Exam 4 Flashcards
What is localized bleeding? What is an example of it?
Bleeding from a single location such as an ineffectively sutured surgical site or AVM
What is generalized bleeding? Example?
Bleeding from multiple sites, spontaneous/recurring bleeding such as disorders of primary or secondary hemostasis
What is mucocutaneous bleeding? Example?
Bleeding in skin or at body orifices such as petechiae, purpura, ecchymoses associated with defects of primary hemostasis
What is anatomic bleeding? Example?
Bleeding in soft tissue, muscles, joints, deep tissues seen in secondary hemostasis - INTERNAL bleeding
What are the most common congenital coagulation deficiencies in order?
- VWD
- Factor VIII (Hemophilia A)
- Factor IX (Hemophilia B)
Acquired vs congenital bleeding disorders (how to differentiate)
Acquired: episodes begin after childhood
Congenital: relatives with similar symptoms, onset in infancy
What factors are decreased in liver disease?
Factor VII first, then Factor V
If you have a decrease in factor VII, but not factor V, is this liver disease?
NO
What factor decrease is a specific marker of liver disease?
Factor V
What increases with liver disease?
Fibrinogen, VWF, Factor VIII, Factor XIII
Chronic DIC - caused by decreased liver production of what?
Antithrombin, protein C, protein S
What test can be used to differentiate between liver disease and vitamin K deficiency? What are the results for each?
Factor V and Factor VII assays - both will be decreased in liver disease and only factor VII will be decreased in vitamin K deficiency
What test confirms dysfibrinogenemia?
Reptilase time test
How can renal disease lead to bleeding tendancies?
Renal failure is associated with PLT dysfunction and mucocutaneous bleeding leading to anemia and thrombocytopenia
How does a vitamin K deficiency or Coumadin treatment lead to bleeding?
Vitamin K deficiency will lead to decreased vitamin K dependent factors leading to increased bleeding, and coumadin treatment is an anticoagulant so too much can lead to bleeding
What is the treatment to overdose of coumadin?
administration of vitamin K
Briefly describe acquired hemophilia
Caused by autoanti-factor VIII often seen in elderly and associated with RA, IBD, and SLE
What is the most common factor inhibitor?
Factor VIII
What is the most prevalent congenital mucocutaneous bleeding disorder?
VWD
What is the cause of VWD?
Quantitative (type 1) and qualitative (type 2) VWF abnormalities
What is the result of VWD?
Decreased PLT adhesion to vessel walls leading to impaired primary hemostasis
Describe Type 1 and Type 2 VWD and which is more common?
Type 1 is a quantitative deficiency and is more common
Type 2 is a qualitative deficiency due to VWF function reduced
What is included in the VWD test panel?
VWF:Ag
VWF activity by ristocetin cofactor assay
Coagulation factor VIII assay
Hemophilia A
Factor VIII deficiency
Hemophilia A occurs mostly in _____ because the gene is present on the _________.
Males; X chromosome
Factor VIII deficiency significantly slows coag pathway’s production of ______.
Thrombin
Test results for Hemophilia A
PTT prolonged; PT, FBG, TT normal
Hemophilia B
Christmas Disease - Factor IX deficiency
Test results for Hemophilia B
PTT prolonged; PT, FBG, TT normal
Hemophilia C
Rosenthal Syndrome (Factor XI deficiency)
Hemophilia C inheritance
Autosomal dominant
Hemophilia B inheritance
Sex linked
Hemophilia A inheritance
X linked
What population is greatly affected by Hemophilia C?
Ashkenazi jews
Lab results for Hemophilia C
PTT prolonged; PT normal
T/F: Frequency and severity of bleeding in hemophilia C is linked to factor XI levels.
False; they do not correlate
Thrombosis
inappropriate formation of a PLT or fibrin clot that obstructs a blood vessel
Thrombophilia
hypercoagulability; predisposition to thrombosis secondary to a condition
Emboli
fragments of thrombi that move through the circulatory system and lodge in vasculature
Ischemia
loss of blood supply
Necrosis
tissue death
Types of venous thromboembolic disease
DVT (deep vein thrombosis)
Types of arterial thrombosis
MI, stroke
Risk factors for thrombosis
Age, immobilization, diet, oral contraceptive use, pregnancy, lipid metabolism imbalance, smoking, inflammation, hormone replacement therapy, etc
What is the most common inherited thrombosis risk factor?
Factor V Leidein (FVL) gene mutation
What is the second most common inherited thrombosis risk factor?
Prothrombin G20210A gene mutation
What are antiphospholipid antibodies (APLAs)?
immunoglobulins that bind protein-phospholipid complexes
What are the 3 types of antiphospholipid antibodies?
LACs (lupus anticoagulants)
Anticardiolipin antibodies (ACL)
Anti-B2-GPI antibodies
What does FVL gene mutation lead to?
APC resistance
What is used to differentiate between a LAC and a factor deficiency?
mixing studies
What are the 2 most common tests required for a LAC profile?
Dilute russel viper venom time (DRVVT) and silica based PTT (SCT)
Describe the pathway of mixing studies.
Prolonged PTT –> TT normal –> perform mixing study
If mixing study corrects, move to incubated mixing study. If that corrects, assay for factor deficiency. If that does not correct, assay for specific factor inhibitor or LAC
What are LACs? How do they affect clot based testing? How do they affect the patient’s hemostasis?
LACs are lupus anticoagulants (non-specific inhibitors, anti-phospholipid antibodies)
Presence of LACs = more at risk of thrombosis
They affect PTT by prolonging it.
Describe the association between FVL and APC resistance. How does FVL affect hemostasis?
FVL mutation in factor V gene lacks arginine which is the usual cleavage site for APC so the substitution of arginine for glutamine slows or resists APC hydrolysis. Resistant factor V remains active and raises production of thrombin.
Mutated factor V will not be inactivated by protein C, so it will continue with the coag cascade and patient is at risk of clot.
How does prothrombin G20210A lead to clotting?
Leads to elevated factor II (prothombin)
How does AT (antithrombin) lead to clotting?
AT is a serine protease inhibitor, so less AT leads to less inhibition - increasing factors, so leads to more clotting
How do PC and PS deficiencies lead to clotting?
PC and PS slow down clot formation, so having a deficiency will cause too much clots
At onset of Coumadin therapy, ____ activity will drop rapidly. What can this lead to?
PC; can lead to Coumadin-induced skin necrosis because PC activity drops more rapidly than other vitamin K dependent factors
How does lipoprotein a lead to clotting?
Increased lipoprotein a = increased thrombosis
How does C-reactive protein lead to clotting?
Increased CRP = increased thrombosis
How does fibrinogen lead to clotting?
Increased fibrinogen = increased clotting
How does homocysteine lead to clotting?
increased MTHFR gene mutations = increased homocysteine = increased thrombosis
How are D-dimer results used in DVT/PE diagnosis?
Increased D-dimers can be from DVT or PE. Normal D-dimer results rules out DVT and PE
What is HIT?
Heparin-induced thrombocytopenia caused by anti-PF4, patients are more likely to clot
In DIC, which of the following are increased/decreased: PLT count, coag factors, PT/PTT/TT, FSP, D-dimers, what is seen in lab smear
PLT count: decreased
Coag factors: decreased
PT/PTT/TT: prolonged
FSP: increased
Fibrinogen: decreased
D-dimer: increased
Schistocytes in lab smear
