L25 - Coagulation and platelets Flashcards
Clinical evaluation of the bleeding patient involves determining if the cause is either a __________ or ________. Give examples for each.
- platelet disorder (thrombocytopenia, qualitative platelet disorders)
- coagulation factor disorder (hemophilia A and B, coag factor inhibitors, von Willebrand disease)
Petechiae, ecchymoses, mucocutaneous bleeding suggest ____?
A. von Willebrand Disease
B. platelet defect
C. coagulation factor defect
B
Hemarthrosis, hematuria, deep hematoma suggest
A. von Willebrand Disease
B. platelet defect
C. coagulation factor defect
C
Presence of both types of bleeding suggests
A
Which medication does not have a side effect of bleeding? Al. heparin B. Warfarin C. rivaroxaban D. Aspirin E. Clopidogrel F. dabigatran G. apixaban H. Tylenol
H
Which lab tests assess platelets?
- Platelet count
2. Platelet function (PFA-100, platelet aggregation testing, thromboelastography)
Which is false regarding platelet count?
A. Normal range: 150,000 to 450,000/µL
B. In the absence of qualitative platelet dysfunction >100,000/uL has possible increased risk of bleeding with major trauma or surgery
C. In the absence of qualitative platelet dysfunction
B. there is no increased risk of bleeding, this is for values 50,000-100,000uL
Also, increased risk of bleeding with minor trauma or surgery
for 5,000-50,000
system for analysing platelet function in which citrated whole blood is aspirated at high shear rates through disposable cartridges containing an aperture within a membrane coated with either collagen and epinephrine (CEPI) or collagen and ADP (CADP)
PFA-100
PFA-100 measures the time required for the platelets in a sample of blood to plug a small hole in a tiny tube after being exposed to various activating substances. This is called the _______. If prolonged, this indicates ____ platelet function but do not identify the cause
- closure time
2. lower
- Which lab tests assess coagulation (3)?
2. which factors or parts of the coagulation cascade do they test?
- Prothrombin time (PT) - 7
- Activated partial thromboplastin time (APTT) - 8, 9
- Thrombin time (TT) - thrombin
liver disease, vitamin K deficiency, or warfarin prolong which of the following?
A. TT
B. PT
C. APTT
B
• Prothrombin time (PT)
• Most sensitive to Factor VII
• Prolonged by liver disease, vitamin K deficiency, or warfarin
• Often reported as INR (International Normalized Ratio)
hemophilia, coagulation factor inhibitors, or heparin prolong which of the following? A. TT B. PT C. APTT
C
• Activated partial thromboplastin time (APTT)
• Sensitive to Factors VIII and IX
Prolonged by hemophilia, coagulation factor inhibitors, or heparin
direct thrombin inhibitors prolong which of the following?
A. TT
B. PT
C. APTT
A
• Thrombin time (TT)
• Prolonged by direct thrombin inhibitors (too sensitive)
Low fibrinogen
1:1 mix corrects to normal
A. coagulation factor deficiency
B. coagulation factor inhibitor
A. coagulation factor deficiency
clotting tests give normal values when 50% activity of the involved coagulation factors is present. A 1:1 mix will reduce the activity of all the factors in normal pooled plasma to 50 percent.
• Thus, if the clotting test returns to normal after a 1:1 mix with normal pooled plasma, a factor deficiency was the cause of the abnormal test.
1:1 mix does not correct to normal
A. coagulation factor deficiency
B. coagulation factor inhibitor
B. coagulation factor inhibitor
- Most agents that inhibit clotting factor activity (such as antibodies) will not be effectively diluted out after addition of an equal volume of normal pooled plasma.
- Thus, if the test remains abnormal after 1:1 dilution, an inhibitor was the cause of the abnormal test
Platelet count less than 150,000/ul
Thrombocytopenia
Which is not a possible cause of thrombocytopenia? A. Drug-induced : heparin, quinine, thiazide diuretics, ethanol B. decreased platelet production C. increased platelet destruction D. splenic sequestration (hypersplenism) E. idiopathic/immune F. hemolytic anemia G. Pregnancy H. infections I. BM failure/infiltration J. hemorrhage K. Hereditary
None of the above
F is TTP
A. What kind of thrombocytopenia?
- Children: acute, self-limited - due to viral infections
- Adults: chronic
- Severe thrombocytopenia due to anti-platelet antibodies
- Normal or increased numbers of megakaryocytes in bone marrow
- May be associated with other autoimmune disorders
- Treated with corticosteroids, IVIG, anti-D immunoglobulin, splenectomy, rituximab, thrombopoietin
B. symptoms
A. ITP - idiopathic/immune thrombocytopenic purpura
B. easy bruising, epistaxis (nose bleeds), gingival petechiae, ecchymosis on upper and lower extremities
- What drug? anti- CD20 monoclonal antibody - reduce lymphocytes –> dec antibodies
- What does it treat?
- Rituximab
2. ITP
- How does TPO (thrombopoietin) receptor agonists work?
2. What is it used for?
- Increase BM production to compensate for loss
2. ITP
TTP is a syndrome of:
• Thrombocytopenia
• Fever
• acute renal insufficiency
• CNS dysfunction
• microangiopathic hemolytic anemia
1. Many cases caused by deficiency of ________?
2. Schistocytes and (inc/dec) LDH
3. PT and APTT are usually (prolonged/normal)
4. T/F: TTP is a medical emergency that is often fatal if not treated urgently with plasma exchange
- vWF-cleaving protease (ADAMTS13)
- Increased
- Normal
- T
Which is false regarding von Willebrand factor?
A. Is an adapter molecule
B. Binds and stabilizes factor VII
C. Binds collagen and binds platelets which enable platelets to recognize sites of vascular injury
D. Forms large multimers through disulfied bonds
B. Factor VIII
Why does TPP have extra large multimers?
Due to deficiency in ADAMTS13 which would normally cleave the ultralarge multimers
Which is true regarding Hemolytic Uremic Syndrome (HUS)
A. Variant of ITP
B. Predominant liver involvement
C. Often associated with pathogenic E. coli harboring a plasmid encoded Shiga toxin
D. Leading cause of liver failure in children worldwide
E. Caused by deficiency of ADAMTS13
C
A. Variant of TTP
B. Predominant renal involvement
D. Leading cause of renal failure in children worldwide
E. Not caused by deficiency of ADAMTS13
- When is an example of when you would consider a qualitative platelet disorder?
- What are the 2 types of qualitative Platelet Disorders
- Which is more common?
- decreased platelets, increased PFA-100 closure time, increased creatinine and BUN, normal blood smear.
- congenital and acquired
- Acquired (due to drugs, uremia, liver failure)
Hemophilia types (A or B)?
- Deficiency of factor IX
- Deficiency of factor VIII
B
Hemophilia types (A or B)?
- Deficiency of factor IX
- Deficiency of factor VIII
A
Which is false regarding hemophilia? A. Both are X-linked recessive (males) B. Prolonged PT that corrects to normal on 1:1 mix C. Decreased level of factor VIII or IX • Severe --------- 5%
B. APTT
Which is not a clinical finding of hemophilia? A. hemarthrosis B. hematuria C. hematoma D. mild surgical bleeding E. Arthropathy
D. excessive surgical bleeding
Treatment of hemophilia A or B?
- Desmopressin
- Factor VIII concentrate
- Epsilon amiocaproic acid
- Gene therapy
A
Treatment of hemophilia A or B?
- Factor IX concentrate
- Epsilon aminocaproic acid
- Gene therapy
B
What are 3 complications of hemophilia treatment?
- high cost of factor replacement
- Inhibitors - antibodies develop to factor VIII or IX
- infections (hep B, HIV, hep C)
Coagulation Factor Inhibitors
1. T/F: Prolonged APTT that corrects on 1:1 mix
2. T/F: Inhibitors are immunoglobulin antibodies to coagulation factors (e.g. factor VIII or factor IX)
3. Factor (VIII/IX) Inhibitors
• May arise in patients with hemophilia A
• May be spontaneous (“acquired hemophilia”)
• Severe and difficult to control bleeding
- True: Does not correct
- T
- VIII
Which is true on how you treat bleeding in patients with Factor VIII Inhibitors
A. Easy to control bleeding
B. Low-dose human factor VIII (low level inhibitors)
C. Activated prothrombin complex concentrate
D. Recombinant factor VIII
E. Immunotherapy
C
A. Extremely difficult to control bleeding
B.• High-dose human factor VIII (low level inhibitors)
D.• Recombinant factor VIIa
E. Immune tolerance therapy
von Willebrand Disease
• Deficiency of von Willebrand Factor
1. Autosomal recessive/dominant (men and women)
2. Dual role of vWF (supports platelet __________ and stabilizes factor ____)
3. Four clinical Findings (platelet and coag factor disorder symptoms)
- dominant
- adhesion; VIII
- Mucocutaneous bleeding; Excessive surgical bleeding; Hemarthrosis; hematoma (severe cases)
What kind of von Willebrand disease has a quantitative deficiency of vWF normal multimer pattern
A. Type I
B. Type 2
C. Type 3
Type 1
What kind of von Willebrand disease has a qualitative deficiency of vWF abnormal multimer pattern
A. Type I
B. Type 2
C. Type 3
Type 2
What kind of von Willebrand disease has a complete absence of vWF
A. Type I
B. Type 2
C. Type 3
Type 3
Lab findings in von Willebrand disease
- (Prolonged/normal) bleeding time or PFA-100
- Prolonged APTT that (corrects/does not correct) on 1:1 mix
- (decreased/increased) levels of vWF and Factor VIII
- prolonged
- corrects
- decreased
Treatment for von Willebrand disease:
- drug that releases vWF from endothelium
- This drug is not a recombinant factor VIII
- Desmopressin (DDAVP)
2. Factor VIII concentrates that contain vWF
