Hemostasis review excel Flashcards
Another name for prothrombin
Factor II
Another name for fibrinogen
Factor I
Zymogens in the coagulation cascade
Factor II, VII, IX, X, XI, XII, XIII ; Not Factor I, V, VIII
Large molecular weight cofactors in the coagulation cascade
Factor V, VIII, Tissue factor
Vitamin K dependent factors
Factor II, VII, IX, X, Protein C and S
Members of the “tenase” complex
Factor VIII, Factor IX, calcium, phospholipid surface. Hint for remembering - tenase activates Factor X
Members of the “prothrombinase” complex
Factor V, Factor X, calcium, phospholipid surface. Hint for remembering - prothrombinase activates thrombin
Members of the common pathway
Factor I, II, V, X, XIII
Members of the extrinsic pathway
Factor VII, tissue factor (aka tissue thromboplastin)
Members of the intrinsic pathway
Factor VIII, IX, XI, XII
Physiologic anticoagulants
Protein C, S, Tissue factor pathway inhibitor, antithrombin III, thrombomodulin
Factor deficient with hemophilia A
Factor VIII
Factor deficient with hemophilia B
Factor IX
Factor that acts as a carrier for factor VIII in the plasma
Von Willebrand factor
Factor that cleaves and inactivates factors Va and VIIIa
Protein C
Cofactor for protein C
Protein S
Factors that affect the PT/INR
Factor I, II, V, VII, X
Factors that affect the aPTT
Factor I, II, V, VIII, IX, X, XI, XII
Factor that crosslinks fibrin to form a “hard clot”
Factor XIII
Factor that binds to exposed collagen in a damaged blood vessel, promoting platelet adherence at the site of injury
Von Willebrand factor
Key protein in the fibrinolytic pathway
Plasmin
Factor exposed after vessel injury that initiates clotting
Tissue factor
Factor that when deficient prolongs the aPTT but doesn’t lead to bleeding risk
Factor XII
Binds with high affinity to heparin, which increases its activity many fold
Antithrombin III
What is the first thing that happens to blood vessels following injury?
Vasoconstriction. Result of release of endothelin by endothelial cells and neuro response.
What platelet receptor binds vWF?
Gp1b
Where does vWF come from?
Endothelial cell Weibel-Palade body and platelet granules, also some circulating in plasma
What receptors do platelets use to adhere to each other?
Gp2b/3a
What do platelets release after binding to vWF?
ADP and TXA2
What does ADP do for platelets?
Upregulates Gp2b/3a
What does TXA2 do for platelets?
Promotes aggregation
What drug irreversibly inhibits the production of TXA2?
Aspirin
What molecule do platelets use to link their Gp2b/3a receptors?
Fibrinogen
What is a primary hemostasis disorder?
Disorder of platelet aggregation either due to abnormal platelets or platelet destruction.
What are the typical clinical and lab findings of a primary hemostasis disorder?
Mucosal or skin bleeding (epistaxis is most common, intracranial is most serious), petechiae, purpura, ecchymoses, prolonged bleeding time, dec platelet count, increased megakaryocytic
What is the most common cause of thrombocytopenia?
ITP (autoantibody typically to Gp2b/3a)
T or F: You will see increase PT or PTT in ITP?
FALSE
How can you treat someone with ITP?
Given them IVIG. Distracts the splenic macrophages into eating IVIG rather than IG coated platelets.
What causes thrombotic thrombocytopenia purpura?
Decreased ADAMTS13 which normally cleaves vWF multimers into monomers. Usually due to an acquired antibody to ADAMTS13.
What causes hemolytic uremic syndrome?
infection with E. coli O157:H7 which damages endothelial cells
What are a classic smear finding of TTP and HUS?
Shistocytes (helmet cells)
In which disorder to you classically see enlarged platelets?
Bernard-Soulier syndrome. Due to Gp1b deficiency.
What is Glanzmann thrombasthenia?
Decreased platelet aggregation due to Gp2b/3a deficiency.
What is a secondary hemostasis disorder?
A problem with the coagulation cascade
Where are coagulation cascade factors produced?
The liver
What activates the extrinsic pathway?
Tissue thromboplastin which activates Factor VII
What activates the intrinsic pathway?
Subendothelial collagen which activates factor XII
T or F: Calcium is necessary for the coagulation cascade?
TRUE
T or F: Phospholipid surface is necessary for the coagulation cascade?
True. It is the surface of the platelet
PT tests for deficiency in which pathway(s)?
Extrinsic (and common)
PTT tests for deficiency in which pathway(s)?
Intrinsic (and common)
T or F: PT will be elevated in hemophilia A.
False. PTT will be elevated
T or F: PTT will be elevated in von Willebrand Disease.
True. vWF stabilizes factor VIII
How do you test for vW Disease?
Ristocetin test - ristocetin induces vWF to bind to platelets and promote aggregation, but if the patient has dec vWF or abn vWF, then platelet aggregation will be decreased.
How do you treat for vW Disease?
Give desmopressin (arginine vassopressin, a type of ADH analog) which releases vWF from Weibel-Palade bodies.
What does Vit K do in the coagulation cascade?
In the liver, gamma carboxylates factors II, VII, IX, X, protein C and S. Gamma carboxylation is the carboxylation of a glutamate residue which is important for calcium and platelet binding.
Where does vitamin K come from?
Produced by gut flora
What are the most common causes of vit K deficiency?
Malabsorption, disruption of gut flora (long-term antibiotic therapy), newborns who are not yet colonized.
What is the most common cause of loss of coagulation factors?
Liver failure and large volume transfusion (dilutes blood)
Which side of the coagulation pathway does heparin inhibit?
Intrinsic
T or F: Your body can develop antibodies to heparin?
True.
What is DIC?
Pathologic activation of the coagulation cascade. This results in clotting which uses up coag factors, resulting in bleeding other places.
What are the most common causes of DIC?
Obstetric complications, adenocarcinoma, sepsis, APL, exercise induced heat stroke, rattlesnake bite
What lab tests can done to find DIC?
Platelet count (dec), PT/PTT (inc), fibrinogen (inc), smear (shistocytes), fibrin split products/D-dimers (inc)
How is DIC treated?
Find the underlying cause and give cryoprecipitate
What is the final goal of the coagulation cascade?
Activation of thrombin (factor IIa)
What does thrombin do? (4)
1.) convert fibrinogen to fibrin 2.) promote platelet aggregation 3.) activates FV and VIII 4.) activates fibrinolytic factors and protein C 5.) activates Factor XIII
Which factor generates thrombin?
Factor X
Which factors generate Factor X?
Factors VIII and IX or Factor VII and tissue factor (aka tissue thromboplastin)
What does Factor XIII do?
Crosslinks fibrin and hardens the fibrin clot
How does Factor X generate thrombin?
It binds to cofactor V and converts prothrombin to thrombin
What is the Propagation Phase of coagulation?
The formation of the tenase/prothrombinase complexes which leads to the generation of thrombin
What is the Acceleration Phase of coagulation?
When thrombin enhances the activity of cofactors V and VIII greatly enhancing the activity of the tenase/prothrombinase complexes.
Which factors has no known function and does not affect bleeding?
Factors XII
What does Antithrombin III do?
1.) Inactivates thrombin 2.) inactivates Factors XII, XI, IX, and X
What does protein C do?
Cleaves Va and VIIIa (decreasing coagulation)
What does tissue factor pathway inhibitor do?
Inhibits Factor Xa and the VIIa-TF complex
What does tissue plasminogen activator do?
Activates plasminogen to plasmin
What does plasmin do?
Degrades fibrin => forming fibrin split products and D-dimer
What does alpha 2-antiplasmin do?
inhibits plasmin
What does Warfarin do?
Interferes with Vit K modification of cofactors (II, VII, IX, X)
What does plasminogen activator inhibitor-1 do?
Inhibits tissue plasminogen activator
What is normal bleeding time?
2-9 minutes
What is normal thrombin time (TT)?
12-18 seconds
What is thrombin time?
Measure the procoagulant activity of fibrinogen
What is normal activated thromboplastin time (aPTT)?
25-32 seconds
What is normal protime (PT)?
9-12 seconds
What is INR?
International normalized ratio - normal value 1.0. Allows the reporting of PT as ratio for controls in order to control for potency of thromboplastin used in the lab to start the reaction.
What is the inheritance patterns of hemophilia A and B?
both are X-linked recessive
When are minor hemophilia problems typically diagnosed?
After trauma or surgery which fails to heal well.
What is the inheritance pattern for Factor XI and Factor VII deficiency?
both autosomal recessive
What are the types of vW Disease?
Type 1 - partial vWF deficiency. Type 2 - abnormal vWF. Type 3 - total vWF deficiency
What is the most common acquired factor inhibitor disorder?
Autoantibodies to Factor VIII
How are acquired factor inhibitor disorders treated?
Immunosuppressants
What is the differential for prolonged PT > prolonged PTT?
Liver disease, Vit K deficiency, warfarin. Why? because liver disease affect the vit K modification of factors II, VII, X to a very high degree
What is the differential for prolonged PTT > prolonged PT?
DIC
What is the differential for prolonged PTT but not PT?
Heparin, Hemophilia A or B, Factor IX deficiency, Factor XII deficiency, Acquired hemophilia, von Willebrand Disease, Lupus anticoagulant
What is the lupus anticoagulant?
An IgG which reacts in the platelet membrane or endothelial cells. This results in prolonged PTT by binding up the phospholipid used to test PTT.
What are the most common causes of inherited hypercoaguable state?
Deficiencies of antithrombin III, protein C, protein S, or mutant Factor V which is not deactivated by protein C.
