4.2 Secondary hemostasis and related bleeding disorders Flashcards
(29 cards)
Anticoagulantion factors, list them (3)
- Protein C and S
- ATIII
Secondary hemostasis, main idea
- Stabilization of weak platelet clot with thrombin (converts fibrinogen to fibrin for cross-linking)
- thrombin formed by Coag cascade
Pt with long-term antibiotic therapy:
-what coagulation problem to be concerned about?
- Vit K deficiency
- long term abx can kill gut bacteria that produce Vit K
Pt with deep bleeding into muscles and joints–suspect what?
Suspect a coagulation disorder (Secondary hemostasis disorder)
-primary hemostasis usu presents with mucosal, skin bleeding instead
If Vit K cannot be absorbed in the gut, what else might not be absorbed?
- fat-soluble vitamins: D,E,A,K
- possible reason: lack of bile
Why does liver failure lead to hemostasis problems? (2 reasons)
-also, what lab test to follow effect of liver failure on coagulation
Secondary hemostasis is affected by liver failure:
- lack of coag factor production
- lack of epoxide reductase activation of Vit K
Lab test: PT
What does vWF do other than bind to SEC?
- it stabilizes coag factor 8.
- loss of vWF (VW disease) leads to increased PTT
Von Willebrand Disease
- mech, etiology
- labs (platelets, PT/PTT, coag factors)
- Tx
- genetic vWF deficiency
- platelets cannot adhere to SEC. Decreased coagulation, skin and mucosal bleeding
- labs:
- platelets: normal
- PT: normal
- PTT: elevated (because vWF stabilizes F.8)
- Ristocetin test: abnormal (test shows binding of vWF to GP1b)
-Tx: Desmopressin (ADH analog)–it increases vWF release from Weibel-Palade bodies in endothelial cells
Tissue factor pathway inhibitor
Inhibits F.7 at the start of the extrinsic tissue factor pathway
Disorders of Secondary Hemostasis
- usual etiology
- clinical presentation
- usually Factor abnormalities
- deep tissue bleeding into muscles and hemarthrosis
- rebleeding after surgery (eg wisdom tooth extraction)
Epoxide reductase
- enzyme that activates Vitamin K in liver.
- coumadin inhibits this
Heparin vs Coumadin:
- mechs
- what lab test to monitor effect of each
Heparin:
- activate ATIII, which inactivates thrombin and coag factors
- use PTT
Coumadin:
- inhibit epoxide reductase, which activates Vit.K
- use PT
Disorders of Secondary hemostasis: -list them (7)
- Hemophilia A (F.8)
- Hemophila B (F.9)(Christmas disease)
- Coagulation Factor Inhibitor (Ab against coag factor)
- Von Willibrand Disease–vWF deficiency
- Vit K deficiency
- Liver failure:
1) decreased production of coag factors
2) decreased activation of Vit. K by epoxide reductase - Large-volume transfusion
Pt with suspected hemophilia. You ask about family history of bleeding disorders but none. Is hemophilia still on your differential?
Yes. 30% of hemophilia A and B are de novo mutations.
Desmopressin
- what does it tx other than diabetes insipidus
- mech?
- tx Von Willebrand disease
- it increases vWF release from the Weidel-palade bodies of endothelial cells.
Hemorrhagic disease of the newborn
- what is it
- tx
- Lack of GI colonization in newborns means little Vit K is produced.
- Vit K injections are given to all newborns as prophylaxis
Ristocetin test
- observe binding of vWF to GP1b
- Ristocetin induces this, inducing platelet adhesion/agglutination
- Used to diagnose VW disease: if there is a vWF deficiency, the platelets do not agglutinate. (abnormal result)
What is most common inherited coagulation disorder?
Von Willebrand Disease
Coagulation Factor Inhibitor
- what is this?
- how to differentiate this from Hemophilia
- Ab against coag factor (autoimmune).
- F.8 most common, resembling Hemophilia A
- how to differentiate: give F.8 to patient. If PTT is back to normal, then Hemophilia. If PTT still elevated, it is anti-F.8 Ab.
Vit K deficiency
- mech
- where does intake of Vit K come from (2)
- loss of activation of 2,7,9,10,C,S leads to coagulation problem
- Remember, Vit K is made by gut bacteria in addition to being in leafy vegetables
Vit K deficiency:
-what classic populations does this occur in (3)
- Newborns–lack of GI bacteria colonization that normally synthesize Vit K–Vit K injections are given to all newborns to prevent hemorrhagic disease of the newborn
- Long-term antibiotic therapy–can kill gut bacteria that synthesize Vit K
- Malabsorption–problem in fat-soluble vitamin absorption (eg no bile from bile duct obstruction). (problem absorbing all D,E,A,K vitamins)
Coagulation cascade, draw it out
- left side: contact pathway–SEC, 12, 11, 9, 8. (measure with PTT)
- right side: Tissue factor pathway–Trauma + Tissue factor (thromboplastin), 7 (measure with PT)
- bottom: X, 5, 2, 1
Hemophilia
-characteristic symptoms
-intramuscular bleeding, hemarthrosis
ATIII
- inhibits thrombin and coag factors
- activated by Heparin
