Secondary Hemostasis and Related Disorders Flashcards
What is the purpose of secondary hemostasis?
Stabilizes the weak platelet plug via the coagulation cascade
What is generated during the coagulation cascade?
Thrombin
What does thrombin convert during the coagulation cascade?
Fibrinogen→ fibrin in the platelet plug
What is the outcome of secondary hemostasis?
Platelet-fibrin thrombus stabilizing the platelet plug
Factors of the coagulation pathway are produced by the liver in an inactive form. What are the 3 requirements for activation of these factors?
1) Exposure to an activating substance
2) Phospholipid surface of platelets
3) Calcium (derived from platelet dense granules)
What are the common clinical features seen with disorders of secondary hemostasis?
Deep tissue bleeding into muscles and joints (hemarthrosis) and rebleeding after surgical procedures
What does prothrombin time (PT) measure?
Measures extrinsic (Factor VII) and common (factors II, V, X and fibrinogen) pathways of the coagulation cascade
What does partial throboplastin time (PTT) measure?
Intrinsic (factors XII, XI, IX, VIII) and common (factors II, V, X, and fibrinogen) pathways of the coagulation cascade
Factor VIII deficiency that can either be X-linked recessive or arise from a new mutation without family history…
Hemophilia A
What is the common presentation for Hemophilia A?
Deep tissue, joint, and postsurgical bleeding
What are the findings on laboratory studies of a patient with Hemophilia A with respect to PT, PTT, FVIII, platelet count, and bleeding time?
PT: normal PTT: elevated FVIII: decreased Platelet count: normal Bleeding time: normal
What is the treatment for Hemophilia A?
Give recombinant FVIII
Factor IX deficiency that resembles Hemophilia A, except Factor IX is deficient…
Hemophilia B
Disease involving an acquired antibody against a coagulation factor that results in impaired factor function…
Coagulation factor inhibitor
What is the most common antibody involved in coagulation factor inhibitors?
Anti-FVIII
How is a coagulation factor inhibitor anti-FVIII differentiated from Hemophilia A?
A mixing study
Mix normal plasma with patient’s plasma—If PTT is corrected then Hemophilia A and if PTT remains elevated then its most likely a coagulation factor inhibitor against FVIII
The most common inherited coagulation disorder…
Von Willebrand disease
How does Von Willebrand disease present?
With mild mucosal and skin bleeding
What causes the mild mucosal and skin bleeding seen with Von Willebrand disease?
Low vWF impairing platelet adhesion
What is found on the labs of a patient with Von Willebrand disease with respect to bleeding time, PTT, and PT?
Bleeding time: increased
PTT: increased—vWF is needed to stabilize FVIII
PT: normal
What abnormal test is found when performed on patients with Von Willebrand disease?
Ristocetin test
Ristocetin induces platelet agglutination by causing vWF to bind platelet GPIb—No vWF=impaired agglutination→ abnormal test
What is the treatment for Von Willebrand disease?
Desmopression and ADH analog
Desmopression is used for the treatment of Von Willebrand disease. What is the mechanism of action of desmopression?
Increases vWF released from Weibel-Palade bodies of endothelial cells
What is disrupted when an individual has a vitamin K deficiency?
Disruption of multiple coagulation factors
Where and how is Vitamin K activated?
Activated in the liver by epoxide reductase
What is the function of activated vitamin K?
Gamma carboxylates factors II, VII, IX, X, proteins C and S
This is necessary for factor function
What are the 3 most common causes of Vitamin K deficiency?
- Newborn
- Long-term antibiotic therapy
- Malabsorption
Why is vitamin K deficiency common in newborns?
Lack of GI colonization by bacteria that normally synthesize vitamin K
What is given to newborns to prevent hemorrhagic disease?
Vitamin K injection
How does long-term antibiotic therapy cause a vitamin K deficiency?
The antibiotic disrupts the vitamin K-producing bacteria in the GI tract
How does malabsorption cause a vitamin K deficiency?
Malabsorption causes a deficiency of fat-soluble vitamins—AEDK
How does liver disease cause abnormal secondary hemostasis?
Decreased production of coagulation factors
Decreased activation of vitamin K by epoxide reductase
Which laboratory test is used to follow the effect of liver failure on secondary hemostasis?
PT
How does a large-volume transfusion cause abnormal secondary hemostasis?
Dilutes the coagulation factors
