Hematology Flashcards
What is the function of thrombin?
Key to coagulation
Converts fibrinogen to fibrin
Activates factors V and VIII
Activates platelets
What is the function of antithrombin III?
Key to anticoagulation
Binds and inhibits thrombin
Inhibits factors IX, X, and XI
Heparin activates antithrombin III
What is the function of protein C?
Degrades factors V and VIII
Degrades fibrinogen
What is the function of plasmin?
Degrades factors V and VIII, fibrinogen, and fibrin
What factor has the shortest half life?
Factor VII
What is the only factor not synthesized in the liver?
Factor VIII —synthesized in the endothelium with vWF
The activity of what factors are lost in stored blood, but NOT FFP?
Factor V and VIII
What factors are vitamin K dependent?
Factors II, VII, IX, X, protein C and S
What works faster, PO or IV potassium?
PO. IV K+ takes 12 hours to take effect
How long does it take FFP to work?
Immediately
What is factor II?
Prothrombin
What is the half life of RBC?
120 days
What is the half life of platelets?
7 days
What is the half life of PMNs?
1-2 days
What is the function of prostacyclin (PGI2)?
From endothelium
Decreased platelet aggregation
Causes vasodilation
Increases cAMP in platelets
What is the function of thromboxane?
From platelets
Increases platelet aggregation
Causes vasoconstriction
Triggers release of calcium in platelets —> exposes GpIIb/IIIa receptor to initiate platelet-platelet binding and platelet-collagen binding (GpIb)
What product has the highest concentration of vWF-VIII?
Cryoprecipitate
What product has high levels of fibrinogen?
Cryoprecipitate
What product has the highest levels of all coagulation factors, protein C and S, and AT-III?
FFP
What 2 things cause release of factor VIII and vWF from endothelium?
DDAVP and conjugated estrogen
What lab is best to measure liver synthesis function?
Prothrombin time (PT)—measures factors II, V, VII, and X, fibrinogen
What is the normal activated clotting time (ACT)?
150-200 sec for routine anticoagulation
What is the goal ACT for cardiopulmonary bypass?
> 480 seconds
At what INR is it a relative contraindication for performing surgical procedures?
> 1.5
At what INR is it a relative contraindication to central line placement, percutaneous needle biopsies, and eye surgery?
> 1.3
What is the MCC of surgical bleeding?
Incomplete hemostasis
What is the MC congenital bleeding disorder?
Von Wilebrand’s disease
What is the MC symptom of vWF disease?
Epistaxis
What is the function of vWF?
Links GpIb receptor on platelets to collagen
What is the inheritance pattern of types I, II, and III VWF disease?
Types I and II are autosomal dominant
Type III is autosomal recessive
What test is abnormal in vWF disease?
Ristocetin test = bleeding time
PT normal
PTT can be normal or abnormal
What is the dysfunction in type I vWF disease?
Reduced quantity of vWF
What is the treatment for type I vWF?
Recombinant VIII:vWF, DDAVP, cryoprecipitate
What is the dysfunction in type II vWF disease?
Defect in vWF molecule so it doesn’t work well
What is the treatment for type II vWF disease?
Recombinant VIII:vWF, DDAVP, cryoprecipitate
What is the dysfunction in type III vWF disease?
Complete vWF deficiency (rare)
What is the treatment for type III vWF disease?
Recombinant VIII:vWF , cryoprecipitate
DDAVP will not work because there is no vWF to be released
What is hemophilia A?
Factor VIII deficiency
How is hemophilia A inherited?
Sex link recessive
What is the MC symptom of hemophilia A?
Hemarthrosis
If a patient has hemophilia A, what should the levels of factor VIII be pre-op and post-op?
Pre-op, need levels to be 100%
Post-op, levels should be 80-100% for 10-14 days post-op
What test is abnormal in hemophilia A?
Prolonged PTT and normal PT
Follow PTT Q8H after surgery
Which factor crosses the placenta?
Factor VIII—this is why newborns with hemophilia A may not bleed at circumcision
What should you do if patient with hemophilia A has joint bleeding?
DO NOT ASPIRATE
Ice, keep joint mobile with range of motion exercises, factor VIII concentrate or cryoprecipitate
What should you do if patient with hemophilia A has epistaxis, intractable hemorrhage, or hematuria?
Recombinant factor VIII, cryoprecipitate
What is hemophilia B?
Factor IX deficiency. Also known as Christmas disease
How is hemophilia B inherited?
Sex-linked recessive
If a patient has hemophilia B, what should the levels be pre-op and post-op?
Need level 100% pre-op
Must keep 30-40% for 2-3 days after surgery
What test is abnormal in hemophilia B?
Prolonged PTT and normal PT
What is the treatment for hemophilia B?
Recombinant factor IX or FFP
What labs are abnormal in factor VII deficiency?
Prolonged PT and normal PTT
Treatment for factor VII deficiency?
Recombinant factor VII or FFP
What signs are usually present in platelet disorders?
Bruising, epistaxis, petechiae, and purpura
What is Glanzmann’s thrombocytopenia?
GpIIb/IIIa receptor deficiency on platelets (usually links fibrin between platelets)
What is the treatment for Glanzmann’s thrombocytopenia?
Platelets
What is Bernard Soulier syndrome?
GpIb receptor deficiency on platelets —cant bind to collagen
What is the treatment for Bernard Soulier syndrome?
Platelets
What can cause acquired thrombocytopenia?
H2 blockers, heparin
How do we define uremia?
BUN > 60-80
What is the effect of uremia on hemostasis?
Inhibits platelet function by inhibiting release of vWF from endothelium
What is the treatment of bleeding due to uremia?
Hemodialysis-first line
DDAVP for acute reversal
Cryoprecipitate for moderate to severe bleeding
What causes heparin-induced thrombocytopenia (HIT)?
Thrombocytopenia due to anti-heparin antibodies (IgG heparin
What signs would you expect to see in a patient with HIT?
Platelets <100, a drop in platelets >50% of admission levels, thrombosis while on heparin
What kind of clot forms in HIT?
A white clot
How do you diagnose HIT?
ELISA for heparin Ab’s
Serotonin release assay
What is the treatment for HIT?
Stop heparin, start argatroban (direct thrombin inhibitor) for anticoagulation
Should you give platelets in HIT?
NO! Increases the risk of thrombosis
What lab values would be abnormal in disseminated intravascular coagulation (DIC)?
Decreased platelets
Low fibrinogen
High fibrin split products (high D-dimer)
Prolonged PT and PTT
What often initiates DIC?
Tissue factor
What is the treatment for DIC?
Treat the underlying cause
How long before surgery should a patient stop taking ASA?
7 days before
What lab value will be abnormal in a patient taking ASA?
Bleeding time
MOA of ASA?
Inhibits cyclooxygenase in platelets and decreases TXA2 —> irreversibly inhibits COX.
Platelets have no DNA, so cannot resynthesize COX
How soon should a patient stop clopidogrel (Plavix) before surgery?
7 days before surgery
MOA of Plavix?
ADP receptor antagonist
If patient on Plavix is bleeding, what should you do?
Give platelets
How soon should Coumadin be stopped before surgery?
7 days before surgery. COnsider starting heparin while Coumadin wears off
If patient on Coumadin starts bleeding, what should you do?
Give vitamin K and FFP
What do you want platelet levels to be before surgery?
> 50,000
What do you want platelet levels to be after surgery?
> 20,000
During what surgery is urokinase released, causing thrombolysis?
Prostate surgery
What is a Amicar and what is it used for?
Aminocaproic acid. Inhibits fibrinolysis by inhibiting plasmin
Does no bleeding at circumcision rule out bleeding disorders?
No because can still have clotting factors from mother
What is the most common congenital hypercoagulability disorder?
Factor V Leiden mutation
What is factor V Leiden?
Defect on factor V that causes resistance to activated protein C
What is the treatment for factor V Leiden mutation?
Heparin, warfarin
What is the treatment for hyperhomocysteinemia?
Folic acid and vitamin B12
What is the prothrombin gene mutation?
G20210A
Treatment for prothrombin gene defect?
Heparin, warfarin
Treatment for protein C and S deficiency?
Heparin, warfarin
Does heparin work for patients with AT-III deficiency?
Heparin does not work in these patients
What can cause AT-III deficiency?
Exposure to heparin
What is the treatment for AT-III deficiency?
Recombinant AT-III concentrate or FFP (highest concentration of AT-III) followed by heparin then warfarin
What is the treatment for dysfibrinogenemia, dysplasminogenemia?
Heparin, warfarin
What causes polycythemia Vera?
Bone marrow overproduction
What do we worry about in patients with polycythemia Vera?
Thrombosis
What is the goal before surgery in patients with polycythemia Vera?
Keep Hct < 48 and platelets <400 before surgery
What is treatment for polycythemia Vera?
Phlebotomy, ASA, hydroxyurea
What are the symptoms of anti-phospholipid syndrome?
Thrombosis, loss of pregnancy
Do all patients with anti-phospholipid antibody syndrome have SLE?
NO
What causes anti-phospholipid antibody syndrome?
Antibodies to phospholipids including cardiolipin and lupus anticoagulant
What lab values are abnormal in anti-phospholipid antibody syndrome?
Prolonged PTT —> BUT STILL HYPERCOAGULABLE
How to diagnose anti-phospholipid antibody syndrome?
Prolonged PTT (not corrected with FFP)
Positive Russell viper venom time
False-positive RPR test for syphilis
Treatment for anti-phospholipid antibody syndrome?
Heparin, warfarin
What is the most common factor causing hypercoagulability?
Tobacco
Name acquired hypercoagulability syndromes?
Malignancy, inflammatory states, IBD, infections, oral contraceptives, pregnancy, RA, post-op patients, myeloproliferative disorders
When does warfarin-induced skin necrosis occur?
When placed on Coumadin without being heparinized first
What causes warfarin-induced skin necrosis?
Due to short half-life of proteins C and S, which are first to decrease in levels compared with the procoagulation factors —> results in hyperthrombotic state
What patients are especially susceptible to warfarin-induced skin necrosis?
Patients with protein C deficiency
What are the key elements in the development of venous thrombosis?
Virchow’s triad
What is Virchow’s triad?
Stasis, hypercoagulability, and endothelial injury
What is the key element for development of arterial thrombosis?
Endothelial injury
Why does a hypercoagulable state occur during cardiopulmonary bypass? How do we prevent it?
Due to factor XII (Haegman factor) activation. Give heparin to prevent
What is the treatment for DVT after first, second third one? PE?
First: warfarin for 6 months
Second: warfarin for 1 year
Third or significant PE: warfarin for life
What are the indications for IVC filter?
Contraindications to anticoagulation
PE while on anticoagulation
Free-floating IVC, Iloilo-femoral, or deep femoral DVT
Recent pulmonary embolectomy
Should IVC be placed above or below renal veins?
Below
What is the source if a patient has a PE with a filter in place?
SVC (upper extremity), IVC above the filter, or gonadal veins
If your clinical suspension for a PE is high, what should you do?
Do not wait for the CT scan, give heparin bolus, unless there is a contraindication
If patient with PE is in shock despite massive knot ropes and pressors, what should you do?
Go to the OR for open removal or angiography for suction catheter
What is the most common region where PEs come from?
Ilio-femoral region
In what instances is aminocaproic acid used?
Used in DIC, persistent bleeding following cardiopulmonary bypass, and thrombolytic overdoses
What is the MOA of warfarin?
Prevents vitamin K-dependent decarboxylation of glutamic residues on vitamin-K dependent factors
Name the 3 oral, direct thrombin inhibitors
Dabigatran (Pradaxa), apixaban (Eliquis), and rivaroxaban (Xarelto)
In what patients are oral direct thrombin inhibitors used?
Patients with a. Fib NOT due to heart valve problem and in patients with DVT or PE
How do sequential compression devices help prevent DVT?
Improve venous return and induces fibrinolysis with compression (release of tPA from endothelium)
How does heparin work?
Binds and activates ATIII (1000x more activity) and increased neutralization of factors IIa and Xa
What is used to reverse effects of heparin?
Protamine (binds directly to heparin)
What is the half life of heparin?
60-90 minutes
What is the goal PTT when a patient is on heparin?
60-90 seconds
What are some long-term side effects of heparin?
Osteoporosis, alopecia
How is heparin cleared?
By the reticuloendothelail system (spleen, macrophages)
Which anticoagulant can be used during pregnancy, warfarin or heparin?
Heparin because it does not cross the placental barrier. Warfarin does cross placental barrier
What do we worry about when giving protamine?
Cross reaction with NPH insulin or previous protamine exposure
In 1% of patient, they get protamine reaction (hypotension, bradycardia, and decreased heart function)
What is the difference between low molecular weight heparin (enoxaparin) and unfractionated heparin?
Low molecular weight heparin has a lower risk of HIT and binds to antithrombin III but increased neutralization of JUST factor Xa —> not reversed with protamine
What is argatroban?
Reversible direct thrombin inhibitor
Where is argatroban metabolized?
In the liver
What is the half-life of argatroban?
50 minutes
When is argatroban often used?
In patients with HIT
What is bivalirudin?
Reversible direct thrombin inhibitor
Also known as angiomax
How is bivalirudin metabolized?
By proteinase enzymes in the blood
What is the half life of bivalirudin?
25 minutes
What is Hirudin?
Irreversible direct thrombin inhibitor
Where is hirudin derived from?
Leeches
WHat isn’t eh most potent direct inhibitor of thrombin?
Hirudin
What is Ancrod?
Malayan pit viper venom that stimulates tPA release
What are the 3 MC thrombolytics?
TPA, streptokinase, and urokinase
How do thrombolytics work?
Activate plasminogen
How do you follow effects fo thrombolytics?
Follow fibrinogen levels
Fibrinogen leaves <100 is associated with increased risk and severity of bleeding
What are absolute contraindications to thrombolytics?
Active internal bleeding
Recent CVA or neurosurgery (<3 months)
Intracranial pathology
Recent GI bleeding
What are major contraindications to thrombolytic use?
Recent surgery (<10 days), organ biopsy, or obstetric delivery, left heart thrombus, active peptic ulcer, recent major trauma, uncontrolled HTN, recent eye surgery
What are minor contraindications to thrombolytic use?
Minor surgery, recent CPR, atrial fibrillation with mitral valve disease, bacterial endocarditis, hemostasis defects (renal or liver disease), diabetic hemorrhagic retinopathy, pregnancy
