopidogrel do?
ADP receptor antagonist. Tx w/platelets
PCN/cephalosporins do what to platelets?
bind platelets, can increase bleeding time.
HIT is caused by what antibody?
IgG PF4- causes platelet destruction
What type of clot does HIT cause?
White clot
What is the treatment for HIT?
stop heparin, argatroban, hirudin, ancrod, or dextran
What are the lab findings in DIC?
decreased platelets, prolonged PT and PTT, Low fibrinogen, high fibrin splits, high D-Dimer. Tx underlying cause
How many days before surgery should ASA be stopped?
7
How many days before surgery should coumadin be stopped?
7
What should platelets be at before surgery? after surgery?
50k; 20k
Prostate surgery has what effect bleeding?
can relase urokinase, activates plasminogen= thrombolysis. Treate with e Aminocaproic acid. Amicar.
Tooth extraction or tonsillectomy will pick up what percentage of Pt’s with a bleeding disorder?
99%
What is the most common cause of congenital hypercoagulability?
defect of factor V Leiden. resistance to activated protein C. Tx with heparin, warfarin
What is the treatment of hyperhomocysteinemia
folic acid and B12 (10% of spontaneous DVT’s)
What is the treatment for G20210 prothrombin gene defect?
heparin warfarin (5% of spontaneous DVT’s)
How does Antithrombin III deficiency develop and how is it treated?
can develop after previous heparin exposure. Treat with recombinant AT-III or FFP.
What antibody is the lupus anticoagulant, what does it do to PTT and to coagulation?
antiphospholipid antibodies. Cuases a procoagulant state. PTT is prolonged and is not corrected by FFP. Diagnose by positive russell viper venom time
What are some causes of acquired hypercoagulability?
Tobacco (#1), malignancy, inflammatory state, Inflammatory Bowel disease, oral contraceptives, pregnancy, rheumatoied, postop, myeloproliferative
How does cardiopulmonary bypass cause hypercoagulable state and what is the treatment?
Causes factor XII activation. Tx with heparin.
What is the pathogenesis of warfarin skin necrosis?
no heparin bridge. Protein C and S have short half life. Transient hypercoaculable state. Protein C deficiency especially susceptible.
What is Virchow’s Triad?
Stasis, Endothelial injury, hypercoagulable state
What is the key element in the development of an arterial thrombus?
endothelial injury.
How long must a pt be on warfarin for their 1st, 2nd, or 3rd DVT?
1= 6 months; 2= 1 year; 3 or significant PE= lifetime
What are the indications for a greenfield filter?
contraindications to anticoagulation, documented PE on anticoagulation, free floating ileofemoral, IVC, or femoral DVT, those that have had pulmonary embolectomy
Patient has pulmonary embolism and is in shock despite massive ionotropes, what do you do?
OR. If not in shock, give heparin (thrombolytics not proven to increase survival)
What percentage on positive V/Q scans have negative duplexes?
1/3
PE’s come from which site most commonly?
Iliofemoral region
How does warfarin work?
prevents vitamin K dependent decarboxylation of glutamic resudues on vitamin K-dependent factors
How does Dextran work?
Inhibits platelets and coagulation factors
How do SCD’s work?
improve venous return but also induce fibrinolysis with compression (TPA)
How does Heparin work?
potentiates antithrombin III
How is heparin reversed?
Protamine (1-1.5 protamine/100U heparin) follow PTT’s
What is the half life of heparin and how is it cleared?
60-90 minutes. Cleared by retuculoendothelial system
What are the long term side effects of heparin? Does it cross Placenta?
osteoporosis, alopecia. No- warfarin does
What are the problems/reactions of protamine?
cross reacts with NPH insulin or previous heparin exposure. 4-5% of patients get reaction- hypotension, bradycardia, decreased cardiac fxn
How dies Hirudin work? is it reversible?
From leeches- direct thrombin inhibitor. Irreversible. Want PTT 60-90. High risk of bleeding.
How does Argatroban work? where is it metabolized? half life?
Direct thrombin inhibitor; metabolized in the liver. half life 50 mins. Use for HITT
How does Bivalirudin work? where is it metabolized? half life?
Reversible direct thrombin inhibitor, metabolyzed by proteinase enzymes in the blood; half life 25-30 mins.
How does Ancrod work? where does it come from?
Malaysian pit viper venom; stimulates tPA release.
How does Amicar (e-aminocaproic acid) work?
Inhibits fibrinolysis by inhibiting plasmin. Use in DIC, persistent bleeding after cardiopulmonary bypass, thrombolytic overdose.
What are common thrombolytics? which one has high antigenicity?
urokinase, tPA, streptokinase. Streptokinase has high antigenicity
What is required for thrombolytics to work?
Guidewire must get past obstruction
What are acceptable Fibrinogen levels when using thrombolytics?
>
- <100 is associated with increased risk and severity of bleeding.
What is an absolute contraindication to using thrombolytics?
active internal bleeding, recent CVA (<2 months), intracranial pathology
Major contraindications to thrombolytics?
Recent surgery (<10 days); organ biopsy; left heart thrombus; active peptic ulcer; major trauma; uncontrolled htn
Minor contraindications to thrombolytics?
Minor surgery; cpr; afib with mitral valve disease; bacterial endocarditits; hemostatic defects; hemorrhagic retinopathy; preggers
