Coagulation Disorders Flashcards
1
Q
List 3 phases of primary hemostasis (platelet response).
A
Adhesion
Activation
Aggregation
2
Q
Hemostasis refers to the ability to maintain blood in a ______ state and prevent loss from sites of _______ damage.
A
fluid
vascular
3
Q
Name the three major components of the hemostatic system.
A
vascular wall
platelets
coagulation proteins
4
Q
What occurs during adhesion?
A
- adhesion of platelets to the damaged endothelial site
- involves activation of a surface membrane receptor (glycoprotein Ib/IX), an adhesive protein (von Willebrand factor), and an appropriate surface (sub endothelial collagen)
5
Q
What mediates the adherence of platelets to the subendothelial collagen?
A
vWF
glycoprotein Ib/IX binds to vWF
6
Q
During activation, additional _______ are recruited into the local site.
A
platelets
7
Q
As platelets are activated by binding to vWF, there is release of secondary messengers within the platelet that lead to a shape change from ________ to ________
A
discoid flatter (elongated) Note: this shape change increases surface area
8
Q
During aggregation, platelet-platelet binding is mediated through…
A
fibrinogen and the glycoprotein IIb/IIIa receptor
9
Q
Fibrin clot formation is referred to as _________ hemostasis.
A
secondary
10
Q
Thrombin converts ______ to ______ which adds stability to the clot after ______ monomers are covalently cross linked by Factor ___.
A
fibrin
fibrinogen
fibrin
XIII
11
Q
The _________ pathway refers to the sequence of activation of Factor XII by Kallikrein.
A
intrinsic
12
Q
After activation of Factor XII during the intrinsic pathway, Factor XIIa activates Factor __.
A
XI
13
Q
Factor ___ activates IX.
A
XIa
14
Q
The ________ pathway refers to the sequence of activation of Factor VII by tissue factor.
A
extrinsic
15
Q
The _______ pathway involves activation of X to __, followed by conversion of prothrombin (II) to _______, followed by conversion of fibrinogen (I) to ________ monomers.
A
common
Xa
thrombin
fibrin
16
Q
What is formed when fibrin monomers generated by thrombin polymerize to form a long strand?
A
fibrin clot
17
Q
What makes the fibrin monomers more stable?
A
covalent cross-linking by Factor XIII
18
Q
These inhibit the activity of thrombin and other serine proteases (factors IXa, Xa, XIa, XIIa) of the coagulation cascade by forming inactive ________-________ complex.
A
antithrombins
enzyme-inhibitor
19
Q
This is one of the best known antithrombins that, in the presence of heparin, becomes activated to that it can form a complex with thrombin (preventing thrombin from generating fibrin monomers).
A
antithrombin III
20
Q
What system regulates the major cofactors of the coagulation cascade, factor Va and VIIIa.
A
protein C system
21
Q
What is the major effector enzyme in the protein C system?
A
Activated protein C (APC)
22
Q
What is a major cofactor in the protein C system?
A
protein S
23
Q
Protein C or protein S deficiencies lead to __________ states.
A
hypercoaguable
24
Q
Factor V Leiden mutation promotes _________.
A
coagulation
25
Tissue plasminogen activator (TPA) can bind to __________ and convert it to an active enzyme, _______.
plasminogen
| plasmin
26
Plasmin breaks down previously cross-linked fibrin monomers into _____ _________ ______ or (____).
fibrin degradation products (FDP)
27
Uncontrolled activation of plasmin can result in ________ complications due to fibrinolysis.
bleeding
28
Shifts in the balance that favor the procoagulant side result in _________, whereas shifts that favor the regulatory side can result in _________ disorders.
thrombosis
| bleeding
29
The most important part of defining the cause of a bleeding disorder is a careful _______ _______.
clinical history
30
This lab test is a measurement of the time needed for plasma to form a clot in the presence of added tissue thromboplastin (to initiate extrinsic coagulation cascade) and calcium ions.
Prothrombin time (PT)
31
Prolonged PT results from _________ or ________ in Factors VII, X, V, II, and/or fibrinogen
decreases
| abnormalities
32
This lab test is routinely used to measure degree of anticoagulation in patients receiving coumadin.
PT
33
This is a ratio of the patient PT time/control PT time. Also used to monitor coumadin patients.
INR
34
This lab test is a measurement of the time needed for plasma to form a clot in the presence of added ground glass or kaolin (to activate contact-dependent Factor XII), cephalin (phospholipid), and calcium ions.
partial thromboplastin time (PTT)
35
This lab test primarily accesses the intrinsic coagulation cascade.
PTT
36
Prolonged PTT can result from decreases or abnormalities of which 7 factors and fibrinogen?
```
II
V
VIII
IX
X
XI
XII
```
37
This lab test is routinely used to measure degree of anticoagulation in patients receiving heparin therapy.
PTT
38
This lab test is a measurement of platelet number in anticoagulated blood quantitated by an automated instrument.
platelet count
39
Normal range of platelet count is generally ________ to ________ /uL.
150,000
| 400,000
40
This term refers to a decrease in platelet number.
thrombocytopenia
41
These two terms denote an increase in platelet number.
thrombocytosis
| thrombocythemia
42
This lab test is a measurement of platelet function as determined by the time taken for a standardized skin incision to stop bleeding.
bleeding time
43
This lab test is no longer used and has been replaced by the ___-___.
bleeding time
| PFA-100
44
When either PT or PTT is prolonged, a ________ study with 1:1 ratio of normal plasma:patient plasma can be performed.
mixing
45
If the mixing study corrects the clotting time, a deficiency of some _______ is felt to be present.
factors
46
If the mixing study does not correct the clotting time, an _________ is felt to be present.
inhibitor
47
More specialized test may be necessary to precisely define a coagulation defect - these include:
- assays for specific coagulation factors
- measurement of fibrinogen quantity and function
- platelet aggregation tests
48
What are the 3 classifications of bleeding disorders?
Disorders of:
primary hemostasis
secondary hemostasis
regulatory system
49
Clinical manifestations of these types of disorders include mucotaneous bleeding/bleeding associated with trauma.
Labs will show prolonged bleeding time and thrombocytopenia.
Disorders of primary hemostasis
50
Clinical manifestations of these types of disorders include soft tissue bleeding/bleeding associated with trauma.
Labs will show prolonged PT/PTT/thrombin time.
Disorders of secondary hemostasis
51
Clinical manifestations of these types of disorders include soft tissue bleeding/bleeding associated with trauma.
Labs will often be normal in screening tests.
Disorders of the regulatory system
52
Name the 3 congenital bleeding disorders discussed in class.
von Willebrand Disease
Hemophilia A
Hemophilia B
53
Name the 3 platelet disorders discussed in class.
thrombocytopenia
Immune Thrombocytopenic Purpura (ITP)
Thrombotic Thrombocytopenic Purpura (TTP)
54
This disorder results from uncontrolled activation of the hemostatic system.
Both systemic thrombin formation and systemic plasmin formation occur.
Disseminated Intravascular Coagulation (DIC)
55
What are the two components of the Factor VIII complex?
vWF
| Factor VIII procoagulant
56
What are 2 functions of vWF?
- carrier molecule for Factor VIII
| - the "glue" between damaged endothelium and platelets (in primary hemostasis)
57
When is Factor VIII procoagulant released from vWF?
when a clot is formed (Factor VIII then participates in generating Factor X)
58
T/F
| The half life of vWF when not bound to Factor VIII is very long.
False
| very short
59
Where is Factor VIII believed to be synthesized?
liver
60
Where is vWF present?
in platelets and endothelial cells
61
This disease is associated with decreased amounts of a normal protein (quant. abnormality) or production of a protein with abnormal function (qual. abnormality), or both.
von Willebrand Disease
62
This is the most common inherited bleeding disorder affected approximately 1% of the U.S. population.
von Willebrand Disease
63
What is the predominant clinical manifestation of von Willebrand Disease?
mucocutaneous bleeding
| nosebleeds, bruising, mucosal bleeding, excessive bleeding with trauma/surgery, or excessive menstrual flow
64
When do symptoms of von Willebrand Disease often improve?
after adolescence
65
The most common form of vWD results in production of _________ amounts of vWF which also results in ________ amounts of Factor VIII.
decreased
| decreased
66
Labs of vWD patients show prolonged _______ ____ and prolonged ___. Platelet aggregation studies may be abnormal in about ___ of patients.
bleeding time
PTT
1/3
67
What 2 drugs can be given as treatment for mild vWD?
- desmopressin
| - anti-fibrinolytic agents
68
What does desmopressin do in the body?
releases vWF from endothelial cells
69
What is given in more severe cases of vWD?
- Factor VIII concentrates containing vWF
| - cryoprecipitate
70
This disease is due to decreased production of Factor VIII and is the most common hereditary cause for serious bleeding.
Hemophilia A
71
The clinical hallmark of Hemophilia A is recurrent...
| Symptoms usually start ______ in life.
soft tissue bleeding
| early
72
Other clinical manifestations of Hemophilia A are:
- hemarthrosis
- bleeding with trauma
- intramuscular hematomas
- intracranial hemorrhage
- excessive bleeding in general
73
T/F
| There is a high rate for de novo mutations resulting in Hemophilia A.
True
| about 30%
74
Labs of patients with Hemophilia A will show _______ bleeding time, ________ PTT, ________ VIII, and normal ___ and ___.
```
normal
prolonged
decreased
vWF
IX
```
75
Severe Hemophilia A is characterized by a Factor VIII level of...
<1%
76
Moderate forms of Hemophilia A have ____% VIII and mild forms have ___%
1-5
| >5
77
The severity of bleeding with Hemophilia A is directly proportional to the amount of ____ present.
VIII
78
Treatment of Hemophilia A involves replacement of ________ in the form of concentrates.
Factor VIII
79
These two things may be given to treat mild forms with minor bleeding in Hemophilia A.
- desmopressin
| - fibrinolytic inhibitors
80
Complications of Hemophilia A include:
joint disease
pseudotumors (hematomas)
fatal hemorrhage
81
This disease is due to decreased production of Factor IX.
Hemophilia B
82
Clinically, Hemophilia B is similar to Hemophilia A except for which lab values?
Factor IX will be decreased (VIII will be normal)
83
This refers to a decrease in platelet count (<100,000/uL).
Thrombocytopenia
84
Evaluation of thrombocytopenia is made using ________ information and peripheral _______ smear morphology.
clinical
| blood
85
Name a few conditions that can result in increased destruction of platelets.
```
immune-mediated conditions
sepsis
DIC
TTP
vasculitis
burns
drugs
fat emboli
hemorrhage
```
86
This disorder is characterized by immune-mediated destruction of platelets.
Immune Thrombocytopenic Purpura (ITP)
87
These are common targets of autoantibodies in the ITP disease process.
GP Ib/IX and IIb/IIIa
88
The acute form of ITP occurs in ________ and is typically severe, while the chronic form is more typical in _______ with gradual onset.
childhood
| adults
89
Therapy of ITP includes:
corticosteroids
IV immunoglobulin
splenectomy
90
This disorder is characterized by intravascular platelet activation with formation of platelet-rich micro thrombi throughout the circulation.
Thrombotic Thrombocytopenic Purpura (TTP)
91
The cause of TTP is a deficiency of a _____________ ADAMTS 13, which normally degrades very-high-molecular-weight multimers of vWF.
metalloproteinase
92
Deficiency of ADAMTS 13 results in accumulation of ____ in plasma.
vWF
93
Classic manifestations of TTP include:
```
fever
marked thrombocytopenia
microangiopathic hemolytic anemia
acute renal failure
neurologic changes
```
94
Labs of TTP patient will show thrombocytopenia, ________ in peripheral blood smear, anemia, reticulocytosis, ______ coagulation parameters, and _______ bilirubin and LD (intravascular hemolysis)
schistocytes
normal
increased
95
Clinical manifestations of DIC include bleeding from _______ sites, thrombotic problems, hypotension/shock, and dysfunction in which systems?
multiple
| respiratory, hepatic, renal, CNS
96
What clinical situations increase risk of developing DIC?
```
bleeding/thromboembolic problems
dysfunction of organ system
infections (Gram negative)
tissue injury
OB complications
malignancies
venomous snake bites
vascular lesions
hemolytic transfusion reaction
```
97
Therapy of DIC is directed at:
removing the initiating stimulus
| support patient' s coagulation protein reserve (transfusions of FFP and cryoprecipitates)
