Graham Hemostasis 2012 / Exam 2 / 2nd deck Flashcards
How does fibrinogen change to fibrin ?
The enzyme Thrombin converts fibrinogen into Fibrin Monometer, Fibrinopeptide A&B. Fibrin Monometers then connect to each other and form the fibrin clot.
- ) What Lab Test can we run to measure Fibrinogen quantification (see if Fibrinolysis is taking place) ?
- ) What are the normal values?
1.) D Dimer
2.) 200 - 400 mg/dL
Newborns = 150 - 300 mg/dL
Preparation of a Sample for Coagulation Testing ?
- Sodium citrate
- Ratio of blood to
anticoagulant 9:1 - Tube must be full
- Should not be the first tube drawn
Prothrombin Time (PT)
3 minutes @ 37 degrees
- Measures the amount of clotting factors 7, 10, 5, & 2 in the Extrinsic System.
Activated Partial Thromboplastin Time (APTT)
5 min @ 37 degrees
(Plasma) + Activator phospholipid + surface contact + Calcium Chloride = Time it takes to clot
APTT Normal Lab Value:
25 - 35 sec
PT Normal Lab Values:
- Normal Lab Value: 50 - 150 % of normal activity
- Normal Lab Value: 10-13 sec
Thrombin Time
3 min at 37 degrees
Test to diagnose Thrombin Inhibition.
- Normal Lab Value: 10-15 sec
What study can you use to determine deficiency vs. inhibitor ?
Mixing Study
- Patient plasma is mixed with an equal amount of normal plasma and the APTT is then repeated.
- If the time corrects = Deficiency
- If the time does not correct = Inhibitor is present; heparin or antibody.
Plasminogen
Anticoagulant Protein
Plasminogen may be activated to the proteolytic enzyme PLASMIN by a number or agents, name 2 of them?
TPA
Urokinase
Plasmin
proteolytic enzyme that digests fibrin
Explain the D -Dimer test ?
Antibody-d-dimer + Plasma = Positive if Agglutination occurs.
Congenital factor deficiencies that may prolong PT ?
I II V X VII
Aquired factor deficiencies that may prolong PT or APTT ?
- May be single factor deficiency or multiple factor deficiency. that my prolong PT ?
- It could be a production problem.
- or a Consumption problem.
Inhibitors that may prolong PT ?
- Heparin (some heparins in some test systems)
- Lupus-like anticoagulant (high dose)
- Paraproteins
- Elevated FSP
Congenital factor deficiencies
that may prolong APTT ?
I II V X VIII IX XI XII
Inhibitors that may prolong APTT ?
- Heparin
- Specific factor inhibitor
- Lupus-like anticoagulant
- Paraproteins
- Elevated FSP
Patient is
Bleeding,
Mixing study corrects Abnormal APTT.
What Factors are deficient?
I II V X VII (vWF) IX
Patient is
NOT bleeding,
Mixing study corrects Abnormal APTT.
What Factors are deficient?
XI
XII
Patient is
Bleeding,
Mixing study does NOT correct Abnormal APTT.
What’s the problem?
INHIBITORS
- Heparin
- Specific factor inhibitor
- Paraproteins
- Elevated FSP
Patient is
NOT bleeding,
Mixing study does NOT correct Abnormal APTT.
What’s the problem?
LLAC
Factors that may prolong the Thrombin Time ?
- Decreased fibrinogen
- Abnormal fibrinogen
- Thrombin Inhibitors
Heparin
Paraproteins
Increased FSP
What is the most common congenital bleeding disorder ?
von Willebrand Disease
Criteria for diagnosis of LUPUS
- Prolongation of PT / PTT
- Uncorrectable prolongation of the PT / PTT with addition of normal plasma.
- Absence of specific inhibitory activity against any specific coagulation inhibitor
Natural Anticoagulants
- Antithrombin
- Protein C & Protein S
- Tissue factor pathway
inhibitor
What natural anticoagulant neutralizes serine proteases ?
Antithrombin
What natural anticoagulant inhibit Va and VIIIa ?
Protein C & Protein S
What natural anticoagulant neutralizes VIIa and Xa ?
Tissue factor pathway inhibitor
Thrombotic Complications in CPB
- Consumptive and hemodilutional losses of natural anticoagulants
- Transfusion of hemostatic products can result in excessive thrombin generation
- HIT
- Inherited hypercoagulable states
Heparin Induced Thrombocytopenia (HIT)
- 1-5% of pts exposed to unfractionated heparin will develop HIT.
- 30% of those will develop thrombosis
- Patient forms antibodies to the complex of heparin with PF4 found in the alpha granules of platelets
Name 5 Inherited Hypercoagulable States?
- Factor V Leiden
- Prothrombin G20210A
- Elevation of vWF, VIII,
fibrinogen - Deficiency of natural
anticoagulants - Increased levels of
Lipoprotein (a) inhibits fibrinolysis
Disseminated Intravascular Coagulation (DIC) definition ?
Secondary condition that results in the increased generation of thrombin. Making clots leads to fibrinolysis (the breaking down of clots) which leads to a vicious cycle.
Disseminated Intravascular Coagulation (DIC) fibrinolytic example ?
Hemorrhagic PurpuraMeningococcal Septicemia
Disseminated Intravascular Coagulation (DIC) Thrombotic example ?
GangreneHaemophilus B Septicemia
Thrombin Removes fibrinopeptides A and B, forming fibrin monomers which
results in ?
Decreased Fibrinogen
Thrombin Activates V, VIII, and XIII. As it is formed, it consumes what ?
factor II
Thrombin also Stimulates platelets, which leads to what ?
thrombocytopenia
Activation of Fibrinolysis leads to 4 things, what are they?
- Increased plasmin generation
- Lysis of clots
- Consumption of fibrinogen
- Increased levels of FSP and
D-Dimer
Laboratory Results in DIC
↑ PT, PTT, TT ↑ Fibrin Split Products ↓ Fibrinogen ↓ Platelets - Schistocytes on peripheral smear
6 Conditions Associated with DIC?
- Infections
- Obstetric complications
- Surgery, including CPB
- Malignancies
- Massive tissue injury
- Snakebite
Anticoagulant Therapy
- Thrombin Inhibitors
- Heparin
- Direct thrombin inhibitors
- Warfarin compounds
(Coumadin) - Antiplatelet therapy