Ch4 - 2) Secondary Hemostasis and Related Disorders Flashcards
What does secondary hemostasis do?
Stabilizes the weak platelet plug via the coagulation cascade
In secondary hemostasis the coagulation cascade generates?
thrombin, which converts fibrinogen in the platelet plug to fibrin.
In secondary hemostasis what happens to fibrin?
It is cross-linked, yielding a stable platelet-fibrin thrombus.
Where are the factors of the coagulation cascade produced?
In the liver in an inactive state.
What does activation of the factors of the coagulation cascade require?
exposure to an activating substance, Phospholipid surface of platelets, calcium
What are the activating substances involved in the activation of the factors of the coagulation cascade?
Tissue thromboplastin activates factor VII (extrinsic pathway). Subendothelial collagen activates factor XII (intrinsic pathway).
Where does the Calcium involved in the activation of the factors of the coagulation cascade come from?
derived from platelet dense granules
Disorders of secondary hemostasis are usually due to?
factor abnormalities
What are the clinical features of disorders of secondary hemostasis?
they include deep tissue bleeding into muscles and joints (hemarthrosis) and rebleeding after surgical procedures (e.g circumcision and wisdom tooth extraction).
Laboratory studies for Disorders of secondary hemostasis include?
PT (prothrombin time) and PTT (partial thromboplastin time)
Prothrombin time (PT)
measures extrinsic (factor VII) and common (factors II, V, X, and fibrinogen) pathways of the coagulation cascade
Extrinsic pathway of the coagulation cascade
factor VII
Common pathway of the coagulation cascade
factors II, V, X, and fibrinogen
Partial thromboplastin time (PTT) measures
intrinsic (factors XII, XI, IX, VIII) and common (factors II, V, X, and fibrinogen) pathways of the coagulation cascade
What is involved in Hemophilia A?
Genetic factor VIII (FVIII) deficiency, X-linked recessive (predominantly affects males)
Does Hemophilia A require a family history of it?
Can arise from a new mutation (de novo) without any family history
Hemphilia A presents with?
deep tissue, joint, and postsurgical bleeding
Clinical severity of hemophilia A depends on?
the degree of deficiency
Laboratory findings of hemophilia A include
- increased PTT; normal PT 2. decreased FVIII 3. Normal platelet count and bleeding time
What does treatment of hemophilia A involve?
recombinant FVIII.
What is christmas disease?
Hemophilia B - Genetic factor IX deficiency, Resembles hemophilia A, except FIX levels are decreased instead of FVIII
What is coagulation factor inhibitor?
Acquired antibody against a coagulation factor resulting in impaired factor function; anti-FVIII is most common,
Clinical and lab findings for hemophilia B?
its similar to hemophilia A, PTT does not correct upon mixing normal plasma with patient’s plasma (mixing study) due to inhibitor; PTT does correct in hemophilia A.
How can you tell the difference between hemophilia A and B?
mixing study
von Willebrand Disease
Genetic vWF deficiency
What is the most common inherited coagulation disorder?
von Willebrand disease
Does von Willebrand Disease result in qualitative or quantitative disorders?
Multiple subtypes exist, causing quantitative and qualitative defects;
What is the most common type of von Willebrand Disease?
is autosomal dominant with decreased vWF levels
von Willebrand Disease presents with?
mild mucosal and skin bleeding; low vWF impairs platelet adhesion.
Laboratory findings for von Willebrand Disease include
- increased bleeding time 2. increased PTT: normal PT ? Decreased FVIII half-life (vWF normally stabilizes FVIII); 3. Abnormal ristocetin test
What is usually not seen with von Willebrand Disease that is unusual
deep tissue, joint, and postsurgical bleeding are usually not seen.
Why is there an Abnormal ristocetin test in von Willebrand disease
Ristocetin induces platelet aggregation by causing vWF to bind platelet GPIb; lack ofvWF ?> impaired aggregation ?> abnormal test.
What is the treatment for von willebrand disease?
desmopressin (ADH analog), which increases vWF release from Weibel-Palade bodies of endothelial cells
How does vitamin K deficiency relate to hemostasis?
Disrupts function of multiple coagulation factors
What is involved in Vitamin K activation?
Vitamin K is activated by epoxide reductase in the liver
What does Activated vitamin K do?
it gamma carboxvlates factors II, VII, IX, X, and proteins C and S; gamma carboxylation is necessary for factor function.
Vitamin K deficiency occurs in?
- Newborns 2. Long-term antibiotic therapy 3. Malabsorption
Why is there vitamin K deficiency in newborns?
its due to lack of GI colonization by bacteria that normally synthesize vitamin K; vitamin K injection is given prophylactic ally to all newborns at birth to prevent hemorrhagic disease of the newborn
How does Long-term antibiotic therapy elad to Vitamin K deficiency?
disrupts vitamin K-producing bacteria in the GI tract
How does Malabsorption lead to Vitamin K deficincy?
leads to deficiency of fat-soluble vitamins, including vitamin K
What are some other causes of secondary hemostasis?
liver failure, large volume transfusion,
How does liver failure lead to secondary hemostasis?
decreased production of coagulation factors and decreased activation of vitamin K by epoxide reductase;
How is the effect of liver failure on coagulation followed?
followed using PT.
How does Large-volume transfusion lead to secondary hemostasis?
it dilutes coagulation factors, resulting in a relative deficiency
