Hemostasis Defects (complete) Flashcards
What are the major congenital disease states causing bleeding and/or clotting?
1) Hemophilia A (F8)
2) Hemophilia B (F9)
3) Hemophilia C (F11)
4) von Willebrand Disease
5) Factor VII deficiency
What are the major acquired disease states causing bleeding and/or clotting?
1) Liver disease
2) Vit K deficiency/Warfarin administration
3) Disseminated Intravascular Coagulation (DIC)
What is PT/INR? What is it testing?
- Prothrombin time (PT), international normalized ratio (INR)
- Measures extrinsic and common pathway
- Sensitive to Warfarin
PT: Time to clot in seconds (nl: 9-12)
INR: 1 is normal, 2 is twice normal (this is a standardized measurement b/c each test manufacturer is different)
What is APTT? What is it testing?
- Measures intrinsic and common pathways
- Sensitive to inhibition by heparin and fibrin split products
- Nl: 25-32 seconds
What is TT? What is it testing?
- Measures procoagulant activity of fibrinogen
- Sensitive to inhibition by heparin and fibrin split products
- Nl: 12-18 seconds
What is bleeding time? What is it testing?
- Measures platelet and vessel interaction
- Standardized cut + simplate bleeding time device on forearm => time to clot is measured
- Nl: 2-9 minutes
What is PFA? What is it testing?
- New device => perform in vitro bleeding time
- Can also determine platelet response to agonists
What is a differential diagnosis for an abnormal PT/INR?
Prolong PT:
- Vit K deficiency
- Warfarin therapy
- Liver Disease
- Factor 2, 7, 5, 10 deficiencies
- Fibrinogen deficiency
What is a differential diagnosis for an abnormal APTT?
Prolonged APTT:
- Hemophilia
What is a differential diagnosis for an abnormal TT?
Prolonged TT:
- Heparin contamination
- Fibrinogen deficiency
- Abnormal fibrinogen
What is a differential diagnosis for an abnormal bleeding time?
Prolonged BT:
- Thrombocytopenia
- von Willebrand disease
- abnormalities in platelet function
What are some other tests used to evaluate patients w/ thrombotic or bleeding disorders?
PFA-100: determines platelet response to agonists
Describe the clinical features for hemophilia A&B
- Unexplained hematomas, bruises, post-surgical or traumatic bleeding
- Joint bleeding => joint fusion/destructive arthritis
- CNS bleeds (COD usually)
- Retroperitoneal/psoas bleeds
Describe the molecular basis for hemophilia A&B
- X-linked deficiency of Factor 8 (A) or Factor 9 (B)
- Affects males, females = carriers
Describe the clinical features for factor 7 deficiency
- Severe bleeding disorder similar to hemophilia (joints, muscles, soft tissue, retroperitoneal space, CNS)
- Prolonged PT
- Normal PTT
Describe the molecular basis for factor 7 deficiency
- AR genetics
- Severe = homozygous
- underproduction of Factor 7
Describe the clinical features for von Willebrand disease
Primary hemostasis problems: bleeding in mucosa, under skin
- Prolonged BT
- Prolonged PTT
Describe the molecular basis for von Willebrand disease
- Platelets can’t adhere to exposed collagen/subendo
- Also deficiency in Factor 8 (vWF normally carries this guy)
- AD genetics
Describe the role of liver disease in coagulopathy
Liver produces almost all coag factors
Liver disease => deficiencies in those factors
Prolonged PT, PTT, TT
Describe disseminated intravascular coagulation (DIC)
- Systemic activation of coagulation => intravascular fibrin deposition & depletion of platelets and coag factors
- Fibrin dep => thrombosis and organ failure
- Depletion => bleeding
Explain diagnostic testing for DIC
- Low fibrinogen level
- Low platelet count
- Increased D-dimers
- Prolonged PTT
- Prolonged TT
Overall: TREAT THE UNDERLYING CONDITION
What is a lupus anticoagulant?
- IgG Ab => reacts against phospholipid in platelet membrane or endo cell
- causes Antiphospholipid Antibody Syndrome (APS)
How does a lupus anticoagulant affect coagulation?
- Although there is a prolonged PTT, there is no bleeding problem
- Actually causes thrombosis!!
How can one test for a lupus anticoagulant?
- dilute Russell’s Viper Venom Test (dRVVT) => directly activates factor 10
- Reveals a prolonged clotting time w/ dRVVT
