Hematology Flashcards
Thrombin function
Converts fibrinogen to fibrin and split products
Activates factors V and VIII
Activates platlets
Initial 3 responses to vascular injury
Vasoconstriction
Platelet adhesion
Thrombin generation
Actions of Antithrombin III
Anticoagulant ( no clot)
Inhibits thrombin
Inhibits factors IX, X, XI
Heparin binds Antithrombin III
Protein C and S function
Protein C- vitamin K dependent, degrades factors V & VIII, degrades fibrinogen
(No clot)
Protein S- vitamin K dependent, protein C cofactor
Factors that cause fibrinolysis (no clot)
TPA- tissue plasminogen activator: released from endothelium -> converts plasminogen (follow fibrinogen levels)
Plasmin: degrades factors V & VIII, fibrinogen, fibrin
-> lose platelet plug
Alpha 2 antiplasmin: inhibits plasmin, released from endothelium
Clotting factor with shortest half life
Factor VII (7)
Only clotting factor NOT synthesized in liver
Factor VIII (8)
Synthesized in endothelium
Vitamin K dependent factors
II, VII, IX, X (2,7,9,10)
Protein C, S
Thromboxane (TXA2)
From platelets
Increases platelet aggregation and promotes vasoconstriction
Triggers Ca release-> expose GpIIb/IIIa->plt to plt binding
“Box in platelets”
Coagulation factor with highest amount of vWF VIII
Cryoprecipitate
Tx in Von Willebrand dz, hemophilia A VIII def
Coagulation factor with highest amount of all factors
FFP
Causes release of VIII and vWF from endothelium
DDAVP
Conjugated estrogens
PT measures
Factors II, V, VII, X, fibrinogen
Best test for liver synthetic function
Factors not measured with PTT
VII and XIII (does not pick up factor VII deficiency)
For anticoagulation: PTT 60-90
Want ACT (activated clotting time)
Routine anticoag 150-200
Cardiopulmonary bypass 400
What is most common congenital bleeding disorder?
VonWillebrand dz
Vonwillebrand dz
Type I & II - auto dominate - type I =most common
Reduced quantity
Type III - auto recessive - most severe bleeding
Defect in vWF
Links GpIb receptor on plts to collagen
Long bleeding time
What is factor VIII deficiency?
Hemophilia A
Sex-linked rec
Need 100% preop
Long PTT, normal PT
What is Christmas Dz?
Hemophilia B
IX (9) def
Need 50% preop
Long PTT, normal PT
Tx:factor IX or FFP
GpIIb/IIIa receptor deficiency on platlets ( can’t bind to each other)
Glanzmann’s thrombocytopenia
Platelet disorders
Acquired: H2 blockers, heparin
Glanzmann’s : receptor def- can’t bind to each other
Bernard soulier: GpII rec def- can’t bind to collagen
Uremia: inhibits receptors, vWF (tx: HD, DDAVP,cryo,plts, cong estrogens)
Plavix works by…
ADP rec antagonist- blocks so plts can’t bind
Tx: platlets
HIT - Heparin Induced Thrombocytopenia
Due to anti platlet antibodies - IgG PF4 antibody = platelet destruction
Forms: white clot
LMWH- May have decreased risk
Tx: stop heparin
Argatroban, hirudin, ancrod or dextran for anticoag
DIC disseminated intravascular coagulation
Low plts, fibrinogen
High fibrin split prod, D-Dimer
Long PT and PTT
Tx: underlying cause
ASA
Inhibits cyclooxygenase in platelets
Stop 7d before sx
Keep platelets > 50,000 before sx, > 20,000 after sx
Conditions causing hypercoagulability
Factor V Leiden Hyper homocysteinemia Protein C or S deficiency Anti-thrombin III deficiency Lupus Polycythemia Vera
Most common congenital hypercoagulability disorder
Factor V Leiden
Factor V Leiden
Factor V Leiden is a variant (mutated form) of human factor V that causes an increase in blood clotting (hypercoagulability). In this disorder, the Leiden form of factor V cannot be inactivated by protein C, and so clotting is increased
Tx: heparin, warfarin
Hyperhomocysteinemia
Homocysteine auto-oxidizes and reacts with reactive oxygen intermediates, damaging endothelial cells and increasing the risk of thrombus formation
Tx: folic acid & B12
Anti thrombin III Def causes?
Thrombus formation
Heparin does not work for treatment
Tx: AT III concentrate or FFP
Most common cause of acquired hypercoagulability
Tobacco
Warfarin induced skin necrosis
Due to short half life of protein C, S- increased likelihood of clotting
Tx: heparin
Key element in the development of arterial thrombosis
Endothelial injury
Most common location that PE come from
ileofemoral region
Tx of refractory bleeding in AV malformations
Thalidomide- stops angiogenesis
Way heparin works
Activates AT III (no clot)
Reverse: protamine (1-1.5 protamine/100U heparin)
Protamine cross reacts with NPH insulin
Protamine reaction: hypotension, bradycardia, decreased heart function
Argatroban
Direct thrombin inhibitor (stop clot)
Metabolized in liver
Good for pts with HIT
Bivalirudin
Reversible direct thrombin inhibitor ( no clot)
Procoagulants: amicar (aminocaproic acid)
Stops fibrinolysis by stopping plasmin
Use: DIC, thrombolytic overdoses
Thrombolytics
Streptokinase
Urokinase
tPA
To work- need guidewire past obstruction
Follow fibrinogen levels (fibrinogen <100- inc risk of bleeding)
Treatment of DIC
Treat underlying cause
Decreased ATIII, plasminogen
Platelet function
Adhesion
Activation
Granule release- ADP, thromboxane A2, PDGF, serotonin
Vascular endothelium maintains no clotting by these factors…
Prostacyclin, NO, tPA, thromboxane A2, serotonin, PDGF
The liver synthesizes all coagulation factors except….
Factor VIII (8)
Thrombin works by….
Activating platelets
Activating the coagulation cascade - factors 5,7,8
In order to avoid widespread Thrombosis fibrinolysis must occur…..how does this work?
Activation of plasmin
Plasminogen activated by tPA/urokinase/strepokinase—-> activates plasmin
Plasmin—> digests fibrin! factors 5, 8, 12, 2(prothrombin)
Aspirin and NSAIDs work by….
Block COX—> mediates synthesis of thromboxanes and prostaglandins
Asa - not reversible
NSAIDs - reversible
Thromboxane A2 works by…
Vasoconstriction
Platelet aggregation
Platelet activation
Plavix works by…
Blocking platelet receptors
